Determining Ancestry between Rodent- and Human-Derived Lassa Virus Sequences in Endemic Foci within West Africa: Indications of Reverse Zoonosis

Abstract

Background: Lassa fever is a viral haemorrhagic illness responsible for thousands of human deaths in West Africa yearly. Rodents are known as natural reservoirs of the causative Lassa virus (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. Methods: In this study we phylogenetically compare 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 185 taxa including 89 sequences from rodents and 96 from humans. Findings: 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. Interpretation: This indicates humans are likely more involved in maintaining and spreading LASV than is currently realized. It also suggests there may have been certain emergence events where rodents became infected, even if indirectly, by humans. While this finding does not dispel the basic concept of rodent-to-human transmission, it recommends a broader, bi-directional model; one that recognises the role of reverse zoonosis in LASV epidemiology. Funding Statement: European Foundation Initiative for African Research into Neglected Tropical Diseases (EFINTD) under grants 1/85/022 & 89 540 and the German Research Foundation (DFG) under grant FI 1781/2-1. Declaration of Interests: The authors declare they have no conflict of interest.