tag:theconversation.com,2011:/ca/topics/viral-reproduction-number-18453/articlesViral reproduction number – The Conversation2021-05-05T12:10:12Ztag:theconversation.com,2011:article/1587332021-05-05T12:10:12Z2021-05-05T12:10:12ZWhere coronavirus variants emerge, surges follow – new research suggests how genomic surveillance can be an early warning system<figure><img src="https://images.theconversation.com/files/398759/original/file-20210504-19-16ael83.jpg?ixlib=rb-1.1.0&rect=80%2C0%2C4417%2C3090&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Sequencing the whole genome of patient virus samples lets scientists watch for new variants.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/an-employee-collects-a-sample-in-a-gemotest-lab-in-the-city-news-photo/1208719050">Sergei Malgavko/TASS via Getty Images</a></span></figcaption></figure><p>Genomic surveillance programs have let scientists track the coronavirus over the course of the pandemic. By testing patient samples, researchers are able to diagnose COVID-19. But they’re also able to use genetic changes in the virus to recreate its travel routes and identify the emergence of new viral variants.</p>
<p><a href="https://scholar.google.com/citations?user=jdNYfp4AAAAJ&hl=en&oi=sra">As</a> <a href="https://scholar.google.com/citations?user=_BegzMEAAAAJ&hl=en&oi=ao">microbiologists</a>, we examined how quickly the coronavirus genome has mutated during the pandemic and then <a href="https://doi.org/10.1038/s41598-021-86265-4">figured out how quickly these changes led to new cases</a> and rapid disease spread.</p>
<p>By connecting genetic change with the appearance of new clusters of disease, our research suggests how genome surveillance can provide a new early warning of what’s to come. Daily reports on how the virus is evolving could sound the alarm before case numbers explode.</p>
<h2>Mutations happen and can be tracked</h2>
<p>Starting around 2012, researchers began to develop genome sequencing as a way for public health experts <a href="https://doi.org/10.1128/genomeA.00594-17">to track infectious diseases</a>. Basically they are able to “read” an organism’s whole genetic code, the long list of A, C, G and T molecules that comprise the blueprints for the proteins that carry out the cell’s functions.</p>
<p>When pathogens infect a host, they reproduce themselves. Changes to the genetic code can happen at this point – like typos you might make copying down a page of text, substituting an A for a T in one spot, for instance. These changes are mutations. They provide new instructions to the next generation that can give them new capabilities – maybe they are better able to move between hosts, survive and initiate outbreaks or cause new symptoms.</p>
<p>Multiple versions of the same organism, but with variations in the genetic code, circulate during a disease outbreak. Depending on how successful they are at infecting new hosts and spreading, various versions can become more or less common.</p>
<p>Historically, public health labs tracked disease outbreaks by the name of the pathogen – SARS, salmonella, Ebola and so on. But as the speed and accuracy of genome sequencing increased, researchers realized that the same pathogen can be divided into many different subpopulations based on genetic variation.</p>
<p>These are the variants you hear about with regard to the coronavirus – the B.1.1.7 strain that first emerged in the U.K., the B.1.617 version that was identified in India, and the B.1.427 and B.1.429 variants that both originated in California. All are technically classified as the same SARS-CoV-2 virus, but they may have quite different features.</p>
<h2>Screening isn’t the same as sequencing</h2>
<p>When a person’s sample is tested for SARS-CoV-2, the lab uses <a href="https://my.clevelandclinic.org/health/diagnostics/21462-covid-19-and-pcr-testing">a technique called PCR</a> to identify whether certain coronavirus genes are present. This method is good for screening – diagnosing whether the person in fact has COVID-19 or not. It also provides important surveillance data about how many people have the coronavirus in a particular time and place.</p>
<p>But it doesn’t sequence the whole genome, which is made up of 30,000 nucleotides – those As, Gs, Cs and Ts. The PCR screening test just looks for one small stretch of the coronavirus’s genetic code – the gene related to the virus’s spike protein that helps it infect human cells. This technique won’t flag mutations happening in other parts of the genome because it’s not looking for them.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/398925/original/file-20210505-17-1yqzzhp.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="diagram of how scientists can use genetic sequence data from coronavirus" src="https://images.theconversation.com/files/398925/original/file-20210505-17-1yqzzhp.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/398925/original/file-20210505-17-1yqzzhp.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/398925/original/file-20210505-17-1yqzzhp.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/398925/original/file-20210505-17-1yqzzhp.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/398925/original/file-20210505-17-1yqzzhp.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/398925/original/file-20210505-17-1yqzzhp.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/398925/original/file-20210505-17-1yqzzhp.png?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">Sequencing the genetic material of the coronavirus can help researchers trace the travel routes of the virus, diagnose infected people and inform research into vaccines and therapeutics.</span>
