Current sampling and sequencing biases of Lassa mammarenavirus limit inference from phylogeography and molecular epidemiology in Lassa fever endemic regions

Arruda, Liã Bárbara; Free, Hayley Beth; Simons, David; Ansumana, Rashid; Elton, Linzy; Haider, Najmul; Honeyborne, Isobella; Asogun, Danny; McHugh, Timothy D.; Ntoumi, Francine; Zumla, Alimuddin; Kock, Richard

Abstract

Lassa fever (LF) is a potentially lethal viral haemorrhagic infection of humans caused by Lassa mammarenavirus (LASV). It is an important endemic zoonotic disease in West Africa with growing evidence for increasing frequency and sizes of outbreaks. Phylogeographic and molecular epidemiology methods have projected expansion of the Lassa fever endemic zone in the context of future global change. The Natal multimammate mouse (Mastomys natalensis) is the predominant LASV reservoir, with few studies investigating the role of other animal species. To explore host sequencing biases, all LASV nucleotide sequences and associated metadata available on GenBank (n = 2,298) were retrieved. Most data originated from Nigeria (54%), Guinea (20%) and Sierra Leone (14%). Data from non-human hosts (n = 703) were limited and only 69 sequences encompassed complete genes. We found a strong positive correlation between the number of confirmed human cases and sequences at the country level (r = 0.93 (95% Confidence Interval = 0.71–0.98), p < 0.001) but no correlation exists between confirmed cases and the number of available rodent sequences (r = -0.019 (95% C.I. -0.71–0.69), p = 0.96). Spatial modelling of sequencing effort highlighted current biases in locations of available sequences, with increased sequencing effort observed in Southern Guinea and Southern Nigeria. Phylogenetic analyses showed geographic clustering of LASV lineages, suggestive of isolated events of human-to-rodent transmission and the emergence of currently circulating strains of LASV from the year 1498 in Nigeria. Overall, the current study highlights significant geographic limitations in LASV surveillance, particularly, in non-human hosts. Further investigation of the non-human reservoir of LASV, alongside expanded surveillance, are required for precise characterisation of the emergence and dispersal of LASV. Accurate surveillance of LASV circulation in non-human hosts is vital to guide early detection and initiation of public health interventions for future Lassa fever outbreaks.

Citation

Arruda, L. B., Free, H. B., Simons, D., Ansumana, R., Elton, L., Haider, N., …Kock, R. (in press). Current sampling and sequencing biases of Lassa mammarenavirus limit inference from phylogeography and molecular epidemiology in Lassa fever endemic regions. PLOS Global Public Health, 3(11), Article e0002159. https://doi.org/10.1371/journal.pgph.0002159

• Journal Article Type: Article
• Acceptance Date: Oct 16, 2024
• Online Publication Date: Nov 8, 2023
• Deposit Date: Dec 16, 2024
• Journal: PLOS Global Public Health
• Publisher: Public Library of Science (PLoS)
• Peer Reviewed: Peer Reviewed
• Volume: 3
• Issue: 11
• Article Number: e0002159
• DOI: https://doi.org/10.1371/journal.pgph.0002159
• Public URL: https://keele-repository.worktribe.com/output/1018677
• Publisher URL: https://journals.plos.org/globalpublichealth/article/comments?id=10.1371/journal.pgph.0002159