tag:theconversation.com,2011:/fr/topics/infectious-disease-research-6212/articlesInfectious disease research – The Conversation2023-04-26T12:29:00Ztag:theconversation.com,2011:article/2034582023-04-26T12:29:00Z2023-04-26T12:29:00ZLeprosy-causing bacteria found in armadillo specimens highlight value of museum collections for tracking pathogens<figure><img src="https://images.theconversation.com/files/522875/original/file-20230425-26-v4ci28.jpg?ixlib=rb-1.1.0&rect=0%2C54%2C2804%2C1958&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Museum specimens are like time capsules from where and when the organisms and their pathogens lived.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/learning-by-touch-a-youngster-above-touches-the-tail-of-a-news-photo/162008261">Ed Maker/The Denver Post 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>Years-old tissue samples from <a href="https://doi.org/10.3201/eid2903.221636">armadillos in museum collections</a> may harbor <em>Mycobacterium leprae</em>, the <a href="https://www.cdc.gov/leprosy/">bacteria that causes Hansen’s disease</a>, also called leprosy, according to recent research my colleagues <a href="https://scholar.google.com/citations?user=-zU5O_AAAAAJ&hl=en&oi=ao">and I</a> conducted.</p>
<p><a href="https://www.niaid.nih.gov/diseases-conditions/leprosy-hansens-disease">Leprosy can cause nerve damage</a> that, without early effective treatment, can lead to paralysis and blindness in the most severe cases. Approximately <a href="https://apps.who.int/neglected_diseases/ntddata/leprosy/leprosy.html">140,000 new patients were diagnosed</a> worldwide in 2021, mostly concentrated in India, Brazil and Indonesia. Since 2010, evidence has accumulated that the nine-banded armadillo, <em>Dasypus novemcinctus</em>, is <a href="https://doi.org/10.1056/NEJMoa1010536">transmitting leprosy to people in North America</a> and potentially <a href="https://doi.org/10.1371/journal.pntd.0008276">elsewhere</a>.</p>
<p>To investigate this connection, we turned to 10 natural history museums in the U.S. <a href="https://doi.org/10.1073/pnas.1522680112">These institutions offer more</a> than just public exhibitions. They also host thousands of biological samples, collected over many years. Examining these historical specimens could help researchers identify pathogen prevalence and diversity across time and space.</p>
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<a href="https://images.theconversation.com/files/519981/original/file-20230408-4224-et8tzb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram illustrating number of museums, locations where armadillos were collected and prevalence of pathogen in samples tested." src="https://images.theconversation.com/files/519981/original/file-20230408-4224-et8tzb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/519981/original/file-20230408-4224-et8tzb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=296&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519981/original/file-20230408-4224-et8tzb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=296&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519981/original/file-20230408-4224-et8tzb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=296&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519981/original/file-20230408-4224-et8tzb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=373&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519981/original/file-20230408-4224-et8tzb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=373&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519981/original/file-20230408-4224-et8tzb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=373&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Molecular diagnostic techniques identified the leprosy-causing <em>Mycobacterium leprae</em> bacteria in archived tissue samples from 14.8% of nine-banded armadillos tested.</span>
<span class="attribution"><span class="source">Daniel Romero-Alvarez</span></span>
</figcaption>
</figure>
<p>In our study, we used online repositories such as <a href="http://vertnet.org/">VertNet</a> to identify armadillo specimens held by museums. We then physically examined tissue samples from 159 individual animals from 10 armadillo species. Specimens were collected between 1974 and 2017 from eight countries in the Americas.</p>
<p>Using molecular diagnostic techniques, we identified <em>M. leprae</em> bacteria in muscle, spleen and liver tissues in 18 out of 122 nine-banded armadillos – a prevalence of 14.8%. All positive samples were collected between 1996 and 2014. Our research allowed us to peek into the immediate past to see that <em>M. leprae</em> was circulating in armadillos in previously unknown locations.</p>
<h2>Why it matters</h2>
<p>How leprosy is transmitted is still under debate. The bacteria can apparently spread in aerosols and droplets <a href="https://doi.org/10.47276/lr.86.2.142">released by the coughs or sneezes</a> of infected patients. But because some people become sick without being exposed to an infected person or traveling to an area where leprosy is present, researchers think there must be <a href="https://doi.org/10.1371/journal.pntd.0008276">another way it spreads</a>.</p>
<p>In the last decade, molecular examinations of nonhuman samples, water and soils have suggested that wildlife and the environment are potential <a href="https://doi.org/10.1371/journal.pntd.0008276">sources of leprosy</a>. Our analysis revealed that the <em>M. leprae</em> strain identified in the positive museum samples is very similar to one that has been circulating in North American armadillos since the 1990s, when transmission of leprosy through wildlife <a href="https://doi.org/10.1067/mjd.2000.106368">was still only suggested</a>. </p>
<h2>What other research is being done</h2>
<p>In animals, researchers have used museum specimens to study <a href="https://doi.org/10.3201/eid2707.204864">snake fungal disease</a> and the <a href="https://doi.org/10.1007/s10530-017-1390-8">chytrid fungus that affects frogs</a>.</p>
<p>Scientists less often examine museum archives for <a href="https://doi.org/10.1371/journal.ppat.1009583">pathogens that affect humans</a>. Researchers have, however, identified <em>Tripanosoma cruzi</em>, the agent that causes <a href="https://doi.org/10.3201/eid1602.090998">Chagas disease, in wood rats</a> in natural history museum collections, as well as <a href="https://doi.org/10.1641/0006-3568(2002)052%5B0989:TEAEHO%5D2.0.CO;2">hantaviruses in deer mouse</a> specimens.</p>
<p>Since approximately 70% of emerging human infectious diseases <a href="https://doi.org/10.1098/rstb.2001.0888">originate in wildlife</a>, examining museum specimens will likely help identify where and when particular pathogens have existed. Ultimately, understanding more about which pathogens are emerging, and where – as we did with leprosy and armadillos – can help scientists anticipate potential outbreaks and maybe even head them off. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/522705/original/file-20230424-24-ozr82v.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="a rack of centrifuge tubes and a vial of sample" src="https://images.theconversation.com/files/522705/original/file-20230424-24-ozr82v.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/522705/original/file-20230424-24-ozr82v.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/522705/original/file-20230424-24-ozr82v.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/522705/original/file-20230424-24-ozr82v.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/522705/original/file-20230424-24-ozr82v.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/522705/original/file-20230424-24-ozr82v.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/522705/original/file-20230424-24-ozr82v.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">Molecular techniques extracted and amplified DNA from the historical samples housed in museum collections.</span>
<span class="attribution"><span class="source">Daniel Romero-Alvarez</span></span>
</figcaption>
</figure>
<h2>What still isn’t known</h2>
<p>Scientists discovered in 2008 that another pathogen, <a href="https://doi.org/10.1073/pnas.1421504112"><em>Mycobacterium lepromatosis</em>, can also cause leprosy</a>. Researchers have yet to untangle the role of this second bacteria in the worldwide incidence of the disease.</p>
<p>All our 159 armadillo samples were negative for <em>M. lepromatosis</em>. But this bacteria has infected humans in <a href="https://doi.org/10.3389/fmicb.2021.698588">Mexico, Colombia, Canada and elsewhere</a>, along with <a href="https://doi.org/10.1126/science.aah3783">red squirrels in the British Isles</a>.</p>
<p>My colleagues and I <a href="https://www.romerostories.com/post/lepra-en-armadillos-parte-i-museos-y-tejidos">hope our discovery</a> prompts further research on the role of nonhuman sources of leprosy transmission across the Americas. <a href="https://doi.org/10.3201/eid2903.221636">Our work</a> is another case study demonstrating that natural history collections can <a href="https://theconversation.com/museums-preserve-clues-that-can-help-scientists-predict-and-analyze-future-pandemics-141175">play an important role</a> in human infectious disease research.</p><img src="https://counter.theconversation.com/content/203458/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Daniel Romero-Alvarez 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>Museum archives hold biological specimens that have been collected over years or even decades. Modern molecular analysis of these collections can reveal information about pathogens and their spread.Daniel Romero-Alvarez, Ph.D. Candidate in Ecology of Infectious Diseases, University of KansasLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1913952022-09-28T12:32:45Z2022-09-28T12:32:45ZLouis Pasteur’s scientific discoveries in the 19th century revolutionized medicine and continue to save the lives of millions today<figure><img src="https://images.theconversation.com/files/486616/original/file-20220926-26-u8ycb1.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C8764%2C5689&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Louis Pasteur was a pioneer in chemistry, microbiology, immunology and vaccinology.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/louis-pasteur-royalty-free-illustration/1176911773?adppopup=true">pictore/DigitalVision Vectors via Getty Images</a></span></figcaption></figure><p>Some of the greatest scientific discoveries haven’t resulted in Nobel Prizes.</p>
<p><a href="https://doi.org/10.1111/j.1469-0691.2012.03945.x">Louis Pasteur</a>, who lived from 1822 to 1895, is arguably the world’s best-known microbiologist. He is widely credited for the <a href="https://www.ncbi.nlm.nih.gov/books/NBK24649/">germ theory of disease</a> and for inventing the process of pasteurization – which is named after him – to preserve foods. Remarkably, he also developed <a href="https://doi.org/10.1111%2Fj.1365-2249.2012.04592.x">the rabies</a> and <a href="https://www.cdc.gov/anthrax/basics/anthrax-history.html#">anthrax</a> vaccines and made major contributions to <a href="https://www.vbivaccines.com/evlp-platform/louis-pasteur-attenuated-vaccine/#">combating cholera</a>.</p>
<p>But because he died in 1895, six years before the first <a href="https://www.nobelprize.org/">Nobel Prize</a> was awarded, that prize isn’t on his resume. Had he lived in the era of Nobel Prizes, he would undoubtedly have been deserving of one for his work. Nobel Prizes, which are awarded in various fields, <a href="https://www.nobelprize.org/the-nobel-prize-organisation/#">including physiology and medicine</a>, are not given posthumously.</p>
<p>During the current time of ongoing threats from emerging or reemerging infectious diseases, from <a href="https://www.contagionlive.com/view/virus-spillover-and-emerging-pathogens-pick-up-speed">COVID-19</a> and polio to <a href="https://theconversation.com/what-is-monkeypox-a-microbiologist-explains-whats-known-about-this-smallpox-cousin-183499">monkeypox</a> and <a href="https://doi.org/10.12703/b/9-9">rabies</a>, it is awe-inspiring to look back on Pasteur’s legacy. His efforts fundamentally changed how people view infectious diseases and how to fight them via vaccines. </p>
<p>I’ve worked in <a href="https://rodneyerohde.wp.txstate.edu/">public health and medical laboratories</a> specializing in viruses and other microbes, while <a href="https://www.health.txstate.edu/cls/">training future medical laboratory scientists</a>. My career started in virology with a <a href="https://scholar.google.com/citations?user=8XtvOZ8AAAAJ&hl=en">front-row seat to rabies detection and surveillance</a> and zoonotic agents, and it rests in large part on Pasteur’s pioneering work in microbiology, immunology and vaccinology. </p>
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<a href="https://images.theconversation.com/files/486641/original/file-20220926-8928-88tfgu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A black and white illustration of Pasteur with a group of patients." src="https://images.theconversation.com/files/486641/original/file-20220926-8928-88tfgu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/486641/original/file-20220926-8928-88tfgu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=492&fit=crop&dpr=1 600w, https://images.theconversation.com/files/486641/original/file-20220926-8928-88tfgu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=492&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/486641/original/file-20220926-8928-88tfgu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=492&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/486641/original/file-20220926-8928-88tfgu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=618&fit=crop&dpr=1 754w, https://images.theconversation.com/files/486641/original/file-20220926-8928-88tfgu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=618&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/486641/original/file-20220926-8928-88tfgu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=618&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">An illustration of Louis Pasteur, right, supervising the administration of the rabies vaccine at the Pasteur Institute in Paris in 1886.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/an-illustration-shows-french-biologist-louis-pasteur-right-news-photo/1266883710">Library of Congress/Interim Archives via Getty Images</a></span>
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<h2>First, a chemist</h2>
<p>In my assessment, Pasteur’s strongest contributions to science are his remarkable achievements in the field of medical microbiology and immunology. However, his story begins with chemistry. </p>
<p>Pasteur studied under the <a href="https://www.britannica.com/biography/Jean-Baptiste-Andre-Dumas">French chemist Jean-Baptiste-André Dumas</a>. During that time, Pasteur became interested in the origins of life and worked in the field of <a href="https://www.pasteur.fr/en/institut-pasteur/history/early-years-1847-1862">polarized light and crystallography</a>. </p>
<p>In 1848, just months after receiving his doctorate degree, Pasteur was studying the properties of crystals formed in the process of wine-making when he discovered that <a href="https://www.nytimes.com/2017/06/14/science/louis-pasteur-chirality-chemistry.html">crystals occur in mirror-image forms</a>, a property known as chirality. This discovery became the foundation of a subdiscipline of chemistry known as <a href="https://doi.org/10.1002/hlca.201900098">stereochemistry</a>, which is the study of the spatial arrangement of atoms within molecules. This chirality, or handedness, of molecules was a “<a href="https://doi.org/10.1007/BF03401596">revolutionary hypothesis</a>” at the time. </p>
<p>These findings led Pasteur to suspect what would later be proved through molecular biology: All life processes ultimately stem from the precise arrangement of atoms within biological molecules.</p>
<h2>Wine and beer – from fermentation to germ theory</h2>
<p>Beer and wine were <a href="https://ageofrevolutions.com/2016/12/05/intoxication-and-the-french-revolution/">critical to the economy of France</a> and Italy in the 1800s. It was not uncommon during Pasteur’s life for products to spoil and become bitter or dangerous to drink. At the time, the scientific notion of “spontaneous generation” held that life can arise from nonliving matter, which was believed to be the culprit behind wine spoiling. </p>
<p>While many scientists tried to disprove the theory of spontaneous generation, in 1745, English biologist <a href="https://royalsocietypublishing.org/doi/pdf/10.1098/rstl.1748.0072">John Turberville Needham</a> believed he had created the perfect experiment favoring spontaneous generation. Most scientists believed that heat killed life, so Needham created an experiment to show that microorganisms could grow on food, even after boiling. After boiling chicken broth, he placed it in a flask, heated it, then sealed it and waited, not realizing that air could make its way back into the flask prior to sealing. After some time, microorganisms grew, and Needham claimed victory. </p>
<p>However, his experiment <a href="https://pubmed.ncbi.nlm.nih.gov/17940406/">had two major flaws</a>. For one, the boiling time was not sufficient to kill all microbes. And importantly, his flasks allowed air to flow back in, which enabled microbial contamination.</p>
<p>To settle the scientific battle, the French Academy of Sciences sponsored a contest for the best experiment <a href="https://doi.org/10.1080/00033798800200281">to prove or disprove spontaneous generation</a>. Pasteur’s response to the contest was a series of experiments, including a <a href="https://doi.org/10.3389%2Ffimmu.2012.00068">prize-winning 1861 essay</a>. </p>
<p>Pasteur deemed one of these experiments as “unassailable and decisive” because, unlike Needham, after he sterilized his cultures, he kept them free from contamination. By using his now famous swan-necked flasks, which had a long S-shaped neck, he allowed air to flow in while at the same time preventing falling particles from reaching the broth during heating. As a result, the flask remained free of growth for an extended period. This showed that if air was not allowed directly into his boiled infusions, then no “living microorganisms would appear, even after months of observation.” However, importantly, if dust was introduced, living microbes appeared.</p>
<p>Through that process, Pasteur not only refuted the theory of spontaneous generation, but he also demonstrated that microorganisms were everywhere. When he showed that food and wine spoiled because of contamination from invisible bacteria rather than from spontaneous generation, <a href="https://doi.org/10.3389%2Ffimmu.2012.00068">the modern germ theory of disease was born</a>.</p>
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<figcaption><span class="caption">Pasteur’s discoveries resonate to this very day.</span></figcaption>
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<h2>The origins of vaccination in the 1800s</h2>
<p>In the 1860s, when the silk industry was being devastated by two diseases that were <a href="https://www.pasteur.fr/en/institut-pasteur/history/middle-years-1862-1877">infecting silkworms</a>, Pasteur <a href="https://doi.org/10.1111/j.1469-0691.2012.03945.x">developed a clever process</a> by which to examine silkworm eggs under a microscope and preserve those that were healthy. Much like his efforts with wine, he was able to apply his observations into industry methods, and he became something of <a href="https://doi.org/10.3390%2Fbiom12040596">a French hero</a>.</p>
<p>Even <a href="https://www.biography.com/scientist/louis-pasteur">with failing health</a> from a severe stroke that left him partially paralyzed, Pasteur continued his work. In 1878, he succeeded in identifying and culturing the bacterium that <a href="https://doi.org/10.3389/fimmu.2012.00068">caused the avian disease fowl cholera</a>. He recognized that old bacterial cultures were no longer harmful and that chickens vaccinated with old cultures could survive exposure to wild strains of the bacteria. And his observation that surviving chickens excreted harmful bacteria helped establish an important concept now all too familiar in the age of COVID-19 – asymptomatic “healthy carriers” can still spread germs during outbreaks.</p>
<p>After bird cholera, Pasteur turned to the prevention of <a href="https://rarediseases.org/rare-diseases/anthrax/">anthrax</a>, a widespread plague of cattle and other animals caused by the bacterium <em>Bacillus anthracis</em>. Building on his own work and that of German physician <a href="https://doi.org/10.12816/0003334">Robert Koch</a>, Pasteur developed the concept of the <a href="https://doi.org/10.3389/fimmu.2012.00068">attenuated, or weakened, versions of microbes</a> for use in vaccines.</p>
<p>In the late 1880s, he showed beyond any doubt that exposing cattle to a weakened form of anthrax vaccine could lead to what is now well known as immunity, dramatically reducing cattle mortality.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/486643/original/file-20220926-25-dha566.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A computer-generated image of the rabies virus, colored brown in this illustration and resembling a pinecone." src="https://images.theconversation.com/files/486643/original/file-20220926-25-dha566.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/486643/original/file-20220926-25-dha566.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=337&fit=crop&dpr=1 600w, https://images.theconversation.com/files/486643/original/file-20220926-25-dha566.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=337&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/486643/original/file-20220926-25-dha566.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=337&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/486643/original/file-20220926-25-dha566.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/486643/original/file-20220926-25-dha566.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/486643/original/file-20220926-25-dha566.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&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 deadly rabies virus. Although preventable by vaccination, rabies still kills approximately 59,000 people worldwide every year.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/rabies-virus-illustration-royalty-free-illustration/1191008423">Nano Clustering/Science Photo Library via Getty Images</a></span>
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<h2>The rabies vaccine breakthrough</h2>
<p>In my professional assessment of Louis Pasteur, the discovery of vaccination against rabies is the most important of all his achievements. </p>
<p>Rabies has been called the “<a href="https://www.goodreads.com/book/show/13403051-rabid">world’s most diabolical virus</a>,” spreading from animal to human <a href="https://doi.org/10.12703/b/9-9">via a bite</a>. </p>
<p>Working with rabies virus is incredibly dangerous, as <a href="https://www.elsevier.com/books/rabies/wilson/978-0-323-63979-8">mortality approaches 100%</a> once symptoms appear and without vaccination. Through astute observation, Pasteur discovered that drying out the spinal cords of dead rabid rabbits and monkeys resulted in a weakened form of rabies virus. Using that weakened version as a vaccine to gradually expose dogs to the rabies virus, Pasteur showed that he could effectively immunize the dogs against rabies.</p>
<p>Then, in July 1885, Joseph Meister, a 9-year-old boy from France, was severely bitten by a rabid dog. With Joseph facing almost certain death, his mother took him to Paris to see Pasteur because <a href="https://www.pbs.org/newshour/health/louis-pasteurs-risky-move-to-save-a-boy-from-almost-certain-death">she had heard</a> that he was working to develop a cure for rabies.</p>
<p>Pasteur took on the case, and alongside two physicians, he gave the boy a series of injections over several weeks. Joseph survived and Pasteur shocked the world with a cure for a universally lethal disease. This discovery opened the door to the widespread use of Pasteur’s rabies vaccine around 1885, which <a href="https://doi.org/10.3390%2Ftropicalmed2020005">dramatically reduced rabies’ deaths in humans and animals</a>. </p>
<h2>A Nobel Prize-worthy life</h2>
<p>Pasteur once famously <a href="https://www.nhlbi.nih.gov/directors-messages/serendipity-and-the-prepared-mind">said in a lecture</a>, “In the fields of observation, chance favors only the prepared mind.” </p>
<p>Pasteur had a knack for applying his brilliant – and prepared – scientific mind to the most practical dilemmas faced by humankind.</p>
<p>While Louis Pasteur died prior to the initiation of the Nobel Prize, I would argue that his amazing lifetime of discovery and contribution to science in medicine, infectious diseases, vaccination, medical microbiology and immunology place him among the all-time greatest scientists.</p><img src="https://counter.theconversation.com/content/191395/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rodney E. Rohde has received funding from the American Society of Clinical Pathologists (ASCP), American Society for Clinical Laboratory Science (ASCLS), U.S. Department of Labor (OSHA), and other public and private entities/foundations. Rohde is affiliated with ASCP, ASCLS, ASM, and serves on several scientific advisory boards. See <a href="https://rodneyerohde.wp.txstate.edu/service/">https://rodneyerohde.wp.txstate.edu/service/</a>.</span></em></p>On World Rabies Day – which is also the anniversary of French microbiologist Louis Pasteur’s death – a virologist reflects on the achievements of this visionary scientist.Rodney E. Rohde, Regents' Professor of Clinical Laboratory Science, Texas State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1888992022-09-18T20:15:03Z2022-09-18T20:15:03ZI’ve had COVID and am constantly getting colds. Did COVID harm my immune system? Am I now at risk of other infectious diseases?<figure><img src="https://images.theconversation.com/files/483171/original/file-20220907-24-ekxrkx.jpg?ixlib=rb-1.1.0&rect=2%2C2%2C1914%2C1276&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.pexels.com/photo/photo-of-a-cold-woman-6753163/">Pavel Danilyuk/Pexels</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>So you’ve had COVID and have now recovered. You don’t have ongoing symptoms and luckily, you don’t seem to have developed <a href="https://theconversation.com/long-covid-how-researchers-are-zeroing-in-on-the-self-targeted-immune-attacks-that-may-lurk-behind-it-169911">long COVID</a>. </p>
<p>But what impacts has COVID had on your overall immune system?</p>
<p>It’s early days yet. But growing evidence suggests there are changes to your immune system that may put you at risk of other infectious diseases.</p>
<p>Here’s what we know so far.</p>
<h2>A round of viral infections</h2>
<p>Over this past winter, many of us have had what seemed like a <a href="https://theconversation.com/why-do-i-and-my-kids-get-so-many-colds-and-with-all-this-covid-around-should-we-be-isolating-too-179302">continual round</a> of viral illness. This may have included COVID, <a href="https://www.who.int/health-topics/influenza-seasonal#tab=tab_1">influenza</a> or infection with <a href="https://www.mayoclinic.org/diseases-conditions/respiratory-syncytial-virus/symptoms-causes/syc-20353098">respiratory syncytial virus</a>. We may have recovered from one infection, only to get another.</p>
<p>Then there is the re-emergence of infectious diseases globally such as <a href="https://theconversation.com/we-need-to-talk-about-monkeypox-without-shame-and-blame-188295">monkeypox</a> or <a href="https://theconversation.com/the-latest-polio-cases-have-put-the-world-on-alert-heres-what-this-means-for-australia-and-people-travelling-overseas-188989">polio</a>.</p>
<p>Could these all be connected? Does COVID somehow weaken the immune system to make us more prone to other infectious diseases?</p>
<p>There are <a href="https://www.sciencedirect.com/science/article/pii/B9780128009475000168?via%3Dihub">many reasons</a> for infectious diseases to emerge in new locations, after many decades, or in new populations. So we cannot jump to the conclusion COVID infections have given rise to these and other viral infections.</p>
<p>But evidence is building of the negative impact of COVID on a healthy <em>individual’s</em> immune system, several weeks after symptoms have subsided.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-latest-polio-cases-have-put-the-world-on-alert-heres-what-this-means-for-australia-and-people-travelling-overseas-188989">The latest polio cases have put the world on alert. Here's what this means for Australia and people travelling overseas</a>
</strong>
</em>
</p>
<hr>
<h2>What happens when you catch a virus?</h2>
<p>There are three possible outcomes after a viral infection:</p>
<p>1) your immune system clears the infection and you recover (for instance, with <a href="https://www.healthychildren.org/English/health-issues/conditions/ear-nose-throat/Pages/Rhinovirus-Infections.aspx">rhinovirus</a> which causes the common cold)</p>
<p>2) your immune system fights the virus into “latency” and you recover with a virus dormant in our bodies (for instance, <a href="https://www.healthdirect.gov.au/chickenpox">varicella zoster virus</a>, which causes chickenpox) </p>
<p>3) your immune system fights, and despite best efforts the virus remains “chronic”, replicating at very low levels (this can occur for <a href="https://www.who.int/news-room/fact-sheets/detail/hepatitis-c">hepatitis C virus</a>).</p>
<p>Ideally we all want option 1, to clear the virus. In fact, most of us <a href="https://biosignaling.biomedcentral.com/articles/10.1186/s12964-022-00856-w">clear SARS-CoV-2</a>, the virus that causes COVID. That’s through a complex process, using many different parts of our immune system.</p>
<p>But international evidence suggests changes to our immune cells after SARS-CoV-2 infection may have other impacts. It may affect our ability to fight other viruses, as well as other pathogens, such as bacteria or fungi. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/no-the-extra-hygiene-precautions-were-taking-for-covid-19-wont-weaken-our-immune-systems-143690">No, the extra hygiene precautions we're taking for COVID-19 won't weaken our immune systems</a>
</strong>
</em>
</p>
<hr>
<h2>How much do we know?</h2>
<p>An <a href="https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-02228-6">Australian study</a> has found SARS-CoV-2 alters the balance of immune cells up to 24 weeks after clearing the infection. </p>
<p>There were changes to the relative numbers and types of immune cells between people who had recovered from COVID compared with healthy people who had not been infected.</p>
<p>This included changes to cells of the <a href="https://www.khanacademy.org/test-prep/mcat/organ-systems/the-immune-system/a/innate-immunity">innate immune system</a> (which provides a non-specific immune response) and the <a href="https://www.ncbi.nlm.nih.gov/books/NBK21070/">adaptive immune system</a> (a specific immune response, targeting a recognised foreign invader).</p>