<span class="attribution"><span class="source">Bart Weimer and Darwin Bandoy</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Other mutations are definitely occurring, though. Sequencing the entire genomes of coronavirus samples creates a massive list of variants. Our work tackles this ever-changing list to show that not only do mutations in the spike gene lead to new outbreak clusters – additional mutations in other genes increase outbreaks, too.</p>
<h2>Connecting variants and outbreaks</h2>
<p>To figure out the role of these mutations, we directly linked the variants present at a certain time and place with the coronavirus’s <a href="https://theconversation.com/r0-how-scientists-quantify-the-intensity-of-an-outbreak-like-coronavirus-and-predict-the-pandemics-spread-130777">reproductive number, known as R for short</a>. R is a way to quantify the intensity of an infectious disease outbreak. It stands for how many additional people an infected person will spread the germ to.</p>
<p>But R doesn’t tell you what version of the viral genome was passed along. By directly linking R and the variant present, we were able to pinpoint the specific mutation that was emerging and increasing viral spread. We found that as new variants became more common, COVID-19 diagnoses surged. </p>
<p>By merging genomics with classical epidemiology, we created a tool that factors in rising variants and R to warn how quickly cases will spread and which variants are more likely to trigger new outbreaks.</p>
<p>To test this approach, we linked the SARS-CoV-2 genotype to the daily R during the first three months of the pandemic using 150 genomes. Our method predicted the near future of outbreaks in four different countries that each had various levels of mandated social interventions.</p>
<p>This preliminary evidence relied on a small number of genome sequences, but it was all the data available from the early stages of the pandemic. As the pandemic continues, <a href="https://doi.org/10.1038/d41586-021-01069-w">labs are sequencing thousands of genomes</a> across the globe weekly. We replicated our initial estimates using 20,000 genomes from the U.K. and arrived at the same observation – new variants led to more transmission, variants are continuing to expand and will continue to increase in prevalence as the pandemic continues.</p>
<p>By incorporating genome sequencing data with information about transmissibility, we created a kind of early warning system, allowing us to forecast spreading events. In the real world, advance warning like this could inform public health decisions about social interventions. People can prepare for predicted outbreaks. A bonus is that our model also would show when highly contagious variants are declining – providing solid evidence to support loosening restrictions to allow a return to normalcy.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/398760/original/file-20210504-20-1xmyzu2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="People walk past a COVID restrictions sign on a city street" src="https://images.theconversation.com/files/398760/original/file-20210504-20-1xmyzu2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/398760/original/file-20210504-20-1xmyzu2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/398760/original/file-20210504-20-1xmyzu2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/398760/original/file-20210504-20-1xmyzu2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/398760/original/file-20210504-20-1xmyzu2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/398760/original/file-20210504-20-1xmyzu2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/398760/original/file-20210504-20-1xmyzu2.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>
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<span class="caption">Just as valuable as early warning, variant information could help officials know when it’s safer to lift restrictions.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/covid-19-marshals-walk-past-a-covid-19-road-sign-in-old-news-photo/1232427963">SOPA Images/LightRocket via Getty Images</a></span>
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<h2>Scanning the horizon for future threats</h2>
<p>We believe that public health is at the dawn of integrating genome sequencing with infectious disease tracking. We envision a reference library of pathogen genomes, representing the diversity of their many emerging variants. It could be a new tool for epidemiologists, a part of routine surveillance programs that can last beyond the current pandemic.</p>
<p>In the future, scientists hopefully won’t need to wait for an outbreak to grow. Our research suggests that by identifying a rise in variants early, public health officials can quickly respond – before the inevitable rise in new disease cases. We think this kind of early warning system can increase the public’s safety for any pathogen and reduce outbreaks for all types of organisms.</p>
