Lassa fever — the road ahead

Abstract

Lassa virus (LASV) is endemic in the rodent populations of Sierra Leone, Nigeria and other countries in West Africa. Spillover to humans occurs frequently and results in Lassa fever, a viral haemorrhagic fever (VHF) associated with a high case fatality rate. Despite advances, fundamental gaps in knowledge of the immunology, epidemiology, ecology and pathogenesis of Lassa fever persist. More frequent outbreaks, the potential for further geographic expansion of Mastomys natalensis and other rodent reservoirs, the ease of procurement and possible use and weaponization of LASV, the frequent importation of LASV to North America and Europe, and the emergence of novel LASV strains in densely populated West Africa have driven new initiatives to develop countermeasures for LASV. Although promising candidates are being evaluated, as yet there are no approved vaccines or therapeutics for human use. This Review discusses the virology of LASV, the clinical course of Lassa fever and the progress towards developing medical countermeasures.

Vaccine Candidates against Arenavirus Infections

“…OW arenaviruses are distributed predominantly on the African continent, with the exception of LCMV, which has been isolated from laboratory mice ( Mus Musculus ) worldwide. LASV is the etiological agent of LF and is endemic in West African countries including Guinea, Liberia, Sierra Leone, and Nigeria ( Figure 2 ), corresponding with habitats of its natural rodent host, Mastomys natalensis [ 3 ]. Mopeia virus (MOPV) is also found in this rodent throughout Mozambique and Zimbabwe, but has not been shown to cause human disease [ 12 , 13 , 14 ].…”

“…Mammarenaviruses are enveloped viruses with bi-segmented, single-stranded, negative-sense RNA as their viral genome ( Figure 3 and Figure 4 ) [ 2 , 3 ]. The segmented genome consists of small (S) and large (L) segments.…”

“…Mammarenaviruses belong to the family Arenaviridae and the genus Mammarenavirus . According to their geographic distribution and phylogenetic relationships, mammarenaviruses are further divided into Old World (OW) and New World (NW) arenaviruses [ 1 , 2 , 3 ]. Several of these cause infections in humans, ranging from asymptomatic to fatal outcomes.…”

“…Lassa virus (LASV) is an OW arenavirus and the causative agent of Lassa fever (LF), a fatal hemorrhagic fever. Outbreaks of LF are reported annually in endemic western African countries, with high mortality in symptomatic patients [ 3 , 4 ]. Junin virus (JUNV) is a NW arenavirus and causes Argentine hemorrhagic fever (AHF).…”

Design, Synthesis, and Biological Evaluation of Benzimidazole Derivatives as Potential Lassa Virus Inhibitors

“…Currently, the therapeutic strategies for Lassa fever are limited to the off-label use of broad-spectrum antiviral ribavirin, which is usually used in the early stages of the disease [ 20 , 21 ]. As we know, drug repurposing is a promising strategy to identify new uses from approved or experimental drugs, which has also been used in searching for LASV inhibitors [ 22 ].…”