Therapeutic efficacy of chloroquine and sequence variation in pfcrt gene among patients with falciparum malaria in central India

Bharti, Praveen Kumar ; Alam, Mohammad Tauqeer ; Boxer, Robert ; Shukla, Man Mohan ; Gautam, Sant P. ; Sharma, Yagya D. ; Singh, Neeru (2010) Therapeutic efficacy of chloroquine and sequence variation in pfcrt gene among patients with falciparum malaria in central India Tropical Medicine and International Health, 15 (1). pp. 33-40. ISSN 1360-2276

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Official URL: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-...

Related URL: http://dx.doi.org/10.1111/j.1365-3156.2009.02425.x

Abstract

Objectives: To assess the therapeutic efficacy of chloroquine (CQ) treatment against uncomplicated Plasmodium falciparum infections in a tribal population of central India (Madhya Pradesh) and to investigate the prevalence of mutant P. falciparum chloroquine-resistant transporter (pfcrt) gene in the parasite population. Methods: Clinical and parasitological response was determined by in-vivo testing. For molecular testing, the parasite DNA was extracted from blood samples and used to amplify and sequence parts of the pfcrt (44-177 codons), MSP1 (block 2) and MSP2 (central repeat region) genes. Results: Of 463 patients presenting fever, 137 tested positive for P. falciparum. They were treated with CQ. Of these, 58% participated in the study. Overall, treatment failure occurred in 53% of participants. Children under 5 years of age showed significantly more CQ resistance than adults. Mutant genotype S72V73M74N75T76 was prevalent among both CQ responders (61.29%) and non-responders (66.7%). Interestingly, several patients from the CQ non-responder group (33.3%, n=39) were harbouring parasite with wild type C72V73M74N75K76 genotype of the pfcrt gene. Microsatellite sequences downstream of exon 2 varied widely among both wild type and mutant pfcrt haplotypes. Conclusion: The high rate of treatment failure in the present study clearly indicates the need to reassess the use of CQ as first-line antimalarial therapy in central India. This is supported by the presence of mutant pfcrt genotype among majority of the parasite population of the CQ non-responder group of patients. However, the presence of wild type amino acid at codon 76 of the pfcrt gene among several patients with CQ non-responders requires further investigations.

Item Type:Article
Source:Copyright of this article belongs to John Wiley and Sons.
Keywords:CQ; Central India; Resistance; pfcrt Gene; Mutant; Wild Type
ID Code:48673
Deposited On:15 Jul 2011 07:59
Last Modified:15 Jul 2011 07:59

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