<p>[<em>Over 100,000 readers rely on The Conversation’s newsletter to understand the world.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=100Ksignup">Sign up today</a>.]</p><img src="https://counter.theconversation.com/content/158733/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bart C. Weimer receives funding from multiple federal agencies and foundations to support his academic research. </span></em></p><p class="fine-print"><em><span>Darwin Bandoy receives funding from Philippine California Advanced Research Institute and University of the Philippines for his PhD studies . </span></em></p>By merging genomics with classical epidemiology, researchers are able to predict new disease outbreaks based on which viral variants are on the rise.Bart C. Weimer, Professor of Population Health & Reproduction, University of California, DavisDarwin Bandoy, Ph.D. Student in Integrative Pathobiology, University of California, DavisLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1458432020-09-10T20:08:28Z2020-09-10T20:08:28ZVital Signs: batch testing and contact tracing are the two keys to stop the lockdown yo-yo<figure><img src="https://images.theconversation.com/files/357366/original/file-20200910-20-6w2whm.jpg?ixlib=rb-1.1.0&rect=330%2C9%2C5686%2C2602&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption"></span> </figcaption></figure><p>Back in March and April I (<a href="https://theconversation.com/open-letter-from-265-australian-economists-dont-sacrifice-health-for-the-economy-136686">and many other economists</a>) argued for lockdowns to get COVID-19 infections under control and to give health systems time to put in place testing and tracing regimes to contain the virus in the longer term.</p>
<p>This was done pretty effectively everywhere in Australia except for Victoria. But if things go to plan, all states will be back on the same page by the end of October. </p>
<p>Or will they?</p>
<p>Concerns about Victoria’s contact-tracing regime remain, and although there is a lot of testing, how it is being done might not be as effective as possible.</p>
<p>More still needs to be done to avoid the “yo-yoing” Victorian premier Dan Andrews has warned about – in which relaxation of distancing rules leads to yet another outbreak big enough to require reimposing restrictions.</p>
<p>There is room for not just incremental improvement but dramatic improvement of testing and tracing.</p>
<h2>Keeping the reproduction rate below 1</h2>
<p>The key to avoiding the need for lockdown (unless and until a vaccine is widely deployed) is to keep what epidemiologist call the “effective” reproduction rate (R) below 1. </p>
<p>That is, on average each person infected with the virus must give it to less than one other person (R<1). </p>
<p>If R>1 infections will grow exponentially, overwhelming human contact-tracing systems and eventually the hospital system.</p>
<p>To keep the reproduction rate below 1 requires testing and contact tracing to be incredibly fast and effective.</p>
<h2>Effective contact tracing</h2>
<p>Victoria’s contact-tracing system is generally regarded as having <a href="https://theconversation.com/view-from-the-hill-morrison-signals-a-long-battle-as-the-experts-descend-into-the-weeds-of-victorias-modelling-145734">performed poorly</a> compared with systems such as in New South Wales. </p>
<p>The clunky system includes notifications of new infections <a href="https://www.theage.com.au/national/victoria/victoria-too-swamped-by-first-wave-to-consider-it-fix-for-contact-tracers-20200908-p55tnj.html">still being sent by fax</a>.</p>
<p>Only now is the state moving to adopt a more automated approach, using a data management system developed by <a href="https://www.theguardian.com/australia-news/2020/sep/08/salesforce-to-digitise-victorias-covid-contact-tracing-after-federal-criticism">IT giant Salesforce</a>. The Victorian government rejected the system earlier in the year, on the grounds the state was too swamped by the first wave to implement and bed down a new system.</p>
<p>My University of NSW colleague, epidemiologist Raina MacIntyre, <a href="https://www.smh.com.au/national/critics-of-victoria-s-contact-tracing-system-misunderstand-some-key-facts-20200908-p55tju.html">has observed</a> that Victoria’s health system was less prepared than NSW because of 20 years of governments “stripping the health system bare”, and that:</p>
<blockquote>
<p>No health workforce in the world, no matter how organised, well-resourced and efficient, can do manual contact tracing successfully when an epidemic becomes too large.</p>
</blockquote>
<p>We could go down the more aggressive digital contact-tracing path akin to South Korea. But as the <a href="https://www.ft.com/content/f00483e1-d5f9-4ef4-8dac-01b89cf50ec9">Financial Times has noted</a>, the Korean systems:</p>
<blockquote>
<p>include an extensive trawl of data from other sources, such as security cameras and credit card transactions, as well as smartphone apps that use wireless signals to detect who might have encountered an infected individual.</p>
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<p>Given the relatively low voluntary uptake of the Australian government’s COVIDSafe smartphone tracing app, getting enough people to use it to make it effective will also require strong incentives – or compulsion. </p>
<p>Now, I’m strongly for such incentives (as well as smarter testing). But given the amount of bedwetting about the existing COVIDSafe app from the libertarian right and some elements of the soft left (who are paranoid about every smart light bulb spying on us), this is unlikely to happen.</p>
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<strong>
Read more:
