Genotyping of Plasmodium vivax Reveals Both Short and Long Latency Relapse Patterns in Kolkata

Abstract

Background The Plasmodium vivax that was once prevalent in temperate climatic zones typically had an interval between primary infection and first relapse of 7–10 months, whereas in tropical areas P.vivax infections relapse frequently at intervals of 3–6 weeks. Defining the epidemiology of these two phenotypes from temporal patterns of illness in endemic areas is difficult or impossible, particularly if they overlap. Methods A prospective open label comparison of chloroquine (CQ) alone versus CQ plus unobserved primaquine for either 5 days or 14 days was conducted in patients presenting with acute vivax malaria in Kolkata. Patients were followed for 15 months and primary and recurrent infections were genotyped using three polymorphic antigen and up to 8 microsatellite markers. Results 151 patients were enrolled of whom 47 (31%) had subsequent recurrent infections. Recurrence proportions were similar in the three treatment groups. Parasite genotyping revealed discrete temporal patterns of recurrence allowing differentiation of probable relapse from newly acquired infections. This suggested that 32 of the 47 recurrences were probable relapses of which 22 (69%) were genetically homologous. The majority (81%) of probable relapses occurred within three months (16 homologous, 10 heterologous) and six genetically homologous relapses (19%) were of the long latency (8–10 month interval) phenotype. Conclusions With long follow-up to assess temporal patterns of vivax malaria recurrence, genotyping of P.vivax can be used to assess relapse rates. A 14 day unobserved course of primaquine did not prevent relapse. Genotyping indicates that long latency P.vivax is prevalent in West Bengal, and that the first relapses after long latent periods are genetically homologous. Trial Registration Controlled-Trials.com ISRCTN14027467

In Vivo Therapeutic Efficacy of Chloroquine Alone or in Combination with Primaquine against Vivax Malaria in Kolkata, West Bengal, India, and Polymorphism in pvmdr1 and pvcrt-o Genes

“…Thus, in Kolkata, CQ alone was 99% and CQ plus PQ was 100% effective against P. vivax malaria. Similar observations were also made from 1998 to 2001 (29) (30). Therefore, during the past 15 years, the efficacy of CQ remained unchanged in P. vivax malaria, but in P. falciparum malaria, the CQ resistance level reached 76.3% (31).…”

A study on relapse/re-infection rate of Plasmodium vivax malaria and identification of the predominant genotypes of P. vivax in two endemic districts of Nepal

“…This suggested that the prescribed primaquine regimen as per the WHO recommendations [24] possibly was not absolutely efficient for preventing all relapses. This kind of therapeutic response variability and inadequacy has also been observed in many endemic regions [20,25,26]. However, it must be pointed out that, since the primaquine treatment provided to study subjects was an unmonitored 14-day course, an absolute compliance cannot be assured.…”

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.…”