tag:theconversation.com,2011:/uk/topics/pneumonic-plague-11669/articlesPneumonic plague – The Conversation2019-11-06T12:35:16Ztag:theconversation.com,2011:article/1203162019-11-06T12:35:16Z2019-11-06T12:35:16ZPlague was around for millennia before epidemics took hold – and the way people lived might be what protected them<figure><img src="https://images.theconversation.com/files/300676/original/file-20191107-10905-609qr4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">What happened to make plague able to cause devastating epidemics, as in this depiction from 1349?</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Doutielt3.jpg">Pierart dou Tielt/Wikimedia</a></span></figcaption></figure><p>One of civilization’s most prolific killers shadowed humans for thousands of years without their knowledge. </p>
<p>The bacteria <em>Yersinia pestis</em>, which causes the plague, is thought to be responsible for up to <a href="https://emedicine.medscape.com/article/967495-overview">200 million deaths</a> across human history — more than twice the casualties of <a href="https://www.nationalww2museum.org/students-teachers/student-resources/research-starters/research-starters-worldwide-deaths-world-war">World War II</a>.</p>
<p>The <em>Y. pestis</em> death toll comes from three widespread disease outbreaks, known as <a href="https://www.cdc.gov/csels/dsepd/ss1978/lesson1/section11.html">epidemics</a>: the sixth century Justinianic Plague that ravaged the Eastern Roman Empire; the 14th century Black Death that killed somewhere between 40% and 60% of the European population; and the ongoing Third Pandemic, which <a href="https://doi.org/10.1016/j.tim.2015.11.008">began in China</a> in the mid-19th century and currently afflicts <a href="https://www.who.int/news-room/fact-sheets/detail/plague">thousands worldwide</a>. </p>
<p>Scientists long assumed that the deadly disease began infecting humans just before the earliest epidemic, the Justinianic Plague. </p>
<p>But recent <a href="https://doi.org/10.1038/s41576-019-0119-1">paleogenetics research reveals</a> that plague has been with us for millennia longer: Ancient DNA (aDNA) from the bacteria was recovered from human skeletons <a href="https://doi.org/10.1016/j.cell.2018.11.005">as old as 4,900 years</a>. This means people were contracting and dying from plague at least 3,000 years before there’s any archaeological or historical evidence for an epidemic.</p>
<p>Why didn’t these earlier infections lead to devastating outbreaks like the Black Death? It seems the answer is part biological — genetic mutations to the bacteria itself — and part cultural — changes to human lifestyles that encouraged the spread of the disease.</p>
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<a href="https://images.theconversation.com/files/300192/original/file-20191105-88399-1h0syw4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/300192/original/file-20191105-88399-1h0syw4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/300192/original/file-20191105-88399-1h0syw4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=465&fit=crop&dpr=1 600w, https://images.theconversation.com/files/300192/original/file-20191105-88399-1h0syw4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=465&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/300192/original/file-20191105-88399-1h0syw4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=465&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/300192/original/file-20191105-88399-1h0syw4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=585&fit=crop&dpr=1 754w, https://images.theconversation.com/files/300192/original/file-20191105-88399-1h0syw4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=585&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/300192/original/file-20191105-88399-1h0syw4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=585&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">Electron micrograph scan of <em>Yersinia pestis</em> bacteria.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/niaid/7316086176/">NIAID/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<h2>New proof of ancient plague</h2>
<p><a href="https://doi.org/10.1146/annurev-micro-090817-062436">To identify cases</a> of ancient plague, researchers extract aDNA from a skeleton’s dental pulp chamber and search for genetic code from <em>Y. pestis</em> bacteria. If fossil teeth contain <em>Y. pestis</em> DNA, it’s safe to assume that person died from plague. </p>
<p><a href="https://doi.org/10.1016/j.cell.2015.10.009">Several studies</a> <a href="https://doi.org/10.1016/j.cub.2017.10.025">have found</a> <a href="https://doi.org/10.1038/s41467-018-04550-9">plague victims</a> who lived nearly 5,000 years ago — more than three millennia before the first known plague epidemic. </p>
<p>Pathogen aDNA analysis also revealed how <em>Y. pestis</em> bacteria have evolved over time. The oldest genomes recovered belong to a now-extinct lineage, which was missing certain mutations that make plague so contagious for humans. For example, later <em>Y. pestis</em> strains evolved a gene that allows the bacteria to <a href="https://doi.org/10.1016/j.chom.2014.04.003">efficiently infect fleas</a>, the main carriers of the disease in recent times. More ancient <em>Y. pestis</em> samples lack the gene.</p>
<p>So far, the <a href="https://doi.org/10.1038/s41467-018-04550-9">earliest plague genome</a> recovered with these mutations dates to around 1800 BC from the Samara Valley, Russia. The mutations were also identified in a skeleton from Iron Age Armenia that was dated to <a href="https://doi.org/10.1016/j.cell.2015.10.009">around 950 BC</a>. </p>
<h2>Missing evidence for epidemics</h2>
<p>It seems the more contagious form of plague has been infecting humans for nearly 4,000 years.</p>
<p>But there are no indications in the archaeological record of epidemics in the ancient societies in Russia and Armenia — despite the fact that some individuals died from the highly contagious plague strain. </p>
<p>It’s possible outbreaks occurred but the evidence simply hasn’t been found yet. For example, if future excavations were to uncover a series of mass graves that differed from the usual burial customs of those cultures, this could suggest societal disruption consistent with an epidemic.</p>
