tag:theconversation.com,2011:/global/topics/infection-11149/articlesInfection – The Conversation2024-01-29T14:53:48Ztag:theconversation.com,2011:article/2215112024-01-29T14:53:48Z2024-01-29T14:53:48ZFrom mud and vinegar to 3D printing skin, the way we treat wounds still challenges humanity<p>Whether it’s the sting of a paper cut or the trauma of battle injury, wounds are woven into the tapestry of human experience. And since ancient times, we’ve fought the enemy that lurks within them – infection. </p>
<p>The constant threat of injury on the battlefield led to the search for new ways to combat wound infection. But early surgical procedures lacked the sterile instruments available today, meaning that for many years, surgery came with the added risk of post-operative <a href="https://cha.com/wp-content/uploads/2017/11/AJIC-2012-Infection-Control-Through-the-Ages.pdf">wound infection</a>, resulting in high numbers of deaths. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601883/">Ancient practices</a>, such as using oils, mud, turpentine, or honey to treat wounds, were common around 2000BC. The Greek physician Hippocrates (460-377BC) <a href="https://www.dermatologytimes.com/view/acetic-acid-and-wound-healing">used vinegar</a> to clean wounds, followed by bandaging to keep dirt at bay.</p>
<p>While the first hospitals were <a href="https://scientificsurgery.bjs.co.uk/article/the-surgery-of-theodoric-ca-a-d-1267-translated-from-the-latin-by-eldridge-campbell-m-d-and-james-colton-m-a-volume-i-books-i-and-ii-8-38-x-5-12-in-pp-223-xi-with-coloured-front/">established</a> in Europe in the middle ages, they were dangerous and brutal places. Wound infection rates were high because of unsanitary conditions and the use of cautery, which involved pushing a burning iron into a patient’s wound until it reached the bone.</p>
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<img alt="A drawing of a pot containing a fire with several medical instruments poking out of it." src="https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=403&fit=crop&dpr=1 600w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=403&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=403&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=506&fit=crop&dpr=1 754w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=506&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=506&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">A receptacle for burning coal to heat cautery instruments.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/gcg933n2/images?id=jghkdnp4">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>By the 1860s, the pioneering surgeon Joseph Lister had revolutionised wound infection treatment by introducing <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895849/">carbolic-acid-soaked bandages</a>. And Robert Wood Johnson, who founded Johnson & Johnson, <a href="https://wounds-uk.com/journal-articles/sterilised-gauze-and-baby-powder-robert-wood-johnson-i-and-frederick-barnett-kilmer/">produced</a> the first sterile gauze bandages by 1890. The combination of antiseptic and sterile bandage marked a turning point in the evolution of wound treatment and infection control.</p>
<p>The discovery of penicillin by <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520913/">Alexander Fleming</a> in 1928 was also a pivotal moment in the treatment of wound infections. By the 1940s, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369031/">penicillin</a> was being used to treat second world war soldiers who had wound infections that would have been deemed fatal in previous years. For less serious wounds, Lister’s approach of using a dressing and an antiseptic was still used.</p>
<p>Substances like <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756674/">silver</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/12914356/">iodine</a> have also been recognised for their antimicrobial properties since the 1800s. Iodine, though effective, caused pain and skin discolouration until safer and less painful formulations were developed in 1949. <a href="https://bnf.nice.org.uk/wound-management/antimicrobial-dressings/">These formulations</a> endure in modern wound dressings.</p>
<p>For everyday cuts and scrapes, a simple cleaning with water and application of antiseptic cream is usually enough. This helps to prevent the inadvertent introduction of bacteria into the wound, minimising the risk of additional pain and swelling. </p>
<p>But while most wounds nowadays heal without issue, some become become infected. Research published in 2021 showed that <a href="https://wounds-uk.com/wp-content/uploads/sites/2/2023/02/68803cd147c4d81a02b9cc56823f19a1.pdf">3.8 million</a> people were having their wounds managed by the NHS between 2017 and 2018, up 71% from between 2012 and 2013. They included surgical wounds, leg ulcers and burns. This shows how hard it can be to care for wounds that are difficult to heal and particularly susceptible to infections.</p>
<h2>Modern-day challenges</h2>
<p>One of the biggest challenges in the modern-day treatment of wound infection is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">antibiotic resistance</a>. This happens when bacteria develop the ability to defeat the drugs designed to kill them. Resistant infections can be difficult, and sometimes impossible, to treat. </p>
<p>Many bacteria have also become resistant to the antimicrobial ingredients used in wound dressings. This is the case for <a href="https://www.sciencedirect.com/science/article/pii/S0195670104005201">silver-based</a> wound dressings, which are often used to treat chronic wound infections. This type of wound characteristically <a href="https://www.nature.com/articles/s41572-022-00377-3">fails to heal</a>, and can remain an open, infected wound for many months – or even years. As well as the devastating effect on people’s quality of life, this also places a huge financial burden on the NHS.</p>
<p>The constant fight against wound infections drives extensive research for new, safe and effective treatments. While progress is being made, a crucial hurdle lies in the <a href="https://academic.oup.com/jacamr/article/3/1/dlab027/6186407">limitations</a> of laboratory testing methods. These tests, while necessary for regulatory approval, often fail to capture the nuanced realities of wounds in the human body. </p>
<p>No two people are the same and no two wounds are the same either. This can lead to situations where treatments shine in the lab but ultimately prove ineffective in real patients.</p>
<h2>Creating wound models</h2>
<p>In response to this, scientists are tackling the limitations of lab tests by creating more realistic synthetic wound models. Some are even <a href="https://pubmed.ncbi.nlm.nih.gov/30172300/">3D printing</a> human skin (using leftovers from surgical procedures), or animal skin, complete with artificial body fluids, such as pus. The aim is to create a model environment that mimics real wounds more accurately. </p>
<p>Recently, my own <a href="https://pubmed.ncbi.nlm.nih.gov/36678466/">research group</a> has made strides in developing lab models that act like real chronic wounds when treated with antimicrobial dressings. While not perfect, our models are a step in the right direction, contributing to the development of formulations with promising potential for treating wound infections in the future.</p>
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Read more:
<a href="https://theconversation.com/we-built-a-human-skin-printer-from-lego-and-we-want-every-lab-to-use-our-blueprint-203170">We built a human-skin printer from Lego and we want every lab to use our blueprint</a>
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<p>As we navigate the complexities of wound care, the quest for new, effective and safe treatments continues, driven by the efforts of scientists worldwide. We are working towards a future where the management of difficult-to-heal wounds and infections improves, enhancing both individual wellbeing and the efficiency of health systems.</p><img src="https://counter.theconversation.com/content/221511/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sarah Maddocks does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Keeping wounds clean and infection free has challenged people for thousands of years.Sarah Maddocks, Lecturer in Microbiology, Cardiff Metropolitan UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2202852024-01-25T20:46:49Z2024-01-25T20:46:49ZThe emergence of JN.1 is an evolutionary ‘step change’ in the COVID pandemic. Why is this significant?<figure><img src="https://images.theconversation.com/files/571359/original/file-20240125-15-2lt45r.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C7667%2C3900&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/evolution-covid19-sarscov2-mutating-coronavirus-virus-2344854903">Lightspring/Shutterstock</a></span></figcaption></figure><p>Since it was detected in <a href="https://www.gavi.org/vaccineswork/seven-things-you-need-know-about-jn1-covid-19-variant">August 2023</a>, the JN.1 variant of COVID has <a href="https://news.un.org/en/story/2023/12/1145012">spread widely</a>. It has become dominant in Australia and <a href="https://outbreak.info/situation-reports?xmin=2023-07-05&xmax=2024-01-05&pango=JN.1">around the world</a>, driving the <a href="https://www.cdc.gov/respiratory-viruses/whats-new/JN.1-update-2024-01-05.html">biggest COVID wave</a> seen in many jurisdictions for at least the past year.</p>
<p>The World Health Organization (WHO) <a href="https://news.un.org/en/story/2023/12/1145012">classified</a> JN.1 as a “variant of interest” in December 2023 and in January <a href="https://x.com/UNGeneva/status/1745782729558348212?s=20">strongly stated</a> COVID was a continuing global health threat causing “far too much” preventable disease with worrying potential for long-term health consequences. </p>
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<p>JN.1 is significant. First as a pathogen – it’s a surprisingly new-look version of SARS-CoV-2 (the virus that causes COVID) and is rapidly displacing other circulating strains (omicron XBB). </p>
<p>It’s also significant because of what it says about COVID’s evolution. Normally, SARS-CoV-2 variants look quite similar to what was there before, accumulating just a few mutations at a time that give the virus a meaningful advantage over its parent. </p>
<p>However, occasionally, as was the case when omicron (B.1.1.529) arose two years ago, variants emerge seemingly out of the blue that have markedly different characteristics to what was there before. This has significant implications for disease and transmission. </p>
<p>Until now, it wasn’t clear this “step-change” evolution would happen again, especially given the ongoing success of the steadily evolving omicron variants. </p>
<p>JN.1 is so distinct and causing such a wave of new infections that many are wondering whether the <a href="https://www.who.int/activities/tracking-SARS-CoV-2-variants">WHO</a> will recognise JN.1 as the next variant of concern with its own Greek letter. In any case, with JN.1 we’ve entered a new phase of the pandemic.</p>
<h2>Where did JN.1 come from?</h2>
<p>The JN.1 (or BA.2.86.1.1) story begins with the emergence of its <a href="https://erictopol.substack.com/p/from-a-detour-to-global-dominance">parent lineage</a> BA.2.86 around mid 2023, which originated from a much earlier (2022) omicron sub-variant BA.2.</p>
<p><a href="https://www.nature.com/articles/d41586-022-01613-2">Chronic infections</a> that may linger unresolved for months (if not years, in some people) likely play a role in the emergence of these step-change variants. </p>
<p>In chronically infected people, the virus silently tests and eventually retains many mutations that help it avoid immunity and survive in that person. For BA.2.86, this resulted in <a href="https://theconversation.com/how-evasive-and-transmissible-is-the-newest-omicron-offshoot-ba-2-86-that-causes-covid-19-4-questions-answered-212453">more than 30 mutations</a> of the spike protein (a protein on the surface of SARS-CoV-2 that allows it to attach to our cells). </p>
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<a href="https://theconversation.com/covid-is-surging-in-australia-and-only-1-in-5-older-adults-are-up-to-date-with-their-boosters-220839">COVID is surging in Australia – and only 1 in 5 older adults are up to date with their boosters</a>
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<p>The sheer volume of infections occurring globally sets the scene for major viral evolution. SARS-CoV-2 continues to have a <a href="https://nextstrain.org/ncov/gisaid/global/all-time?dmin=2021-04-07&l=clock">very high rate of mutation</a>. Accordingly, JN.1 itself is already <a href="https://twitter.com/dfocosi/status/1744982175508771190">mutating and evolving</a> quickly.</p>
<h2>How is JN.1 different to other variants?</h2>
<p>BA.2.86 and now JN.1 are behaving in a manner that looks unique in laboratory studies in two ways.</p>
<p>The first relates to how the virus evades immunity. JN.1 has inherited <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00813-7/fulltext#%20">more than 30 mutations</a> in its spike protein. It also acquired a new mutation, <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00744-2/fulltext">L455S</a>, which further decreases the ability of antibodies (one part of the immune system’s protective response) to bind to the virus and prevent infection.</p>
<p>The second involves changes to the way JN.1 <a href="https://www.nature.com/articles/s41580-021-00418-x">enters</a> and replicates in our cells. Without delving in to the molecular details, recent high-profile lab-based research from the <a href="https://www.cell.com/action/showPdf?pii=S0092-8674%2823%2901400-9">United States</a> and <a href="https://www.cell.com/action/showPdf?pii=S0092-8674%2823%2901399-5">Europe</a> observed BA.2.86 to enter cells from the lung in a similar way to pre-omicron variants like delta. However, in contrast, preliminary work by Australia’s Kirby Institute <a href="https://www.biorxiv.org/content/10.1101/2023.09.22.558930v2">using different techniques</a> finds replication characteristics that are aligned better with omicron lineages. </p>
<p>Further research to resolve these different cell entry findings is important because it has implications for where the virus may prefer to replicate in the body, which could affect disease severity and transmission. </p>
<p>Whatever the case, these findings show JN.1 (and SARS-CoV-2 in general) can not only navigate its way around our immune system, but is finding new ways to infect cells and transmit effectively. We need to further study how this plays out in people and how it affects clinical outcomes.</p>
<h2>Is JN.1 more severe?</h2>
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<img alt="A woman in a supermarket wearing a mask." src="https://images.theconversation.com/files/571362/original/file-20240125-17-9zn8rj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/571362/original/file-20240125-17-9zn8rj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/571362/original/file-20240125-17-9zn8rj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/571362/original/file-20240125-17-9zn8rj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/571362/original/file-20240125-17-9zn8rj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/571362/original/file-20240125-17-9zn8rj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/571362/original/file-20240125-17-9zn8rj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">JN.1 has some characteristics which distinguish it from other variants.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/alarmed-female-wears-medical-mask-against-1708365295">Elizaveta Galitckaia/Shutterstock</a></span>
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<p>The step-change evolution of BA.2.86, combined with the immune-evading features in JN.1, has given the virus a <a href="https://www.who.int/docs/default-source/coronaviruse/18122023_jn.1_ire_clean.pdf?sfvrsn=6103754a_3">global growth advantage</a> well beyond the XBB.1-based lineages we faced in 2023. </p>
<p>Despite these features, evidence suggests our <a href="https://www.news-medical.net/news/20231208/T-cells-can-recognize-and-fight-the-Pirola-variant-new-study-suggests.aspx">adaptive immune system</a> could still recognise and respond to BA.286 and JN.1 effectively. Updated monovalent vaccines, tests and treatments <a href="https://publichealth.jhu.edu/2024/jn1-the-dominant-variant-in-the-covid-surge">remain effective</a> against JN.1. </p>
<p>There are two elements to “severity”: first if it is more “intrinsically” severe (worse illness with an infection in the absence of any immunity) and second if the virus has greater transmission, causing greater illness and deaths, simply because it infects more people. The latter is certainly the case with JN.1. </p>
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<a href="https://theconversation.com/how-long-does-immunity-last-after-a-covid-infection-221398">How long does immunity last after a COVID infection?</a>
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<h2>What next?</h2>
<p>We simply don’t know if this virus is on an evolutionary track to becoming the “next common cold” or not, nor have any idea of what that timeframe might be. While <a href="https://www.science.org/content/article/four-cold-causing-coronaviruses-may-provide-clues-covids-future">examining the trajectories</a> of four historic coronaviruses could give us a glimpse of where we may be heading, this should be considered as just one possible path. The emergence of JN.1 underlines that we are experiencing a continuing epidemic with COVID and that looks like the way forward for the foreseeable future. </p>
<p>We are now in a new pandemic phase: post-emergency. Yet COVID remains the major infectious disease causing harm globally, from both acute infections and <a href="https://theconversation.com/long-covid-symptoms-can-improve-but-their-resolution-is-slow-and-imperfect-212015">long COVID</a>. At a societal and an individual level we need to re-think the risks of accepting wave after wave of infection. </p>
<p>Altogether, this underscores the importance of <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01585-9/fulltext">comprehensive strategies to reduce COVID transmission and impacts</a>, with the least imposition (such as <a href="https://www.mja.com.au/journal/2022/217/11/healthy-indoor-air-our-fundamental-need-time-act-now">clean indoor air interventions</a>). </p>
<p>People are <a href="https://www.health.vic.gov.au/health-alerts/increase-in-covid-19-cases">advised</a> to continue to take active steps to protect themselves and those around them. </p>
<p>For better pandemic preparedness for emerging threats and an improved response to the current one it is crucial we <a href="https://www.who.int/publications/m/item/virtual-press-conference-on-global-health-issues-transcript-10-january-2024">continue global surveillance</a>. The low representation of low- and middle- income countries is a concerning blind-spot. Intensified research is also crucial.</p><img src="https://counter.theconversation.com/content/220285/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Suman Majumdar, through the Burnet Institute receives grant funding from the Australian Government via the National Health & Medical Research Council of Australia, the Medical Research Future Fund and DFAT's Centre for Health Security.</span></em></p><p class="fine-print"><em><span>Brendan Crabb and the Institute he leads receives research grant funding from the National Health & Medical Research Council of Australia, the Medical Research Future Fund, DFAT's Centre for Health Security and other Australian federal and Victorian State Government bodies. He is the Chair of The Australian Global Health Alliance and the Pacific Friends of Global Health, both in an honorary capacity. And he serves on the Board of the Telethon Kids Institute, on advisory committees of mRNA Victoria, the Sanger Institute (UK), the Institute for Health Transformation (at Deakin University), The Brain Cancer Centre (Australia), the WHO Malaria Vaccine Advisory Committee; MALVAC, and is a member of OzSAGE and The John Snow Project, all honorary positions.</span></em></p><p class="fine-print"><em><span>Stuart Turville receives funding from NHMRC through an Ideas Grant and MRFF grant related to SARS CoV-2 immunology. </span></em></p><p class="fine-print"><em><span>Emma Pakula does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The JN.1 variant has become dominant in Australia and around the world, causing large waves of infections. Here’s what we know about it so far – and why it’s so important.Suman Majumdar, Associate Professor and Chief Health Officer - COVID and Health Emergencies, Burnet InstituteBrendan Crabb, Director and CEO, Burnet InstituteEmma Pakula, Senior Research and Policy Officer, Burnet InstituteStuart Turville, Associate Professor, Immunovirology and Pathogenesis Program, Kirby Institute, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2161392023-11-21T13:26:58Z2023-11-21T13:26:58ZHow do viruses get into cells? Their infection tactics determine whether they can jump species or set off a pandemic<figure><img src="https://images.theconversation.com/files/560185/original/file-20231117-23-zg89fr.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2309%2C1299&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Surface proteins on a virus enable it to attach to and get inside a cell to start replicating.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/new-omicron-sub-variant-bq-1-1-royalty-free-image/1435658319">koto_feja/E+ via Getty Images</a></span></figcaption></figure><p>COVID-19, flu, mpox, noroviral diarrhea: How do the viruses that cause these diseases actually infect you?</p>
<p>Viruses <a href="https://www.khanacademy.org/science/biology/biology-of-viruses/virus-biology/a/intro-to-viruses">cannot replicate on their own</a>, so they must infect cells in your body to make more copies of themselves. The life cycle of a virus can thus be roughly described as: get inside a cell, make more virus, get out, repeat. </p>
<p>Getting inside a cell, or <a href="https://doi.org/10.1016/j.jmb.2018.03.034">viral entry</a>, is the part of the cycle that most vaccines target, as well as a key barrier for viruses jumping from one species to another. <a href="https://scholar.google.com/citations?user=OQ7vzu0AAAAJ&hl=en">My lab</a> and many others study this process to better anticipate and combat emerging viruses.</p>
<h2>How viruses enter cells</h2>
<p>Different viruses travel into the body in <a href="https://www.oregon.gov/oha/ph/diseasesconditions/communicabledisease/pages/transmission.aspx">various ways</a> – via airborne droplets, on food, through contact with mucous membranes or through injection. They typically first infect host cells near their site of entry – the cells lining the respiratory tract for most airborne viruses – then either remain there or spread throughout the body.</p>
<p>Viruses <a href="https://doi.org/10.1016/j.jmb.2018.06.024">recognize specific proteins or sugars</a> on host cells and stick to them. Each virus gets only one shot at putting its genome inside a cell – if their entry machinery misfires, they risk becoming inactivated. So they <a href="https://doi.org/10.1016/j.virol.2015.02.037">use several mechanisms</a> to prevent triggering entry prematurely.</p>
<p>After the virus binds to the cell, specific molecules on the cell’s surface or within the cell’s recycling machinery <a href="https://doi.org/10.1111/tra.12389">activate viral coat proteins for entry</a>. An example is the SARS-CoV-2 spike that COVID-19 vaccines target. These proteins need to modify the cell membrane to allow the viral genome to get through without killing the cell in the process. Different viruses use different tricks for this, but most work like cellular secretion – how cells release materials into their environment – in reverse. Specialized viral proteins help <a href="https://doi.org/10.1146/annurev-virology-111821-093413">merge the membranes of the virus and the cell</a> together and release the viral core into the interior of the cell.</p>
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<figcaption><span class="caption">This animation depicts HIV fusing its membrane with a cell in order to release its contents inside.</span></figcaption>
</figure>
<p>At this point, the viral genome can enter the cell and <a href="https://doi.org/10.1016%2FB978-0-12-800947-5.00004-1">start replicating</a>. Some viruses use only the cell’s machinery to replicate, while others carry along portions of their own replication machinery and borrow some parts from the cell. After replicating their genomes, viruses assemble the components required to make new viruses.</p>
<p>Two central questions scientists are studying about viral entry are how your body’s defenses can disrupt it and what determines whether a virus from other species can infect people.</p>
<h2>Immune defenses against viruses</h2>
<p>Your body has a multilayered defense system against viral threats. But the part of your immune system called the <a href="https://doi.org/10.1016/j.jaci.2009.12.980">antibody response</a> is generally thought to be most effective at <a href="https://doi.org/10.1016/j.immuni.2022.10.017">sterilizing immunity</a> – preventing an infection from taking hold in the first place as opposed to just limiting its scope and severity. </p>
<p>For many viruses, antibodies target the part of the virus that binds to cells. This is the case not just for current COVID-19 vaccines but also the majority of immunity against influenza, whether from vaccines or from prior infection. </p>
<p>However, some antibodies target the entry machinery instead: Rather than preventing the virus from sticking, they prevent the virus from working altogether. Such antibodies are often harder for the viruses to escape from but are difficult to reproduce with vaccines. For that reason, developing antibodies that inhibit cell entry has the been the goal of many <a href="https://doi.org/10.1016/j.coviro.2016.02.002">next-generation vaccine efforts</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of the mechanisms of four classes of HIV antivirals" src="https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=496&fit=crop&dpr=1 600w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=496&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=496&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=623&fit=crop&dpr=1 754w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=623&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=623&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This diagram shows how four different classes of antiviral drugs inhibit HIV. One stops viruses from entering cells, and three inhibit different viral enzymes.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:HIV-drug-classes.svg">Thomas Splettstoesser/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>Species-hopping and pandemics</h2>
<p>The other key question researchers are asking about viral entry is <a href="https://www.cdc.gov/flu/pandemic-resources/national-strategy/risk-assessment.htm">how to tell when</a> a virus from another species poses a threat to people. This is particularly important because many viruses are first identified in animals such as bats, birds and pigs before they spread to humans, but it’s unclear which ones may cause a pandemic.</p>
<p>The part of viruses that stick to human cells varies the most across species, while the part that gets the virus into cells <a href="https://doi.org/10.1016/bs.aivir.2016.08.004">tends to stay mostly the same</a>. Many researchers have thought that viruses changing in ways that bind better to human cells, like influenza viruses that bind to cells in the nose and throat, are some of the most important warning signs for pandemic risk. </p>
<p>However, coronaviruses – the family of viruses containing SARS-CoV-2 – are prompting re-examination of that idea. This is because several animal coronaviruses can actually <a href="https://doi.org/10.1038/s41564-020-0688-y">bind to human cells</a>, but only a few seem to be able to transmit well between people.</p>
<p>Only time will tell whether researchers need to broaden their pandemic prevention horizons or if their current prioritization of risky viruses is correct. The one grim reality of pandemic research, like earthquake research, is that there will always be another one – we just don’t know when or where, and we <a href="https://www.niaid.nih.gov/sites/default/files/pandemic-preparedness-plan.pdf">want to be ready</a>.</p><img src="https://counter.theconversation.com/content/216139/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter Kasson receives funding from the National Institutes of Health, the National Science Foundation, the Commonwealth Health Research Board, and the Knut and Alice Wallenberg Foundation. He is affiliated with the University of Virginia, Uppsala University, and Georgia Institute of Technology.</span></em></p>Viruses can get into cells in several ways. Figuring out how to stop them from entering in the first place is a key to developing better vaccines and stopping future pandemics.Peter Kasson, Professor of Molecular Physiology and Biomedical Engineering, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2146222023-10-12T12:31:00Z2023-10-12T12:31:00ZHorseshoe crab blood is vital for testing intravenous drugs, but new synthetic alternatives could mean pharma won’t bleed this unique species dry<figure><img src="https://images.theconversation.com/files/552874/original/file-20231010-19-onfdw4.jpg?ixlib=rb-1.1.0&rect=33%2C8%2C5579%2C3728&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Horseshoe crabs in spawning season at Reeds Beach, N.J., on June 13, 2023.</span> <span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/HorseshoeCrabHarvest/053d4f924f9c453f808a4d3724a87e73/photo">AP Photo/Matt Rourke</a></span></figcaption></figure><p>If you have ever gotten a vaccine or received an intravenous drug and did not come down with a potentially life-threatening fever, you can thank a horseshoe crab (<em>Limulus polyphemus</em>).</p>
<p>How can animals that are <a href="https://www.britannica.com/animal/horseshoe-crab">often called living fossils</a>, because they have barely changed over millions of years, be so important in modern medicine? Horseshoe crab blood is used to produce a substance called limulus amebocyte lysate, or LAL, which scientists use to test for <a href="https://www.britannica.com/science/endotoxin">toxic substances called endotoxins</a> in intravenous drugs. </p>
<p>These toxins, produced by bacteria, are ubiquitous in the environment and can’t be removed simply through sterilization. They can cause a reaction historically referred to as “<a href="https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-technical-guides/pyrogens-still-danger">injection fever</a>.” A strong concentration can lead to shock and even death. </p>
<p>Identifying LAL as a highly sensitive detector of endotoxins was a 20th-century medical safety breakthrough. Now, however, critics are raising questions about environmental impacts and the process for reviewing and approving synthetic alternatives to horseshoe crab blood.</p>
<p>We study <a href="https://scholar.google.com/citations?user=Dd_T980AAAAJ&hl=en&authuser=1&oi=ao">science, technology</a> and <a href="https://www.linkedin.com/in/jolie-crunelle/%20student">public policy</a>, and recently published a <a href="https://osf.io/3tm9g/">white paper</a> examining social, political and economic issues associated with using horseshoe crabs to produce LAL. We see this issue as a test case for complicated problems that cut across multiple agencies and require attention to both nature and human health.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/CgRn3T7vcMw?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Protecting horseshoe crabs will require persuading the heavily regulated pharmaceutical industry to embrace change.</span></figcaption>
</figure>
<h2>An ocean solution</h2>
<p>Doctors began injecting patients with various solutions <a href="https://doi.org/10.1016/j.socscimed.2004.06.044">in the mid-1800s</a>, but it was not until the 1920s that biochemist <a href="https://lemelson.mit.edu/resources/florence-seibert">Florence Seibert</a> discovered that febrile reactions were due to contaminated water in these solutions. She created a method for detecting and removing the substances that caused this reaction, and it became the medical standard in the 1940s.</p>
<p>Known as the <a href="https://www.matresearch.com/pyrogen-testing/">rabbit pyrogen test</a>, it required scientists to inject intravenous drugs into rabbits, then monitor the animals. A feverish rabbit meant that a batch of drugs was contaminated.</p>
<p>The LAL method was discovered by accident. Working with horseshoe crabs at the <a href="https://www.mbl.edu/">Marine Biological Laboratory</a> at Woods Hole, Massachusetts, in the 1950s and ’60s, <a href="https://www.goldengooseaward.org/01awardees/horseshoe-crab-blood">pathobiologist Frederik Bang and medical researcher Jack Levin</a> noticed that the animals’ <a href="https://hub.jhu.edu/magazine/2021/summer/horseshoe-crabs-covid19-medical-uses/">blue blood</a> coagulated in a curious manner. Through a series of experiments, they isolated endotoxin as the coagulant and devised a method for extracting LAL from the blood. This compound would gel or clot nearly instantaneously in the presence of fever-inducing toxins.</p>
<p>Academic researchers, biomedical companies and the U.S. Food and Drug Administration refined LAL production and measured it against the rabbit test. By the 1990s, LAL was the <a href="https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-technical-guides/bacterial-endotoxinspyrogens">FDA-approved method</a> for testing medicines for endotoxin, largely replacing rabbits.</p>
<p>Producing LAL requires harvesting horseshoe crabs from oceans and beaches, <a href="https://www.theatlantic.com/technology/archive/2014/02/the-blood-harvest/284078/">draining up to 30% of their blood</a> in a laboratory and returning the live crabs to the ocean. There’s dispute about <a href="https://www.scientificamerican.com/article/medical-labs-may-be-killing-horseshoe-crabs/">how many crabs die in the process</a> – estimates range from a few percent to 30% or more – and about possible harmful effects on survivors. </p>
<p>Today there are five FDA-licensed <a href="https://asmfc.org/uploads/file/645bf065HSC_Biomedical_BMPs_2023.pdf">LAL producers</a> along the U.S. East Coast. The amount of LAL they produce, and its sales value, are proprietary. </p>
<h2>Bait versus biotech</h2>
