Increasing Occurrence of Marburg Virus Outbreaks in Africa: Risk Assessment for Public Health

Abstract

In this millennium, Marburgvirus (MARV) outbreaks with very high mortality but still small case numbers (< 400) were observed with increasing frequency in Africa. Ecologists identified Egyptian Rousettus bats (ERB) as viral reservoir species causing occasional zoonotic spillover events, mostly in humans intruding into their cave habitats as miners or tourists. So far only short human-to-human transmission chains have been documented. ERB can be experimentally infected with MARV but show no clinical signs. MARV transmission is inefficient among adult bats and occurs mostly between older juvenile ERB. WHO has modified infection control measures, requiring a high level of personal protective equipment when treating Marburgvirus disease (MVD) patients or burying the dead. If patients are quickly identified and isolated after symptom onset and contacts traced and also isolated, epidemics can be controlled. Researchers explored a number of antivirals against MARV in non-human primate (NHP) MVD models. Compounds included galidesivir, an adenosine nucleoside analogue; favipiravir, a synthetic guanine base analog; remdesivir, an injectable; and obeldesivir, an oral prodrug which are intracellularly metabolised to an adenosine triphosphate nucleotide analog; small interfering RNA drugs that target short segments of the MARV nucleoprotein NP mRNA; and a human neutralising monoclonal antibody directed against MARV glycoprotein. All compounds mediated various levels of survival in challenged NHPs depending on dose and time of application. Various vaccine approaches (alphavirus replicons, adenovirus and vesicular stomatitis virus vectors, virus-like particles, recombinant proteins, DNA vaccines) were explored in NHPs and conferred various degrees of protection against lethal MARV challenge. DNA vaccines were well tolerated in humans but showed only low immunogenicity. The African CDC has attributed an upper tier risk attribution to MVD when comparing 18 pathogens. For the moment, the short human MARV infection chains make large international outbreaks unlikely, but viral genome analysis in future outbreaks for transmission mutants is warranted.