{"id":56526,"date":"2018-03-29T11:06:19","date_gmt":"2018-03-29T15:06:19","guid":{"rendered":"http:\/\/www.bumc.bu.edu\/busm\/?p=56526"},"modified":"2018-03-29T12:15:17","modified_gmt":"2018-03-29T16:15:17","slug":"diagnosing-ebola-before-symptoms-arrive","status":"publish","type":"post","link":"https:\/\/www.bumc.bu.edu\/camed\/2018\/03\/29\/diagnosing-ebola-before-symptoms-arrive\/","title":{"rendered":"Diagnosing Ebola Before Symptoms Arrive"},"content":{"rendered":"<div class=\"entry-title\">\n<h3>BU researchers, colleagues: early immune response may lead to diagnosis sooner<\/h3>\n<\/div>\n<div class=\"entry sc\">\n<div class=\"banner-container\">\n<p><img loading=\"lazy\" src=\"http:\/\/www.bu.edu\/today\/files\/2018\/03\/ebola.jpg\" class=\"banner\" alt=\"Ebola virus\" height=\"497\" width=\"550\" \/><\/p>\n<p class=\"caption\">Ebola virus. Symptoms like fever and fatigue appear anywhere from 2 to 21 days after exposure to the virus; the average is 8 to 10 days. The 2014\u20132016 Ebola epidemic killed 11,000 people. Photo courtesy of the National Institute of Allergy and Infectious Diseases<\/p>\n<\/div>\n<ul>\n<li><strong>Doctors currently diagnose Ebola when symptoms like fever emerge<\/strong><\/li>\n<li><strong>Diagnosing infected people earlier could save lives<\/strong><\/li>\n<li><strong> Primates\u2019 antiviral response kicks in up to four days before symptoms appear, making early diagnosis a possibility<\/strong><strong><br \/>\n<\/strong><\/li>\n<\/ul>\n<hr \/>\n<p>In 2014, an Ebola <a href=\"https:\/\/www.cdc.gov\/vhf\/ebola\/outbreaks\/2014-west-africa\/index.html\">epidemic<\/a> began to ravage West Africa. It became the largest Ebola outbreak in history, lasting two years and infecting an estimated 28,000 people\u2014most in Liberia, Guinea, and Sierra Leone. Ultimately, it took more than 11,000 lives.<\/p>\n<p>Many of those lives might have been saved if health-care workers could have treated and quarantined infected people during the early stages of the disease. Currently, however, there is no way to diagnose Ebola until symptoms arrive\u2014and the fever, severe headache, and muscle pain that mark Ebola can strike victims anytime <a href=\"http:\/\/www.bu.edu\/today\/2018\/diagnosing-ebola\/%5bhttps:\/www.cdc.gov\/vhf\/ebola\/symptoms\/index.html%5d\">between 2 and 21 days after exposure<\/a>. \u201cRight now, we wait for diagnosis until the virus spills out of primary infection sites into the blood,\u201d says Emily Speranza (GRS\u201918). \u201cAt that point, it\u2019s already tremendously far along.\u201d<\/p>\n<p>Speranza may have found a better way. Working with colleagues at BU\u2019s National Emerging Infectious Diseases Laboratories (<a href=\"http:\/\/www.bu.edu\/neidl\/\">NEIDL<\/a>), as well as the US Army Medical Research Institute of Infectious Diseases (<a href=\"http:\/\/www.usamriid.army.mil\/\">USAMRIID<\/a>), Speranza, who recently earned a PhD in the interdisciplinary bioinformatics program, studied data from 12 monkeys exposed to Ebola virus and discovered a common pattern of immune response among the ones that got sick. This response occurred four days before the onset of fever\u2014the first observable symptom of infection. The work, funded by the <a href=\"https:\/\/www.nih.gov\/\">National Institutes of Health<\/a>, the <a href=\"https:\/\/www.nsf.gov\/\">National Science Foundation<\/a>, and others and published on March 28, 2018, in the journal <a href=\"http:\/\/stm.sciencemag.org\/lookup\/doi\/10.1126\/scitranslmed.aaq1016\"><em>Science Translational Medicine<\/em><\/a>, suggests a possible biomarker for early diagnosis of the disease.<\/p>\n<p>\u201cFour days! Think about it,\u201d says paper\u00a0senior author <a href=\"https:\/\/profiles.bu.edu\/John.Connor\">John Connor,<\/a>\u00a0a School of Medicine associate professor of microbiology and a NEIDL researcher. \u201cIf I could tell you four days before you were going to be sick, that would be fantastic.\u201d<\/p>\n<div id=\"attachment19230\" class=\"wp-caption aligncenter\">\n<p><img loading=\"lazy\" src=\"http:\/\/www.bu.edu\/research\/files\/2017\/01\/h_research_Connor_Speranza.jpg\" alt=\"John Connor, associate professor of microbiology at BU\u2019s National Emerging Infectious Diseases Laboratories (NEIDL), and Emily Speranza, National Science Foundation Graduate Research Fellowship Program fellow at Boston University\" class=\"size-full wp-image-19230\" height=\"367\" width=\"550\" \/><\/p>\n<p class=\"wp-caption-text\">John Connor and Emily Speranza detected a response in interferon-stimulated genes four days before Ebola symptoms emerged. They published their findings in <em>Science Translational Medicine<\/em>. Connor photo by Mark Fleming; Speranza photo by Cydney Scott<\/p>\n<\/div>\n<p>\u201cIf you can start treating someone very, very early on after exposure, they\u2019re less likely to develop really severe disease,\u201d says Speranza, one of the paper\u2019s first authors, now a postdoctoral fellow at Rocky Mountain Laboratories in Montana. \u201cAnd if you can identify people who are sick before they even show symptoms, you can better quarantine and actually control outbreaks.