{"id":13665,"date":"2017-11-17T09:08:33","date_gmt":"2017-11-17T09:08:33","guid":{"rendered":"https:\/\/www.revoscience.com\/en\/?p=13665"},"modified":"2017-11-17T09:08:33","modified_gmt":"2017-11-17T09:08:33","slug":"heart-devastating-outbreak-research-team-unlocks-secrets-ebola","status":"publish","type":"post","link":"https:\/\/www.revoscience.com\/en\/heart-devastating-outbreak-research-team-unlocks-secrets-ebola\/","title":{"rendered":"In the heart of devastating outbreak, research team unlocks secrets of Ebola"},"content":{"rendered":"
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UW-Madison\u2019s Yoshihiro Kawaoka, Peter Halfmann and Alhaji Njai stand outside of a military hospital with Foday Sahr, a Sierra Leone military official and chair of microbiology at the University of Sierra Leone.<\/figcaption><\/figure>\n

In a comprehensive and complex molecular study of blood samples from Ebola patients in Sierra Leone, published today (Nov. 16, 2017) in\u00a0Cell Host & Microbe<\/a>, a scientific team led by the University of Wisconsin\u2013Madison has identified signatures of Ebola virus disease that may aid in future treatment efforts.<\/span><\/p>\n

Conducting a sweeping analysis of everything from enzymes to lipids to immune-system-associated molecules, the team \u2014 which includes researchers from Pacific Northwest National Laboratory (PNNL), Icahn School of Medicine at Mount Sinai, the University of Tokyo and the University of Sierra Leone \u2014 found 11 biomarkers that distinguish fatal infections from nonfatal ones and two that, when screened for early symptom onset, accurately predict which patients are likely to die.<\/span><\/p>\n

With these results, says senior author\u00a0Yoshihiro Kawaoka<\/a>, a virology professor at the UW\u2013Madison School of Veterinary Medicine, clinicians can prioritize the scarce treatment resources available and provide care to the sickest patients.<\/span><\/p>\n

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A vial is labeled and prepared to hold blood from an Ebola patient in Sierra Leone. ALL PHOTOS COURTESY OF KAWAOKA LAB<\/figcaption><\/figure>\n

Studying Ebola in animal models is difficult; in humans, next to impossible. Yet, in Sierra Leone in 2014, a natural and devastating experiment played out. In September of that year, an Ebola outbreak like no other was beginning to surge in the West African nation. By December, as many as 400 Ebola cases would be\u00a0reported there<\/a>\u00a0each week.<\/span><\/p>\n

That fall, Kawaoka sought access to patient samples. He has spent a career trying to understand infectious diseases like Ebola \u2014 how do they make people sick, how do\u00a0bodies respond<\/a>\u00a0to infection, how can public health officials stay at least a step ahead?<\/span><\/p>\n

\u201cHere, there is a major outbreak of Ebola. It is very rare for us to encounter that situation,\u201d says Kawaoka, who is also a professor of virology at the University of Tokyo.<\/span><\/p>\n

Yet blood samples were proving difficult to obtain and people continued to die.<\/span><\/p>\n

Then, just weeks before Christmas,\u00a0Kawaoka learned<\/a>about a colleague in his very own department at UW\u2013Madison, a research fellow from Sierra Leone named Alhaji N\u2019jai, who was producing radio stories for people back home to help them protect themselves from Ebola. The pair forged\u00a0a fortuitous partnership<\/a>.<\/span><\/p>\n

\u201cHe knows many people high up in the Sierra Leone government,\u201d says Kawaoka. \u201cHe is very smart and very good at explaining things in lay terms.\u201d<\/span><\/p>\n

By Christmas, Kawaoka, N\u2019jai and Peter Halfmann, a senior member of Kawaoka\u2019s team, were in Sierra Leone.<\/span><\/p>\n

\u201cOn the first trip, Alhaji took me to Parliament and we talked to a special advisor to the president, then the vice chancellor of the University of Sierra Leone,\u201d says Kawaoka. \u201cWe got the support of the university, which helped us identify military hospitals and provided space. We went to the Ministry of Health and Sanitation and the chief medical officer and we explained what we hoped to do.\u201d<\/span><\/p>\n

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Health workers tend to a patient at one of Sierra Leone\u2019s military hospitals, where many of the country\u2019s 8,000 Ebola patients have received treatment since an outbreak began in West Africa in December 2013.<\/figcaption><\/figure>\n

By February of 2015, Kawaoka and other select senior researchers on his \u00a0team, including Amie Eisfeld, set up a lab in a military hospital responding to the outbreak in the capital city of Freetown (the researchers never entered patient wards). With the approval of patients and the government of Sierra Leone, health workers collected blood samples from patients after they were diagnosed with Ebola and at multiple points thereafter.<\/span><\/p>\n

