The WHO just released the latest statistics on what has turned into the largest ever outbreak of Ebola virus (EBOV) in Africa. The epidemic started in Guinea around December 2013.
CDC director has expressed confidence that health officials will be able to contain the spread of the virus in the U.S.
– Ref. ii
As of 7/27/2014, Guinea, Liberia, Nigeria, and Sierra Leone have reported a total of 1323 cases, with 729 fatalities [i]. Most patients are from Guinea and Sierra Leone. The 1 Nigerian case was an international traveller, a major concern as the epidemic unfolds and drastic containment measures are taken by the countries affected.
Since first posted here, things have worsened considerably. As of Sept. 28, 2014, there were 7157 cases and 3330 deaths from the epidemics. This is more than twice the count from only 1 month earlier (Aug 26, 2014) when a total of 3069 cases and 1552 deaths were reported.
As the first case has now been diagnosed in the US, we can observe first hand how successfull our hospital system is in managing Ebola, and how successful we are in tracing contacts. I wish our representatives from CDC and NIH were a little bit less self-assured when they proclaim on TV that we are not likely to see Ebola gaining a foothold in the US, that spread of the disease in the US is highly unlikely.
Why should we have a lot of respect for the ingenuity of the Filovirus family?
Reason #1: they have survived and outfoxed us a few times already;
Reason #2: our state of blissful ignorance: we just know so little about their survival strategies and virulence factors;
Reason #3: the early disease symptoms are fever and non-specific signs/symptoms. Hence, by the time we can suspect infection and quarantine a potential case, it’s already too late.
EBOV GP glycans direct the immune system to produce antibodies against highly variable or dispensable regions on the viral surface
Ref: J. Cook. PLoS
Below a table of major virologic and clinical facts relating to Ebola virus infection. Some therapeutic approaches are mentioned without any claim of completeness.
| Category | Core Facts |
|---|---|
| Epidemiol | Named after Ebola river in Zaire where the first documented outbreak occurred (in 1976) |
| Epidemiol | Almost all outbreaks in sub-Saharan Africa |
| Epidemiol | Reservoir unknown |
| Epidemiol | Infection through direct contact with body fluids (blood, organs, secretions, breast milk) of infected animals (monkeys, other) or humans |
| Epidemiol | Vector unknown (bats?) |
| Epidemiol | Close personal contact and Iatrogenic spread = major contributing factors |
| Virology | Lipid-enveloped filovirus with neg. strand RNA; 7 genes, 19 kb |
| Virology | Cell attachment via GP transmembrane glycoprotein |
| Virology | Viral cell entry via the Nieman-Pick NPC1 receptor, a cholesterol transporter protein |
| Pathogenesis | Immune response impaired and late |
| Pathogenesis | Envelope glycoprotein GP1 helps evade host immune responses |
| Pathogenesis | Essential adherence factor masked by ‘mucin shield’ from neutralizing abs |
| Pathogenesis | Secreted GP antigens trap virus-directed antibodies |
| Clinical | Mortality 80-90% (the Zaire strain has the highest mortality) |
| Clinical | Initially flu-like syndrome, later hemorrhagic fever with DIC and organ failure (liver, kidney) |
| Clinical | Coagulopathy occurs early but findings are usually subtle (conjunctival hemorrhage) |
| Clinical | Labs: leukopenia, thrombopenia, abnl LFT |
| Clinical | PCR of viral RNA = best tool |
| Clinical | Virus can persist in semen for 3 months after recovery |
| Therapy | Current therapy is non-specific / supportive |
| Therapy | Vaccines and Therapeutics in Phase 1 testing: |
| Therapy | Adeno-vector |
| Therapy | NPC1 attachment inhibitors - Benzylpiperazine adamantane diamide derivatives, |
| Therapy | DNA plasmid vaccine (VRC-EBODNA023-00-VP, VRC-EBODNA012-00-VP) |
| Therapy | Phosphorodiamidate morpholino antisense oligomer (AVI-6002) - Sarepta Therapeutics |
| Therapy | Interrupting PI3K-Akt/Rac1 signaling pathway |
| Therapy | RNAi (interfering RNA) (TKM-300803) – Tekmira, a lipid nanoparticle formulation was protective in monkey models and given FDA Fast Track status; put on hold in 2014 to clarify issues related to cytokine release |
| Other | Bioterrorism agent |
References:
M Salvaggio. Other viral bioweapons: Ebola and Marburg hemorrhagic fever. Dermatol Clin 22 (2004) 291 – 302
Cote. Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebolavirus infection. Nature 2011; 477: 344
J. Cook. The Secret Life of Viral Entry Glycoproteins: Moonlighting in Immune Evasion. PLoS Pathog 9(5): e1003258. doi:10.1371/journal.ppat.1003258
[i] http://www.afro.who.int/en/clusters-a-programmes/dpc/epidemic-a-pandemic-alert-and-response/outbreak-news/4236-ebola-virus-disease-west-africa-29-july-2014.html
[ii] http://www.politico.com/story/2014/10/ebola-us-border-111581.html#ixzz3F72LYrCE