<p><a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009742">Another study</a> focused specifically on <a href="https://www.immunology.org/public-information/bitesized-immunology/cells/dendritic-cells">dendritic cells</a> – the immune cells that are often considered the body’s “first line of defence”.</p>
<p>Researchers found fewer of these cells circulating after people recovered from COVID. The ones that remained were less able to activate white blood cells known as <a href="https://www.britannica.com/science/T-cell">T-cells</a>, a critical step in activating anti-viral immunity.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Dendritic cells (red) attacking viruses (green)" src="https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.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">Fewer dendritic cells (red) were circulating after COVID.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/antiviral-immunity-dendritic-cells-binding-viruses-1781314607">Shutterstock</a></span>
</figcaption>
</figure>
<p>Other studies have found different impacts on T-cells, and other types of white blood cells known as <a href="https://askabiologist.asu.edu/b-cell">B-cells</a> (cells involved in producing antibodies).</p>
<p>After SARS-CoV-2 infection, one study <a href="https://doi.org/10.1172/JCI140491">found evidence</a> many of these cells had been activated and “exhausted”. This suggests the cells are dysfunctional, and might not be able to adequately fight a subsequent infection. In other words, sustained activation of these immune cells after a SARS-CoV-2 infection may have an impact on other inflammatory diseases.</p>
<p><a href="https://www.nature.com/articles/s41392-021-00749-3#citeas">One study</a> found people who had recovered from COVID have changes in different types of B-cells. This included changes in the cells’ metabolism, which may impact how these cells function. Given B-cells are critical for producing antibodies, we’re not quite sure of the precise implications.</p>
<p>Could this influence how our bodies produce antibodies against SARS-CoV-2 should we encounter it again? Or could this impact our ability to produce antibodies against pathogens more broadly – against other viruses, bacteria or fungi? The study did not say.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-the-immune-system-19240">Explainer: what is the immune system?</a>
</strong>
</em>
</p>
<hr>
<h2>What impact will these changes have?</h2>
<p>One of the main concerns is whether such changes may impact how the immune system responds to other infections, or whether these changes
might worsen or cause other chronic conditions. </p>
<p>So more work needs to be done to understand the long-term impact of SARS-CoV-2 infection on a person’s immune system.</p>
<p>For instance, we still don’t know how long these changes to the immune system last, and if the immune system recovers. We also don’t know if SARS-CoV-2 triggers other chronic illnesses, such as <a href="https://www.healthdirect.gov.au/chronic-fatigue-syndrome-cfs-me">chronic fatigue syndrome</a> (myalgic encephalomyelitis). Research into this is ongoing.</p>
<p>What we do know is that having a healthy immune system and being vaccinated (when a vaccine has been developed) is critically important to have the best chance of fighting any infection.</p><img src="https://counter.theconversation.com/content/188899/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lara Herrero receives funding from NHMRC.</span></em></p>Evidence is growing there are changes to your immune system that may put you at risk of other infectious diseases.Lara Herrero, Research Leader in Virology and Infectious Disease, Griffith UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1862092022-07-10T20:27:15Z2022-07-10T20:27:15ZThe next breakthrough tool in biology? It’s maths. Here are some ways mathematical biology is helping change the world<figure><img src="https://images.theconversation.com/files/473158/original/file-20220708-21-mwxmyr.jpeg?ixlib=rb-1.1.0&rect=132%2C109%2C3702%2C2046&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Biology is rich in patterns. You’ll find them everywhere – from the number of petals on a flower (which generally correspond to a number in the Fibonacci sequence), to the number of vertebrae in mammals (giraffes, humans and quokkas all have seven neck vertebrae). Even many viruses follow patterns and have symmetry in their shells.</p>
<p>Mathematics is, at its core, the science of patterns. Patterns can be subtle. So without using maths to formally describe and understand them, we could miss them completely. </p>
<p>For a long time, biological research had largely progressed without the advanced mathematical modelling that has now become core to physics, engineering and climate science. But this is changing.</p>
<p>Mathematical biology is a growing field which promises to revolutionise microbiology, biotechnology, evolutionary biology and health care. With maths, scientific breakthroughs that previously required years of trial-and-error experimentation (and tonnes of waste) can be achieved in a fraction of the time. </p>
<p>Here are some of the latest advances being made in mathematical biology. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/weve-discovered-a-new-rule-of-nature-it-explains-why-animals-pointy-parts-grow-the-way-they-do-157229">We've discovered a new rule of nature. It explains why animals' pointy parts grow the way they do</a>
</strong>
</em>
</p>
<hr>
<h2>Viruses and the natural world</h2>
<p>As children, most of us would have played rock, paper, scissors, that game where rock crushes scissors, scissors cut paper and paper covers rock.</p>
<p>Well, the same maths we use to describe rock, paper, scissors can also be used to predict the cycle of dominance between animal species in a region that allows their coexistence. For example, there are three varieties of side-blotched lizards in south-western United States. Each variety has an advantage over one of the others, and a disadvantage to the third. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/473160/original/file-20220708-23-bog7bk.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A male side-blotched lizard sits diagonally on a rock" src="https://images.theconversation.com/files/473160/original/file-20220708-23-bog7bk.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/473160/original/file-20220708-23-bog7bk.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/473160/original/file-20220708-23-bog7bk.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/473160/original/file-20220708-23-bog7bk.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/473160/original/file-20220708-23-bog7bk.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/473160/original/file-20220708-23-bog7bk.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/473160/original/file-20220708-23-bog7bk.jpeg?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">Each variety of the side-blotched lizard has distinct advantages and disadvantages compared to the others.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Maths has also been at the forefront of our fight against COVID-19. If you watch the news you’ve probably heard of R0, a mathematical concept that indicates if an epidemic will occur. When R0 is greater than 1 the number of infections rises. With R0 less than 1 the epidemic will eventually die out.</p>
<p>This crucial concept in infectious disease epidemiology is a result of the power of maths and statistics to detect patterns in data that are too subtle to notice otherwise. It has been the key to predicting and managing the spread of the COVID-19 virus. What’s perhaps less well known is maths is also being used to:</p>
<ul>
<li>design <a href="https://www.sciencedirect.com/science/article/pii/S2667119022000039">viruses</a> to kill cancer cells, such as by making combination therapies to treat <a href="https://onlinelibrary.wiley.com/doi/full/10.1002/cso2.1035">ovarian cancer</a> </li>
<li>design interventions to help <a href="https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002453#">eliminate malaria</a> </li>
<li><a href="https://aricjournal.biomedcentral.com/articles/10.1186/s13756-018-0406-1">identify</a> the cause of antimicrobial resistance</li>
<li>create clean drinking water for developing nations and arid regions</li>
<li>unlock the inner workings of living cells.</li>
</ul>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-to-flatten-the-curve-of-coronavirus-a-mathematician-explains-133514">How to flatten the curve of coronavirus, a mathematician explains</a>
</strong>
</em>
</p>
<hr>
<h2>Whole cell models</h2>
<p>We’re now at the onset of a new era in biology – one in which we can build mathematical models to comprehensively describe an individual biological cell in order to predict its fate. This is called the “whole cell model”. It allows us to compute the life of a cell and is helping us understand how the human body works.</p>
<p>One writer for The New Yorker magazine <a href="https://www.newyorker.com/magazine/2022/03/07/a-journey-to-the-center-of-our-cells">called</a> the quest to understand the intracellular world the “final frontier”. And despite the field still being in its infancy, potential applications are everywhere.</p>
<p>Imagine for a moment if we could build a mathematical replica model of the inner cellular workings of the Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA), a bacterial superbug that doesn’t respond to standard antibiotics. </p>
<p>With a whole cell model of MSRA, we could use computer simulations informed by biological experiments to engineer new ways of both preventing and treating MRSA bacterial infections. This would add another layer of defence in our fight against resistant superbugs.</p>
<p>The benefit of whole cell modelling extends to cancer treatment too. For example, cancer immunotherapy relies on using a patient’s own immune system to fight the cancer. If we had a complete cell model of immune cells, we could fine-tune specific anti-tumour responses to improve therapies against cancer – and do so without any invasive exploration of the patient. </p>
<h2>Clean water</h2>
<p>Beyond health care, whole cell models are giving us methods to provide clean water for agriculture and food production. Effective water treatment produces high-quality water by removing microorganisms, organic matter and micropollutants. </p>
<p>However, buildup of the removed biological matter will cause the filters to become blocked by a layer of biological material, or “biofilm”. The biofilm must be removed for the filtration process to work again. In water desalination plants, around one-quarter of the running costs are <a href="https://www.researchgate.net/publication/347520309_Cost_of_fouling_in_full-scale_reverse_osmosis_and_nanofiltration_installations_in_the_Netherlands">attributed</a> to the removal of biofilms — it’s a big problem. </p>
<p>Whole cell models will allow us to dissect the mechanisms underpinning how biofilms form. We’ll then be able to identify suitable targets to inhibit biofilm formation in the first place, or destroy biofilms once they’re created, to restore the integrity of the water supply.</p>
<p>This is just one of many examples. Being able to understand, predict and control the behaviour of cells will fast-track discoveries in biotechnology and health care, ensuring a healthier, more secure and prosperous future for everyone. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/covid-19-heightens-water-problems-around-the-world-140167">COVID-19 heightens water problems around the world</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/186209/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jennifer Flegg receives funding from the Australian Research Council (ARC). </span></em></p><p class="fine-print"><em><span>Michael P.H. Stumpf has received funding from the Biotechnology and Biological Sciences Research Council.</span></em></p>Our ability to use mathematical modelling is accelerating breakthrough discoveries in health care and biotechnology.Jennifer Flegg, Associate Professor in Applied Mathematics, The University of MelbourneMichael P.H. Stumpf, Professor for Theoretical Systems Biology, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1847722022-06-15T11:54:54Z2022-06-15T11:54:54ZThe inside story of Recovery: how the world’s largest COVID-19 trial transformed treatment – and what it could do for other diseases<figure><img src="https://images.theconversation.com/files/468547/original/file-20220613-16-58megq.JPG?ixlib=rb-1.1.0&rect=0%2C293%2C3017%2C2113&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Recovery team members Mark Campbell, Guilherme Pessoa-Amorim and Leon Peto photographed at the Big Data Institute in Oxford</span> <span class="attribution"><span class="source">Photograph: Adam Gasson/UKRI</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><blockquote>
<p><strong>Guilherme</strong> – June 16, 2020. Evening TV news shows across the world were suddenly opening with the result of our research, and rightly so. <a href="https://www.bbc.co.uk/news/health-53061281">Dexamethasone</a> was the first drug to be shown to save the lives of people infected with COVID-19. To a young researcher like me, that day felt like being part of history. It was a gift from the UK to the world.</p>
</blockquote>
<p>Two years ago this week, the <a href="https://www.recoverytrial.net/">Recovery trial</a> transformed the care of COVID patients with its <a href="https://www.recoverytrial.net/news/low-cost-dexamethasone-reduces-death-by-up-to-one-third-in-hospitalised-patients-with-severe-respiratory-complications-of-covid-19#:%7E:text=The%20UK%20Government%27s%20Chief%20Scientific,an%20inexpensive%20widely%20available%20medicine.">dexamethasone</a> announcement. Within four hours, the steroid was included in <a href="https://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAlert.aspx?AlertID=103054">NHS treatment recommendations</a>. Almost overnight, treatment of COVID patients around the world <a href="https://www.nature.com/articles/d41586-020-01824-5">changed completely</a>. It has been estimated that dexamethasone may have saved <a href="https://www.england.nhs.uk/2021/03/covid-treatment-developed-in-the-nhs-saves-a-million-lives/">a million lives</a> in the first nine months following the announcement.</p>
<p>Recovery, jointly led by <a href="https://www.ndph.ox.ac.uk/about">Oxford Population Health</a> and the <a href="https://www.ndm.ox.ac.uk/about">Nuffield Department of Medicine</a>, is a groundbreaking scientific machine which, from the outset, moved at unprecedented speed. Within 15 days, more than 1,000 participants around the UK had joined the trial; five weeks later, that number had risen to 10,000. In the first 100 days alone, the trial produced three groundbreaking results that would completely reshape COVID care.</p>
<p>From an impromptu discussion between two professors on a London bus to headlines around the world – and a baby being born at home in the midst of the pandemic – this is the inside story of Recovery, by three medics who have been part of this extraordinary journey.</p>
<p>The vast and unique nature of the NHS provided the perfect setting for the trial’s rapid development. Indeed, if a similar approach could now be employed for other common and important diseases, we believe it could transform the quality of evidence supporting treatments for millions more people in the UK and around the world.</p>
<h2>How it all began</h2>
<blockquote>
<p><strong>Mark</strong> – Working on hospital wards during the first wave of the pandemic was at times a haunting experience. Patients of all ages were severely ill, and could deteriorate rapidly with little warning. I spent many hours talking to patients at their bedside and to their relatives on the phone – not knowing when the last conversation might be; wanting to offer hope but not false hope. The emotional toll was profound, but the privilege of being there for patients and their families at such a terrifying time was enormous.</p>
</blockquote>
<p>Early March 2020. Despite growing concerns about the worldwide spread of COVID-19, life in the UK continued pretty much unchanged. Daily commuting, <a href="https://www.theguardian.com/world/2020/jun/03/we-were-packed-like-sardines-evidence-grows-of-mass-event-dangers-early-in-pandemic">large sporting events</a> and international travel all kept going, even after the virus began circulating within the UK and the <a href="https://www.gov.uk/government/speeches/pm-statement-on-coronavirus-12-march-2020">first deaths occurred</a>.</p>
<p>But in scientific circles, discussions were already under way about how to respond to this mysterious virus. Following a <a href="https://webarchive.nationalarchives.gov.uk/ukgwa/20200223201041/https://www.ukri.org/news/20-million-rapid-response-for-novel-coronavirus-research/">call for research proposals</a> in early February, public funding for a UK-based trial was agreed on March 5.</p>
<p>Four days later <a href="https://www.ox.ac.uk/news-and-events/find-an-expert/professor-martin-landray">Professor Martin Landray</a>, an experienced clinical trialist based at Oxford Population Health, and <a href="https://wellcome.org/who-we-are/people/jeremy-farrar">Sir Jeremy Farrar</a>, director of Wellcome, happened to meet on a <a href="https://www.bbc.co.uk/news/health-56508369">No.18 London bus journey</a>. Both agreed that a major public health crisis was looming.</p>
<p>“What we agreed on that bus trip was that the tsunami would arrive within a fortnight,” Landray later recalled. “So we had to have the trial up and running within two weeks.” On March 11, the World Health Organization declared COVID-19 a <a href="https://pubmed.ncbi.nlm.nih.gov/32191675/#:%7E:text=The%20World%20Health%20Organization%20(WHO,a%20global%20pandemic%20(1).">global pandemic</a>, and on March 23, the UK imposed its <a href="https://www.bbc.co.uk/news/uk-60847932">first national lockdown</a>.</p>
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<img alt="" src="https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<p><strong><em>This story is part of Conversation Insights</em></strong>
<br><em>The Insights team generates <a href="https://theconversation.com/uk/topics/insights-series-71218">long-form journalism</a> and is working with academics from different backgrounds who have been engaged in projects to tackle societal and scientific challenges.</em></p>
<hr>
<p>Landray joined forces with <a href="https://www.ndm.ox.ac.uk/team/peter-horby">Professor Peter Horby</a>, a specialist in emerging infectious diseases at the Nuffield Department of Medicine. They recognised that COVID-19 was an <a href="https://www.nature.com/articles/d41586-020-01056-7">entirely new disease</a> for which no proven treatments were available. Many were making educated guesses regarding what did and didn’t work, resulting in a <a href="https://www.bmj.com/content/bmj/369/bmj.m1936.full.pdf">jigsaw of different clinical recommendations</a> around the world, but no one knew much for certain.</p>
<p>And so Recovery (short for the Randomised Evaluation of COVID-19 Therapy) was established to embrace, rather than deny, these uncertainties – and to harness the best scientific methods to resolve them, rather than relying on hype or hope.</p>
<p>But this mantra <a href="https://www.nature.com/articles/d41586-021-01246-x">did not land well</a> with some people, who mistook scientific rigour and the quest for definitive answers for dangerous delaying tactics, thinking they already knew which treatments would and wouldn’t work. As Horby later recalled: “I’ve got a drawer full of letters telling me I’m killing people.”</p>
<h2>The guiding principles of Recovery</h2>
<blockquote>
<p><strong>Leon</strong> – I was working on the <a href="https://www.ouh.nhs.uk/services/departments/specialist-medicine/infectious-diseases/">Infectious Diseases</a> ward at Oxford’s John Radcliffe Hospital in March 2020 when I first heard about the Recovery trial. In over a decade working in hospital medicine, I had never known a trial that felt accessible to normal clinicians, but Recovery was different. Involvement of medical teams was encouraged and made easy.</p>
<p>Already, various drugs had been proposed as treatments for COVID-19, but there was no good evidence that any of them actually helped. We knew that by randomising participants, we would discover if any of the drugs being tested actually did anything. In those early days, I remember that many of us thought dexamethasone was the least promising – until June 2020, when we were delighted to be proved wrong.</p>
</blockquote>
<p>To be successful, Recovery needed a mechanism for conducting randomised controlled trials at a scale large enough to provide <a href="https://www.nature.com/articles/d41586-021-01246-x">conclusive evidence</a>. Unless the number of patients involved in such a trial is large, the play of chance can mean sicker patients are more common in one group, masking any effect of the treatment being tested (in the same way you need to toss lots of coins for the number of heads and tails to be reliably balanced).</p>
<p>Thousands of patients had to be enlisted as soon as possible. This was no trivial task – especially given the immediate impact of the pandemic on <a href="https://www.nature.com/articles/d41586-021-01569-9">clinical research</a> due to staff shortages and redeployment. Healthcare workers were under <a href="https://theconversation.com/covid-19-2020-was-horrendous-for-health-workers-early-2021-was-even-worse-159503">unprecedented strain</a>, and there was little room for additional research commitments.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/468278/original/file-20220610-43540-am4w3z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/468278/original/file-20220610-43540-am4w3z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=436&fit=crop&dpr=1 600w, https://images.theconversation.com/files/468278/original/file-20220610-43540-am4w3z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=436&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/468278/original/file-20220610-43540-am4w3z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=436&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/468278/original/file-20220610-43540-am4w3z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=548&fit=crop&dpr=1 754w, https://images.theconversation.com/files/468278/original/file-20220610-43540-am4w3z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=548&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/468278/original/file-20220610-43540-am4w3z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=548&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Recovery’s daily recruitment rate over the first year of the trial. Oxford Population Health, University of Oxford.</span>
</figcaption>
</figure>
<p>To achieve the scale required, Recovery had to be simple, making it easy for busy frontline staff to enlist unwell patients, while at the same time adhering to high scientific and ethical standards. The trial achieved this with a disruptive yet beautifully streamlined design. In part, it relied on clinical trial methodology <a href="https://www.sciencedirect.com/science/article/abs/pii/S0140673686916077?via%3Dihub">first used in the 1980s</a> – a highly pragmatic approach, focused on collecting small amounts of data on large numbers of people.</p>
<p>But it also made use of the latest available data technology – notably, the NHS’s <a href="https://www.gov.uk/government/publications/data-saves-lives-reshaping-health-and-social-care-with-data-draft/data-saves-lives-reshaping-health-and-social-care-with-data-draft">healthcare data collection system</a>. Much of the data generated as part of routine NHS care is gathered centrally to help allocate resources to hospitals and disease surveillance. This information can be quickly repurposed to <a href="https://www.bmj.com/content/374/bmj.n2280">help scientists run clinical research</a>, and has been instrumental in the UK’s fight against COVID-19.</p>
<p>Professors Landray and Horby put together a small team in Oxford, drafted a protocol and submitted it to the research regulators. On March 19 – less than a fortnight after funding had been agreed – <a href="https://www.recoverytrial.net/news/the-recovery-trial-is-two-years-old-today">the first patient entered the Recovery trial</a>. The speed at which this occurred was in itself a major breakthrough from traditional clinical trials, which typically <a href="https://www.statnews.com/2018/03/28/clinical-trials-startup-speed/">take months</a> (and sometimes years) to take off.</p>
<p>Every day the trial got bigger as more hospital sites were included. By the end of spring 2020, every single acute hospital in the UK – 176 in total – was a recruiting Recovery site. Now every person admitted to a hospital with COVID-19 could be asked to participate in the trial. Within 12 weeks, Recovery had grown into a truly national endeavour.</p>
<h2>Why the structure of the NHS was key</h2>
<blockquote>
<p><strong>Guilherme</strong> – I became involved in Recovery in April 2020. As a junior investigator working in clinical trials, my main role was to provide remote support to frontline staff recruiting ill patients. I was answering tens of phone calls in quick succession, replying to even more emails. Despite sitting all day in my small flat in Oxford, I felt part of something meaningful – a small cog in a big machine that was helping to fight COVID-19.</p>
<p>This sense of working together for a common goal was one of the most powerful aspects of the trial. Everyone – <a href="https://www.recoverytrial.net/case_studies">doctors, nurses, pharmacists, data analysts and patients</a> – was made to feel part of it, wherever they were. Suddenly regular clinical staff, many of whom had never been given the opportunity to do research before, were part of a major clinical trial that would soon change the trajectory of the COVID pandemic.</p>
</blockquote>
<p>In total, around <a href="https://www.rcpjournals.org/content/futurehosp/8/2/e243">10% of all those admitted</a> to hospital with COVID-19 in the UK participated in the Recovery trial over the first year. In the city of Leicester alone, <a href="https://www.recoverytrial.net/news/leicester2019s-hospitals-recruit-over-1-000-patients-for-the-recovery-trial">well over 1,000 people had taken part</a> by the end of 2020. By itself, this one NHS Trust randomised more patients than most of the world’s largest COVID trials.</p>
<p>Due to its integrated nature, the NHS provided the <a href="https://www.rcpjournals.org/content/futurehosp/8/2/e243">perfect setting</a> for Recovery. Unlike other healthcare systems in the US and Europe, the NHS is a unified, single-payer system that does not rely on medical insurance. This means in each UK nation, primary care practices and hospital sites all work in collaboration under a common leadership structure.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/468468/original/file-20220613-20-zisci4.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Three clinicians inside Big Data Institute, Oxford" src="https://images.theconversation.com/files/468468/original/file-20220613-20-zisci4.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/468468/original/file-20220613-20-zisci4.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=357&fit=crop&dpr=1 600w, https://images.theconversation.com/files/468468/original/file-20220613-20-zisci4.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=357&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/468468/original/file-20220613-20-zisci4.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=357&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/468468/original/file-20220613-20-zisci4.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=449&fit=crop&dpr=1 754w, https://images.theconversation.com/files/468468/original/file-20220613-20-zisci4.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=449&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/468468/original/file-20220613-20-zisci4.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=449&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 sense of working together for a common goal was one of the most powerful aspects of Recovery.’</span>
<span class="attribution"><span class="source">Adam Gasson/UKRI</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
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<p>Drug supplies are provided and managed nationally. Each patient has a unique identifier (NHS number) assigned to them, enabling the linkage of data recorded in different places. Most information used for hospital reimbursement, disease surveillance and clinical auditing is collected centrally for the entire nation.</p>
<p>These features may not have been thought up or designed to enable clinical research but serendipitously, they ended up providing the precise infrastructure that was needed to deploy large-scale randomised COVID trials at rapid pace.</p>
<p>The process for obtaining ethical approval of studies in the NHS is also governed by a central body, the <a href="https://www.hra.nhs.uk/about-us/">Health Research Authority</a>, which eliminates the need for lengthy and cumbersome approval processes at each participating institution. This could have been a major limitation for Recovery, given that it spanned more than 170 hospitals across the UK. Instead, the study was <a href="https://www.recoverytrial.net/for-site-staff/site-set-up-1/regulatory-documents">approved</a> and regularly reviewed by a <a href="https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/recovery-trial/">single</a> research ethics committee, greatly streamlining the entire process.</p>
<p>Throughout the second half of 2020 and beyond, the desire of doctors to help with the wider medical effort against COVID-19 could, in part, be channelled into making the Recovery trial a success. Instead of every department in each UK hospital trying to work out how to best care for their COVID patients, Recovery offered the prospect of a united response: “We don’t know the answers yet, but we do know how to find out – and we’re going to do it together.”</p>
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<h2>Three groundbreaking results in 100 days</h2>
<blockquote>
<p><strong>Guilherme</strong> – Out of five main COVID-19 treatments recommended for people in hospital by the <a href="https://www.nice.org.uk/guidance/ng191/resources/managing-covid-19-treatments-may-2022-v24.0-pdf-11070542125">current NHS guidelines</a>, four were proven effective by Recovery. This gives me an enormous sense of pride whenever I look after someone with COVID in hospital, or hear colleagues discussing their patients. Prescribing one of these treatments comes with a feeling of joy because we helped move medicine forward. That will be our legacy for future generations.</p>
</blockquote>
<p>In the first 100 days alone, Recovery produced three groundbreaking results that, almost overnight, changed COVID care around the world.</p>