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<a href="https://images.theconversation.com/files/300170/original/file-20191104-88419-i0bxwh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/300170/original/file-20191104-88419-i0bxwh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/300170/original/file-20191104-88419-i0bxwh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=447&fit=crop&dpr=1 600w, https://images.theconversation.com/files/300170/original/file-20191104-88419-i0bxwh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=447&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/300170/original/file-20191104-88419-i0bxwh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=447&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/300170/original/file-20191104-88419-i0bxwh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=562&fit=crop&dpr=1 754w, https://images.theconversation.com/files/300170/original/file-20191104-88419-i0bxwh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=562&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/300170/original/file-20191104-88419-i0bxwh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=562&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 mass grave of plague victims from the early 18th C in Martigues, France.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Bubonic_plague_victims-mass_grave_in_Martigues,_France_1720-1721.jpg">S. Tzortzis</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>Or perhaps the bacterial strains, though genetically similar to the plagues of Justinian and the Black Death, lacked some other critical mutation, still unidentified.</p>
<p>Alternatively, there could be another explanation, related to the behavior of the people being infected. Did the ancient people of the Samara Valley and Armenia live in a way that protected them from plague — perhaps without even knowing it?</p>
<h2>Investigating plague protections</h2>
<p>We sought to answer this by investigating whether the populations of 1800s BC Samara Valley and Iron Age Armenia behaved differently from people in Justinian’s Empire in crucial ways.</p>
<p>First we established conditions that make a population more or less vulnerable to an outbreak. We identified criteria known to be associated with plague virulence, or how infectious the bacterium is.</p>
<p><a href="https://doi.org/10.1016/j.mbs.2013.04.013">Population density</a> is important; the number of people in contact with an infected individual affects the rate of disease spread.</p>
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<a href="https://images.theconversation.com/files/300168/original/file-20191104-88372-11ubnlw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/300168/original/file-20191104-88372-11ubnlw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/300168/original/file-20191104-88372-11ubnlw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=639&fit=crop&dpr=1 600w, https://images.theconversation.com/files/300168/original/file-20191104-88372-11ubnlw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=639&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/300168/original/file-20191104-88372-11ubnlw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=639&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/300168/original/file-20191104-88372-11ubnlw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=803&fit=crop&dpr=1 754w, https://images.theconversation.com/files/300168/original/file-20191104-88372-11ubnlw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=803&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/300168/original/file-20191104-88372-11ubnlw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=803&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Fleas spread bubonic plague, and tend to proliferate where rodents do.</span>
<span class="attribution"><a class="source" href="https://phil.cdc.gov/Details.aspx?pid=22256">CDC/Ken Gage</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p><a href="https://doi.org/10.1484/J.AT.1.103096">Permanent</a> <a href="https://doi.org/10.1371/journal.pntd.0000997">agricultural</a> settlements accumulate food storage and waste, which supports <a href="https://doi.org/10.1038/s41598-017-14880-1">co-habitating rodent species</a>. These rodents make ideal hosts for fleas that harbor plague bacteria. </p>
<p>As East Asia is the <a href="https://www.jstor.org/stable/10.13173/jasiahist.47.1.0001?seq=1#page_scan_tab_contents">likely geographic source of plague</a>, <a href="https://doi.org/10.1007/s10393-018-1347-0">regular trade</a> with the region is another factor.</p>
<p>And we examined <a href="https://www.simonandschuster.com/books/Black-Death/Robert-S-Gottfried/9780029123706">reliance on horses</a>, because some scholars suggest — though it’s not yet biologically tested — that the animals carry natural immunity to plague. Regular contact with horses could reduce a population’s susceptibility to the disease. </p>
<h2>Comparing cultures point by point</h2>
<p>We then compared three populations on these six criteria using archaeological and historical data.</p>
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<a href="https://images.theconversation.com/files/300316/original/file-20191105-88409-19jlf4w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/300316/original/file-20191105-88409-19jlf4w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/300316/original/file-20191105-88409-19jlf4w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=525&fit=crop&dpr=1 600w, https://images.theconversation.com/files/300316/original/file-20191105-88409-19jlf4w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=525&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/300316/original/file-20191105-88409-19jlf4w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=525&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/300316/original/file-20191105-88409-19jlf4w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=659&fit=crop&dpr=1 754w, https://images.theconversation.com/files/300316/original/file-20191105-88409-19jlf4w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=659&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/300316/original/file-20191105-88409-19jlf4w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=659&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">Byzantine Emperor Justinian presided over a booming metropolis in Constantinople.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/byzantine-emperor-justinian-archbishop-maximianus-constantinople-101972674">Hein Nouwens/Shutterstock.com</a></span>
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<p>For the Justinianic Plague, we focused on Constantinople, the capital of Justinian’s Empire and an epicenter of the outbreak. Constantinople’s culture created a perfect storm of conditions for an epidemic.</p>
<p>It was a congested urban center with a population of over 500,000 people, or <a href="https://lib.dr.iastate.edu/arch_pubs/76/">140 individuals per acre</a>. All of Constantinople’s staple foods, including grain, were <a href="https://www.penguinrandomhouse.com/books/294333/justinians-flea-by-william-rosen/9780143113812/">shipped from surrounding areas</a> and stored in large warehouses, creating ideal breeding grounds for rodents. Flourishing trade also introduced the rat species — <em>Rattus rattus</em> — <a href="https://www.penguinrandomhouse.com/books/294333/justinians-flea-by-william-rosen/">from India</a> that would later be identified as the main carrier of fleas harboring plague.</p>