<p>As biomedical LAL production ramped up in the 1990s, so did harvesting horseshoe crabs to use as bait for other species, particularly eel and whelk for foreign seafood markets. Over the past 25 years, hundreds of thousands – and in the early years, millions – of horseshoe crabs have been harvested each year for these purposes. Combined, the two fisheries kill <a href="https://asmfc.org/species/horseshoe-crab">over half a million</a> horseshoe crabs every year.</p>
<p>There’s no agreed total population estimate for <em>Limulus</em>, but the most recent <a href="https://asmfc.org/uploads/file/63d2ed62HSCAssessment_PeerReviewReport_May2019.pdf">federal assessment of horseshoe crab fisheries</a> found the population was neither strongly growing nor declining.</p>
<p>Conservationists are worried, and not just about the crabs. Millions of shorebirds <a href="https://atlanticflywayshorebirds.org/">migrate along the Atlantic coast</a>, and many stop in spring, when horseshoe crabs spawn on mid-Atlantic beaches, to feed on the crabs’ eggs. Particularly for <a href="https://www.allaboutbirds.org/guide/Red_Knot/overview">red knots</a> – a species that can migrate up to 9,000 miles between the tip of South America and the Canadian Arctic – gorging on horseshoe crab eggs provides a critical energy-rich boost on their grueling journey.</p>
<p>Red knots were <a href="https://www.federalregister.gov/documents/2014/12/11/2014-28338/endangered-and-threatened-wildlife-and-plants-threatened-species-status-for-the-rufa-red-knot">listed as threatened</a> under the Endangered Species Act in 2015, largely because horseshoe crab fishing threatened this key food source. As biomedical crab harvests came to equal or <a href="https://asmfc.org/species/horseshoe-crab">surpass bait harvests</a>, conservation groups began calling on the LAL industry to find new sources.</p>
<p><div data-react-class="InstagramEmbed" data-react-props="{"url":"https://www.instagram.com/p/Ct2Aji4xcPJ/?utm_source=ig_web_copy_link\u0026igshid=MzRlODBiNWFlZA==","accessToken":"127105130696839|b4b75090c9688d81dfd245afe6052f20"}"></div></p>
<h2>Biomedical alternatives</h2>
<p>Many important medicines are derived from living organisms. Penicillin, the first important antibiotic, was <a href="https://www.sciencemuseum.org.uk/objects-and-stories/how-was-penicillin-developed">originally produced from molds</a>. Other medicines currently in use come from sources including <a href="https://www.goodrx.com/well-being/diet-nutrition/medications-that-contain-animal-byproducts">cows, pigs, chickens and fish</a>. The ocean is a <a href="https://oceanexplorer.noaa.gov/facts/medicinesfromsea.html">promising source</a> for such products.</p>
<p>When possible, synthesizing these substances in laboratories – especially widely used medications like <a href="https://www.cityofhope.org/breakthroughs/art-riggs-tribute">insulin</a> – offers many benefits. It’s typically cheaper and more efficient, and it avoids putting species at risk, as well as addressing <a href="https://www.uspharmacist.com/article/animal-derived-medications-can-be-problematic-for-some-patients">concerns some patients have</a> about using animal-derived medical products.</p>
<p>In the 1990s, researchers at the National University of Singapore <a href="https://patents.google.com/patent/WO1999015676A1/en?inventor=Jeak+Ling+Ding">invented and patented</a> the first process for creating a synthetic, endotoxin-detecting compound using horseshoe crab DNA and <a href="https://www.genome.gov/genetics-glossary/Recombinant-DNA-Technology">recombinant DNA technology</a>. The result, dubbed recombinant Factor C (rFC), mimicked the first step in the three-part cascade reaction that occurs when LAL is exposed to endotoxin. </p>
<p>Later, several biomedical firms <a href="https://www.americanpharmaceuticalreview.com/Featured-Articles/569887-Historical-Milestones-and-Industry-Drivers-in-the-Development-of-Recombinant-Lysate-for-Bacterial-Endotoxin-Testing/">produced their own versions</a> of rFC and compounds called recombinant cascade reagents (rCRs), which reproduce the entire LAL reaction without using horseshoe crab blood. Yet, today, LAL remains the dominant technology for detecting endotoxins in medicine. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A vial partly filled with pale blue fluid" src="https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A sample of horseshoe crab blood.</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/riAZsU">Florida Fish and Wildlife Commission</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>The main reason is that the <a href="https://www.usp.org/">U.S. Pharmacopeia</a>, a quasi-regulatory organization that sets safety standards for medical products, considers rFC and rCR as “alternative” methods for detecting endotoxins, so they require case-by-case validation for use – a potentially lengthy and expensive process. The FDA generally defers to the U.S. Pharmacopeia.</p>
<p>A few large pharmaceutical companies with deep pockets have committed to <a href="https://www.esg.lilly.com/environmental/biodiversity?redirect-referrer=https%3A%2F%2Fwww.google.com%2F#case-studies">switching from LAL to rFC</a>. But most drug producers are sticking with the tried-and-true method. </p>
<p>Conservation groups want the U.S. Pharmacopeia to <a href="https://www.audubon.org/magazine/summer-2018/inside-biomedical-revolution-save-horseshoe-crabs">fully certify rFC</a> for use in industry with no extra testing or validation. In their view, LAL producers are stalling rFC and rCR approval to protect their <a href="https://www.npr.org/2023/06/10/1180761446/coastal-biomedical-labs-are-bleeding-more-horseshoe-crabs-with-little-accountabi">market in endotoxin detection</a>. The U.S. Pharmacopeia and LAL producers counter that they are doing due diligence to <a href="https://hsc.criver.com/#lal-endo">protect public health</a>.</p>
<h2>Change in the offing</h2>
<p>Change may be coming. All major LAL producers now have their own recombinant products – a tacit acknowledgment that markets and regulations are moving toward <em>Limulus</em>-free ways to test for endotoxins. </p>
<p>Atlantic fisheries regulators are currently considering <a href="https://www.asmfc.org/home/2023-annual-meeting">new harvest limits for horseshoe crabs</a>, and the U.S. Pharmacopeia is <a href="https://www.uspnf.com/notices/86-bet-using-recombinant-tests-gen-annc-20230822">weighing guidance</a> on recombinant alternatives to LAL. Public comments will be solicited over the winter of 2024, followed by U.S. Pharmacopeia and FDA review. </p>
<p>Even if rFC and rCR don’t win immediate approval, we believe that collecting more complete data on horseshoe crab populations and requiring more transparency from the LAL industry on <a href="https://asmfc.org/uploads/file/645bf065HSC_Biomedical_BMPs_2023.pdf">how it handles the crabs</a> would represent progress. So would directing medical companies to use recombinant products for testing during the manufacturing process, while saving LAL solely for final product testing. </p>
<p>Making policy on complex scientific issues across diverse agencies is never easy. But in our view, incremental actions that protect both human health and the environment could be important steps forward.</p><img src="https://counter.theconversation.com/content/214622/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>This material is based upon work supported by the National Science Foundation under Award No. 2121146, as well as the Leverhulme Trust through a Leverhulme Trust Research Project Grant. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation or the Leverhulme Trust.</span></em></p><p class="fine-print"><em><span>Jolie Crunelle receives funding from the Aberg Family Fellowship at Rochester Institute of Technology. </span></em></p>Horseshoe crabs play a unique role in medicine, but they’re also ecologically important in their home waters along the Atlantic coast. Can regulators balance the needs of humans and nature?Kristoffer Whitney, Associate Professor of Science, Technology and Society, Rochester Institute of TechnologyJolie Crunelle, Master's Degree Student in Science, Technology, and Public Policy, Rochester Institute of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2125952023-10-04T12:33:20Z2023-10-04T12:33:20ZCell death is essential to your health − an immunologist explains when cells decide to die with a bang or take their quiet leave<figure><img src="https://images.theconversation.com/files/550723/original/file-20230927-27-m1brzw.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1732%2C1732&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Programmed cell death such as apoptosis is a common stage of cellular life.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/cell-udergoing-lysis-process-illustration-royalty-free-illustration/1414392472">Nanoclustering/Science Photo Library via Getty Images</a></span></figcaption></figure><p>Living cells work better than dying cells, right? However, this is not always the case: your cells often <a href="https://nigms.nih.gov/education/Inside-Life-Science/Pages/Cellular-Suicide-An-Essential-Part-of-Life.aspx">sacrifice themselves to keep you healthy</a>. The unsung hero of life is death.</p>
<p>While death may seem passive, an unfortunate ending that just “happens,” the death of your cells is often extremely purposeful and strategic. The intricate details of how and why cells die can have significant effects on your overall health. </p>
<p>There are over 10 different ways cells can “decide” to die, each serving a particular purpose for the organism. <a href="https://scholar.google.com/citations?hl=en&user=XokicmoAAAAJ">My own research</a> explores how immune cells switch between different types of programmed death in scenarios like cancer or injury.</p>
<p>Programmed cell death can be broadly <a href="https://www.the-scientist.com/sponsored-article/programmed-cell-death-mechanisms-for-cellular-self-destruction-70955">divided into two types</a> that are crucial to health: silent and inflammatory. </p>
<h2>Quietly exiting: silent cell death</h2>
<p>Cells can often become damaged because of age, stress or injury, and these abnormal cells <a href="https://theconversation.com/cells-become-zombies-when-the-ends-of-their-chromosomes-are-damaged-a-tactic-both-helpful-and-harmful-for-health-186445">can make you sick</a>. Your body runs a tight ship, and when cells step out of line, they must be quietly eliminated before they overgrow into tumors or cause <a href="https://theconversation.com/what-is-inflammation-two-immunologists-explain-how-the-body-responds-to-everything-from-stings-to-vaccination-and-why-it-sometimes-goes-wrong-193503">unnecessary inflammation</a> where your immune system is activated and causes fever, swelling, redness and pain. </p>
<p>Your body <a href="https://doi.org/10.1016%2Fj.it.2017.06.009">swaps out cells every day</a> to ensure that your tissues are made up of healthy, functioning ones. The parts of your body that are more likely to see damage, like your skin and gut, turn over cells weekly, while other cell types can take months to years to recycle. Regardless of the timeline, the death of old and damaged cells and their replacement with new cells is a normal and important bodily process.</p>
<p><a href="https://www.genome.gov/genetics-glossary/apoptosis">Silent cell death, or apoptosis</a>, is described as silent because these cells die without causing an inflammatory reaction. Apoptosis is an active process involving many proteins and switches within the cell. It’s designed to strategically eliminate cells without alarming the rest of the body.</p>
<p>Sometimes cells can detect that their own functions are failing and <a href="https://doi.org/10.1101%2Fcshperspect.a008656">turn on executioner proteins</a> that chop up their own DNA, and they quietly die by apoptosis. Alternatively, healthy cells can order overactive or damaged neighbor cells to activate their executioner proteins. </p>
<p>Apoptosis is important to maintaining a healthy body. In fact, you can thank apoptosis for your <a href="https://embryo.asu.edu/pages/apoptosis-embryonic-development">fingers and toes</a>. Fetuses initially have webbed fingers until the cells that form the tissue between them undergo apoptosis and die off. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/550728/original/file-20230927-15-kh9avn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of mouse foot at embryonic stage" src="https://images.theconversation.com/files/550728/original/file-20230927-15-kh9avn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/550728/original/file-20230927-15-kh9avn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=904&fit=crop&dpr=1 600w, https://images.theconversation.com/files/550728/original/file-20230927-15-kh9avn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=904&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/550728/original/file-20230927-15-kh9avn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=904&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/550728/original/file-20230927-15-kh9avn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1135&fit=crop&dpr=1 754w, https://images.theconversation.com/files/550728/original/file-20230927-15-kh9avn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1135&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/550728/original/file-20230927-15-kh9avn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1135&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The toes of this embryonic mouse foot are forming through apoptosis.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Embryonic_foot_of_mouse.jpg">Michal Maňas/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Without apoptosis, cells can grow out of control. A well-studied example of this is cancer. Cancer cells are abnormally good at growing and dividing, and those that can <a href="https://www.mskcc.org/news/what-apoptosis">resist apoptosis</a> form very aggressive tumors. Understanding how apoptosis works and why cancer cells can disrupt it can potentially improve cancer treatments. </p>
<p>Other conditions can benefit from apoptosis research as well. Your body makes a lot of immune cells that all respond to different targets, and occasionally one of these cells can accidentally target your own tissues. Apoptosis is a crucial way your body can eliminate these immune cells before they cause unnecessary damage. When apoptosis fails to eliminate these cells, sometimes because of genetic abnormalities, this can lead to <a href="https://doi.org/10.5772/48164">autoimmune diseases</a> like lupus.</p>
<p>Another example of the role apoptosis plays in health is <a href="https://medlineplus.gov/endometriosis.html">endometriosis</a>, an understudied disease caused by the overgrowth of tissue in the uterus. It can be extremely painful and debilitating for patients. Researchers have recently linked this <a href="https://doi.org/10.1210/endocr/bqad057">out-of-control growth in the uterus</a> to dysfunctional apoptosis. </p>
<p>Whether it’s for development or maintenance, your cells are quietly exiting to keep your body happy and healthy.</p>
<h2>Going out with a bang: inflammatory cell death</h2>
<p>Sometimes, it is in your body’s best interest for cells to raise an alarm as they die. This can be beneficial when cells detect the presence of an infection and need to eliminate themselves as a target while also alerting the rest of the body. This <a href="https://sitn.hms.harvard.edu/flash/2021/when-cells-die-a-fiery-death-pyroptosis-as-a-cells-response-to-damage-and-infection/">inflammatory cell death</a> is typically triggered by bacteria, viruses or stress.</p>
<p>Rather than quietly shutting down, cells undergoing inflammatory cell death will make themselves burst, or lyse, killing themselves and exploding inflammatory messengers as they go. These messengers tell your immune cells that there is a threat and prompts them to treat and fight the pathogen.</p>
<p>An inflammatory death would not be healthy for maintenance. If the normal recycling of your skin or gut cells caused an inflammatory reaction, you would feel sick a lot. This is why inflammatory death is <a href="https://doi.org/10.3390%2Fijms21041456">tightly controlled</a> and requires multiple signals to initiate. </p>
<p>Despite the riskiness of this grenadelike death, many infections would be impossible to fight without it. Many bacteria and viruses need to live around or inside your cells to survive. When specialized sensors on your cells detect these threats, they can simultaneously activate your immune system and remove themselves as a home for pathogens. Researchers call this <a href="https://cshperspectives.cshlp.org/content/12/2/a036459.full">eliminating the niche</a> of the pathogen.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/oRmbWj2ZITM?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Cells die in many ways, including lysis.</span></figcaption>
</figure>
<p>Inflammatory cell death plays a major role in pandemics. <a href="https://doi.org/10.1101/cshperspect.a036459"><em>Yersinia pestis</em></a>, the bacteria behind the Black Death, has evolved various ways of stopping human immune cells from mounting a response. However, immune cells developed the ability to sense this trickery and die an inflammatory death. This ensures that additional immune cells will infiltrate and eliminate the bacteria despite the bacteria’s best attempts to prevent a fight. </p>
<p>Although the Black Death is not as common nowadays, close relatives <em>Yersinia pseudotuberculosis</em> and <em>Yersinia enterocolitica</em> are behind outbreaks of <a href="https://edis.ifas.ufl.edu/publication/FS193">food-borne illnesses</a>. These infections are rarely fatal because your immune cells can aggressively eliminate the pathogen’s niche by inducing inflammatory cell death. For this reason, however, <em>Yersinia</em> infection can be more dangerous in immunocompromised people.</p>
<p>The <a href="https://doi.org/10.1016/j.it.2020.10.005">virus behind the COVID-19 pandemic</a> also causes a lot of inflammatory cell death. Studies show that without cell death the virus would freely live inside your cells and multiply. However, this inflammatory cell death can sometimes get out of control and <a href="https://theconversation.com/long-covid-19-and-other-chronic-respiratory-conditions-after-viral-infections-may-stem-from-an-overactive-immune-response-in-the-lungs-186970">contribute to the lung damage</a> seen in COVID-19 patients, which can greatly affect survival. Researchers are still studying the role of inflammatory cell death in COVID-19 infection, and understanding this delicate balance can help improve treatments. </p>
<p>In good times and bad, your cells are always ready to sacrifice themselves to keep you healthy. You can thank cell death for keeping you alive.</p><img src="https://counter.theconversation.com/content/212595/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Zoie Magri does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Your cells die to keep you alive. Cell death does everything from fighting cancer cells and pathogens to forming your fingers and toes.Zoie Magri, Ph.D. Candidate in Immunology, Tufts UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2136212023-09-25T12:21:07Z2023-09-25T12:21:07ZFlesh-eating bacteria infections are on the rise in the US − a microbiologist explains how to protect yourself<figure><img src="https://images.theconversation.com/files/549431/original/file-20230920-17-vywy11.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1576%2C1080&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">_Vibrio vulnificus_ infections are spreading across the U.S. because of climate change.</span> <span class="attribution"><a class="source" href="https://phil.cdc.gov/Details.aspx?pid=7812">CDC/Janice Haney Carr</a></span></figcaption></figure><p>Flesh-eating bacteria sounds like the premise of a bad horror movie, but it’s a growing – and potentially fatal – threat to people.</p>
<p>In September 2023, the Centers for Disease Control and Prevention <a href="https://emergency.cdc.gov/han/2023/han00497.asp">issued a health advisory</a> alerting doctors and public health officials of an increase in flesh-eating bacteria cases that can cause serious wound infections. </p>
<p><a href="https://medicine.iu.edu/faculty/13502/sullivan-william">I’m a professor</a> at the Indiana University School of Medicine, where <a href="https://www.sullivanlab.com/">my laboratory</a> studies <a href="https://scholar.google.com/citations?user=mN6ZaFkAAAAJ&hl=en">microbiology and infectious disease</a>. Here’s why the CDC is so concerned about this deadly infection – and ways to avoid contracting it.</p>
<h2>What does ‘flesh-eating’ mean?</h2>
<p>There are several types of bacteria that can infect open wounds and cause a rare condition called <a href="https://doi.org/10.1097%2F01.NURSE.0000694752.85118.62">necrotizing fasciitis</a>. These bacteria do not merely damage the surface of the skin – they release toxins that destroy the underlying tissue, including muscles, nerves and blood vessels. Once the bacteria reach the bloodstream, they gain ready access to additional tissues and organ systems. If left untreated, necrotizing fasciitis can be fatal, sometimes within 48 hours.</p>
<p>The bacterial species <a href="https://www.cdc.gov/groupastrep/index.html">group A <em>Streptococcus</em></a>, or group A strep, is the most common culprit behind necrotizing fasciitis. But the CDC’s latest warning points to an additional suspect, a type of bacteria called <a href="https://www.cdc.gov/vibrio/wounds.html"><em>Vibrio vulnificus</em></a>. There are only <a href="https://emergency.cdc.gov/han/2023/han00497.asp">150 to 200 cases</a> of <em>Vibrio vulnificus</em> in the U.S. each year, but the mortality rate is high, with 1 in 5 people succumbing to the infection.</p>
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<figcaption><span class="caption">Climate change may be driving the rise in flesh-eating bacteria infections in the U.S.</span></figcaption>
</figure>
<h2>How do you catch flesh-eating bacteria?</h2>
<p><em>Vibrio vulnificus</em> primarily lives in warm seawater but can also be found in brackish water – areas where the ocean mixes with freshwater. Most infections in the U.S. occur in the <a href="https://doi.org/10.1001/jama.2023.0174">warmer months, between May and October</a>. People who swim, fish or wade in these bodies of water can contract the bacteria through an open wound or sore.</p>
<p><em>Vibrio vulnificus</em> can also get into seafood harvested from these waters, especially shellfish like oysters. Eating such foods raw or undercooked can lead to <a href="https://www.cdc.gov/vibrio/food.html">food poisoning</a>, and handling them while having an open wound can provide an entry point for the bacteria to cause necrotizing fasciitis. In the U.S., <em>Vibrio vulnificus</em> is a leading cause of <a href="https://doi.org/10.3389/fmicb.2017.00997">seafood-associated fatality</a>.</p>
<h2>Why are flesh-eating bacteria infections rising?</h2>
<p><em>Vibrio vulnificus</em> is found in warm coastal waters around the world. In the U.S., this includes southern Gulf Coast states. But rising ocean temperatures due to global warming are creating new habitats for this type of bacteria, which can now be found along the East Coast as far north as <a href="https://emergency.cdc.gov/han/2023/han00497.asp">New York and Connecticut</a>. A <a href="https://doi.org/10.1038/s41598-023-28247-2">recent study</a> noted that <em>Vibrio vulnificus</em> wound infections increased eightfold between 1988 and 2018 in the eastern U.S. </p>
<p><a href="https://www.pbs.org/newshour/health/flesh-eating-bacteria-on-the-rise-in-florida-following-hurricane-ian">Climate change</a> is also fueling stronger hurricanes and storm surges, which have been associated with spikes in flesh-eating bacteria infection cases.</p>
<p>Aside from increasing water temperatures, the number of people who are <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762295/">most vulnerable to severe infection</a>, including those <a href="https://theconversation.com/global-diabetes-cases-on-pace-to-soar-to-1-3-billion-people-in-the-next-3-decades-new-study-finds-208832">with diabetes</a> and those taking medications that suppress immunity, is on the rise.</p>
<h2>What are symptoms of necrotizing fasciitis? How is it treated?</h2>
<p><a href="https://www.cdc.gov/groupastrep/diseases-public/necrotizing-fasciitis.html#symptoms">Early symptoms</a> of an infected wound include fever, redness, intense pain or swelling at the site of injury. If you have these symptoms, seek medical attention without delay. Necrotizing fasciitis can <a href="https://www.cdc.gov/groupastrep/diseases-public/necrotizing-fasciitis.html#symptoms">progress quickly</a>, producing ulcers, blisters, skin discoloration and pus.</p>
<p><a href="https://www.cdc.gov/groupastrep/diseases-public/necrotizing-fasciitis.html">Treating flesh-eating bacteria</a> is a race against time. Clinicians administer antibiotics directly into the bloodstream to kill the bacteria. In many cases, damaged tissue needs to be surgically removed to stop the rapid spread of the infection. This sometimes <a href="https://pubmed.ncbi.nlm.nih.gov/33623768/">results in amputation</a> of affected limbs.</p>
<p>Researchers are concerned that an increasing number of cases are becoming impossible to treat because <em>Vibrio vulnificus</em> has evolved <a href="https://doi.org/10.3389/fmicb.2017.00997">resistance to certain antibiotics</a>.</p>
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<figcaption><span class="caption">Necrotizing fasciitis is rare but deadly.</span></figcaption>
</figure>
<h2>How do I protect myself?</h2>
<p>The CDC offers several recommendations to help <a href="https://www.cdc.gov/vibrio/wounds.html">prevent infection</a>. </p>
<p>People who have a fresh cut, including a new piercing or tattoo, are advised to stay out of water that could be home to <em>Vibrio vulnificus</em>. Otherwise, the wound should be completely covered with a waterproof bandage. </p>
<p>People with an open wound should also avoid handling raw seafood or fish. Wounds that occur while fishing, preparing seafood or swimming should be washed immediately and thoroughly with soap and water.</p>
<p>Anyone can contract necrotizing fasciitis, but people with weakened immune systems are <a href="https://doi.org/10.1001/jama.2023.0174">most susceptible to severe disease</a>. This includes people taking immunosuppressive medications or those who have pre-existing conditions such as liver disease, cancer, HIV or diabetes.</p>
<p>It is important to bear in mind that necrotizing fasciitis presently <a href="https://doi.org/10.1097%2F01.NURSE.0000694752.85118.62">remains very rare</a>. But given its severity, it is beneficial to stay informed.</p><img src="https://counter.theconversation.com/content/213621/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bill Sullivan receives funding from the National Institutes of Health.</span></em></p>Warmer ocean waters are fueling the spread of the bacteria Vibrio vulnificus. Infections can lead to a rare but fatal condition called necrotizing fasciitis.Bill Sullivan, Professor of Pharmacology & Toxicology, Indiana UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2129552023-09-17T12:07:36Z2023-09-17T12:07:36ZWhat Canadians need to know about West Nile virus, a mosquito-borne infection that can be life-threatening<iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/what-canadians-need-to-know-about-west-nile-virus-a-mosquito-borne-infection-that-can-be-life-threatening" width="100%" height="400"></iframe>
<p>During the late summer of 1999, New York City recorded an <a href="https://doi.org/10.2105%2Fajph.92.8.1218">unusual number of cases of encephalitis</a> (inflammation of the brain). At the same time, the <a href="https://www.nationalgeographic.com/science/article/west-nile-virus-the-stranger-that-came-to-stay">Bronx Zoo</a> reported a massive death of birds and mammals. </p>
<p>The human encephalitis cases might have been attributed to a flare-up of an endemic arbovirus (<a href="https://ndc.services.cdc.gov/case-definitions/arboviral-diseases-neuroinvasive-and-non-neuroinvasive-2015/">a virus transmitted by a tick or mosquito bite</a>) such as <a href="https://www.cdc.gov/sle/index.html">St. Louis encephalitis</a>, but the concurrent bird and mammal deaths suggested the human illnesses warranted further investigation. </p>
<p>Scientists eventually identified these as the first confirmed cases of West Nile virus (WNV) in North America.</p>
<h2>West Nile virus in North America</h2>
<p>WNV was first reported in a woman with a fever in Uganda in 1937. An <a href="https://doi.org/10.2214/ajr.184.3.01840957">outbreak in Israel in 1957</a> established WNV as a cause of <a href="https://doi.org/10.3201/eid0704.017416">severe meningoencephalitis</a> (inflammation of the spinal cord and brain) in elderly patients. </p>
<p>Several clusters or medium-range outbreaks were reported from Asia, Europe and Africa in the 20th century. Finally, the virus managed to cross the Atlantic and landed in North America in 1999.</p>
<figure class="align-center ">
<img alt="Round blue particles nestled in a red matrix" src="https://images.theconversation.com/files/548213/original/file-20230914-19-x6rm98.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/548213/original/file-20230914-19-x6rm98.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=454&fit=crop&dpr=1 600w, https://images.theconversation.com/files/548213/original/file-20230914-19-x6rm98.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=454&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/548213/original/file-20230914-19-x6rm98.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=454&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/548213/original/file-20230914-19-x6rm98.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=570&fit=crop&dpr=1 754w, https://images.theconversation.com/files/548213/original/file-20230914-19-x6rm98.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=570&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/548213/original/file-20230914-19-x6rm98.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=570&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Microscopic view of West Nile virus particles in a cell.</span>
<span class="attribution"><span class="source">(NIAID)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>In 1999, the <a href="https://www.cdc.gov/westnile/statsmaps/historic-data.html">case number</a> was limited to 62 in New York City, and there was concern about a huge surge in 2000. Fortunately, the case number in 2000 was 21, which is exceedingly low, but it had spread to New Jersey and Connecticut. The case number remained in a similar low range (only 66 cases) in 2001. </p>
<p>However, the virus hit hard the following year. In 2002, the case number rose to over 4,000 in the United States. The same year, <a href="https://www.canada.ca/en/public-health/services/diseases/west-nile-virus/surveillance-west-nile-virus.html">Canada experienced its first cases</a> in Ontario.</p>
<p>The U.S. has reported a <a href="https://www.cdc.gov/westnile/statsmaps/historic-data.html">cumulative total</a> of 56,569 cases and 2,773 deaths, while <a href="https://www.canada.ca/en/public-health/services/diseases/west-nile-virus/surveillance-west-nile-virus.html#a1">Canada has reported 6,683 cases</a> and about 150 deaths (I’m told by the Centre for Food-borne, Environmental & Zoonotic Infectious Diseases, Public Health Agency of Canada), with the highest number of cases observed in the U.S. in 2003 and in Canada in 2007.</p>
<p>This virus spread across the entire continent very quickly, and covered most of North America by 2005. However, it took almost 10 years for the virus to <a href="https://doi.org/10.1089/vbz.2010.0062">show up in British Columbia</a>. In Canada, most of the cases were found in the Prairie region (Alberta, Saskatchewan and Manitoba). <a href="https://www.cdc.gov/westnile/statsmaps/historic-data.html">In the U.S.</a>, Midwestern states have been most affected.</p>
<p>West Nile virus is an RNA virus, a close cousin of <a href="https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue">Dengue</a>, <a href="http://www.bccdc.ca/health-info/diseases-conditions/yellow-fever">Yellow fever</a>, St. Louis encephalitis and <a href="http://www.bccdc.ca/health-info/diseases-conditions/zika-virus">Zika virus</a>, to name a few. It belongs to the family Flaviviridae. </p>
<h2>Symptoms and transmission</h2>
<p><a href="https://www.cdc.gov/westnile/symptoms/index.html">Approximately 80 per cent of people</a> exposed to WNV are asymptomatic. <a href="https://doi.org/10.14745/ccdr.v40i10a01">The incubation period</a> in humans is about a week; however, this ranges from two to 15 days after the virus enters the body.</p>
<p>Among symptomatic individuals, all of them experience fever, and many also experience headaches, body aches, a mild rash and swollen lymph glands to varying degrees. </p>
<p>Although most cases go unnoticed, the virus still has deadly potential. <a href="https://nccid.ca/debrief/west-nile-virus/">A small number of people</a> (around one per cent) experience severe symptoms, including encephalitis. However, over the years, the <a href="https://doi.org/10.1038/ncpneuro0176">number of neurological cases has been increasing</a>.</p>
<p>This virus is mostly <a href="https://www.who.int/news-room/fact-sheets/detail/west-nile-virus">transmitted via mosquito bites</a>; however, very rarely it could transmit via blood transfusion, organ or tissue transplants, from mother to unborn babies and through exposure to infected animals. </p>
<p>A number of birds, predominantly corvids such as crows, jays and magpies, act as reservoirs as well as <a href="https://www.biologyonline.com/dictionary/amplifier-host">amplifying hosts</a>. When an uninfected mosquito feeds on an infected bird and then bites a healthy human, the human becomes infected. </p>
<p>Humans are considered dead-end hosts, meaning that even if a mosquito feeds on an infected individual, that mosquito cannot transmit the virus to another individual <a href="https://www.who.int/news-room/questions-and-answers/item/dengue-and-severe-dengue">as can happen with the dengue virus</a>.</p>
<p>Once people are severely infected with West Nile virus, they <a href="https://www.cdc.gov/westnile/symptoms/index.html">acquire longer immunity</a>. Older people are usually at high risk for severe infection due to underlying health conditions. People with diabetes and uncontrolled hypertension <a href="https://www.canada.ca/en/public-health/services/diseases/west-nile-virus/risks-west-nile-virus.html">have a greater risk</a> of developing severe neurological disease from the West Nile virus. </p>
<h2>Diagnosis</h2>
<p>Patients who become ill with a fever and severe headache within a few days of a mosquito bite should visit their family physician or any health-care facility.</p>
<p>Because WNV is closely related to other pathogens, diagnosis is often challenging.