<p>Early in the pandemic in the US, the antimalarial drug <a href="https://bnf.nice.org.uk/drugs/hydroxychloroquine-sulfate/">hydroxychloroquine</a> had received emergency-use authorisation by the US Food and Drug Administration (FDA). Around the world, it was being widely touted by highly influential figures including the <a href="https://www.bbc.co.uk/news/world-us-canada-53575964">US president, Donald Trump</a>, and Brazil’s <a href="https://www.nytimes.com/2020/07/08/world/americas/brazil-bolsonaro-covid-coronavirus.html">Jair Bolsonaro</a>.</p>
<p>But on June 5 2020, Recovery released its first result, showing the drug had no clinical benefits and hinting at <a href="https://www.sciencemediacentre.org/expert-reaction-to-the-recovery-trial-reporting-no-clinical-benefit-from-use-of-hydroxychloroquine-in-patients-admitted-to-hospital-with-covid-19/">the potential risk of harm</a>. Shortly after this result was made public, the FDA <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-chloroquine-and">revoked its recommendation</a>. This led to an immediate impact on clinical care strategies around the world.</p>
<p>Owing to the extreme urgency of the situation, Recovery’s approach was to issue a press release as soon as each trial’s findings had been ratified. In every case, this was followed as quickly as possible – usually within a few days – by an open-access “pre-print” scientific paper. The fully peer-reviewed version would follow in due course.</p>
<p>Then on June 16 came Recovery’s landmark <a href="https://www.recoverytrial.net/news/low-cost-dexamethasone-reduces-death-by-up-to-one-third-in-hospitalised-patients-with-severe-respiratory-complications-of-covid-19#:%7E:text=The%20UK%20Government%27s%20Chief%20Scientific,an%20inexpensive%20widely%20available%20medicine.">dexamethasone result</a>, which concluded: “One death would be prevented by treatment [with dexamethasone] of around eight ventilated COVID-19 patients, or around 25 patients requiring oxygen alone.” This cheap steroid, widely available since the beginning of the pandemic, was now a key element of COVID treatment strategies.</p>
<p>In modern medicine most treatments, such as statins for cholesterol and anti-inflammatory drugs for rheumatic diseases, only have “small-to-moderate” effect sizes – around 10-20% reductions in the likelihood of having a bad outcome. This is comparable to the overall effect seen in Recovery with dexamethasone, although the impact in the sickest patients was larger. While effects of this size may not seem much, when used at the scale of a pandemic or in combination with other treatments with similar “modest” effects, they can have a tremendous impact on population health.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/dexamethasone-what-is-the-breakthrough-treatment-for-covid-19-140966">Dexamethasone: what is the breakthrough treatment for COVID-19?</a>
</strong>
</em>
</p>
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<p>However, small trials (involving hundreds of people) are not usually sufficient to convincingly identify these beneficial treatments because of the natural differences between people. Recovery was designed to overcome this problem – each possible treatment was studied in many thousands of patients to ensure the results could be relied on, and were not just down to the play of chance.</p>
<p>To conclude a rollercoaster month, Recovery announced its preliminary results on the antiviral drug combination lopinavir/ritonavir in late June 2020. Like hydroxychloroquine, this drug had already been recommended by some national clinical guidelines. It was being widely used around the world based on hints of efficacy in laboratory tests, but had not yet been proven to help hospitalised COVID patients. Recovery showed the drug combination was <a href="https://www.recoverytrial.net/news/no-clinical-benefit-from-use-of-lopinavir-ritonavir-in-hospitalised-covid-19-patients-studied-in-recovery">not effective</a> at preventing deaths in hospitalised patients, helping to redirect busy clinical staff and stretched healthcare resources towards treatments that would actually make a difference.</p>
<blockquote>
<p><strong>Mark</strong> – After the first wave of the pandemic subsided, an opportunity arose to join Recovery’s central coordinating office as a research clinician. Part of my role was monitoring and extracting evidence about tocilizumab (an immunosuppressing rheumatoid arthritis drug treatment) for a separate meta-analysis alongside the Recovery trial results. By the time those results were imminent in early 2021, my wife was nine months pregnant.</p>
<p>Living through our pregnancy during the pandemic was another reminder of how skilled and dedicated our NHS staff are. Despite everything that was going on, every single person we came across performed their role with compassion and expertise, normalising our experience as best they could. At five o’clock one morning it became clear the contractions weren’t going away. We were blessed with a healthy new son, born at home. By the time I returned from paternity leave, we also knew that <a href="https://www.recoverytrial.net/news/tocilizumab-reduces-deaths-in-patients-hospitalised-with-covid-19">tocilizumab saved lives</a> in hospitalised COVID patients, and we never looked back.</p>
</blockquote>
<figure class="align-center ">
<img alt="Two clinicians talking" src="https://images.theconversation.com/files/468480/original/file-20220613-22566-r6fnal.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/468480/original/file-20220613-22566-r6fnal.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=396&fit=crop&dpr=1 600w, https://images.theconversation.com/files/468480/original/file-20220613-22566-r6fnal.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=396&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/468480/original/file-20220613-22566-r6fnal.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=396&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/468480/original/file-20220613-22566-r6fnal.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=498&fit=crop&dpr=1 754w, https://images.theconversation.com/files/468480/original/file-20220613-22566-r6fnal.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=498&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/468480/original/file-20220613-22566-r6fnal.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=498&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Mark Campbell, left, became a father for the second time during the pandemic.</span>
<span class="attribution"><span class="source">Adam Gasson/UKRI</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>A disappointing but equally important result</h2>
<blockquote>
<p><strong>Leon</strong> – I started working with the Recovery coordinating team in late October 2020, mainly on a new treatment that had been introduced to the trial in May. The story of convalescent plasma therapy in COVID-19 illustrates what has made Recovery a success, and why more big trials like it are needed in future.</p>
</blockquote>
<p>Convalescent plasma has been tried as a treatment for various infections for <a href="https://jamanetwork.com/journals/jama/fullarticle/220020">more than a century</a>, without any definitive evidence to show whether it works or not. The idea is simple and appealing: people recently recovered from an infection usually have high levels of antibodies in their blood against the pathogen responsible. By collecting that blood and separating the plasma (the antibody-containing liquid in which blood cells are suspended), antibodies can then be given to other people in the early stages of the same infection, in whom it might prevent severe disease or death.</p>
<p>This was one of the earliest treatments tried for COVID-19, but could Recovery find definitive proof of whether it worked?</p>
<p>The most influential early data came from a large US observational study – a non-randomised study comparing people who happened to receive different treatments as part of their medical care. This found that hospitalised COVID patients who received convalescent plasma with high antibody levels had <a href="https://www.nejm.org/doi/full/10.1056/nejmoa2031893">a third lower chance of death</a> than those given plasma with low antibody levels (the control group in this study). This finding was used to justify widespread use of convalescent plasma <a href="https://www.uscovidplasma.org/">in the US</a>, where it <a href="https://publichealth.jhu.edu/2022/an-update-on-convalescent-plasma-for-covid-19">has been given</a> to <a href="https://pubmed.ncbi.nlm.nih.gov/34085928/">hundreds of thousands</a> of COVID patients.</p>
<p>However, this study had serious limitations – not only was there no control group that didn’t receive any convalescent plasma, but the study was not randomised. Many factors determine which treatments different patients receive, including considerations that aren’t reflected in the medical records. For example, we know that experienced doctors often place more weight on how unwell a patient looks than individual test results. If patients receiving a particular treatment are on average sicker than those who don’t, any conclusions about the effects of that treatment could be false.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/coronavirus-what-is-plasma-therapy-137813">Coronavirus: what is plasma therapy?</a>
</strong>
</em>
</p>
<hr>
<p>Non-randomised observational studies can’t typically find a way around this issue, so while they have many uses, they don’t reliably tell us if a particular treatment works. Yet this long-recognised limitation did not stop some misleading observational results being widely promoted and <a href="https://www.bmj.com/content/369/bmj.m1335">acted upon</a> for the treatment of COVID-19.</p>
<p>What was needed was evidence from a study that was both randomised and sufficiently large to provide clear results. By the time Recovery had finished testing convalescent plasma in January 2021, 10 small randomised trials of the same treatment had already been reported, totalling more than 1,600 COVID patients. Yet even taken together, they were too small to tell us whether convalescent plasma reduced the risk of death by 40%, or had no effect at all. Recovery randomised 11,000 patients, increasing the statistical power more than tenfold, and showed very clearly that convalescent plasma was of <a href="https://www.nhsbt.nhs.uk/covid-19-research/research-and-trials/plasma-trials/">no material benefit</a> for patients with severe COVID-19.</p>
<p>While disappointing, this negative result was definitive enough to enable UK research and clinical practice to move on to new COVID treatment targets. In fact, Recovery subsequently showed that <a href="https://www.recoverytrial.net/news/recovery-trial-finds-regeneron2019s-monoclonal-antibody-combination-reduces-deaths-for-hospitalised-covid-19-patients-who-have-not-mounted-their-own-immune-response-1#:%7E:text=The%20Randomised%20Evaluation%20of%20COVID,antibody%20response%20of%20their%20own.">higher doses of human antibodies targeted specifically at the virus</a>, but <a href="https://jamanetwork.com/journals/jama/fullarticle/2776307">produced in the lab</a> instead of collected from recovered patients, did reduce the risk of death in patients with low antibody levels. Other studies continue to investigate whether convalescent plasma could be effective if given at much higher doses, or very early in an individual’s COVID infection.</p>
<h2>We now know more about COVID-19 than most older diseases</h2>
<blockquote>
<p><strong>Guilherme</strong> – Even now, the initial excitement of witnessing practice-changing results still lingers. Medicine is hard, and clinicians need to be familiar with many different treatments and the circumstances in which they are, or are not, likely to be effective. But it is rare for us to know exactly how and when these treatments came to be part of our arsenal – and to feel an emotional connection with those moments.</p>
</blockquote>
<p>In all, Recovery has now demonstrated the effectiveness of four life-saving medical treatments for COVID-19, and given clear conclusions on six other treatments that do not work. The effective treatments, which had mostly inconclusive results in other trials, were each found to reduce the risk of death among hospitalised COVID patients by 10-20%. Since their effects are additive, given in combination they can reduce the risk of death by around 40-50% for severely ill patients, compared with the likelihood of death when the pandemic was declared in March 2020.</p>
<p>Because of Recovery, we now know more about the treatment of COVID-19 than most much older diseases. Recovery was part of an extraordinary response by the NHS, the <a href="https://www.nihr.ac.uk/about-us/what-we-do/">National Institute for Health and Care Research</a>, <a href="https://www.ukri.org/about-us/">UK Research and Innovation</a> and many other organisations that, hopefully, won’t need to be repeated soon. However, it offers a roadmap for how much progress could be made in other areas of medicine by randomising more patients in treatment trials, and integrating these trials within routine care to minimise the burden on clinical staff.</p>
<p>Importantly, establishing simple trials with broad eligibility criteria in all UK hospitals opened up Recovery’s research to COVID patients from disparate backgrounds, avoiding the <a href="https://www.webmd.com/a-to-z-guides/news/20220505/why-do-clinical-trials-still-underrepresent-minorities">usual under-representations</a>. For example, the ethnic group breakdown in the dexamethasone result is very close to the overall distribution of the UK population, and also the proportions among hospitalised COVID patients. This has helped to provide practice-changing results for all patients both within and outside the UK.</p>
<p>Recovery has always focused on the effect of different drugs on mortality. This ensures that everyone can easily understand the answers the trial delivers: does the treatment save lives or not? Information on mortality can also be easily collected from national databases, providing additional sources of comparison for evaluating longer-term survival. </p>
<p>Recovery was thus able to deliver the sort of certainty that could be understood by everyone – doctors, patients and politicians alike – anywhere in the world, and be put into practice quickly.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/468481/original/file-20220613-45684-d2g0mr.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Three clinicians inside Big Data Institute, Oxford" src="https://images.theconversation.com/files/468481/original/file-20220613-45684-d2g0mr.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/468481/original/file-20220613-45684-d2g0mr.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=324&fit=crop&dpr=1 600w, https://images.theconversation.com/files/468481/original/file-20220613-45684-d2g0mr.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=324&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/468481/original/file-20220613-45684-d2g0mr.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=324&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/468481/original/file-20220613-45684-d2g0mr.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=407&fit=crop&dpr=1 754w, https://images.theconversation.com/files/468481/original/file-20220613-45684-d2g0mr.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=407&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/468481/original/file-20220613-45684-d2g0mr.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=407&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 our view, Recovery could be the catalyst for a seismic shift in the way clinical research is conducted.’</span>
<span class="attribution"><span class="source">Adam Gasson/UKRI</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>What could Recovery mean for the future of drug testing?</h2>
<blockquote>
<p><strong>Mark</strong> – My experience of the pandemic and Recovery has impassioned me to pursue opportunities to narrow the gap between randomised trials and normal NHS clinical care. In my field of infectious diseases, randomised trials of common conditions are barely performed, despite a lack of high-quality evidence in many areas.</p>
<p><strong>Guilherme</strong> – Societies cannot flourish when they are not healthy. This was made critically clear by the pandemic. For me, this means working to develop the processes needed to integrate NHS data into randomised trials even further, so we can accelerate and facilitate the delivery of new treatments to patients suffering from diseases other than COVID-19 through a combination of clinical knowledge and large-scale data science. In this way, we can perpetuate the core lessons learnt in the Recovery trial.</p>
</blockquote>
<p>The results of the <a href="https://www.recoverytrial.net/files/baricitinib-announcement-final_sites_web.pdf">Recovery baricitinib comparison</a> in March 2022 demonstrated that, while some may try to “move on” from COVID-19, the search for new and better treatments continues. Baricitinib (another anti-inflammatory drug used to treat rheumatoid arthritis) was found to reduce death by an <a href="https://www.medrxiv.org/content/10.1101/2022.03.02.22271623v1">additional 13%</a> on top of the mortality reductions achieved with existing treatments. Recovery was the only baricitinib trial that included large numbers of patients receiving other immunosuppressive drugs, meaning we now have more confidence about using combinations of COVID treatments in larger groups of people.</p>
<p>In our view, Recovery could be the catalyst for a seismic shift in the way clinical research is conducted in the UK and elsewhere. The trial has shown that, in a time of crisis, an entire country can break through the established status quo to collaborate together for a common goal, to enormous effect.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/468482/original/file-20220613-27912-7lyn6q.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="External view of the Big Data Institute, Oxford." src="https://images.theconversation.com/files/468482/original/file-20220613-27912-7lyn6q.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/468482/original/file-20220613-27912-7lyn6q.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=374&fit=crop&dpr=1 600w, https://images.theconversation.com/files/468482/original/file-20220613-27912-7lyn6q.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=374&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/468482/original/file-20220613-27912-7lyn6q.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=374&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/468482/original/file-20220613-27912-7lyn6q.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=470&fit=crop&dpr=1 754w, https://images.theconversation.com/files/468482/original/file-20220613-27912-7lyn6q.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=470&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/468482/original/file-20220613-27912-7lyn6q.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=470&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Recovery is part-based at Oxford University’s Big Data Institute.</span>
<span class="attribution"><span class="source">Adam Gasson/UKRI</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Tens of thousands of patients are admitted to hospital each year for conditions such as heart attacks, influenza, stroke and pneumonia. These diseases kill large numbers of people each year – many more than COVID-19 – yet the evidence base for treatment of some of them is now of worse quality.</p>
<p>Enrolling the majority of these patients into nationwide, randomised trials such as Recovery could provide definitive answers to many treatment dilemmas within months. Decisions about which treatments are better for a particular patient group are being made by doctors every day, based on limited evidence and without improving the evidence base for future patients. Instead, through a national randomised trial programme, we could all be learning with each patient who requires clinical care.</p>
<p>Furthermore, such opportunities for clinical research should not be limited to the UK. Recovery is now recruiting patients <a href="https://www.recoverytrial.net/international">in six countries in Africa and Asia</a>. By including clinically relevant common diseases and evaluating widely-available treatments, future benefits could be accessible across the world. Large collaborative trials can be managed via <a href="https://www.recoverytrial.net/">online resources</a>, randomisation can be performed online, and (where available) follow-up can be facilitated through electronic healthcare records and simple questionnaires.</p>
<p>We also hope that <a href="https://www.gov.uk/government/publications/the-future-of-uk-clinical-research-delivery/saving-and-improving-lives-the-future-of-uk-clinical-research-delivery">governments and research funders</a> can make it easier for similar large trials to happen – and for doctors and patients everywhere to be involved. The ball has already started rolling at the highest levels <a href="https://www.gov.uk/government/news/oxford-to-play-host-to-crucial-g7-health-talks">including the G7</a>, but this transformation needs continued support.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/testing-sewage-has-helped-track-covid-soon-it-could-reveal-much-more-about-the-uks-health-178141">Testing sewage has helped track COVID – soon it could reveal much more about the UK's health</a>
</strong>
</em>
</p>
<hr>
<p>Recovery has shown that these trials do not require complicated technology, expensive drugs or fancy laboratories. In the UK, pragmatic trials can be run at exceedingly low cost by making better use of the wealth of existing NHS clinical research and healthcare data infrastructure. Using this approach, we could achieve small but continuous improvements in healthcare that, when combined, lead to increased longevity and reduced disability, easing the strain on our health services. This would represent a major financial saving for the UK as a whole.</p>
<p>Recovery has also underlined the importance of embedding clinical trials in routine medical practice. Well-designed trials are carried out <a href="https://www.goodtrials.org/">with patients and for patients</a> in a healthcare system that recognises we don’t always know which treatments work, but that is committed to finding out. Through such a system we can achieve multiple, incremental improvements in patients’ health outcomes, and focus scarce medical resources on those things we know work while abandoning the many that do not.</p>
<p>As a result of <a href="https://www.recoverytrial.net/">Recovery</a>, the chances of survival for a patient admitted to hospital with COVID-19 today are substantially better than they were two years ago. Now is the time to apply these lessons to the many other health challenges we face.</p>
<p><em>This is the first in a series of Insights articles developed with <a href="https://www.ukri.org/about-us/">UK Research and Innovation</a> (UKRI) to explore the wider impacts and implications of COVID-19 research</em></p>
<hr>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=112&fit=crop&dpr=1 600w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=112&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=112&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=140&fit=crop&dpr=1 754w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=140&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=140&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<p><em>For you: more from our <a href="https://theconversation.com/uk/topics/insights-series-71218?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">Insights series</a>:</em></p>
<ul>
<li><p><em><a href="https://theconversation.com/inside-a-reintegration-camp-for-colombias-ex-guerrilla-fighters-words-of-reconciliation-are-our-only-weapons-now-184074?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">Inside a reintegration camp for Colombia’s ex-guerrilla fighters: ‘Words of reconciliation are our only weapons now’</a></em></p></li>
<li><p><em><a href="https://theconversation.com/david-bowie-and-the-birth-of-environmentalism-50-years-on-how-ziggy-stardust-and-the-first-un-climate-summit-changed-our-vision-of-the-future-181033?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">David Bowie and the birth of environmentalism: 50 years on, how Ziggy Stardust and the first UN climate summit changed our vision of the future
</a></em></p></li>
<li><p><em><a href="https://theconversation.com/chinas-covid-crisis-and-the-dilemma-facing-its-leaders-by-experts-who-have-monitored-it-since-the-wuhan-outbreak-182451?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">China’s COVID crisis and the dilemma facing its leaders, by experts who have monitored it since the Wuhan outbreak</a></em></p></li>
</ul>
<p><em>To hear about new Insights articles, join the hundreds of thousands of people who value The Conversation’s evidence-based news. <a href="https://theconversation.com/uk/newsletters/the-daily-newsletter-2?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK"><strong>Subscribe to our newsletter</strong></a>.</em></p><img src="https://counter.theconversation.com/content/184772/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 organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Two years ago, the Recovery trial transformed COVID treatments around the world with a landmark finding that may have saved a million lives in just nine monthsGuilherme Pessoa-Amorim, Clinical Research Fellow, University of OxfordLeon Peto, Senior Clinical Research Fellow, University of OxfordMark Campbell, Clinical Research Fellow, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1777212022-03-15T12:15:32Z2022-03-15T12:15:32ZThe Ebola virus can ‘hide out’ in the brain after treatment and cause recurrent infections<figure><img src="https://images.theconversation.com/files/452000/original/file-20220314-13-5nsas.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2048%2C1536&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">This image shows Ebola virus particles (red) budding from the surface of kidney cell (blue).</span> <span class="attribution"><a class="source" href="https://flic.kr/p/oq68Cn">National Institute of Allergy and Infectious Diseases/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</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>The Ebola virus can hide in the brains of monkeys that have recovered after medical treatment without causing symptoms and lead to recurrent infections, according to a study by a <a href="https://www.researchgate.net/profile/Xiankun-Zeng">team I led</a> that was published in the journal <a href="https://doi.org/10.1126/scitranslmed.abi5229">Science Translational Medicine</a>.</p>
<p><a href="https://www.cdc.gov/vhf/ebola/index.html">Ebola is one of the deadliest</a> infectious disease threats known to humankind, with an <a href="https://www.afro.who.int/health-topics/ebola-virus-disease">average fatality rate of about 50%</a>. Ebola is known for a high level of <a href="https://doi.org/10.1038/nmicrobiol.2017.124">viral persistence</a>, meaning the virus remains lurking in the body even after a patient has recovered. But where this hiding place is remains largely unknown.</p>
<p>In 2021, there were <a href="https://www.cdc.gov/vhf/ebola/outbreaks/index-2018.html">three Ebola outbreaks in Africa</a>, all linked to previously infected survivors. Ebola also reemerged in <a href="https://doi.org/10.1038/s41586-021-03901-9">Guinea</a> that same year, linked to a survivor of the 2013-2016 Ebola outbreak.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/452004/original/file-20220314-131639-4tbiwk.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A laboratory technician in full Personal protective equipment pipettes samples under a lab hood." src="https://images.theconversation.com/files/452004/original/file-20220314-131639-4tbiwk.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/452004/original/file-20220314-131639-4tbiwk.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/452004/original/file-20220314-131639-4tbiwk.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/452004/original/file-20220314-131639-4tbiwk.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/452004/original/file-20220314-131639-4tbiwk.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/452004/original/file-20220314-131639-4tbiwk.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/452004/original/file-20220314-131639-4tbiwk.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">The researchers conducted their study in a Biosafety Level 4 lab, the highest level of biocontainment required to safely study hazardous pathogens like Ebola.</span>
<span class="attribution"><span class="source">John W. Braun, USAMRIID</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>We wanted to better understand where the Ebola virus “hides” in the body of survivors and what triggers recurrent infections. So we examined 36 rhesus monkeys that had been treated for Ebola with <a href="https://www.uptodate.com/contents/overview-of-therapeutic-monoclonal-antibodies">monoclonal antibody therapy</a>, a type of treatment that helps the immune system mount an attack against an infection. These monkeys were deemed fully recovered with no symptoms of infection or detectable virus in their blood. </p>
<p>When we looked more closely at the tissues of different organs under a microscope, however, we found that about 20% of recovered monkeys still had visible Ebola virus located exclusively in the <a href="https://www.ncbi.nlm.nih.gov/books/NBK11083/">ventricular system</a> of the brain. This brain region produces, circulates and stores <a href="https://medlineplus.gov/lab-tests/cerebrospinal-fluid-csf-analysis/">cerebrospinal fluid</a>, which protects, supplies nutrients to and removes waste products from the brain.</p>
<p>Importantly, despite being asymptomatic at the start of our study, two of the monkeys we observed developed Ebola symptoms before dying at 30 and 39 days after their initial infection, respectively. Our findings suggest that the Ebola virus can hide dormant in the brains of survivors even after treatment, and the virus can reactivate and cause fatal infections later on.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/452005/original/file-20220314-101106-3uxlee.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Ventricular system of rhesus monkey that survived Ebola virus infection, with brown stains indicating viral persistence lining the edges" src="https://images.theconversation.com/files/452005/original/file-20220314-101106-3uxlee.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/452005/original/file-20220314-101106-3uxlee.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=301&fit=crop&dpr=1 600w, https://images.theconversation.com/files/452005/original/file-20220314-101106-3uxlee.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=301&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/452005/original/file-20220314-101106-3uxlee.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=301&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/452005/original/file-20220314-101106-3uxlee.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=379&fit=crop&dpr=1 754w, https://images.theconversation.com/files/452005/original/file-20220314-101106-3uxlee.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=379&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/452005/original/file-20220314-101106-3uxlee.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=379&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 image shows the brain ventricular system of a rhesus monkey that survived Ebola virus infection, where brown indicates viral persistence.</span>