<a href="https://theconversation.com/vital-signs-modelling-tells-us-the-coronavirus-app-will-need-a-big-take-up-economics-tells-us-how-to-get-it-136944">Vital Signs: Modelling tells us the coronavirus app will need a big take-up, economics tells us how to get it</a>
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<h2>Batch testing</h2>
<p>The other crucial tool to keep R below 1 is efficient and large-scale testing.</p>
<p>Australia did well early in the pandemic ramping up testing capacity. Test results have been typically returned within <a href="https://www.abc.net.au/news/2020-08-11/how-long-should-it-take-to-get-a-coronavirus-covid19-test-result/12545150">a few days</a>, though there have also been reports of results taking <a href="https://theconversation.com/got-a-covid-19-test-in-victoria-and-still-havent-got-your-results-heres-what-may-be-happening-and-what-to-do-142821">more than five days</a>.</p>
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<p><iframe id="tc-infographic-496" class="tc-infographic" height="400px" src="https://cdn.theconversation.com/infographics/496/0598668018a5666e15da133b092ce9a6dc3b6534/site/index.html" width="100%" style="border: none" frameborder="0"></iframe></p>
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<p>What we have not done is embrace the benefits of targeted batch testing. </p>
<p>Batch testing is a way to cost-effectively test large numbers of people <a href="https://theconversation.com/vital-signs-were-testing-50000-australians-a-day-for-covid-19-should-it-be-65-million-142255">by pooling together</a> samples – say by postcode. </p>
<p>If the pooled sample comes back negative, then everyone who contributed to the batch is cleared. If it is positive, more targeted testing is done, using smaller batches (by suburb, then residential block, then by household). </p>
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Read more:
<a href="https://theconversation.com/vital-signs-were-testing-50-000-australians-a-day-for-covid-19-should-it-be-6-5-million-142255">Vital Signs: We're testing 50,000 Australians a day for COVID-19. Should it be 6.5 million?</a>
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<p>As <a href="https://theconversation.com/vital-signs-were-testing-50-000-australians-a-day-for-covid-19-should-it-be-6-5-million-142255">I’ve noted before</a>, the optimal batch size depends on the base rate of the virus in the community. But this general idea has been around since World War II and is well understood. It is a way to stretch resources to test more of the population more often.</p>
<p>For Australia at this point of the pandemic, this kind of testing would enable rapid detection and isolation of any new infections, allowing social and economic activity to get back to a new normal. </p>
<h2>The strategy going forward</h2>
<p>Once the Victorian outbreak is under control, we need to reopen Australia’s internal borders. Then we can start thinking about easing external border restrictions with places such as New Zealand.</p>
<p>All of this will require keeping the reproduction rate below 1, which means catching any new infections fast. Really fast.</p>
<p>Yo-yoing lockdowns are costly and to be avoided if at all possible.</p>
<p>Automated contact tracing could help a lot, as could smart and aggressive batch testing. We should be doing both until a vaccine is deployed.</p>
<p>Some commentators talk about “living with this virus” which is basically code for letting it rip. Instead, what we need to do is engage in “relentless suppression” to keep the reproduction rate low and our economy open.</p><img src="https://counter.theconversation.com/content/145843/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Richard Holden 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>Yo-yoing lockdowns are costly and to be avoided if at all possible. Here is what we can do to dramatically improve testing and tracing.Richard Holden, Professor of Economics, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1307772020-02-05T12:55:16Z2020-02-05T12:55:16ZR0: How scientists quantify the intensity of an outbreak like coronavirus and predict the pandemic’s spread<figure><img src="https://images.theconversation.com/files/313588/original/file-20200204-41516-vr3j0h.jpg?ixlib=rb-1.1.0&rect=622%2C142%2C7441%2C5341&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">To how many others will one infected person spread the infection?</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/large-group-of-people-royalty-free-image/937887974">Bim/E+ via Getty Images</a></span></figcaption></figure><p><em>Leer en <a href="https://theconversation.com/que-es-el-r0-el-numero-que-siguen-los-cientificos-para-ver-la-intensidad-del-coronavirus-137744">español</a></em></p>
<p>If you saw the 2011 movie “<a href="https://www.imdb.com/title/tt1598778/">Contagion</a>,” about a worldwide pandemic of a new virus, then you’ve heard the term “R0.” </p>
<p>Pronounced “R naught,” this isn’t just jargon made up in Hollywood. It represents an important concept in epidemiology and is a crucial part of public health planning during an outbreak, like the current coronavirus pandemic that’s spread globally since it was first identified in China.</p>
<p>Scientists use R0 – <a href="https://doi.org/10.3201/eid2501.171901">the reproduction number</a> – to describe the intensity of an infectious disease outbreak. R0 estimates have been an important part of characterizing pandemics or large publicized outbreaks, including the <a href="https://www.jstor.org/stable/20486145">2003 SARS pandemic</a>, the <a href="https://doi.org/10.1186/1471-2334-14-480">2009 H1N1 influenza pandemic</a> and the <a href="https://doi.org/10.1371/currents.outbreaks.91afb5e0f279e7f29e7056095255b288">2014 Ebola epidemic in West Africa</a>. It’s something epidemiologists are racing to nail down about SARS-CoV-2, the virus that causes COVID-19.</p>
