The Use of TKM-100802 and Convalescent Plasma in 2 Patients With Ebola Virus Disease in the United States

Abstract

It is unclear what role the experimental drug and convalescent plasma had in the recovery of these patients. Prospective clinical trials are needed to delineate the role of investigational therapies in the care of patients with EVD.

Post-exposure treatments for Ebola and Marburg virus infections

“…The importance of advanced supportive care, including electrolyte balance, ventilation and dialysis, was likely pivotal in the successful treatment of individuals infected with EBOV in developed countries during the recent EBOV epidemic 32,[125][126][127]148,149,188,217,218 . Only two of the twelve patients with EBOV (17%) treated in the USA during this epidemic (two imported cases, two infections identified in the USA and eight medically evacuated patients) died.…”

“…Although convalescent blood products were used in repatriated patients with EBOV infection during the 2013-2016 outbreak, those patients also received other experimental therapies and advanced supportive care, thus confounding interpretation of therapeutic benefit [124][125][126][127] . Furthermore, host rejection is a risk -acute respiratory distress was reported in a healthcare worker in Spain and was attributed to treatment with convalescent plasma 126 .…”

“…During the early part of the 2013-2016 EBOV epidemic, TKM-100802 was administered to five patients infected with EBOV who were medically evacuated to Europe and the USA and to one individual as post-exposure prophylaxis 127,146,156,157 . Because the patients were also treated with other experimental products and received advanced supportive care, it was not possible to assess the effectiveness or safety of TKM-100802 in this setting.…”

Tackling emerging infections: clinical and public health lessons from the West African Ebola virus disease outbreak, 2014–2015

“…Detailed case reports of repatriated health workers support the use of invasive ventilation for pulmonary oedema and renal replacement therapy for acute renal failure, although these will not be available in many resource-limited settings. [17][18][19][20] Inferences on the efficacy of interventions from observational data are limited by selection bias and confounding from external factors, such as health-seeking behaviour and internal factors, such as human resources, which varied between Ebola care facilities and over time. Randomised controlled studies of specific interventions are still lacking despite efforts to improve this and it is a shame that the opportunity to systematically study simple interventions, such as intravenous hydration was missed.…”

Ebola virus disease and the search for a cure

“…The infectious disease specialists worked on the treatment of the virus, health care worker protection, equipment decontamination, and investigational new drug applications for the Food and Drug Administration 5 . In addition to the optimized supportive care, the patients admitted to the University of Nebraska Medical Center received several investigational drugs as compassionate use through the FDA: convalescent plasma, small interfering RNA nanoparticles, polymerase inhibitors, and monoclonal antibodies 7,8 . The problem with uncontrolled administration of investigational drugs is that inferences about the effects of these potential therapies are very difficult to make since many factors can contribute to the survival or demise of these patients with EVD: patients' own immune system, quality of supportive care, and effects of specific investigational drugs 7 .…”