<span class="attribution"><span class="source">Kevin Zeng</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<h2>Why it matters</h2>
<p>Treatment with monoclonal antibodies is the current <a href="https://www.statnews.com/2020/10/15/thank-this-ebola-fighting-african-doctor-muyembe-tamfum-for-monoclonal-antibody-treatments/">standard of care for Ebola</a>. But recurrent infections can occur even after apparently successful treatment, and patients can inadvertently transmit the virus and cause new outbreaks.</p>
<p>Our study underscores the importance of careful long-term medical follow-up of successfully treated Ebola survivors to counter the individual and public health cost of recurrent disease. This follow-up, however, will need to be conducted in a way that does not further <a href="https://longreads.trust.org/item/Ebola-survivors-DRC-combat-stigma-misinformation">stigmatize survivors of the disease</a>.</p>
<h2>What still isn’t known</h2>
<p>We still don’t know why the Ebola virus persists in the brain and causes recurrent infections. It is also unclear whether this persistence might be related to monoclonal antibody treatments, and whether other types of therapies, such as antivirals, might produce a different effect. Researchers are still looking into what triggers relapses and whether there might be other parts of the body that may act as reservoirs.</p>
<h2>What’s next</h2>
<p>Our work highlights the need to more deeply investigate why the Ebola virus persists in the brain. Because the brain is <a href="https://doi.org/10.4161/mabs.3.2.14239">less accessible</a> to monoclonal antibodies, treatments <a href="https://doi.org/10.1016/S1473-3099(20)30282-6">combining both monoclonal antibodies and antiviral drugs</a> may help prevent and clear persistent Ebola infection and related disease in the brain. Analyzing viral persistence at the <a href="https://doi.org/10.1038/s41579-020-0354-7">molecular level</a> may provide more insight.</p>
<p>[<em>Research into coronavirus and other news from science</em> <a href="https://memberservices.theconversation.com/newsletters/?nl=science&source=inline-science-corona-research">Subscribe to The Conversation’s new science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/177721/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kevin Zeng 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>Although treatments for Ebola have helped many people overcome this deadly disease, the virus can persist in the brain and cause a lethal relapse.Kevin Zeng, Principal Investigator of Infectious Diseases, U.S. Army Medical Research Institute of Infectious DiseasesLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1631972021-07-14T12:24:12Z2021-07-14T12:24:12ZWe work with dangerous pathogens in a downtown Boston biocontainment lab – here’s why you can feel safe about our research<figure><img src="https://images.theconversation.com/files/410851/original/file-20210712-70807-1iay608.JPG?ixlib=rb-1.1.0&rect=600%2C0%2C4959%2C3275&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Security precautions, thoughtful facilities design, careful training and safe lab practices help keep pathogens isolated.</span> <span class="attribution"><span class="source">Boston University Photography</span></span></figcaption></figure><p><em><a href="http://www.bumc.bu.edu/microbiology/people/faculty/ronald-b-corley-phd/">Microbiologist Ronald Corley</a> has gone to work every day throughout the pandemic as director of the <a href="https://www.bu.edu/neidl/">National Emerging Infectious Diseases Laboratories</a>. Within this secure lab facility in Boston, scientists study pathogens as diverse as tuberculosis, Ebola virus, yellow fever virus and Zika virus. Many investigators there quickly turned their attention in 2020 to SARS-CoV-2, the virus that causes COVID-19.</em></p>
<p><em>Here Corley answers some of the most frequently asked questions about this kind of biosecure lab and the work researchers do inside it.</em></p>
<h2>What is the purpose of a biocontainment facility?</h2>
<p><a href="https://doi.org/10.1016/j.cell.2020.08.021">A newly emerging or reemerging human pathogen</a> is detected somewhere around the globe <a href="http://infectiousdiseases.edc.org/">every 12 to 18 months</a>.</p>
<p>Infectious diseases don’t respect borders. Because of the global economy and unprecedented mobility, everyone on the planet is vulnerable to potentially devastating infectious diseases that may have originated halfway across the world. In this age of high-speed travel, we are as little as 36 hours away from any outbreak.</p>
<p>As with SARS-CoV-2, scientists may know little about emerging pathogens or the diseases they cause. Studying these germs – whether bacteria, viruses or other microorganisms – in the safe environment of a biocontainment laboratory is the best protection humankind has against these diseases. In the lab, researchers can safely test new diagnostics, therapeutics and vaccines. The more scientists learn about these new diseases, the better prepared we are for the ones that will come after.</p>
<p>This is where labs like the NEIDL, and our stringent safety measures, are important. I feel safer from infection working in the NEIDL than I do in my apartment building. We know what we’re working with in the lab and how to keep ourselves and others safe. But outside, I don’t know who I might pass who could have a transmissible pathogen, including the coronavirus.</p>
<p>This is not to say that there is no risk working within the laboratory – there is. But we minimize it through a series of safety measures – including building systems, laboratory design, personal protective equipment, training and safety protocols – that have been tried and tested in laboratories across the world.</p>
<h2>How do you try to minimize risk?</h2>
<p><a href="http://www.bu.edu/researchsupport/compliance/ibc/#biosafety-manual-tab">Our biosafety manual</a> sets the standards for all work with biological material in the NEIDL. Requirements increase in complexity from Biosafety Level 2 (BSL-2) on to BSL-3 and BSL-4.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=329&fit=crop&dpr=1 600w, https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=329&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=329&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=413&fit=crop&dpr=1 754w, https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=413&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=413&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Biosafety levels are defined by how much risk is involved in working with particular pathogens.</span>
<span class="attribution"><span class="source">The Conversation</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>In the U.S., the Centers for Disease Control and Prevention determines each pathogen’s biocontainment level, based on what’s known about how it infects its host, the severity of the disease it causes, how easily transmissible the pathogen may be and the nature of the work itself – does it potentially create aerosols, for example.</p>
<p>The biosafety levels require <a href="https://www.cdc.gov/cpr/infographics/biosafety.htm">different types of engineering controls</a> – such as the building materials the space uses, directional air flow to ensure pathogens can’t get out, HEPA filtration so that only sterile air is discharged from the lab space and so on.</p>
<p>The administrative controls required vary by biosafety level, as well – safety protocols, requirements for personnel training, limiting access and so forth.</p>
<p>Each level requires different types of personal protective equipment: gloves and lab coats in a BSL-2 laboratory, protective lab wear and N95 or PAPR respirators in BSL-3 or a fully encapsulating suit in a BSL-4 laboratory.</p>
<p>“Safety First” is not just a bumper-sticker phrase at the NEIDL. Everyone from public safety officers to support staff to researchers has fully bought into the culture of safety. It informs the way we’re trained and drilled, the way pathogens are transported to the facility, and policies that govern our employees. We know the risks of the work, train on protective measures, and ensure every member of our staff follows our protocols.</p>
<h2>What does containment look like with these safety strategies in place?</h2>
<p>Everyone undergoes annual background checks, medical clearances and training. Only cleared staff can enter the building alone. </p>
<p>There are limited ways into the space, one for pedestrians, and one for vehicles, like delivery trucks. Entry requires access via biometric or card access or both, and screening by security. Access controls limit staff members to entering spaces where they have permission to work, based on their training, clearances and biosafety protocols. A network of security systems and closed-circuit cameras monitors the facility.</p>
<p>Entering laboratories requires that workers don the appropriate PPE for the area. Within the labs, we know what pathogen we are working with and how it is being used and are confident staff are following the safety measures required to keep them safe. This ensures the safety of others in the building as well as the surrounding community.</p>
<p>Importantly, the biosafety practices ensure that each pathogen we’re studying is restricted to the appropriate spaces. Researchers work at biosafety cabinets that sterile-filter the air before releasing it back into the lab.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/410845/original/file-20210712-27-1o9ypjl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Scientist in full PPE works under the hood of a biosafety cabinet" src="https://images.theconversation.com/files/410845/original/file-20210712-27-1o9ypjl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/410845/original/file-20210712-27-1o9ypjl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/410845/original/file-20210712-27-1o9ypjl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/410845/original/file-20210712-27-1o9ypjl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/410845/original/file-20210712-27-1o9ypjl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/410845/original/file-20210712-27-1o9ypjl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/410845/original/file-20210712-27-1o9ypjl.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">Working with pathogens only within a specially ventilated biosafety cabinet provides another layer of security.</span>
<span class="attribution"><span class="source">Boston University Photography</span></span>
</figcaption>
</figure>
<h2>What kinds of regulation and oversight are there?</h2>
<p>Biocontainment laboratories do not function in a vacuum. The building and laboratory designs, and the PPE and operating procedures that protect staff, meet the guidelines set by the CDC and by the 574-page book “<a href="https://www.cdc.gov/labs/pdf/SF__19_308133-A_BMBL6_00-BOOK-WEB-final-3.pdf">Biosafety in Microbiological and Biomedical Laboratories</a>” from the CDC and National Institutes of Health.</p>
<p>To carry out a project, the lead scientist begins with an application to the Institutional Biosafety Committee. Experts in biosafety and science review the application, as do laypersons who provide a community perspective. These deliberations are open and transparent thanks to public participation on the committee. Its <a href="https://www.bu.edu/researchsupport/compliance/ibc/about-the-ibc/ibc-meeting-minutes/">minutes are posted online</a>. Safety professionals also inspect the laboratory facilities before work gets underway. </p>
<p>In the city of Boston, projects that involve any BSL-3 or BSL-4 work require review and approval from the Boston Public Health Commission, one of the only local public health departments with this type of oversight. Work with certain types of pathogens called “<a href="https://www.selectagents.gov/sat/list.htm">select agents</a>” that pose a severe threat is further regulated by the <a href="https://www.cdc.gov/cpr/dsat/fsap.htm">Division of Select Agents and Toxins</a> within the CDC.</p>
<p>Here at the NEIDL, both city and federal officials inspect the laboratories, interviewing personnel and reviewing records, including maintenance records. They also inspect pathogen inventories. Inspections can be announced or unannounced. </p>
<h2>What would happen if something went wrong?</h2>
<p>An important aspect of safety is making sure everyone knows what to do in an emergency. Three trainings per year involve first responders from the city as well as from Boston University. These are done as either live drills or tabletop exercises with experts walking through what an emergency would look like. Afterward we review how we did and develop plans for improvement.</p>
<p>Community members are also part of the exercises, and this keeps our neighbors involved and hopefully provides assurance of our ability to handle accidents, keeping ourselves and the community safe.</p>
<p>At Boston University, we post all laboratory incidents, including those at the NEIDL, on a quarterly basis to ensure that we remain transparent in our activities. Depending on what went wrong, we may also report to the BPHC and the CDC. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/410846/original/file-20210712-27-14f8fjq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="exterior of a building" src="https://images.theconversation.com/files/410846/original/file-20210712-27-14f8fjq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/410846/original/file-20210712-27-14f8fjq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/410846/original/file-20210712-27-14f8fjq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/410846/original/file-20210712-27-14f8fjq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/410846/original/file-20210712-27-14f8fjq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/410846/original/file-20210712-27-14f8fjq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/410846/original/file-20210712-27-14f8fjq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&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 safety of a facility like the NEIDL benefits from the expertise and resources available in a densely populated area.</span>
<span class="attribution"><span class="source">Boston University Photography</span></span>
</figcaption>
</figure>
<h2>Why place these high-security labs in urban environments with lots of neighbors instead of the middle of nowhere?</h2>
<p>Scientific research is a communal activity, and advances happen in places where diverse expertise is concentrated. It’s no different for research on emerging pathogens. Research on pathogens relies on faculty with expertise in not only the pathogens themselves but chemistry, engineering, stem cell biology, structural biology, immunology and more.</p>
<p>Biocontainment research also requires facilities engineers, safety professionals and security personnel. You can find personnel with diverse experience and expertise in metropolitan areas that are already home to biomedical research.</p>
<p>The original permitting process of the NEIDL mandated a <a href="https://www.bu.edu/neidl/files/2013/01/SFEIR-Volume-III.pdf">comprehensive risk assessment</a> to determine any potential danger for the community. After two years and independent review by two scientific panels, we ended up with the most extensive analysis of risk for any BSL-3 or BSL-4 facility in the U.S. It considered hundreds of possible scenarios that might result in exposure of a worker to a pathogen, or the release of a biological agent. The report concluded that it’s as safe, or even safer, to have such a facility in an urban environment than in a rural or suburban environment.</p>
<p>“Near misses” have occurred at these kinds of labs within the U.S. and Europe. A near miss might, for example, involve glove tears and a potential exposure to a pathogen during laboratory work, but these have never resulted in any community infections. At the NEIDL, we intend to maintain this track record.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/410849/original/file-20210712-25-gcc2ln.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="three men in full PPE gather around lab equipment" src="https://images.theconversation.com/files/410849/original/file-20210712-25-gcc2ln.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/410849/original/file-20210712-25-gcc2ln.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/410849/original/file-20210712-25-gcc2ln.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/410849/original/file-20210712-25-gcc2ln.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/410849/original/file-20210712-25-gcc2ln.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/410849/original/file-20210712-25-gcc2ln.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/410849/original/file-20210712-25-gcc2ln.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">Scientists put their intellectual curiosity to work on problems that challenge public health.</span>
<span class="attribution"><span class="source">Boston University Photography</span></span>
</figcaption>
</figure>
<h2>What are the risks of not doing this research?</h2>
<p>Science builds on what’s been learned before, accelerating our ability to respond to new outbreaks. The data we generate speeds progress on other pathogens as well, and informs how we develop and test potential therapeutics and vaccines. The risk of not doing this work is to leave ourselves more vulnerable to emerging pathogens as they arise.</p>
<p>Professionals working on emerging infectious diseases are interested in solving problems that benefit the public’s health. We take pride in our work and are serious about our responsibility to perform our work safely and securely. We recognize that this research is often viewed skeptically and thus strive to keep the trust of the public by ensuring transparency around the work we do.</p>
<p>[<em>The Conversation’s science, health and technology editors pick their favorite stories.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-favorite">Weekly on Wednesdays</a>.]</p><img src="https://counter.theconversation.com/content/163197/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ronald Corley receives funding from the National Institutes of Health, and the Massachusetts Consortium on Pathogen Readiness. </span></em></p>The microbiologist who directs the National Emerging Infectious Diseases Laboratories at Boston University explains all the biosafety precautions in place that help him feel safer in the lab than out.Ronald Corley, Director of the National Emerging Infectious Diseases Laboratories and Chair of Microbiology, Boston UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1617212021-06-10T12:36:13Z2021-06-10T12:36:13ZWorking with dangerous viruses sounds like trouble – but here’s what scientists learn from studying pathogens in secure labs<figure><img src="https://images.theconversation.com/files/405550/original/file-20210610-23-dvc6ay.jpg?ixlib=rb-1.1.0&rect=105%2C0%2C6285%2C3592&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Microbes are everywhere – and they aren't all friendly.
</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/bacterium-closeup-royalty-free-image/1203775802">spawns/E+ via Getty Images</a></span></figcaption></figure><p>There are about <a href="https://www.nature.com/articles/nrmicro2644">1,400 known human pathogens</a> – viruses, bacteria, fungi, protozoa and helminths that can cause a person’s injury or death. But in a world with <a href="https://doi.org/10.1073/pnas.1521291113">a trillion individual species of microorganisms</a>, where scientists have counted only <a href="https://aeon.co/ideas/there-are-more-microbial-species-on-earth-than-stars-in-the-sky">one one-thousandth of one percent</a>, how likely is it researchers have <a href="https://doi.org/10.1038/nmicrobiol.2016.48">discovered and characterized</a> everything that might threaten people?</p>
<p>Not very likely at all. And there’s a lot to be gained from knowing these microscopic enemies better. </p>
<p>So even though in day-to-day life it makes sense to avoid these dangerous microorganisms, scientists <a href="https://scholar.google.com/citations?view_op=list_works&hl=en&user=ZvAUt2kAAAAJ">like me</a> are motivated to study them up close and personal to learn how they work. Of course, we want to do it in as safe a way as possible.</p>
<p>I’ve worked in biocontainment laboratories and have published scientific articles on both bacteria and viruses, including influenza <a href="https://doi.org/10.3389/fgene.2020.612571">and the SARS-CoV-2 coronavirus</a>. Here at Oklahoma State University, 10 research groups are currently studying pathogens in biosecure labs. They’re identifying genetic variations of viruses and bacteria, studying how they operate within cells of their hosts. Some are untangling how the host immune system responds to these invaders and is affected by so-called comorbidities of obesity, diabetes or advanced age. Others are investigating how to detect and eliminate pathogens.</p>
<p>This kind of research, to understand how pathogens cause harm, is crucial to human and veterinary medicine, as well as the health of mammals, birds, fish, plants, insects and other species around the globe.</p>
<h2>Forewarned is forearmed</h2>
<p>Think about all scientists have learned in the past century about how to prevent diseases based on understanding which microorganism is responsible, where it is in the environment and how it overcomes humans’ natural defenses.</p>
<p>Understanding what these organisms do, how they do it, and how they spread helps researchers develop measures to detect, mitigate and control their expansion. The goal is to be able to cure or prevent the disease they cause. The more dangerous the pathogen, the more urgently scientists need to understand it.</p>
<p>This is where lab research comes in. </p>
<p>Scientists have basic questions about how a pathogen conducts itself. What machinery does it use to enter a host cell and replicate? What genes does it activate, to make which proteins? This kind of information can be used to pinpoint strategies to eliminate the pathogen or lead to disease treatments or vaccines.</p>
<p>As the library of what is known about pathogens grows, there’s more chance researchers can apply some of that knowledge when faced with an emerging pathogen.</p>
<p>People might encounter new pathogens as they move into different parts of the world, or alter ecosystems. Sometimes a pathogen adapts to a new vector – meaning it can be carried by a different organism – allowing it to spread into new areas and infect new populations. <a href="https://doi.org/10.1098/rstb.2001.0888">Roughly 70% of emerging infectious diseases</a> around the world are transmitted through animals to people; these are called zoonotic diseases. It is critical to understand how these pathways work in order to have even a modest ability to predict what could happen.</p>
<p>While there are patterns in nature that can provide clues, the tremendous diversity of the microbial world and the rate at which these organisms evolve new strategies for their own defense and survival makes it imperative to study and understand each one as it’s discovered.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/405532/original/file-20210610-14622-yakcdd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="seated researcher in PPE seen from behind in lab" src="https://images.theconversation.com/files/405532/original/file-20210610-14622-yakcdd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/405532/original/file-20210610-14622-yakcdd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/405532/original/file-20210610-14622-yakcdd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/405532/original/file-20210610-14622-yakcdd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/405532/original/file-20210610-14622-yakcdd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/405532/original/file-20210610-14622-yakcdd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/405532/original/file-20210610-14622-yakcdd.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">A scientist wearing personal protective gear works with coronavirus within a biosafety cabinet.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/scientists-wearing-ppe-carry-out-tests-in-a-bio-safety-news-photo/1266591090?adppopup=true">Pallava Bagla/Corbis News via Getty Images</a></span>
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<h2>Can this research be done safely?</h2>
<p>There is no such thing as zero risk in any endeavor, but over many years, researchers have developed safe laboratory methods for working with dangerous pathogens.</p>
<p>Each study must document in advance what is to be done, how, where and by whom. These descriptions are reviewed by independent committees to make sure the plans outline the safest way to do the work. There’s independent follow-up by trained professionals within the institution and, in some cases, by the U.S. Centers for Disease Control and Prevention, the U.S. Department of Agriculture, or both, to ensure researchers are following the approved procedures and regulations.</p>
<p>Those who work with dangerous pathogens <a href="https://doi.org/10.3389/fbioe.2020.00650">adhere to two</a> <a href="https://www.who.int/influenza/pip/BiosecurityandBiosafety_EN_20Mar2018.pdf">sets of principles</a>. There’s biosafety, which refers to containment. It includes all the engineering controls that keep the scientists and their surroundings safe: enclosed, ventilated workspaces called biosafety cabinets, directional airflows and anterooms to control air movement inside the lab. Special high-efficiency particulate air filters (HEPA) clean the air moving in and out of the laboratory.</p>
<p>We stick to good laboratory work practices, and everyone suits up in personal protective equipment including gowns, masks and gloves. Sometimes we use special respirators to filter the air we breathe while in the lab. Additionally we often inactivate the pathogen we’re studying – essentially taking it apart so it is not functional – and work on the pieces one or a few at a time.</p>
<p>Then there’s biosecurity, meaning the measures designed to prevent loss, theft, release or misuse of a pathogen. They include access controls, inventory controls and certified methods for decontaminating and disposing of waste. Part of these security measures is keeping the details close.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=329&fit=crop&dpr=1 600w, https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=329&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=329&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=413&fit=crop&dpr=1 754w, https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=413&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/341976/original/file-20200615-65961-1md20md.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=413&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Biosafety levels are defined by how much risk is involved in working with particular pathogens.</span>
<span class="attribution"><span class="source">The Conversation</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p>The research community recognizes <a href="https://www.who.int/csr/resources/publications/biosafety/Biosafety7.pdf">four levels of biosafety practices</a>. Biosafety level-1 (BSL-1) and BSL-2 are applied to general laboratory spaces where there is low to no risk. They would not work with microorganisms that pose a serious threat to people or animals.</p>
<p>BSL-3 refers to laboratories where there is high individual risk but low community risk, meaning there is a pathogen that can cause serious human disease but treatments are available. This is the kind of work my colleagues and I, and many medical and veterinary schools, will do.</p>
<p>BSL-4 refers to work with pathogens that pose a high risk of significant disease in people, animals or both that is transmitted among individuals and for which an effective treatment may not be available. BSL-4 laboratories are relatively rare, by one estimate <a href="https://en.wikipedia.org/wiki/Biosafety_level">only about 50 exist in the world</a>.</p>
<p>At each level the increased risk requires increasingly stringent precautions to keep workers safe and prevent any accidental or malicious misuse.</p>
<p>[<em><a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-corona-important">The Conversation’s most important coronavirus headlines, weekly in a science newsletter</a></em>]</p>
<h2>What’s at risk if science ignores these microbes?</h2>
<p>In recent years, the world has seen <a href="https://doi.org/10.1111/1556-4029.14034">outbreaks of severe disease</a> caused by several types of pathogens. Even for the pathogens scientists do know about, much remains unknown. It is reasonable to expect there are more threats out there yet to be discovered.</p>
<p>It is critical for scientists to study new disease pathogens in the lab as they’re discovered and to understand how they move from host to host and are affected by conditions; what variations develop over time; and what effective control measures can be developed. In addition to more well-known viruses such as rabies, West Nile virus and Ebola, there are <a href="https://doi.org/10.1016/j.tmaid.2019.101471">several critically important pathogens</a> circulating in the world today that pose a serious threat. <a href="https://doi.org/10.1016/j.onehlt.2017.12.002">Hantaviruses</a>, <a href="https://doi.org/10.1038/nrmicro2460">dengue</a>, <a href="http://dx.doi.org/10.2471/BLT.16.171082">Zika virus</a> and the <a href="https://doi.org/10.1080/01652176.2019.1580827">Nipah virus</a> are all under investigation in various labs, where researchers are working to understand more about how they’re transmitted, develop rapid diagnostics and produce vaccines and therapeutics.</p>
<p>Microorganisms are the most abundant form of life on the planet and extremely important to human health and the health of plants and animals. In general, people have adapted to their presence, and vice versa. For those microbes with the capacity to do real harm, it makes sense to study as many as scientists can now, before the next pandemic hits.</p>
