Multiplicity of Infection and Disease Severity in Plasmodium vivax

Abstract

BackgroundMultiplicity of infection (MOI) refers to the average number of distinct parasite genotypes concurrently infecting a patient. Although several studies have reported on MOI and the frequency of multiclonal infections in Plasmodium falciparum, there is limited data on Plasmodium vivax. Here, MOI and the frequency of multiclonal infections were studied in areas from South America where P. vivax and P. falciparum can be compared.Methodology/Principal FindingsAs part of a passive surveillance study, 1,328 positive malaria patients were recruited between 2011 and 2013 in low transmission areas from Colombia. Of those, there were only 38 P. vivax and 24 P. falciparum clinically complicated cases scattered throughout the time of the study. Samples from uncomplicated cases were matched in time and location with the complicated cases in order to compare the circulating genotypes for these two categories. A total of 92 P. vivax and 57 P. falciparum uncomplicated cases were randomly subsampled. All samples were genotyped by using neutral microsatellites. Plasmodium vivax showed more multiclonal infections (47.7%) than P. falciparum (14.8%). Population genetics and haplotype network analyses did not detect differences in the circulating genotypes between complicated and uncomplicated cases in each parasite. However, a Fisher exact test yielded a significant association between having multiclonal P. vivax infections and complicated malaria. No association was found for P. falciparum infections.ConclusionThe association between multiclonal infections and disease severity in P. vivax is consistent with previous observations made in rodent malaria. The contrasting pattern between P. vivax and P. falciparum could be explained, at least in part, by the fact that P. vivax infections have lineages that were more distantly related among them than in the case of the P. falciparum multiclonal infections. Future research should address the possible role that acquired immunity and exposure may have on multiclonal infections and their association with disease severity.

Prospective Study of Plasmodium vivax Malaria Recurrence after Radical Treatment with a Chloroquine-Primaquine Standard Regimen in Turbo, Colombia

“…The detection of 52 haplotypes in 112 day zero samples and the high percentage of unique haplotypes (65.4%) show high genetic diversity, consistent with other reports from South America using P. vivax microsatellites (37,(47)(48)(49)(50). Overall, the percentage of samples with polyclonal infection was 12.5%, which is similar to reports from other populations in Colombia, Venezuela, and Peru (47,50,51).…”

Higher Complexity of Infection and Genetic Diversity of Plasmodium vivax Than Plasmodium falciparum Across All Malaria Transmission Zones of Papua New Guinea

“…59,60 Therefore, accurate detection of parasite clones circulating within the host is crucial and depends on the assay sensitivity, the type and number of the molecular markers analyzed, and the criteria used to identify predominant and minor alleles. 55,61 The use of relaxed criteria to score minor peaks significantly increases artifacts that falsely increase multiclonal infections. 62 Because the markers used are highly diverse, we used more stringent criteria to minimize the introduction of artifacts (see Methods).…”

“…However, relapses of P. vivax infection due to the reactivation of heterologous hypnozoites from previous infections can directly contribute to increased MOI, which may sustain high diversity in low transmission areas for a longer period than P. falciparum after reduction in transmission. 3,22,61 This unique biology thus may explain the high complexity of P. vivax infection at a range of parasite prevalences in PNG.…”

Within-infection diversity ofPlasmodium falciparumantigens reflects host-mediated selection

“…The utility of this approach, however, extends beyond questions of immune selection. There is growing recognition that intra-host dynamics must be considered when studying diverse aspects of Plasmodium biology, including drug resistance [52,53], disease severity [54][55][56][57], and transmission rate [58,59]. Our observations show that human-mediated selection on P. falciparum is sufficiently strong to be detected using measures of within-infection diversity and demonstrate the utility of incorporating evolutionary approaches into Plasmodium studies.…”