Abstract
Summary: Individuals living in endemic areas generally harbour multiple parasite strains. Multiplicity of infection (MOI) can be an indicator of immune status and transmission intensity. It has a potentially confounding effect on a number of population genetic analyses, which often assume isolates are clonal. Polymerase chain reaction-based approaches to estimate MOI can lack sensitivity. For example, in the human malaria parasite Plasmodium falciparum, genotyping of the merozoite surface protein (MSP1/2) genes is a standard method for assessing MOI, despite the apparent problem of underestimation. The availability of deep coverage data from massively parallizable sequencing technologies means that MOI can be detected genome wide by considering the abundance of heterozygous genotypes. Here, we present a method to estimate MOI, which considers unique combinations of polymorphisms from sequence reads. The method is implemented within the estMOI software. When applied to clinical P.falciparum isolates from three continents, we find that multiple infections are common, especially in regions with high transmission.Availability and implementation: estMOI is freely available from http://pathogenseq.lshtm.ac.uk.Contact: samuel.assefa@lshtm.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online.
Highlights
Multiplicity of infection (MOI) refers to the number of different parasite genotypes co-infecting a single host
It is an epidemiological measure that can improve the understanding of many areas of parasitology, including the dynamics of infections, pathogenesis, effect of transmission intensity, drug efficacy and parasite genetics (Ross et al, 2012)
MOI can be a useful indicator of the transmission level, where the latter is positively correlated with the average number of malaria parasite strains in an individual (Babiker et al, 1999)
Summary
Multiplicity of infection (MOI) refers to the number of different parasite genotypes co-infecting a single host. Approaches that consider the whole genome rather than candidate regions, and exploit the potentially high depth of coverage from sequencing technologies allowing detection of parasite at low levels, are likely to be more informative (Bowman et al, 2013). Parallelizable sequencing technologies are providing whole-genome data on various parasites including P.falciparum (haploid genome, 14 chromosomes, size 23 Mb, 19% GC content) isolates to high coverage depth (Robinson et al, 2011). In this setting, the presence of heterozygous genotypes provides evidence of MOI and complicates population genetic and diversity analysis. Our approach has been implemented in the estMOI software package
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