Relapses ofPlasmodium vivaxInfection Usually Result from Activation of Heterologous Hypnozoites

Abstract

The P. vivax populations emerging from hypnozoites commonly differ from the populations that caused the acute episode. Activation of heterologous hypnozoite populations is the most common cause of first relapse in patients with vivax malaria.

A closer look at multiple-clone Plasmodium vivax infections: detection methods, prevalence and consequences

“…This suggested that molecular methods could easily discriminate relapses, which would have the same genotype as the primary infection, from new infections, which would have a different genotype. This view has been challenged by the recent discovery of different parasite genotypes in primary infections and relapses in 72% of P. vivax-infected patients from Thailand, India and Myanmar (Imwong et al 2007b). Accurate detection of multiple-clone P. vivax infections becomes even more important in light of this report.…”

“…In general, multilocus analysis, such as microsatellite genotyping, detected greater numbers of multiple-clone infections when compared to single-locus analysis. The extensive clonal diversity of P. vivax infections in areas with relatively low malaria transmission, such as in Brazil and Colombia, is particularly surprising , Imwong et al 2007b). The only published comparison of microsatellite diversity in two human malaria parasite species co-circulating in the same area suggests that P. vivax infections comprise multiple clones (12 multiple-clone infections among 25 isolates typed) more often than P. falciparum infections (6 multiple-clone infections among 34 isolates typed) in rural Amazonia .…”

Molecular markers and genetic diversity of Plasmodium vivax

“…This suggested that molecular methods could easily discriminate relapses, which would have the same genotype as the primary infection, from new infections, which would have a different genotype. This view has been challenged by the recent discovery of different parasite genotypes in primary infections and relapses for 72% of P. vivax-infected patients from Thailand, India and Myanmar (Imwong et al 2007b). Accurate detection of multiple-clone P. vivax infections is even more important in light of this report.…”

“…For example, in 90 P. vivax isolates from Thailand, Cui et al (2003b) found a multiple-clone infection rate of 25.6% using the PvCSP encoding gene alone, 19.3% using PvMSP-3α alone and 35.6% when the markers were combined. Particularly surprising is the extensive clonal diversity of P. vivax infections in areas with relatively low malaria transmission, such as Brazil, Colombia and Sri Lanka (Ferreira et al 2007, Imwong et al 2007b, Karunaweera et al 2008, Orjuela-Sánchez et al 2009a, Gunawardena et al 2010. The evolutionary and epidemiological consequences of multiple-clone P. vivax infections have not been well-investigated.…”

Diagnosis and Treatment of Plasmodium vivax Malaria

“…A variety of methodologies have been developed for P. vivax with as few as three polymorphic markers proving to be sufficient to discriminate homologous from heterologous infections. [73][74][75][76] However, recurrence of P. vivax genetically identical to the pretreatment isolate can occur from either a true recrudescence of the initial infection or a relapse from hypnozoites generated from the prior blood-stage infection 74,77 ; unsurprisingly molecular methods are unable to distinguish between these alternatives. Relapses are also commonly genetically heterologous.…”