Healio
Healio
Issue: November 2015
ByDonald Kaye, MD, MACP
ByJack P. Woodall, PhD
November 19, 2015
7 min read
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Why didn't Ebola just go away this time? Plus other issues ...

Issue: November 2015
ByDonald Kaye, MD, MACP
ByJack P. Woodall, PhD

The world became aware that there was an Ebola outbreak in West Africa when the first confirmed cases were identified in southeastern Guinea on March 23, 2014, and within 1 week more cases were confirmed in neighboring Liberia. Ho-hum was the reaction — a nasty, scary disease, with only a single case previously reported from West Africa, so it would soon be over like all other Ebola outbreaks in Central and East African forests. There have been many Ebola outbreaks in Gabon since 1994 in bushmeat hunters and funeral attendees, but they never reached the capital. An outbreak in late 2014 in the Democratic Republic of the Congo ended after 3 months and only 66 recorded cases.

However, this time it did not fizzle out, but spread like wildfire, reaching the capitals of Guinea, Sierra Leone and Liberia. Cases were exported to Nigeria, Mali, Senegal, the United States, Europe (Italy, Spain and United Kingdom) and to India, creating a worldwide panic. The outbreak spread for multiple reasons, including lack of basic infection control in hospitals, traditional burial rites, belief in witchcraft and distrust of health officials and their motives, among others.

In retrospect, the index case is suspected to have been a child playing with an infected bat in the Guinea rainforest in December 2013. Forest bats are known to be one of the wildlife reservoirs of Ebola virus in equatorial Africa. WHO declared the outbreak a Public Health Emergency of International Concern on Aug. 8, 2014 after a teleconference of the Emergency Committee convened under the revised International Health Regulations, or IHR (2005). The months-long delay was due to concerns about the negative impact on tourism and commerce in the region, rapidly confirmed by the unilateral suspension of most international flights and other interruptions to trade.

Jack Woodall, PhD
Jack Woodall

WHO has been unfairly criticized for not responding adequately to the Ebola epidemic. However, the organization was never set up or staffed to deal with outbreaks other than to give the best advice for dealing with them and other health problems. It had always relied on the CDC to send experts to the field to respond to epidemics when a country requests assistance, and the CDC has always reacted expeditiously, as it did again this time. Other UN agencies exist to deal with emergencies and disasters, with their logistics and air support, and they weighed in later in the form of the UN Mission for Ebola Emergency Response (UNMEER), established on Sept. 19, 2014. The UN has not been criticized for closing UNMEER on July 31, before the end of the epidemic, while WHO, severely criticized for an inadequate response, has staff still on the ground.

The epidemic in Liberia peaked in late summer and early fall of 2014, when more than 200 confirmed and probable cases were reported each week. Then cases declined rapidly and in May, when there had been no more cases reported for weeks, WHO declared Liberia free of Ebola. Unhappily, six new cases appeared, so the countdown began again until WHO declared Liberia free of Ebola for the second time on Sept. 3.

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Sierra Leone was counting down to Ebola-free status when five more cases appeared, starting on the last day of August. Also worrying is a case in a teenage girl in an area that had been free of the disease for 24 weeks; sexual transmission from a survivor is the suspected route. The difficulty in eliminating Ebola in these countries is that some contacts have been lost to tracing, some cases are still being covered up and their bodies buried unsafely, and other cases of suspected sexual transmission by survivors have occurred. Ebola cannot be eradicated from West Africa given the presence of the virus in wildlife, killed for sale as bushmeat.

Donald Kaye, MD
Donald Kaye

By mid-September, the weekly rate of new cases in the region had slowed down to single-digit figures. Official numbers for the outbreak supplied to WHO were: more than 15,000 laboratory confirmed, 2,600 probable and 10,000 suspected cases, with a cumulative total of more than 28,000 cases and 11,000 deaths (crude mortality rate, 40%). The mortality rate is half of the approximately 90% recorded in the first Ebola epidemic in 1976, following recent improvements in supportive treatment. It must be remembered that initially, lab capacity was not adequate to test every case, so many cases and deaths were likely due to clinically similar endemic diseases such as Lassa fever, yellow fever, severe malaria, typhoid and others. But a shocking statistic is that as of Sept. 13, 881 doctors, nurses, other health care staff and burial workers have been infected, and 513 (58%) died from the disease. These numbers resulted from the failure to use personal protective equipment correctly or through contamination by the blood or other liquids from cases they attended of childbirth or other conditions not suspected of being due to Ebola. Health care workers affected by Ebola were mostly Africans; only a few of the hundreds of international volunteers from countries outside Africa acquired the disease, and just two of those who were repatriated died, including a Sierra Leonean doctor, who was legally a resident in the U.S., and a Spanish missionary. But Liberia had only about 60 doctors for its entire population of 4.7 million before the epidemic, and the country lost a number of its high-profile and most competent medical professionals. Health workers are 20 to 30 times more likely to be infected with Ebola than the general adult population.

