An Ebola cloud with a silver lining

Photo shows Nowa Paye, 9, as she is taken to an ambulance after showing signs of Ebola infection. File photo

Photo shows Nowa Paye, 9, as she is taken to an ambulance after showing signs of Ebola infection. File photo   | Photo Credit: Jerome Delay

At the height of West African Ebola epidemic in 2014, the medicine chest was all but empty; no approved drug was available to facilititate treatment. With no signs of the disease abating and the fatality rate hovering around 70 per cent, the World Health Organization (WHO) in August 2014 declared that it was not unethical to use experimental medicines under the exceptional circumstances witnessed in West Africa.

The immediately available candidate therapy used before the advent of antibiotics and antivirals was transfusing plasma (the clear part of the blood) drawn from Ebola survivors into those infected with the virus. Convalescent plasma had once been used successfully to treat measles, mumps, pneumonia, influenza and diphtheria. The rationale is that the plasma taken from survivors will have antibodies (against the virus) that would fight the virus.

But the results of the first human clinical trial (published on January 7 in The New England Journal of Medicine) at the Donka Ebola treatment centre in Conakry, Guinea’s capital, have been disappointing. The passive immunotherapy did not result in a “significant improvement in survival”, which was the primary objective of the trial.

The death rate was 31 per cent of 88 patients in the treatment group compared with 38 per cent of 418 patients in the group that did not receive plasma transfusion (control). The difference shrunk even further to 3 percentage points when the researchers adjusted for other factors that affect survival like age and quantity of virus; the WHO target was 20 per cent reduction in fatality.

Trying to explain why plasma from survivors failed to save Ebola patients, Dr. Calum Semple, Senior Lecturer in Child Health, University of Liverpool, and a co-author said in an e-mail to The Hindu: “The honest answer is we just don’t know. It may be that making a good antibody response (the humoral immune response) is not the only way to survive Ebola disease and that the cell-mediated immune response is just as important.” However, there is evidence from non-human primate studies that transfusing enough quantity of the right anti-Ebola antibody does work.

One reason why the therapy failed could be because people delayed going to a health-care centre for fear of being diagnosed with Ebola. “The delay in presentation makes it less likely that any therapy will work”, Dr. Semple said.

‘Don’t write it off’

Despite the trial’s disappointing outcome, it may be premature to write off the plasma therapy. The fact that no benefit was seen “does not mean antibodies to Ebola are not going to be a good treatment”, Dr. William Schaffner, of Vanderbilt University Medical Center in Nashville, U.S., told Reuters.

The potential of passive immunity (which results when a person is given someone else’s antibodies) to prevail over viruses depends on the amount of antibodies introduced. In this case, the researchers contend that the amount of neutralising antibodies present per unit of plasma transfused might not have been sufficient enough. The correlation between antibody level and effectiveness has been seen in studies involving non-human primates.

During the trial, the level of antibodies could not be ascertained prior to transfusion due to lack of laboratory facilities in West Africa; shipping them overseas for testing would have delayed the trial.

According to Nature, stored plasma samples have now been sent to Lyon, France, to understand the correlation between antibody level and patient survival. But researchers have to wait for another Ebola outbreak to conduct the next round of trial using transfusions with higher antibody level as WHO may declare West Africa Ebola-free on January 14, provided there are no new infections.

The silver lining is that children younger than five and pregnant women, who have poor outcomes once infected, have been found to benefit the most when compared with others. However, the trial has been successful on several other counts. The plasma was found to be safe for treatment of the Ebola virus disease. More importantly, since the virus has been found in semen and in the eye long after it was cleared from the blood, researchers took great care to avoid giving plasma containing the virus.

Finally, it has been possible to conduct a trial that is “acceptable” to all stakeholders — patients, family, health-care providers and researchers.

Experimental therapy

  • A trial 'acceptable' to all stakeholders
  • Trial was conducted in Guinea, Africa, from February 17, 2015 to August 3, 2015.
  • 400-500 ml of plasma transfused on the day of the diagnosis or up to two days later.
  • Patients' survival rate recorded 3 to 16 days after plasma transfusion.
  • In survivors, live Ebola virus can persist for two months in the eye and nine months in semen after recovery.



This article has been corrected for a factual error

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Printable version | Aug 14, 2020 7:10:57 PM | https://www.thehindu.com/opinion/An-Ebola-cloud-with-a-silver-lining/article13992072.ece

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