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

PLOS Glob Public Health. 2023 Nov 8;3(11):e0002159. doi: 10.1371/journal.pgph.0002159. eCollection 2023.

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.

Grants and funding

Linzy Elton, Timothy D McHugh, Francine Ntoumi, and Alimuddin Zumla acknowledge support from EDCTP-Central Africa and East African Clinical Research Networks (CANTAM-3, EACCR-3). Sir Zumla is an NIHR Senior Investigator, a Mahathir Science Award, Sir Patrick Manson Medal and EU-EDCTP Pascoal Mocumbi Prize laureate. Liã Bárbara Arruda, David Simons, Rashid Ansumana, Linzy Elton, Najmul Haider, Isobella Honeyborne, Danny Asogun, Timothy D McHugh, Francine Ntoumi, Alimuddin Zumla and Richard Kock acknowledge support from the Pan-African Network for Rapid Research, Response and Preparedness for Infectious Diseases Epidemics – PANDORA-ID-NET, funded through the European and Developing Countries Clinical Trials Partnership (EDCTP) (grant number RIA2016E-1609). David Simons is supported by a PhD studentship from the UK Biotechnology and Biological Sciences Research Council (BB/M009513/1).