Determining Ancestry between Rodent- and Human-Derived Virus Sequences in Endemic Foci: Towards a More Integral Molecular Epidemiology of Lassa Fever within West Africa

Abstract

Lassa fever is a viral hemorrhagic illness responsible for thousands of human deaths in West Africa yearly. Rodents are known as natural reservoirs of the causative Lassa mammarenavirus (LASV) while humans are regarded as incidental, spill-over hosts. Analysis of genetic sequences continues to add to our understanding of the evolutionary history, emergence patterns, and the epidemiology of LASV. Hitherto, the source of data in such investigations has mainly comprised human clinical samples. Presently, a rise in the quantity of virus strains accessed through ecological studies over the last 15 years now allows us to explore how LASV sequences obtained from rodents might affect phylogenetic patterns. In this study, we phylogenetically compared LASV sequences obtained from both rodents and humans across West Africa, including those from two localities highly endemic for the disease: Ekpoma in Nigeria and Kenema in Sierra Leone. We performed a time-calibrated phylogeny, using a Bayesian analysis on 198 taxa, including 102 sequences from rodents and 96 from humans. Contrary to expectation, our results show that LASV strains detected in humans within these localities, even those sampled recently, are consistently ancient to those circulating in rodents in the same area. We discuss the possibilities connected to this preliminary outcome. We also propose modalities to guide more comprehensive comparisons of human and rodent data in LASV molecular epidemiological studies.

Lassa fever in Benin: description of the 2014 and 2016 epidemics and genetic characterization of a new Lassa virus

“…On the other hand, this study showed that certain pygmy mice, Mus baoulei, circulating in the fields around the houses were carriers of the LASV virus belonging to the same cluster as the Beninese strains, but genetically very distant. This is specific to this new lineage, because when humans are infected with strains circulating in rodents in their environment, phylogenetic analysis shows some trees with very close "rodent" branches and "human" branches [35][36][37]. For example, the GP-LASV sequences observed in M. natalensis and Homo sapiens living in the Ekpoma zone of Nigeria showed an amino-acid similarity of approximately 95-99% [36], whereas we observed a similarity of approximately 90-92%.…”

The niche of One Health approaches in Lassa fever surveillance and control

“…While a LASV vaccine is still unavailable, increasing insight into LF ecology, particularly where LASV rodent hosts are concerned, can provide a more dependable assessment of zoonotic risk. In this regard molecular analysis as a tool has proven useful, driving a series of advances in the mapping of LASV occurrence, lineage clustering and more accurate identification of rodent hosts [ 35 ]. Most of the findings so far have enabled virus and rodent genetic categorisation across the West African region at the ‘lineage’ level.…”

“…1 ) should aim to link human and rodent data more directly at a finer scale. They also recommended that longitudinal sampling regimes be supported by opportunistic rodent screening at home addresses where humans test LASV-positive [ 35 ].…”

A Sporadic and Lethal Lassa Fever Case in Forest Guinea, 2019

“…In Guinea, numerous LASV sequences have been largely described in rodents, notably in the region of Faranah (221 sequences), Kindia (6 sequences) and Guékedou (9 sequences) [ 9 , 10 , 11 , 20 , 21 ]. However, only 5 sequences are derived from humans, 2 complete from Faranah and Macenta [ 22 , 23 ], and 3 partials from Kissidougou and Nzérékoré [ 14 ].…”