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Drug resistance in Plasmodium vivax malaria

Currently, Plasmodium vivax is the most widely distributed human malaria species in the world causing an estimated 80-90 million cases each year. P.vivax infections remain a major source of morbidity in Pakistan and the most widely used antimalarial for treatment of P.vivax was chloroquine and primaquine until recently. Emerging resistance to chloroquine in P.vivax is a major problem to this normally considerd benign malaria. However, benign status of P.vivax infection has been challenged by studies from Pakistan and India with reported hospitalization, severe disease, and death.[1]

The global prevalence of chloroquine resistant P. vivax remains poorly defined due to limited information on mechanism of P. vivax chloroquine resistance. The first cases of chloroquine resistant P. vivax were reported in 1989 from Papua New Guinea followed by reports from several vivax malaria endemic countries. However no chloroquine resistance has been reported from Pakistan. Sulphadoxine-pyrimethamine (SP) in combination with artesunate have become the drug of choice against vivax malaria which is also a recommended first line therapy for uncomplicated P.falciparum in Pakistan.[2]

However, in private sector, treatment of uncomplicated falciparum malaria with SP monotherapy is still common and inadvertently exposes P.vivax to doses of SP. This may lead to accumulation of single nucleotide polymorphisms (SNPs) in pvdhps and pvdhfr genes confering resistance to SP. This situation is alarming, as mutations in these genes are reported from Madagascar, Afghanistan andThailand with treatment failure in these regions. 

 Similarly, mutations in isolates from Pakistan has been documented  indicating SP resistant allelies are circulating in Pakistan.[3] Therefore, there is an urgent need to improve diagnosis and genotyping of P.vivax isolates from Pakistan to understand transmission dynamics of the resistant strains and to assess prevalence of drug resistance in our population.
References

1.  Beg, M.A., et al., Cerebral involvement in benign tertian malaria. Am J Trop Med Hyg, 2002. 67(3): p. 230-2.

2. Leslie, T., et al., Sulfadoxine-pyrimethamine, chlorproguanil-dapsone, or chloroquine for the treatment of Plasmodium vivax malaria in Afghanistan and Pakistan: a randomized controlled trial. Jama, 2007. 297(20): p. 2201-9.

3. Khatoon L., et al., Prevalence of antimalarial drug resistance mutations in Plasmodium vivax and P. falciparum from a malaria-endemic area of Pakistan. Am J Trop Med Hyg, 2009. 81(3): p. 525-8.

 

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