<p>In contrast, lifestyles in Samara and Armenia may have kept the epidemic at bay. </p>
<p>These populations were significantly more mobile and less congested than the urban population of Constantinople. The Samara population shows <a href="https://doi.org/10.2307/j.ctvdjrq7b.7">little evidence for agriculture</a> and tended to occupy small settlements of extended families. These communities managed shared herds, and horse tools found in their characteristic <a href="https://doi.org/10.1038/nature16152">burial mounds</a> suggest the animals were highly valued. Remember, horses may have had some natural immunity to the disease. </p>
<p>Due to shifting local powers, <a href="https://oi.uchicago.edu/research/publications/oip/archaeology-and-geography-ancient-transcaucasian-societies-volume-1">Early Iron Age Armenia</a> appears to have been home to farmers as well as nomadic pastoralists. Generally, though, archaeologists presume the populations practiced <a href="https://www.amazon.com/History-Armenia-Review-Armen-Khachikyan/dp/9939522940">cattle farming</a>, which would have made people substantially more mobile and dispersed than inhabitants of Constantinople. </p>
<p>Less congestion would have made contaminating nearby villages more difficult. Lacking agriculture, Samara could not have supported human-dependent rodents, the way Constantinople did. Both populations potentially benefited from a high ratio of horses to people.</p>
<p>While Samara and Armenia saw occasional plague victims, the structure of their societies likely protected them from the devastation wrought in Constantinople. </p>
<h2>Cultural perspectives on disease</h2>
<p>While encouraging economic and technological gains, urban development and trade created ideal conditions for an epidemic in Constantinople. Vulnerability to plague was an unintended consequence of this society’s lifestyle. </p>
<p>Meanwhile, it seems earlier cultures unwittingly shielded themselves from the same threat.</p>
<p>The harsh reality is that it’s exceedingly difficult, if not impossible, to control a pathogen, its possible mutations or its next outbreak. But understanding how human behaviors affect the spread and virulence of a disease can inform preparations for the future. </p>
<p>As a society, we can take organized measures to reduce the spread of infection, whether by limiting over-congestion, controlling food waste, or restricting access to contaminated areas. Human behaviors are just as critical to our disease susceptibility as are the characteristics of the pathogen itself. </p>
<p><em>This article has been updated to include a lead image that depicts a plague outbreak.</em></p>
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<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>People caught and died from plague long before it caused major epidemics like the Black Death in the middle ages. Could what scientists call cultural resistance be what kept the disease under control?Sonja Eliason, MPhil Candidate in Bioscience Enterprise, University of CambridgeBridget Alex, Lecturer, California State University, Long BeachLicensed 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>
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<span class="caption"></span>
<span class="attribution"><span class="source">World Health Organization 2016</span></span>
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<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/573602016-04-08T04:21:39Z2016-04-08T04:21:39ZExplainer: understanding plague in the 21st century<figure><img src="https://images.theconversation.com/files/117864/original/image-20160407-16252-17u3bir.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Uncollected rubbish provides food and shelter for rodents which can spread plague if they pick up the bacteria. </span> <span class="attribution"><span class="source">Reuters/Siphiwe Sibeko</span></span></figcaption></figure><p><em>In medieval times, plague was known as the “black death” and resulted in millions of Europeans dying. Plague still persists in many areas, with the highest annual burden of disease in Africa.
The advent of antibiotics means that milder versions of plague can be treated. But according to the World Health Organization, pneumonic plague is still one of the most <a href="http://www.who.int/topics/plague/en/">deadly infectious diseases</a>. If someone contracts it, they can be dead within 24 hours.
Health and Medicine Editor Candice Bailey spoke to John Frean, Head of the Centre for Opportunistic, Tropical and Hospital Infections at the National Institute for Communicable Diseases in South Africa, about the deadly disease.</em></p>
<p><strong>Why is plague considered dangerous?</strong></p>
<p>Plague is a zoonotic disease caused by the bacterium <a href="http://web.uconn.edu/mcbstaff/graf/Student%20presentations/Y.%20pestis/Yersinia%20pestis.html"><em>Yersinia pestis</em></a>. It is found mainly in rodents and is spread by fleas from rodent to rodent. It can also spread from rodents to humans and other mammals, including dogs and cats. </p>
<p>Rodents are susceptible to plague bacteria and usually become ill or die after they are infected. An outbreak of plague in rodents is recognised by an unusual number of rodents dying. In these situations, rodent fleas are more likely to bite and infect other animals or humans, as their natural hosts have died.</p>
<p>People are at risk of getting plague if they:</p>
<ul>
<li><p>are bitten by rodent fleas that are infected with plague; </p></li>
<li><p>handle rodents that have died from plague, as infected blood or tissue could contaminate skin or be ingested; or</p></li>
<li><p>are in contact with humans or animals infected with plague, as infected pus or sputum droplets could carry the organism.</p></li>
</ul>
<p>If plague is not recognised and treated promptly, it can produce potentially serious or fatal disease. In its pneumonic form, plague may rapidly spread from person to person, which could constitute a public health hazard.</p>
<p><strong>How does plague manifest in humans?</strong></p>
<p>There are three forms of the plague that humans can get, all of which are potentially deadly: </p>
<p><strong>1. Bubonic plague:</strong> This happens after someone is bitten by a flea from an infected rat. There is a sudden onset of fever, chills, headache, weakness and the swelling of lymph nodes (glands) near the bite site. The patient may complain of abdominal pain, nausea, vomiting and diarrhoea. If treated, symptoms resolve in three to five days. If untreated, the disease can become more severe and can be fatal. Complications may include bubonic plague progressing to septicaemic or pneumonic forms, which could result in death.</p>