Patient signs and symptoms, history of mosquito bites and laboratory tests are all important when assessing patients for possible infection with West Nile virus.</p>
<p>The most common <a href="https://www.publichealthontario.ca/en/Laboratory-Services/Test-Information-Index/West-Nile-Virus-Serology">laboratory test</a> is to detect antibodies against WNV in the blood. However, WNV antibodies cross-react with dengue, Zika or other flaviviruses, so if this test is positive, an additional test is required to confirm the diagnosis. </p>
<p>This additional test is called the Plaque Reduction Neutralization Test or PRNT for short. It requires a live virus, so it must be done in a containment level 3 (CL3) laboratory. </p>
<p>The laboratory can also diagnose viral RNA using molecular tests, but interestingly, the virus often disappears from the blood when people exhibit symptoms. For encephalitic patients, cerebrospinal fluid can be used to detect the virus using molecular methods such as a polymerase chain reaction (PCR) test.</p>
<h2>Preventive measures</h2>
<p>There is no human vaccine for the West Nile virus. The most important preventive measure to avoid West Nile virus infection is to avoid mosquito bites. This seems simple but is often very challenging. </p>
<figure class="align-center ">
<img alt="Close-up view of a mosquito held with tweezers" src="https://images.theconversation.com/files/548224/original/file-20230914-17-vsdb54.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/548224/original/file-20230914-17-vsdb54.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/548224/original/file-20230914-17-vsdb54.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/548224/original/file-20230914-17-vsdb54.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/548224/original/file-20230914-17-vsdb54.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/548224/original/file-20230914-17-vsdb54.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/548224/original/file-20230914-17-vsdb54.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">A Culex tarsalis mosquito, a species that can transmit West Nile virus to humans, and is found across Canada.</span>
<span class="attribution"><span class="source">(AP Photo/Rick Bowmer)</span></span>
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</figure>
<p>People should use common sense during outdoor and indoor activities. Mosquito bites can be prevented by using bug spray, wearing protective clothing and avoiding areas that may have mosquitoes during the times when the species is most active, typically dusk and dawn. </p>
<p>A few species of mosquitoes can transmit WNV to humans. Among these, two of the most common species — the Culex pipiens and Culex tarsalis — are found across Canada, and their habitat is <a href="https://ncceh.ca/resources/evidence-reviews/impacts-canadas-changing-climate-west-nile-virus-vectors">predicted to expand with climate change</a>. Mosquitoes not only transmit WNV, but also transmit <a href="https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/california-serogroup-pathogen-safety-data-sheet.html">California serogroup viruses</a>, which cause encephalitis, as well as <a href="https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/eastern-equine-encephalitis.html">eastern equine encephalitis</a> viruses. </p>
<p>There is also no specific treatment for West Nile virus; medical management is supportive. Patients with severe symptoms often require pain control for headaches and medication and rehydration to treat nausea and vomiting. </p>
<p><a href="https://www.canada.ca/en/public-health/services/diseases/west-nile-virus/surveillance-west-nile-virus/west-nile-virus-weekly-surveillance-monitoring.html">So far in 2023</a>, only a <a href="https://www.cbc.ca/news/canada/hamilton/hamilton-west-nile-virus-2023-1.6957260">few human cases</a> have been identified in Ontario. However, a few mosquito pools in Manitoba and Ontario also tested positive, and also a few WNV-positive birds were found in Saskatchewan, Manitoba, Ontario and Québec.</p>
<p>No matter how many cases we are seeing, everyone is advised to take precautions against mosquito bites to avoid these life-threatening diseases.</p><img src="https://counter.theconversation.com/content/212955/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Muhammad Morshed does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>West Nile virus arrived in North America in 1999 and spread across the continent by 2005. Here’s what you need to know about this mosquito-borne pathogen.Muhammad Morshed, Clinical Professor, Department of Pathology and Laboratory Medicine, University of British ColumbiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2102402023-09-11T12:34:57Z2023-09-11T12:34:57ZHow does fever help fight infections? There’s more to it than even some scientists realize<figure><img src="https://images.theconversation.com/files/547038/original/file-20230907-17-4s7zuu.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Being feverish is unpleasant, but it can help your body overcome invading pathogens.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/mother-measuring-the-temperature-of-her-ill-royalty-free-image/1458502274">Narisara Nami/Moment via Getty Images</a></span></figcaption></figure><p>When you’re <a href="https://doi.org/10.1038%2Fnri3843">sick with a fever</a>, your doctor will likely tell you it’s a sign that your immune system is defending you against an infection. Fever typically results from immune cells at infected sites sending chemical signals to the brain to raise the set point of your body’s thermostat. So, you <a href="https://youtu.be/jRvxnpfCDSo">feel chills</a> when the fever starts and feel hot when the fever breaks.</p>
<p>However, if you were to ask your doctor exactly how fever protects you, don’t expect a completely satisfactory answer.</p>
<p>Despite scientific consensus that fever is beneficial in fighting infections, exactly how is contentious. We are a <a href="https://scholar.google.com/citations?user=2o9r-L8AAAAJ&hl=en">veterinary pathologist</a> and an <a href="https://scholar.google.com/citations?user=RI7ng_YAAAAJ&hl=en">emergency physician</a> interested in <a href="https://isemph.org/what-is-evolutionary-medicine">applying evolutionary principles</a> to medical problems. The evolution of fever is a classic conundrum because fever’s effects seem so harmful. Besides making you feel uncomfortable, you may also worry you’ll dangerously overheat. It is also metabolically costly to generate that much heat. </p>
<p>In our research and review, we propose that since fever occurs throughout much of the animal kingdom, this costly response <a href="https://doi.org/10.1093/emph/eoaa044">must have benefits</a> or it never would have evolved or been retained across species over time. We highlight several important but rarely considered points that help explain how the heat of fever helps your body fight infections.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/jRvxnpfCDSo?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Fever is a physiological response that has persisted for hundreds of millions of years across species.</span></figcaption>
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<h2>How fever fights infection</h2>
<p>Infections are <a href="https://doi.org/10.1186%2Fs12915-017-0433-z">caused by pathogens</a>. Pathogens can be microbes such as certain species of bacteria, fungi or protozoans. If microbes or viruses have infected your cells and are using them to replicate, your own cells can also be considered pathogens and are treated that way by your immune system.</p>
<p>The main explanation for how fever helps control infections is that <a href="https://theconversation.com/normal-human-body-temperature-is-a-range-around-98-6-f-a-physiologist-explains-why-139270">higher temperatures</a> put heat-induced stress on pathogens, killing them or at least inhibiting their growth. But why would the somewhat higher body temperatures of fever – an increase of about 1.8 to 5.4 degrees Fahrenheit (<a href="https://doi.org/10.1038/nri3843">1 to 4 degrees Celsius</a>) – which can’t even kill your own healthy cells, harm such a wide variety of pathogens?</p>
<p>Immunologists have noted that slight heat <a href="https://doi.org/10.1038/nri3843">makes immune cells work better</a>. The implication is that fever is needed to enhance their defensive function. However, from an evolutionary perspective, it seems strange to require the massive energy cost of generating a fever just to get more activity from immune cells, especially since there are already plentiful and faster molecular signals available to activate them.</p>
<p>In addition to heat, <a href="https://doi.org/10.1186%2Far2632">slightly low oxygen levels</a> and <a href="https://doi.org/10.1155%2F2018%2F1218297">slight acidity</a> <a href="https://doi.org/10.1371/journal.ppat.1000282">also boost</a> immune cell function. Since these stressful conditions also occur at infected sites, it makes sense that immune cells evolved to have their maximum functionality match their stressful working conditions. In fact, since anything in a state of growth is inherently vulnerable to stress – and pathogens are typically growing – researchers, including one of us, have proposed that a function of immune cells is to actively <a href="https://doi.org/10.1098%2Frspb.2016.0266">make local conditions stressful</a> to preferentially harm the growing pathogens.</p>
<h2>Heating up pathogens locally</h2>
<p><a href="https://openstax.org/books/microbiology/pages/17-5-inflammation-and-fever">Inflammation</a> is a local defensive response to infection. It <a href="https://theconversation.com/what-is-inflammation-two-immunologists-explain-how-the-body-responds-to-everything-from-stings-to-vaccination-and-why-it-sometimes-goes-wrong-193503">typically involves</a> heat, pain, redness and swelling in the areas where the immune system is most active. While some scientists are aware that infected sites generate heat, many believe that the feeling of warmth from inflammation is only from dilated blood vessels bringing in warmer blood from core body tissues.</p>
<p>However, researchers have found that inflamed tissues, even in core body tissues, are up to 1.8 to 3.6 F (<a href="https://doi.org/10.1016/j.jacc.2005.11.050">1 to 2 C</a>) warmer than adjacent normal tissues, so warmth is not just a byproduct of more blood flow. Much of that extra heat is coming from the immune cells themselves. When they generate reactive oxygen species to kill pathogens in a process known as the respiratory burst, <a href="https://doi.org/10.1093/infdis/150.3.366">substantial heat</a> is also produced. To date, however, the temperatures involved have not been measured.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Over-the-shoulder view of someone holding a thermometer reading 38.5 degrees Celsius." src="https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Even an increase of a few degrees can affect how well your body kills pathogens.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/from-above-sick-lady-looking-at-thermometer-while-royalty-free-image/1393759427">Israel Sebastian/Moment via Getty Images</a></span>
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<p>While cells can tolerate a wide range of temperatures, all cells experience a sharp decline in their ability to grow and survive at higher temperatures. For mammalian cells, and presumably the pathogens that infect them, even a single degree or two above temperatures around 113 F (45 C) is <a href="https://doi.org/10.1016/S1040-8428(01)00179-2">almost always deadly</a>. So the heat of fever adds to already warmer local temperatures.</p>
<p>There is evidence that pathogens are exposed to temperatures that are much higher than the body temperature routinely measured with a thermometer in the emergency department. A 2018 study finding that local temperatures can be <a href="https://doi.org/10.1371/journal.pbio.2003992">as high as 122 F (50 C) in mitochondria</a> – the powerhouse of the cell – came as a <a href="https://doi.org/10.1371/journal.pbio.2005113">surprise to researchers</a>. The heat mitochondria generate is put to good use in warming the body and <a href="https://doi.org/10.1016/j.bbi.2020.11.031">for fever</a>. Likewise, we suggest that the local heat the respiratory burst produces at the surface of immune cells helps kill pathogens.</p>
<h2>Heat and other stressors</h2>
<p>Immune cells target pathogens with a <a href="https://doi.org/10.1155/2017/9671604">variety of stressors</a> meant to kill or inhibit them. These include reactive oxygen species, toxic peptides, digestive enzymes, high acidity and nutrient deprivation. Most chemical reactions are sped up by increased temperatures, so it isn’t surprising that heat enhances these defenses.</p>
<p>Researchers have shown heat to be <a href="https://pubmed.ncbi.nlm.nih.gov/34477/">synergistic with low oxygen and acidity</a> in killing pathogens. Notably, neither febrile temperatures nor iron restriction on their own were able to inhibit the growth of the infectious bacteria <a href="https://doi.org/10.1126/science.760197"><em>Pasteurella multocida</em></a>, but they could when combined. The stress of heat doesn’t act alone when controlling infections.</p>
<p>The standard view that the heat of fever kills pathogens and enhances immune responses is correct but incomplete. Fever’s ability to control infections comes from the few extra, but critical, degrees it adds to enhance existing locally generated heat to harm vulnerable growing pathogens. And fever also always acts with other defenses, never alone. </p>
<p>At <a href="https://doi.org/10.1038%2Fnri3843">over 600 million years old</a>, fever is an ancient feature of life on this planet that deserves respect. In fact, you owe it to infection-fighting heat that you are still here – alive – to read this. Something to think about the next time you’re sick.</p><img src="https://counter.theconversation.com/content/210240/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The heat and chills that come with fever are not only uncomfortable but also metabolically costly. Increased body temperature, however, can make all the difference when you’re sick.Edmund K. LeGrand, Adjunct Professor of Biomedical and Diagnostic Sciences, University of TennesseeJoe Alcock, Professor of Emergency Medicine, University of New MexicoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2108792023-08-02T22:51:06Z2023-08-02T22:51:06ZDoes picking your nose really increase your risk of COVID?<figure><img src="https://images.theconversation.com/files/540914/original/file-20230802-26619-e8ybza.jpg?ixlib=rb-1.1.0&rect=1%2C0%2C997%2C666&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/young-man-picking-his-nose-167161349">Shutterstock</a></span></figcaption></figure><p>Picking your nose is linked to an increased risk of COVID, according to a <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0288352">study</a> out today.</p>
<p>The study was conducted in health workers. This raises two main questions.</p>
<p>One, were these health workers <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588529/">washing</a> <a href="https://www.safetyandquality.gov.au/our-work/infection-prevention-and-control/national-hand-hygiene-initiative/what-hand-hygiene/5-moments-hand-hygiene">their hands</a> at work? Two, what does this study mean for the rest of us nose pickers? </p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/when-you-pick-your-nose-youre-jamming-germs-and-contaminants-up-there-too-3-scientists-on-how-to-deal-with-your-boogers-185052">When you pick your nose, you're jamming germs and contaminants up there too. 3 scientists on how to deal with your boogers</a>
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<h2>What did the study find?</h2>
<p>Some 219 Dutch health workers were monitored for COVID infection. They had regular antibody testing, which tells us if they had been exposed to SARS-CoV-2, the virus that causes COVID. They also reported the results of their own COVID tests.</p>
<p>Some 12-18 months later, the health workers were asked about their nose picking habits, and exposure to COVID via symptomatic workmates or from contacts outside work.</p>
<p>Just over 17% of health workers who reported picking their nose caught COVID versus about 6% of those who did not report nose picking.</p>
<p>At first glance, it might appear feasible that people who pick their noses would be at increased risk of contracting COVID.</p>
<p>That’s because COVID infection relies on the SARS-CoV-2 virus coming into contact with mucous membranes that line the respiratory system, including those in the nose. </p>
<p>So if someone touches a contaminated object or hand, then sticks their finger up their nose, this so-called fomite transmission can occur. </p>
<p>But the risk is comparatively low. The United States Centers for Disease Control <a href="https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/surface-transmission.html">estimates</a> about one in 10,000 contacts with a contaminated surface results in SARS-CoV-2 transmission.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/how-clean-is-your-hospital-room-to-reduce-the-spread-of-infections-it-could-probably-be-cleaner-122185">How clean is your hospital room? To reduce the spread of infections, it could probably be cleaner</a>
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<hr>
<h2>Hang on a minute</h2>
<p>But there are some odd results. For example, people who picked their noses only monthly had a higher chance of infection than daily nose pickers. Logically, you would expect the daily nose pickers to have a higher risk of infection due to more transmission opportunities.</p>
<p>There were also several aspects of how the study was designed that may have influenced the results.</p>
<p>Just over half of the people approached to participate in the study actually did so, which may cause <a href="https://www.iwh.on.ca/what-researchers-mean-by/selection-bias#">selection bias</a>. This is where people who choose to participate may differ in some key characteristic from those who don’t. These different characteristics can be “<a href="https://www.sciencedirect.com/topics/nursing-and-health-professions/confounding-variable">confounders</a>” that influence the results.</p>
<p>This was a cohort study, which followed a defined group of people for a set time and asked them questions about their habits and exposure. This study design may also be subject to bias.</p>
<p>That’s because people tend to answer in ways that are <a href="https://www.ajan.com.au/archive/Vol25/Vol_25-4_vandeMortel.pdf">socially desirable</a>, even in anonymous surveys. They tend to under-report behaviours seen as socially unacceptable (such as binge drinking); they over-report those that are socially acceptable.</p>
<p>This study did not control for this type of bias. So we cannot say for certain if someone’s report of whether and how often they picked their nose is a true reflection of what actually happened.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/540705/original/file-20230802-17-b2qkwo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Health worker wearing surgical mask, scrubs and gloves outside carrying folder or clipboard" src="https://images.theconversation.com/files/540705/original/file-20230802-17-b2qkwo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/540705/original/file-20230802-17-b2qkwo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/540705/original/file-20230802-17-b2qkwo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/540705/original/file-20230802-17-b2qkwo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/540705/original/file-20230802-17-b2qkwo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/540705/original/file-20230802-17-b2qkwo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/540705/original/file-20230802-17-b2qkwo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">How often do you pick your nose? Your answer may not be accurate.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/young-female-ems-key-worker-doctor-1844975320">Shutterstock</a></span>
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<p>People in the study may also have had trouble correctly remembering past behaviour (picking their nose) or exposures (to symptomatic people with COVID). The long time lag between when the infection data was collected and the retrospective survey increases the risk of recall error.</p>
<p>There is also some level of “guestimating” in the study, particularly when it comes to the risk of COVID exposure. Health workers were asked to note their contact with symptomatic people or working with COVID patients. But we can’t say if these were real “exposures”. That’s because people may not have symptoms and still have COVID (this would have under-estimated their exposure risk). Alternatively, COVID patients may not be that infectious if they don’t shed much virus (which may have over-estimated the COVID risk).</p>
<p>Then, it appears the analysis did not control for gender. This is potentially an issue as female health workers tend to be <a href="https://pubmed.ncbi.nlm.nih.gov/11743487/">better</a> at following hand hygiene guidelines. The study reported a higher rate of nose picking in males and doctors, and males and <a href="https://www.australiancriticalcare.com/article/S1036-7314(00)70630-8/pdf">doctors</a> are also worse at hand hygiene.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/540700/original/file-20230802-15-ma6m83.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Surgeon washing hands in hospital" src="https://images.theconversation.com/files/540700/original/file-20230802-15-ma6m83.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/540700/original/file-20230802-15-ma6m83.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=285&fit=crop&dpr=1 600w, https://images.theconversation.com/files/540700/original/file-20230802-15-ma6m83.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=285&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/540700/original/file-20230802-15-ma6m83.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=285&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/540700/original/file-20230802-15-ma6m83.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=358&fit=crop&dpr=1 754w, https://images.theconversation.com/files/540700/original/file-20230802-15-ma6m83.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=358&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/540700/original/file-20230802-15-ma6m83.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=358&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">How often did health workers wash their hands? The study didn’t say.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/surgeon-hospital-washing-thorouughly-his-hands-1155417787">Shutterstock</a></span>
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<p>So the nose pickers may also be worse at sanitising their hands. In other words, we don’t know if nose picking is the reason for the reported increased risk of COVID, the lack of hand hygiene, or both.</p>
<p>Another way of saying this is the researchers reported a <em>correlation</em> between nose picking and an increased risk of COVID. We cannot say one <em>causes</em> the other or if additional factors are involved.</p>
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Read more:
<a href="https://theconversation.com/does-picking-your-nose-really-increase-your-risk-of-dementia-193463">Does picking your nose really increase your risk of dementia?</a>
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</p>
<hr>
<h2>So, what now?</h2>
<p>Given the above limitations, the study conclusions seem overly confident. Overall, the risk of SARS-CoV-2 transmission via nose picking is probably comparatively low, particularly for the general public who are not working in high COVID environments. </p>
<p>But you can definitely decrease your risk through good hand hygiene (and using a tissue that you dispose of afterwards).</p>
<p>Better still, avoid inhaling airborne viral particles, which is the <a href="https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/surface-transmission.html">most common</a> mode of transmission of SARS-CoV-2. Wear a good fitting mask or respirator in public, particularly in poorly ventilated or crowded inside spaces.</p><img src="https://counter.theconversation.com/content/210879/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Thea van de Mortel teaches into the Griffith University Master of Infection Prevention and Control program. </span></em></p>Health workers who picked their noses were more likely to contract COVID, according to a new study. But here’s what the study means for the rest of us.Thea van de Mortel, Professor, Nursing, School of Nursing and Midwifery, Griffith UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2097742023-07-19T15:02:22Z2023-07-19T15:02:22ZAsymptomatic COVID-19 is linked to a gene variant that boosts immune memory after exposure to prior seasonal cold viruses<figure><img src="https://images.theconversation.com/files/538083/original/file-20230718-33186-1uz5zq.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2429%2C1220&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Genetics may play a role in COVID-19 disease severity.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/virus-wide-royalty-free-image/1312985523">BlackJack3D/E+ via Getty Images</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>A <a href="https://www.nature.com/articles/s41586-023-06331-x">common genetic variant</a> explains why some people are asymptomatic after being infected with the virus that causes COVID-19, according to our recently published study in the journal Nature.</p>
<p>Early in the pandemic, we were intrigued that many people did not develop COVID-19 symptoms while still testing positive for it. Because asymptomatic people are unlikely to seek medical help, we knew that collecting DNA samples to study the role of genetics in asymptomatic infections would be difficult. So instead, we took advantage of existing genetic data stored in the <a href="https://bethematch.org/about-us/how-we-help-patients/be-the-match-registry/">Be The Match</a> U.S. bone marrow donor registry. </p>
<p>We invited volunteers registered as donors to track their experience with COVID-19 via a smartphone app developed by the <a href="https://covid19.eurekaplatform.org">COVID-19 Citizen Science Study</a>. This allowed us to analyze the genetics of nearly 30,000 people without collecting biological samples and to identify COVID-19 positive individuals who never became sick.</p>
<p>We were particularly interested in analyzing the variation of <a href="https://www.uptodate.com/contents/human-leukocyte-antigens-hla-a-roadmap">human leukocyte antigen, or HLA, genes</a>. These key components of the immune system encode for proteins that display the viral particles that <a href="https://theconversation.com/coronavirus-b-cells-and-t-cells-explained-141888">T cells</a> – a group of immune system cells critical for fighting infections – recognize. Because HLA molecules are important in the immune response to pathogens and are highly variable among people, we thought they might play a role in COVID-19.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Computer illustration of HLA-B*1501." src="https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=815&fit=crop&dpr=1 600w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=815&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=815&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1024&fit=crop&dpr=1 754w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1024&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1024&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This is a 3D model of the protein that the gene variant HLA-B*15:01 codes for.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:HLA_B%5E1501.png">Pdeitiker/Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>We found that 1,428 unvaccinated individuals reported a positive COVID-19 test, of whom 136 reported no COVID-19 symptoms. Our analysis identified a common variant of an HLA gene <a href="https://www.nature.com/articles/s41586-023-06331-x">called <em>HLA-B*15:01</em></a> that is associated with asymptomatic infection. This variant is present in <a href="https://doi.org/10.1016/j.humimm.2013.06.025">about 10% of the population with European ancestry</a>. </p>
<p>We found that people carrying the variant were more than twice as likely to remain asymptomatic after being infected with COVID-19, and those carrying two copies of this variant were more than eight times more likely to not have any symptoms. </p>
<p>Next, we used cells from people with the HLA variant who donated blood several years before the pandemic to see whether they had preexisting immunity to the virus that causes COVID-19. We found that people who had never been exposed to COVID-19 had memory T cells that worked against a specific particle of the virus, enabling them to elicit a very effective immune response against COVID-19. We also found that, when bound to HLA, this viral particle looks very similar to fragments of seasonal coronaviruses recognized by T cells. </p>
<p>Our findings suggest that <a href="https://www.nature.com/articles/s41586-023-06331-x">preexposure to seasonal cold viruses</a> allowed people with <em>HLA-B*15:01</em> to develop a very effective immune memory that helped them to quickly kill the virus before they developed symptoms. </p>
<h2>Why it matters</h2>
<p>Identifying the genetic factors associated with how the disease progresses after infection provides the basis for understanding why people respond differently to the virus that causes COVID-19 as well as other viral illnesses. Focusing on asymptomatic infections also sheds light on the early stages of infection and how the immune system fights against COVID-19. </p>
<p>Most existing vaccines protect against severe COVID-19 symptoms. Therefore, identifying the viral fragments that mediate asymptomatic infection, such as the one we discovered, can help develop more specific vaccines or therapies for COVID-19.</p>
<h2>What still isn’t known</h2>
<p>Although the genetic association we identified is strong, the immune system is very complex. It remains unclear what other mechanisms regulate asymptomatic infections, or why not everyone carrying this specific variant remains without symptoms.</p>
<h2>What’s next</h2>
<p>We want to know if the genetic variant we identified is shared by individuals from different ancestries. This will help us understand which genetic variants are important among those in these groups with asymptomatic COVID-19. We also hope to learn what makes the cross-reactive T cells in people with <em>HLA-B*15:01</em> so remarkably effective at keeping the symptoms associated with this virus at bay.</p><img src="https://counter.theconversation.com/content/209774/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jill Hollenbach receives funding from National Institutes of Health</span></em></p><p class="fine-print"><em><span>Danillo Augusto receives funding from the National Institutes of Health</span></em></p>Researchers found that people with a specific gene variant were two to eight times more likely to not have symptoms after infection.Jill Hollenbach, Professor of Neurology, University of California, San FranciscoDanillo Augusto, Assistant Professor of Biological Sciences, University of North Carolina – CharlotteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2072862023-07-12T12:38:49Z2023-07-12T12:38:49ZStrep throat can easily be confused with throat infections caused by viruses – here are a few ways to know the difference<figure><img src="https://images.theconversation.com/files/536374/original/file-20230707-23-bxbi1g.jpg?ixlib=rb-1.1.0&rect=0%2C9%2C6640%2C4220&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Strep is most common in children between the ages of 5 and 15.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/male-pediatrician-examining-little-child-patients-royalty-free-image/1306247195?phrase=doctor+checking+for+strep&adppopup=true">aquaArts studio/E+ via Getty Images</a></span></figcaption></figure><p>“My sore throats, you know, are always worse than anybody’s.”</p>
<p>So declares Mary to Anne in “<a href="https://jasna.org/austen/works/persuasion/">Persuasion</a>,” Jane Austen’s 1817 book. Most of us can relate to this feeling. There is no such thing as “just a sore throat.” The pain, headache, fever and aches associated with a sore throat can make you feel terrible.</p>
<p>While sore throats can occur at any time of year, strep throat is <a href="https://www.cdc.gov/groupastrep/surveillance.html#">more common in the fall, winter and early spring</a>.</p>
<p>I am a <a href="https://facultyprofiles.tufts.edu/allen-shaughnessy">professor of family medicine</a>, a pharmacist and an expert on evidence-based medicine. My work involves the evaluation of research performed by others, and I have been following and analyzing research findings on strep for the past 30 years. </p>
<p>Many people incorrectly assume that all sore throats are due to strep throat, a bacterial infection of the pharynx, the middle throat area behind the nose and mouth, and patients often come to our family medicine office wanting to be checked and treated for strep with antibiotics.</p>
<p>However, neither testing nor treatment is always needed for a sore throat. Regardless of the cause, rest and pain relievers form the cornerstone of sore throat treatment.</p>
<p>Here’s some guidance on whether and when testing is necessary.</p>
<h2>Bacterial versus viral sore throats</h2>
<p>Most <a href="https://www.cdc.gov/antibiotic-use/sore-throat.html">sudden-onset sore throats</a> are caused by viruses – the same ones that cause the common cold, the seasonal flu and COVID-19. There are <a href="https://www.nih.gov/news-events/nih-research-matters/understanding-common-cold-virus#">more than 200 viruses</a> that can cause sore throat and other symptoms related to the common cold. </p>
<p>But bacteria can also be the culprits behind a sore throat. One of the most common examples is <a href="https://www.cdc.gov/groupastrep/diseases-hcp/strep-throat.html#">strep throat</a>, or <a href="https://www.cdc.gov/streplab/groupa-strep/index.html">group A pharyngitis</a>.</p>
<p>Strep is caused by certain strains of <em>Streptococcus pyogenes</em> bacteria.
