Emerging Infectious Diseases

Ebola and Marburg

Ebola disease and Marburg disease are caused by the Ebola and Marburg filoviruses. Six species of the genus Ebolavirus have been identified: Zaire (EBOV), Bombali, Bundibugyo, Reston, Sudan, and Taï Forest; the genus Marburgvirus contains Marburg virus and Ravn virus. Bats are known reservoirs of the Marburg virus and suspected reservoirs of Ebola viruses. Human outbreaks begin following exposure to blood or secretions of infected animals, such as fruit bats, gorillas, and monkeys. Once introduced into the human population, human-to-human transmission primarily occurs through contact with virus-infected bodily fluids. Their symptoms are similar and may include fatigue, headache, dizziness, vomiting and diarrhoea, and, in severe cases, haemorrhage, organ failure and shock. Ebola’s average case fatality ratio is around 50%, but can vary between 25% and 90%.

Since 1976, there have been 27 known African Ebola outbreaks, 11 of which were in the Democratic Republic of Congo (DRC). The largest recorded outbreak of Ebola occurred in 2013-16 in West Africa, affecting Guinea, Sierra Leone, and Liberia, causing more than 28,000 infections and 11,000 deaths (a confirmed-case fatality ratio of 63%). Between August 2018 and June 2020, there was a further outbreak focused in North Kivu, DRC, which was declared a Public Health Emergency of International Concern by the WHO in July 2019. It represents the second-largest Ebola epidemic on record, with more than 3,400 infections and 2,200 deaths.

Since its discovery in 1967, there have been more than a dozen recorded outbreaks of Marburg, mostly in Central Africa, and most recently in Uganda in 2017. Average Marburg case fatality ratio is around 50%, varying between 24% and 88%. The largest recorded Marburg outbreak occurred in 2004-2005 in Angola (252 known cases with 227 deaths; 90% case fatality ratio).

R&D needs

In December 2019, ERVEBO became the first FDA-approved Ebola vaccine, and is now licensed in four African countries. It was also a vital part of the outbreak response in the North Kivu, DRC Ebola epidemic – the first Ebola outbreak in which a vaccine was widely deployed – with approximately 300,000 people vaccinated. In 2020, EMA gave marketing authorisation to Janssen’s multivalent heterologous prime-boost vaccine. Although vital progress has been made in developing vaccines since the 2014 West African Ebola outbreak, neither approved vaccine meets the requirement of providing protection against multiple strains, including the Marburg virus, as set out in the WHO’s Ebola vaccine Target Product Profile (TPP).

During the 2014 Ebola outbreak, the absence of bench-top or point-of-care diagnostic tools meant that laboratory-designed tests were the only tool available for confirmatory diagnosis. Since then, the Ebola diagnostics pipeline has improved significantly, with multiple point-of-care (POC) molecular and rapid diagnostic tests (RDTs) now available. The increased speed at which field laboratories with molecular testing capabilities became functional (from months to days) in the 2018-2020 DRC outbreak is testimony to the remarkable progress made in the past seven years. While these developments have indeed been life-saving, to date only one of the available POC diagnostic tests meet the WHO TPP requirements for sensitivity and specificity benchmarks of >98% and >99% respectively. There is therefore a need for continued product development efforts focused on improving existing diagnostic tools and designing novel approaches.

While no TPP for a Marburg virus diagnostic test currently exists, the WHO Ebola/Marburg Research and Development Roadmap points to the need for similar rapid and deployable multiplex POC diagnostic tests, effective against both Filoviruses, with rapid turnaround times and requiring minimal laboratory infrastructure.

Pipeline spotlight

A Phase I trial has been launched by the University of Oxford, for a new ChAdOx1 biEBOV vaccine candidate effective against both Zaire and Sudan Ebola virus species. It seeks to establish the safety and immunogenicity of the new candidate for subsequent studies. In October 2020, the US FDA approved Inmazeb (REGN-EB3), the first biologic candidate for treating Zaire Ebola virus. A second biologic – Ebanga (Ansuvimab-zykl) was approved in December of the same year.