<p><strong>2. Septicaemic plague:</strong> This may arise as a complication of untreated bubonic plague but could be the first presentation of plague in a person. Aside from the fever, chills, extreme weakness, abdominal pain and shock experienced with bubonic plague, septicaemic plague can also result in bruises and bleeding in organs. Skin and other tissues – especially on the person’s extremities, such as the fingers, toes and nose – may turn black and die. </p>
<p><strong>3. Pneumonic plague:</strong> This can come about after bubonic or septicaemic plague is not treated, but it can also develop when someone inhales infectious droplets from a patient with pneumonic plague. People who have pneumonic plague have a fever, headache, weakness and a rapidly-developing pneumonia. They experience shortness of breath, chest pain, coughing and sometimes bloody or watery sputum.</p>
<p><strong>How common is plague?</strong></p>
<p>Plague has been reported in several African countries in the past decade. These include Madagascar, the Democratic Republic of Congo, Uganda, Mozambique, Malawi, Tanzania, Angola, Namibia and Zimbabwe.</p>
<p>There is currently a plague outbreak in Madagascar that was first reported in December 2013. It is affecting humans and there have been more than 170 cases of bubonic plague and a single case of pneumonic plague reported.</p>
<p>The last case of human plague in South Africa was reported in 1982 in Coega in the Eastern Cape province after being dormant for more than ten years. There were seven laboratory-proven infections and one death.</p>
<p><strong>How is plague diagnosed and treated?</strong> </p>
<p>Symptoms of plague may start showing two to eight days after the person has been exposed to the organism.</p>
<p>Plague may be diagnosed through culture of clinical specimens. For example, pus from the swollen lymph node, or blood or sputum could be cultured. This takes a few days. There are rapid tests that can identify the presence of a specific plague antigen in these samples, but they are generally only available in high plague transmission areas. They are relatively quick. </p>
<p>Plague can also be detected by finding <em>Yersinia pestis</em> antibodies in a blood specimen. Laboratory testing is done in specialised laboratories under strict biosafety conditions. Antibody testing takes a few hours.</p>
<p>Antibiotics are effective to treat all forms of plague and should be started as soon as possible to prevent complications. A vaccine is available for people at high risk, such as laboratory workers, but its effectiveness is not fully known.</p>
<p><strong>Can plague be prevented?</strong></p>
<p>Rodent and flea control, and monitoring of the wild rodent population, are the main measures to monitor the risk of outbreaks. Rodents are trapped and tested for plague antibodies. Their tissues might be cultured if plague infection is strongly suspected. </p>
<p>If there is a positive result, public health measures are implemented to prevent humans becoming infected. These include insecticide spraying in and around dwellings to kill fleas. Rodent surveillance and elimination measures such as trapping and poisoning also take place. Rubbish cleanup is an important element of control as it reduces the availability of food and shelter for rodents.</p>
<p>In South Africa, there are currently two national plague surveillance sites: the Coega area of the Nelson Mandela Bay Metropolitan Municipality in the Eastern Cape, and the City of Johannesburg Metropolitan Municipality in Gauteng province. </p>
<p>A rat that was plague antibody-positive was recently trapped in the greater Johannesburg area in an informal settlement. Although the origin of the rat’s infection is unknown, plague typically survives at low or undetectable levels in wild rodent populations. A wild rodent flea may have been the source. </p>
<p>Public health measures were rolled out by the city’s environmental health officers and to date no further plague-positive rodents have been found. </p>
<p>South Africa has been a plague risk area for many years but the number of animal and human outbreaks dwindled to zero in the past 34 years, so the risk of a major outbreak is low. Environmental health officers are, however, alert to the possibility of new plague outbreaks.</p><img src="https://counter.theconversation.com/content/57360/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Frean previously received funding from the SA Medical Research Council for molecular plague epidemiology research, but the project has terminated.</span></em></p>Plague, one of the deadliest diseases in the world, has been reported in several African countries in the past decade.John Frean, Principal Pathologist and Head of the Centre for Opportunistic, Tropical and Hospital Infections, National Institute for Communicable DiseasesLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/439892015-06-30T15:04:07Z2015-06-30T15:04:07ZHow Yersinia pestis evolved its ability to kill millions via pneumonic plague<figure><img src="https://images.theconversation.com/files/86771/original/image-20150629-9093-195roq6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">How did _Yersinia pestis_ bacteria start to target the lungs and become so deadly?</span> <span class="attribution"><a class="source" href="http://phil.cdc.gov/phil/details.asp">National Institute of Allergy and Infectious Diseases</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>The mere mention of the plague brings to mind the devastating <a href="http://www.bbc.co.uk/history/british/middle_ages/black_01.shtml">“Black Death”</a> pandemic that spread across Europe in the 1300s. Mass graves were piled high with the corpses of its millions of victims, while the disease rampaged across Europe for many decades. <em>Yersinia pestis</em>, the bacterium responsible for that plague pandemic, still persists in the environment among rodent and flea populations today, and human outbreaks regularly occur around the world. Most recently, an outbreak of plague was confirmed late last year in <a href="http://www.who.int/csr/don/21-november-2014-plague/en/">Madagascar</a> as well as within a prairie dog colony in <a href="http://www.denverpost.com/news/ci_28390231/prairie-dog-plague-shuts-down-part-bear-creek">Colorado</a> just this June.