Abstract
BackgroundFour of five Plasmodium species infecting humans are present in Madagascar. Plasmodium vivax remains the second most prevalent species, but is understudied. No data is available on its susceptibility to sulphadoxine-pyrimethamine, the drug recommended for intermittent preventive treatment during pregnancy. In this study, the prevalence of P. vivax infection and the polymorphisms in the pvdhfr and pvdhps genes were investigated. The correlation between these polymorphisms and clinical and parasitological responses was also investigated in P. vivax-infected patients.MethodsPlasmodium vivax clinical isolates were collected in eight sentinel sites from the four major epidemiological areas for malaria across Madagascar in 2006/2007. Pvdhfr and pvdhps genes were sequenced for polymorphism analysis. The therapeutic efficacy of SP in P. vivax infections was assessed in Tsiroanomandidy, in the foothill of the central highlands. An intention-to-treat analysis of treatment outcome was carried out.ResultsA total of 159 P. vivax samples were sequenced in the pvdhfr/pvdhps genes. Mutant-types in pvdhfr gene were found in 71% of samples, and in pvdhps gene in 16% of samples. Six non-synonymous mutations were identified in pvdhfr, including two novel mutations at codons 21 and 130. For pvdhps, beside the known mutation at codon 383, a new one was found at codon 422. For the two genes, different combinations were ranged from wild-type to quadruple mutant-type. Among the 16 patients enrolled in the sulphadoxine-pyrimethamine clinical trial (28 days of follow-up) and after adjustment by genotyping, 3 (19%, 95% CI: 5%–43%) of them were classified as treatment failure and were pvdhfr 58R/117N double mutant carriers with or without the pvdhps 383G mutation.ConclusionThis study highlights (i) that genotyping in the pvdhfr and pvdhps genes remains a useful tool to monitor the emergence and the spread of P. vivax sulphadoxine-pyrimethamine resistant in order to improve the national antimalarial drug policy, (ii) the issue of using sulphadoxine-pyrimethamine as a monotherapy for intermittent preventive treatment of pregnant women or children.
Highlights
Four of five Plasmodium species infecting humans are present in Madagascar
All patients with fever or a history of fever in the 48 h before their arrival at the health centre were screened with the rapid diagnostic test (RDT), which is based on the detection of Plasmodium-specific lactate dehydrogenase (OptiMAL-ITTM, DiaMed AG©, Cressier sur Morat, Switzerland)
Prevalence of P. vivax infections From January to October 2006 and March to July 2007, 8,363 patients were screened by using RDT
Summary
Plasmodium vivax remains the second most prevalent species, but is understudied. The prevalence of P. vivax infection and the polymorphisms in the pvdhfr and pvdhps genes were investigated. Plasmodium vivax remains the second most common cause of malaria in the world, infecting more than 80 million people annually. It is the most geographically widespread malaria parasite and it is found throughout South and Central America, Asia, the Middle East and parts of Africa [1]. Plasmodium falciparum is the dominant malaria species, but P. vivax and Plasmodium malariae have an increased prevalence in the foothills of the central highlands [2,3]. P. vivax causes less mortality than P. falciparum, it is responsible for significant morbidity and economic loss
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