There are many species of strep; other common forms of strep that cause different infections in humans include “<a href="https://www.cdc.gov/groupbstrep/index.html">group B strep</a>” and “<a href="https://www.icliniq.com/articles/infectious-diseases/group-d-streptococcus-infections">group D strep</a>.” Group A strep usually lives peacefully among the many other types of bacteria growing on our skin and doesn’t cause any problems, until we get a break in the skin such as a cut or a scrape. This allows it to overwhelm the immune system’s ability to keep it in check.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A teenage girl is lying on a sofa, feeling unwell and holding a thermometer in her mouth to check her temperature." src="https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Fever, headache and confusion can be symptoms of a severe case of strep.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/sick-teenager-resting-at-home-and-monitoring-royalty-free-image/1482421648?phrase=strep+throat&adppopup=true">RealPeopleGroup/E+ via Getty Images</a></span>
</figcaption>
</figure>
<p>Group A strep can also live in the back of the throat – up to 30% of people without any evidence of a sore throat will have <a href="https://doi.org/10.3389/fcimb.2019.00137">this strain in their throat</a>. <a href="https://www.cdc.gov/groupastrep/diseases-public/strep-throat.html#">Up to 3 in 10 children and 1 in 10 adults</a> feeling sick with a sore throat due to a virus or other cause will test <a href="https://doi.org/10.1371/journal.pntd.0006335">positive for group A strep</a>. That means that people with a sore throat caused by a virus could also be positive for strep, even if it’s not causing the symptoms.</p>
<p>Not all group A strep bacteria are the same, though. Some varieties are better at evading the immune system than others and can grow quickly. Others produce byproducts that can cause a sore throat and sometimes lead to <a href="https://www.mayoclinic.org/diseases-conditions/tonsillitis/symptoms-causes/syc-20378479">tonsillitis</a>, an infection of the tonsils, or cause ear or <a href="https://www.cdc.gov/antibiotic-use/sinus-infection.html">sinus infections</a>. </p>
<p>Still other strep strains produce a toxin that can cause a characteristic <a href="https://www.cdc.gov/groupastrep/diseases-public/scarlet-fever.html">skin rash</a> or lead to effects on the <a href="https://www.cdc.gov/groupastrep/diseases-public/rheumatic-fever.html">heart</a>, <a href="https://www.cdc.gov/groupastrep/diseases-public/post-streptococcal.html">kidneys</a> or even the <a href="https://www.nimh.nih.gov/health/publications/pandas">brain</a>. </p>
<p>Rarer still, group A strep can enter the bloodstream and cause <a href="https://www.mayoclinic.org/diseases-conditions/toxic-shock-syndrome/symptoms-causes/syc-20355384">toxic shock syndrome</a>, a life-threatening, overwhelming infection. These latter conditions are examples of invasive strep, meaning that the infection is in parts of the body typically free from germs; they <a href="https://www.cdc.gov/groupastrep/igas-infections-investigation.html">seem to be on the rise</a> after a marked <a href="https://www.cdc.gov/groupastrep/igas-infections-investigation.html">reduction in their occurrence during the COVID-19 pandemic</a>. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/W50S0dCCFPs?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Like other illnesses that made a comeback after COVID-19 prevention measures were relaxed, strep cases have returned to pre-pandemic levels.</span></figcaption>
</figure>
<h2>To test or not to test</h2>
<p>Doctors or other clinicians can easily test for strep by using a swab to collect a bit of the fluid from the back of the throat. This sample can identify group A strep in about a minute. </p>
<p>While researchers have been studying group A strep <a href="https://www.ncbi.nlm.nih.gov/books/NBK333430/">for over 75 years</a> and there are thousands of research papers focused on infections caused by strep, there is still <a href="https://www.nice.org.uk/guidance/ng84/chapter/Summary-of-the-evidence">controversy</a> over whether it needs to be tested for and treated. </p>
<p>To decide whether to test for group A strep, clinicians use a set of criteria based on <a href="https://www.mdcalc.com/calc/104/centor-score-modified-mcisaac-strep-pharyngitis">five questions</a> that can help determine whether strep testing is needed. These are:</p>
<p>– How old is the patient? Strep throat is most common in children <a href="https://www.cdc.gov/groupastrep/diseases-public/strep-throat.html#">between ages 5 and 15</a> and least common in <a href="https://www.cdc.gov/groupastrep/diseases-hcp/strep-throat.html#">adults over age 45</a>. </p>
<p>– Are the tonsils swollen or do they have a white or yellow coating? Both conditions often accompany strep. However, this question alone isn’t definitive, since viruses can also affect the tonsils.</p>
<p>– Are the <a href="https://www.verywellhealth.com/cervical-lymph-nodes-2252142">cervical lymph nodes</a> swollen or tender? Normally these bumps, which are in the front of the neck along the sides of the windpipe, cannot be seen or felt, but are often palpable when strep is present.</p>
<p>– Does the person have a fever? Lack of a fever makes strep less likely.</p>
<p>– Does the person have a cough? A cough is indicative of a viral cause and makes strep the less likely cause of the sore throat.</p>
<p>While none of these questions alone can provide a clear answer, taken together they can tell your clinician whether strep is more or less likely. </p>
<p>Using this scoring tool, an adult with a sore throat but without changes to the tonsils or lymph nodes, without a fever and with a cough has only a <a href="https://www.mdcalc.com/calc/104/centor-score-modified-mcisaac-strep-pharyngitis">1 in 40 chance, or 2.5%, of having strep throat</a>. For such patients, a strep test is not necessary. </p>
<p>On the other hand, when a first grader meets all five of these criteria, there is a 50% chance that strep is causing his or her sore throat. Based on recent research I have reviewed, by using these questions <a href="https://doi.org/10.7326/0003-4819-159-9-201311050-00003">adults can determine</a> when strep is the likely cause of a sore throat. </p>
<p>In the <a href="https://www.nice.org.uk/guidance/ng84">United Kingdom</a> and <a href="https://doi.org/10.1370/afm.741">other European countries</a>, doctors do not routinely test for strep. Antibiotic treatment can at times <a href="https://www.cdc.gov/antibiotic-use/community/pdfs/aaw/au_arent_always_the_answer_fs_508.pdf">cause allergic reactions, rash, diarrhea, stomach upset, yeast infections and other side effects</a>. Authorities in these countries feel any benefit of testing and treatment does not outweigh these risks.</p>
<h2>Treatments for strep</h2>
<p>Once group A strep is confirmed, doctors may prescribe an antibiotic treatment. </p>
<p>Penicillin or amoxicillin are the most commonly prescribed antibiotics for strep. These medicines will not reduce pain or tiredness but may help symptoms resolve earlier, typically by <a href="https://www.nice.org.uk/guidance/ng84/chapter/Summary-of-the-evidence">about a day</a>. Doctors may also suggest use of a pain reliever such as acetaminophen or ibuprofen to help relieve symptoms.</p>
<p>Antibiotic treatment does not seem to lower the likelihood of <a href="https://doi.org/10.1136/bmj.38503.706887.AE1">spread of the infection between children</a> – which is common in schools and dormitories – <a href="https://doi.org/10.1136/bmj.f6867">or adults</a>.</p>
<p>Health care practitioners recommend staying home until fever has subsided. They also recommend taking the full course of antibiotics, even if the symptoms have abated. </p>
<p>With sore throats causes by viruses – against which antibiotics are ineffective – few treatments exist aside from using pain relievers to help soothe immediate symptoms. For this reason and because <a href="https://www.cdc.gov/antibiotic-use/index.html">antibiotic overuse is a major problem in the U.S.</a>, it is best not to assume that your sore throat is caused by strep and to treat it accordingly.</p><img src="https://counter.theconversation.com/content/207286/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Allen Shaughnessy does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Despite an abundance of research on strep, there is still a great deal of debate in the scientific community over whether and when people should get tested and treated for it.Allen Shaughnessy, Professor of Family Medicine, Tufts UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2074782023-07-07T12:28:11Z2023-07-07T12:28:11ZTuberculosis on the rise for first time in decades after COVID-19 interrupted public health interventions and increased inequality<figure><img src="https://images.theconversation.com/files/535903/original/file-20230705-15-j8nls.jpg?ixlib=rb-1.1.0&rect=323%2C0%2C6192%2C4067&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Tuberculosis is a dangerous bacterial infection of the lungs.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/shot-of-a-young-man-coughing-while-hes-sick-royalty-free-image/1358069629?phrase=Coughing&adppopup=true">Moyo Studio/E+ via Getty Images</a></span></figcaption></figure><p>Before SARS-CoV-2, the virus that causes COVID-19, spread across the world in 2020, tuberculosis was responsible for more deaths globally than any other <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022">infectious disease</a>. But thanks to <a href="https://doi.org/10.15585%2Fmmwr.rr6901a1">targeted public health efforts</a> in the U.S. and globally, tuberculosis cases had been <a href="https://doi.org/10.15585/mmwr.mm7212a1">steadily falling for decades</a>. </p>
<p>I am an <a href="https://scholar.google.com/citations?user=ECuj1XkAAAAJ&hl=en&oi=ao">infectious disease clinician and public health practitioner</a> who has been caring for underserved communities in the U.S. for more than two decades. </p>
<p>During the pandemic, it at first appeared that, as with many other common illnesses like the flu, <a href="https://www.who.int/news/item/27-10-2022-tuberculosis-deaths-and-disease-increase-during-the-covid-19-pandemic">COVID-19 prevention efforts reduced tuberculosis cases</a>, too. But tuberculosis numbers have quickly climbed back up to <a href="https://doi.org/10.1016/S1473-3099(22)00500-X">pre-pandemic levels</a>, marking the first time in decades that <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022/tb-disease-burden/2-2-tb-mortality">cases and deaths have risen globally</a>.</p>
<p>The pandemic not only interrupted important health interventions for tuberculosis, it also caused a <a href="https://doi.org/10.3389/fpubh.2020.00241">decrease in social and economic opportunities</a> for marginalized people around the globe. Together, these effects appear to have put a serious dent in the fight against tuberculosis. </p>
<p><iframe id="9iPuv" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/9iPuv/1/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<h2>Tuberculosis before and during COVID-19</h2>
<p>Tuberculosis is a contagious bacterial infection of the lungs that is normally spread <a href="https://doi.org/10.5588%2Fijtld.22.0685">through the air</a>. Most tuberculosis <a href="https://www.cdc.gov/tb/topic/basics/tbinfectiondisease.htm">infections are asymptomatic</a> and not contagious. </p>
<p>About 5% to 10% of <a href="https://doi.org/10.15585%2Fmmwr.rr6901a1">infected individuals</a> develop active tuberculosis, which is characterized by cough, fever, decreased appetite and weight loss. If left untreated, tuberculosis is a very contagious and dangerous disease that <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022">can result in death</a>. </p>
<p>Total estimated tuberculosis infections globally have been <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022/tb-disease-burden/2-1-tb-incidence">falling for years</a>. The lowest number, 10.1 million cases, occurred in 2020, according to the World Health Organization. 2021 saw a significant increase in infections, to 10.5 million, the first rise in more than a decade. Global tuberculosis deaths followed a similar pattern, reaching a low point of an estimated 1.4 millions deaths in 2019, then rising to <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022/tb-disease-burden/2-2-tb-mortality">1.5 million in 2020 and 1.6 million in 2021</a>.</p>
<p>The number of confirmed cases of tuberculosis – infections detected through direct testing – tells a different part of the story. As testing efforts have improved, confirmed cases have been rising globally to a <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022/covid-19-and-tb">peak in 2019</a>. As the coronavirus disrupted lives in 2020, confirmed cases of tuberculosis fell significantly before <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022">quickly rising again in 2021</a>.</p>
<p>A similar pattern <a href="https://www.cdc.gov/media/releases/2022/s0324-tuberculosis-covid-19.html">played out in the U.S.</a> There was a sharp drop in confirmed cases in 2020 – mostly driven by lack of testing – followed by a <a href="https://www.cnn.com/2023/03/23/health/tuberculosis-2022-cdc-report/index.html">sharp rise back to pre-pandemic levels</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/535922/original/file-20230705-19-ap4h7k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An man standing in a hospital next to a sign with TB Ward written on it." src="https://images.theconversation.com/files/535922/original/file-20230705-19-ap4h7k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/535922/original/file-20230705-19-ap4h7k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/535922/original/file-20230705-19-ap4h7k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/535922/original/file-20230705-19-ap4h7k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/535922/original/file-20230705-19-ap4h7k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/535922/original/file-20230705-19-ap4h7k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/535922/original/file-20230705-19-ap4h7k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Places with limitations in access to health care, economic mobility and social stability – including many parts of sub-Saharan Africa and India – carry the highest numbers of tuberculosis cases every year.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/an-indian-patient-who-has-been-diagnosed-with-tubercolosis-news-photo/937243906?adppopup=true">Shammi Mehra/AFP via Getty Images</a></span>
</figcaption>
</figure>
<h2>Tuberculosis is a social disease</h2>
<p>Tuberculosis is a preventable disease, thanks to <a href="https://www.cdc.gov/tb/topic/basics/vaccines.htm">effective vaccines</a>, testing and treatments. But millions of people around the world still suffer from this disease, not because of a lack of medical knowledge, but because of <a href="https://doi.org/10.2105%2FAJPH.2010.199505">persistent social inequities</a>.</p>
<p>Unequal access to economic opportunities, limited health care, poor sanitation, crowded living conditions, malnutrition and <a href="https://doi.org/10.1016/s1473-3099(09)70282-8">illnesses such as diabetes or HIV</a> are all <a href="https://doi.org/10.5588%2Fijtld.12.0385">associated with increased risk of tuberculosis</a>.</p>
<p>In the U.S. in 2021, <a href="https://doi.org/10.1001/jama.2023.4899">racial and ethnic minority groups</a> accounted for more than 85% of tuberculosis cases, with <a href="https://www.cdc.gov/tb/topic/populations/healthdisparities/default.htm">71% of cases occurring in persons born outside the U.S.</a> </p>
<h2>Increased inequality causing more tuberculosis</h2>
<p>Even as the world witnessed a rapid <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022/covid-19-and-tb">decline in confirmed cases in 2020</a>, experts were worried that interruption of prevention and treatment efforts might <a href="https://www.reuters.com/article/us-health-tuberculosis-who-idUSKBN26Z1VJ">result in a rise in tuberculosis</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/535925/original/file-20230705-17-7oyx2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A sign announced an emergency room is closed because of the pandemic." src="https://images.theconversation.com/files/535925/original/file-20230705-17-7oyx2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/535925/original/file-20230705-17-7oyx2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=598&fit=crop&dpr=1 600w, https://images.theconversation.com/files/535925/original/file-20230705-17-7oyx2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=598&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/535925/original/file-20230705-17-7oyx2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=598&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/535925/original/file-20230705-17-7oyx2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=751&fit=crop&dpr=1 754w, https://images.theconversation.com/files/535925/original/file-20230705-17-7oyx2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=751&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/535925/original/file-20230705-17-7oyx2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=751&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The COVID-19 pandemic disrupted many medical systems and increased inequality more broadly, leading to an increase in tuberculosis cases globally.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/the-exterior-of-the-mt-sinai-south-nassau-hosptials-news-photo/1355659170?adppopup=true">J. Conrad Williams Jr./Newsday RM via Getty Images</a></span>
</figcaption>
</figure>
<p>These fears were warranted. <a href="https://www.nytimes.com/2020/08/03/health/coronavirus-tuberculosis-aids-malaria.html">Many health experts</a>, along with the U.S. Centers for Disease Control and Prevention, have confirmed the pandemic disrupted access to tuberculosis testing and diagnosis. It is likely that many cases were missed because of the interruption of tuberculosis control activities, since funding, resources and staff were reassigned to assist in <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022">COVID-19 control efforts</a>. Additionally, during health encounters, similarities in symptoms between COVID-19 and tuberculosis may have led to <a href="https://www.cdc.gov/media/releases/2022/s0324-tuberculosis-covid-19.html">missed diagnoses</a>.</p>
<p>The drop in confirmed cases seems to be, in large part, driven by a lack of testing. The rapid increase since the pandemic, and especially the rise in deaths, confirms that progress made in tuberculosis control over the past 20 years has stalled, slowed or reversed. These two troubling trends are also almost certainly connected to the increase in <a href="https://doi.org/10.3389/fpubh.2020.00241">inequality brought about by the pandemic</a>.</p>
<p>The existence of multigenerational households, overcrowding in low-income neighborhoods, lack of paid sick leave, inability to shield from the pandemic, use of public transportation and lack of health insurance all converged to heighten the risk of both COVID-19 and tuberculosis among the most vulnerable people. </p>
<p>Of course, the pandemic is not the only factor that has increased human hardship – and therefore, tuberculosis – in recent years. For example, Ukraine now has one of the <a href="https://doi.org/10.1016/S1473-3099(23)00220-7">world’s highest tuberculosis disease burdens</a> as a result of Russia’s invasion and the resulting harm to Ukraine’s medical, social and economic systems. Ongoing conflicts in other parts of the world, energy shortages and the effects of climate change and associated impacts on food security are expected to worsen the broader <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022">social and political determinants of tuberculosis</a>. </p>
<p>There are many <a href="https://doi.org/10.1371%2Fjournal.pntd.0000256">neglected diseases of poverty</a>, and tuberculosis is a great example of how social forces produce human disease. With an estimated <a href="https://doi.org/10.1183/13993003.00655-2019">one-third of the world’s population at risk for tuberculosis</a> today, fostering social justice interventions to reduce health inequities is a critically important step to relieving the global medical burden of this relentless disease.</p><img src="https://counter.theconversation.com/content/207478/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Carlos Franco-Paredes does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Tuberculosis is a preventable and curable disease, yet before the pandemic, it killed more people than any other infectious disease.Carlos Franco-Paredes, Associate Faculty Mycobacteria Research Laboratories, Colorado State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2081562023-06-23T13:39:47Z2023-06-23T13:39:47ZDirty tea towels are breeding grounds for harmful bacteria – here’s how to clean them properly<figure><img src="https://images.theconversation.com/files/533147/original/file-20230621-15-81vklh.jpg?ixlib=rb-1.1.0&rect=123%2C0%2C6227%2C4218&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Yep, when you've finished, both of those need to go in the wash.</span> <span class="attribution"><a class="source" href="https://www.pexels.com/photo/close-up-of-women-in-pattern-dresses-drying-cutlery-with-tea-towels-6956744/">pexels/karolina grabowska</a></span></figcaption></figure><p><a href="https://link.springer.com/article/10.1023/A:1016378226861">Kitchens</a> can harbour all sorts of germs and bacteria. These can arrive via humans, pets, uncooked food or even plants, meaning that a high proportion of <a href="https://academic.oup.com/jambio/article-abstract/119/2/582/6717307?redirectedFrom=fulltext">foodborne infections</a> are acquired directly within the home. </p>
<p>An important cleaning aid in most kitchens is the tea towel, also known as a dishcloth. Usually made of cotton or linen, they are used to dry wet hands and kitchen implements as well as wiping down surfaces – so play an important role in kitchen hygiene. </p>
<p>But, because hands and uncooked fresh produce are often rich in a diverse variety of germs, tea towels are prone to picking up the bacteria they come into contact with. </p>
<p>Indeed, in a <a href="https://www.semanticscholar.org/paper/Achieving-hygiene-in-the-domestic-kitchen%3A-the-of-Cogan-Slader/ffc798f7219afc6f986d6f18c62e6e496e7e0161">study</a> that used tea towels to wipe down chopping boards that had been used to prepare raw chicken with salmonella (which can cause diarrhoea, fever and stomach cramps), 90% of the cloths became contaminated with salmonella, too.</p>
<p><a href="https://www.tandfonline.com/doi/abs/10.1080/09603129509356839?src=recsys">Several studies</a> have looked at the germs tea towels typically carry in domestic kitchens. One study sampled 100 used tea towels and found a marked presence of <a href="https://www.tandfonline.com/doi/abs/10.1080/09603120050127202?src=recsys">staphylococcus aureus</a> <em>Staphylococcus aureus</em>, which is often found on the skin but is also a pathogen that can cause a variety of issues such as abscesses, joint infections and even pneumonia.</p>
<figure class="align- centre ">
<img alt="Tea towels hanging to dry on the oven door." src="https://images.theconversation.com/files/533151/original/file-20230621-15-620nos.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/533151/original/file-20230621-15-620nos.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=382&fit=crop&dpr=1 600w, https://images.theconversation.com/files/533151/original/file-20230621-15-620nos.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=382&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/533151/original/file-20230621-15-620nos.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=382&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/533151/original/file-20230621-15-620nos.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=480&fit=crop&dpr=1 754w, https://images.theconversation.com/files/533151/original/file-20230621-15-620nos.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=480&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/533151/original/file-20230621-15-620nos.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=480&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Dirty tea towels are a breeding ground for bacteria and foodborne illnesses.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/closeup-teatowels-on-rack-2293555605"> Joe Kuis/Shutterstock</a></span>
</figcaption>
</figure>
<p>Tea towels are good at picking up germs which is important as another <a href="https://www.tandfonline.com/doi/abs/10.1080/09603129509356839?src=recsys">study of 46 kitchens</a> found a wide range of harmful bacterial species living on kitchen surfaces, which are often cleaned by tea towels. </p>
<p>Surfaces were found to have <em>Enterobacter</em> (which can cause respiratory tract infections, skin infections, urinary tract infections and heart, bone and eye infections), <em>Klebsiella</em> (which has been linked to serious infections of the lungs, bladder, brain and blood), and <em>E. coli</em> (which can cause upset stomachs and urinary tract infections). </p>
<p>Several kitchens also had <em>Pseudomonas aeruginosa</em>, which can cause lung infections. <em>Bacillus subtilis</em>, which can lead to eye infections and abscesses, was also found in more than half of the kitchens sampled. And all of the samples from the kitchens were found to have <em>Staphylococcus</em> and <em>Micrococcus</em>. In people with weak immune systems, <em>Micrococcus</em> has been linked to lung infections, such as pneumonia and septic arthritis along with eye and heart infections.</p>
<p>The levels and types of germs found on these tea towels were influenced by how they were used, how often they were washed and how long they were dried for. <a href="https://www.sciencedirect.com/science/article/pii/S0956713522003887?via%3Dihub">Rinsing tea towels in hot water</a> at 60°C was found to reduce levels of bacteria later spread by contaminated cloths, which is important as infection likelihood is often related to how many bacteria you ingest.</p>
<h2>Clean your cloths</h2>
<p>These studies suggest there is an infection risk from tea towels and that most kitchen cloths may be contaminated with high levels of bacteria. It’s easy, then, for these germs to transfer on to food preparation surfaces, potentially causing serious food poisoning. </p>
<p>The infection risk of using tea towels is well-recognised by the medical profession. Indeed, in UK hospitals, fabric <a href="https://www.leicspart.nhs.uk/wp-content/uploads/2021/02/Food-Hygiene-for-Ward-and-Therapy-kitchens-Infection-Prevention-Policy-exp-Feb-24.pdf">tea towels are not allowed</a>. Instead, patient crockery, cutlery and food preparation work surfaces are cleaned and dried with disposable paper towels. </p>
<p>One of the reasons tea towels act as such good microbial reservoirs is that they are often damp as they are used to absorb moisture and mop up spills. <a href="https://www.sciencedirect.com/science/article/pii/S0956713522003887?via%3Dihub">Water enables germs to grow</a>. And so a moist tea towel left in a warm kitchen provides an ideal environment for bacteria to multiply. This is particularly the case if food traces are present, too. </p>
<p>So what’s the best way to sanitise your used tea towel? Tea towels that are hung up in the air tend to dry faster than cloths stored and squeezed into balls, which can affect levels of bacteria in the towels. </p>
<p><a href="https://www.sciencedirect.com/science/article/pii/S0956713522003887?via%3Dihub">Laboratory experiments</a> that involved covering tea towels in salmonella, found that the bacteria multiplied in all types of cloths that were crumpled. But levels of bacteria were reduced by 1,000 times if the tea towels were hung to dry for 24 hours at room temperature. </p>
<h2>Reduce the germs</h2>
<p>To avoid tea towels spreading germs around the kitchen, it’s recommended that the cloths are washed regularly and when they get wet, are allowed to dry completely before being used again. Using <a href="https://www.food.gov.uk/sites/default/files/media/document/cloths.pdf">disposable cloths</a> or paper towels for heavily contaminated areas, such as those involving raw meat, could also help to stop the spread of bacteria. </p>
<p>In terms of tea towel hygiene, you should clean and thoroughly dry your kitchen towel <a href="https://www.food.gov.uk/sites/default/files/media/document/cloths.pdf">at least once a day</a> or after each use. The UK government recommends that tea towels should be sanitised by washing them in a washing machine with laundry detergent on a hot wash cycle of 90°C. </p>
<figure class="align-center ">
<img alt="Tea towels drying on a clothesline." src="https://images.theconversation.com/files/533152/original/file-20230621-18-piu85o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/533152/original/file-20230621-18-piu85o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/533152/original/file-20230621-18-piu85o.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/533152/original/file-20230621-18-piu85o.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/533152/original/file-20230621-18-piu85o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/533152/original/file-20230621-18-piu85o.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/533152/original/file-20230621-18-piu85o.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Daily washing of tea towels is crucial for kitchen hygiene.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/colourful-towels-tea-hung-outside-dry-1655802655"> Tony Skerl/Shutterstock</a></span>
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</figure>
<p>Laundry detergents contain hard water softeners, surfactants (which increase the wetting effect of water by reducing its surface tension), detergents, bleaches and digestive enzymes. Food stains on tea towels will probably be a mixture of proteins, fats and carbohydrates, which the enzymes degrade. </p>
<p>And the detergent helps to dissolve the stains, which are released into the washing water. Since proteins and fats are also involved in the attachment of bacteria to surfaces, laundry detergents will help to detach and so reduce bacteria levels in tea towels. </p>
<p>If you <a href="https://www.food.gov.uk/sites/default/files/media/document/cloths.pdf">wash tea towels</a> by hand, ensure any obvious food and dirt are removed by rinsing in hot water with detergent before disinfection. After washing, you can sanitise any microbes remaining using boiling water or a disinfectant such as bleach, diluted as per the manufacturer’s instructions. </p>
<p>Ironing tea towels on a hot setting will also effectively sanitise as the temperature is <a href="https://www.food.gov.uk/sites/default/files/media/document/cloths.pdf">above 90°C</a>.