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/86772/original/image-20150629-9054-tap4qz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/86772/original/image-20150629-9054-tap4qz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/86772/original/image-20150629-9054-tap4qz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=449&fit=crop&dpr=1 600w, https://images.theconversation.com/files/86772/original/image-20150629-9054-tap4qz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=449&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/86772/original/image-20150629-9054-tap4qz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=449&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/86772/original/image-20150629-9054-tap4qz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=565&fit=crop&dpr=1 754w, https://images.theconversation.com/files/86772/original/image-20150629-9054-tap4qz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=565&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/86772/original/image-20150629-9054-tap4qz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=565&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The various routes of transfer between hosts of <em>Y. pestis</em> bacteria, which are the cause of bubonic plague in the United States.</span>
<span class="attribution"><a class="source" href="http://phil.cdc.gov/phil/details.asp">CDC</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p><em>Y. pestis</em> can cause three different forms of <a href="http://www.cdc.gov/plague/">plague</a>: bubonic, pneumonic and septicemic. Pneumonic plague infects the lungs, causing severe pneumonia. It’s the most serious form of the disease, with fatality rates approaching 100% if untreated, although recovery is possible with antibiotics if caught in time. While increased basic hygiene and developments in modern medicine have greatly reduced the severity of plague outbreaks, the symptoms of pneumonic plague are so similar to that of the flu that misdiagnosis or delays in treatment can have fatal consequences.</p>
<p><em>Y. pestis</em> is known to have evolved from the relatively mild gut pathogen <em>Yersinia pseudotuberculosis</em> sometime within the last <a href="http://dx.doi.org/10.1073/pnas.96.24.14043">5,000 to 10,000 years</a> – very recently on an evolutionary timescale. Sometime during this evolution <em>Y. pestis</em> developed new modes of transmission and disease manifestations, which allowed it to adapt to new animals and environments. Rather than simply causing an upset stomach, the bacterium became the killer we know from the Middle Ages.</p>
<p>One of <a href="http://www.feinberg.northwestern.edu/sites/microbiology-immunology/research/bacteriology.html#lathem">our lab’s</a> major research goals is to figure out how <em>Y. pestis</em> developed its ability to specifically cause pneumonic plague. Our research, <a href="http://dx.doi.org/10.1038/ncomms8487">recently published</a> in <em>Nature Communications</em>, offers new insights into how small genetic changes fundamentally affected the emergence of <em>Y. pestis</em> as a severe respiratory pathogen.</p>
<p>Prior to our study, the consensus in the field has been that pneumonic plague was a secondary byproduct of the invasive disease associated with bubonic plague. As pneumonic plague represents only 5%–10% of current plague infections in humans, the field has presumed that pneumonic plague occurs only once <em>Y. pestis</em> reaches the lungs following systemic infection, as might occur during bubonic plague. While this may be the case now, it may not necessarily represent what occurred in the past, especially as <em>Y. pestis</em> was just emerging from its ancestor <em>Y. pseudotuberculosis</em>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/86773/original/image-20150629-9105-1cap9jk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/86773/original/image-20150629-9105-1cap9jk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/86773/original/image-20150629-9105-1cap9jk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=456&fit=crop&dpr=1 600w, https://images.theconversation.com/files/86773/original/image-20150629-9105-1cap9jk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=456&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/86773/original/image-20150629-9105-1cap9jk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=456&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/86773/original/image-20150629-9105-1cap9jk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=573&fit=crop&dpr=1 754w, https://images.theconversation.com/files/86773/original/image-20150629-9105-1cap9jk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=573&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/86773/original/image-20150629-9105-1cap9jk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=573&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Plague infection in the lungs. Untreated, death results within a week.</span>
<span class="attribution"><a class="source" href="http://phil.cdc.gov/phil/details.asp">CDC/ Dr Jack Poland</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>First, target the lungs</h2>
<p>Therefore, we began our study by asking a relatively simple question: “When did <em>Y. pestis</em> develop the ability to infect the lung and cause pneumonic plague?” Remember, it was only recently, evolutionarily speaking, that it started targeting the lungs rather than the gut. <em>Y. pestis</em> is believed to have emerged as a species 5,000–10,000 years ago, but the first known pandemic of plague in humans didn’t occur until the <a href="https://en.wikipedia.org/wiki/Plague_of_Justinian">Justinian Plague</a> that afflicted the Byzantine empire about 1,500 years ago. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/86785/original/image-20150630-9093-o2ni7t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/86785/original/image-20150630-9093-o2ni7t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/86785/original/image-20150630-9093-o2ni7t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1024&fit=crop&dpr=1 600w, https://images.theconversation.com/files/86785/original/image-20150630-9093-o2ni7t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1024&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/86785/original/image-20150630-9093-o2ni7t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1024&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/86785/original/image-20150630-9093-o2ni7t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1287&fit=crop&dpr=1 754w, https://images.theconversation.com/files/86785/original/image-20150630-9093-o2ni7t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1287&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/86785/original/image-20150630-9093-o2ni7t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1287&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Excavation of skeletal remains of victims of the Black Death.</span>