<p><em>This article has been updated to clarify the kinds of pathogens studied in BSL-3 laboratories.</em></p><img src="https://counter.theconversation.com/content/161721/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jerry Malayer 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>Scientists get up close and personal with deadly pathogens to give doctors the tools they need to treat people sickened by germs. The key is keeping the researchers – and everyone around them – safe.Jerry Malayer, Associate Dean for Research and Graduate Education and Professor of Physiological Sciences in the College of Veterinary Medicine, Oklahoma State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1505962020-12-17T13:29:19Z2020-12-17T13:29:19Z10 reasons why Anthony Fauci was ready to be the face of the US pandemic response<figure><img src="https://images.theconversation.com/files/374923/original/file-20201214-17-1s3m7ar.jpg?ixlib=rb-1.1.0&rect=1086%2C718%2C2874%2C1864&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Fauci is an accomplished scientist who also excels at connecting with the public.</span> <span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/WashingtonIdeasForum/429cb8132c184c1fbd3ccbe28a3dc87d/photo?boardId=d7f2514f50804466b15dfb81ed00d9cd&st=boards&mediaType=audio,photo,video,graphic&sortBy=&dateRange=Anytime&totalCount=26&currentItemNo=8">AP Photo/Cliff Owen</a></span></figcaption></figure><p>His call to “Wear a mask” tops a <a href="https://apnews.com/article/joe-biden-fred-shapiro-anthony-fauci-coronavirus-pandemic-racial-injustice-e91a67237ab395eb63105d4bfb811247">list of 2020’s notable quotes</a>. Brad Pitt <a href="https://www.youtube.com/watch?v=uW56CL0pk0g">portrayed him – and praised him – on “Saturday Night Live</a>.” Time magazine <a href="https://time.com/guardians-of-the-year-2020-anthony-fauci-frontline-health-workers/">named him a 2020 guardian of the year</a>. Amazon features seven pages of T-shirts, mugs and more emblazoned with his face.</p>
<p>Longtime <a href="https://www.niaid.nih.gov/about/director">director of the National Institute of Allergy and Infectious Diseases</a> Anthony S. Fauci has been everywhere in 2020.</p>
<p>Although perhaps only recently a household name, Fauci is no Tony-come-lately. Over the past four decades he’s played prominent roles as a scientist, physician, administrator and spokesman. You know what he’s been up to over the past several months. But what of his previous nearly 80 years? And what made him the figure he has become?</p>
<h2>From Brooklyn to Washington</h2>
<p><a href="https://en.wikipedia.org/wiki/Anthony_Fauci">Fauci, son of a pharmacist</a>, was <a href="https://www.biography.com/scientist/anthony-fauci">born in Brooklyn</a> on Dec. 24, 1940. He attended Regis High, a tuition-free Jesuit boys’ school. Passionate about basketball, he captained the high school team – despite his height of 5 feet 7 inches.</p>
<p>He then attended the College of the Holy Cross, in Massachusetts, choosing a premedical major combining humanities and science. He graduated first in his class from Cornell University Medical College and went on to complete a medical residency.</p>
<p>The Vietnam War was underway, and male med school graduates were required to serve their country. One option was the U.S. Public Health Service, which includes the National Institutes of Health, based outside Washington, D.C. Fauci entered a <a href="https://history.nih.gov/download/attachments/1016824/YellowBerets.pdf">highly selective training program</a> there. He’s worked at NIH essentially ever since.</p>
<p>At NIH, Fauci initially conducted specialized research on the immune system and related rare diseases – for example, one now termed <a href="https://medlineplus.gov/granulomatosiswithpolyangiitis.html">granulomatosis with polyangiitis</a>, in which blood vessels in the respiratory system and kidneys become inflamed. His work led to effective treatment of these previously largely fatal conditions.</p>
<h2>The age of AIDS</h2>
<p>As the 1980s arrived, what came to be called AIDS emerged. Fauci soon redirected his research to focus on the new disease. <a href="https://www.washingtonpost.com/opinions/2020/07/16/anthony-fauci-built-truce-trump-is-destroying-it/?arc404=true">He accepted the directorship of NIAID in 1984</a>, in part to increase its emphasis on AIDS.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/375430/original/file-20201216-21-5fkz11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="protesters holding signs with flare smoke in background" src="https://images.theconversation.com/files/375430/original/file-20201216-21-5fkz11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/375430/original/file-20201216-21-5fkz11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=396&fit=crop&dpr=1 600w, https://images.theconversation.com/files/375430/original/file-20201216-21-5fkz11.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=396&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/375430/original/file-20201216-21-5fkz11.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=396&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/375430/original/file-20201216-21-5fkz11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=497&fit=crop&dpr=1 754w, https://images.theconversation.com/files/375430/original/file-20201216-21-5fkz11.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=497&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/375430/original/file-20201216-21-5fkz11.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=497&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Protesters demonstrating at the National Institutes of Health, May 21, 1990.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/AIDSCrisis1990/c87a4dad94ff403b8eb5895a047ffcca/photo?boardId=d7f2514f50804466b15dfb81ed00d9cd&st=boards&mediaType=audio,photo,video,graphic&sortBy=&dateRange=Anytime&totalCount=27&currentItemNo=0">AP Photo/Bob Daugherty</a></span>
</figcaption>
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<p>While continuing research and patient care, Fauci as institute director entered other realms. He <a href="https://www.c-span.org/person/?anthonyfauci">testified repeatedly before Congress</a>. He gained visibility in the media. He was confronted by AIDS activists – and eventually <a href="https://www.newyorker.com/magazine/2020/04/20/how-anthony-fauci-became-americas-doctor">included them in setting priorities for developing treatments</a>. Doing so <a href="https://www.washingtonpost.com/history/2020/05/20/fauci-aids-nih-coronavirus/">set a precedent for involving patients</a> in decisions about research on their diseases.</p>
<p>Fauci’s leadership has expanded over the years. He was among the main architects of the President’s Emergency Plan for AIDS Relief, or <a href="https://www.state.gov/pepfar/">PEPFAR</a>, a major program <a href="https://doi.org/10.1056/NEJMp1714773">begun under President George W. Bush in 2003</a>, to <a href="https://www.hiv.gov/federal-response/pepfar-global-aids/pepfar">help control AIDS internationally</a>. He provided leadership regarding responses to <a href="https://doi.org/10.1097/01.COT.0000295196.65807.39">bioterrorism</a> and to <a href="http://dx.doi.org/10.3201/eid1104.041167">SARS</a>, <a href="https://doi.org/10.1056/NEJMp1600297">Zika</a> and <a href="https://doi.org/10.1056/NEJMp1409494">Ebola</a>. He is a member of the Trump administration’s White House Coronavirus Task Force, and he has accepted President-elect Joe Biden’s <a href="https://www.nytimes.com/2020/12/04/us/fauci-says-he-accepted-bidens-offer-to-be-chief-medical-adviser-right-on-the-spot.html">invitation to serve as chief medical adviser</a>.</p>
<h2>Prolific in publication</h2>
<p>Along the way, Fauci has <a href="https://pubmed.ncbi.nlm.nih.gov/?term=fauci+as">authored or co-authored well over 1,000 journal articles</a>, including <a href="https://pubmed.ncbi.nlm.nih.gov/?term=fauci+as&filter=subject.aids">more than 500 about AIDS</a>. Of the articles, strikingly many appeared in top journals such as Science, Proceedings of the National Academy of Sciences and the New England Journal of Medicine. Fauci also is one of the editors of <a href="https://www.mhprofessional.com/medical/harrisons-principles-of-internal-medicine">a major medical textbook</a>.</p>
<p>Over the years Fauci published on topics that attest to his readiness for the coronavirus: <a href="https://doi.org/10.1086/511989">past pandemics</a> as well as <a href="https://doi.org/10.1097/00001888-200512000-00002">emerging infectious diseases</a> and <a href="https://doi.org/10.1126/scitranslmed.3009872">how to confront them</a>, even how to <a href="https://doi.org/10.1177/1740774515618198">conduct clinical trials in the midst of an outbreak</a>.</p>
<p>A recent study <a href="http://www.webometrics.info/en/hlargerthan100">ranks Fauci as the 32nd most highly cited</a> living researcher. His papers have been <a href="https://app.webofknowledge.com/author/record/30304308">cited more than 50,000 times</a> by other publications, and his journal articles have been mentioned tens of thousands of times in social media.</p>
<h2>Sources of success</h2>
<p>Clearly, Fauci is a remarkably successful scientist and a highly visible public figure. What factors seem to have contributed? Here are 10.</p>
<ol>
<li><p>Smarts: Clearly Fauci is extraordinarily bright and knowledgeable. He has studied both science and humanities. The mix has fostered proficiency in lab and clinic, skill in communication and an ability to navigate the halls of power.</p></li>
<li><p>Integrity: “I believe I have a personal responsibility to make a positive impact on society,” he <a href="https://www.npr.org/templates/story/story.php?storyId=4761448">has stated</a>. “I’ve tried to accomplish this goal by choosing a life of public service.” Strong values have directed his choices, such as that to remain at NIAID <a href="https://www.nature.com/articles/nm0102-10">despite offers</a> to become director of NIH or take more lucrative positions elsewhere.</p></li>
<li><p>Empathy: Fauci’s values include concern for others’ well-being. Upon being confronted by AIDS activists, he said, “<a href="https://www.holycross.edu/departments/publicaffairs/hcm/summer02/features/fauci.html">I saw people who were in pain</a>.” He cared for, and about, people with AIDS even while the disease still was tremendously stigmatized.</p></li>
<li><p>Flexibility: Fauci can pivot. He redirected his work with the emergence of AIDS, contributing importantly to the understanding and treatment of the disease. Despite insults from AIDS activist Larry Kramer, he developed a <a href="https://www.nytimes.com/2020/05/27/health/larry-kramer-anthony-fauci.html">productive alliance and warm friendship</a> with him.</p></li>
<li><p>Energy: Fauci has an exceptional work ethic and is blessed with amazing energy. <a href="https://doi.org/10.1126/science.337.6091.152">Account</a> after <a href="https://www.huffpost.com/entry/anthony-fauci-fighting-covid-19_n_5fc7fed7c5b61bea2b14e3ee">account</a> details the staccato pace of his ultra-long days – rising before dawn, rushing from commitment to commitment with barely a break and answering email until late at night.</p></li>
<li><p>Trustworthiness: Fauci has earned credibility – through research and publication, impact on patient health and long service. In his communications, his values keep him focusing on the facts. An essay in the <a href="https://www.washingtonpost.com/opinions/2020/07/16/anthony-fauci-built-truce-trump-is-destroying-it/?arc404=true">Washington Post</a> terms him “the singular referee the country trusts” during the pandemic.</p></li>
<li><p>Connections: Adviser to six U.S. presidents and the current president-elect, Fauci has abundant ties in Washington among both politicians and the media. Some science reporters have covered his work since the 1980s.</p></li>
<li><p>Communication: Termed “<a href="https://www.nytimes.com/2020/03/08/health/fauci-coronavirus.html">the explainer-in-chief of the coronavirus epidemic</a>,” Fauci is a master communicator. He knows how the media function. He explains clearly. He speaks in sound bites – think “<a href="https://apnews.com/article/travel-public-health-colorado-health-anthony-fauci-45ef103e241a14e8760b6bb417fcabb3">we are likely going to see a surge upon a surge</a>” of cases after the Thanksgiving holiday – and his comments are tweetable. He is accessible to the press. He listens as well as speaks.</p></li>
<li><p>Recognizability: Fauci has a distinctive look and voice. His name is unusual yet not unwieldy.</p></li>
<li><p>Teamwork: “It’s almost impossible to do anything meaningful without either leading a team or being part of the team,” Fauci <a href="https://www.wsj.com/articles/the-mentor-who-made-dr-anthony-fauci-11587040520?page=1">has said</a>. A <a href="https://www.niaid.nih.gov/research/lab-immunoregulation">photo of Fauci’s lab group</a> shows some 80 members, including senior researchers. <a href="https://servicetoamericamedals.org/honorees/anthony-s-fauci-m-d/">Highly regarded for his mentorship</a>, Fauci even <a href="https://news.yahoo.com/fauci-read-undergraduate-thesis-now-171950882.html">made himself available to an undergrad</a> writing a thesis – and then commented extensively on the finished product.</p></li>
</ol>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/375434/original/file-20201216-23-ey0q7r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Fauci throws out a pitch at an MLB stadium" src="https://images.theconversation.com/files/375434/original/file-20201216-23-ey0q7r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/375434/original/file-20201216-23-ey0q7r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/375434/original/file-20201216-23-ey0q7r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/375434/original/file-20201216-23-ey0q7r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/375434/original/file-20201216-23-ey0q7r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/375434/original/file-20201216-23-ey0q7r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/375434/original/file-20201216-23-ey0q7r.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">Fauci found time to throw out the ceremonial first pitch at a Major League Baseball game in July 2020.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/YankeesNationalsBaseball/9e70a8a5d3404c358eb82083cfd8fb14/photo?boardId=d7f2514f50804466b15dfb81ed00d9cd&st=boards&mediaType=audio,photo,video,graphic&sortBy=&dateRange=Anytime&totalCount=27&currentItemNo=3">AP Photo/Andrew Harnik</a></span>
</figcaption>
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<p>In many ways, Fauci has been the face of the fight against COVID-19 in the U.S. “If we’re going to get through this, we’ve got to all pull together as a country,” Fauci <a href="https://asm.org/Articles/2020/August/Fauci-Calls-for-American-to-Pull-Together-to-Fight">has stated</a>. His blunt, evidence-based approach has helped make him famous in 2020. With any luck, he can lead the way to controlling COVID-19 in 2021.</p>
<p>[<em>Get facts about coronavirus and the latest research.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=coronavirus-facts">Sign up for The Conversation’s newsletter.</a>]</p><img src="https://counter.theconversation.com/content/150596/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Barbara Gastel 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>Fauci turns 80 this Dec. 24 – and he’s been on the national stage for decades. Here’s more about his work before COVID-19 and why he was perfectly poised to help the US respond to the pandemic.Barbara Gastel, Professor of Veterinary Integrative Biosciences and of Humanities in Medicine, Texas A&M UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1411752020-06-24T12:17:48Z2020-06-24T12:17:48ZMuseums preserve clues that can help scientists predict and analyze future pandemics<figure><img src="https://images.theconversation.com/files/343602/original/file-20200623-188891-x6loby.jpg?ixlib=rb-1.1.0&rect=5%2C0%2C3445%2C2302&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Specimens like these at Dublin's Natural History Museum contain valuable information about the evolution of pathogens and host organisms. </span> <span class="attribution"><a class="source" href="https://flic.kr/p/7ZaWsq">Kieran Guckian/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>In less than 20 years, communities around the globe have been hit by a string of major disease outbreaks: SARS, MERS, Ebola, Zika and now, COVID-19. Nearly all emerging infectious diseases in humans originate from microorganisms that are harbored by wildlife and subsequently “jump,” either directly or indirectly – for example, through mosquitoes or ticks – to humans.</p>
<p>One factor driving the increase in zoonotic disease outbreaks is that human activities – including population growth, migration and consumption of wild animals – are leading to <a href="https://doi.org/10.1098/rspb.2019.2736">increased encounters with wildlife</a>. At the same time, genetic mutations in viruses and other microbes are creating new opportunities for disease emergence. </p>
<p>But humans remain largely ignorant of our planet’s biodiversity and its natural ecosystems. Only two million species – about 20% of all the estimated species on Earth – <a href="https://www.scientificamerican.com/article/all-2-3-million-species-are-mapped-into-a-single-circle-of-life/">have even been named</a> In our view, this fundamental ignorance of nearly all aspects of biodiversity has resulted in an inefficient, poorly coordinated and minimally science-based response to key aspects of the COVID-19 pandemic. </p>
<p>We have diverse backgrounds in <a href="https://www.researchgate.net/profile/Pamela_Soltis">plant</a> and <a href="https://scholar.google.com/citations?user=WSfSPbgAAAAJ&hl=en">mammal</a> evolution and <a href="https://scholar.google.com/citations?user=dOknrtAAAAAJ&hl=en">emerging infectious diseases</a>. In a newly published commentary that we wrote with colleagues from across the U.S. and in six other countries, we identify <a href="http://dx.doi.org/%2010.1093/biosci/biaa064">a largely untapped resource for predicting future pandemics</a>: natural history collections in museums around the world.</p>
<p>These collections preserve specimens of animals, plants and other organisms that illustrate the diversity of life on Earth. They are <a href="https://cetaf.org/covid19-taf-communities-taking-action">reservoirs of information and samples</a> that can help scientists identify likely pathogen sources, hosts and transmission pathways. We believe that leveraging collections in this way will require more resources and more collaboration between biodiversity scientists and disease outbreak sleuths.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/8ltsM-LoBGQ?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Sir David Attenborough explains how museum collections contribute to our understanding of the natural world.</span></figcaption>
</figure>
<h2>Archives of life on Earth</h2>
<p>Research shows that zoonotic diseases have increased due to <a href="https://doi.org/10.1098/rspb.2019.2736">human intrusion into animal habitats</a>. In particular, <a href="https://theconversation.com/explainer-where-did-zika-virus-come-from-and-why-is-it-a-problem-in-brazil-53425">destruction of tropical rain forests</a> throughout the world has brought us face to face with microbes that occur naturally in wild animals and can cause disease in our own species. </p>
<p>Earth’s biodiversity is connected through a <a href="http://www.onezoom.org/otop/@biota=93302?img=best_any&anim=flight#x1068,y2073,w4.9401">family tree</a>. Viruses, bacteria and other microbes have evolved with their hosts for millions of years. As a result, a virus that resides in a wild animal host such as a bat without causing disease can be highly pathogenic when transmitted to humans. This is the case with zoonotic diseases. </p>
<p>Unfortunately, national responses to disease outbreaks are often based on very limited knowledge of the basic biology, or even the identity, of the pathogen and its wild host. As scientists, we believe that harnessing centuries of biological knowledge and resources from natural history collections can provide an informed road map to identify the origin and transmission of disease outbreaks. </p>
<p>These collections of animals, plants and fungi date back centuries and are the richest sources of information available about life on Earth. They are housed in museums ranging from the <a href="https://naturalhistory.si.edu/">Smithsonian Institution</a> to <a href="http://scnet.acis.ufl.edu/">small colleges</a>. </p>
<p>Together, the world’s natural history collections are estimated to contain <a href="http://dx.doi.org/10.1126/science.352.6287.762">more than three billion specimens</a>, including preserved specimens of possible hosts of the coronaviruses that have led to SARS, MERS and COVID-19. They provide a powerful distribution map of our planet’s biodiversity over space and through time.</p>
<p><div data-react-class="InstagramEmbed" data-react-props="{"url":"https://www.instagram.com/p/B5I8lD0FzSz/?utm_source=ig_web_copy_link","accessToken":"127105130696839|b4b75090c9688d81dfd245afe6052f20"}"></div></p>
<h2>Preserved pathogens</h2>
<p>How can researchers channel these collections toward disease discovery? Each specimen – say, a species of pitcher plant from Florida or a deer mouse from arid New Mexico – is catalogued with a scientific name, a collection date and the place where it was collected, and often with other relevant information. These records underpin scientists’ understanding of where host species and their associated pathogens are found and when they occurred there. </p>
<p>Connecting the site of a disease outbreak to potential pathogen hosts that occur in that area can help to pinpoint likely hosts, sources of pathogens, and pathways of transmission from hosts to humans and from one human to another. These natural history collections are connected worldwide through massive online databases, so a researcher anywhere in the world can find information on potential hosts in far-off regions. </p>
<p>But that’s just the beginning. A preserved specimen of a rodent, a bat or any other potential host animal in a collection also carries preserved pathogens, such as coronaviruses. This means that researchers can quickly survey microbes using specimens that were collected decades or more before for an entirely different purpose. They can use this information to quickly identify a pathogen, associate it with particular wild hosts, and then reconstruct the past distributions and evolution of disease-causing microbes and hosts across geographic space. </p>
<p>Many collections contain frozen samples of animal specimens stored in special low-temperature freezers. These materials can be quickly surveyed for microbes and possible human pathogens <a href="https://www.idigbio.org/content/idigbio%E2%80%99s-directory-genetic-resources-enhances-discoverability-materials-covid-19-and-beyond">using genetic analysis</a>. Scientists can compare DNA sequences of the pathogens found in animal specimens with the disease-causing agent to identify and track pathways of transmission. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/343603/original/file-20200623-188886-1bg2pd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/343603/original/file-20200623-188886-1bg2pd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/343603/original/file-20200623-188886-1bg2pd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/343603/original/file-20200623-188886-1bg2pd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/343603/original/file-20200623-188886-1bg2pd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/343603/original/file-20200623-188886-1bg2pd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/343603/original/file-20200623-188886-1bg2pd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/343603/original/file-20200623-188886-1bg2pd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Nitrogen freezers for cryo-preserving specimens in the Smithsonian National Museum of Natural History’s Biorepository.</span>
<span class="attribution"><a class="source" href="https://naturalhistory.si.edu/education/teaching-resources/life-science/dna-genomics">Donald E. Hurlbert/Smithsonian</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>For example, museum specimens of deer mice at the University of New Mexico were key to the rapid identification of a <a href="https://dx.doi.org/10.3201/eid2411.180381">newly discovered species of hantavirus</a> that caused 13 deaths in the southwest United States in 1993. Subsequent studies of preserved specimens have revealed many new species and variants of hantaviruses in other rodents, shrews, moles and, recently, bats worldwide.</p>
<h2>Equipping museums and connecting scientists</h2>
<p>Natural history collections have the potential to help revolutionize studies of epidemics and pandemics. But to do this, they will need more support. </p>
<p>Even though they play a foundational role in biology, collections are generally underfunded and understaffed. Many of them lack recent specimens or associated frozen tissues for genetic analyses. Many regions of our planet have been poorly sampled, especially the most biodiverse countries near the tropics.</p>
<p>To leverage biodiversity science for biomedical research and public health, museums will need more field sampling; new facilities to house collections, especially in biodiverse countries; and expanded databases for scientists who collect the samples, analyze DNA sequences and track transmission routes. These investments will require increased funding and innovations in biomedical and biodiversity sciences. </p>
<p>Another challenge is that natural history curators and pathobiologists who study the mechanisms of disease work in separate scientific communities and are only vaguely aware of each other’s resources, despite clear benefits for both basic and clinical research. We believe now is the time to reflect on how to leverage diverse resources and <a href="https://www.feinstein.senate.gov/public/_cache/files/8/1/81a51199-e72e-480c-b0b1-1c6919c7ae62/D4FF9185D7B48C250A9B0EEEB4269B7F.national-one-health-awareness-month-resolution.pdf">build stronger ties</a> between natural history museums, pathobiologists and public health institutions. Collaboration will be key to our ability to predict, and perhaps forestall, future pandemics.</p>
<p>[<em>Get our best science, health and technology stories.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-best">Sign up for The Conversation’s science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/141175/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Pamela Soltis receives funding from the National Science Foundation. She serves on leadership boards of the American Institute of Biological Sciences and the American Society of Plant Taxonomists.</span></em></p><p class="fine-print"><em><span>Joseph Cook receives funding from the National Science Foundation. </span></em></p><p class="fine-print"><em><span>Richard Yanagihara receives funding from the National Institutes of Health. He works at the John A. Burns School of Medicine, of the University of Hawaii at Manoa.</span></em></p>Genetic information that could help finger the next infectious threat is stored in museums around the world.Pamela Soltis, Distinguished Professor and Curator, Florida Museum of Natural History, University of FloridaJoseph Cook, Professor of Biology and Curator, Division of Mammals, Museum of Southwestern Biology, University of New MexicoRichard Yanagihara, Professor of Pediatrics and Principal Investigator, Pacific Center for Emerging Infectious Diseases Research, University of HawaiiLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1362182020-04-15T22:30:38Z2020-04-15T22:30:38ZCoronavirus may wane this summer, but don’t count on any seasonal variation to end the pandemic<figure><img src="https://images.theconversation.com/files/328217/original/file-20200415-153308-kleblr.jpg?ixlib=rb-1.1.0&rect=187%2C113%2C3413%2C2411&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Plenty of warm and humid places – including Miami – are seeing the spread of SARS-CoV-2.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/miami-beach-lummus-park-closed-due-to-pandemic-sign-and-man-news-photo/1217550661">Jeff Greenberg/Universal Images Group via Getty Images</a></span></figcaption></figure><p>Will SARS-CoV-2, the virus that causes COVID-19, fade away on its own this summer?</p>
<p>After all, other viruses – including influenza and respiratory syncytial virus
<a href="https://www.cdc.gov/rsv/research/us-surveillance.html">(RSV)</a>, which causes bronchiolitis in little children – are <a href="https://www.cdc.gov/flu/about/season/flu-season.htm">mostly seen in the winter</a>.</p>
<p>The National Academies’ Standing Committee on <a href="https://www.nationalacademies.org/our-work/standing-committee-on-emerging-infectious-diseases-and-21st-century-health-threats#sectionCommittee">Emerging Infectious Diseases and 21st Century Health Threats</a> <a href="https://www.nap.edu/catalog/25771/rapid-expert-consultation-on-sars-cov-2-survival-in-relation-to-temperature-and-humidity-and-potential-for-seasonality-for-the-covid-19-pandemic-april-7-2020">recently addressed the question</a> of whether SARS-CoV-2 will follow the same pattern. The group of experts corralled the research that’s been done so far – much of it not yet peer-reviewed – to assess the evidence.</p>
<p>While there is some reason to hope that things may get better as the weather warms up, there is plenty of reason for the U.S. to keep its guard up.</p>
<h2>Are heat and humidity reason for hope?</h2>
<p>Although the U.S. is early in the course of the pandemic, there is evidence from other countries that SARS-CoV-2 spreads more rapidly in cold, dry weather.</p>
<p><a href="https://doi.org/10.1101/2020.03.30.20044099">One preprint study of 30 Chinese provinces</a> showed that the number of COVID-19 cases went down by between 36% and 57% for every 1.8 degree Fahrenheit increase in temperature. When temperatures held steady in the low 40s F, the number of cases went down between 11% and 22% with each 1% increase in relative humidity (how much water is in the air).</p>
<p><a href="https://doi.org/10.1101/2020.03.27.20045658">A larger preprint study looking at 310 regions in 116 countries</a> found that 11% more cases were reported when the temperature went down 9 degrees, the relative humidity went down 10% and when the wind speed went up. </p>
<p>Laboratory research also suggest that the virus survives longer in cold conditions. One study showed that SARS-CoV-2 lasts for 14 days at 40 F in lab media but <a href="https://doi.org/10.1016/S2666-5247(20)30003-3">is gone after one day at 98.6 F</a>.</p>
<p>These and other studies suggest that warm, humid weather may slow the spread of this virus, <a href="https://doi.org/10.1101/2020.02.12.20022467">although not all</a> <a href="https://doi.org/10.1101/2020.03.29.20046706">commentators agree</a>.</p>
<p>New research on this topic appears almost daily, and scientists are watching to see what happens as summer comes to the Northern Hemisphere. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/328218/original/file-20200415-153334-18rts5r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/328218/original/file-20200415-153334-18rts5r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/328218/original/file-20200415-153334-18rts5r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=372&fit=crop&dpr=1 600w, https://images.theconversation.com/files/328218/original/file-20200415-153334-18rts5r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=372&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/328218/original/file-20200415-153334-18rts5r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=372&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/328218/original/file-20200415-153334-18rts5r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=468&fit=crop&dpr=1 754w, https://images.theconversation.com/files/328218/original/file-20200415-153334-18rts5r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=468&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/328218/original/file-20200415-153334-18rts5r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=468&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Summer in the Southern Hemisphere hasn’t stopped SARS-CoV-2 from spreading in Australia.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/residents-of-sydney-keep-to-the-rules-of-social-distancing-news-photo/1218492661">James D. Morgan/Getty Images News via Getty Images</a></span>