You should also store your laundered tea towels in a dry, clean area, away from any uncooked food and grubby hands.</p><img src="https://counter.theconversation.com/content/208156/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Primrose Freestone does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A microbiologist on the deadly germs lurking in your kitchen and why you need to wash tea towels and dishcloths more often.Primrose Freestone, Senior Lecturer in Clinical Microbiology, University of LeicesterLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2029322023-05-31T12:38:14Z2023-05-31T12:38:14ZCytomegalovirus lies dormant in most US adults and is the leading infectious cause of birth defects, but few have heard of it<figure><img src="https://images.theconversation.com/files/529162/original/file-20230530-19-du6gsi.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cytomegalovirus belongs to the same virus family, _Herpesviridae_, as cold sores and chickenpox.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/electron-microscope-image-of-cytomegalovirus-royalty-free-image/1134489724">Callista Images/Image Source via Getty Images</a></span></figcaption></figure><p>“Why didn’t anyone tell me about this virus?” is a frequent response I hear from parents upon learning their newborn is infected with <a href="https://www.nationalcmv.org/">cytomegalovirus, or CMV</a>. Although <a href="https://doi.org/10.1186/s12889-022-13971-7">more than half of the U.S. population</a> will be infected with CMV by the age of 40 and the disease is <a href="https://doi.org/10.1002/rmv.2034">common worldwide</a>, few people have ever heard of it.</p>
<p>CMV belongs to the <a href="https://www.merckmanuals.com/home/infections/herpesvirus-infections/overview-of-herpesvirus-infections">same virus family</a> as cold sores and <a href="https://theconversation.com/the-chickenpox-virus-has-a-fascinating-evolutionary-history-that-continues-to-affect-peoples-health-today-168636">chickenpox</a> and, like those viruses, <a href="https://theconversation.com/chickenpox-and-shingles-virus-lying-dormant-in-your-neurons-can-reactivate-and-increase-your-risk-of-stroke-new-research-identified-a-potential-culprit-194627">lives in the body for life</a>. Most children and adults experience <a href="https://www.merckmanuals.com/home/infections/herpesvirus-infections/cytomegalovirus-cmv-infection">very mild or even no symptoms</a> with their initial infection. A healthy immune system is typically able to keep CMV under control so people don’t become sick or even know the virus is living in their body.</p>
<p>So if most people are unlikely to get sick from CMV at any age, then why is the virus so important to understand? As an <a href="https://www.researchgate.net/profile/Laura-Gibson-7">infectious disease and immunology specialist</a>, I have focused on this question for most of my two-decade career. One major reason is that CMV – unlike the other viruses in its family – can <a href="https://www.cdc.gov/cmv/index.html">pass from mother to fetus</a> during pregnancy. </p>
<p>Congenital CMV, or cCMV, is the most common infection before birth and the <a href="https://www.marchofdimes.org/find-support/topics/planning-baby/cytomegalovirus-and-pregnancy">leading infectious cause of birth defects</a>. About <a href="https://www.cdc.gov/cmv/congenital-infection.html">one in every 200 infants</a> – typically 20,000 to 30,000 infants in the U.S. – are born with cCMV per year, and <a href="https://doi.org/10.1016/j.jcv.2009.09.002">nearly 20%</a> of them have permanent neurodevelopmental disabilities such as hearing loss or cerebral palsy. Every year, more children are <a href="https://doi.org/10.1186/1471-2458-5-70">affected by cCMV</a> than several familiar childhood conditions like Down syndrome and fetal alcohol syndrome. Compared to later stages of pregnancy, CMV infection in the <a href="https://doi.org/10.1016/j.ajog.2020.05.038">first trimester carries the highest risk</a> of stillbirth or severe effects when the immune system and organs like the brain are developing. </p>
<p>Rates of cCMV differ significantly by race, ethnicity and other demographic factors, with Black and multiracial infants <a href="https://doi.org/10.1016/j.jpeds.2018.04.043">twice as likely</a> to have cCMV compared to other groups. Black and Native American infants also have a <a href="https://doi.org/10.1371/journal.pntd.0001140">higher risk of death</a> from cCMV compared to white infants. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/FTw6vE-xSwY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Herpesviruses share the ability to stay latent in the body for life.</span></figcaption>
</figure>
<h2>Looking for CMV during pregnancy</h2>
<p>Screening for rubella, HIV and syphilis is <a href="https://www.cdc.gov/nchhstp/pregnancy/screening/index.html#">routine for early prenatal care</a> in the U.S. Counseling to avoid kitty litter to <a href="https://theconversation.com/toxoplasma-cat-poo-parasite-infects-billions-so-why-is-it-so-hard-to-study-120688">prevent toxoplasmosis</a> is also common. If CMV can infect a fetus and cause birth defects, then why aren’t pregnant people tested and treated for this virus too? </p>
<p>Prenatal CMV screening is not standard of care <a href="https://doi.org/10.1016/s1473-3099(17)30143-3">due to several limitations</a> of the current testing approach. Some available tests can be <a href="https://doi.org/10.1016/j.jcv.2012.09.015">difficult for health care providers to interpret</a>. Testing provides information about whether the parent has CMV, but it does not sufficiently predict the risk of fetal transmission or severe symptoms. </p>
<p>Prenatal screening for a healthy person with a normal pregnancy does not usually offer useful information. That’s because <a href="https://doi.org/10.1128/jvi.02392-16">anyone can have a baby with cCMV</a> regardless of whether <a href="https://doi.org/10.1093/infdis/jiy321">they tested positive or negative for it</a> before or earlier in pregnancy. CMV testing may be useful for pregnant people who are experiencing acute illness, such as prolonged fever and fatigue, or who have an abnormal fetal ultrasound.</p>
<p>Even if more accurate tests were available, there are currently no medical interventions approved by the Food and Drug Administration to reduce the risk of fetal CMV infection. <a href="https://doi.org/10.1002/uog.23596">Biweekly antibodies against CMV</a> seem to reduce fetal transmission when given around conception or during the first trimester, but CMV is rarely diagnosed that early in pregnancy.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/529171/original/file-20230530-21-eyj9a0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Pregnant person touching belly" src="https://images.theconversation.com/files/529171/original/file-20230530-21-eyj9a0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/529171/original/file-20230530-21-eyj9a0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529171/original/file-20230530-21-eyj9a0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529171/original/file-20230530-21-eyj9a0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529171/original/file-20230530-21-eyj9a0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529171/original/file-20230530-21-eyj9a0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529171/original/file-20230530-21-eyj9a0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Most available drugs to treat CMV are unsafe to take during pregnancy.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/pregnant-woman-touching-her-belly-royalty-free-image/1390901979">FG Trade/E+ via Getty Images</a></span>
</figcaption>
</figure>
<p>Researchers are currently evaluating the drug valacyclovir as a potential treatment to prevent fetal transmission. Valacyclovir is commonly used to prevent or treat <a href="https://www.cdc.gov/stiapp/herpes-genital_ado_adult.html">genital herpes</a> during pregnancy. Findings from a recent clinical trial in Israel suggest that valacyclovir <a href="https://doi.org/10.1016/s0140-6736(20)31868-7">may reduce the risk</a> of CMV transmission to the fetus.</p>
<p>In general, valacyclovir does not work as well as <a href="https://www.drugs.com/pregnancy/ganciclovir.html">other CMV drugs</a> that people cannot take during pregnancy. As a result, a <a href="https://doi.org/10.1016/s0140-6736(20)31868-7">much higher dose is required</a> to reduce the risk of fetal CMV infection, which may cause significant side effects for pregnant people. </p>
<p>Although the use of valacyclovir to prevent cCMV is not standard in the U.S., and research on its effectiveness <a href="https://doi.org/10.1016/j.cmi.2020.04.006">remains limited</a>, the drug is used for this purpose <a href="https://doi.org/10.1016/j.jcv.2020.104351">in some areas</a> <a href="https://doi.org/10.1016/j.ajog.2016.04.003">of the world</a>.</p>
<h2>Screening newborns for CMV</h2>
<p>Like pregnant people, babies are <a href="https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp">screened for many potentially serious conditions</a>. An accurate <a href="https://doi.org/10.1056/nejmoa1006561">CMV test for newborns</a> is available, and many studies <a href="https://doi.org/10.1002/rmv.1790">support the benefit</a> of <a href="https://doi.org/10.1038/s41372-019-0501-z">early CMV diagnosis</a>. So why isn’t there universal CMV screening for infants?</p>
<p>While some birth centers <a href="https://www.nationalcmv.org/overview/newborn-screening">provide early CMV testing</a>, most U.S. states <a href="https://www.nationalcmv.org/about-us/advocacy">do not mandate newborn CMV screening</a>. My team and I surveyed 33 hospitals in Massachusetts from late 2020 to early 2021 and found that <a href="https://doi.org/10.3390/ijns8040065">less than half</a> are consistently screening infants for cCMV infection. Of those, only a few have a written testing protocol. Only two hospitals performed cCMV screening on all infants admitted to the newborn nursery.</p>
<p>Standardizing public health education and CMV screening guidelines could help reduce the incidence and burden of cCMV disease on children and their families. In July 2013, <a href="https://le.utah.gov/%7E2013/bills/static/hb0081.html">Utah became the first state</a> to pass legislation mandating a CMV public education program and testing for infants who do not pass the newborn hearing screen. In February 2022, <a href="https://www.revisor.mn.gov/statutes/cite/144.064">Minnesota became the first</a> – and remains the only – state to require CMV screening of all newborns, although <a href="https://malegislature.gov/Bills/192/SD1810">Massachusetts</a> and <a href="https://iga.in.gov/legislative/2021/bills/house/1362#document-aa892856">Indiana</a> have pending universal screening bills. So far, 17 states have enacted laws requiring cCMV education or targeted screening of newborns who meet certain criteria, and many others are considering similar options.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/529163/original/file-20230530-17-eip1bt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Person holding baby closely" src="https://images.theconversation.com/files/529163/original/file-20230530-17-eip1bt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/529163/original/file-20230530-17-eip1bt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529163/original/file-20230530-17-eip1bt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529163/original/file-20230530-17-eip1bt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529163/original/file-20230530-17-eip1bt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529163/original/file-20230530-17-eip1bt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529163/original/file-20230530-17-eip1bt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Negative health effects from cCMV may not show for a newborn until later.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/side-view-of-new-mother-comforting-her-newborn-royalty-free-image/1367022758">Juanma Hache/Moment via Getty Images</a></span>
</figcaption>
</figure>
<p>On the other hand, designing, funding and implementing a new infant screening program is <a href="https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp">complex and time-consuming</a>, and may potentially divert resources from other equally important health initiatives. Most newborns with cCMV appear physically normal at birth and <a href="https://www.cdc.gov/cmv/congenital-infection.html">develop normally over their lifetime</a>, leading some to question the benefits of CMV screening for those children. </p>
<p>However, infants may have abnormalities that are <a href="https://doi.org/10.1038/s41372-019-0501-z">not visible at birth</a>, and there isn’t a reliable way to predict whether they will have progressive health problems. Without screening all newborns for CMV, those who appear normal at birth will not be fully evaluated, considered for treatment or monitored for effects that develop later, such as hearing loss.</p>
<h2>Spreading CMV awareness, not infection</h2>
<p>Decreasing the incidence of cCMV infection is unlikely without increasing awareness. Most people <a href="https://doi.org/10.1089/jwh.2007.0523">have not heard of CMV</a> or are <a href="https://doi.org/10.1016/j.ypmed.2012.03.009">unwaware of what they can do</a> to reduce their chances of getting CMV during pregnancy. </p>
<p>Many adults are repeatedly exposed to one of the major risk factors for CMV infection: a young child who <a href="https://doi.org/10.1016/s0022-3476(88)80314-7">regularly attends</a> <a href="https://doi.org/10.1056/nejm198911093211903">large-group child care</a>. Infections like CMV spread easily among children in settings where group play, meals and diaper changes become daily opportunities for transmission. Children can appear quite healthy but carry CMV in their saliva and urine for weeks or even months after infection. When an <a href="https://doi.org/10.1542/peds.2005-1142">unsuspecting</a> <a href="https://doi.org/10.1056/nejm198605293142204">pregnant</a> <a href="https://doi.org/10.1097/00006454-199108000-00008">caretaker</a> comes into contact with those body fluids, they can become infected as well. </p>
<p>For people who are pregnant, <a href="https://doi.org/10.1097/00006454-199603000-00013">simple behavior changes</a> such as kissing a child on the head instead of the lips, not sharing food or utensils, and frequent handwashing can significantly reduce the risk of getting CMV.</p>
<p>Educating the public, policymakers and health care providers will improve the diagnosis, prevention and treatment of cCMV, so no parent suffers the thought “If I had only known…”</p><img src="https://counter.theconversation.com/content/202932/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Laura Gibson is a member of the Scientific Advisory Board for the CMV Program at Moderna Therapeutics, Inc. She also receives research funding from Moderna. She is affiliated with the Massachusetts Congenital CMV Coalition.</span></em></p>Although testing for CMV during pregnancy isn’t routine and there isn’t universal screening for infants, there are steps pregnant people can take to protect themselves and their newborns.Laura Gibson, Associate Professor of Medicine and of Pediatrics, UMass Chan Medical SchoolLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2037632023-04-18T03:28:33Z2023-04-18T03:28:33ZWhen did you have your last tetanus vaccine? A booster dose may save your life<figure><img src="https://images.theconversation.com/files/521445/original/file-20230418-18-3hqftn.jpg?ixlib=rb-1.1.0&rect=327%2C35%2C7482%2C5199&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/covid-vaccine-plaster-doctor-patient-consulting-2211549193">Shutterstock</a></span></figcaption></figure><p>NSW Health <a href="https://twitter.com/NSWHealth/status/1646283387496443906">recently reported</a> three cases of tetanus and the tragic death of a woman in her 80s – the first tetanus fatality in the state in 30 years. </p>
<p>Tetanus is a rare but potentially fatal disease. Thankfully, it’s preventable – being up to date with tetanus vaccination is your best protection.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1646359040266731520"}"></div></p>
<h2>What is tetanus and how do you get it?</h2>
<p>The bacteria that causes tetanus is called <em>Clostridium tetani</em>. Spores can enter your body usually following a skin wound, puncture or injury. </p>
<p>Tetanus cannot be transmitted from person to person. </p>
<p>The spores are ubiquitous, found in soil, dust and animal waste. They can <a href="https://www.elsevierhealth.com.au/plotkins-vaccines-9780323357616.html">persist</a> in the environment for months to years, and are remarkably hardy – they’re even resistant to boiling and a number of disinfectants. </p>
<figure class="align-center ">
<img alt="Person gardens in soil with their bare hands" src="https://images.theconversation.com/files/521442/original/file-20230418-28-vlw6xx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/521442/original/file-20230418-28-vlw6xx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/521442/original/file-20230418-28-vlw6xx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/521442/original/file-20230418-28-vlw6xx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/521442/original/file-20230418-28-vlw6xx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/521442/original/file-20230418-28-vlw6xx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/521442/original/file-20230418-28-vlw6xx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The bacteria that causes tetanus can remain in soil for years.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/q13Zq1Jufks">Sandie Clarke/Unsplash</a></span>
</figcaption>
</figure>
<p>Once in a wound, the bacteria can grow and produce a toxin. It is the toxin that acts on your nervous system to cause muscle rigidity and painful spasms. </p>
<h2>What are the symptoms?</h2>
<p>One <a href="https://www.uptodate.com/contents/tetanus">classic symptom</a> of tetanus is “lockjaw”, where the muscles around your mouth go into spasms. This makes it difficult to eat and speak but patients maintain full consciousness or awareness. The muscle contractions and spasms are intensely painful and can be triggered by loud noises, physical contact or even light.</p>
<p>Patents with tetanus are commonly treated in an intensive care unit and require cleaning of the wound, antibiotics and injections of anti-toxin, known as human tetanus immunoglobulin, as well as a vaccine. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/at-least-five-reasons-you-should-wear-gardening-gloves-89451">(At least) five reasons you should wear gardening gloves</a>
</strong>
</em>
</p>
<hr>
<p>In severe cases, spasms of muscles surrounding your airways and lungs, alongside high and low blood pressure and heart rhythm abnormalities can lead to death. </p>
<p>Despite the best treatment, about <a href="https://link.springer.com/article/10.17269/s41997-022-00732-7#:%7E:text=From%201995%20to%202019%2C%20a,range%3A%2043%E2%80%9393">2</a>-<a href="https://www.gov.uk/government/publications/tetanus-in-england-annual-reports/tetanus-in-england-2021#:%7E:text=tetanus%20is%20a%20severe%2C%20potentially,per%20year%20over%20previous%20years">10</a>% of patients die. </p>
<h2>How does the vaccine work?</h2>
<p>In Australia, tetanus is rare because of high vaccination coverage, with around <a href="https://www1.health.gov.au/internet/main/publishing.nsf/Content/2A15CD097063EF40CA2587CE008354F1/$File/summary_of_national_surveillance_data_on_vaccine_preventable_diseases_in_australia_2016_2018_final_report.pdf">14 cases</a> reported to health authorities a year.</p>
<p>Tetanus can occur at any age, but is more common in older adults who have never been vaccinated or were vaccinated more than ten years ago. </p>
<p>The vaccine is very effective in preventing tetanus. Tetanus vaccination stimulates the production of antibodies, also known as antitoxin. This means vaccination doesn’t stop <em>Clostridium tetani</em> growing in contaminated wounds. Rather, it protects against the effects of the toxin.</p>
<figure class="align-center ">
<img alt="Nurse vaccinates child" src="https://images.theconversation.com/files/521447/original/file-20230418-18-jwzs1z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/521447/original/file-20230418-18-jwzs1z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/521447/original/file-20230418-18-jwzs1z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/521447/original/file-20230418-18-jwzs1z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/521447/original/file-20230418-18-jwzs1z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/521447/original/file-20230418-18-jwzs1z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/521447/original/file-20230418-18-jwzs1z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Vaccination protects you from the effects of the toxin.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/woman-doctor-putting-medical-plaster-girl-1921268393">Shutterstock</a></span>
</figcaption>
</figure>
<h2>When do we need a tetanus shot?</h2>
<p>Tetanus vaccination has been available in Australia since <a href="https://www.health.vic.gov.au/immunisation/vaccine-history-timeline">1925</a>. It’s currently on the National Immunisation Program (NIP) as an initial five-dose schedule for infants and children until five years of age, administered as a combined diphtheria-tetanus-acellular pertussis (DTPa) vaccine. </p>
<p><a href="https://doi.org/10.33321/cdi.2022.46.60">Most children</a> (97%) in Australia complete this primary immunisation schedule. </p>
<p>The <a href="https://www.who.int/publications/i/item/WHO-WER9206">level of antitoxin needed</a> for protection from tetanus is 0.1-0.2 international units (IU) per millilitre (mL). This level is <a href="https://pubmed.ncbi.nlm.nih.gov/16822597/">reached</a> following a fifth dose, at age four to six years. </p>
<p>But by middle age, <a href="https://pubmed.ncbi.nlm.nih.gov/30318003/">about 20%</a> of Australians have low or undetectable levels of antitoxin. This places them at risk of contracting tetanus after a wound or injury. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/health-check-are-you-up-to-date-with-your-vaccinations-116510">Health Check: are you up to date with your vaccinations?</a>
</strong>
</em>
</p>
<hr>
<p>A single dose of tetanus vaccine produces protective levels of antitoxin in these people. This is why a booster dose of tetanus vaccine is <a href="https://immunisationhandbook.health.gov.au/contents/vaccine-preventable-diseases/tetanus">recommended</a> for the following people if their last dose was more than ten years ago: </p>
<ul>
<li><p>adults at 50 years of age</p></li>
<li><p>adults aged 65 years or over</p></li>
<li><p>travellers, of any age, to countries where it may be difficult to access timely health services if you sustain a tetanus-prone wound (any wound other than a clean, minor cut).</p></li>
</ul>
<p>If you have a tetanus-prone wound and there is any doubt about your tetanus immunisation status, you should receive tetanus immunoglobulin as soon as possible. You should also receive a tetanus vaccine. </p>
<p>If you’re overseas, it could be hard and expensive to get access to both tetanus immunoglobulin and tetanus vaccine.</p>
<h2>How do I check my vaccination status?</h2>
<p>If you’re over 14 years of age, you can check your vaccine history:</p>
<ul>
<li><p>online, by setting up a myGov account and accessing your Medicare online account through the Express Plus Medicare mobile app</p></li>
<li><p>by calling the <a href="https://www.servicesaustralia.gov.au/australian-immunisation-register">Australian Immunisation Register</a> on 1800 653 809</p></li>
<li><p>by asking your doctor or immunisation provider to <a href="https://www.health.gov.au/topics/immunisation/getting-vaccinated/check-immunisation-history">print a copy</a> of your immunisation records. </p></li>
</ul>
<p>If it has been more than ten years since your last dose, ask your GP about getting a booster. It could save your life.</p><img src="https://counter.theconversation.com/content/203763/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nicholas Wood has previously received funding from the NHMRC for a Career Development Fellowship.</span></em></p><p class="fine-print"><em><span>Helen Quinn does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Tetanus is a rare but potentially fatal disease. Being up to date with tetanus vaccination is your best protection.Nicholas Wood, Associate Professor, Discipline of Childhood and Adolescent Health, University of SydneyHelen Quinn, Senior Research Fellow, National Centre for Immunisation Research and Surveillance & Senior Lecturer, Children’s Hospital Westmead Clinical School, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1991562023-02-02T22:18:37Z2023-02-02T22:18:37ZGuinea worm: A nasty parasite is nearly eradicated, but the push for zero cases will require patience<figure><img src="https://images.theconversation.com/files/507952/original/file-20230202-14714-ndbz5k.jpg?ixlib=rb-1.1.0&rect=3%2C3%2C510%2C334&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Guinea worms are long, white parasites that emerge from the legs of infected people through painful blisters.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Dracunculus_medinensis.jpg#/media/File:Dracunculus_medinensis.jpg">CDC/Wikimedia Commons</a></span></figcaption></figure><p>A painful, parasitic disease that once infected 3.5 million people per year is tantalizingly close to being eradicated.</p>
<p>On Jan. 24, 2023, <a href="https://www.cartercenter.org">The Carter Center</a>, a nonprofit founded by former U.S. President Jimmy Carter, announced that “Guinea worm is poised to become the second human disease in history <a href="https://www.cartercenter.org/news/pr/2023/2022-guinea-worm-worldwide-cases-announcement.html">to be eradicated</a>,” having recorded just 12 cases worldwide in 2022. It represents the lowest annual figure since 1986, when the <a href="https://www.cartercenter.org">Carter Center</a> began leading global efforts to eradicate Guinea worm disease. </p>
<p>I have been <a href="https://scholar.google.com/citations?user=yb246-8AAAAJ&hl=en&oi=ao">working as a parasitologist</a> for over two decades. I know the suffering that parasitic diseases like Guinea worm infections inflict on humanity, especially on the world’s most vulnerable and poor communities. <a href="https://www.clemson.edu/science/academics/departments/genbio/about/profiles/kpaul">My own research</a> on African sleeping sickness – a deadly disease caused by a parasite carried by tsetse flies – has shown me how difficult it is to fight these diseases.</p>
<p>Thanks to a massive global effort, Guinea worm is now almost gone. However, humanity has been <a href="https://www.who.int/teams/control-of-neglected-tropical-diseases/dracunculiasis/dracunculiasis-eradication-portal">tantalizingly close to fully eradicating Guinea worm</a> for many years. To take the final step from almost gone to fully eradicated is not easy, but with patience and vigilance, it is possible.</p>
<h2>A painful and persistent parasite</h2>
<p>Guinea worms are parasitic nematodes that infect humans and a few other animals. They live in ponds, rivers and creeks all across Africa but are mostly endemic to sub-Saharan Africa. </p>
<p>A Guinea worm infection is a nasty experience. The worm mainly infects people after they drink water that is contaminated with tiny crustaceans called <a href="https://www.cdc.gov/parasites/guineaworm/biology.html">copepods that are infected with worm larvae</a>. Most people don’t realize they are infected for about a year – roughly the time it takes for the larvae to burrow their way out of the stomach and into the abdominal cavity, develop into adults and mate. Once the females mature into pregnant worms, the horror show begins. </p>
<p>The pregnant worms must get back to the water to give birth, so they crawl down to the lower leg or foot. Once there, they <a href="https://www.cartercenter.org/news/multimedia/slideshows/guinea-worm-photo-downloads.html">burrow out through an incredibly painful blister</a> in a process that can take weeks. The intense pain causes people to plunge their leg into water to get relief, and this is when the worm expels her larvae, starting the cycle anew. </p>
<p>There are no vaccines or drugs for Guinea worm. The current best treatment is very low-tech: treat the wound and <a href="https://www.cdc.gov/parasites/guineaworm/treatment.html">slowly extract the worm over several painful weeks</a>. Due to the intense pain, infected adults cannot work or provide for their families. Infected kids miss school and fall behind on their education. Though there are usually no long-term complications, infection confers no immunity, so people can get infected repeatedly over their lifetimes, too.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/507953/original/file-20230202-14479-wj9b1v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Three children with black filtration straws." src="https://images.theconversation.com/files/507953/original/file-20230202-14479-wj9b1v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/507953/original/file-20230202-14479-wj9b1v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/507953/original/file-20230202-14479-wj9b1v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/507953/original/file-20230202-14479-wj9b1v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/507953/original/file-20230202-14479-wj9b1v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1005&fit=crop&dpr=1 754w, https://images.theconversation.com/files/507953/original/file-20230202-14479-wj9b1v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1005&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/507953/original/file-20230202-14479-wj9b1v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1005&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Tools like filtration straws, the black tubes being held by these children in the north-central African country of Chad, can prevent Guinea worm infection.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Preventing_Guinea_worm_disease_in_Chad_(34173755220).jpg#/media/File:Preventing_Guinea_worm_disease_in_Chad_(34173755220).jpg">CDC Global/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>Path to eradication</h2>
<p>Guinea worm is awful, so I welcome any news of removing it from the list of diseases that affect people. But alongside hope, a healthy dose of realism is needed: Eradicating any disease is difficult. So far, humanity has succeeded only with smallpox, which was <a href="https://www.who.int/news-room/feature-stories/detail/the-smallpox-eradication-programme---sep-(1966-1980)">eradicated with the help of vaccines in the late 1970s</a> after 200 years of effort.</p>
<p>A disease like Guinea worm is a distinctly different challenge. Eradication will not come from a medical solution like a pill or vaccine. Instead, people will have to change their behavior. The ideas are simple, but that does not mean this will be easy.</p>
<p>The Guinea worm eradication program has employed a two-part strategy to <a href="https://www.cartercenter.org/health/guinea_worm/index.html">interrupt the Guinea worm’s transmission cycle</a>. The first part was to prevent people from getting infected from contaminated water and food. The program launched educational campaigns, ran surveillance programs and distributed millions of tools – like filtration cloths, filters and chemical water treatments – for people to secure clean water.</p>
<p>The second part of the plan was aimed at preventing reintroduction of the parasite into the environment. Again, education programs were a key component, but so were Guinea worm treatment centers. These centers acted as places where infected people and their families could receive care, food and shelter during the long treatment process. By giving infected people a place to stay, treatment centers prevent a person from putting their leg into a body of water and inevitably releasing the larva.</p>
<p><iframe id="pyuwi" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/pyuwi/6/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<h2>A difficult last step</h2>
<p>Since the eradication effort began in the mid-1980s, annual Guinea worm infections have fallen from the millions down to the dozens. But the final push to zero has been difficult and slow. In 2015, there were <a href="https://www.cartercenter.org/news/pr/guinea-worm-worldwide-cases-Jan2016.html">just 22 recorded cases</a>, but infections have stayed in the low double-digits since then.</p>