<h2>How much will a disease spread?</h2>
<p>The formal definition of a disease’s R0 is the number of cases, on average, an infected person will cause during their infectious period. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/312353/original/file-20200128-120039-bogv2t.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/312353/original/file-20200128-120039-bogv2t.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=621&fit=crop&dpr=1 600w, https://images.theconversation.com/files/312353/original/file-20200128-120039-bogv2t.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=621&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/312353/original/file-20200128-120039-bogv2t.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=621&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/312353/original/file-20200128-120039-bogv2t.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=780&fit=crop&dpr=1 754w, https://images.theconversation.com/files/312353/original/file-20200128-120039-bogv2t.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=780&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/312353/original/file-20200128-120039-bogv2t.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=780&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">R0 describes how many cases of a disease an infected person will go on to cause – in this imagined scenario R0=2.</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 term is used in two different ways. </p>
<p>The basic reproduction number represents the maximum epidemic potential of a pathogen. It describes what would happen if an infectious person were to enter a fully susceptible community, and therefore is an estimate based on an idealized scenario.</p>
<p>The effective reproduction number depends on the population’s current susceptibility. This measure of transmission potential is likely lower than the basic reproduction number, based on factors like whether some of the people are vaccinated against the disease, or whether some people have immunity due to prior exposure with the pathogen. Therefore, the effective R0 changes over time and is an estimate based on a more realistic situation within the population.</p>
<p>It’s important to realize that both the <a href="https://dx.doi.org/10.3201/eid2501.171901">basic and effective R0 are situation-dependent</a>. It’s affected by the properties of the pathogen, such as how infectious it is. It’s affected by the host population – for instance, how susceptible people are due to nutritional status or other illnesses that may compromise one’s immune system. And it’s affected by the environment, including things like demographics, socioeconomic and climatic factors.</p>
<p>For example, <a href="https://doi.org/10.1016/S1473-3099(17)30307-9">R0 for measles ranges from 12 to 18</a>, depending on factors like population density and life expectancy. This is a large R0, mainly because the measles virus is highly infectious.</p>
<p>On the other hand, the influenza virus is less infectious, with <a href="https://doi.org/10.1186/1471-2334-14-480">its R0 ranging</a> <a href="https://doi.org/10.1017/S0950268807009144">from 0.9 to 2.1</a>. Influenza, therefore, does not cause the same explosive outbreaks as measles, but it persists due to its ability to mutate and evade the human immune system. </p>
<h2>What makes R0 useful in public health?</h2>
<p>Demographer Alfred Lotka proposed the reproduction number in the 1920s, as a measure of the rate of reproduction in a given population.</p>
<p>In the 1950s, <a href="https://doi.org/10.1371/journal.ppat.1002588">epidemiologist George MacDonald suggested</a> using it to describe the transmission potential of malaria. He proposed that, if R0 is less than 1, the disease will die out in a population, because on average an infectious person will transmit to fewer than one other susceptible person. On the other hand, if R0 is greater than 1, the disease will spread.</p>
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<p>When public health agencies are figuring out how to deal with an outbreak, they are trying to bring R0 down to less than 1. This is tough for diseases like measles that have a high R0. It is <a href="https://www.cdc.gov/mmwr/PDF/rr/rr4711.pdf">especially challenging for measles in densely populated regions</a> like India and China, where R0 is higher, compared to places where people are more spread out.</p>
<p>For the <a href="https://doi.org/10.1126/science.1086478">SARS pandemic in 2003</a>, scientists estimated the original R0 to be around 2.75. A month or two later, the effective R0 dropped below 1, thanks to the tremendous effort that went into intervention strategies, including isolation and quarantine activities.</p>