</figcaption>
</figure>
<h2>Which clues call for caution?</h2>
<p>COVID-19 is already spreading in many parts of the world where it’s hot, including Australia and South America, demonstrating that high temperatures are not enough to stop the disease.</p>
<p>The most important reason to be concerned about ongoing spread is the fact that this is a brand new virus for humans, so almost everyone is susceptible to being infected.</p>
<p>In fact, weather actually appears to <a href="https://doi.org/10.1101/2020.03.18.20036731">play a minor role</a> in the rate at which this virus spreads.</p>
<p><a href="https://www.nytimes.com/2020/04/13/opinion/coronavirus-what-we-know.html">Other influences on infection rates</a> include individual behaviors, cultural practices, geography, income and living conditions. <a href="https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/social-distancing.html">Public health practices</a> such as social distancing, the intensity of testing for infection, contact tracing, quarantine of people who are exposed and isolation of people who are actually infected also play a big role in how the coronavirus spreads.</p>
<p>The news from other viral diseases <a href="https://www.nap.edu/catalog/25771/rapid-expert-consultation-on-sars-cov-2-survival-in-relation-to-temperature-and-humidity-and-potential-for-seasonality-for-the-covid-19-pandemic-april-7-2020">is not encouraging either</a>. The two most serious coronavirus diseases that are closely related to COVID-19, the first SARS outbreak and MERS, <a href="https://www.nap.edu/catalog/25771/rapid-expert-consultation-on-sars-cov-2-survival-in-relation-to-temperature-and-humidity-and-potential-for-seasonality-for-the-covid-19-pandemic-april-7-2020">did not vary with the seasons after they emerged</a>. In fact, MERS is still <a href="https://www.cdc.gov/coronavirus/mers/index.html">found year-round in the Middle East</a>, where it is hot and dry. Pandemic influenza infections have emerged at different times of the year as well.</p>
<h2>What should we do?</h2>
<p>The <a href="https://doi.org/10.1056/NEJMp2003762">long-term solution to SARS-CoV-2</a> will be to develop a <a href="https://blogs.scientificamerican.com/observations/can-we-really-develop-a-safe-effective-coronavirus-vaccine/">safe and effective vaccine</a>. This work is proceeding at unprecedented speed, but it will still take anywhere from months to a few years and will require trials involving thousands of people and massive international leadership and collaboration.</p>
<p>Until there’s a vaccine, prevention will require avoiding exposure to people who can spread the virus. Communities need to test people to find out who is contagious and engage in serious contact tracing, quarantine and isolation. Scientists need to learn more about how to determine if someone is immune and how long immunity lasts, <a href="https://www.nytimes.com/2020/04/13/opinion/coronavirus-immunity.html">a big open question at the moment</a>. As individuals, each of us will need to follow expert scientific advice about good hygiene practices and distancing.</p>
<p><a href="http://doi.org/10.1126/science.abb5793">SARS-CoV-2 is likely to keep circulating</a> until the human population has widespread immunity, which hopefully will come not from an unchecked pandemic but from developing and deploying a safe and effective vaccine.</p>
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<p class="fine-print"><em><span>Ellen Wright Clayton reviewed the statement on seasonality by the NASEM Standing Committee.</span></em></p>Winter is flu season – could it be coronavirus season as well? The research is mixed, but other factors besides temperature and humidity have more to do with the spread of SARS-CoV-2.Ellen Wright Clayton, Professor of Pediatrics and Law and Health Policy, Vanderbilt UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1307732020-02-06T13:44:11Z2020-02-06T13:44:11ZRe-creating live-animal markets in the lab lets researchers see how pathogens like coronavirus jump species<figure><img src="https://images.theconversation.com/files/313831/original/file-20200205-149796-b6cnv8.jpg?ixlib=rb-1.1.0&rect=0%2C298%2C3521%2C2432&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Places where lots of animals come into contact can help pathogens move from species to species.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/chickens-in-cages-royalty-free-image/1001442114">Baloncici/iStock via Getty Images Plus</a></span></figcaption></figure><p>Nobody yet knows for sure the definitive origins of the <a href="https://theconversation.com/us/topics/wuhan-coronavirus-81516">newly recognized coronavirus</a> now known as 2019-nCoV that’s currently spreading across the globe as a human respiratory pathogen. Early reports indicate that the <a href="https://doi.org/10.3390/v12020135">source of the virus was the Huanan seafood market in Wuhan, China</a>, where an eclectic mix of animals including rodents, rabbits, bats and other wild animals and seafood are all on display for consumption and in contact with human shoppers.</p>
<p>Over the past two decades, the world has seen the <a href="https://doi.org/10.1038/nature06536">emergence of multiple pandemic threats</a>, including bird flu (H5N1 avian influenza), SARS, Ebola, Middle East Respiratory Syndrome, chikungunya, Zika and now the new coronavirus from Wuhan. The viruses that cause these diseases, and indeed <a href="https://www.cdc.gov/onehealth/basics/zoonotic-diseases.html">roughly two-thirds of all recent emergent viruses</a>, originate in animals before they jump to humans. </p>
<p>Each of these events underscores that multiple parts of an ecosystem are at play during an outbreak. For instance, <a href="https://doi.org/10.1098/rspb.2012.2753">wild bats and rodents harbor numerous viruses</a> that have the potential to infect humans and animals. When these wild animals are extracted from their natural habitat and come into close contact with people, very rare transmission events become much more likely.</p>
<p>These pathogen jumps are complex. They can occur via direct contact, consumption of bushmeat or transmission by insect vectors that carry the germs among a variety of species. And a range of environmental conditions – such as temperature, humidity, sunlight and even seasonal rain and soil conditions – can affect transmission. </p>
<p>Despite the complexity of the natural world, the research approach to understanding how potentially pandemic pathogens and their animal and human hosts interact has been relatively simple. Scientists typically focus on a single species at a time, studied under conditions of constant temperature, humidity and airflow. This strategy has clearly helped researchers understand infectious disease processes.</p>
<p>But <a href="https://scholar.google.com/citations?user=aDassZsAAAAJ&hl=en&oi=ao">as biologists</a>, <a href="https://www.research.colostate.edu/executive-committee/alan-rudolph/">we believe</a> that more explicitly acknowledging the complexity of the natural world will provide a more robust understanding of emerging infectious diseases. We’ve set up what we call “artificial ecosystems” in the lab to mimic the complicated conditions out in the real world. They’re helping us gather new insights into how viruses and other pathogens actually emerge to become global threats.</p>
<h2>Reconstructing live-animal markets and barnyards</h2>
<p>It’s undoubtedly rare for pathogens to jump directly from animals in nature into people. But within markets like the one in Wuhan, there are abundant opportunities for the type of interactions that promote pathogen transmission among species.</p>
<p>To mimic these scenarios, we’ve established artificial ecosystems in our lab. That way, we can study the transmission and spread of pathogens, such as influenza viruses, among diverse groups of birds and mammals all housed together and interacting freely.</p>
<p>Because the pathogens we’re studying are potentially deadly and contagious, we need to be very careful they can’t escape from the lab. We establish our ecosystems under strict biocontainment conditions: All exhaust air is filtered and personnel use respirators, wear facility apparel and shower before exiting.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/313396/original/file-20200203-41490-1ndvdft.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/313396/original/file-20200203-41490-1ndvdft.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/313396/original/file-20200203-41490-1ndvdft.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=369&fit=crop&dpr=1 600w, https://images.theconversation.com/files/313396/original/file-20200203-41490-1ndvdft.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=369&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/313396/original/file-20200203-41490-1ndvdft.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=369&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/313396/original/file-20200203-41490-1ndvdft.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=464&fit=crop&dpr=1 754w, https://images.theconversation.com/files/313396/original/file-20200203-41490-1ndvdft.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=464&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/313396/original/file-20200203-41490-1ndvdft.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=464&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 live-animal market in Indonesia (left) and an artificial market established to study interspecies transmission of avian influenza viruses as viewed through the window of a biosafety containment level 3 room.</span>
<span class="attribution"><span class="source">Richard Bowen</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>For our studies with bird flu, we created artificial barnyards that housed ducks, chickens, pigeons, blackbirds and rats all together. They freely interacted with one another, sharing access to common feed and water. As occurs in real barnyards, the rats were never seen outside of their enclosed nests during daylight hours, though video recordings showed them cavorting around the room, bathing in the water pool and harassing the ducks in the dark. We then <a href="https://doi.org/10.1371/journal.pone.0017643">introduced a small number of infected ducks</a> into the room and watched to see how infection spread. </p>
<p>In a different setup, we investigated transmission of another avian influenza virus among chickens, quail, pheasants and rabbits caged as in a live-animal market. Additionally, sparrows and pigeons were loose in the room and able to interact with the caged animals. As anticipated, <a href="https://doi.org/10.1016/j.virol.2016.04.032">birds housed beneath those inoculated with virus</a> were more likely be become infected, as waste runs downhill. Quail were the most susceptible to infection.</p>
<p>Key discoveries have emerged from our artificial ecosystem approach. For example, we were able to show that avian influenza viruses pass among diverse birds and mammals interacting freely with one another in an artificial barnyard or artificial live-animal market. We found that there’s <a href="https://doi.org/10.1371/journal.pone.0017643">massive accumulation of virus in shared water sources</a>.</p>
<p>More recently, we’ve created even more sophisticated artificial ecosystems that allow us to modulate temperature and humidity. We can even impose rain and wind onto an ecosystem, allowing us to evaluate environmental conditions that facilitate virus transmission.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/313833/original/file-20200205-149772-88nj5l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/313833/original/file-20200205-149772-88nj5l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/313833/original/file-20200205-149772-88nj5l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/313833/original/file-20200205-149772-88nj5l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/313833/original/file-20200205-149772-88nj5l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/313833/original/file-20200205-149772-88nj5l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/313833/original/file-20200205-149772-88nj5l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/313833/original/file-20200205-149772-88nj5l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Artificial ecosystems complement other research approaches that identify viruses and their properties.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/coronavirus-virus-royalty-free-image/1203566633">xia yuan/Moment via Getty Images</a></span>
</figcaption>
</figure>
<h2>Lessons from inside the artificial ecosystems</h2>
<p>Despite the known complexity of these sorts of interactions in the real world, it’s more typical to study emerging pathogens by focusing on infection in a single species at a time. This is partly due to the <a href="https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/animal-model-qualification-amqp-program">regulatory processes</a> by which diagnostics or vaccines are approved. They require definitive demonstration of safety and efficacy in individual animal models.</p>
<p>We hope this new approach could foster a more realistic understanding of how pathogens are transmitted among species, including jumping into human populations, and will facilitate development of new diagnostic tests, vaccines or therapeutics.</p>
<p>Our ecosystem method fits in with what’s called the <a href="https://www.cdc.gov/onehealth/index.html">One Health</a> approach to public health. One Health is based on the concept that human health is inextricably tied to the health of animals and the environment. Understanding infection in natural hosts in mixed ecosystems that mimic real-world scenarios of transmission is crucial for developing disease control methods.</p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p><img src="https://counter.theconversation.com/content/130773/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Richard Bowen receives funding from NIH, CDC, DTRA.</span></em></p><p class="fine-print"><em><span>Alan Rudolph is a member of the board of the Colorado Biosciences Association.</span></em></p>In the real world, new diseases emerge from complex environments. To learn more about how, scientists set up whole artificial ecosystems in the lab, instead of focusing on just one factor at a time.Richard Bowen, Professor of Biomedical Sciences, Colorado State UniversityAlan Rudolph, Professor of Biomedical Sciences and Vice President for Research, Colorado State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1234922019-09-18T17:17:46Z2019-09-18T17:17:46ZLive attenuated vaccines: should we rethink vaccination strategies?<figure><img src="https://images.theconversation.com/files/292265/original/file-20190912-190035-1s8y7nj.jpg?ixlib=rb-1.1.0&rect=50%2C0%2C5615%2C3564&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Industrial vaccine production has enabled mass vaccination campaigns that have reduced infectious diseases.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>In less than 50 years, the industrial production and use of <a href="https://en.wikipedia.org/wiki/Attenuated_vaccine">live attenuated vaccines</a>, which contain a living pathogen treated to be less virulent, has led to an <a href="https://jamanetwork.com/journals/jama/fullarticle/209448">exceptional reduction</a> in <a href="https://en.wikipedia.org/wiki/Disease#Morbidity">morbidity</a> and mortality due to infections in the world.</p>
<p>Vaccines of this type have been used successfully in many mass prevention campaigns: the tuberculosis vaccine (the famous Bacillus Calmette–Guérin or <a href="https://en.wikipedia.org/wiki/BCG_vaccine">BCG vaccine</a>, in 1921), Sabin’s <a href="https://en.wikipedia.org/wiki/Polio_vaccine#Attenuated">oral polio vaccine</a> (OPV, 1962) or the <a href="https://en.wikipedia.org/wiki/MMR_vaccine">combined measles, rubella and mumps vaccine</a> (MMR II, 1971) are all live attenuated vaccines.</p>
<p>However, we still have a long way to go before fully understanding the protective effects of this type of vaccine. Recent studies have revealed that they generate not only specific protection against the infectious agents against which they were developed, but also non-specific protection. This calls into question the fundamentals of the current vaccine paradigm, and also has important implications for vaccine policy in general.</p>
<h2>The basics</h2>
<p>Live attenuated vaccines contain infectious agents (viruses or bacteria) whose <a href="https://en.wikipedia.org/wiki/Virulence">virulence</a> has been weakened by a series of treatments. One method is to cultivate the virus for which a vaccine is to be developed for a long period of time on cells of another species. This makes it multiply less effectively in humans but retain its immunising effect. The OPV was designed by this procedure.</p>
<p>Even when a virus is attenuated, however, its use is not without risk, especially in individuals whose immune system isn’t yet fully developed or has been weakened (newborns, pregnant women, the elderly, etc.).</p>
<p>As knowledge of immunology progressed, second-generation vaccines, called <a href="https://en.wikipedia.org/wiki/Protein_subunit#Subunit_Vaccines">subunit vaccines</a>, were developed to address this problem. They were developed based on the paradigm of the specificity of acquired immunity to infections.</p>
<h2>Specificity of acquired immunity</h2>
<p>Throughout the 20th century it was widely accepted that after a natural infection or vaccination, our body develops specific <a href="https://en.wikipedia.org/wiki/Immunity_(medical)">immunity</a> to the <a href="https://en.wikipedia.org/wiki/Antigen">antigens</a> expressed by infectious agents. These antigens – which may be composed of proteins, sugars or lipids of the pathogen – are recognised by <a href="https://en.wikipedia.org/wiki/Lymphocyte">lymphocytes</a>, the body’s specialized immune cells.</p>
<p>Each lymphocyte has the exceptional ability to recognise one given antigen. Because the human immune system produces an immense number of lymphocytes (there are over 10<sup>8</sup> in humans), it can potentially recognise all possible antigens.</p>
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<p>After vaccination or a natural infection, the pathogen triggers the proliferation of lymphocytes that recognise its antigens and constitute a long-lasting <a href="https://en.wikipedia.org/wiki/Memory_T_cell">immune “memory”</a>. When the pathogen is encountered again, these cells respond and neutralise the pathogen before it damages the body.</p>
<p>This paradigm has served as the conceptual basis for the development of new vaccine strategies involving subunit vaccines, which contain only the pathogen’s “dominant” (i.e., most expressed and least variable) antigens and an <a href="https://en.wikipedia.org/wiki/Immunologic_adjuvant">adjuvant</a>, which stimulates the immune system. Unlike live attenuated vaccines, subunit vaccines do not contain living components and are therefore considered safe for at-risk individuals.</p>
<h2>Live vaccines also confer non-specific immunity</h2>
<p>However, the paradigm of specific acquired immunity against antigens of the infectious agent has been questioned more recently. Studies have shown that live attenuated vaccines can provide, in addition to immunity against the targeted infectious agent, immunity against unrelated pathogens. The vaccinated individual therefore benefits from <a href="https://www.cell.com/trends/immunology/fulltext/S1471-4906(13)00058-6">non-specific protective immunity</a>.</p>
<p>For example, individuals vaccinated against <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1439-0450.2004.00763.x?sid=nlm%3Apubmed">smallpox</a> are not only protected against smallpox but are also statistically less susceptible to infectious diseases such as measles, scarlet fever, whooping cough and syphilis compared to their unvaccinated counterparts. The same phenomenon has been reported for the <a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30546-2">BCG</a>, <a href="https://academic.oup.com/cid/article/61/10/1504/302404">OPV</a> and <a href="https://www.ebiomedicine.com/article/S2352-3964(16)30321-8/fulltext">measles vaccines</a>.</p>
<p>The persistence of a pathogen following natural infection, even at very low levels, has also been shown to possibly affect the ability of the immune system to respond to unrelated infectious agents. For example, <a href="https://www.nature.com/articles/nature05762">chronic infection with the herpes virus</a> may confer protection against <em>Listeria monocytogenes</em> and <em>Yersinia pestis</em> bacteria.</p>
<p>Alongside these results, <a href="https://www.nature.com/articles/nri3535">numerous studies</a> have shown that our <a href="https://en.wikipedia.org/wiki/Flora_(microbiology)">microbiota</a> (all bacteria, fungi and viruses that live in <a href="https://en.wikipedia.org/wiki/Symbiosis">symbiosis</a> with our body) also contributes to the control of infections. For example, it can <a href="https://www.nature.com/articles/ni.2608">compete with pathogens</a> to acquire nutrients or <a href="https://www.nature.com/articles/nri3535">induce an immune repertoire</a> that can cross-react to recognise and neutralise certain pathogens.</p>
<p>All these observations argue in favour of <a href="https://www.frontiersin.org/articles/10.3389/fmicb.2015.01525/full">looking at acquired immunity in a novel way</a>.</p>
<h2>Toward a new paradigm of acquired immunity?</h2>
<p>Contrary to accepted doctrine, it seems that a non-negligible part of acquired immunity is not specific to the antigens expressed by pathogens encountered previously. This acquired protection may depend on the immune history, chronic infections and microbiota composition. It is thought to be strongly influenced by the individual’s experience and way of life and thus vary widely.</p>
<p>From an evolutionary point of view, partially non-specific immune mechanisms seems very advantageous. Among other things, it could help fight against certain highly polymorphic and rapidly evolving pathogens. Furthermore, individual variability would <a href="https://www.frontiersin.org/articles/10.3389/fimmu.2014.00208/full">increase the resistance of a population to epidemics</a>.</p>
<p>This new paradigm could have important practical implications for vaccination strategies. Attenuated live vaccines are well known to induce non-specific protective effects. Should we then continue to use them even if their respective target diseases are now rare or have been eliminated? They could indeed have important beneficial effects for populations by protecting them against other infectious agents.</p>
<p>Before restricting the use of a live attenuated vaccine, it would therefore be wise to quantify its non-specific beneficial effects. Unfortunately, such a precautionary principle is difficult to apply in the <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(13)70108-7/fulltext">current climate of mistrust of vaccines</a>.</p>
<h2>When pathogens adapt</h2>
<p>Another implication of this discovery is that, for safety reasons, modern vaccination strategies focus on the development and use of adjuvanted subunit vaccines. However, this approach neglects the adaptive capacity of some pathogens whose antigenic composition is very complex and fluctuating.</p>
<p>This is the case of <a href="https://en.wikipedia.org/wiki/RNA_virus">small RNA viruses</a>, such as <a href="https://en.wikipedia.org/wiki/HIV">HIV</a>, which have a limited number of genes but produce an <a href="https://mmbr.asm.org/content/76/2/159.long">extraordinarily high number of variants</a> in the host in a very short period. Some <a href="https://academic.oup.com/jid/article/200/1/118/993703">bacteria can also evolve</a> during an infection. A pathogen capable of evolving rapidly is likely to escape the immune system if the selection pressure is put on its most specific and stable form. The development of <a href="https://royalsocietypublishing.org/doi/full/10.1098/rspb.2016.2562?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&">resistance to some subunit vaccines</a> has recently been documented.</p>
<p>Unlike subunit vaccines, live attenuated vaccines induce not only specific protection against a wide range of antigens, but also non-specific protection. They are therefore potentially able to cope better with infectious agents able to evolve rapidly. Consequently, the replacement of first-generation live attenuated vaccines with subunit vaccines should be based on the specific and non-specific benefits of each vaccine. The World Health Organization has <a href="https://www.who.int/wer/2014/wer8921.pdf">recognized the importance of the non-specific effects of vaccines</a> and recommended that research be continued in this new direction.</p><img src="https://counter.theconversation.com/content/123492/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Eric Muraille received funding from the Fonds de la Recherche Scientifique (FNRS-FRS), Belgium.</span></em></p>Recent discoveries on the effects of live attenuated vaccines challenge the current vaccine paradigm and question vaccination policies.Eric Muraille, Biologiste, Immunologiste. Maître de recherches au FNRS, Université Libre de Bruxelles (ULB)Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/906102018-02-26T11:16:11Z2018-02-26T11:16:11ZPlague bacteria may be hiding in common soil or water microbes, waiting to emerge<figure><img src="https://images.theconversation.com/files/207585/original/file-20180222-152375-1m2bpf6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Children at a school in Antananarivo, Madagascar, during a plague outbreak, Oct. 3, 2017. </span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Madagascar-Plague/53f6b085f3874bcbac5722f0a919c8c8/64/0">AP Photo/Alexander Joe, File</a></span></figcaption></figure><p>Plague is a highly contagious disease that has killed millions of people over the past 1,400 years. Outbreaks still sporadically occur in as many as <a href="http://www.who.int/mediacentre/factsheets/fs267/en">36 countries worldwide</a>. Perhaps one of the greatest remaining mysteries surrounding plague is how and where it survives between outbreaks.</p>
<p>Like many other pathogens, the bacteria that causes plague, <em>Yersinia pestis</em>, <a href="https://doi.org/10.1051/vetres:2008039">cannot survive for long periods of time</a> in the environment without protection. Despite this, plague outbreaks continually recur in many locations. This suggests that the bacteria are able to find refuge and survive for several years after an outbreak before <a href="https://doi.org/10.1093/biosci/biv179">reappearing, seemingly out of nowhere</a>, and starting another infection cycle. Understanding where they hide and how they survive and reappear is extremely important for preventing future outbreaks.</p>
<p>Our <a href="http://dx.doi.org/10.3201/eid2402.171065">2018 study</a> conducted at Colorado State University’s <a href="https://www.research.colostate.edu/idrc/">Infectious Disease Research Center</a> shows that amoebae – common soil and waterborne microorganisms that eat bacteria – could play a role in protecting this dangerous pathogen between outbreaks. This relationship may give plague bacteria a place to replicate and bide their time before conditions are right for another outbreak to occur.</p>
<h2>An ancient and mysterious killer</h2>
<p>Plague has caused <a href="http://dx.doi.org/10.1146/annurev.ento.50.071803.130337">three deadly worldwide pandemics</a>. <a href="http://content.time.com/time/specials/packages/article/0,28804,2027479_2027486_2027546,00.html">The Plague of Justinian</a> killed millions of people in the Byzantine Empire between the years 541 and 750. Next, the notorious <a href="http://content.time.com/time/specials/packages/article/0,28804,2027479_2027486_2027547,00.html">Black Death</a> ravaged much of Asia and Europe from 1330 to 1480, killing approximately 30 percent of all Europeans. Most recently, plague reappeared in <a href="http://content.time.com/time/specials/packages/article/0,28804,2027479_2027486_2027498,00.html">China</a> in 1855 and spread to ports worldwide over the following century, killing some 12 million people. Thousands of small outbreaks have occurred between and following these events. </p>
<p>Part of what makes understanding plague so difficult is its ability to infect <a href="https://pubs.usgs.gov/circ/1372">over 250 mammals and many species of insects</a> via multiple routes of transmission. For example, it can be transmitted through a bite from an infected flea or by inhaling bacteria coughed up by an infected animal.</p>
<p>Plague outbreaks also occur across very diverse environments. They range from prairie ecosystems in the western United States to highland forests in central Madagascar and temperate deserts in western China. The fact that few characteristics unify all of these regions may indicate that plague bacteria use <a href="https://doi.org/10.1371/journal.pntd.0004949">different survival mechanisms in each location</a>. However, one unifying factor is the presence of amoebae in the soil.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=350&fit=crop&dpr=1 600w, https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=350&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=350&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=440&fit=crop&dpr=1 754w, https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=440&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=440&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">World Health Organization 2016</span></span>
</figcaption>
</figure>
<h2>Abundant hosts</h2>
<p>Amoebae are single-celled microorganisms that live in almost all soils and water bodies across the globe. They feed on bacteria, but scientists have discovered that some bacteria are <a href="http://dx.doi.org/10.1128/CMR.17.2.413-433.2004">resistant to being digested by amoebae</a>. Interestingly, they include <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811209/">plague’s most closely related ancestors</a>, <em>Y. pseudotuberculosis</em> and <em>Y. enterocolitica</em>. </p>
<p>Living in the soil, alongside amoebae, required these bacteria to evolve ways to avoid being eaten. Given this evolutionary history, our research team hypothesized that when plague evolved from <em>Y. pseudotuberculosis</em> approximately 10,000 to 40,000 years ago, it may have retained the ability to survive inside amoebae.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">David Markman</span></span>
