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

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 S(72)V(73)M(74)N(75)T(76) 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 C(72)V(73)M(74)N(75)K(76) 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.

• Authors: Praveen Kumar Bharti, Mohammad Tauqeer Alam, Robert Boxer, Man Mohan Shukla, Sant P Gautam, Yagya D Sharma, Neeru Singh
• Journal: Tropical medicine & international health : TM & IH (Trop Med Int Health) Vol. 15 Issue 1 Pg. 33-40 (Jan 2010) ISSN: 1365-3156 [Electronic] England
• PMID: 19912592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Protozoan
• Antimalarials
• DNA, Protozoan
• Membrane Transport Proteins
• Merozoite Surface Protein 1
• PfCRT protein, Plasmodium falciparum
• Protozoan Proteins
• merozoite surface protein 2, Plasmodium
• Chloroquine

Topics

• Adolescent
• Adult
• Age Factors
• Animals
• Antigens, Protozoan (genetics)
• Antimalarials (therapeutic use)
• Child
• Child, Preschool
• Chloroquine (therapeutic use)
• DNA Mutational Analysis (methods)
• DNA, Protozoan (genetics)
• Drug Resistance (genetics)
• Female
• Humans
• India (epidemiology)
• Infant
• Malaria, Falciparum (drug therapy, epidemiology, parasitology)
• Male
• Membrane Transport Proteins (genetics)
• Merozoite Surface Protein 1 (genetics)
• Middle Aged
• Mutation
• Plasmodium falciparum (genetics)
• Polymerase Chain Reaction (methods)
• Protozoan Proteins (genetics)
• Treatment Failure
• Young Adult