<p>However, the pandemic continued. While on average, an infectious person transmitted to fewer than one susceptible individual, occasionally one person transmitted to tens or even hundreds of other cases. This phenomenon <a href="https://theconversation.com/what-is-a-super-spreader-an-infectious-disease-expert-explains-130756">is called super spreading</a>. Officials documented super spreader events a number of times during the SARS epidemic in Singapore, Hong Kong and Beijing.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/313590/original/file-20200204-41495-8uhzhq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/313590/original/file-20200204-41495-8uhzhq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/313590/original/file-20200204-41495-8uhzhq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=408&fit=crop&dpr=1 600w, https://images.theconversation.com/files/313590/original/file-20200204-41495-8uhzhq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=408&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/313590/original/file-20200204-41495-8uhzhq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=408&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/313590/original/file-20200204-41495-8uhzhq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=512&fit=crop&dpr=1 754w, https://images.theconversation.com/files/313590/original/file-20200204-41495-8uhzhq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=512&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/313590/original/file-20200204-41495-8uhzhq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=512&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">People in Hong Kong, concerned about coronavirus spreading from mainland China, wear face masks in February 2020.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Hong-Kong-China-Outbreak/3e0e13e1d7c44ce3a8439c982e27c797/1/0">AP Photo/Vincent Yu</a></span>
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<h2>R0 for coronavirus SARS-CoV-2</h2>
<p>A number of groups have estimated R0 for this new coronavirus. The Imperial College group has estimated R0 to be <a href="https://www.imperial.ac.uk/mrc-global-infectious-disease-analysis/news--wuhan-coronavirus/">somewhere between 1.5 and 3.5</a>. Most modeling simulations that project future cases are using R0s in that range.</p>
<p>These differences are not surprising; there’s uncertainty about many of the factors that go into estimating R0, such as in estimating the number of cases, especially early on in an outbreak. </p>
<p>Based on these current estimates, projections of the future number of cases of coronavirus are fraught with high levels of uncertainty and will likely be somewhat inaccurate.</p>
<p>The difficulties arise for a number of reasons. </p>
<p>First, the basic properties of this viral pathogen – like the infectious period – are as yet unknown.</p>
<p>Second, researchers don’t know how many mild cases or infections that don’t result in symptoms have been missed by surveillance but nevertheless are spreading the disease.</p>
<p>Third, the majority of people who come down with this new coronavirus do recover, and are likely then immune to coming down with it again. It’s unclear how the changing susceptibility of the population will affect the future spread of infection. As the virus moves into new regions and communities, it encounters people with varying health conditions that affect their susceptibility to disease, as well as different social structures, both of which affect its transmissibility. </p>
<p>Finally, and likely the most important reason, no one knows the future impacts of current disease control measures. Epidemiologists’ current estimates of R0 say nothing about how measures such as <a href="https://www.washingtonpost.com/local/trafficandcommuting/white-house-considers-moving-all-of-europe-to-level-3-travel-advisory/2020/03/11/844090d0-63bc-11ea-b3fc-7841686c5c57_story.html">travel restrictions</a>, <a href="https://www.cdc.gov/coronavirus/2019-ncov/php/risk-assessment.html">social distancing</a> and <a href="https://theconversation.com/coronavirus-control-measures-arent-pointless-just-slowing-down-the-pandemic-could-save-millions-of-lives-133468">self-quarantine efforts</a> will influence the virus’s continued spread.</p>
<hr>
<p><em>This is an updated version of an article originally published on Feb. 5, 2020. The reproduction number for seasonal flu was corrected on March 27, 2020.</em></p><img src="https://counter.theconversation.com/content/130777/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Joseph Eisenberg 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>Epidemiologists want to quickly identify any emerging disease’s potential to spread far and wide. Dependent on a number of factors, this R0 number helps them figure that out and plan accordingly.Joseph Eisenberg, Professor and Chair of Epidemiology, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/365552015-07-06T05:09:23Z2015-07-06T05:09:23ZHealth Check: when are we most likely to catch viral diseases?<figure><img src="https://images.theconversation.com/files/87436/original/image-20150706-17494-3qdcz2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Children in particular experience a multitude of viral illnesses during their early years.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/mujitra/12363377564/">MIKI Yoshihito/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Viruses have been described as “organisms at the edge of life”, unable to reproduce outside the cells of those they infect. But this status has not impeded their evolutionary success. Children, in particular, experience a multitude of viral illnesses during their early years, which gradually reduce over time as their natural immunity develops.</p>