</figcaption>
</figure>
<h2>Natural disease incubators</h2>
<p>To test our hypothesis we collected soil samples from prairie dog burrows in northeastern Colorado because prairie dogs are known hosts of plague. This involved finding prairie dog colonies that were experiencing a plague outbreak and inserting a long flexible probe into burrows to collect samples from deep within, while avoiding potentially infectious fleas emerging from the burrow. After isolating amoebae from the soil in our lab, we identified five species to use in future experiments.</p>
<p>The next step was to determine how plague bacteria interacted with the various amoeba species we identified. In a special high-containment laboratory, designed to prevent dangerous pathogens from accidentally escaping, we combined amoebae and various strains of plague bacteria obtained from the U.S. Centers for Disease Control’s <a href="http://co-labs.org/labs?id=3">laboratory</a> in Fort Collins, Colorado. We used a genetically altered strain of plague that fluoresces neon green to determine if and when amoebae were ingesting plague bacteria by viewing them under a high- powered microscope.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=457&fit=crop&dpr=1 600w, https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=457&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=457&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=574&fit=crop&dpr=1 754w, https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=574&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=574&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Fluorescent plague bacteria inside amoebae. Scale bar indicates 30 microns.</span>
<span class="attribution"><span class="source">David Markman</span></span>
</figcaption>
</figure>
<p>Next we used a transmission electron microscope to obtain even more detailed images of the inside of infected amoebae. This revealed that the plague bacteria were alive and possibly replicating. To confirm this, we selectively cracked open the infected amoebae at different time points to compare the number of bacteria inside. Our results are the first to demonstrate that plague bacteria are able to survive and replicate inside amoebae.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=587&fit=crop&dpr=1 600w, https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=587&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=587&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=738&fit=crop&dpr=1 754w, https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=738&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=738&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Transmission electron microscope image of plague bacteria inside an amoeba. YP indicates <em>Yersinia pestis</em> (plague bacteria). The red lines indicate bacteria that appear to be replicating.</span>
<span class="attribution"><span class="source">David Markman</span></span>
</figcaption>
</figure>
<p>The next challenge is understanding how long plague bacteria can survive in amoebae. Part of an amoeba’s life cycle includes transforming into a cyst – a form in which it can <a href="http://dx.doi.org/10.1128/JCM.01903-08">lie dormant for up to 20 years</a> before it reanimates and resumes eating and multiplying. This enables it to survive during adverse environmental conditions, such as extreme temperatures or drought. If plague bacteria can survive inside dormant amoebae cysts for many years, this could explain how and where they persists between outbreaks.</p>
<h2>Amoebae as disease training grounds</h2>
<p>Amoebae are already recognized for their potential role in <a href="http://dx.doi.org/10.1128/CMR.17.2.413-433.2004">protecting</a>, <a href="http://dx.doi.org/10.1111/j.1469-0691.2009.03011.x">amplifying</a> or <a href="https://doi.org/10.1111/j.1574-6976.2009.00190.x">guiding</a> the evolution of over 225 other bacteria, viruses, and fungi. Famously, it is hypothesized that they played a role in the first known outbreak of <a href="https://doi.org/10.1016/j.clinmicnews.2010.11.001">Legionnaires’ disease</a> in 1976 by providing a protected space for <em>Legionella</em> bacteria to multiply. Amoebae can also act as transport vessels for pathogens, enabling the bacteria to enter and infect new hosts. </p>
<p>Some scientists hypothesize that amoebae can guide harmless bacteria to evolve into dangerous pathogens. The reasoning behind this is that amoebae are very similar to macrophages – the white blood cells in mammals that are responsible for finding and killing invading bacteria. If harmless soil bacteria evolve the ability to survive and multiply within amoebae, then they might also be able to do so in the white blood cells that comprise our immune system, thereby becoming new human pathogens.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=505&fit=crop&dpr=1 754w, https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=505&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=505&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Human plague cases and deaths in the United States, 2000-2016.</span>
<span class="attribution"><a class="source" href="https://www.cdc.gov/plague/maps/index.html">CDC</a></span>
</figcaption>
</figure>
<p>The idea of amoebae acting as “<a href="http://aem.asm.org/content/71/1/20">training grounds</a>” for the evolution of dangerous pathogens like plague conforms with what scientists already know about human plague infections. In human cases, plague is engulfed by white blood cells, but has <a href="http://dx.doi.org/10.3389/fcimb.2013.00106">evolved a way to avoid destruction</a> by escaping the portion of the cell responsible for digestion. Then it multiplies inside the white blood cell before exiting and disseminating throughout the human body. </p>
<p>This process is nearly identical to the process our research team observed in amoebae. Did this ability to avoid destruction and multiply within white blood cells – which is found in many human pathogens – arise from ancient soilborne bacteria learning to exploit amoebae? Perhaps practice really does make perfect.</p>
<p>Pathogen-harboring amoebae could be serious public health threats, since we currently have no way to efficiently monitor them in the environment or predict when they might release infectious agents. They may also pose a biosecurity threat that a hostile power could use to disperse existing pathogens or create new ones. We need more research on the complex interactions that allow pathogens to survive, disseminate and evolve so that we can learn to predict and prevent disease outbreaks and their consequences.</p><img src="https://counter.theconversation.com/content/90610/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Markman receives funding from the Department of Defense through the National Defense, Science, and Engineering Graduate Fellowship program.</span></em></p>Where do plague bacteria go between outbreaks? Research demonstrates that they can survive and replicate inside amoebae that are widely present in soil and water worldwide.David Markman, PhD Candidate, Colorado State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/796152017-06-27T12:17:05Z2017-06-27T12:17:05ZHow flu changes within the human body may hint at future global trends<figure><img src="https://images.theconversation.com/files/174656/original/file-20170620-24880-xnvg6g.png?ixlib=rb-1.1.0&rect=25%2C8%2C1822%2C1028&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">What can a single person's flu infection tell you about how the virus changes around the world?</span> <span class="attribution"><span class="source">Xue and Bloom</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Evolution is usually very slow, a process of change that takes thousands or millions of years to see.</p>
<p>But for influenza, evolution is fast – and deadly. Flu viruses <a href="https://www.cdc.gov/flu/about/viruses/change.htm">change rapidly</a> to escape the body’s defenses. Every few years, new variants of flu emerge and cause epidemics around the world.</p>
<p>Controlling the spread of flu means dealing with this ongoing evolution. Each year, <a href="http://www.who.int/influenza/en/">experts from the World Health Organization</a> (WHO) must make their best guess about how the virus will change in order to <a href="http://www.who.int/influenza/vaccines/virus/recommendations/en/">choose which flu strains</a> to include in the annual vaccine.</p>
<p>This work is difficult and uncertain, and mistakes have real consequences. Worldwide, <a href="http://www.who.int/mediacentre/factsheets/fs211/en/">flu infects several million people each year</a> and causes hundreds of thousands of deaths. In years when predictions miss the mark and the flu shot is very different from circulating strains, <a href="https://www.cdc.gov/flu/professionals/vaccination/effectivenessqa.htm">more people are vulnerable</a> to infection.</p>
<p>In the past several years, advances in genome sequencing have begun to shed light on the beginnings of viral evolution, deep within individual infections. We wondered whether, for flu, this information might give us an early glimpse of future global evolutionary trends.</p>
<p>What could a single person’s flu infection tell us about how the virus changes across the world? As it turns out, a surprising amount.</p>
<h2>Looking deep inside an infection</h2>
<p>Every step in flu’s evolution begins with a mistake. As viruses copy themselves within an infected person, they sometimes mutate, creating small changes to their genetic blueprint.</p>
<p><a href="https://doi.org/10.7554/eLife.03300">Most mutations are harmful to the virus</a> because they break the machinery it needs to function. But every so often, a mutant virus survives, and even thrives. Viruses play a constant game of cat-and-mouse with the human immune system. Sometimes, a mutant virus may be just different enough to escape the body’s notice.</p>
<p>A mutant virus with this kind of advantage can multiply quickly and come to dominate the infection. Eventually, it may even spread from person to person, and from there, start spreading around the world.</p>
<p>Recently, it’s become easier to track how viruses change within the human body. The same advances that have made it <a href="https://www.genome.gov/sequencingcosts/">cheap and easy</a> to sequence human genomes are changing how we study viruses. For the cost of sequencing a single human genome, we can sequence thousands of viruses from throughout an infection to track new mutations as they arise. </p>
<p>These mutations can show us how the virus reacts to challenging environments within the human body. For HIV, where infections often last years or even decades, <a href="https://doi.org/10.7554/eLife.11282">evolution can be substantial</a>, even within a single person. In particular, viruses often <a href="https://doi.org/10.7554/eLife.10670">evolve drug resistance</a> in response to antiviral treatment.</p>
<h2>Tracking flu evolution in four long infections</h2>
<p>We recently <a href="https://doi.org/10.7554/eLife.26875">tracked viral evolution in four cancer patients</a> who had flu infections lasting several months. Most flu infections last about a week, which limits the amount of change that can occur. But in patients with weak immune systems, infections can last a long time, with <a href="https://doi.org/10.1086/425004">severe effects</a>.</p>
<p>How did flu change within these long infections? By sequencing viruses from different times during the infection and comparing their genomes, we were able to identify new mutations and track their fates.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=389&fit=crop&dpr=1 600w, https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=389&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=389&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=489&fit=crop&dpr=1 754w, https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=489&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=489&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Each subplot represents one site in the virus where mutations can occur. Mutant viruses are shown in orange, and their frequencies rise and fall over time.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.7554/eLife.26875">Xue et al. eLife 2017;6:e26875</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Evolution acted in a matter of weeks. One clear example was resistance to Tamiflu. The patients we studied were taking the drug to control their infections. But, <a href="https://doi.org/10.1128/mBio.02464-14">as in prior studies</a>, viruses carrying drug-resistance mutations eventually emerged. These mutations might partly explain why the infections lasted so long.</p>
<p>Drug-resistance mutations weren’t the only evolutionary changes we saw. Half a dozen mutant viruses, all just slightly different from one another, would sometimes compete simultaneously in a single person.</p>
<p>These competing viruses made evolution a complicated affair. A mutation that started spreading one week would sometimes go extinct the next. Presumably, it was outcompeted by an even better mutation.</p>
<p>In some cases, we found the exact same mutations in viruses from different patients in our study, even though we could tell that the patients did not infect each other. We’d only very rarely expect such similarities to happen due to chance. The viruses may have hit on similar adaptations in response to evolutionary challenges. Some of these mutations may have helped the virus avoid the immune system, <a href="https://doi.org/10.1128/JVI.03248-15">echoing other studies</a>.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/SxW7SUGsZKA?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Author Katherine Xue explains her Ph.D. research on how flu evolves inside you.</span></figcaption>
</figure>
<h2>Forecasting the future</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&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 3-D structure of influenza virus as imaged by electron tomography. The spike proteins poke out from the virus’ coat.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Steven_H3N2_Flu_ET.jpg">Audray Harris, Bernard Heymann and Alasdair C. Steven, LSBR, NIAMS, NIH</a></span>
</figcaption>
</figure>
<p>What’s more, many mutations within these patients matched mutations that later spread around the world. In the spikes of flu’s outer coat, which help the virus enter host cells, the mutation N225D emerged in three of the four patients in our study. By 2015, about eight years after our patients were infected, most flu viruses around the world carried the exact same change.</p>
<p>For us, this was unexpected. Evolution is full of trade-offs, and some mutations that help flu adapt within people <a href="https://doi.org/10.1038/440435a">may slow its transmission</a> from person to person. We also didn’t know whether evolution in such unusually long flu infections would match patterns of change around the world. </p>
<p>But in our study, flu evolution in individual people showed striking similarities to evolution around the globe. We could see hints of some global evolutionary trends within just a few individuals.</p>
<p>As technologies continue to improve, it’s becoming easier to look deep inside flu infections, like we did. WHO labs <a href="http://www.who.int/influenza/gisrs_laboratory/en/">sequence flu strains</a> from thousands of people every year to monitor flu evolution. Researchers are sequencing more and more strains in ways that let us catch mutations as they first arise within individual people.</p>
<p>Each of these thousands of infections is like a separate evolutionary experiment. By comparing mutations that appear in different infections, we may get a sense of evolutionary possibilities and constraints.</p>
<p>Somewhere down the line, this kind of information may help forecast flu’s evolution. For now, at least, it’s uncovering some of the dynamic processes of evolution that take place within each of us.</p><img src="https://counter.theconversation.com/content/79615/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Katherine Xue is supported by the National Science Foundation and the Hertz Foundation. </span></em></p><p class="fine-print"><em><span>Jesse Bloom's research is supported by the NIH (NIAID and NIGMS), the Burroughs Wellcome Fund, and a Faculty Scholars grant from the HHMI and Simons Foundation.</span></em></p>New genetic technologies are letting us look at flu evolution right where it starts: within individual people, while they’re sick.Katherine Xue, Doctoral Student in Genome Sciences, University of WashingtonJesse Bloom, Associate Member, Fred Hutchinson Cancer Research Center and Affiliate Associate Professor of Genome Sciences and Microbiology, University of WashingtonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/777252017-06-21T04:13:57Z2017-06-21T04:13:57ZSpeaking with: Peter Doherty about infectious disease pandemics<p>Humans have had to deal with infectious diseases for centuries. Ancient Greeks and Egyptians suffered from smallpox, leprosy and tuberculosis. And when an outbreak occurs, it can be devastating. </p>
<p>Pandemics like the <a href="https://theconversation.com/explainer-what-is-the-plague-29574">Black Plague</a>, <a href="https://theconversation.com/world-war-ones-role-in-the-worst-ever-flu-pandemic-29849">Spanish Flu</a> and <a href="https://theconversation.com/au/topics/hiv-677">HIV</a> have killed millions of people around the world. </p>
<p>While improved sanitation and a better understanding of how infections spread has helped halt some pandemics, we are never truly safe. Recent outbreaks of Ebola in Western Africa and the Zika virus in the Americas show how vulnerable we are. </p>
<p>William Isdale speaks with Melbourne University Professor and Nobel prize winner Peter Doherty about how infectious diseases start and spread, and what can be done by governments, health organisations and individuals to minimise the threat of a pandemic. </p>
<hr>
<p><a href="https://itunes.apple.com/au/podcast/speaking-with.../id934267338">Subscribe</a> to The Conversation’s Speaking With podcasts on iTunes, or <a href="http://tunein.com/radio/Speaking-with---The-Conversation-Podcast-p671452/">follow</a> on Tunein Radio.</p>
<p><strong>Additional Audio</strong></p>
<ul>
<li><p><a href="https://www.youtube.com/watch?v=iKp7ZTAOdlY">Ebola outbreak: Deadliest on record - BBC News</a></p></li>
<li><p><a href="https://www.youtube.com/watch?v=ULw9HIEkR0M">Bird flu returns to Europe</a></p></li>
<li><p><a href="https://www.youtube.com/watch?v=JxdHjK1RME8">On this day 8th April 2003 SARS deadly virus</a></p></li>
<li><p><a href="https://www.youtube.com/watch?v=VbG9E2f7DWM">Hong Kong H7N9 Outbreak Thousands of Birds Culled Over H7N9 Discovery</a></p></li>
</ul>
<p><strong>Music</strong></p>
<ul>
<li><p><a href="http://freemusicarchive.org/music/Blue_Dot_Sessions/The_Contessa/Wisteria">Free Music Archive: Blue Dot Sessions - Wisteria</a></p></li>
<li><p><a href="http://freemusicarchive.org/music/johnny_ripper/lesprit_descalier/03_gael">Free Music Archive: Johnny_Ripper - Gaël</a></p></li>
</ul><img src="https://counter.theconversation.com/content/77725/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>William Isdale 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>William Isdale speaks with the University of Melbourne's Professor Peter Doherty about infectious disease pandemics.William Isdale, Research Assistant, Melbourne Law School, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/673262016-11-06T10:37:46Z2016-11-06T10:37:46ZUnderstanding Africa’s diverse gene pool can help fight lifestyle diseases<figure><img src="https://images.theconversation.com/files/144402/original/image-20161103-25339-1r777jp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">shutterstock</span> </figcaption></figure><p>Africa is home to about 16% of the world’s population. That’s 1.2 billion people. But the continent is disproportionately burdened by a double health challenge: infectious diseases and a <a href="https://theconversation.com/africa-needs-a-fresh-approach-to-lifestyle-diseases-research-66527">recent increase</a> in non-communicable diseases. </p>
<p>Non-communicable diseases such as hypertension, cardiovascular diseases and diabetes are on the march due to an ageing population, a transition to increased urbanisation, dietary changes, a more sedentary lifestyle and an increase in the prevalence of obesity.</p>
<p>Non-communicable diseases result in deaths everywhere in the world. But in Africa they are also a major reason for premature deaths, that is people dying between the ages of 40 and 70. In South Africa there is more than a 25% chance of dying prematurely from non-communicable diseases. On the rest of the continent it ranges between 15% and 24%. This compares to the average of less than 15% for the US and Europe.</p>
<p>The continent’s health systems are struggling to bring these diseases under control. One of the key strategies explored elsewhere is the use of genomics for a precision medicine approach. This opens the door to understanding which genetic drivers are responsible for an increased risk to a particular disease and how genetic variants in a population dictate responses to treatment. </p>
<p>Once scientists understand which treatments have the largest impact they can target therapy accordingly, this known as precision public health.</p>
<p>This approach could help to alleviate the health burden in Africa too but implementing it is more difficult than elsewhere. This is because the continent has added challenges. It has a genomic spectrum that is more diverse than other continents. In addition it has a wide range of different environments, cultures and levels of poverty. </p>
<p>That’s not to say it’s impossible. A precision public health approach would be possible if it was driven by research at a population level with large cohorts. This could help scientists understand how genes respond in the presence of certain environments, and interact with them (known as gene-environment interactions). Cracking this would open a new frontier in the drive against rising non-communicable diseases. </p>
<h2>Genomic research challenges</h2>
<p>There are four main problems with advancing genomic research in Africa. </p>
<p>Firstly, there is sparse data on genomics and gene-environment interactions in African populations. Scientists still do not know how populations with a particular genetic variant spectrum react to changes in the environment, such as an increase in poverty or lifestyle change during urbanisation, and what the likely impact of a particular genetic variants is. </p>
<p>In addition, scientists are prone to using interpretations based on research conducted elsewhere. There’s a particular bias, for example, to apply Eurocentric interpretations. In fact, people’s genetic background could have a profound effect on the way people react to their environment and to treatments. Applying a Eurocentric approach therefore doesn’t make sense. For example, sickle cell disease would not be very relevant in a European setting, but is very common in many regions of Africa and causes an enormous disease burden.</p>
<p>The second challenge is around the regulatory framework and how good practice guidelines are implemented. In many African countries privacy and genetic information is not protected or legislated. There is therefore the potential for harm.</p>
<p>Thirdly, there is a lack of resources to conduct primary research to inform precision public health approaches. These include money, people, infrastructure and electronic public health records. All are critical.</p>
<p>Implementing a precision public health approach is costly and it needs to be reviewed and updated continuously as understanding deepens and the environments that people live in change. </p>
<p>The fourth challenge is around informing people about the approach and what’s involved. Without this there is unlikely to be any buy in.</p>
<h2>First steps</h2>
<p>Genomic research has gained considerable momentum on the continent over the past decade. Two initiatives are boosting the capacity for genomic research on African populations. These are expected to benefit health initiatives elsewhere in the world too. </p>
<p>The International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) does two things: it collects data on populations. In addition it has launched a new initiative to collect biological specimens from populations. On the basis of this the project, known as <a href="http://www.thelancetnorway.com/pdfs/journals/langlo/PIIS2214-109X(15)00180-1.pdf">CHESS</a>, can provide data on diseases, pathogens and causes of death in specific populations.</p>
<p>The second initiative, the Human Heredity and Health in Africa <a href="http://www.h3africa.org">(H3Africa) Consortium</a>, studies infectious and non-communicable diseases from a genomics point of view. </p>
<p>These initiatives are important because they are studying populations that have been under-represented. </p>
<h2>Longterm goals</h2>
<p>There are several examples for successful use of precision medicine in the developed world (for example in some cancers). </p>
<p>Before Africa can boast its own examples it will first need to generate knowledge and data. This will take time which means that a precision public health approach to tackle disease won’t be yielding immediate results. </p>
<p>Many people on the continent do not get the treatment they need. In the short-term genomic research on drug responses could make a difference by providing governments with guidelines for what effective medication they should be giving their populations. </p>
<p>For longer term impact, researchers need to understand how genetic predisposition works in Africa. Only then will we begin to know how to treat the diseases more effectively.</p><img src="https://counter.theconversation.com/content/67326/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michèle Ramsay receives funding from the SA Department of Science, the NRF and SAMRC and the National Institute of Health (USA).</span></em></p>Cracking genetic responses to the changing environment in Africa would open a new frontier in the drive against rising non-communicable diseases on the continent.Michèle Ramsay, Director of the Sydney Brenner Institute for Molecular Bioscience, Professor in the Division of Human Genetics , University of the WitwatersrandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/557512016-03-28T10:06:00Z2016-03-28T10:06:00ZIs global warming causing marine diseases to spread?<figure><img src="https://images.theconversation.com/files/116050/original/image-20160322-32306-101jp1t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Coral affected by black band disease, Bahamas</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/jsjgeology/15511287394/in/photolist-pCFpky-q82zTg-cQXGpA-o5y8bi-sqa31K-fjzidX-bhvVn6-bhvPHx-8hjAJ8-qTZXPX-mLfKp-7Yo1zp-8hjARe-e1BaDZ-QL5BB-dYJ3Az-akmFZY-fj82yP-gsZK5-89y45V-akjsmq-pjfb8v-bQ2dq6-akiTog-akgEsZ-bQ1oeZ-akmFNG-akjsfh-bQ2dwR-bB7zhL-bQ2dHZ-8S58Cz-akiTbp-akwaLZ-bQ1oaP-po9r3q-2aByNj-MZyBW-bQ2dNr-akgEFV-akgECv-N6JVK-p6EMmk-bCYd5g-8U1cRa-8yh8Pj-rydaf5-rQHgrn-neu3pL-6tqSRY">James St. John/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Global climate change is altering the world’s oceans in many ways. Some impacts have received wide coverage, such as shrinking Arctic sea ice, rising sea levels and ocean warming. However, as the oceans warm, marine scientists are observing other forms of damage. </p>
<p>My research focuses on diseases in marine ecosystems. Humans, animals and plants are all susceptible to diseases caused by bacteria, viruses, parasites and fungi. Marine diseases, however, are an <a href="http://rstb.royalsocietypublishing.org/content/371/1689">emerging field</a>. </p>
<p>Infectious agents have the potential to alter ocean life in many ways. Some threaten our food security by attacking important commercial species, such as <a href="http://rstb.royalsocietypublishing.org/content/371/1689/20150203">salmon</a>. Others, such as <a href="http://rstb.royalsocietypublishing.org/content/371/1689/20150209">bacteria in oysters</a>, may directly harm human health. Still others damage valuable marine ecosystems – most notably <a href="http://rstb.royalsocietypublishing.org/content/371/1689/20150205">coral reefs</a>. </p>
<p>To anticipate these potential problems, we need a better understanding of marine diseases and how climate change affects their emergence and spread.</p>
<h2>Warming waters promote marine diseases</h2>
<p>Recent studies show that for some marine species <a href="http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0020120">diseases are spreading and increasing</a>. <a href="http://www.ncbi.nlm.nih.gov/pubmed/23808894">Climate change</a> may also promote the spread of infectious agents in oceans. Notably, warming water temperatures can expand these agents’ ranges and introduce diseases to areas where they were previously unknown. </p>
<p>Many diseases of marine species are secondary opportunist infections that take advantage when a host organism is stressed by other conditions, such as changes in pH, salinity or temperature. A bacterium that is dormant (and therefore noninfective) at a certain temperature may thrive at a slightly higher temperature. </p>
<p>One well-documented example is the emergence of epizootic shell disease (ESD) in American lobsters. This disease, thought to be caused by <a href="http://www.vims.edu/research/departments/eaah/programs/crustacean/research/lobster_shell_disease/Lobster-Project-Resources/Publications/Lobster-pdf-files/2005%20Proceedings%20of%20the%20Shell%20Disease%20Workshop.pdf">bacteria</a>, is characterized by lesions that penetrate inward from a lobster’s shell surface towards the inner flesh, making infected lobsters unmarketable. ESD can also kill lobsters by making it difficult for them to shed their shells in order to grow.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/116074/original/image-20160322-32285-3qhtns.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/116074/original/image-20160322-32285-3qhtns.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/116074/original/image-20160322-32285-3qhtns.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/116074/original/image-20160322-32285-3qhtns.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/116074/original/image-20160322-32285-3qhtns.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/116074/original/image-20160322-32285-3qhtns.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/116074/original/image-20160322-32285-3qhtns.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">An American lobster with epizootic shell disease (ESD).</span>
<span class="attribution"><span class="source">para_sight/flickr</span></span>
</figcaption>
</figure>
<p>In the 1990s, following almost a decade of above-normal summer temperatures, ESD affected so many lobsters that the Atlantic States Marine Fisheries Commission declared that the Southern New England fishery (Connecticut, Massachusetts, New York and Rhode Island) was in <a href="http://www.crustaceancrl.eu/publications/2012_DAO%20Lobster%20overview.pdf">collapse</a> and recommended <a href="http://www.asmfc.org/uploads/file/2009LobsterStockAssessmentReport.pdf">closing it</a>.