<span class="attribution"><a class="source" href="http://www.pnas.org/content/108/38/E746.figures-only">Museum of London, Schuenemann et al PNAS vol. 108 no. 38</a></span>
</figcaption>
</figure>
<p>A recent discovery helped us investigate. Scientists successfully recovered DNA from <em>Y. pestis</em> from human skeletons in a <a href="http://dx.doi.org/10.1073/pnas.1105107108">Black Death mass grave</a> in London, England. The genetic material from the historic site is very similar to DNA isolated from recent modern plague outbreaks. The fact that the DNA from then is similar to the DNA from now indicates that today’s <em>Y. pestis</em> has maintained its devastating disease-causing capability.</p>
<p>To answer the question of how <em>Y. pestis</em> made that crucial leap to targeting the lung and therefore being able to cause pneumonic plague, we used strains of both ancestral and modern <em>Y. pestis</em> in our study. These <a href="http://dx.doi.org/10.1099/mic.0.021170-0">ancestral strains</a> of <em>Y. pestis</em>, isolated from voles in the Transcauscaian highland, carry characteristics of both modern, pandemic <em>Y. pestis</em> and the relatively benign predecessor species <em>Y. pseudotuberculosis</em> that still exists today.</p>
<p>Thus, these ancestral versions can be considered “intermediate” strains, trapped somewhere between the gut <em>Yersiniae</em> and modern, virulent <em>Y. pestis</em>. Indeed, these “intermediate” lineage ancestral strains are as closely related to <em>Y. pseudotuberculosis</em> as we can get while still technically representing species of <em>Y. pestis</em>. Because of their unique genetic characteristics, these ancestral strains can provide crucial insights into how this bacterium may have adapted to new host environments as it evolved from <em>Y. pseudotuberculosis</em>.</p>
<p>Surprisingly, we found that these ancestral strains were able to cause pneumonic plague in a manner indistinguishable from that of modern <em>Y. pestis</em> in mice – but only if the bacteria carried the gene for a single protein called Pla. Pla is unique to <em>Y. pestis</em> and was acquired very early in the evolution of the species.</p>
<p>Almost all ancestral strains of <em>Y. pestis</em> carry the gene for Pla, but there still exist a few that represent ancestral <em>Y. pestis</em> just prior to acquisition of Pla. We were able to test if these pre-Pla strains were able to cause pneumonic plague – and they did not. But as soon as <em>Y. pestis</em> picked up this gene, the bacteria could cause epidemics of pneumonic plague. No further changes were necessary, even though there are dozens of additional differences between these ancestral strains and modern <em>Y. pestis</em>. So <em>Y. pestis</em> was able to cause pneumonic plague much earlier in its history than had previously been thought – as soon as it acquired this single gene for Pla.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/86794/original/image-20150630-9093-23uh0v.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/86794/original/image-20150630-9093-23uh0v.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/86794/original/image-20150630-9093-23uh0v.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=477&fit=crop&dpr=1 600w, https://images.theconversation.com/files/86794/original/image-20150630-9093-23uh0v.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=477&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/86794/original/image-20150630-9093-23uh0v.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=477&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/86794/original/image-20150630-9093-23uh0v.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=600&fit=crop&dpr=1 754w, https://images.theconversation.com/files/86794/original/image-20150630-9093-23uh0v.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=600&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/86794/original/image-20150630-9093-23uh0v.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=600&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Scanning electron micrograph of Yersinia pestis.</span>
<span class="attribution"><a class="source" href="http://dx.doi.org/10.1371/journal.pone.0107002">Justin Eddy, Lindsay Gielda, et al</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Second, increase infectiousness</h2>
<p>But that’s not where the story ends. It turns out that all modern pandemic strains of <em>Y. pestis</em> contain a single amino acid mutation in Pla compared to ancestral <em>Y. pestis</em>. This change slightly alters the function of the Pla protein. The mutation, however, plays no role in the ability of any <em>Y. pestis</em> isolates to cause pneumonic plague – ancestral or modern.</p>
<p>Quite surprisingly, this modification allowed the <em>Y. pestis</em> to spread deeper into host tissue following a bite from an infected flea or rodent, leading to the development of bubonic plague with its trademark swollen lymph nodes. This suggests that <em>Y. pestis</em> was first a respiratory pathogen before it was able to efficiently cause invasive infections.</p>
<p>This discovery challenges our traditional notion of how plague evolved. Rather than pneumonic plague being a late addition to <em>Y. pestis</em>‘s arsenal as commonly believed, its ability to target the lung came before the change that makes it such an infectious pathogen. Our research suggests that the acquisition of Pla and its ability to cause pneumonic plague occurred well before 1,500–5,000 years ago. But the amino acid modification didn’t occur until just prior to 1,500 years ago, allowing <em>Y. pestis</em> to become much more deadly. All strains of <em>Y. pestis</em> from the time of the Justinian Plague and after have the deadly modification of Pla, while strains prior do not.</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/86795/original/image-20150630-9090-1h0t7ru.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/86795/original/image-20150630-9090-1h0t7ru.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/86795/original/image-20150630-9090-1h0t7ru.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=724&fit=crop&dpr=1 600w, https://images.theconversation.com/files/86795/original/image-20150630-9090-1h0t7ru.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=724&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/86795/original/image-20150630-9090-1h0t7ru.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=724&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/86795/original/image-20150630-9090-1h0t7ru.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=910&fit=crop&dpr=1 754w, https://images.theconversation.com/files/86795/original/image-20150630-9090-1h0t7ru.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=910&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/86795/original/image-20150630-9090-1h0t7ru.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=910&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Physician attire for protection from the Black Death.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Doktorschnabel_430px.jpg">Paul Fürst</a></span>