<p>The massive drop in Guinea worm cases showed that this strategy was working, but there was a complication. In 2020, researchers discovered that a Guinea worm outbreak in the Central African country of Chad was <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255611/">driven by infected dogs</a>, adding a new set of challenges to interrupting the transmission cycle. This led to public health officials returning to the field, increasing surveillance and urging people to <a href="https://doi.org/10.4269/ajtmh.20-1525">report and contain infected dogs</a>.</p>
<p>These many eradication efforts since 2015 have slowly brought case numbers down to the current record low of 12 total cases.</p>
<p>As the world approaches zero cases of Guinea worm disease, the laborious epidemiological detective work of chasing down infection reports and finding hidden water sources gets tougher. Some of the few remaining communities affected by Guinea worm are nomadic or very remote. And as Guinea worm infections grow rare, vigilance can wane and people revert to their old ways, opening the door for Guinea worm to reemerge.</p>
<p>The final push to full eradication will be a challenge that requires patience and faith on the part of institutions and governments supporting the effort. But it also requires that millions of people living in endemic areas do what they can to break the transmission cycle and kick Guinea worm out for good.</p><img src="https://counter.theconversation.com/content/199156/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kimberly Paul receives funding from the National Institutes of Health. </span></em></p>After nearly 40 years of effort, Guinea worm disease is on the cusp of being the second human disease – after smallpox – to be eradicated on Earth.Kimberly Paul, Associate Professor of Biochemistry, Clemson UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1965682022-12-23T18:59:52Z2022-12-23T18:59:52ZSepsis is one of the most expensive medical conditions in the world – new research clarifies how it can lead to cell death<figure><img src="https://images.theconversation.com/files/502237/original/file-20221220-20-d0pk4l.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1639%2C1001&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Bacteria (clusters of light pink, surrounded by larger magenta blood cells) can cause deadly infections, but overreactive immune responses can deliver the lethal blow.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/gram-negative-bacterial-bloodstream-infection-seen-royalty-free-image/1063050118">Scharvik/iStock via Getty Images Plus</a></span></figcaption></figure><p><a href="https://www.cdc.gov/sepsis/what-is-sepsis.html">Sepsis</a> is a life-threatening condition arising from the body’s overreactive response against an infection, leading it to injure its own tissues and organs. The first known reference to “sepsis” dates back <a href="https://doi.org/10.1007/s00134-006-0392-2">more than 2,700 years</a>, when the Greek poet Homer used it as a derivative of the word “sepo,” meaning “I rot.”</p>
<p>Despite dramatic improvements in understanding the immunological mechanisms behind sepsis, it still remains a major medical concern, affecting <a href="https://doi.org/10.3949/ccjm.87a.18143">750,000 people in the U.S.</a> and <a href="https://doi.org/10.1016/S0140-6736(19)32989-7">nearly 50 million people globally</a> each year. Sepsis accounted for <a href="https://doi.org/10.1016/S0140-6736(19)32989-7">11 million deaths worldwide</a> in 2017, and is the <a href="https://doi.org/10.1177/2050312119835043">most expensive medical condition</a> in the U.S., costing <a href="https://doi.org/10.1097/CCM.0000000000003342">over tens of billions of dollars</a> annually.</p>
<p><a href="https://medicine.tufts.edu/people/faculty/alexander-poltorak">We</a> <a href="https://scholar.google.com/citations?user=VMa6rFgAAAAJ&hl=en">are</a> <a href="https://medicine.tufts.edu/people/faculty/hayley-muendlein">researchers</a> who study how certain types of bacteria <a href="https://doi.org/10.1126/science.282.5396.2085">interact with cells</a> during infections. We wanted to understand exactly how an overreactive immune response can result in detrimental and even lethal effects like sepsis. In our <a href="https://www.science.org/doi/10.1126/sciimmunol.add0665">newly published research</a>, we discovered the cells and molecules that potentially trigger death from sepsis.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/NsPDjOX8QHA?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Sepsis results from a potentially lethal overreactive immune response to infection.</span></figcaption>
</figure>
<h2>TNF in autoimmunity and sepsis</h2>
<p>The body’s response to infection starts when immune cells recognize components of the invading pathogen. These cells then release molecules like cytokines that help eliminate the infection. Cytokines are a broad group of small proteins that recruit other immune cells to the site of infection or injury.</p>
<p>While cytokines play an essential role in the immune response, excessive and uncontrolled cytokine production can lead to a dangerous <a href="https://doi.org/10.1007/s00281-017-0639-8">cytokine storm</a> associated with sepsis. Cytokine storms were first seen in the context of <a href="https://pubmed.ncbi.nlm.nih.gov/8442093/">graft versus host disease</a>, arising from transplant complications. They can also occur during <a href="https://doi.org/10.1089/vim.2019.0032">viral infections</a>, including <a href="https://doi.org/10.1016/S0140-6736(20)30628-0">COVID-19</a>. This uncontrolled immune response can lead to <a href="https://doi.org/10.3389/fimmu.2020.01446">multi-organ failure and death</a>. </p>
<p>Among the hundreds of cytokines that exist, <a href="https://doi.org/10.1073/pnas.72.9.366">tumor necrosis factor, or TNF</a>, stands tall as the most potent and the most studied for nearly the past 50 years. </p>
<p>Tumor necrosis factor owes its name to its ability to induce tumor cells to die when the immune system is stimulated by a bacterial extract called <a href="https://pubmed.ncbi.nlm.nih.gov/1984929/">Coley’s toxin</a>, named after the researcher who identified it over a century ago. This toxin was later recognized to be <a href="https://doi.org/10.1073/pnas.72.9.3666">lipopolysaccharide, or LPS</a>, a component of the outer membrane of certain types of bacteria. LPS is the strongest known trigger of TNF, which, once on alert, aids in the recruitment of immune cells to the infection site to eliminate invading bacteria.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/xnlCjudODyI?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Severe COVID-19 infections can trigger cytokine storms.</span></figcaption>
</figure>
<p>In normal conditions, TNF promotes beneficial processes such as <a href="https://doi.org/10.1038/nrrheum.2015.169">cell survival and tissue regeneration</a>. However, TNF production must be tightly regulated to avoid sustained inflammation and continuous proliferation of immune cells. Uncontrolled TNF production can lead to the <a href="https://doi.org/10.3389/fimmu.2020.591365">development of rheumatoid arthritis</a> and similar inflammatory conditions. </p>
<p>In infection conditions, TNF must also be tightly regulated to prevent excessive tissue and organ damage from inflammation and an overactive immune response. When TNF is left uncontrolled during infections, it can <a href="https://doi.org/10.1016/0090-1229(92)90036-N">lead to sepsis</a>. For several decades, studies of septic shock were modeled by investigating responses to bacterial LPS. In this model, LPS activates certain immune cells that trigger the production of inflammatory cytokines, in particular TNF. This then leads to excessive immune cell proliferation, recruitment and death, ultimately resulting in tissue and organ damage. Too strong of an immune response is not a good thing.</p>
<p>Researchers have shown that <a href="https://doi.org/10.3390/ijms22052719">blocking TNF activity</a> can effectively treat numerous autoimmune diseases, including rheumatoid arthritis, psoriatic arthritis and inflammatory bowel disease. Use of TNF blockers has dramatically increased in the past decades, reaching a market size of <a href="https://www.reportlinker.com/p06151677/TNF-Alpha-Inhibitors-Global-Market-Report-COVID-19-Growth-And-Change-To.html">roughly $40 billion</a>.</p>
<p>However, <a href="https://doi.org/10.1001/jama.1995.03520360048038">TNF blockers have been unsuccessful</a> in preventing the cytokine storm that can arise from COVID-19 infections and sepsis. This is in part because exactly how TNF triggers its toxic effects on the body is still poorly understood despite years of research.</p>
<h2>How TNF can be lethal</h2>
<p>Studying sepsis might provide some clues as to how TNF mediates how the immune system responds to infection. In acute inflammatory conditions such as sepsis, TNF blockers are less able to address TNF overproduction. However, studies in mice show that <a href="https://doi.org/10.1126/science.3895437">neutralizing TNF</a> can prevent the death of the animal from bacterial LPS. Although researchers do not yet understand the reason for this discrepancy, it highlights the need for further understanding how TNF contributes to sepsis.</p>
<p>Blood cells made in the bone marrow, or myeloid cells, are known to be the <a href="https://pubmed.ncbi.nlm.nih.gov/1083433/">major producers of TNF</a>. So we wondered if myeloid cells also mediate TNF-induced death. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of TNF bound to a cell membrane" src="https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">TNF (blue) is implicated in a number of inflammatory diseases.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/the-tumor-necrosis-factor-receptor-with-tnf-bound-royalty-free-image/1247890721">selvanegra/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<p>First, we identified which particular molecules might offer protection from TNF-induced death. When we injected mice with a lethal dose of TNF, we found that mice lacking either <a href="https://www.science.org/doi/10.1126/sciimmunol.add0665">TRIF or CD14</a>, two proteins typically associated with immune responses to bacterial LPS but not TNF, had improved survival. This finding parallels our <a href="https://doi.org/10.1038/s41467-020-20357-z">earlier work</a> identifying these factors as regulators of a protein complex that controls cell death and inflammation in response to LPS.</p>
<p>Next, we wanted to figure out which cells are involved in TNF-induced death. When we injected a lethal dose of TNF in mice lacking the two proteins in two specific types of myeloid cells, neutrophils and macrophages, mice had reduced symptoms of sepsis and improved survival. This finding positions macrophages and neutrophils as major triggers for TNF-mediated death in mice.</p>
<p>Our results also suggest TRIF and CD14 as potential treatment targets for sepsis, with the ability to both reduce cell death and inflammation.</p><img src="https://counter.theconversation.com/content/196568/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>An overactive immune response to infection can be deadly. Studying how one key player called tumor necrosis factor, or TNF, induces lethal immune responses could provide new treatment targets.Alexander (Sasha) Poltorak, Professor of Immunology, Tufts UniversityHayley Muendlein, Research Assistant Professor of Immunology, Tufts UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1925672022-12-14T13:14:47Z2022-12-14T13:14:47ZNasal vaccines promise to stop the COVID-19 virus before it gets to the lungs – an immunologist explains how they work<figure><img src="https://images.theconversation.com/files/493959/original/file-20221107-19718-xu583n.jpg?ixlib=rb-1.1.0&rect=0%2C11%2C7360%2C4891&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nasal vaccines for COVID-19 are still in early development.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/little-cute-blonde-boy-getting-vaccinated-covid-19-royalty-free-image/1282728128?phrase=COVID-19%20nasal%20vaccine&adppopup=true">Paul Biris/Moment via Getty Images</a></span></figcaption></figure><p><em>The Pfizer-BioNTech and Moderna mRNA vaccines have played a large role in preventing deaths and severe infections from COVID-19. But researchers are still in the process of developing alternative approaches to vaccines to improve their effectiveness, including how they’re administered. Immunologist and microbiologist <a href="https://www.researchgate.net/profile/Michael-Russell-10">Michael W. Russell</a> of the University at Buffalo explains how nasal vaccines work, and where they are in the development pipeline.</em></p>
<h2>How does the immune system fight pathogens?</h2>
<p>The immune system has two distinct components: mucosal and circulatory.</p>
<p>The <a href="http://dx.doi.org/10.1016/B978-0-12-415847-4.00001-X">mucosal immune system</a> provides protection at the mucosal surfaces of the body. These include the mouth, eyes, middle ear, the mammary and other glands, and the gastrointestinal, respiratory and urogenital tracts. Antibodies and a variety of other anti-microbial proteins in the <a href="https://theconversation.com/slime-is-all-around-and-inside-you-new-research-on-its-origins-offers-insight-into-genetic-evolution-189278">sticky secretions</a> that cover these surfaces, as well as immune cells located in the lining of these surfaces, directly attack invading pathogens.</p>
<p>The <a href="https://doi.org/10.1186/1741-7007-8-84">circulatory part of the immune system</a> generates antibodies and immune cells that are delivered through the bloodstream to the internal tissues and organs. These circulating antibodies do not usually reach the mucosal surfaces in large enough amounts to be effective. Thus mucosal and circulatory compartments of the immune system are largely <a href="http://dx.doi.org/10.3389/fimmu.2022.957107">separate and independent</a>.</p>
<h2>What are the key players in mucosal immunity?</h2>
<p>The immune components people may be most familiar with are proteins known as <a href="https://www.ncbi.nlm.nih.gov/books/NBK513460/">antibodies, or immunoglobulins</a>. The immune system generates antibodies in response to invading agents that the body identifies as “non-self,” such as viruses and bacteria.</p>
<p>Antibodies bind to specific antigens: the part or product of a pathogen that induces an immune response. Binding to antigens allows antibodies to either inactivate them, as they do with toxins and viruses, or kill bacteria with the help of additional immune proteins or cells.</p>
<p>The mucosal immune system generates a specialized form of antibody called <a href="http://dx.doi.org/10.1038/mi.2011.39">secretory IgA, or SIgA</a>. Because SIgA is located in mucosal secretions, such as saliva, tears, nasal and intestinal secretions, and breast milk, it is resistant to digestive enzymes that readily destroy other forms of antibodies. It is also superior to most other immunoglobulins at neutralizing viruses and toxins, and at preventing bacteria from attaching to and invading the cells lining the surfaces of organs.</p>
<p>There are also many <a href="http://dx.doi.org/10.1002/9780470015902.a0000942.pub2">other key players</a> in the mucosal immune system, including different types of anti-microbial proteins that kill pathogens, as well as immune cells that generate antibody responses.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/WW4skW6gucU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Mucus is one of the central secretions of the mucosal immune system.</span></figcaption>
</figure>
<h2>How does the COVID-19 virus enter the body?</h2>
<p>Almost all infectious diseases in people and other animals are <a href="https://www.ncbi.nlm.nih.gov/books/NBK209710/">acquired through mucosal surfaces</a>, such as by eating or drinking, breathing or sexual contact. Major exceptions include infections from wounds, or pathogens delivered by insect or tick bites.</p>
<p>The virus that causes COVID-19, SARS-CoV-2, enters the body via droplets or aerosols that get into your <a href="http://dx.doi.org/10.1038/s41385-020-00359-2">nose, mouth or eyes</a>. It can cause severe disease if it descends deep into the lungs and causes an <a href="https://theconversation.com/long-covid-19-and-other-chronic-respiratory-conditions-after-viral-infections-may-stem-from-an-overactive-immune-response-in-the-lungs-186970">overactive, inflammatory immune response</a>.</p>
<p>This means that the virus’s first contact with the immune system is probably through the surfaces of the nose, mouth and throat. This is supported by the presence of SIgA antibodies against SARS-CoV-2 <a href="http://dx.doi.org/10.3389/fimmu.2020.611337">in the secretions of infected people</a>, including their saliva, nasal fluid and tears. These locations, especially the tonsils, have specialized areas that specifically trigger mucosal immune responses.</p>
<p><a href="http://dx.doi.org/10.3390/pathogens11040397">Some research suggests</a> that if these SIgA antibody responses form as a result of vaccination or prior infection, or occur quickly enough in response to a new infection, they could prevent serious disease by confining the virus to the upper respiratory tract until it is eliminated.</p>
<h2>How do nasal vaccines work?</h2>
<p>Vaccines can be <a href="http://dx.doi.org/10.1016/B978-0-12-415847-4.00055-0">given through mucosal routes</a> via the mouth or nose. This induces an immune response through areas that stimulate the mucosal immune system, leading mucosal secretions to produce SIgA antibodies.</p>
<p>There are <a href="http://dx.doi.org/10.1016/B978-0-12-811924-2.00001-8">several existing mucosal vaccines</a>, most of them taken by mouth. Currently only one, the flu vaccine, is delivered nasally.</p>
<p>In the case of nasal vaccines, the viral antigens intended to stimulate the immune system would be taken up by immune cells within the lining of the nose or tonsils. While the exact mechanisms by which nasal vaccines work in people have not been thoroughly studied, researchers believe they <a href="http://dx.doi.org/10.1007/BF00915547">work analogously to oral mucosal vaccines</a>. Antigens in the vaccine induce B cells in mucosal sites to mature into plasma cells that secrete a form of IgA. That IgA is then transported into mucosal secretions throughout the body, where it becomes SIgA.</p>
<p>If the SIgA antibodies in the nose, mouth or throat target SARS-CoV-2, they could neutralize the virus before it can drop down into the lungs and establish an infection.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/jgApmHG5aMY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Nasal vaccines could provide a more approachable alternative to injections for patients leery of needles.</span></figcaption>
</figure>
<h2>What advantage do mucosal vaccines have against COVID-19?</h2>
<p>I believe that arguably the best way to protect an individual against COVID-19 is to block the virus at its point of entry, or at least to confine it to the upper respiratory tract, where it might inflict relatively little damage.</p>
<p>Breaking chains of viral transmission is crucial to controlling epidemics. Researchers know that <a href="http://dx.doi.org/10.1093/cid/ciab691">COVID-19 spreads</a> during normal breathing and speech, and is exacerbated by sneezing, coughing, shouting, singing and other forms of exertion. Because these emissions mostly originate from saliva and nasal secretions, where the predominant form of antibody present is SIgA, it stands to reason that secretions with a sufficiently high level of SIgA antibodies against the virus could neutralize and thereby diminish its transmissibility.</p>
<p><a href="http://dx.doi.org/10.3389/fimmu.2022.957107">Existing vaccines</a>, however, do not induce SIgA antibody responses. Injected vaccines primarily induce circulating IgG antibodies, which are effective in preventing serious disease in the lungs. Nasal vaccines specifically induce SIgA antibodies in nasal and salivary secretions, where the virus is initially acquired, and can more effectively prevent transmission.</p>
<p>Nasal vaccines may be a useful supplement to injected vaccines in hot spots of infection. Since they don’t require needles, they might also help overcome vaccine hesitancy due to <a href="https://theconversation.com/over-half-of-adults-unvaccinated-for-covid-19-fear-needles-heres-whats-proven-to-help-161636">fear of injections</a>.</p>
<h2>How close are researchers to creating a nasal COVID-19 vaccine?</h2>
<p>There have been <a href="https://doi.org/10.1038/d41586-022-02824-3">over 100 oral or nasal COVID-19 vaccines in development</a> around the world.</p>
<p>Most of these have been or are currently being tested in animal models. <a href="http://dx.doi.org/10.1126/scitranslmed.abn6868">Many</a> <a href="http://dx.doi.org/10.1126/science.abo2523">have reported</a> successfully inducing protective antibodies in the blood and secretions, and have prevented infection in these animals. However, few have been successfully tested in people. Many <a href="https://www.pharmalive.com/altimmune-to-halt-trials-for-intranasal-covid-19-vaccine">have been abandoned</a> without fully reporting study details.</p>
<p>According to the <a href="https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines">World Health Organization</a>, 14 nasal COVID-19 vaccines are in clinical trials as of late 2022. Reports from <a href="https://doi.org/10.1038/d41586-022-02851-0">China and India</a> indicate that nasal or inhaled vaccines have been approved in these countries. But little information is publicly available about the results of the studies supporting approval of these vaccines.</p><img src="https://counter.theconversation.com/content/192567/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael W. Russell receives consultation fees from Therapyx, Inc., and has received previous research grants (now inactive) from the National Institutes of Health; he is also named on current grants to Therapyx, Inc. Therapyx has no interests in products for COVID-19.</span></em></p>An effective nasal vaccine could stop the virus that causes COVID-19 right at its point of entry. But devising one that works has been a challenge for researchers.Michael W. Russell, Professor Emeritus of Microbiology and Immunology, University at BuffaloLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1935032022-11-07T13:35:27Z2022-11-07T13:35:27ZWhat is inflammation? Two immunologists explain how the body responds to everything from stings to vaccination and why it sometimes goes wrong<figure><img src="https://images.theconversation.com/files/493585/original/file-20221104-18-efs0p0.jpg?ixlib=rb-1.1.0&rect=107%2C242%2C5883%2C3745&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Insect bites or stings, like the one on this person's hand, are a manifestation of inflammation.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/cropped-hand-with-mosquito-bite-against-white-royalty-free-image/1187314357?phrase=insect%20bite&adppopup=true">Suthep Wongkhad/EyeEm via Getty Images</a></span></figcaption></figure><p>When your body fights off an infection, you develop a fever. If you have arthritis, your joints will hurt. If a bee stings your hand, your hand will swell up and become stiff. These are all manifestations of <a href="https://doi.org/10.1007/s11515-011-1123-9">inflammation</a> occurring in the body.</p>
<p>We are two <a href="https://scholar.google.com/citations?user=jJVj3sUAAAAJ&hl=en&oi=ao">immunologists</a> <a href="https://scholar.google.com/citations?user=af7TahQAAAAJ&hl=en&oi=ao">who study</a> how the immune system reacts <a href="https://pubmed.ncbi.nlm.nih.gov/?term=nagarkatti+p&sort=date">during infections, vaccination and autoimmune diseases</a> where the body starts attacking itself.</p>
<p>While inflammation is commonly associated with the pain of an injury or the many diseases it can cause, it is an important part of the normal immune response. The problems arise when this normally helpful function overreacts or overstays its welcome.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An image showing many small white cells swarming a larger sphere." src="https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=565&fit=crop&dpr=1 754w, https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=565&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=565&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Inflammation is a process in which antibody-producing cells – like the large beige cell on the left of this image – rush to the site of an infection to attack an invader, such as the flu virus in yellow.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/immune-response-to-a-virus-illustration-royalty-free-illustration/724237117?phrase=antibodies%20infection&adppopup=true">Juan Gaertner/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<h2>What is inflammation?</h2>
<p>Generally speaking, the term inflammation refers to all activities of the immune system that occur where the body is trying to fight off potential or real infections, clear toxic molecules or recover from physical injury. There are <a href="https://doi.org/10.1186%2F1476-9255-1-1">five classic physical signs</a> of acute inflammation: heat, pain, redness, swelling and loss of function. Low-grade inflammation might not even produce noticeable symptoms, but the underlying cellular process is the same.</p>
<p>Take a bee sting, for example. The immune system is like a military unit with a wide range of tools in its arsenal. After sensing the toxins, bacteria and physical damage from the sting, the immune system <a href="https://theconversation.com/coronavirus-b-cells-and-t-cells-explained-141888">deploys various types of immune cells</a> to the site of the sting. These include <a href="https://www.niaid.nih.gov/research/immune-cells">T cells, B cells, macrophages and neutrophils</a>, among other cells.</p>
<p>The <a href="https://www.ncbi.nlm.nih.gov/books/NBK26884/">B cells produce antibodies</a>. Those antibodies can kill any bacteria in the wound and neutralize toxins from the sting. <a href="https://doi.org/10.3389/fimmu.2012.00174">Macrophages and neutrophils engulf bacteria</a> and destroy them. <a href="https://doi.org/10.1038/d41586-021-00367-7">T cells don’t produce antibodies, but kill any virus-infected cell</a> to prevent viral spread. </p>
<p>Additionally, these immune cells produce <a href="https://doi.org/10.1177/1091581815584918">hundreds of types of molecules</a> called cytokines – otherwise known as mediators – that help fight threats and repair harm to the body. But just like in a military attack, inflammation comes with collateral damage.</p>
<p>The mediators that help kill bacteria also kill some healthy cells. Other similar mediating molecules cause blood vessels to leak, leading to accumulation of fluid and influx of more immune cells. </p>
<p>This collateral damage is the reason you develop swelling, redness and pain around a bee sting or after getting a flu shot. Once the immune system clears an infection or foreign invader – whether the toxin in a bee sting or a chemical from the environment – different parts of the inflammatory response take over and help repair the damaged tissue.</p>
<p>After a few days, your body will neutralize the poison from the sting, eliminate any bacteria that got inside and heal any tissue that was harmed. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A diagram of a man showing two airways, one open and the other more constricted." src="https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Asthma is caused by inflammation that leads to swelling and a narrowing of airways in the lungs, as seen in the right cutaway in this image.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Asthma_(Lungs).png#/media/File:Asthma_(Lungs).png">BruceBlaus/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>Inflammation as a cause of disease</h2>
<p>Inflammation is a double-edged sword. It is critical for fighting infections and repairing damaged tissue, but when inflammation occurs for the wrong reasons or <a href="https://theconversation.com/long-covid-how-researchers-are-zeroing-in-on-the-self-targeted-immune-attacks-that-may-lurk-behind-it-169911">becomes chronic</a>, the damage it causes <a href="https://theconversation.com/despite-its-disastrous-effects-covid-19-offers-some-gifts-to-medicine-an-immunology-expert-explains-what-it-can-teach-us-about-autoimmune-disease-174952">can be harmful</a>. </p>
<p><a href="https://doi.org/10.1111/j.1600-065x.2011.01020.x">Allergies</a>, for example, develop when the immune system mistakenly recognizes innocuous substances – like peanuts or pollen – as dangerous. The harm can be minor, like itchy skin, or dangerous if someone’s throat closes up.</p>
<p>Chronic inflammation damages tissues over time and can lead to <a href="https://doi.org/10.1038/s41591-019-0675-0">many noninfectious clinical disorders</a>, including cardiovascular diseases, neurodegenerative disorders, obesity, diabetes and some types of cancers. </p>
<p>The immune system can sometimes mistake one’s own organs and tissues for invaders, leading to inflammation throughout the body or in specific areas. This self-targeted inflammation is what causes the symptoms of <a href="https://doi.org/10.1289/ehp.99107s5661">autoimmune diseases</a> such as lupus and arthritis. </p>
<p>Another cause of chronic inflammation that researchers like us are currently studying is defects in the <a href="https://doi.org/10.3389/fimmu.2016.00160">mechanisms that curtail inflammation</a> after the body clears an infection.</p>
<p>While inflammation mostly plays out at a cellular level in the body, it is far from a simple mechanism that happens in isolation. Stress, diet and nutrition, as well as genetic and environmental factors, have all been shown <a href="https://doi.org/10.3389%2Ffimmu.2020.570083">to regulate inflammation</a> in some way. </p>
<p>There is still a lot to be learned about what leads to harmful forms of inflammation, but a <a href="https://doi.org/10.3390%2Fnu11081933">healthy diet</a> and <a href="https://doi.org/10.1016%2Fj.copsyc.2015.03.007">avoiding stress</a> can go a long way toward helping maintain the delicate balance between a strong immune response and harmful chronic inflammation.</p><img src="https://counter.theconversation.com/content/193503/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Prakash Nagarkatti receives funding from the National Science Foundation and the National Institutes of Health. </span></em></p><p class="fine-print"><em><span>Mitzi Nagarkatti receives funding from the National Institutes of Health.</span></em></p>Inflammation is a complicated and important part of how the immune system responds to threats to the body. But when the inflammatory response goes awry, it can lead to serious problems.Prakash Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaMitzi Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1899492022-09-15T12:25:40Z2022-09-15T12:25:40ZViruses may be ‘watching’ you – some microbes lie in wait until their hosts unknowingly give them the signal to start multiplying and kill them<figure><img src="https://images.theconversation.com/files/484664/original/file-20220914-25-l0cplf.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2309%2C1299&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Phages can sense bacterial DNA damage, which triggers them to replicate and jump ship.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/bacteriophage-infecting-bacterium-royalty-free-image/992263464">Design Cells/iStock via Getty Images Plus</a></span></figcaption></figure><p>After more than two years of the COVID-19 pandemic, you might picture a virus as a nasty spiked ball – a mindless killer that gets into a cell and hijacks its machinery to create a gazillion copies of itself before bursting out. For many viruses, including the <a href="https://doi.org/10.1038/s41579-020-00468-6">coronavirus that causes COVID-19</a>, the “mindless killer” epithet is essentially true.</p>
<p>But there’s more to virus biology than meets the eye.</p>
<p>Take HIV, the virus that causes <a href="https://doi.org/10.1002/eji.200737441">AIDS</a>. HIV is a <a href="https://doi.org/10.1101%2Fcshperspect.a006882">retrovirus</a> that does not go directly on a killing spree when it enters a cell. Instead, it integrates itself into your chromosomes and chills, waiting for the right moment to command the cell to make copies of it and burst out to infect other immune cells and eventually cause AIDS.</p>
