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

Abstract

Background

When 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.

Results

On 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 _mol FOB (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.

Author Summary

In areas where P. vivax and P. falciparum parasite species co-occur, immunity to P. vivax seems to be acquired more rapidly. This difference could be caused either by generic differences in the way immunity is acquired or by a relatively higher exposure to P. vivax blood-stage infections in early life. We found that children experienced an average of 14 new P. vivax blood-stage infections per year, and that the number of new infections acquired predicted how often children fell ill with vivax malaria by genotyping all P. vivax infections that occurred in a group of 264 children 1–4 years of age followed for 16 months. The burden of blood-stage infections caused by P. vivax was therefore at least twice as high as that caused by P. falciparum. This higher force-of-blood-stage infection ( _molFOB) caused by P. vivax is at least partially due to the ability of P. vivax hypnozoites to relapse from long-lasting liver stages. A high exposure to P. vivax blood-stage infection resulted in more rapid decrease in the incidence of P. vivax malaria. The high number of P. vivax clones that infect children in early childhood is thus likely to contribute substantially to the rapid acquisition of immunity against clinical P. vivax malaria.