Thursday, January 07, 2016

NEJM: Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea

Credit Wikipedia


Over the years we've looked at a number of attempts to use convalescent plasma - donated by survivors of H5N1, H1N1, H7N9, SARS and most recently MERS and  Ebola - to treat infected patients.

Results have been mixed, but they’ve reported some success along the way.

Although in limited use today, human and animal serum therapy was used extensively during the first half of the 20th century to treat a variety of infectious diseases, including anthrax, scarlet fever, measles, tularemia, diphtheria and rabies.

While often effective, a relatively high percentage of adverse reactions (serum sickness) along with the development of effective antibiotics and drugs, has seen its use decline.

But with a new crop of deadly infectious diseases - with few, if any therapeutic options - convalescent serum is getting a new life.

Earlier this summer we saw Korea Trying Convalescent Serum Treatment For MERS  and,  while in 2011 we saw a study (see CID Journal: Convalescent Plasma Therapy For Severe H1N1) that found a substantial drop in mortality among  hospitalized patients in Hong Kong who received the treatment.

Over the past year there have been several small clinical trials using convalescent plasma conducted in Western Africa for treating Ebola and several Ebola patients in the United States received convalescent blood products as well.

While hopes have run high for this type of treatment, late yesterday the NEJM published the results of the first clinical trial of convalescent plasma therapy from the West African Ebola outbreak, and the results are disappointing:

Of 84 patients treated in this clinical trial, no statistically significant improvement in survival was noted over the control group.

There were limitations to this study, not the least of which was an inability to determine the level of antibodies in the donor plasma due to a lack of a BSL-4 lab in West Africa.  It may well be that a serum containing a higher level of antibodies would produce a better result. 

First a link to the NEJM report, then a link to Lisa Schnirring's excellent review on CIDRAP News. 

Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea

Johan van Griensven, M.D., Ph.D., Tansy Edwards, M.Sc., Xavier de Lamballerie, M.D., Ph.D., Malcolm G. Semple, M.D., Ph.D., Pierre Gallian, Ph.D., Sylvain Baize, Ph.D., Peter W. Horby, M.D., Ph.D., HervĂ© Raoul, Ph.D., N’Faly Magassouba, Ph.D., Annick Antierens, M.D., Carolyn Lomas, M.D., Ousmane Faye, Ph.D., Amadou A. Sall, Ph.D., Katrien Fransen, M.Sc., Jozefien Buyze, Ph.D., Raffaella Ravinetto, Pharm.D., Pierre Tiberghien, M.D., Ph.D., Yves Claeys, M.Sc., Maaike De Crop, M.Sc., Lutgarde Lynen, M.D., Ph.D., Elhadj Ibrahima Bah, M.D., Peter G. Smith, D.Sc., Alexandre Delamou, M.D., Anja De Weggheleire, M.D., and Nyankoye Haba, M.Sc. for the Ebola-Tx Consortium

N Engl J Med 2016; 374:33-42January 7, 2016DOI: 10.1056/NEJMoa1511812


A total of 84 patients who were treated with plasma were included in the primary analysis. At baseline, the convalescent-plasma group had slightly higher cycle-threshold values and a shorter duration of symptoms than did the control group, along with a higher frequency of eye redness and difficulty in swallowing. From day 3 to day 16 after diagnosis, the risk of death was 31% in the convalescent-plasma group and 38% in the control group (risk difference, −7 percentage points; 95% confidence interval [CI], −18 to 4). The difference was reduced after adjustment for age and cycle-threshold value (adjusted risk difference, −3 percentage points; 95% CI, −13 to 8). No serious adverse reactions associated with the use of convalescent plasma were observed.

From CIDRAP News:

Ebola studies pan convalescent plasma, find hope for malaria regimen

Lisa Schnirring | News Editor | CIDRAP News
 | Jan 06, 2016
In a pair of new studies on Ebola treatment, a trial of convalescent plasma at a treatment center in Guinea didn't find a significant survival benefit, while patients at a Liberian treatment unit unexpectedly seemed to benefit from a malaria drug combo clinicians gave in response to a drug shortage.

Both studies were published today in the latest online edition of the New England Journal of Medicine (NEJM), alongside a shorter report on gender differences during the Ebola outbreak, such as higher survival rates in female patients.

(Continue . . . )

While this particular trial did not produce the desired results, the idea of using convalescent serum to treat emerging infectious diseases like MERS, avian flu, and Ebola is far from dead. For some earlier blogs on the use of convalescent therapy, you may wish to revisit:

Int J Infect Dis: Convalescent Plasma Treatment Of An H7N9 Patient In China

JVI: Investigating Dromedary Immune Serum As MERS-CoV Treatment

MERS-CoV: The Long Road To A Pharmacological Solution