</figcaption>
</figure>
<p>Our results may explain how, through one small amino acid change, <em>Y. pestis</em> quickly transitioned from causing only localized outbreaks of disease to the pandemic spread of <em>Y. pestis</em> as seen during the Justinian Plague and the Black Death.</p>
<p>And it raises the ominous possibility that other respiratory pathogens could emerge from similar small genetic changes.</p><img src="https://counter.theconversation.com/content/43989/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Daniel Zimbler receives funding from National Institutes of Health, NIAID</span></em></p><p class="fine-print"><em><span>Wyndham Lathem receives funding from National Institutes of Health, NIAID.</span></em></p>It’s a deadly bacterium that can spread like wildfire. New research suggests Yersinia pestis first developed its ability to cause lung infection and then evolved to be highly infectious.Daniel Zimbler, Postdoctoral Fellow in Bacteriology, Northwestern UniversityWyndham Lathem, Assistant Professor of Microbiology-Immunology, Northwestern UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/295742014-07-26T04:31:10Z2014-07-26T04:31:10ZExplainer: what is the plague?<figure><img src="https://images.theconversation.com/files/54890/original/88n8dvmz-1406270092.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A model of the bubonic plague bacterium, which is known as Yersina pestis. </span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/23165290@N00/7283938624/in/photolist-c6E6bG-6bSYuo-c9uRwQ-9PKhjh-9CjrCJ-bAqdEa-dykRm6-af38yR-5LWHXq-bpcUw6-9x2PUK-BYZfD-6zodFM-6pJ9NG-bNNMGK-bzU9iA-au7MCb-9sTsY2-6cp2p8">Tim Evanson/Flcikr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p><a href="http://www.theguardian.com/world/2014/jul/22/chinese-city-yumen-sealed-bubonic-plague-death">Cases of plague</a> have been reported in the Chinese city of Yumen, where a man has died of the disease. </p>
<p>Control measures taken by the authorities include travel restrictions in and out of the city, and 151 people being <a href="http://www.thedenverchannel.com/news/u-s-world/the-black-death-returns-parts-of-chinese-city-sealed-over-bubonic-plague-outbreak07242014">reportedly put under quarantine</a>. </p>
<p>Plague has been responsible for hundreds of millions of deaths in three devastating pandemics, including the Black Death (1346–53). Despite being readily treatable with antibiotics, infections and deaths continue to occur throughout the world.</p>
<h2>What is plague?</h2>
<p>Plague is a serious disease caused by the bacteria <em>Yersina pestis</em>, which is <a href="http://www.nyu.edu/projects/mediamosaic/essays/epi/EpiDoc3.pdf">transmitted</a> from infected animals to humans by fleas. There are a number of different <a href="http://www.sciencedirect.com/science/article/pii/S0140673607605662">clinical forms</a> – bubonic plague and pneumonic plague being the most important.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/54892/original/8jx96j2n-1406270541.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/54892/original/8jx96j2n-1406270541.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=351&fit=crop&dpr=1 600w, https://images.theconversation.com/files/54892/original/8jx96j2n-1406270541.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=351&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/54892/original/8jx96j2n-1406270541.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=351&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/54892/original/8jx96j2n-1406270541.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=441&fit=crop&dpr=1 754w, https://images.theconversation.com/files/54892/original/8jx96j2n-1406270541.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=441&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/54892/original/8jx96j2n-1406270541.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=441&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Rats have historically been the biggest spreaders of the plague.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/jean-jacquesboujot/9874371664">Jean-Jacques Boujot/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Bubonic plague is named after the presence of buboes, or infected lymph nodes. These develop after an incubation period of two to six days after bites from infected fleas. </p>
<p>Bacteria then drain to local lymph nodes in the groin, under the arm or in the neck, which become swollen and painful. If untreated, infection spreads to the bloodstream and other internal organs.</p>
<p>Pneumonic plague occurs when the lungs are involved and has a much more rapid course. It leads to the build up of pus and fluid in the lungs, followed by bleeding. This severe form of plague, although less common than the bubonic form, is particularly significant because bacteria in the sputum can spread the disease to other people. </p>
<p>A number of common, inexpensive antibiotics, including <a href="http://www.ncbi.nlm.nih.gov/pubmed/16447105">gentamicin and doxycycline</a>, are effective against plague. But the effectiveness of treatment depends on antibiotics being given early, before severe infection is established. </p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/54868/original/xbdk8s9t-1406264353.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/54868/original/xbdk8s9t-1406264353.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=826&fit=crop&dpr=1 600w, https://images.theconversation.com/files/54868/original/xbdk8s9t-1406264353.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=826&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/54868/original/xbdk8s9t-1406264353.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=826&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/54868/original/xbdk8s9t-1406264353.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1038&fit=crop&dpr=1 754w, https://images.theconversation.com/files/54868/original/xbdk8s9t-1406264353.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1038&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/54868/original/xbdk8s9t-1406264353.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1038&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Plague doctors in the 17th century wore protective clothing with nosegays concealed in their masks and carried pomander canes.</span>
