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Sunday, 3 August 2014

Ebola VIrus Disease

The WHO Ebola Response Team have reported in the September 23 issue of the New England Journal of Medicine their analysis of 3343 confirmed and 667 probable Ebola cases collected up to September 14 in 4 of the 5 West African countries to have experienced cases of Ebola Virus Disease: Guinea, Liberia, Nigeria, and Sierra Leone. They report a typical age range of 15-44 years with no difference in gender of those affected. Their estimate of case fatality rate is higher than that noted by the Centers for Disease Control at 71% for people for whom the outcome their infection is known. Based on the number of cases to date, from this they estimate a 95% confidence interval [CI] of 69 to 73% for mortality risk.  They note that features of the disease, including a typical incubation period of 11 days to be similar to that for  previous outbreaks. Based on the initial periods of exponential growth of the outbreaks, they have modelled the doubling times are EVD to be 16 days for Guinea, 24 days for Liberia, and 30 days for Sierra Leone, with by November 2 the cumulative reported numbers of confirmed and probable cases predicted to be "5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone", i.e. over 20,000 total cases for this EVD epidemic.
The current Ebola outbreak is the largest to date, now affecting 4 West African countries: in Guinea, Liberia, Sierra Leone and Nigeria. A further outbreak in the Democratic Republic of Congo is considered due to a separate, independent outbreak in the DRC (reported 24 suspected cases and 13 reported DRC suspected Ebola deaths to July 28 - August 28, 2014 (and to 9th September 65 suspected cases, 32 attributed deaths and 14 laboratory confirmed cases).
Risk factors include high fever with or without associated Ebola features (see below) in people from epidemic regions, and in those who have been in contact with Ebola cases, including funeral and burial related, and in those who have prepared or eaten affected bush meat. Key public health measures in unaffected countries include health questionnaires and non-invasive temperature recording at national or remote air, land, water ports of entry.
Ebola virus disease is caused by any of 4 subtypes of the thread-like Ebola RNA virus. EVD causes a
Ebola virion CDC Public Health Image Library
systemic illness in humans associated with bleeding and multi-organ failure (Ebola haemorrhagic fever). The disease was first identified around 40 years in Sub-Saharan Africa and is named after the river Ebola north of Yambuku, in what was then called Zaire, now the Democratic Republic of Congo. Mortality may be as high as 90%, highest with the Zaire strain of the virus, mortality reduced when effective supportive treatment is provided. 
Up to late July 2014, there had been around 3800 cases, with overall reported mortality of
Based on CDC reports
around 61%,
in reported outbreaks over the past 4 decades, including the current West African outbreak.
In the current outbreak, 1400 cases had been reported up to July 2014 and 1848 cases (1013 deaths) up to 9 August 2014 (4253 cases reported from 1976 to 9th August). A CDC update on West African cases to 22 August from the Centers for Disease Control and Prevention in Atlanta USA reports 2615 suspected cases, 1427 suspected case deaths and 1528 laboratory confirmed cases. A further CDC update to 28th August reported a suspected and confirmed case count: 3069; suspected case deaths: 1552; and laboratory confirmed cases: 1752 in 4 West African countries: Liberia, Guinea, Sierra Leone and Nigeria. One case in a patient from Guinea has been reported from Senegal, with no further cases reported there since August 29, and no further cases reported from Nigeria since September 5.
A further update from the CDC to September 18 notes an increase to a total case count of 5347, total deaths 2630 (laboratory confirmed cases 3095).
The reported mortality rate in the current outbreak was 55% both to August 9 and to August 22, and 51% to 28 August and 49% to September 18, lower than the 66% cumulative mortality rate prior to the current epidemic. Reported mortality appears to vary widely in currently affected countries. This may reflect local differences in presentation for treatment and in disease management, but may also be in part spurious due to uncertainty in case-finding ascertainment.
Ebola virus is one of several viruses, rickettsial, treponemal and other bacterial infections, and non-infectious conditions which may cause serious haemorrhagic illnesses (associated with bleeding internally and into the skin), presenting with a similar spectrum of symptoms, clinical signs and laboratory abnormalities. In the body the ebolavirus targets the lining cells of blood vessels (endothelial cells), white blood cells and liver cells (hepatocytes).
The incubation period can be short, as rapid as 2-3 days after exposure to the virus, either from animal hosts or after contact with infected blood or other human bodily fluids. Typical incubation is reported to be around 8-10 days, in some cases up to 3 weeks before an initial 'flu'-like syndrome. Around half of the affected patients develop a flat and raised (maculo-papular) rash. It has been reported that survivors of the illness may continue to carry the virus for up 2 months after the infection.
Animal vectors of the virus are thought to include the fruit bat (without developing clinical signs). Other animal hosts (through eating fruit contaminated by fruit bats) may include non-human primates, duikers (small antelopes) and pigs.
Treatment should involve a wide range of health professionals, from acute care doctors and nurses, to experts working in laboratory diagnostic services, and public health officials who have an important role in contact tracing and containment of the disease. Care needs to include effective protective clothing for health professionals, disinfection, avoiding re-use of needles, isolation of affected patients, and quarantine.
Current approaches to treatment are supportive, from effective isolation, to monitoring for biomarkers of target organ damage, maintaining fluid and electrolyte balance, if needed, providing oxygen, treating secondary infections, and providing organ support in the event of failure of major organs, often kidneys and liver.
Acquiring effective anti-ebola drugs and vaccines are the subject of current R & D efforts. 
Specific anti-viral treatments, combined with rapid point of care tests, need to be developed, with the aim of achieving medicines which are effective and safe for prophylaxis as well as for treating all stages of the disease. In view of the very high mortality of the disease, new approaches to clinical trials need to be considered. Experimental treatments have been reported to be effective in animal models but not yet tested in humans (see below for compassionate use access to experimental treatments).
An effective vaccine is also a priority, with promising developments of candidate vaccines in recent years. Vaccine programmes will need to take into account the possible development of new Ebola viral strains over time - early September said to have been the start of human clinical testing of a vaccine to prevent the disease and November the estimated start date for clinical trials.

See information on Ebola virus infection from the Centers for Disease Control and Prevention

Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430 Nature April 2014

Ebola virus vaccines: an overview of current approaches

Compassionate use provision to Liberia of experimental antibody-based anti-Ebola treatment 

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