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Saturday, September 29, 2012

Anatomy of the Discovery of the Deadly Bas-Congo Virus


Virus hunters published a paper today in the science journal PLOS Pathogens, describing how a team spanning a number of institutions identified a deadly virus unknown to exist until it killed three people within a few days in the Democratic Republic of the Congo. They used sophisticated technologies and techniques to detect the new virus, which could cause fatal hemorrhagic fever outbreaks similar to Ebola. Research like this can isolate viruses before they can cause epidemics.
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By Nathan D. Wolfe, Joseph Fair,  and Charles Chiu

In the summer of 2009 a teenager living in the rural village of Mangala in the Democratic Republic of Congo (DRC) suddenly fell ill and developed symptoms of a hemorrhagic fever, including bleeding from mucous membranes and blood in the vomit. He died within three days of the first signs of illness. A week later, a 13-year-old girl who attended the same school and lived in the same neighborhood came down with a similar illness and died within three days.
Within a week, yet a third patient showed the same symptoms — this time a male nurse who attended to the first two patients. Recognizing the severity of the disease in the first two patients, the nurse was transferred to a regional general hospital, where he recovered after receiving care for a few days.
These were the first known cases of the outbreak that would lead to the discovery of the Bas-Congo virus (BASV), named after the province in the southwest corner of the Democratic Republic of the Congo where the three people lived.

Choreography of Efforts

We’re proud to be part of a global consortium responsible for the discovery and identification of BASV, which was announced today in Plos Pathogens. (Read the research paper “A Novel Rhabdovirus Associated with Acute Hemorrhagic Fever in Central Africa.”) But the journey from the first patient’s illness to the publication of our paper was only possible through the carefully choreographed efforts of a large number of health workers, researchers, laboratories, institutions and governments concerned with public health.
Through close collaboration between DRC’s hospitals, Doctors Without Borders (MSF), and the DRC’s Institut National de Recherche Biom√©dicale (INRB), the samples from the third patient were transferred for diagnostic testing to Dr. Eric Leroy, the Director of CIRMF, an advanced virology laboratory based in the neighboring country of Gabon, and an expert in viral hemorrhagic fevers. Dr. Leroy tested the sample for evidence of every known cause of hemorrhagic fever. The sample was negative for all of them, suggesting whatever caused these deaths was something completely new.

Most Deadly Infections Known to Man

With funding by the U.S. Agency for International Development (USAID) and the U.S. Department of Defense, provided in part to identify undiscovered viruses that can cause viral hemorrhagic fevers, some of the most deadly infections known to man, Metabiota and partners sought to determine the cause of the outbreak. [Founded by Nathan Wolfe, Metabiota is a San Francisco-based company whose primary mission is to mitigate threats from the microbial world. Wolfe is also a National Geographic Emerging Explorer.]
As a first step, Metabiota enlisted the help of close collaborator Dr. Eric Delwart at Blood Systems Research Institute (BSRI). Using sophisticated genetic sequencing techniques, Dr. Delwart detected a fragment of genetic information related to the rhabdovirus family. Rhabdoviruses are a large family of viruses that infect plants, insects, and mammals, including humans. The most famous member of the family is the virus that causes rabies.
Unable to derive further information from the sample, Metabiota then brought the University of California in San Francisco (UCSF) on board to employ its extensive experience in identifying unknown viruses.

Genetic Codes

UCSF’s approach, known as unbiased deep sequencing, involves reading the complete genetic material of a sample and identifying and assembling that information into genomes – the genetic codes of organisms. It is technology that has become available only in the past few years. Utilizing this technology, we were able to reconstruct nearly 100 percent of the genome of BASV from less than one-tenth of one milliliter of the third patient’s blood. The viral genome is so distinct from any other known virus that it would likely not have been detectable by any other method.
These findings, along with further studies and follow-up investigation at the site of the initial outbreak, provided greater certainty that BASV was indeed responsible for the outbreak.
While the symptoms associated with BASV are similar to those caused by well-known viruses such as Ebola, members of BASV’s viral family, rhabdoviruses, have not previously been known to cause hemorrhagic fever in humans. Rabies, for instance, can be a deadly disease if untreated, but the course and symptoms of rabies in humans are nothing like the rapid and deadly onset of BASV. There is some precedent, however, for hemorrhagic disease caused by rhabdoviruses in the animal kingdom – some other rhabdoviruses that affect fish are known to cause hemorrhagic septicemia, acute bleeding and death.
While we’re proud to be part of the consortium responsible for the discovery of BASV, in our line of work the excitement of scientific discovery is often dampened by the reality of the suffering of individuals intimately impacted by viruses such as BASV. Such is the case today, where Metabiota is actively responding to an outbreak of Ebola in DRC in conjunction with DRC’s Ministry of Health and its national biomedical research institute INRB, the World Health Organization, the U.S. Centers for Disease Control, and others in the Democratic Republic of Congo. These ongoing challenges and the BASV discovery emphasize the importance of research into the identification, prevention and management of deadly scourges from emerging viruses, now more than ever.

Curbing Epidemics

Fortunately, programs like those supported by USAID and the DoD have begun to create robust systems for identifying viruses like BASV and curbing epidemics at their earliest stages.  And new techniques like unbiased deep sequencing permit findings like this that would have been missed before.
Discoveries like this are essential to the maintenance of a globally sensitive and responsive public health system. Such systems are vitally needed in an interconnected world like ours, where a virus can circumnavigate the globe in less than 24 hours. BASV represents only one of perhaps thousands of potential threats which must be identified before they strike.
Nathan D. Wolfe, DSc, is Founder of Global Viral and Founder and CEO of Metabiota; Joseph Fair, PhD, is Vice President, Metabiota; Charles Chiu, MD, PhD, is Assistant Professor, Laboratory Medicine and Medicine, Infectious Diseases and Director, University of California, San Francisco – Abbott Viral Diagnostics and Discovery Center.
Nathan Wolfe will write on more benevolent microbes in the January issue of National Geographic magazine.

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