Chloroquine efficacy studies confirm drug susceptibility of Plasmodium vivax in Chennai, India

Malaria Journal

Research

Jane M Carlton¹  Patrick L Sutton¹  Joseph K David²  Alex Eapen³  K John Ravindran³  Neelima Mishra⁴  Saumyadripta Chaudhuri⁴  Sneh Shalini⁴  Nalini Srivastava⁵ 

[1] Department of Biology, Center for Genomics and Systems Biology, New York University, 12 Waverly Place, 10003, New York, NY, USA;National Institute of Epidemiology (Indian Council of Medical Research), Second Main Road, Tamil Nadu Housing Board, Ayapakkam, 600 077, Chennai, India;National Institute of Malaria Research (Indian Council of Medical Research), National Institute of Epidemiology Campus, Second Main Road, Tamil Nadu Housing Board, Ayapakkam, 600 077, Chennai, Tamil Nadu, India;National Institute of Malaria Research (Indian Council of Medical Research), Sector 8, 110 077, Dwarka, New Delhi, India;School of Studies in Biochemistry, Jiwaji University, 474 011, Gwalior, India;

关键词: Plasmodium vivax;    Chloroquine;    In vitro;    In vivo;    Genetic diversity;    Chennai;   

DOI  :  10.1186/1475-2875-13-129

 received in 2014-01-10, accepted in 2014-03-24,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundAssessing the Plasmodium vivax burden in India is complicated by the potential threat of an emerging chloroquine (CQ) resistant parasite population from neighbouring countries in Southeast Asia. Chennai, the capital of Tamil Nadu and an urban setting for P. vivax in southern India, was selected as a sentinel site for investigating CQ efficacy and sensitivity in vivax malaria.MethodsCQ efficacy was evaluated with a 28-day in vivo therapeutic study, while CQ sensitivity was measured with an in vitro drug susceptibility assay. In both studies, isolates also underwent molecular genotyping to investigate correlations between parasite diversity and drug susceptibility to CQ. Molecular genotyping included sequencing a 604 base pair (bp) fragment of the P. vivax multidrug resistant gene-1 (Pvmdr1) for single nucleotide polymorphisms (SNPs) and also the amplification of eight microsatellite (MS) loci located across the genome on eight different chromosomes.ResultsIn the 28-day in vivo study (N=125), all subjects were aparasitaemic by Day 14. Passive case surveillance continuing beyond Day 28 in 22 subjects exposed 17 recurrent infections, which ranged from 44 to 148 days post-enrollment. Pvmdr1 sequencing of these recurrent infections revealed that 93.3% had identical mutant haplotypes (958M/Y976/1076L) to their baseline Day 0 infection. MS genotyping further revealed that nine infection pairs were related with ≥75% haplotype similarity (same allele at six or more loci). To test the impact of this mutation on CQ efficacy, an in vitro drug assay (N=68) was performed. No correlation between IC50 values and the percentage of ring-stage parasites prior to culture was observed (rsadj: -0.00063, p = 0.3307) and the distribution of alleles among the Pvmdr1 SNPs and MS haplotypes showed no significant associations with IC50 values.ConclusionsPlasmodium vivax was found to be susceptible to CQ drug treatment in both the in vivo therapeutic drug study and the in vitro drug assay. Though the mutant 1076L of Pvmdr1 was found in a majority of isolates tested, this single mutation did not associate with CQ resistance. MS haplotypes revealed strong heterogeneity in this population, indicating a low probability of reinfection with highly related haplotypes.

【 授权许可】

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© Shalini et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.