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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.
J Antimicrob Chemother. 2010 Jun; 65(6):1258-61.JA

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+Show Affiliations

National Institute of Malaria Research, F.U., T.B. Sanatorium Complex, Itki, Ranchi 835301, Jharkhand, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20363804

Citation

Das, Manoj K., et al. "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." The Journal of Antimicrobial Chemotherapy, vol. 65, no. 6, 2010, pp. 1258-61.
Das MK, Lumb V, Mittra P, et al. 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. J Antimicrob Chemother. 2010;65(6):1258-61.
Das, M. K., Lumb, V., Mittra, P., Singh, S. S., Dash, A. P., & Sharma, Y. D. (2010). 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. The Journal of Antimicrobial Chemotherapy, 65(6), 1258-61. https://doi.org/10.1093/jac/dkq090
Das MK, et al. 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. J Antimicrob Chemother. 2010;65(6):1258-61. PubMed PMID: 20363804.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Das,Manoj K, AU - Lumb,Vanshika, AU - Mittra,Pooja, AU - Singh,Shiv S, AU - Dash,Aditya P, AU - Sharma,Yagya D, Y1 - 2010/04/02/ PY - 2010/4/6/entrez PY - 2010/4/7/pubmed PY - 2010/8/10/medline SP - 1258 EP - 61 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 65 IS - 6 N2 - 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. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/20363804/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_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkq090 DB - PRIME DP - Unbound Medicine ER -