Evidence map›Paper›PMID 24885535›Full record

ArticleMalaria journal2014

Characterization of drug resistance associated genetic polymorphisms among Plasmodium falciparum field isolates in Ujjain, Madhya Pradesh, India.

Ashish Pathak, Andreas Mårtensson, Sudhir Gawariker, Jagdish Mandliya, Ashish Sharma, Vishal Diwan, Johan Ursing

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Article in Malaria journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.

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11citing papers in PubMed, 2 pooled it
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1 · What the graph read from it

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3 · Its place in the literature

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11 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Ashish Pathak
Andreas Mårtensson
Sudhir Gawariker
Jagdish Mandliya
Ashish Sharma
Vishal Diwan
Johan UrsingMalaria Research, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. johan.ursing@karolinska.se.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSince 2011, artesunate + sulphadoxine-pyrimethamine (ASP), instead of chloroquine, has been recommended for treatment of uncomplicated malaria in India. In Ujjain, central India, with an annual parasite index <0.1, the prevalence of drug-resistant Plasmodium falciparum is unknown. In other parts of India chloroquine and sulphadoxine-pyrimethamine-resistant P. falciparum is prevalent. The aim of this study was to determine the prevalence of anti-malarial drug resistance-associated genetic polymorphisms in P. falciparum collected in Ujjain in 2009 and 2010, prior to the introduction of ASP.

methodsBlood samples from 87 patients with P. falciparum mono-infection verified by microscopy were collected on filter-paper at all nine major pathology laboratories in Ujjain city. Codons Pfcrt 72-76, pfmdr1 1034-1246, pfdhfr 16-185, pfdhps 436-632 and pfnhe1 ms4760 haplotypes were identified by sequencing. Pfcrt K76T and pfmdr1 N86Y were identified by restriction fragment length polymorphism, and pfmdr1 gene copy number by real-time PCR.

resultsSulphadoxine-pyrimethamine resistance-associated pfdhfr 108 N and 59R alleles were found in 75/78 (96%) and 70/78 (90%) samples, respectively, and pfdhps 437G was found in 7/77 (9%) samples. Double mutant pfdhfr 59R + 108 N were found in 62/76 (82%) samples. Triple mutant pfdhfr 59R + 108 N and pfdhps 437G were found in 6/76 (8%) samples. Chloroquine-resistance-associated pfcrt 76 T was found in 82/87 (94%). The pfcrt 72-76 haplotypes found were: 80/84 (95%) SVMNT, 3/84 (4%) CVMNK and 1/84 (1%) CVMNT. Pfmdr1 N86 and 86Y were identified in 70/83 (84%) and 13/83 (16%) samples, respectively. Pfmdr1 S1034 + N1042 + D1246 were identified together in 70/72 (97%) of successfully sequenced samples. One pfmdr1 gene copy was found in 74/75 (99%) successfully amplified samples.

conclusionThis is the first characterization of key anti-malarial drug resistance-associated genetic markers among P. falciparum collected in Ujjain, Madhya Pradesh, India. The results indicate that the efficacy of standard dose chloroquine at the time of the study was likely to be poor, whereas ASP was likely to be efficacious, supporting the changed drug treatment policy. However, P. falciparum with reduced susceptibility to sulphadoxine-pyrimethamine is highly prevalent, highlighting the need for continuous surveillance of ASP efficacy in the study area.

Indexed as

Drug ResistancePolymorphism, GeneticAdolescentAdultAntimalarialsFemaleHaplotypesHumansIndiaMalaria, FalciparumMalePlasmodium falciparumPolymorphism, Restriction Fragment LengthProtozoan ProteinsReal-Time Polymerase Chain ReactionSequence Analysis, DNAAntimalarialsProtozoan Proteins

Identifiers

PMID24885535
PMCPMC4036110

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