\u201d<\/p>\n<p>Speranza\u2019s study began with an unexpected result from USAMRIID scientists.<\/p>\n<p>They had been trying to simulate the course of Ebola in monkeys in a way that more closely mimicked the way humans become infected. Traditionally, scientists studying Ebola in primates inject a high dose of virus directly into a muscle. When infected that way, all the animals die within 10 days.<\/p>\n<p>That\u2019s not how it works in people. \u201cHumans are not necessarily going to be exposed to a needle injection of Ebola virus,\u201d says Speranza. \u201cYou\u2019re more likely to be exposed through cuts on your skin or through mucosal surfaces in your eyes, nose, or mouth.\u201d<\/p>\n<p>So the USAMRIID scientists tried a similar tactic. They infected 12 monkeys through the nose, using much less Ebola virus than usual. The researchers expected all the animals to grow sick at the same time, but they didn\u2019t: some died within the usual 10 days, one group died around day 13, another group lived to 21 to 22 days, and\u00a0two of the animals never got sick at all.<\/p>\n<p>\u201cPrior to this result, there was no model that behaved like the disease that you and I would get, which is, we would probably be exposed, we\u2019d walk around for somewhere from 2 to 21 days, and then we\u2019d get sick,\u201d says Connor. \u201cAnd that\u2019s what this was trying to model: if I get sick in 5 days, and you get sick in 12 days or 17 days, are our immune responses different? All of a sudden you can ask that question.\u201d<\/p>\n<p>Speranza, who studies the body\u2019s immune response to Ebola virus, sought to answer the question by looking at genes. \u201cWe were very curious to find out what was going on,\u201d she says. She started by looking at the innate immune response, the body\u2019s first defense against disease, trying to see which genes turned on, and when. When she looked at a group of signaling proteins called interferons, she found a pattern. In all the monkeys, no matter how long it took them to show symptoms, a handful of genes triggered by interferons\u2014called the interferon-stimulated genes\u2014kicked into gear four days before the animals spiked a fever. The genes showed up in the same pattern across all the subjects who got sick.<\/p>\n<p>Speranza then compared the results to humans, using Ebola victim blood samples that had been collected and preserved during the outbreak in Guinea. \u201cWe found not only the same genes going up,\u201d she says, \u201cbut in a similar order.\u201d<\/p>\n<p>Connor notes that other scientists have found similar early immune responses in, for instance, monkeys exposed to Lassa fever and humans exposed to influenza. Scientists still need to tease out more specific details of the human response to Ebola. \u201cWe looked at the most obvious things, which is this very loud innate immune response. Those are the trumpets,\u201d he says. \u201cAnd there may be some piccolos playing that we can\u2019t hear. There may be some other specific signals that say, \u2018Oh, this actually is Ebola.\u2019\u201d<\/p>\n<p>Finding those subtle signals will take more research, the scientists say, but this work, although preliminary, offers a promising first step toward early diagnosis. \u201cWe can now take the next step,\u201d says Speranza, \u201cand actually start building that information into a biomarker for infection.\u201d<\/p>\n<p>This <em>BU Today<\/em> story was written by <a href=\"mailto: bmoran@bu.edu\">Barbara Moran<\/a>.<\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Researchers hope that early immune response may lead to diagnosis sooner. <\/p>\n","protected":false},"author":903,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[91,90],"tags":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/56526"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/users\/903"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/comments?post=56526"}],"version-history":[{"count":3,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/56526\/revisions"}],"predecessor-version":[{"id":56530,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/56526\/revisions\/56530"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/media?parent=56526"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/categories?post=56526"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/tags?post=56526"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}