But apart from the Liberian who arrived symptomless in Texas, fell ill and died from Ebola after infecting two nurses (but none of his close housemates), only those two expatriate health workers died after being repatriated.

While neither the Liberian hospitalized in Texas nor an American doctor who fell ill in New York after returning symptomless from treating Ebola patients in West Africa had transmitted the virus to their female sex partners while they were incubating the disease, the virus has been cultured from the semen of survivors more than 6 weeks after clinical cure, and viral RNA has been found many months later. Furthermore, there is mounting circumstantial evidence of transmission by semen months after recovery.

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Post-Ebola syndrome

A worrying development in West Africa is the increasing incidence of visual problems and blindness (reversible with early treatment) in Ebola survivors, as well as physical complaints and neurological symptoms in about half of the thousands of survivors. One of the two nurses infected in Texas also has noted multiple symptoms. Ebola viral RNA has been detected in the vitreous humor of the eye but not in the conjunctiva or tears, and in semen samples of survivors months after recovery, which was suspected as the mode of transmission to a number of women who had no known contact with active Ebola cases.

Vaccines

Several candidate Ebola vaccines are in trials in West Africa and other countries. One already in use in the field is rVSV-ZEBOV, developed by the Public Health Agency of Canada’s National Microbiology Laboratory in consultation with the NIH and WHO and funded by the U.S. Defense Department. The vaccine initially was licensed to NewLink Genetics, and in 2014, the vaccine was licensed to Merck. Vaccination of volunteers by the U.S. Army and clinical trials in Gabon, Kenya and Germany started in late 2014. In March 2015, a trial of front-line health care workers began in Guinea, and ring vaccination for contacts of confirmed Ebola cases now has been extended in Sierra Leone for 200 close contacts of the cases that surfaced in September.

rVSV-ZEBOV is constructed by attaching a Zaire ebolavirus protein, which produces antibodies to the virus but does not cause disease, to the coat of vesicular stomatitis virus, a livestock virus that multiplies in humans but is not associated with human infection. Another vaccine, developed by GlaxoSmithKine, uses the same idea but with a nonhuman-pathogenic chimpanzee adenovirus, and is being tested in a trial in Liberia. Other vaccines are under development in China, Russia, the U.K. and the U.S.

Drugs and therapy

Several drugs have shown anti-Ebola virus activity. ZMapp (U.S.) is a cocktail of three antibodies produced in tobacco plants, credited with helping to cure one of the first American doctors to become infected, but failed to save the lives of a Spanish missionary and a Liberian doctor. It was withdrawn from field trials in West Africa when the number of cases began to decline, but is now being produced by molecular methods in fermenters. ZMapp has been granted fast track status by the FDA. TKM-Ebola (Canada) is an RNA interference drug that blocks replication of the Ebola virus. Favipiravir (Japan) is an RNA polymerase inhibitor developed as an influenza drug, which also blocks replication of the Ebola virus.

A European Union-funded trial of convalescent plasma therapy in more than 100 patients, headed by the Institute of Tropical Medicine in Antwerp, Belgium, was conducted between February and July in Conakry, Guinea, by researchers from Médecins Sans Frontières. Results are pending. Two of 20 drugs shortlisted globally by Public Health England for development have been selected for funding. Code named NCK-8 and D-LANA-14, they are lead candidates from two classes of peptide mimics (a molecule global researchers have created to fight the virus) with high activity against a range of multidrug-resistant bacteria and malarial parasites, including clinical isolates.

  • For more information:
  • Jack Woodall, PhD, is the co-founder and associate editor of the International Society of Infectious Diseases’ ProMED-mail and director of the Nucleus for the Investigation of Emerging Infectious Diseases, Institute of Medical Biochemistry, Center for Health Sciences, Federal University of Rio de Janeiro, Brazil (retired).
  • Donald Kaye, MD, is a professor of medicine at Drexel University College of Medicine, associate editor of ProMED-mail, section editor of news for Clinical Infectious Diseases and an Infectious Disease News Editorial Board member.

Disclosures: Kaye and Woodall report no relevant financial disclosures.