Inference from phylogeography and molecular epidemiology of Lassa virus is limited by sampling and sequencing bias in endemic regions.
The viral haemorrhagic infection caused by Lassa virus (LASV) is an important endemic zoonotic disease in West AfricanAfrica with evidence for increasing outbreak sizes. The Natal multimammate mouse (Mastomys natalensis) is the predominant viral reservoir, although few studies have investigated the role of other animal species. To identify host sequencing biases, all LASV nucleotide sequences and associated metadata (n = 2,298) available on GenBank were retrieved. Most data originated from Nigeria (56%), Guinea (20%) and Sierra Leone (14%). Data from non-human hosts (n = 703) were limited, only 69 sequences encompassed complete genes. Spatial modelling of sequencing effort highlighted the bias in locations of available sequences. Using available sequences phylogenetic analyses showed geographic clustering of LASV lineages, suggested 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 species. Further investigation of the non-human reservoir of this virus, alongside improved surveillance in other endemic countries, are required for further characterisation of the historic emergence and dispersal of LASV. Accurate assessment on viral circulation in non-human hosts is vital to guide public health interventions to prevent recurrent Lassa fever epidemics.
This project developed from Hayley Free’s MSc project based at the Royal Veterinary College. We obtained GenBank data on Lassa mammarenavirus sequences to investigate the phylogeny of these samples and to understand how biased these may be as a dataset. We were particularly interested in how many human derived sequences were obtained from the different regions with known outbreaks of human disease and comparing this to the coverage of rodent derived sequences.
We found that there is important spatial heterogeneity in where samples are obtained from that does not match the known distribution of rodent infections and human cases. For example, most human sequences came from Nigeria and Eastern Sierra Leone. While most rodent sequences came from Guinea and Eastern Sierra Leone with very few from Nigeria. This disparity likely has an important impact on the inference that can be drawn from phylogeographic studies of Lassa mammarenavirus.
Citation
@online{free2022,
author = {Hayley Free and David Simons and Isobella Honeyborne and
Linzy Elton and Najmul Haider and Rashid Ansumana and Richard Kock
and Francine Ntoumi and Alimuddin Zumla and Timothy D McHugh and Liã
Arruda},
title = {Inference from Phylogeography and Molecular Epidemiology of
{Lassa} Virus Is Limited by Sampling and Sequencing Bias in Endemic
Regions.},
date = {2022-10-01},
url = {https://www.dsimons.org/lassa_phylogenetics.html},
langid = {en},
abstract = {The viral haemorrhagic infection caused by Lassa virus
(LASV) is an important endemic zoonotic disease in West
AfricanAfrica with evidence for increasing outbreak sizes. The Natal
multimammate mouse (*Mastomys natalensis*) is the predominant viral
reservoir, although few studies have investigated the role of other
animal species. To identify host sequencing biases, all LASV
nucleotide sequences and associated metadata (n = 2,298) available
on GenBank were retrieved. Most data originated from Nigeria (56\%),
Guinea (20\%) and Sierra Leone (14\%). Data from non-human hosts (n
= 703) were limited, only 69 sequences encompassed complete genes.
Spatial modelling of sequencing effort highlighted the bias in
locations of available sequences. Using available sequences
phylogenetic analyses showed geographic clustering of LASV lineages,
suggested 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 species. Further investigation of the non-human reservoir
of this virus, alongside improved surveillance in other endemic
countries, are required for further characterisation of the historic
emergence and dispersal of LASV. Accurate assessment on viral
circulation in non-human hosts is vital to guide public health
interventions to prevent recurrent Lassa fever epidemics.}
}