<span class="attribution"><a class="source" href="http://commons.wikimedia.org/wiki/File:Paul_F%C3%BCrst,_Der_Doctor_Schnabel_von_Rom_(Holl%C3%A4nder_version).png">Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Fortunately, antibiotic resistance does not appear to be common, despite a concerning <a href="http://www.nejm.org/doi/full/10.1056/NEJM199709043371004">1995 report</a> that described a multi-drug resistant strain. </p>
<p>Like many infectious diseases that cause outbreaks, plague is a zoonosis, meaning that it normally occurs in animals, with humans becoming involved as a spillover phenomenon. </p>
<p><em>Yersinia pestis</em> is found in a number of animals – most importantly rats, but also in a range of other mammals and is transmitted to humans via fleas. In modern times, most cases of plague occur in African countries, particularly <a href="http://wwwnc.cdc.gov/eid/article/4/1/98-0114_article">Madagascar</a>.</p>
<h2>Pandemics</h2>
<p>There have been three major pandemics of plague described throughout history, the most famous being the <a href="http://www.ncbi.nlm.nih.gov/pubmed/21876176">Black Death</a> in the 14th century. </p>
<p>Both the bubonic and pneumonic forms spread quickly through crowded, unsanitary cities and were carried by rats between urban centres. It’s been estimated that a third to a half of all people in affected regions died. </p>
<p>This event is thought to have left its mark on human genetic makeup, as an example of natural selection. <a href="http://www.ncbi.nlm.nih.gov/pubmed/9585595?dopt=Abstract">Genetic studies</a> have found a higher prevalence of changes (the CCR5-delta 32 mutation) in affected regions that are thought to provide relative protection against plague (although others argue that <a href="http://qjmed.oxfordjournals.org/content/99/8/497.full">different diseases</a> may be involved). </p>
<p>Ironically, this mutation is also thought to provide <a href="http://www.ncbi.nlm.nih.gov/pubmed/8751444?dopt=Abstract">protection</a> against a very different modern plague, HIV. </p>
<p>Pandemics of plague also had a profound influence on religion and culture. <a href="http://muse.jhu.edu/journals/chq/summary/v013/13.3.butler.html">Contrary to popular opinion</a>, the nursery rhyme “Ring a ring o’ roses” probably does not describe pneumonic plague.</p>
<p>But the extreme responses of humanity in horrific circumstances has provided a rich vein to mine for generations of writers, including <a href="http://www.gutenberg.org/ebooks/17221">Daniel Defoe</a> and <a href="http://www.gutenberg.org/ebooks/4125">Samuel Pepys</a>, <a href="http://www.theguardian.com/books/2003/apr/26/classics.albertcamus">Albert Camus</a> and more recently, <a href="http://geraldinebrooks.com/the-books/year-of-wonders/">Geraldine Brooks</a>.</p>
<p>DNA studies from plague victims have been able to confirm that plague was the cause of the <a href="http://www.ncbi.nlm.nih.gov/pubmed/21876176">Black Death</a> as well as the earlier <a href="http://www.ncbi.nlm.nih.gov/pubmed/24480148">Plague of Justinian</a>(AD 541-542). </p>
<p>Genetic studies of the causative organism <em>Y. pestis</em> suggest that there are no particular <a href="http://www.nature.com/nature/journal/v478/n7370/full/nature10549.html">bacterial factors</a> present in pandemic strains. This suggests that, given the right environmental conditions, all strains of bacteria are probably equally likely to cause outbreaks.</p>
<h2>Quarantine and plague</h2>
<p>The practice of quarantine, or restriction of the movement of people to prevent the spread of disease, was <a href="http://wwwnc.cdc.gov/eid/article/19/2/12-0312_article">first employed</a> in the 1370s in Dubrovnik, and later in 1423 in Venice during plague outbreaks. </p>
<p>The word itself comes the word <em>quaranta</em> (Italian for “40”) referring to the number of days for which travellers were isolated. </p>
<p>The isolation of whole villages or cities, as has been reported in the current Chinese outbreak, is termed <em>cordon sanitaire</em>. This practice also dates back to medieval times, most famously in the English <a href="http://www.bbc.co.uk/legacies/myths_legends/england/derby/article_3.shtml">village of Eyam</a> which voluntarily adopted this policy in 1665.</p>
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<img alt="" src="https://images.theconversation.com/files/54887/original/2xt5xjb8-1406269011.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/54887/original/2xt5xjb8-1406269011.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/54887/original/2xt5xjb8-1406269011.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/54887/original/2xt5xjb8-1406269011.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/54887/original/2xt5xjb8-1406269011.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/54887/original/2xt5xjb8-1406269011.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/54887/original/2xt5xjb8-1406269011.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">
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<span class="caption">Detail of the Saxon cross from a churchyard in Eyam, a village which famously voluntarily introduced quarantine in 1665.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/heandfi/2277005175">Fiona in Eden/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
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<p>Plague control programs involve educating the population on measures to improve sanitation to reduce exposure to rats and fleas; other rat and flea control measures, particularly on ships and around warehouses; and surveillance of infection in rats. </p>
<p>Case identification and treatment in humans also provides an effective method of control by preventing ongoing spread. </p>
<p>A number of vaccines have been developed, but are not widely available in most countries due to <a href="http://www.ncbi.nlm.nih.gov/pubmed/10796565">concerns about their lack of effectiveness</a>. </p>
<p>Plague is an example of how bacteria, animals, humans and the environment interact together to produce the conditions that enable infections to occur. Although we may never see outbreaks on the scale of the Black Death again, the ongoing reports of cases remind us that improvements in basic sanitation are still needed in many parts of the world</p><img src="https://counter.theconversation.com/content/29574/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Allen Cheng receives funding from the Australian National Health and Medical Research Council.</span></em></p>Cases of plague have been reported in the Chinese city of Yumen, where a man has died of the disease. Control measures taken by the authorities include travel restrictions in and out of the city, and 151…Allen Cheng, Associate Professor in Infectious Diseases Epidemiology, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.