Abstract
The dynamics of Plasmodium vivax infection is characterized by reactivation of hypnozoites at varying time intervals. The relative contribution of new P. vivax infection and reactivation of dormant liver stage hypnozoites to initiation of blood stage infection is unclear. In this study, we investigate the contribution of new inoculations of P. vivax sporozoites to primary infection versus reactivation of hypnozoites by modeling the dynamics of P. vivax infection in Thailand in patients receiving treatment for either blood stage infection alone (chloroquine), or the blood and liver stages of infection (chloroquine + primaquine). In addition, we also analysed rates of infection in a study in Papua New Guinea (PNG) where patients were treated with either artesunate, or artesunate + primaquine. Our results show that up to 96% of the P. vivax infection is due to hypnozoite reactivation in individuals living in endemic areas in Thailand. Similar analysis revealed the around 70% of infections in the PNG cohort were due to hypnozoite reactivation. We show how the age of the cohort, primaquine drug failure, and seasonality may affect estimates of the ratio of primary P. vivax infection to hypnozoite reactivation. Modeling of P. vivax primary infection and hypnozoite reactivation provides important insights into infection dynamics, and suggests that 90–96% of blood stage infections arise from hypnozoite reactivation. Major differences in infection kinetics between Thailand and PNG suggest the likelihood of drug failure in PNG.
Highlights
Plasmodium vivax is one of the major agents of malaria infection, with around 2.5 billion people living in areas at risk of infection, and more than 70 million estimated annual infections [1,2,3]
Understanding the rate of primary infection versus hypnozoite reactivation is important to understanding primaquine efficacy and drug resistance, as PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd
From the fact that primaquine can kill liver stage hypnozoites[15, 16] we classified the data in two groups: individuals retreated with chloroquine+primaquine (CQ+PQ) group and individuals retreated with chloroquine only (CQ only) group
Summary
Plasmodium vivax is one of the major agents of malaria infection, with around 2.5 billion people living in areas at risk of infection, and more than 70 million estimated annual infections [1,2,3]. Comparison of P. vivax genotypes may be useful in distinguishing recrudescence of the blood stage parasites after treatment, it is not always useful in differentiating reactivation of a dormant hypnozoite from new primary infection [10,11,12]. This is because the parasites causing relapses are often genetically different from those observed in the most recent blood-stage infection, so it is not possible to differentiate reactivation from new primary infection using genotyping[13, 14]. It is difficult to know the proportion of blood stage infections due to hypnozoite reactivation versus new primary infection by P. vivax
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