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Review
. 2021 Jun 11;16(6):e0249382.
doi: 10.1371/journal.pone.0249382. eCollection 2021.

Systematic review of Plasmodium falciparum and Plasmodium vivax polyclonal infections: Impact of prevalence, study population characteristics, and laboratory procedures

Luis Lopez  1 , Cristian Koepfli  1   2
Affiliations
Review

Systematic review of Plasmodium falciparum and Plasmodium vivax polyclonal infections: Impact of prevalence, study population characteristics, and laboratory procedures

Luis Lopez et al. PLoS One. .

Abstract

Multiple infections of genetically distinct clones of the same Plasmodium species are common in many malaria endemic settings. Mean multiplicity of infection (MOI) and the proportion of polyclonal infections are often reported as surrogate marker of transmission intensity, yet the relationship with traditional measures such as parasite prevalence is not well understood. We have searched Pubmed for articles on P. falciparum and P. vivax multiplicity, and compared the proportion of polyclonal infections and mean MOI to population prevalence. The impact of the genotyping method, number of genotyping markers, method for diagnosis (microscopy/RDT vs. PCR), presence of clinical symptoms, age, geographic region, and year of sample collection on multiplicity indices were assessed. For P. falciparum, 153 studies met inclusion criteria, yielding 275 individual data points and 33,526 genotyped individuals. The proportion of polyclonal infections ranged from 0-96%, and mean MOI from 1-6.1. For P. vivax, 54 studies met inclusion criteria, yielding 115 data points and 13,325 genotyped individuals. The proportion of polyclonal infections ranged from 0-100%, and mean MOI from 1-3.8. For both species, the proportion of polyclonal infections ranged from very low to close to 100% at low prevalence, while at high prevalence it was always high. Each percentage point increase in prevalence resulted in a 0.34% increase in the proportion of polyclonal P. falciparum infections (P<0.001), and a 0.78% increase in the proportion of polyclonal P. vivax infections (P<0.001). In multivariable analysis, higher prevalence, typing multiple markers, diagnosis of infections by PCR, and sampling in Africa were found to result in a higher proportion of P. falciparum polyclonal infections. For P. vivax, prevalence, year of study, typing multiple markers, and geographic region were significant predictors. In conclusion, polyclonal infections are frequently present in all settings, but the association between multiplicity and prevalence is weak.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Relationship between prevalence and the proportion P. falciparum and P. vivax polyclonal infections (A, C) or mean multiplicity (B, D).
Dot sizes represent the number of individuals genotyped. Dark red/dark blue = samples collected form clinical patients. Orange/light blue = samples collected form asymptomatic individuals. Overlapping data points result in darker colors.
Fig 2
Fig 2. Relationship between year of sample collection and the proportion P. falciparum and P. vivax polyclonal infections (A, C) or mean multiplicity (B, D).
Dot sizes represent the number of individuals genotyped. Dark red/dark blue = samples collected form clinical patients. Orange/light blue = samples collected form asymptomatic individuals. Overlapping data points result in darker colors.
Fig 3
Fig 3. Impact of presence of laboratory methods (method for diagnosis, number of genotyping markers, method to size size-polymorphic amplicons) and patient characteristics (presence of clinical symptoms, age group, geographic region) on the proportion P. falciparum (A-F) and P. vivax (G-L) polyclonal infections.
Black line denotes median. Groups were compared by Mann-Whitney test (if 2 groups), or regression analysis (if 3 groups). * P ≤ 0.05, **P ≤ 0.01, *** P ≤ 0.001, **** P ≤ 0.0001, ns = not significant.
Fig 4
Fig 4. Relationship between the proportion P. falciparum polyclonal infections (A) or mean multiplicity (B) and prevalence based on typing of marker msp2.
Dot sizes represent the number of individuals genotyped. Dark red = samples collected form clinical patients. Orange = samples collected form asymptomatic individuals. Overlapping data points result in darker colors.
See this image and copyright information in PMC

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