High chloroquine treatment failure rates and predominance of mutant genotypes associated with chloroquine and antifolate resistance among falciparum malaria patients from the island of Car Nicobar, India.

Abstract

OBJECTIVES:

An in vivo chloroquine efficacy study was undertaken on the island of Car Nicobar because a temporal rise in the Plasmodium falciparum parasite population containing mutations in the chloroquine resistance transporter (PfCRT) protein has been reported there.

METHODS:

A WHO protocol with a 28 day follow-up schedule was used for chloroquine efficacy studies. Finger-prick blood from P. falciparum malaria patients was used for sequencing the genes encoding PfCRT (exon 2), dihydrofolate reductase (PfDHFR) and dihydropteroate synthetase (PfDHPS).

RESULTS:

The majority of patients showed chloroquine treatment failure (60.42%, n=48). A higher early treatment failure (ETF) rate was recorded among non-responders (23 of 29, 79.31%). Each patient, irrespective of their chloroquine response, was infected with P. falciparum that contained mutated PfCRT (predominantly genotype C72V73I74E75T76) associated with high chloroquine resistance and none with the wild-type pfcrt gene. Therefore, mutated PfCRT was also present in the P. falciparum isolates of all the chloroquine responders. The majority of individuals from both groups also contained parasites with a high number of two-locus PfDHFR-PfDHPS mutations, associated with a high level of antifolate resistance.

CONCLUSIONS:

There is a predominance of chloroquine- and antifolate-resistant P. falciparum malaria in Car Nicobar, requiring an alternative antimalarial drug treatment policy, such as implementation of artesunate combination therapy (ACT), for this island.

• Authors: Manoj K Das, Vanshika Lumb, Pooja Mittra, Shiv S Singh, Aditya P Dash, Yagya D Sharma
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 65 Issue 6 Pg. 1258-61 (Jun 2010) ISSN: 1460-2091 [Electronic] England
• PMID: 20363804 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• DNA, Protozoan
• Membrane Transport Proteins
• PfCRT protein, Plasmodium falciparum
• Protozoan Proteins
• Chloroquine
• Tetrahydrofolate Dehydrogenase
• Dihydropteroate Synthase

Topics

• Adolescent
• Adult
• Antimalarials (pharmacology, therapeutic use)
• Child
• Child, Preschool
• Chloroquine (pharmacology, therapeutic use)
• DNA, Protozoan (chemistry, genetics)
• Dihydropteroate Synthase (genetics)
• Drug Resistance
• Female
• Gene Frequency
• Genotype
• Humans
• India
• Infant
• Malaria, Falciparum (drug therapy, parasitology)
• Male
• Membrane Transport Proteins
• Middle Aged
• Mutation, Missense
• Plasmodium falciparum (drug effects, genetics, isolation & purification)
• Protozoan Proteins (genetics)
• Sequence Analysis, DNA
• Tetrahydrofolate Dehydrogenase (genetics)
• Treatment Failure
• Young Adult