View Full Version : [Infectious Diseases] Studying “Secret Serums” — Toward Safe, Effective Ebola Treatments

Tue 9th December '14, 5:06pm
Studying “Secret Serums” — Toward Safe, Effective Ebola TreatmentsJesse L. Goodman, M.D., M.P.H.
N Engl J Med 2014; 371:1086-1089September 18, 2014 (http://www.nejm.org/toc/nejm/371/12/)DOI: 10.1056/NEJMp1409817

Ebola virus (EV), the cause of an ongoing deadly epidemic in West Africa, has been one of the world's most feared pathogens, causing catastrophic clinical disease and high mortality. Although the highest priority must be given to public health and infection-control measures that have contained past outbreaks, the current outbreak — the largest ever recorded — also highlights the need for effective treatment.

The report that two seriously ill American volunteers, Kent Brantly and Nancy Writebol, received an experimental cocktail of three monoclonal antibodies, never before administered to humans, has raised questions around the globe. Dubbed “secret serum” by the media, the treatment has generated hope, suspicion, accusations of inequity, and requests for additional product, of which, since the manufacturers provided three remaining doses to Liberia, there is now none.

The product received by Brantly and Writebol is ZMapp, containing antibodies against three EV glycoprotein epitopes, manufactured by expression in tobacco plants.1 (http://www.nejm.org/doi/full/10.1056/NEJMp1409817#ref1) The product conferred a survival benefit in infected nonhuman primates when administered 24 to 48 hours after infection1 (http://www.nejm.org/doi/full/10.1056/NEJMp1409817#ref1)and also appears to be beneficial even if started 4 to 5 days after infection, using fever and positive polymerase chain reaction as the treatment trigger2 (http://www.nejm.org/doi/full/10.1056/NEJMp1409817#ref2) — but these findings may not predict response in humans. No human safety studies were performed before the drug was administered to these two patients, whose condition reportedly improved soon after they received it. Although this report engenders hope, one cannot reach a sound conclusion on the basis of two patients' survival. Moreover, a third patient has now died despite reportedly having received ZMapp.

In addition, the likelihood that the first two recipients would have died without therapy may have been significantly less than the approximately 50% so far noted in the current epidemic. Surviving beyond the first several days of EV illness may be predictive of overall survival, as it was in the 1995 Congo outbreak. Brantly reportedly became ill 9 days before receiving the product, and Writebol may have been sick at least as long. Brantly received a transfusion from a recovered patient, for which there is conflicting evidence of effectiveness, and high-quality supportive medical care may well improve survival, an issue that merits further emphasis. Finally, mortality often decreases over the course of Ebola outbreaks, perhaps because of enhanced diagnosis and care. More detailed clinical information from these and any other patients treated may help clarify the likelihood that any improvement is attributable to the treatment.

Source: MMS: Error (http://www.nejm.org/doi/full/10.1056/NEJMp1409817)