<p>Exactly what moment HIV is waiting for is still an <a href="https://doi.org/10.1016/j.cell.2018.04.005">area of active study</a>. But research on other viruses has long hinted that these pathogens can be quite “thoughtful” about killing. Of course, viruses cannot think the way you and I do. But, as it turns out, evolution has endowed them with some pretty elaborate decision-making mechanisms. Some viruses, for instance, will choose to leave the cell they have been residing in if they detect DNA damage. Not even viruses, it appears, like to stay in a sinking ship.</p>
<p><a href="https://scholar.google.com/citations?user=T1I1sNAAAAAJ&hl=en">My</a> <a href="https://erilllab.umbc.edu/">laboratory</a> has been studying the molecular biology of <a href="https://doi.org/10.4161%2Fbact.1.1.14942">bacteriophages</a>, or phages for short, the viruses that infect bacteria, for over two decades. Recently, my colleagues and I <a href="https://doi.org/10.3389/fmicb.2022.918015">have shown</a> that phages can listen for key cellular signals to help them in their decision-making. Even worse, they can use the cell’s own “ears” to do the listening for them.</p>
<h2>Escaping DNA damage</h2>
<p>If the enemy of your enemy is your friend, phages are certainly your friends. Phages <a href="https://doi.org/10.4161%2Fbact.1.1.14942">control bacterial populations</a> in nature, and clinicians are increasingly using them to <a href="https://doi.org/10.1038/s41591-019-0437-z">treat bacterial infections</a> that do not respond to antibiotics.</p>
<p>The best studied phage, <a href="https://doi.org/10.1016/j.virol.2015.02.010">lambda</a>, works a bit like HIV. Upon entering the bacterial cell, lambda decides whether to replicate and kill the cell outright, like most viruses do, or to integrate itself into the cell’s chromosome, as HIV does. If the latter, lambda harmlessly replicates with its host each time the bacteria divides. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/ZWWH8ZxeV0E?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">This video shows a lambda phage infecting <em>E. coli</em>.</span></figcaption>
</figure>
<p>But, like HIV, lambda is not just sitting idle. It uses a special protein called CI like a stethoscope to listen for signs of DNA damage within the bacterial cell. If the bacterium’s DNA gets compromised, that’s bad news for the lambda phage nested within it. Damaged DNA leads straight to evolution’s landfill because it’s useless for the phage that needs it to reproduce. So lambda turns on its replication genes, makes copies of itself and bursts out of the cell to look for more undamaged cells to infect.</p>
<h2>Tapping the cell’s communication system</h2>
<p>Some phages, instead of gathering intel with their own proteins, tap the infected cell’s very own DNA damage sensor: LexA.</p>
<p>Proteins like CI and LexA are <a href="https://doi.org/10.1016/j.jmb.2019.04.011">transcription factors</a> that turn genes on and off by binding to specific genetic patterns within the DNA instruction book that is the chromosome. Some phages like Coliphage 186 have figured out that they don’t need their own viral CI protein if they have a short DNA sequence in their chromosomes that bacterial LexA can bind to. Upon detecting DNA damage, LexA will activate the phage’s replicate-and-kill genes, essentially double-crossing the cell into committing suicide while allowing the phage to escape.</p>
<p>Scientists first reported CI’s role in phage decision-making <a href="https://doi.org/10.1038/294217a0">in the 1980s</a> and Coliphage 186’s counterintelligence trick <a href="https://doi.org/10.1074/jbc.273.10.5708">in the late 1990s</a>. Since then, there have been a few other reports of phages tapping bacterial communication systems. One example is <a href="https://doi.org/10.1038/sj.emboj.7600826">phage phi29</a>, which exploits its host’s transcription factor to detect when the bacterium is getting ready to generate a spore, or a kind of bacterial egg <a href="https://doi.org/10.1023/A:1020561122764">capable of surviving extreme environments</a>. Phi29 instructs the cell to package its DNA into the spore, killing the budding bacteria once the spore germinates.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/MkUgkDLp2iE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Transcription factors turn genes on and off.</span></figcaption>
</figure>
<p>In our <a href="https://doi.org/10.3389/fmicb.2022.918015">recently published research</a>, my colleagues and I show that several groups of phages have independently evolved the ability to tap into yet another bacterial communication system: the CtrA protein. CtrA integrates multiple internal and external signals to set in motion different developmental processes in bacteria. Key among these is the production of bacterial appendages called <a href="https://doi.org/10.1007/s12275-017-7369-4">flagella and pili</a>. Turns out, these phages attach themselves to the pili and flagella of bacteria in order to infect them.</p>
<p>Our leading hypothesis is that phages use CtrA to guesstimate when there will be enough bacteria nearby sporting pili and flagella that they can readily infect. A pretty smart trick for a “mindless killer.”</p>
<p>These are not the only phages that make elaborate decisions – all without the benefit of even having a brain. Some phages that infect <em>Bacillus</em> bacteria produce a small molecule each time they infect a cell. The phages can sense this molecule and use it to <a href="https://doi.org/10.1016/j.cub.2021.08.072">count the number of phage infections</a> taking place around them. Like alien invaders, this count helps decide when they should switch on their replicate-and-kill genes, killing only when hosts are relatively abundant. This way, the phages make sure that they never run out of hosts to infect and guarantee their own long-term survival.</p>
<h2>Countering viral counterintelligence</h2>
<p>You may be wondering why you should care about the counterintelligence ops run by bacterial viruses. While bacteria are very different from people, the viruses that infect them are <a href="https://doi.org/10.1128/MMBR.00193-20">not that different</a> from the viruses that infect humans. Pretty much <a href="https://doi.org/10.1016/j.virol.2012.09.017">every single trick</a> played by phages has later been shown to be used by human viruses. If a phage can tap bacterial communication lines, why wouldn’t a human virus tap yours?</p>
<p>So far, researchers don’t know what human viruses could be listening for if they hijack these lines, but plenty of options come to mind. I believe that, like phages, human viruses could potentially be able to count their numbers to strategize, detect cell growth and tissue formation and even monitor immune responses. For now, these possibilities are only speculation, but scientific investigation is underway.</p>
<p>Having viruses listening to your cells’ private conversations is not the rosiest of pictures, but it’s not without a silver lining. As intelligence agencies all around the world know well, counterintelligence works only when it’s covert. Once detected, the system can very easily be exploited to feed misinformation to your enemy. Similarly, I believe that future antiviral therapies may be able to combine conventional artillery, like antivirals that prevent viral replication, with information warfare trickery, such as making the virus believe the cell it is in belongs to a different tissue. </p>
<p>But, hush, don’t tell anybody. Viruses could be listening!</p><img src="https://counter.theconversation.com/content/189949/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ivan Erill receives funding from the US National Science Foundation</span></em></p>Phages, or viruses that infect bacteria, can lie dormant within chromosomes until they’re triggered to replicate and burst out of their hosts.Ivan Erill, Associate Professor of Biological Sciences, University of Maryland, Baltimore CountyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1891072022-09-07T12:23:49Z2022-09-07T12:23:49ZFears of a polio resurgence in the US have health officials on high alert – a virologist explains the history of this dreaded disease<figure><img src="https://images.theconversation.com/files/482541/original/file-20220902-13382-7ko4kb.jpg?ixlib=rb-1.1.0&rect=0%2C22%2C2995%2C2308&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Critical-care patients in the emergency polio ward at Haynes Memorial Hospital in Boston in August 1955. </span> <span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/POLIOEPIDEMIC/ade0290b02e5da11af9f0014c2589dfb/photo?Query=polio%20iron%20lungs&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=14&currentItemNo=6">Associated Press photo</a></span></figcaption></figure><p>Fears of polio <a href="https://history.nih.gov/display/history/Polio+Timeline">gripped the U.S. in the mid-20th century</a>. Parents were afraid to send their children to birthday parties, public pools or any place where children mingled. Children in wheelchairs served as a stark reminder of the ravages of the disease.</p>
<p>To prevent polio outbreaks, <a href="https://www.pulitzer.org/winners/david-m-oshinsky">government officials used tactics</a> now familiar in the era of COVID-19: They closed public spaces and shut down restaurants, pools and other gathering places. </p>
<p>In 1952, two years prior to the introduction of a trial polio vaccine, there were an estimated <a href="https://ourworldindata.org/polio">58,000 cases of polio and 3,145 deaths due to polio in the U.S.</a>. These cases included children who were paralyzed for life. But those numbers dropped dramatically following a widespread vaccination campaign against polio, beginning in 1955. </p>
<p>By the 1970s, there were fewer than <a href="https://www.cdc.gov/polio/what-is-polio/polio-us.html">10 cases of paralysis due to polio</a> in the U.S., and the polio virus was <a href="https://www.cdc.gov/polio/why-are-we-involved/index.htm#">considered eliminated from the U.S. by 1979</a>. Since then, collective fear of the virus has been mostly lost to history – many people alive today are lucky enough not to know someone who has experienced polio.</p>
<p>So when news broke in July 2022 that an <a href="https://www.nytimes.com/2022/07/21/nyregion/polio-case-new-york.html">unvaccinated adult man in New York had contracted polio</a> – the first case in the U.S. since 2013 – and developed paralysis from the disease, it sent a ripple of fear throughout the public health community and raised the question of whether an old foe was making a comeback. </p>
<p>I am a <a href="https://medschool.cuanschutz.edu/immunology-and-microbiology/faculty/rochford">virologist and a professor of immunology and microbiology</a> and have spent my career both teaching about and doing research on how viruses can cause disease. </p>
<p>There is no cure for polio. The only treatment is prevention. And the tool for prevention is vaccination, the same tool that <a href="https://historyofvaccines.org/history/polio/timeline">eliminated polio in the U.S. in the first place</a>. </p>
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<figcaption><span class="caption">Health experts are urging unvaccinated Americans to get vaccinated against polio.</span></figcaption>
</figure>
<h2>Life cycle of the poliovirus</h2>
<p><a href="https://www.cdc.gov/polio/what-is-polio/index.htm">Polio – or poliomyelitis – the disease</a>, is caused by the poliovirus, which is passed from person to person through the mouth. And while no one would knowingly ingest a virus, touching a contaminated object like a spoon or a glass or accidentally swallowing contaminated water can unknowingly lead to infection. </p>
<p>When someone is infected with the poliovirus, they shed the infectious virus in their feces. This is why recent reports that poliovirus has been <a href="https://www.cnbc.com/2022/08/16/polio-circulating-locally-in-nyc-area-poses-risk-to-unvaccinated-cdc-says.html">circulating in New York City wastewater for months</a> and that the virus now has been <a href="https://health.ny.gov/diseases/communicable/polio/wastewater.htm">detected in three New York counties</a> are particularly concerning. </p>
<p>In August 2022, New York State Health Commissioner Mary Basset said that the state health department is “treating the single case of polio as just the <a href="https://www.health.ny.gov/press/releases/2022/2022-08-04_polio_detected_nys.htm">tip of the iceberg of much greater potential spread</a>.” </p>
<p>“Based on earlier polio outbreaks,” she added, “New Yorkers should know that for every one case of paralytic polio observed, there may be hundreds of other people infected.” </p>
<p>A single case of polio reflects a larger potential spread of the virus because most people infected either don’t show any symptoms or have a very mild illness with <a href="https://www.who.int/news-room/fact-sheets/detail/poliomyelitis">symptoms similar to the flu</a>. But even without symptoms, an infected person is still excreting virus in their feces, which means they can be a source of infection to others. </p>
<p>The virus, which is very stable in the environment, is easily spread through surface contamination. For this reason, hand-washing is a critical prevention tool. Although many disinfecting agents, such as alcohol or diluted Lysol, fail to inactivate the virus, <a href="https://doi.org/10.1016/j.biologicals.2020.07.007">chlorine bleach does destroy it</a>. This is why public health officials started <a href="https://www.utahhumanities.org/stories/items/show/425#">chlorinating swimming pools</a> decades ago <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2038672/">in order to inactivate the polio virus</a>.<br>
Typically, the human body uses stomach acid to <a href="https://www.elsevier.com/books/mims-pathogenesis-of-infectious-disease/nash/978-0-12-397188-3">protect against ingested viruses</a>. But poliovirus can survive stomach acid to travel to your gastrointestinal tract. There, the virus reproduces itself to establish an infection. </p>
<h2>What is paralytic polio?</h2>
<p>Unfortunately, one person out of about 200 people infected with poliovirus will <a href="https://www.who.int/news-room/fact-sheets/detail/poliomyelitis">develop paralysis</a>. Scientists still don’t know why one person is susceptible to the paralytic disease while most are not. </p>
<p>In the small subset of people that get paralytic polio, <a href="https://doi.org/10.1016/j.virol.2005.09.015">the virus can attack</a> the lower motor neurons found in the brain stem and spinal cord, which are <a href="https://biologydictionary.net/motor-neuron/">important for controlling muscles</a>. Infection of those neurons leads to the muscle paralysis that is characteristic of paralytic polio. The legs are typically affected – often on only one side of the body – and paralysis can range from mild to severe. Other muscle groups can also be affected.</p>
<p>In the worst cases of paralytic polio, the virus can damage the centers of the nervous system that control breathing. <a href="https://www.sciencemuseum.org.uk/objects-and-stories/medicine/iron-lung">Respirators known as “iron lungs”</a> were early medical devices that aided those with damaged respiratory muscles, helping them breathe until their muscles healed enough to work on their own. Patients could die when the paralysis was severe and sustained. </p>
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<figcaption><span class="caption">Anti-vaccination sentiments and an overall drop in routine vaccination rates during the COVID-19 pandemic have likely contributed to the resurfacing of the poliovirus in the U.S.</span></figcaption>
</figure>
<h2>Levels of severity</h2>
<p>Although polio can be devastating for those who contract the severe form of it, most people’s immune systems are well-equipped to combat it. When someone recovers from polio, researchers can detect <a href="https://doi.org/10.1016/j.immuni.2022.04.007">poliovirus-fighting antibodies in the blood</a>.</p>
<p>But even long-term survivors of paralytic polio can develop <a href="https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0003999311001353">late-onset muscle weakness and fatigue</a>, which is <a href="https://doi.org/10.1002/mus.26168">known as post-polio syndrome</a>. While the <a href="https://doi.org/10.1002/mus.20259">muscular effects of post-polio syndrome are well-recognized</a>, a number of <a href="https://doi.org/10.3389/fneur.2019.00773">other symptoms can be associated with post-polio syndrome</a>, including chronic pain, sleep disturbances, cold intolerance and difficulty swallowing.</p>
<p>Because post-polio syndrome is diagnosed only based on symptoms, there is no consensus on the <a href="https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0003999311001353">number of polio survivors who develop it</a>, but <a href="https://doi.org/10.1002/mus.26168">estimates range from 15% to upward of 80%</a>. </p>
<h2>Prevention of polio is key</h2>
<p>The decline in polio in the U.S. and globally is a direct result of the introduction of vaccines and the willingness of the public to accept them. In 1988, the World Health Organization, in partnership with Rotary International, the Centers for Disease Control and Prevention and other national governments, launched the Global Polio Eradication Initiative with the goal <a href="https://polioeradication.org/">to wipe out polio worldwide</a>, as is <a href="https://www.cdc.gov/smallpox/index.html#">the case with smallpox</a>. </p>
<p>When this initiative was launched, there were still an <a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7034a1.htm?s_cid=mm7034a1_w">estimated 350,000 children with polio in 125 countries</a>. In 2021, there were <a href="https://www.who.int/news-room/fact-sheets/detail/poliomyelitis">only six reported cases</a>. </p>
<p>Two types of polio vaccine are in use worldwide. The one used <a href="https://www.cdc.gov/media/pressrel/r990617.htm">in the U.S. since 2000</a> is an injection made from inactivated poliovirus. Inactivation kills the virus and prevents it from spreading. <a href="https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html">Children in the U.S. get this shot</a> at 2 months, 4 months and between 6 to 15 months of age, and it essentially provides lifelong protection from polio. </p>
<p>The second vaccine type, still in use in many parts of the world, is an attenuated – or weakened – form of the virus that is taken orally. In places where community transmission remains significant, <a href="https://www.npr.org/blogs/health/2012/09/21/161549217/on-the-road-to-polio-eradication-in-pakistan">like Pakistan</a>, the oral vaccine is preferred because it prevents people from getting polio and also stops person-to-person transmission. In the U.S., where person-to-person transmission of the poliovirus has been virtually nonexistent for decades, the inactivated vaccine is preferred since the focus is on preventing disease in the vaccinated person and there’s less concern about spreading the virus. </p>
<p>But in extremely rare cases, the vaccine virus mutates after it’s been excreted in feces. And if immunization levels fall below a critical threshold – as is the case in some areas of the world – <a href="https://theconversation.com/polio-in-new-york-an-infectious-disease-doctor-explains-this-exceedingly-rare-occurrence-187518">this poliovirus can cause disease</a>. The recent New York polio case has been traced back to a mutated vaccine-derived poliovirus thought to be acquired overseas.</p>
<p>Most people in the U.S. are vaccinated through routine childhood vaccinations. Because immunity to polio following vaccination is lifelong, the CDC is <a href="https://www.cdc.gov/vaccines/vpd/polio/public/index.html">not recommending booster vaccinations for the general population</a> for people who completed the full series. However, the CDC does recommend that anyone who has not been vaccinated against polio virus get vaccinated, including adults.</p>
<p>In my office, I keep a painting of <a href="https://www.salk.edu/about/history-of-salk/jonas-salk/">Dr. Jonas Salk</a>, the virologist who developed the first polio vaccine. It serves as my reminder of the importance of biomedical research to help eliminate human suffering caused by infectious diseases.</p><img src="https://counter.theconversation.com/content/189107/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rosemary Rochford receives funding from National Institutes of Health.</span></em></p>Health officials say the new case of polio in New York state and the presence of poliovirus in the municipal wastewater suggests that hundreds more could already be infected with the disease.Rosemary Rochford, Professor of Immunology and Microbiology, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1879052022-08-19T12:42:26Z2022-08-19T12:42:26ZWhat is listeria? A microbiologist explains the bacterium behind recent deadly food poisoning outbreaks<figure><img src="https://images.theconversation.com/files/479719/original/file-20220817-21-a18luh.jpg?ixlib=rb-1.1.0&rect=132%2C0%2C3875%2C2951&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Investigators in Florida traced a listeria outbreak to ice cream.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/ice-cream-jar-with-4-flavors-strawberry-vanilla-royalty-free-image/1279372828?adppopup=true">Graiki/Moment via Getty Images</a></span></figcaption></figure><p>Bacteria do, and will, end up in food. Everyone eats – intentionally or unintentionally – <a href="https://doi.org/10.7717/peerj.659">millions to billions</a> of live microbes every day. </p>
<p>Most are completely harmless, but some can cause serious illnesses in humans. Because of these potential pathogens, there is a long <a href="https://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/in-depth/pregnancy-nutrition/art-20043844">list of foods to avoid</a>, including uncooked eggs, raw fish and unwashed fruits and vegetables, particularly for pregnant women. The foods themselves are not bad, but the same cannot be said for certain bacterial passengers, such as <em>Listeria monocytogenes</em>, or listeria for short. </p>
<p>This particular pathogen has found ways to indiscriminately get into our foods. While deli and dairy foods like cold cuts, cheese, milk and eggs are frequently culprits for causing listeriosis – the general name for listeria-caused infections – fresh vegetables and fruits have also been implicated.</p>
<p>The variety of foods responsible for <a href="https://www.cdc.gov/listeria/outbreaks/index.html">U.S. listeria outbreaks in the past decade</a> shows just how easily these bacteria get around. Listeria has turned up in <a href="https://www.cdc.gov/listeria/outbreaks/eggs-12-19/index.html">hard-boiled eggs</a>, <a href="https://www.cdc.gov/listeria/outbreaks/enoki-mushrooms-03-20/index.html">enoki mushrooms</a>, <a href="https://www.cdc.gov/listeria/outbreaks/precooked-chicken-07-21/index.html">cooked chicken</a> and, <a href="https://www.cdc.gov/listeria/outbreaks/packaged-salad-12-21-b/index.html">in 2021, packaged salad</a> – <a href="https://www.cdc.gov/listeria/outbreaks/packaged-salad-mix-12-21/index.html">twice</a>.</p>
<p>Even the frozen aisle is not spared from listeria contamination. Contaminated ice cream in Florida was behind this year’s listeria outbreak, with 25 reported cases spanning 11 states since January 2021, according to <a href="https://www.cdc.gov/listeria/outbreaks/monocytogenes-06-22/details.html">an early August 2022 report</a> from the Centers for Disease Control and Prevention. Those who fell ill ranged in age from less than 1 to 92 years old, and 24 of the cases have involved hospitalizations.</p>
<p>How can such a tiny organism bypass extensive disinfection efforts and wreak such havoc? <a href="https://scholar.google.com/citations?user=G_tH2rUAAAAJ&hl=en">As a microbiologist</a> who has been working with listeria and trying to solve these mysteries, I’d like to share some insider secrets about this unique little pathogen and its strategies of survival inside and outside our bodies.</p>
<h2>Farm to table</h2>
<p>To prevent consumer exposure to listeria, the food industries follow <a href="https://www.fda.gov/files/food/published/Draft-Guidance-for-Industry--Control-of-Listeria-monocytogenes-in-Ready-To-Eat-Foods-%28PDF%29.pdf">stringent disinfection and surveillance guidelines</a> from the Food and Drug Administration and the U.S. Department of Agriculture. Any detection of listeria triggers a recall of potentially contaminated food products. </p>
<p>Since 2017, there have been <a href="https://www.fsis.usda.gov/recalls">over 270 listeria-related food recalls</a>. These are incredibly costly and can sometimes lead to fears in consumers <a href="https://www.npr.org/sections/thetwo-way/2018/01/29/581531318/panera-bread-recalls-cream-cheese-across-u-s-over-listeria-fears">as well as nationwide disruptions in food services</a>. However, the recalls represent one of the few tools that the food industry has to protect consumers from foodborne infections. </p>
<p>Not all listeria strains are created equal. <a href="https://doi.org/10.1016/j.ijmm.2010.05.002">Genetic variations</a> in listeria make a big difference in whether the pathogen ends up being involved in multistate outbreaks or simply hitching a ride harmlessly through our digestive tract. Essentially, based on the <a href="https://doi.org/10.1093/jaoac/85.2.524">different methods used</a>, listeria can be subtyped into different lineages, with some associated with outbreaks more frequently than others.</p>
<p>Researchers are investigating ways to tell these listeria strains apart, distinguishing the less harmful ones from those that are particularly dangerous, or hypervirulent. Being able to accurately identify them can help policymakers assess risks and make economically feasible decisions to improve food safety.</p>
<figure class="align-center ">
<img alt="Illustration of red-orange rod-shaped Listeria bacteria." src="https://images.theconversation.com/files/477025/original/file-20220801-70681-jygdr6.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6000%2C3979&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/477025/original/file-20220801-70681-jygdr6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/477025/original/file-20220801-70681-jygdr6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/477025/original/file-20220801-70681-jygdr6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/477025/original/file-20220801-70681-jygdr6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/477025/original/file-20220801-70681-jygdr6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/477025/original/file-20220801-70681-jygdr6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Listeria is an intracellular pathogen. Inside the body, it can grow inside a cell and spread to neighboring cells.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/listeria-monocytogenes-illustration-royalty-free-illustration/685023881">Kateryna Kon/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<h2>Listeria is tough</h2>
<p>Listeria can live in any place where food is grown, packaged, stored, transported, prepared or served. Our research team has even found listeria in <a href="https://doi.org/10.3390/pathogens7030060">organic lettuce harvested from a backyard garden</a>. </p>
<p>Listeria can survive and grow in temperatures as cold as <a href="https://ask.usda.gov/s/article/Can-Listeria-grow-at-refrigerator-temperatures">24 degrees Fahrenheit</a> (-4.4 Celsius) because it has <a href="https://doi.org/10.1080/10408390701856272">adapted to cold temperatures</a> and developed <a href="https://doi.org/10.4315/0362-028X-69.6.1473">tricks for overcoming cold stress</a>. Considering the average refrigerator maintains a temperature range of 35 F to 38 F (1.7 C to 3.3 C), even when the food is stored properly at refrigeration temperatures, a harmless few listeria can grow to dangerous levels of contamination over time.</p>
<p>Listeria is also extremely versatile in adapting to and surviving all kinds of disinfection processes. When it grows on surfaces, listeria protects itself with <a href="https://doi.org/10.3390%2Fpathogens6030041">a biofilm structure</a>, a kind of coating that forms a physical and chemical barrier and prevents disinfectants from reaching the bacteria within.</p>
<p>Surviving the harsh conditions outside our body is only the first part of the story. Before even beginning to cause infections, listeria needs to get to the intestines without getting caught and destroyed by the body’s defenses.</p>
<p>Traveling and surviving passage through a <a href="https://doi.org/10.3389%2Ffcimb.2014.00009">human digestive tract is not easy</a> for bacteria. Saliva enzymes can degrade bacterial cell walls. So can stomach acids and bile salts. Antibodies in our digestive tract can recognize and target bacteria for degradation. Moreover, <a href="https://doi.org/10.1084%2Fjem.20170495">resident gut microbes</a> are strong competitors for the limited amount of space and nutrients in our intestines.</p>
<p>After digestion, the body’s intestinal movement sends traffic one way – out of the body. In order to stick around and cause infections, bacteria have to attach themselves and hang on against the bowel movement while competing for nutrients. Successful pathogens can establish these survival and attachment tasks while undermining our immune defenses. </p>
<p>Listeria that manage to stick around in our intestines can trigger an immune response. In healthy people, that might manifest as <a href="https://www.cdc.gov/listeria/symptoms.html">minor diarrhea or vomiting that goes away without medical attention</a>. </p>
<p>However, those with compromised immune systems or immune systems temporarily weakened as a result of medication or <a href="https://doi.org/10.3389/fimmu.2020.575197">pregnancy</a> can be more susceptible to severe infections. In the absence of an effective immune system, listeria can invade other tissues and organs by creating an efficient niche for growth.</p>
<h2>Listeria in stealth mode</h2>
<p>Listeria is what we microbiologists call an intracellular pathogen. In an infected individual, listeria can grow inside a cell and <a href="https://doi.org/10.1083%2Fjcb.146.6.1333">spread to neighboring cells</a>. Hiding inside our cells this way, listeria avoids detection by antibodies or other immune defenses that are designed to detect and destroy threats that exist outside of our cells.</p>
<p>Once in stealth mode, listeria can move into and infect different organs. Wherever it goes, inflammation follows as the body’s immune system tries to go after the bacteria. The inflammation eventually results in collateral damage in nearby tissues. </p>
<p>In fact, deaths from listeria infections are often associated with the more invasive forms of the disease in which the microbes have breached the intestinal barriers and moved to other body parts. <a href="https://www.cdc.gov/listeria/symptoms.html">Life-threatening illnesses</a> that can result from listeria include meningitis – inflammation around the brain and spinal cord that can occur when these microbes infect the brain – or <a href="https://doi.org/10.1016/j.ijantimicag.2017.12.032">endocarditis</a>, infection of the heart’s inner lining. And in pregnant individuals, if the pathogen reaches the placenta, it can spread to the fetus and cause stillbirth or miscarriage.</p>
<p>As such, invasive listeria cases often have an alarmingly high <a href="https://www.fda.gov/animal-veterinary/animal-health-literacy/get-facts-about-listeria#">hospitalization rate of more than 90% and a fatality rate that can reach 30%</a>. </p>
<p>The scary statistics argue for a proactive and effective infection control to protect vulnerable populations, such as elderly or pregnant individuals, from listeria exposure. </p>
<h2>Think, cook and eat</h2>
<p>If you have risk factors and want to take extra precautions, maybe turn that unpasteurized cider into a hot, mulled cider to kill the bacteria with boiling and simmering. Eat soft cheeses on foods that get cooked, such as pizzas or grilled sandwiches, instead of eating them cold, straight from the refrigerator. Essentially, use heat to bring out the delicious flavors and eliminate potential listeria contamination in your food. </p>
