Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review

Abstract

The 2013–15 Ebola outbreak was unprecedented due to sustained transmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood. The 2013–15 Ebola outbreak has been much larger and lasted longer than any previous Ebola emergence, and is further unusual because of the thousands of survivors left behind. In 2014 the World Health Organization stated that lack of evidence made it impossible to give confident guidance about which body fluids of Ebola patients or survivors are infectious. This review summarises published evidence on presence of Ebola and the closely related Marburg virus (filoviruses) in body fluids of infected people and survivors though end July 2015. Scientific and other reports were searched for tests to detect filovirus in human body fluids on otherwise confirmed cases. 33 reports had relevant test results. Blood products were confirmed as likely to be highly infectious among actively ill cases. In actively ill patients, filovirus was often found in non-blood body fluids. However, (apart from in semen), it is rare for viable virus to be found in survivors. It is not apparent how relatively infectious most body fluids are, due to inconsistencies in testing techniques and lack of data about how much virus is present at different points of illness and recovery.