A High Force of Plasmodium vivax Blood-Stage Infection Drives the Rapid Acquisition of Immunity in Papua New Guinean Children

Abstract

BackgroundWhen both parasite species are co-endemic, Plasmodium vivax incidence peaks in younger children compared to P. falciparum. To identify differences in the number of blood stage infections of these species and its potential link to acquisition of immunity, we have estimated the molecular force of blood-stage infection of P. vivax (molFOB, i.e. the number of genetically distinct blood-stage infections over time), and compared it to previously reported values for P. falciparum.Methods P. vivax molFOB was estimated by high resolution genotyping parasites in samples collected over 16 months in a cohort of 264 Papua New Guinean children living in an area highly endemic for P. falciparum and P. vivax. In this cohort, P. vivax episodes decreased three-fold over the age range of 1–4.5 years.ResultsOn average, children acquired 14.0 new P. vivax blood-stage clones/child/year-at-risk. While the incidence of clinical P. vivax illness was strongly associated with molFOB (incidence rate ratio (IRR) = 1.99, 95% confidence interval (CI95) [1.80, 2.19]), molFOB did not change with age. The incidence of P. vivax showed a faster decrease with age in children with high (IRR = 0.49, CI95 [0.38, 0.64] p<0.001) compared to those with low exposure (IRR = 0.63, CI95[0.43, 0.93] p = 0.02).Conclusion P. vivax molFOB is considerably higher than P. falciparum molFOB (5.5 clones/child/year-at-risk). The high number of P. vivax clones that infect children in early childhood contribute to the rapid acquisition of immunity against clinical P. vivax malaria.

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

“…Therefore, substantial reductions in transmission by integrated control efforts will be required to impact parasite diversity and population structure in PNG. The mean MOI however was significantly correlated with parasite genetic diversity (R s and H e ) for P. falciparum consistent with within host complexity as a critical factor for creation of new genotypes, 81 whereas there was a lack of association for P. vivax because there was high within host complexity and high levels of diversity across the country. For both species it will therefore be important to investigate diversity using panels of ten or more less diverse genome wide markers such as microsatellite markers 37,82,83 or single nucleotide polymorphisms.…”

Predicting Antidisease Immunity Using Proteome Arrays and Sera from Children Naturally Exposed to Malaria

“…For example, 85% of the symptomatic Pv cases were detected by age 2, whereas only 40% of the symptomatic Pf and Pf/Pv cases had occurred by that age. Although our dataset does not allow us to evaluate the effect of previous exposure to malaria parasites on the development of immunity, this result suggests that children acquire antidisease immunity to Pv more rapidly than they do to Pf (30,36,50).…”

Uncovering the transmission dynamics ofPlasmodium vivaxusing population genetics

“…As a result of their extremely high within population diversity, antigen markers paired with extremely polymorphic microsatellites have identified and tracked individual clones over time within individuals with a high degree of certainty. [23][24][25] As mentioned above, the high diversity and maintenance of balanced allele frequencies by immune selection makes antigen markers extremely useful for measuring MOI and FOI because they ensure the lowest probability of clones having the same allele, and thus being indistinguishable. On the other hand, the pattern of diversity in antigens limits the detection of divergence between populations; therefore, antigen markers should be used with caution if the aim is to measure underlying patterns of gene flow between populations.…”