They obtained 29 blood samples from 11 patients who ultimately survived and nine blood samples from nine patients who died from the virus. The samples were transported to the lab where Kawaoka\u2019s experienced and expertly trained team inactivated the virus according to approved protocols. Blood samples were subsequently shipped to UW\u2013Madison and partner institutions for analysis.<\/span><\/p>\n

For comparison, the research team also obtained blood samples from 10 healthy volunteers with no exposure to Ebola virus.<\/span><\/p>\n

\u201cOur team studied thousands of molecular clues in each of these samples, sifting through extensive data on the activity of genes, proteins and other molecules to identify those of most interest,\u201d says Katrina Waters, a biologist at PNNL and a corresponding author of the study. \u201cThis may be the most thorough analysis yet of blood samples of patients infected with the Ebola virus.\u201d<\/span><\/p>\n

The team found that survivors had higher levels of some immune-related molecules, and lower levels of others compared to those who died. Plasma cytokines, which are involved in immunity and stress response, were higher in the blood of people who perished. Fatal cases had unique metabolic responses compared to survivors, higher levels of virus, changes to plasma lipids involved in processes like blood coagulation, and more pronounced activation of some types of immune cells.<\/span><\/p>\n

Pancreatic enzymes also leaked into the blood of patients who died, suggesting that damage from these enzymes contributes to the tissue damage characteristic of fatal Ebola virus disease.<\/span><\/p>\n

And, critically, the study showed that levels of two biomarkers, known as L-threonine (an amino acid) and vitamin D binding protein, may accurately predict which patients live and which die. Both were present at lower levels at the time of admission in the patients who ultimately perished.<\/span><\/p>\n

\u201cWe want to understand why those two compounds are discriminating factors,\u201d says Kawaoka. \u201cWe might be able to develop drugs.\u201d<\/span><\/p>\n

When Ebola virus leads to death, experts believe it is because of overwhelming viral replication. Symptoms of infection include severe hemorrhaging, vomiting and diarrhea, fever and more.<\/span><\/p>\n

Kawaoka and his collaborators hope to better understand why there are differences in how patients\u2019 bodies respond to infection, and why some people die while others live. The current study is part of a larger, multicenter effort funded by the National Institutes of Health.<\/span><\/p>\n

\u201cThe whole purpose is to study the responses of human and animal bodies to infection from influenza, Ebola, SARS and MERS, and to understand how they occur,\u201d Kawaoka explains. \u201cAmong the various pathways, is there anything in common?\u201d<\/span><\/p>\n

In the current Ebola study, the team found that many of the molecular signals present in the blood of sick, infected patients overlap with sepsis, a condition in which the body \u2014 in response to infection by bacteria or other pathogens \u2014 mounts a damaging inflammatory reaction.<\/span><\/p>\n

And the results contribute a wealth of information for other scientists aimed at studying Ebola, the study authors say.<\/span><\/p>\n

Kawaoka says he is grateful to UW\u2013Madison, University Health Services and Public Health Madison and Dane County for assistance, particularly with respect to his research team\u2019s travel between Madison and Sierra Leone. Each provided protocols, monitoring, approval and other needed support during the course of the study.<\/span><\/p>\n

\u201cI hope another outbreak like this never occurs,\u201d says Kawaoka. \u201cBut hopefully this rare opportunity to study Ebola virus in humans leads to fewer lives lost in the future.\u201d<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

In a comprehensive and complex molecular study of blood samples from Ebola patients in Sierra Leone, published today (Nov. 16, 2017) in\u00a0Cell Host & Microbe, a scientific team led by the University of Wisconsin\u2013Madison has identified signatures of Ebola virus disease that may aid in future treatment efforts. Conducting a sweeping analysis of everything from […]<\/p>\n","protected":false},"author":6,"featured_media":13667,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26,17],"tags":[],"class_list":["post-13665","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicine","category-research"],"featured_image_urls":{"full":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",500,334,false],"thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334-150x150.jpg",150,150,true],"medium":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334-300x200.jpg",300,200,true],"medium_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",500,334,false],"large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",500,334,false],"1536x1536":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",500,334,false],"2048x2048":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",500,334,false],"ultp_layout_landscape_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",500,334,false],"ultp_layout_landscape":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",500,334,false],"ultp_layout_portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",500,334,false],"ultp_layout_square":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",500,334,false],"newspaper-x-single-post":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",500,334,false],"newspaper-x-recent-post-big":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",500,334,false],"newspaper-x-recent-post-list-image":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",95,63,false],"web-stories-poster-portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",500,334,false],"web-stories-publisher-logo":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",96,64,false],"web-stories-thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/11\/Ebola-vial-500x334.jpg",150,100,false]},"author_info":{"info":["Amrita Tuladhar"]},"category_info":"Medicine<\/a> Research<\/a>","tag_info":"Research","comment_count":"0","_links":{"self":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/13665","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/comments?post=13665"}],"version-history":[{"count":0,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/13665\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media\/13667"}],"wp:attachment":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media?parent=13665"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/categories?post=13665"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/tags?post=13665"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}