<p>Ultimately, it’s nearly impossible to live in a completely sterile environment, eating food devoid of all living microorganisms. So enjoy your favorites, but <a href="https://www.fsis.usda.gov/food-safety">stay up to date with ongoing recalls</a> and follow the expiration guidelines, especially for ready-to-eat food.</p><img src="https://counter.theconversation.com/content/187905/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Yvonne Sun does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Listeria causes serious illness and food recalls nearly every year.Yvonne Sun, Assistant Professor of Microbiology, University of DaytonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1870562022-08-17T12:38:37Z2022-08-17T12:38:37ZWhen COVID-19 or flu viruses kill, they often have an accomplice – bacterial infections<figure><img src="https://images.theconversation.com/files/479451/original/file-20220816-9774-ss8ukw.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2059%2C1454&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Bacteria can team up with viruses to cause coinfections.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/microscopic-view-of-bacteria-or-virus-moving-in-a-royalty-free-image/1328434309">Erlon Silva - TRI Digital/Moment via Getty Images</a></span></figcaption></figure><p>The <a href="https://www.cdc.gov/flu/pandemic-resources/1918-pandemic-h1n1.html">1918 influenza pandemic</a> resulted in the loss of over 3% of the world’s population – at least 50 million people. But it wasn’t the flu virus that caused the majority of these deaths.</p>
<p>An <a href="https://doi.org/10.1086/591708">analysis of lung samples</a> collected during that flu pandemic indicated that most of the deaths were likely due to bacterial pneumonia, which ran rampant in the absence of antibiotics. Even in more recent history, like the <a href="https://doi.org/10.1016/S0140-6736(58)90060-6">1957 H2N2</a> and <a href="https://doi.org/10.1378/chest.10-1396">2009 H1N1</a> flu pandemics, nearly 18% of patients with viral pneumonia had additional bacterial infections that increased their risk of death. And the <a href="https://doi.org/10.1186/s41479-021-00083-w">COVID-19 pandemic</a> is no different.</p>
<p>With yet another flu season fast approaching in the midst of the ongoing COVID-19 pandemic, lessening the harm caused by these viruses is important to prevent deaths and reduce infections. However, many deaths associated with the flu and COVID-19 don’t occur at the hand of the virus alone. Instead, it’s a <a href="https://doi.org/10.3390/v13091725">secondary bacterial infection</a> that is often at the root of the devastating consequences attributed to an initial viral infection.</p>
<p>I am an <a href="https://medicine.tufts.edu/people/faculty/hayley-muendlein">immunologist</a> who studies why and how cells die during bacterial and viral infections. Understanding the synergy between these microbes is critical not only for effective diagnosis and treatment, but also for managing current pandemics and preventing future ones. My colleagues and I <a href="https://doi.org/10.1073/pnas.2113872119">published a study</a> showing how an immune system protein crucial to fighting against viruses also plays an indispensable role in fighting bacteria.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/fYYy1ySvAhA?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">One Texas man who died in March 2020 tested positive for COVID-19, strep throat and the flu.</span></figcaption>
</figure>
<h2>Viruses and bacteria team up</h2>
<p>Multiple pathogens can cause multiple infections in different ways. Scientists distinguish each type <a href="https://doi.org/10.1186/s41479-021-00083-w">based on the timing</a> of when each infection occurs. <a href="https://www.biomedcentral.com/collections/CIS">Coinfection</a> refers to two or more different pathogens causing infections at the same time. <a href="https://www.mountsinai.org/health-library/special-topic/secondary-infections#">Secondary or superinfections</a>, on the other hand, refer to sequential infections that occur after an initial infection. They’re often caused by pathogens resistant to antibiotics used to treat the primary infection.</p>
<p>How viral and bacterial infections interact with each other increases the potential harm they can cause. Viral respiratory infections can increase the likelihood of bacterial infections and lead to worse disease. The reason why this happens is often multifaceted.</p>
<p>Within your respiratory tract, the epithelial cells lining your airways and lungs serve as the first line of defense against inhaled pathogens and debris. However, <a href="https://doi.org/10.1164/rccm.200909-1420OC">viruses can kill these cells</a> and disrupt this protective barrier, allowing inhaled bacteria to invade. They can also <a href="https://doi.org/10.1164/arrd.1986.134.5.1040">change the surface of epithelial cells</a> to make them easier for bacteria to attach to. </p>
<p>Viruses can also alter the surface of <a href="https://doi.org/10.1164/rccm.201406-1101PP">epithelial and immune cells</a> by <a href="https://doi.org/10.1159/000335548">reducing the number of receptors</a> that help these cells recognize and mount a response against pathogens. This reduction means fewer immune cells report to the viral infection site, giving bacteria an opening to launch another infection.</p>
<h2>Influenza, COVID-19 and bacterial infections</h2>
<p>Patients who have a bacterial infection at the same time they’re battling the seasonal flu are more likely to wind up in a hospital. <a href="https://doi.org/10.1111/j.1750-2659.2012.00360.x">Nearly a quarter</a> of patients admitted to the ICU with severe influenza also have a bacterial infection. One study on the 2010 to 2018 flu seasons found that <a href="https://doi.org/10.1016/j.jiac.2018.10.014">nearly 20% of patients</a> admitted to the hospital with flu-associated pneumonia had acquired bacterial infections.</p>
<p><a href="https://doi.org/10.1016/j.eclinm.2021.100955">Another study</a> of patients hospitalized with viral or bacterial infections found that nearly half had a coinfection with another pathogen. These patients also had nearly double the risk of dying within 30 days compared to those with only a single infection. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of Staphylococcus aureus (MRSA) bacteria" src="https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=407&fit=crop&dpr=1 600w, https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=407&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=407&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=512&fit=crop&dpr=1 754w, https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=512&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=512&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"><em>Staphylococcus aureus</em>, or MRSA, is a common source of bacterial coinfections.</span>
<span class="attribution"><a class="source" href="https://phil.cdc.gov/Details.aspx?pid=10046">Janice Haney Car/Centers for Disease Control and Prevention</a></span>
</figcaption>
</figure>
<p>Interestingly, the <a href="https://doi.org/10.1111/irv.12398">two bacteria species</a> most commonly involved in coinfections with the influenza virus are <em>Streptococcus pneumoniae</em> and <em>Staphylococcus aureus</em>, which normally exist in the respiratory tract without causing disease. However, the influenza virus can damage the cell barrier of the lungs and disrupt immune function enough to make patients susceptible to infection by these otherwise benign bacteria.</p>
<p>Secondary bacterial infections are also exacerbating the COVID-19 pandemic. A 2021 review estimated that <a href="https://doi.org/10.1371/journal.pone.0251170">16% to 28% of adults</a> hospitalized for COVID-19 also had a bacterial infection. These patients stayed in the hospital for twice as long, were four times more likely to need mechanical ventilation and had three times greater odds of dying compared to patients with only COVID-19.</p>
<h2>Addressing secondary and coinfections</h2>
<p>The immune system <a href="https://courses.lumenlearning.com/suny-ap2/chapter/the-immune-response-against-pathogens/">responds differently</a> to viruses and bacteria. <a href="https://theconversation.com/why-are-there-so-many-drugs-to-kill-bacteria-but-so-few-to-tackle-viruses-137480">Antivirals</a> don’t work on bacteria, and antibiotics don’t work on viruses. A better understanding of what pathways the body uses to regulate both antiviral and antibacterial infections is critical to addressing secondary and coinfections.</p>
<p><a href="https://doi.org/10.1073/pnas.2113872119">Recent work</a> by my colleagues and me may provide a clue. We <a href="https://doi.org/10.1101/pdb.top084970">sequenced the RNA</a> of one type of immune cell, macrophages, in mice to identify what molecules were present in cells that were either protected from or died due to bacterial infection. </p>
<p>We identified <a href="https://doi.org/10.1007/82_2019_190">Z-DNA binding protein (ZBP1)</a>, a molecule already known to play a regulatory role in how the immune system responds to influenza. Specifically, ZBP1 <a href="https://doi.org/10.1007/82_2019_190">detects influenza viruses</a> within the lungs and signals infected epithelial and immune cells to self-destruct. This induced cell death eliminates the virus and promotes recruitment of additional immune cells to the infection site.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/1vaEVcMfa1E?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Programmed cell death takes a number of forms, two of which include apoptosis and necrosis.</span></figcaption>
</figure>
<p>Building off this finding that ZBP1 is important for fighting viral infection, we found that macrophages infected with <em>Yersinia pseudotuberculosis</em>, a type of bacteria that causes foodborne illness, also use this protein to initiate <a href="https://doi.org/10.1038/s41467-020-20357-z">cell death</a>. This limits bacterial replication while also sending <a href="https://doi.org/10.1073/pnas.2113872119">inflammatory signals</a> that help clear bacteria.</p>
<p>These findings raise the possibility that ZBP1 may play a dual role in how the body responds to viral and bacterial infections. It’s possible that treatments that increase ZBP1 in certain types of cells may be useful in managing bacterial and viral coinfections.</p><img src="https://counter.theconversation.com/content/187056/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Hayley Muendlein does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Coinfections with bacteria can make viral infections even deadlier. Researchers have identified a protein in immune cells that may play a role in fighting both types of pathogens.Hayley Muendlein, Research Assistant Professor of Immunology, Tufts UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1882142022-08-04T20:44:37Z2022-08-04T20:44:37ZMonkeypox vaccines: A virologist answers 6 questions about how they work, who can get them and how well they prevent infection<figure><img src="https://images.theconversation.com/files/477723/original/file-20220804-20-4y65ta.jpg?ixlib=rb-1.1.0&rect=86%2C113%2C3683%2C2351&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The Jynneos monkeypox vaccine provides strong protection against infection but is in short supply.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/vial-of-the-jynneos-monkeypox-vaccine-sits-on-a-table-at-a-news-photo/1412754952?adppopup=true">Mario Tama/Getty Images</a></span></figcaption></figure><p><em>Monkeypox isn’t going to be the next COVID-19. But with the outbreak having bloomed to <a href="https://www.cdc.gov/poxvirus/monkeypox/response/2022/us-map.html">thousands of infections, with cases in nearly every state</a>, on Aug. 4, 2022, the <a href="https://www.msn.com/en-us/news/us/as-monkeypox-spreads-u-s-declares-a-health-emergency/ar-AA10j7ha?cvid=d63b6a053efb410ca447e51c2fcde7cc">U.S. declared monkeypox a national public health emergency</a>. One reason health experts did not expect monkeypox to become so widespread is that the U.S. had previously approved two vaccines for the virus. <a href="https://scholar.google.com/citations?user=Dxbq8hkAAAAJ&hl=en&oi=ao">Maureen Ferran</a>, a virologist at Rochester Institute of Technology, has been keeping tabs on the two vaccines that can protect against monkeypox.</em></p>
<h2>1. What are the available monkeypox vaccines?</h2>
<p>Two vaccines are currently approved in the U.S. that can provide protection against monkeypox, the <a href="https://www.fda.gov/vaccines-blood-biologics/jynneos">Jynneos vaccine</a> – known as Imvamune/Imvanex in Europe – and <a href="https://www.fda.gov/media/75800/download">ACAM2000</a>, an older smallpox vaccine.</p>
<p>The Jynneos vaccine is produced by <a href="https://www.bavarian-nordic.com/">Bavarian Nordic</a>, a small company in Denmark. The vaccine is for the prevention of smallpox and monkeypox disease in adults ages 18 and older who are at high risk for infection with either virus. It was approved in Europe in 2013 and by the U.S. <a href="https://www.fda.gov/media/131079/download">Food and Drug Administration in 2019</a>. </p>
<p>The Jynneos vaccine is given in two doses four weeks apart and <a href="https://www.webmd.com/a-to-z-guides/monkeypox-vaccination#">contains a live vaccinia virus</a>. Vaccinia normally infects cattle and is a type of poxvirus, a family of viruses that includes smallpox and monkeypox. The virus in this vaccine has been crippled – or attenuated – so that it is no longer able to replicate in cells. </p>
<p>This vaccine is good at protecting those who are at high risk for monkeypox from getting infected before exposure and can also lessen the severity of disease post-infection. It is effective against smallpox as well as monkeypox. Until the recent monkeypox outbreak, this vaccine was primarily given to health care workers or people who have had confirmed or suspected monkeypox exposure.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/477726/original/file-20220804-14-ckx2sj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A circular mass of squiggly lines." src="https://images.theconversation.com/files/477726/original/file-20220804-14-ckx2sj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/477726/original/file-20220804-14-ckx2sj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=461&fit=crop&dpr=1 600w, https://images.theconversation.com/files/477726/original/file-20220804-14-ckx2sj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=461&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/477726/original/file-20220804-14-ckx2sj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=461&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/477726/original/file-20220804-14-ckx2sj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=580&fit=crop&dpr=1 754w, https://images.theconversation.com/files/477726/original/file-20220804-14-ckx2sj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=580&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/477726/original/file-20220804-14-ckx2sj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=580&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Both the Jynneos and ACAM2000 vaccines use the vaccinia virus, shown here, to produce immunity to smallpox and monkeypox.</span>
<span class="attribution"><a class="source" href="https://phil.cdc.gov/details.aspx?pid=2143">CDC/ Cynthia Goldsmith</a></span>
</figcaption>
</figure>
<p>The <a href="https://www.fda.gov/vaccines-blood-biologics/vaccines/acam2000-smallpox-vaccine-questions-and-answers">ACAM2000 vaccine</a> was <a href="https://www.fda.gov/media/75792/download">approved by the FDA in 2007</a> for protection against smallpox disease. This vaccine is also based on vaccinia virus, however the version of the vaccinia virus in the ACAM2000 vaccine is able to replicate in a person’s cells. Because of this, the ACAM2000 vaccine can be <a href="https://www.fda.gov/vaccines-blood-biologics/vaccines/acam2000-smallpox-vaccine-questions-and-answers#">associated with serious side effects</a>. These can include severe skin infections as well as <a href="https://www.cdc.gov/smallpox/vaccine-basics/vaccination-effects.html">potentially life-threatening heart problems in vulnerable people</a>. Another potential issue with the ACAM2000 vaccine is that it is more <a href="https://www.vox.com/2022/7/29/23281407/monkeypox-vaccine-acam2000-jynneos-smallpox">complicated to administer compared to a normal shot</a>.</p>
<p>The U.S. government has over <a href="https://www.fda.gov/vaccines-blood-biologics/vaccines/acam2000-smallpox-vaccine-questions-and-answers">200 million doses of ACAM2000 stockpiled</a> in case of a biological weapon attack of smallpox. But despite the adequate supply of the vaccine, ACAM2000 is not being used to vaccinate against monkeypox because of the risk of serious adverse side effects. For now, only designated U.S. military personnel and laboratory researchers who work with certain poxviruses may receive this vaccine. </p>
<h2>2. How effective are these vaccines?</h2>
<p>According to the U.S. Centers for Disease Control, there is not <a href="https://www.cdc.gov/poxvirus/monkeypox/considerations-for-monkeypox-vaccination.html">yet any data available</a> on the effectiveness of either vaccine in the current outbreak of monkeypox. But there is older data available from animal studies, clinical trials and studies in Africa.</p>
<p>A number of clinical trials done during the approval process for the Jynneos vaccine show that when given to a person, it <a href="https://www.precisionvaccinations.com/vaccines/jynneos-smallpox-monkeypox-vaccine">triggers a strong antibody response</a> on par with the ACAM2000 vaccine. An additional study done in nonhuman primates showed that vaccinated animals that were infected with monkeypox survived <a href="https://www.fda.gov/media/131078/download">80% to 100% of the time, compared with zero to 40% survival</a> in unvaccinated animals.</p>
<p>Another use of the Jynneos vaccine is as a <a href="https://www.nmhealth.org/publication/view/policy/7661/">post-exposure prophylaxis, or PEP</a>, meaning the vaccine can be effective even when given after exposure to the virus. Because the monkeypox virus incubates in a person’s body for six to 14 days, the body of someone who <a href="https://www.cdc.gov/poxvirus/monkeypox/considerations-for-monkeypox-vaccination.html">gets the Jynneos vaccine shortly after being exposed</a> will produce antibodies that can help fight off infection and protect against a serious monkeypox case.</p>
<p>The ACAM2000 data is older and less precise but shows strong protection. Researchers tested the vaccine during an outbreak of monkeypox in central Africa in the 1980s. Although the study was small and didn’t directly test vaccine efficacy, the authors concluded that unvaccinated people faced an <a href="https://www.cdc.gov/poxvirus/monkeypox/clinicians/smallpox-vaccine.html">85% higher risk of being infected than vaccinated people</a>. </p>
<h2>3. Does a smallpox vaccine protect against monkeypox?</h2>
<p><a href="https://www.charlotteobserver.com/news/state/north-carolina/article264045516.html">According to the CDC</a>, a previous smallpox vaccination does provide some protection against monkeypox, though that <a href="https://www.charlotteobserver.com/news/state/north-carolina/article264045516.html#storylink=cpy">protection wanes over time</a>. Experts advise that anyone who had the <a href="https://www.npr.org/2022/07/24/1113197119/monkeypox-symptoms-prevention-vaccines-what-to-know">smallpox vaccine more than three years ago</a> and is at increased risk for monkeypox get the monkeypox vaccine.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/477725/original/file-20220804-23-gdsh7v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="People lining up for monkeypox vaccines." src="https://images.theconversation.com/files/477725/original/file-20220804-23-gdsh7v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/477725/original/file-20220804-23-gdsh7v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/477725/original/file-20220804-23-gdsh7v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/477725/original/file-20220804-23-gdsh7v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/477725/original/file-20220804-23-gdsh7v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/477725/original/file-20220804-23-gdsh7v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/477725/original/file-20220804-23-gdsh7v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">In California and New York City, demand for vaccines has been high among at-risk communities.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/MonkeypoxVaccineCalifornia/acac850b3b834fe6aa41d421eb737748/photo?Query=monkeypox%20vaccine&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=59&currentItemNo=13">AP Photo/Marcio Jose Sanchez</a></span>
</figcaption>
</figure>
<h2>4. Who should get vaccinated?</h2>
<p>At the national level, anyone who has had close contact with an infected person, who has a weakened immune system or who had dermatitis or eczema is <a href="https://www.cdc.gov/poxvirus/monkeypox/considerations-for-monkeypox-vaccination.html">eligible for a Jynneos vaccine</a>.</p>
<p>Some state and local governments are also making vaccines available to people in communities at higher risk for monkeypox. For example, New York City is allowing men who have sex with men and who have had multiple sexual partners in the past 14 days <a href="https://www.nytimes.com/article/monkeypox-vaccine-nyc.html?action=click&pgtype=Article&state=default&module=styln-monkeypox&region=MAIN_CONTENT_1&block=storyline_levelup_swipe_recirc">to get vaccinated</a>. </p>
<h2>5. What is the supply like for the Jynneos vaccine?</h2>
<p>As of July 29, 2022, a little over <a href="https://aspr.hhs.gov/SNS/Pages/JYNNEOS-Distribution.aspx">300,000 doses have been shipped to points of care or administered</a>, with another 700,000 already allocated to states across the U.S. However, demand is far outpacing supply. Public health officials acknowledge that <a href="https://www.forbes.com/sites/roberthart/2022/07/18/struggling-to-find-a-monkeypox-shot-severe-shortages-and-technical-mishaps-are-slowing-down-rollouts/?sh=2a3b4ed9e018">vaccine supply shortages have resulted in</a> long lines and clinics having to close when they run out of vaccines. The issues have been magnified by <a href="https://www.axios.com/2022/07/13/monkeypox-vaccine-new-york-website">technical problems with online booking systems</a>, particularly in New York City. </p>
<p>To help boost supply, the U.S. has ordered nearly <a href="https://www.nytimes.com/2022/07/15/health/monkeypox-vaccine-supply.html">7 million doses of the Jynneos vaccine</a>, which are expected to arrive over the coming months. </p>
<h2>6. What about just using one dose of Jynneos?</h2>
<p>Although federal health officials advise against withholding the second dose, some places – including <a href="https://www.washingtonpost.com/dc-md-va/2022/07/25/dc-monkeypox-vaccines-first-dose/">Washington, D.C.</a>, and <a href="https://www1.nyc.gov/site/doh/about/press/pr2022/monkeypox-vaccination-prioritization-first-doses.page">New York City</a> – are withholding the second dose until more become available. This strategy is being used in <a href="https://www.gov.uk/government/publications/monkeypox-vaccination-resources/protecting-you-from-monkeypox-information-on-the-smallpox-vaccination">Britain</a> and Canada as well to vaccinate as many people as possible at least one time.</p>
<p>A previous study reported that a <a href="https://doi.org/10.1073/pnas.0804985105">single shot</a> of the Jynneos vaccine <a href="https://doi.org/10.1056/NEJMoa1817307">protected monkeys infected with monkeypox</a> and that this protection lasted for at least two years. If this holds up in the real world, it would support withholding second doses in favor of immunizing more Americans. This would be key as many health experts expect the virus to continue spreading, furthering increasing demand of the vaccine.</p><img src="https://counter.theconversation.com/content/188214/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Maureen Ferran receives funding from the National Institutes of Health.</span></em></p>There are two approved monkeypox vaccines in the US. Both use a related poxvirus called vaccinia to produce an immune response that protects against smallpox and monkeypox.Maureen Ferran, Associate Professor of Biology, Rochester Institute of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1869702022-08-04T12:23:36Z2022-08-04T12:23:36ZLong COVID-19 and other chronic respiratory conditions after viral infections may stem from an overactive immune response in the lungs<figure><img src="https://images.theconversation.com/files/477255/original/file-20220802-23-r6z7fj.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2297%2C1292&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The immune system usually stays dormant in the lungs in times of health.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/lung-virus-infection-royalty-free-image/1205199983">wildpixel/iStock via Getty Images</a></span></figcaption></figure><p>Viruses that cause respiratory diseases like the flu and COVID-19 can lead to mild to severe symptoms within the first few weeks of infection. These symptoms typically resolve within a few more weeks, sometimes with the help of treatment if severe. However, some people go on to experience persistent symptoms that last several months to years. Why and how respiratory diseases can develop into chronic conditions like <a href="https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html">long COVID-19</a> are still unclear.</p>
<p>I am a <a href="https://scholar.google.com/citations?hl=en&user=BNGZA1MAAAAJ">doctoral student</a> working in the <a href="https://www.immunology.virginia.edu/Sun/">Sun Lab</a> at the University of Virginia. We study how the immune system sometimes goes awry after fighting off viral infections. We also develop ways to target the immune system to prevent further complications without weakening its ability to protect against future infections. Our <a href="https://doi.org/10.1126/sciimmunol.abm7996">recently published review</a> of the research in this area found that it is becoming clearer that it might not be an active viral infection causing long COVID-19 and similar conditions, but an overactive immune system.</p>
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<figcaption><span class="caption">Long COVID-19 patients can experience persistent respiratory, cognitive and neurological symptoms.</span></figcaption>
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<h2>The lungs in health and disease</h2>
<p>Keeping your immune system dormant when there isn’t an active infection is essential for your lungs to be able to function optimally. </p>
<p>Your respiratory tract is in constant contact with your external environment, sampling around <a href="https://www.acepnow.com/article/avoid-airway-catastrophes-extremes-minute-ventilation/">5 to 8 liters (1.3 to 2 gallons) of air</a> – and the toxins and microorganisms in it – every minute. Despite continuous exposure to potential pathogens and harmful substances, your body has evolved to <a href="https://doi.org/10.1164/ajrccm.162.supplement_3.15tac6">keep the immune system dormant in the lungs</a>. In fact, allergies and conditions such as asthma are byproducts of an <a href="https://doi.org/10.1513/AnnalsATS.201401-028AW">overactive immune system</a>. These excessive immune responses can cause your airways to constrict and make it difficult to breathe. Some severe cases may require treatment to suppress the immune system. </p>
<p>During an active infection, however, the immune system is absolutely essential. When viruses infect your respiratory tract, immune cells are recruited to your lungs to fight off the infection. Although these cells are crucial to eliminate the virus from your body, their activity often results in collateral damage to your lung tissue. After the virus is removed, your body <a href="https://doi.org/10.1007%2Fs00281-016-0560-6">dampens your immune system</a> to give your lungs a chance to recover.</p>
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<figcaption><span class="caption">An overactive immune system, as in the case of asthma, can damage the lungs.</span></figcaption>
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<p>Over the past decade, researchers have identified a variety of <a href="https://doi.org/10.1016/j.stem.2020.03.009">specialized stem cells in the lungs</a> that can help regenerate damaged tissue. These stem cells can turn into almost all the different types of cells in the lungs depending on the signals they receive from their surrounding environment. <a href="https://doi.org/10.1126/scitranslmed.abo5254">Recent</a> <a href="https://doi.org/10.1016/j.stem.2020.06.020">studies</a> <a href="https://doi.org/10.1016/j.stemcr.2019.02.013">have highlighted</a> the prominent role the immune system plays in providing signals that facilitate lung recovery. But these signals can produce more than one effect. They can not only activate stem cells, but also perpetuate damaging inflammatory processes in the lung. Therefore, your body tightly regulates when, where and how strongly these signals are made in order to prevent further damage.</p>
<p>While the reasons are still unclear, some people are unable to turn off their immune system after infection and <a href="https://doi.org/10.1126/sciimmunol.abk1741">continue to produce tissue-damaging molecules</a> <a href="https://doi.org/10.1038/s41590-021-01113-x">long after</a> the virus has been flushed out. This not only further damages the lungs, but also interferes with regeneration via the lung’s resident stem cells. This phenomenon can result in chronic disease, as seen in several respiratory viral infections including <a href="https://doi.org/10.1016/j.immuni.2022.01.017">COVID-19</a>, <a href="https://doi.org/10.2340/16501977-2694">Middle East Respiratory Syndrome (MERS)</a>, <a href="https://doi.org/10.1056/NEJMoa1211917">respiratory syncytial virus (RSV)</a> and the <a href="https://doi.org/10.1016/j.jaci.2005.06.024">common cold</a>.</p>
<h2>The immune system’s role in chronic disease</h2>
<p>In our review, my colleagues and I found that many <a href="https://doi.org/10.1126/sciimmunol.abm7996">different types of immune cells</a> are involved in the development of chronic disease after respiratory viral infections, including long COVID-19.</p>
<p>Scientists so far have identified one particular type of immune cells, <a href="https://doi.org/10.1126/sciimmunol.abk1741">killer T cells</a>, as potential contributors to chronic disease. Also known as cytotoxic or CD8+ T cells, they specialize in killing infected cells either by interacting directly with them or by producing damaging molecules called cytokines. </p>
<p>Killer T cells are essential to curbing the virus from spreading in the body during an active infection. But their persistence in the lungs after the infection has resolved is linked to extended <a href="https://doi.org/10.1126/sciimmunol.abc4557">reduced respiratory function</a>. Moreover, animal studies have shown that <a href="https://doi.org/10.1126/sciimmunol.abk1741">removing killer T cells from the lungs</a> after infection may improve lung function and tissue repair.</p>
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<figcaption><span class="caption">A legion of immune cells work together to remove invading pathogens.</span></figcaption>
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<p>Another type of immune cells called monocytes are also involved in fighting respiratory infections, serving among the first responders by producing virus- and tissue-damaging cytokines. Research has found that these cells also <a href="https://doi.org/10.1016/j.immuni.2022.01.017">continue to accumulate</a> in the lungs of long COVID-19 patients and promote a pro-inflammatory environment that can cause further damage.</p>
<p>Understanding the immunological mechanisms underlying long COVID-19 is the first step to addressing a <a href="https://www.kff.org/policy-watch/what-are-the-implications-of-long-covid-for-employment-and-health-coverage/">quickly worsening public health problem</a>. Identifying the subtle differences in how the same immune cells that protect you during an active infection can later become harmful could lead to earlier diagnosis of long COVID-19. Moreover, based on our findings, my team and I believe treatments that target the immune system could be an effective approach to manage long COVID-19 symptoms. We believe that this strategy may turn out to be useful not only for COVID-19, but also for other respiratory viral infections that lead to chronic disease as well.</p><img src="https://counter.theconversation.com/content/186970/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Harish Narasimhan does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>While a strong immune response is essential to fight against viral infection, an immune system that continues to stay active long after the virus has been cleared can lead to lung damage.Harish Narasimhan, PhD Candidate in Immunology, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.