Introduction
Ebolaviruses and Marburg virus (MARV) belong to the viral family Filoviridae and can cause severe haemorrhagic fever in humans and non-human primates. Filoviruses are filamentous, negative-sense RNA viruses, with a genome that encodes seven structural proteins: nucleoprotein (NP), polymerase cofactor (VP35), matrix protein (VP40), glycoprotein (GP), replication-transcription protein (VP30), minor matrix protein (VP24) and the non-structural protein RNA-dependent RNA polymerase (L) (figure 1).1 The virus family Filoviridae is divided into three genera, Ebolavirus, Marburgvirus and Cuevavirus. Within the ebolavirus genus are five species: Zaire ebolavirus (EBOV), Sudan ebolavirus (SUDV), Bundibugyo ebolavirus, Tai Forest ebolavirus (TAFV) and Reston ebolavirus. The marburgvirus genus consists of Marburg marburgvirus (MARV), including the MARV POPP, MARV Angola, MARV Durba, MARV Ozolin and MARV Musoke variants, and Ravn virus.2 3
Since the first report in Sudan and Zaire in 1976, ebolavirus disease (EVD) has caused more than 30 outbreaks in the subsequent 40 years (figure 2). EVD is a lethal illness with an average case fatality rate of 78%. Marburg virus disease (MVD) was first identified in 1967 during epidemics in Marburg and Frankfurt in Germany and Belgrade in the former Yugoslavia from the importation of infected monkeys from Uganda.4 Similar to EVD, MVD has a very high case fatality rate, measuring just over 80% in some of the most recent outbreaks.
Sporadic outbreaks of EVD and MVD typically occur and are limited to countries in sub-Saharan Africa.4 However, in 2014, an outbreak of EBOV was detected in rural Guinea, near the border of Liberia and Sierra Leone, resulting in 28 616 total cases of EVD and 11 310 deaths in 10 countries, with a mortality rate between 30% and 70% in Guinea, Liberia and Sierra Leone by 2016.5 The most recent outbreak is located in the Democratic Republic of Congo, with 137 total cases, 106 confirmed cases and 92 deaths (61 confirmed) reported as of 12 September 2018.6
The fruit bat is thought to be the native host for filoviruses (although this has not been definitively demonstrated for ebolaviruses),7 with a large ecological reach ranging from West and Central Africa to Southeast Asia.8–13 Reports show a seasonality in filovirus transmission to humans that may correspond with mating and birthing seasons of fruit bat species.14 15 Primates and other animals can also be infected and suffer disease, although their ability to serve as a reservoir for filoviruses is unknown.9
Filoviruses are primarily transmitted to humans through close contact with blood, secretions, organs, or other bodily fluids of infected humans or animals.8 15–17 They are commonly spread among family and friends of infected individuals, although nosocomial transmission, especially among healthcare workers, occurs.18 As seen in the 2014–2016 ebolavirus outbreak, an increase in population size, the rise of urbanisation and the interconnectedness of travel can expand the spread of filovirus disease beyond endemic regions.19 Isolation of patients, proper use of personal protective equipment (PPE) and disinfection procedures have been effective in reducing human-to-human transmission of EBOV and MARV.16
The incubation period for EVD and MVD is between 2 and 21 days, with an average of 3–10 days.8 Both ebolaviruses and MARV can be clinically detected in blood after onset of fever, which accompanies the rise in circulating virus within the patient’s body and remains elevated in individuals who progress to death, especially among those with EVD.20
Treatment options for EVD and MVD are limited and rely on supportive therapy.8 21 While there are no proven effective drug treatments for EVD or MVD, experimental therapies (ZMapp, brincidofovir, TKM-Ebola and favipiravir) were used during the 2014–2016 ebolavirus outbreak to treat infected patients.21 22 A number of EVD pharmacotherapies and immunological-based agents have been or are currently undergoing accelerated human trials in EVD endemic countries, including favipiravir and ZMapp; some may also be effective for MARV (although ZMapp is specific to ebolavirus).21–23
Two of the most promising EBOV vaccine candidates, rVSV-EBOV and ChAd3-EBO-Z, underwent phase II/III efficacy trials in Liberia, Sierra Leone and Guinea during the peak of the 2014–2016 epidemic, showing high efficacy and long-term antibody responses.24–26 Vaccines for MARV have not seen a similar accelerated development to EBOV, although animal and early clinical studies show potential for MARV vaccine immunogenicity and protection.2 27 28
Due to the sporadic nature of outbreaks, high mortality rates and potential spread from rural to urban regions, filoviruses are some of the high-priority pathogens identified in the WHO R&D Blueprint,29 a global strategy and preparedness plan to strengthen the emergency response to highly infectious diseases. To catalyse diagnostic development for filoviruses, the Foundation for Innovative New Diagnostics (FIND, www.finddx.org) has launched initiatives for needs assessment and partnerships across a broad range of diseases in endemic-prone countries. This landscape analysis describes the current state of filovirus diagnostics, and identifies remaining needs for further research and development.