<p>Viral infections may be fleeting (think influenza) or chronic (HIV, for instance), affecting various parts of the body to cause a diverse array of symptoms. These differences have important implications for the spread of that particular viral disease. </p>
<h2>Reducing reproduction numbers</h2>
<p>The most relevant factor is the infectiousness of a virus, often summarised in a measure known among epidemiologists as its “reproduction number”. This describes the average number of secondary infections produced by one ill individual. </p>
<p>Consider the most commonly transmitted viral illness, the flu: about 10% to 20% of the population is infected by one of the circulating influenza viruses each year. Symptoms vary from a mild “cold” through to severe respiratory infection requiring hospitalisation.</p>
<p>So it’s perhaps surprising that the reproduction number of influenza is relatively low; <a href="http://www.biomedcentral.com/1471-2334/14/480">each infectious person infects only one and a half other people</a> - or put another way, two infectious people produce, on average, three new cases of influenza. If we could get that reproduction number below one, incidence numbers would decline as, on average, each infected person would not necessarily produce a successor.</p>
<p>What makes the flu difficult to control despite its relatively low reproduction number is the fact that people are <a href="http://www.cdc.gov/flu/about/disease/spread.htm">contagious for a day or two before they show any symptoms</a>. Once they become unwell, they’re contagious for a couple more days. But by this stage they’re more likely to stay home and avoid contact with others. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/87430/original/image-20150706-17526-vr24a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/87430/original/image-20150706-17526-vr24a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=444&fit=crop&dpr=1 600w, https://images.theconversation.com/files/87430/original/image-20150706-17526-vr24a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=444&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/87430/original/image-20150706-17526-vr24a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=444&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/87430/original/image-20150706-17526-vr24a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=558&fit=crop&dpr=1 754w, https://images.theconversation.com/files/87430/original/image-20150706-17526-vr24a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=558&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/87430/original/image-20150706-17526-vr24a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=558&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">A virus’ ‘reproduction number’ describes the average number of secondary infections produced by one ill individual.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/69382656@N04/6798474143/">FAKEGRIMLOCK/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>As half or more of their secondary infections will have been produced before the ill people showed any symptoms, influenza control strategies that rely on identifying and isolating them aren’t necessarily going to effectively reduce the incidence of the illness in the community. </p>
<p>This incubation period – the time when a person is infected but not showing symptoms – is a vital consideration for controlling viral illness.</p>
<h2>Incubating viruses</h2>
<p>Consider the outbreak of a deadly strain of the coronavirus that caused <a href="http://www.cdc.gov/sars/">Severe Acute Respiratory Syndrome (SARS)</a> in 2003. Like influenza, SARS leads to fever and cough, and is mostly spread by close contact between people. Even though <a href="http://aje.oxfordjournals.org/content/160/6/509.long">its reproduction number</a> has been estimated to be between three and four, people carrying the virus are most contagious in the second week of their infection, after they have started to show symptoms of the disease. </p>
<p>It was this delay until contagion that made it possible to contain SARS: health-care workers were able to find and quarantine people who had contact with the disease before they infected others. Nonetheless, controlling its outbreak was not an easy task – it spread to around 30 countries and killed about 10% of those infected. </p>
<p>SARS appears to have been eradicated but the recently emerged <a href="http://www.cdc.gov/coronavirus/mers/">Middle East Respiratory Syndrome (MERS)</a>, which also belongs to the coronavirus family, has many similarities. The majority of cases, including the <a href="http://www.who.int/csr/don/03-july-2015-mers-korea/en/">recent outbreak in the Republic of Korea</a>, have arisen from infection spread in health-care settings, where early infections are indistinguishable from other respiratory viruses.</p>
<p>Another virus that’s been grabbing news headlines of late is Ebola. While flu and SARS spread through coughing and sneezing, contracting Ebola requires direct contact with the blood or other bodily fluids of an infected person, or with items such as bedding or clothing contaminated with these fluids. </p>
