Collecting samples in the Jungles of Boma in 2009 after the outbreak.
An isolated outbreak of a deadly disease known as acute hemorrhagic
fever, which killed two people and left one gravely ill in the
Democratic Republic of Congo in the summer of 2009, was probably caused
by a novel virus scientists have never seen before.
Described this week in the open-access journal PLoS Pathogens,
the new microbe has been named Bas-Congo virus (BASV) after the
province in the southwest corner of the Congo where the three people
lived.
It was discovered by an international research consortium that
included the University of California, San Francisco (UCSF) and
University of California, Davis (UCD), Global Viral, the Centre
International de Recherches Médicales de Franceville in Gabon, the
Institut National de Recherche Biomédicale, Kinshasa in the Democratic
Republic of the Congo, Metabiota and others.
"Known viruses, such as Ebola, HIV and influenza, represent just the
tip of the microbial iceberg," said Joseph Fair, PhD, a co-author and
vice president of Metabiota. "Identifying deadly unknown viruses, such
as Bas-Congo virus, gives us a leg up in controlling future outbreaks."
"These are the only three cases known to have occurred, although
there could be additional outbreaks from this virus in the future," said
Charles Chiu, MD, PhD, an assistant professor of laboratory medicine at
UCSF and director of the UCSF-Abbott Viral Diagnostics and Discovery
Center, who spearheaded the UCSF effort to identify the virus. Chiu and
his team continue to work on new diagnostics to detect the virus so that
health officials in Congo and elsewhere can quickly identify it should
it emerge again.
One odd characteristic of the Bas-Congo virus, Chiu said, is that
while a number of other viruses in Africa also cause deadly outbreaks of
acute hemorrhagic fever -- Ebola virus, Lassa virus and Crimean-Congo
Hemorrhagic Fever virus to name a few -- the new virus is unlike any of
them.
Genetically it is more closely related to the types of viruses that
cause rabies, which are known to infect people with a very different
sort of disease -- a neurological illness that is uniformly fatal if
untreated but may take months to develop.
An antibody test developed in this study was applied to the one
patient who survived and to others who had come into contact with him.
It suggested that the disease may be spread from person to person but
likely originated from some other source, such as an insect or rodent.
The identity of this animal "reservoir" and the precise mode of
transmission for the virus remain unclear and are currently being
investigated by Metabiota and the central African members of the
consortium through the PREDICT Project of USAID's Emerging Pandemic
Threats Program. (http://www.vetmed.ucdavis.edu/ohi/predict/index.cfm)
How the New Virus Emerged
In the summer of 2009, a 15-year old boy in a small rural community
called Mangala village suddenly fell ill and developed a bleeding nose,
bleeding gums and bloody vomit. He rapidly worsened, dying 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 as the boy came down with a similar,
serious illness. She declined just as rapidly and also died within three
days. One week after that, the male nurse who cared for this girl began
showing the same symptoms, and he was transferred to a hospital in
Boma, a nearby port city that sits along the Congo River upstream from
Africa's Atlantic coast.
Members of the consortium, who had initiated a project to diagnose
unusual cases of severe hemorrhagic fever, obtained blood samples
collected from the nurse by the Congolese doctors and sent them to the
laboratory of Eric Leroy, PhD, doctor of veterinary medicine at the
Centre International de Recherches Médicales de Franceville in Gabon.
There the samples were tested for traces of any known virus, but nothing
was found. The Metabiota scientists then solicited the expertise of
Chiu at UCSF and Eric Delwart at the Blood Systems Research Institute
(BSRI) in San Francisco to aid in the diagnosis.
The researchers ultimately identified a completely new virus as the
cause of the mysterious illness through a powerful strategy for
identifying novel pathogens known as "deep sequencing," in which
millions of DNA sequences are generated from a clinical sample and then
pieced together using computer algorithms combined with human analysis.
Distinct Attributes of Bas-Congo
The Bas-Congo virus belongs to a family of viruses known as the
rhabdoviruses, a large family of viruses that infect plants, insects and
mammals, including humans. The most famous member of this family is the
virus that causes rabies. But even among the rhabdoviruses, Bas-Congo
is something of an outlier, being very genetically distinct from other
members of the family.
What's most unusual about this virus, though, said Chiu, is what it does to people.
No other rhabdoviruses are known to cause the acute, rapid and deadly
hemorrhagic fever seen in the three cases in the Congo. Rabies, for
instance, can be a deadly disease if untreated, but the course of rabies
in humans is nothing like the rapid and deadly onset seen with the
Bas-Congo virus. There is some precedent, however, for hemorrhagic
disease from rhabdoviruses in the animal kingdom: fish rhabdoviruses are
known to cause hemorrhagic septicemia -- acute bleeding and death -- in
affected fish.
The third patient had enormous amounts of BASV in his bloodstream
just two days after he fell ill -- more than a million copies in every
milliliter of blood.
The BASV sequence was also used to design an antibody test for the
virus, an effort led by Graham Simmons at the BSRI, another member of
the consortium. Antibodies are blood immune proteins produced in
response to an infection. The antibody test allowed the researchers to
screen both the third patient with acute hemorrhagic fever and other
people who had come into contact with the third patient, including the
nurse who cared for him in the Boma hospital. High levels of
BASV-specific antibodies were found in the third patient, establishing
that he indeed had been infected with Bas-Congo virus. The same
antibodies were also found in the second nurse, even though he never
actually became sick.
"What this suggests is that the disease may be transmissible from
person to person -- though it's most likely to have originated from some
other source," said Nathan Wolfe, PhD, founder and chairman of Global
Viral, and a co-author on the paper. "The fact that it belongs to a
family of viruses known to infect a wide variety of mammals, insects and
other animals means that it may perpetually exist in insect or other
'host' species and was accidentally passed to humans through insect
bites or some other means."
The research consortium includes San Francisco-based Global Viral,
Metabiota, UCSF, BSRI, as well as researchers with the Centre
International de Recherches Médicales de Franceville in Gabon; the
Institut de Recherche pour le Développement in Montpellier, France; the
Institut National de Recherche Biomédicale, Kinshasa in the Democratic
Republic of the Congo, the University of Texas Medical Branch in
Galveston, TX; the University of California, Davis; the University of
California, Los Angeles; Stanford University; and the Howard Hughes
Medical Center.
This work was funded by support from Google.org,
the Skoll Foundation, the government of Gabon, Total-Fina-Elf Gabon,
and the Ministère des Affaires Etrangères et Européennes de la France,
the U.S. Department of Defense Armed Forces Health Surveillance Center,
Division of Global Emerging Infections, Surveillance Operations (AFHSC
GEIS) and the Defense Threat Reduction Agency Cooperative Biological
Engagement Program (DTRA-CBEP), and the U.S. Agency for International
Development (USAID) Emerging Pandemic Threats Program, PREDICT project.
Additional funding was provided by the National Institutes of Health
provided via grant numbers R01-HL083254, R01-HL105770, R56-AI089532, and
R01-HL105704 and by an Abbott Viral Discovery Award.
* Global Viral was previously known as Global Viral Forecasting Initiative.
**Metabiota was previously known as Global Viral Forecasting Inc.
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