A deadly Disease  Solon, the sage of Athens, argued that one couldn't judge a person's happiness until one knew the manner of his death.  The Greeks recognized that we're all destined to die and that the best we can hope for is a death that benefits our family or humanity.  NEJM -9/25/2014- Josh Mugele

EVD  “The Ebola outbreak that is ravaging West Africa. More than 400 health care workers in West Africa have been infected with Ebola during the current outbreak, and 233 had died as of 10/8.  More than 8,900 people in Guinea, Liberia, Nigeria, Senegal and Sierra Leone have contracted Ebola since March, according to the World Health Organization, making this the biggest outbreak on record. More than 4,400 people have died.

Ebola cases in health care workers in West Africa Source: WHO 416 Infected Blue 233 Deaths( red) Health Workers infected and Mortality

Numbers of Confirmed and Probable Ebola Cases Reported Weekly from Guinea, Sierra Leone, and Liberia from December 23, 2013, to August 11, Briand S et al. N Engl J Med 2014;371:

Districts Affected by Ebola Virus Disease in Three Countries in Africa. WHO Ebola Response Team. N Engl J Med DOI: /NEJMoa

Public Health Crisis  Public health interventions including characterizing the outbreak epidemiology, contact tracing, social mobilization, and public education are essential steps in stopping Ebola and will ultimately save many more lives than can be saved by individual patient care.  The high mortality associated with Ebola, however, threatens the ability to perform many of these tasks.  NEJM 9/2014 Lamontagne F

Structure of Ebolavirus. Feldmann H. N Engl J Med DOI: /NEJMp

Filoviridae  Ebola is caused by infection with a virus of the family of Filoviridae genus Ebolavirus.  There are five identified Ebola virus species, four of which are known to cause disease in humans: Ebola virus (Zaire ebolavirus); Sudan virus (Sudan ebolavirus); Taï Forest virus (Taï Forest ebolavirus, formerly Côte d’Ivoire ebolavirus); and Bundibugyo virus (Bundibugyo ebolavirus). The fifth, Reston virus (Reston ebolavirus), has caused disease in nonhuman primates, but not in humans.

Transmission  The Ebola virus infects cells by attaching itself to the cell receptor, punching into the cell membrane and injecting a viral RNA in the cytoplasm.  The RNA instructs the nucleus DNA to make viral copies using the cell machinery. The new copies of the Ebola virus are released into the blood stream to infect other cells. The virus can be found in all body fluids and skin.

Ebola Virus Disease  Fatal cases were associated with severe abnormalities of liver and kidney function, marked CD8 lymphocytopenia and elevated plasma levels of several cytokines and chemokines (IL-1 , IL-1RA, IL-6, MCP-1, MCSF and MIP-1  ).  Higher levels of sCD40L were seen in patients who survived compared with those who died. (sCD40L is a member of the TNF superfamily that has prothrombotic and pro-inflammatory activities.)

Ebola Virus Disease  In transgenic mice, I-  B  -mediated blockade of  NF-  B-activation had no effect on the increase in pro- inflammatory cytokines in plasma or in the four target organs, but biomarkers of endothelial activation (ICAM- 1,VCAM-1) in these organs were reduced.  As a result, multi-organ failure did not develop and survival improved. Thus, blockade of NF-  B activation preserved endothelial barrier integrity, demonstrating that endothelial cells were the targets, not necessarily the origin, of sepsis-induced inflammation.

Clinical symptomes  “ EVD presents much as many other viral infections do, with nonspecific signs such as fever, asthenia, body aches but a rash.  After a few days, however, the predominant clinical syndrome is a severe gastrointestinal illness with vomiting, hematemesis and diarrhea.  Volume depletion with a range of metabolic disorders ensues, and hypovolemic shock ultimately occurs”. 

Ebola Virus Disease  Evidence of endothelial activation (elevated levels of sICAM) was observed in those with hemorrhagic disease, and abnormal elevations in biomarkers of coagulopathy (thrombomodulin, Ddimer) were seen in those who died.  These observations of endothelial dysfunction and coagulopathy confirm the findings of other studies of clinical EVD and experimental Ebola virus infection of non-human primates. Moreover, similar findings are seen in experimental and human sepsis.

Diagnosis /Treatment  Blood test to detect the Virus ( Elisa, Western blot)  No treatment available  In US Zmapp a cocktail of Antibodies

Transfusions  WHO issued new interim guidance on "Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion during outbreaks".  The document is addressed to national health authorities and blood transfusion services.

Fluid Ressucitation is Key  Intravenous catheters, fluids, and electrolyte replacement are readily available but thus far are being used much too sparingly.  When patients can no longer drink, placement of an intravenous catheter and delivery of appropriate replacement solutions are required, but we have seen many critically ill patients die without adequate intravenous fluid resuscitation

Recovery  Recovery from Ebola depends on good supportive care and the patient’s immune response. People who recover from Ebola infection develop antibodies that last for at least 10 years, possibly longer.  Do not know people who recover are immune for life or if they can become infected with a different species of Ebola. Some people who have recovered from Ebola have developed long- term complications, such as joint and vision problems.

International Aids  Medecins Sans Frontieres  Chinese Field Hospitals  US Military- CDC  French active in Guinee  Partners in Health  Cuban Doctors are in fields  Russian and British group

For more Info  Centers for Disease Control and Prevention a  CDC latest advice focus on PPE  With no skin exposure