<p>As with SARS, people infected with Ebola are not contagious until they begin to show symptoms, which include diarrhoea, vomiting and bleeding. <a href="http://www.who.int/mediacentre/factsheets/fs103/en/">Contagiousness increases as these symptoms worsen</a> and peaks around the time of death. The body of a deceased person remains contagious after death. Safe burial practices were therefore an <a href="http://www.who.int/mediacentre/news/notes/2014/ebola-burial-protocol/en/">essential component in controlling the recent Ebola outbreak</a>. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/87434/original/image-20150706-17496-fvz2ji.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/87434/original/image-20150706-17496-fvz2ji.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=398&fit=crop&dpr=1 600w, https://images.theconversation.com/files/87434/original/image-20150706-17496-fvz2ji.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=398&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/87434/original/image-20150706-17496-fvz2ji.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=398&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/87434/original/image-20150706-17496-fvz2ji.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/87434/original/image-20150706-17496-fvz2ji.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/87434/original/image-20150706-17496-fvz2ji.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">
<figcaption>
<span class="caption">Measles is most infectious in the time between the appearance of non-specific symptoms, such as fever, runny nose and cough, and the development of its classically identifiable rash.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/minnellium/3480352546/">Dave Haygarth/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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</figure>
<p>The <a href="https://theconversation.com/fast-spreading-killers-how-ebola-compares-with-other-diseases-32944">reproduction number of Ebola</a> in the latest outbreak was as high as four. But, as with SARS, the delay until contagion made it <a href="http://www.cdc.gov/vhf/ebola/outbreaks/what-is-contact-tracing.html">possible to trace and quarantine people</a> who had been in contact with Ebola before they spread the disease any further. </p>
<h2>The importance of vaccines</h2>
<p>In stark contrast to these stories of successful disease control, the <a href="http://www.who.int/hiv/en/">World Health Organisation estimates</a> that 35 million people are living with human immunodeficiency virus (HIV) infection. And more than 39 million have died from the infection to date.</p>
<p>This toll is largely due to the fact that people with HIV infection may take anywhere between two and 15 years to develop symptoms of acquired immune deficiency syndrome (AIDS). Meanwhile, they unknowingly infect others over a period of many years, rather than days or weeks.</p>
<p>HIV spread can be effectively reduced by antiretroviral drugs, which lower virus levels in the blood. Unfortunately, WHO estimates that only a third of the people who need these drugs currently have access to them. Meanwhile, the quest for an HIV vaccine continues. </p>
<p>Vaccines, in fact, are one of the best ways to control the spread of viral illnesses. Consider the numerous childhood illnesses that are now contained thanks to vaccines. </p>
<p>Measles and chicken pox, for instance, are classically identifiable by their distinctive rashes. But they’re most infectious in the time between the appearance of non-specific symptoms, such as fever, runny nose and cough, and the development of this rash. This made it very difficult to control their spread until <a href="http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home">vaccines were developed</a>. </p>
<p>As you can see, different viral diseases are most infectious at different times and this timing of contagiousness plays a key role in how successfully the diseases spread. Knowing a virus’ most infectious period is vital for working out the kinds of measures that are likely to work to control and perhaps even eradicate it from the community.</p><img src="https://counter.theconversation.com/content/36555/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jodie McVernon receives funding from the Australian Government Department of Health, the Australian Research Council and the National Health and Medical Research Council (NHMRC). She leads an NHMRC funded Centre of Research Excellence in Infectious Disease Modelling to Inform Policy, on which all co-authors are co-investigators. She is a member of the Australian Technical Advisory Group on Immunisation and a Director of the Influenza Specialist Group. </span></em></p><p class="fine-print"><em><span>James McCaw receives funding from the ARC and the NHMRC.</span></em></p><p class="fine-print"><em><span>Joshua Ross receives funding from the Australian Research Council and the National Health and Medical Research Council.</span></em></p><p class="fine-print"><em><span>Kathryn Glass receives funding from the ARC and the NHMRC.</span></em></p><p class="fine-print"><em><span>Nicholas Geard receives funding from the Australian Research Council and the National Health and Medical Research Council.</span></em></p>Viruses cause all kinds of infections from relatively mild cases of the flu to deadly outbreaks of Ebola. Clearly, not all viruses are equal and one of these differences is when you can infect others.Jodie McVernon, Associate Professor, Population Health, The University of MelbourneJames McCaw, Associate Professor in Mathematical Biology, The University of MelbourneJoshua Ross, Associate Professor in Applied Mathematics, University of AdelaideKathryn Glass, Fellow, Australian National UniversityNic Geard, ARC DECRA Research Fellow, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.