Researchers report new species of deadly Ebola virus

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Nov 21, 2008 (CIDRAP News) – Researchers from the United States and Uganda today released the first full scientific report on a new Ebola species that struck western Uganda late last year and was linked to 149 suspected cases and 37 deaths, at least 4 of them healthcare providers.

During the midst of the 2007 outbreak the World Health Organization announced Nov 30 that a new subtype of the virus was sickening people in Bundibugyo district. Researchers published a detailed account today on the discovery and an analysis of genetic findings of the new subtype in the Public Library of Science Pathogens (PLoS Pathogens).

Four Ebola subtypes have previously been identified—Zaire, Sudan, Cote d'Ivoire, and Reston—but only the Zaire and Sudan subtypes have been associated with large hemorrhagic fever outbreaks in people in Africa. The Ebola virus is highly contagious and is lethal in about 50% to 90% of cases.

Initial symptoms include fever, headache, joint and muscle aches, sore throat, and weakness, followed by diarrhea, vomiting, and stomach pain, according to the US Centers for Disease Control and Prevention (CDC). Some patients have both internal and external bleeding. There is no vaccine or specific treatment for the disease.

Unusual symptoms point to new species
During the 2007 outbreak, officials were puzzled because patients had unusual initial symptoms such as vomiting and others that resembled malaria, according to previous reports. Officials didn't suspect Ebola right away, because some of the early case patients didn't have external bleeding.

In late November, health officials in Uganda sent 29 blood samples from suspect patients to the CDC. Using a broadly reactive Ebola virus antigen capture assay, the lab determined that eight specimens showed evidence of Ebola infection. However, earlier real-time reverse-transcription polymerase chain reaction (RT-PCR) assays for all known Zaire and Sudan Ebola viruses and Marburg viruses had shown that the specimens were negative.

Using a less sensitive but more broadly reactive filovirus RT-PCR assay on one of the specimens, the scientists found more evidence of infection, which suggested the genetic sequence was distinct from the four known Ebola subtypes. In all, 9 of the 29 blood samples were positive for Ebola virus infection, the group reported.

Using a new metagenomics pyrosequencing method developed by 454 Life Sciences, a Roche company based in Branford, Conn., the researchers were able to rapidly sequence 70% of the virus genome to develop a draft sequence that allowed them to quickly develop real-time PCR assays specific to the new virus subtype, according to the report.

The new assays were quickly sent to the Uganda Virus Research Institute to assist with diagnosis of Ebola patients during the rest of the outbreak.

Before comparing the new subtype with other known filoviruses, the research team had to complete the entire genome of the new Ebola subtype as well as that of the Cote D'Ivoire Ebola virus. When comparing all of the species, they found that the newly discovered subtype—which they proposed naming the Bundibugyo Ebola virus—differed from the four existing types.

The investigators reported that the closest relative to the new species is the Cote d'Ivoire subtype, which shows a 32% nucleotide difference.

Unknown drug susceptibility
The group concluded that researchers who are developing vaccines against the Zaire and Sudan Ebola viruses will probably want to do cross-protection studies to determine of the vaccines can be designed to protect against the Bundibugyo subtype.

They said more studies are needed to determine the pathogenicity of the new virus and if antivirals are effective against it. According to initial findings from the outbreak, the case-fatality rate for Bundibugyo Ebola was about 36%, lower than that of the Zaire (80% to 90%) or Sudan (50% to 55%) subtypes.

Identification of the new virus highlights how quickly powerful molecular detection and characterization tools can identify new pathogens, the group wrote. However, they cautioned against solely relying on molecular techniques such as real-time PCR assays for detecting novel biodefense pathogens or conducting surveillance for emerging diseases.

Towner JS, Sealy TK, Khristova ML, et al. Newly discovered Ebola virus associated with hemorrhagic fever outbreak in Uganda. PLoS Pathog 2008 Nov;4(11) (published online Nov 21)[Full text]

See also:

Nov 21 PLoS press release
http://www.eurekalert.org/pub_releases/2008-11/plos-sdn111908.php

Dec 6, 2007, CIDRAP News story "Suspected cases rise as new Ebola strain strikes Uganda"

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