<a href="http://www.int-res.com/articles/meps2008/376/m376p185.pdf">Fishery models</a> that incorporated shell disease offered convincing evidence that ESD was a major factor in the decline of the stock. This episode underscores the importance of considering marine diseases in stock assessments and fishery management. </p>
<p>Now there are concerns that ESD will continue to <a href="http://www.huffingtonpost.com/2013/08/11/lobster-shell-disease_n_3739676.html">spread north</a> to Maine’s US$465.9 million lobster fishery. In <a href="http://www.asmfc.org/species/american-lobster">2015</a> the Gulf of Maine showed record high abundances of lobster, making it one of the most productive fisheries in the world. </p>
<p>However, sea surface temperatures in the Gulf of Maine have increased faster than <a href="http://onlinelibrary.wiley.com/wol1/doi/10.1002/2015JC011346/abstract">99 percent of the global ocean</a> over the past decade, warming three times faster than the global average. Since temperature is a <a href="http://rstb.royalsocietypublishing.org/content/371/1689/20150208">primary factor</a> in the spread of <a href="http://www.mass.gov/eea/docs/dfg/dmf/publications/glenn-et-al-2006.pdf">this disease</a>, observers fear that it could have devastating effects on Maine’s lobster fishery.</p>
<p>There is also a risk that ESD could spread from American lobsters to other fisheries. Seafood wholesalers have imported live American lobsters into Europe for decades, which can result in their <a href="http://www.reabic.net/journals/bir/2012/1/bir_2012_1_stebbing_etal.pdf">escape into the wild</a>. Last summer the United Kingdom’s Marine Management Organization <a href="https://www.gov.uk/government/news/non-native-crabs-and-lobsters-along-sussex-coast">warned</a> U.K. fishermen that because the European lobster shares similar habitats, food sources and diseases with the American lobster, ESD could spread between the species. </p>
<p>As a doctoral student at Swansea University, U.K., I collaborated with the New England Aquarium in Boston, Massachusetts to investigate this possibility. While we found that European lobsters were <a href="http://onlinelibrary.wiley.com/doi/10.1002/mbo3.174/full">more likely</a> to develop shell disease when reared in the presence of American lobsters, on the positive side, they don’t seem to get the same shell disease as American lobsters. </p>
<p>This means that European lobsters may be <a href="http://www.sciencedirect.com/science/article/pii/S0022201114000032">better equipped</a> to deal with outbreaks of ESD. But with sea surface temperatures in U.K. coastal waters rising since the 1980s by around 0.2-0.9 degrees Celsius <a href="http://www.mccip.org.uk/annual-report-card/">per decade</a>, it is important to monitor U.K. waters for this disease.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/116065/original/image-20160322-32306-1wtuueg.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/116065/original/image-20160322-32306-1wtuueg.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=376&fit=crop&dpr=1 600w, https://images.theconversation.com/files/116065/original/image-20160322-32306-1wtuueg.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=376&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/116065/original/image-20160322-32306-1wtuueg.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=376&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/116065/original/image-20160322-32306-1wtuueg.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=472&fit=crop&dpr=1 754w, https://images.theconversation.com/files/116065/original/image-20160322-32306-1wtuueg.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=472&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/116065/original/image-20160322-32306-1wtuueg.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=472&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">European lobsters with mild, none and severe shell disease.</span>
<span class="attribution"><span class="source">Andrew Rowley/Swansea University</span></span>
</figcaption>
</figure>
<h2>Tropical disease</h2>
<p>Now I am now studying the <em>Panuliris argus_1</em> virus (PaV1) in the Caribbean spiny lobster, where the picture is more dire. Discovered around 2000, this virus is present from the Florida Keys to Venezuela. It can infect up to <a href="http://www.pav1.org/">60 percent</a> of lobsters in some areas. Laboratory studies <a href="http://www.vims.edu/%7Ejeff/biology/2011%20Behringer%20et%20al%20PaV1%20review.pdf">indicate</a> that lobsters held in high-temperature seawater and exposed to PaV1 develop active and more intense infections much more quickly than those held at <a href="http://flseagrant.ifas.ufl.edu/newsletter/2011/05/protecting-floridas-spiny-lobster-fishery/">lower temperatures</a>.</p>
<p>Studies from 1982 to 2012 show that <a href="http://onlinelibrary.wiley.com/doi/10.1002/2015GL065002/full">waters in the Caribbean are warming</a>, with the most significant temperature increase occurring over the past 15 years – approximately the period when PaV1 appeared. If PaV1 continues to spread, it could have significant effects on the health of Caribbean reefs as a whole, as well as on the valuable Caribbean lobster fishery. </p>
<h2>Monitoring more diseases</h2>
<p>Many other species are also showing increasing effects from marine diseases. The frequency of coral diseases has increased significantly over the last 10 years, causing widespread mortality among reef-building coral, which are home to more than 25 percent of all marine fish species. </p>
<p>In the Pacific, more than 20 species of sea stars were devastated by a wasting disease that ranged from Mexico all the way up to Alaska in 2013 and 2014. <a href="http://rstb.royalsocietypublishing.org/content/371/1689/20150212">Research</a> suggests that 90 percent of some populations were wiped out, and some adult populations have been reduced to a quarter of pre-outbreak numbers.</p>
<p>Scientists believe the cause is a virus which becomes more active in warmer conditions. In both <a href="http://www.news.cornell.edu/stories/2016/02/epidemics-warming-oceans-rock-lobster-sea-star-populations">field surveys and laboratory experiments</a>, starfish were found to react faster to the disease in warmer water than in cooler temperatures. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/116071/original/image-20160322-32323-m8eaa8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/116071/original/image-20160322-32323-m8eaa8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/116071/original/image-20160322-32323-m8eaa8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/116071/original/image-20160322-32323-m8eaa8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/116071/original/image-20160322-32323-m8eaa8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/116071/original/image-20160322-32323-m8eaa8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/116071/original/image-20160322-32323-m8eaa8.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">Starfish on the shore at Umpqua Lighthouse State Park - Winchester Bay, Oregon.</span>
<span class="attribution"><span class="source">skipplitt/flickr</span></span>
</figcaption>
</figure>
<p>As the oceans continue to warm, it is crucial to understand how our actions are affecting marine life. Some species will not be able to withstand the increase in temperature. The most recent <a href="http://nca2014.globalchange.gov/report/regions/oceans#narrative-page-16751">U.S. National Climate Change Assessment</a> projects that outbreaks of marine diseases are likely to increase in frequency and severity as waters warm under climate change. Researchers are working around the world to determine whether and how species will survive disease events in our <a href="http://rstb.royalsocietypublishing.org/content/371/1689">increasingly altered oceans</a>.</p><img src="https://counter.theconversation.com/content/55751/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Charlotte Eve Davies has received funding from the Marine Management Organisations Fisheries Challenge Fund and currently receives funding from the National Autonomous University of Mexico </span></em></p>Infectious diseases are a normal part of ocean ecosystems, just as they are on land. But climate change is altering the oceans in ways that could make marine diseases spread farther and faster.Charlotte Eve Davies, Postdoctoral Researcher at the Institute of Marine Sciences and Limnology, Universidad Nacional Autónoma de México (UNAM)Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/408852015-05-22T16:40:00Z2015-05-22T16:40:00ZThe Ebola outbreak highlights shortcomings in disease surveillance and response – and where we can do better<figure><img src="https://images.theconversation.com/files/82440/original/image-20150520-11450-mgtxg3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Two women walk in front of a billboard, which says "Ebola must go. Stopping Ebola is Everybody's Business" in Monrovia, Liberia, January 15 2015.
</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/unmeer/16130327748/in/photolist-qzo9t7-oSscns-pg72Le-mZyb4f-mZyaVE-oHimQn-oCVKH6-op34XZ-oHgPqn-oDu5N9-pR4ewF-rdq1T3-q6bu3C-pQZWrR-purTDK-ocA6u9-oFukiA-oFipFC-sd4xMc-ozymNw-ovHMjj-oxFbgp-oxEVMp-ovCUoB-r5ndGw-qNKeMF-q6bRs1-r617Uh-pyBaz3-pBoeo6-oUu2Gt-piU225-qoCKXE-p58esM-qwihUe-piag7D-oXcJW5-mZyaYW-pxUe6Y-qTfRRp-qTLM78-pvTEb5-pzBsRW-oYBRVh-qN1o9r-oZ1QmQ-oMEPC8-oer9yg-pQTq2G-r3TCGn">UNMEER/Emmanuel Tobey</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>Right now the World Health Organization (WHO) is holding its annual <a href="http://www.who.int/mediacentre/events/2015/wha68/en/">World Health Assembly (WHA)</a>. At this time last year, Ebola Virus Disease (EVD) was rapidly spreading through West Africa, and the outbreak is rightly a major item on this year’s assembly agenda. Attention will be paid to the decisions made in response to the outbreak and what this tells us about how best to respond to the next one, including for advance preparation and early warning.</p>
<p>WHO Director-General Margaret Chan has already outlined her plans for a US$100 million <a href="http://www.who.int/dg/speeches/2015/68th-wha/en/">contingency fund</a> to support emergency response capacity in future outbreaks. This is welcome news. </p>
<p>The EVD outbreak in West Africa demonstrates how important the interaction between human and animal health is. It is a zoonotic infection, which means it originated in animals (bats, in this case) before spreading into humans. So, alongside better strategies to respond to outbreaks in human populations, we also need to have a stronger focus on disease surveillance in animals to identify infectious diseases before they pose a risk to human health. </p>
<p><a href="http://www.onehealthinitiative.com">One Health</a>, a discipline through which we examine how the interactions of humans, animals and the environment come together to allow an infectious threat to arise, develop and become a sustained outbreak, could have informed a better preemptive response to the virus.</p>
<h2>How did Ebola become a major outbreak?</h2>
<p>Ebola causes harmless, asymptomatic infection in bats. It took one encounter (or entry cause) for the virus to spill into humans. After that initial encounter, the disease was able to spread through communities in West Africa because of <a href="http://www.who.int/csr/disease/ebola/one-year-report/factors/en/">limited public health infrastructure</a>. The regional population is <a href="http://currents.plos.org/outbreaks/article/containing-the-ebola-outbreak-the-potential-and-challenge-of-mobile-network-data">highly connected</a>, which led to an exponential increases in cases. There was also a lack of diagnostics for other <a href="http://www.who.int/csr/disease/ebola/one-year-report/factors/en/">infectious diseases</a>. Unfortunately, the global community was slow to take action.</p>
<p>In the affected areas, there was a <a href="http://www.dw.de/ebola-fight-hindered-by-lack-of-awareness/a-17858448">lack of awareness</a> about EVD and its transmission, which allowed the spread of disease. This emphasizes the need for education and communication in the community that involve local leaders as well.</p>
<h2>Responding to the outbreak</h2>
<p>When it became clear that EVD had the potential to go from a severe regional outbreak to a <a href="http://www.sciencedirect.com/science/article/pii/S1201971214016178">pandemic</a>, interdisciplinary teams arrived to help the overwhelmed domestic healthcare system control the epidemic.</p>
<p><a href="http://www.msf.org/article/guinea-mobilisation-against-unprecedented-ebola-epidemic">Doctors Without Borders</a> (MSF) was the first to highlight that this was an unprecedented outbreak, as early as March 2014, following the first reporting of the outbreak. Local development partners such as King’s Sierra Leone Partnership, an international health link through King’s College London, took on leadership roles in <a href="http://kslp.org.uk/about-kings-sierra-leone-partnership/ebola/">outbreak control</a> in partnership with national government response. </p>
<p>But it was only in the latter part of the outbreak that epidemiologists and wildlife scientists began assisting in identifying the potential <a href="http://www.embo.org/news/research-news/research-news-2014/bats-possible-source-of-ebola-virus">source</a> of the outbreak – possibly bats roosting inside a hollow tree in Meliandou, Guinea. </p>
<p>One Health wasn’t applied in the early stages of the outbreak to assess the likelihood of multiple entry points into the human population, and no pre-outbreak surveillance had been undertaken in West Africa.</p>
<h2>The social context of the Ebola outbreak</h2>
<p>The cultural setting of West Africa has been much <a href="http://www.theguardian.com/global-development/poverty-matters/2014/aug/13/ebola-epidemic-poor-facilities-distrust-healthcare">discussed</a>, but <a href="http://www.ghjournal.org/ebola-emerging-the-limitations-of-culturalist-discourses-in-epidemiology/">hinders</a> the understanding of this outbreak by ignoring the political and economic global forces that left West Africa vulnerable. </p>
<p>Long-standing <a href="http://news.nationalgeographic.com/2015/01/150130-ebola-virus-outbreak-epidemic-sierra-leone-funerals/">cultural practices</a>, such as washing deceased relatives, further spread the disease. Early and targeted engagement with local community leaders about infection control should be a key component of future outbreak control. </p>
<p>However, simply focusing on human public health isn’t enough when it comes to a zoonotic infection. We also need to focus on how an outbreak like this can affect animal populations. The debate on the Ebola response has focused nearly entirely on human fatalities, ignoring the potentially far-reaching and largely undocumented <a href="http://www.voanews.com/content/ebola-great-apes-24sept14/2460717.html">impact on nonhuman primates</a>. </p>
<p>And discussions focused on banning <a href="http://www.washingtonpost.com/news/morning-mix/wp/2014/08/05/why-west-africans-keep-hunting-and-eating-bush-meat-despite-ebola-concerns/">bushmeat</a> ignore human economic concerns and the critically endangered nature of at-risk animal populations being <a href="http://www.thedailybeast.com/articles/2015/01/22/ebola-is-wiping-out-the-world-s-gorillas.html">further decimated by EVD in West Africa</a>. </p>
<h2>Prediction and surveillance</h2>
<p>Prediction, or at the very least understanding, of possible threats should be a key goal of future risk reduction strategies, to ensure we prevent another “<a href="http://archinte.jamanetwork.com/article.aspx?articleid=1916610">Black Swan</a>”: an unexpected major event that comes as a complete surprise, “<a href="http://en.m.wikipedia.org/wiki/Black_swan_theory">"rationalized after the fact with the benefit of hindsight</a>.” </p>
<p>For infectious diseases, prediction rests on strong disease surveillance in both human and animal populations. We could have predicted West Africa was susceptible to <a href="http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0030371">EVD</a>, but such surveillance doesn’t currently form any of the decision-making processes that are used globally. </p>
<p>The main international treaty underpinning health security, the <a href="http://www.who.int/topics/international_health_regulations/en/">International Health Regulations (2005)</a> (IHR 2005), requires the 195 member states of the WHO to have in place “core capacity requirements for surveillance and response to events.” </p>
<p>By the initial deadline of 2012, <a href="http://www.who.int/entity/ihr/qa-ihr-rc-11nov.pdf">only 42 countries</a> had met their core capacity requirements. By the end of June 2014, four months into the Ebola outbreak, only a further 21 met these requirements. Fewer than one-third of the WHO member states have declared their compliance with IHR 2005. Efforts to help poorer nations to achieve this have not been forthcoming. This means that the majority of member states still lack adequate human disease surveillance. </p>
<p>However, complying with IHR 2005 does not guarantee that countries are able to detect emerging zoonotic diseases. The checklist for monitoring progress toward IHR core capacities does not include animal or wildlife disease surveillance. </p>
<p>The WHA 2015 has focused on renewed calls to strengthen human disease surveillance. But as an international community, we need to consider early combined surveillance of both humans and animals. There should no longer be a complete division between ministries of health and wildlife agencies. </p>
<p>The goals of the WHO in curbing the spread of the infectious disease must align with those of the <a href="http://www.oie.int">World Organization for Animal Health</a> and <a href="http://www.fao.org">Food and Agriculture Organization of the United Nations</a> to ensure that infectious disease threats are targeted from their transmission from animals to humans through to managing their quarantine and public health control. </p>
<p>The $100 million contingency fund is a welcome step in the right direction. But now international aid needs to focus on developing public health systems that are robust, effective and cross-species. Disregard of animal well-being comes at our own cost.</p><img src="https://counter.theconversation.com/content/40885/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Arinjay Banerjee receives funding from Integrated training program in Infectious Diseases, Food safety and Public policy, University of Saskatchewan and Natural Sciences and Engineering Research Council of Canada.</span></em></p><p class="fine-print"><em><span>Colin Brown and Grant Hill-Cawthorne 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>Along with better strategies to respond to outbreaks in human populations, we need a stronger focus on surveillance in animals to identify infectious diseases before they pose a risk to human health.Arinjay Banerjee, PhD Student in Veterinary Microbiology, University of SaskatchewanColin Brown, Infectious Diseases Lead, King's Sierra Leone Partnership, King's College LondonGrant Hill-Cawthorne, Lecturer in Communicable Disease Epidemiology, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/349062015-01-07T11:11:21Z2015-01-07T11:11:21ZExplainer: what’s the difference between an outbreak and an epidemic?<p>More than <a href="http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.html">8,000 people</a> have died from Ebola in West Africa since February 2014 and it has spread beyond the three countries initially affected. So, it’s an epidemic, right? Or is it an outbreak? </p>
<p>What about H1N1? The 2009 pandemic infected people around the world. But, so did the SARS epidemic in 2003. What’s the difference between an epidemic and pandemic? What about diseases like malaria and Dengue? Dengue fever infects between <a href="http://www.who.int/mediacentre/factsheets/fs117/en/">50 and 100 million</a> people each year in countries all over the world. So that’s the same thing as a pandemic? Not quite. Maybe you’ve seen headlines about West Nile Virus, Chikungunya fever or Middle East Respiratory Syndrome. And what are emerging and reemerging diseases?</p>
<p>It’s time to brush up on the vocabulary that can help you understand just what infectious disease experts are trying to tell us. </p>
<h2>Outbreaks, epidemics and pandemics</h2>
<p>An <a href="http://www.who.int/topics/disease_outbreaks/en/">outbreak</a> is the sudden occurrence of a disease in a community, which has never experienced the disease before or when cases of that disease occur in numbers greater than expected in a defined area. The current <a href="https://www.mja.com.au/journal/2014/201/6/vulnerability-hysteria-and-fear-conquering-ebola-virus">Ebola scenario</a> in West Africa started as an outbreak, which initially affected three countries.</p>
<p>So what exactly is an epidemic? It is an occurrence of a group of illnesses of similar nature and derived from a common source, in excess of what would be normally expected in a community or region. A classic example of an epidemic would be Severe Acute Respiratory Syndrome (SARS). The epidemic killed about 774 people out of 8,098 that were infected. It started as an outbreak in Asia and then spread to <a href="http://www.cdc.gov/sars/about/fs-SARS.html">two dozen countries</a> and took the form of an epidemic. The same is true for Ebola, which is now being termed an <a href="http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/">epidemic</a>. </p>
<p>A pandemic on the other hand refers to a worldwide epidemic, which could have started off as outbreak, escalated to the level of an epidemic and eventually spread to a number of countries across continents. The 2009 flu pandemic is a good example. Between the period of April 2009 and August 2010, there were approximately 18,449 deaths in over <a href="http://www.who.int/csr/don/2010_08_06/en/">214 countries</a>. The flu virus (H1N1) probably originated in <a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0430a2.htm">Mexico</a> and within two months, sustained human-to-human transmission in several countries on different continents was reported, prompting the WHO to announce the highest alert level (<a href="http://www.who.int/csr/disease/swineflu/frequently_asked_questions/levels_pandemic_alert/en/">phase 6, pandemic</a>) on <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073629/">June 12, 2009</a>.</p>
<h2>Endemic diseases</h2>
<p>Some diseases can remain active in a given area for years and years. A disease is described as endemic when it is habitually present within a given geographic area. For example, Dengue, which is spread by mosquitoes, is endemic in more than <a href="http://www.who.int/mediacentre/factsheets/fs117/en/">100 countries</a>. So why isn’t dengue considered a pandemic yet? The point to consider here is that the dengue cases are not from a common source. Mosquitoes do not fly beyond a <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342775/">few hundred meters</a>, so the cases in each country are from a different source. Rotavirus-induced infant diarrhea is another example of an endemic disease, which is rampant in developing <a href="http://www.histopathology-india.net/rota.htm">countries</a>. </p>
<h2>Emerging and reemerging diseases</h2>
<p>We also come across words like “emerging” and “re-emerging.” An <a href="http://www.who.int/topics/emerging_diseases/en/">emerging disease</a> is one that has appeared in a population for the first time or one which may have existed before, but is rapidly increasing in incidence. Examples of emerging infectious diseases are <a href="http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003467">SARS, HIV and H1N1</a>. </p>
<p>Despite advances made in the field of medicine, global travel has added to the complexity of controlling infectious diseases. Both the 2003 SARS epidemic and the 2009 H1N1 pandemic were spread to a large extent due to air travel. </p>
<p>Chikungunya is another <a href="http://wwwnc.cdc.gov/eid/article/20/8/14-0333_article">viral disease</a> that is emerging in the Western Hemisphere. The first known cases in the Western Hemisphere occurred around October 2013 among residents of the French side of St. Martin in the Caribbean. WHO confirmed more than 31,000 probable and confirmed cases, which were not imported but indigenous in nature, from numerous other Caribbean islands as of <a href="http://wwwnc.cdc.gov/eid/article/20/8/14-0333_article">April 2014</a>. </p>
<p>Middle East Respiratory Syndrome (MERS) emerged around <a href="http://www.phac-aspc.gc.ca/phn-asp/2013/ncoronavirus-eng.php">April 2012</a> and has affected countries in the Middle East, Europe, Africa, Asia and North America, with 945 human cases, including 348 deaths as of <a href="http://www.phac-aspc.gc.ca/phn-asp/2013/ncoronavirus-eng.php">January 6, 2015</a>.</p>
<p><a href="http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003467">Reemerging diseases</a> are those that have historically infected humans, but continue to appear in new locations or reappear after apparent control or elimination. Most of the reemerging disease agents appeared long ago and have survived and persisted in the environment. A classic example is the West Nile virus (WNV). It is thought that WNV arrived in the United States via an infected traveler, bird or mosquito, which entered America through air travel from the <a href="http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003467">Middle East</a>. </p>
<h2>Why bother?</h2>
<p>Although people use terms like outbreak and epidemic interchangeably, it would only be fair to understand the definitive meaning behind each word. An outbreak can take the form of an epidemic and eventually a pandemic, but that does not entitle us to use these words incorrectly.</p><img src="https://counter.theconversation.com/content/34906/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Arinjay Banerjee 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>More than 8,000 people have died from Ebola in West Africa since February 2014 and it has spread beyond the three countries initially affected. So, it’s an epidemic, right? Or is it an outbreak? What about…Arinjay Banerjee, PhD Candidate in Veterinary Microbiology, University of SaskatchewanLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/358202014-12-29T22:33:37Z2014-12-29T22:33:37ZWhy Glasgow Ebola case is very unlikely to spread<figure><img src="https://images.theconversation.com/files/68084/original/image-20141229-8221-62ra0k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Glasgow's Gartnavel Hospital has past experience with Ebola-like diseases</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/limowreck666/278521430/in/photolist-qBuHC-dsPs7X-dsPA99-dsPoir-dsPpjz-dsPzV5-dsPxHC-dsPCFq-dsPDYW-caEWH3-dsPnyg-dsPp5P-dsPyvo-dsPBg9-dsPpBK-i92ZBR-7GbZXS-5si1fj-5XLrJu-4C3vzs-5si1f3-5si1f1-7wsDTP-5si1f5-7wsDGM-pWjh5m-pR4CDW-7RJcRJ-dsPACU-i94ZsE-i91R7j-i8xrHh-dsPDiJ-B8VEQ-B8VEN-i82ziX-4BigBd-nXMetR-iFZgbk-nmHXa8-nEZRZc-iRt1Wa-iFPDQw-iFMBw7-nVxjuU-b5fHvD-iGbEpe-b5hY5B-7M28E7-hqngVi">Dave Campbell</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>It has been confirmed that a healthcare worker who has returned from Sierra Leone has contracted the Ebola virus and is being treated in a Glasgow hospital. The female patient tested positive for the virus shortly after returning to Glasgow Airport via Casablanca and London Heathrow. The patient is currently in an isolation unit in the city’s Gartnavel hospital, but will shortly be transferred to a high-containment infectious disease facility in London for treatment. </p>
<p>The diagnosis represents the first case of Ebola to be identified in Scotland and the second case overall in the UK. Both cases in Britain have been health workers who have returned from working in Ebola-affected regions of west Africa and contracted the virus prior to returning to the UK. The first case was volunteer nurse William Pooley, who was discharged from hospital in September after making a full recovery and <a href="http://www.bbc.co.uk/news/health-29680400">subsequently returned to west Africa</a>.</p>
<h2>Risk of transmission</h2>
<p>As has been stated repeatedly by now, Ebola has a low risk of transmission, even to other passengers on the aircraft upon which the Glasgow healthcare worker was travelling. The virus is only passed from person to person by direct contact with infected body fluids, and is not known to be transmissible through the air. This makes it substantially less infectious than other viral infections such as influenza, which is airborne. </p>
<p>Glasgow and indeed Scotland as a whole has excellent infectious disease surveillance and containment facilities. This means the affected patient can be isolated, and will allow for appropriate transport and subsequent treatment in dedicated facilities in London.</p>
<p>It is also reassuring to note that Gartnavel hospital has the experience of dealing with a relevant case in the recent past. In 2012 a patient <a href="http://www.bbc.co.uk/news/uk-scotland-glasgow-west-19839103">was admitted</a> suffering from Crimean-Congo Haemorrhagic Fever, a viral infection that, like Ebola, can cause uncontrolled bleeding and has a significant mortality rate.</p>
<p>As Scotland’s first minister, Nicola Sturgeon, said shortly after the story broke, the risks of infection are “extremely low given the early stage of diagnosis. The patient was displaying no symptoms of the kind that would lead to onwards transmission that would put other people at risk”.</p>
<p>The first Scottish Ebola case will no doubt be at the forefront of the minds of the nation’s people over the coming days as we watch closely to see if it is only a single person affected. Scottish healthcare workers will undoubtedly be using increased vigilance to ensure that any further cases are identified and treated as quickly as possible. With over 7,500 deaths and 19,000 cases of Ebola in West Africa so far, the news is also a reminder that we should continue our focus on a global humanitarian aid effort to halt the spread of this devastating disease.</p><img src="https://counter.theconversation.com/content/35820/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter Barlow 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>It has been confirmed that a healthcare worker who has returned from Sierra Leone has contracted the Ebola virus and is being treated in a Glasgow hospital. The female patient tested positive for the virus…Peter Barlow, Reader in Immunology and Infection , Edinburgh Napier UniversityLicensed as Creative Commons – attribution, no derivatives.