Two novel mutations of pfdhps K540T and I588F, affecting sulphadoxine-pyrimethamine-resistant response in uncomplicated falciparum malaria at Banjar district, South Kalimantan Province, Indonesia

Malaria Journal

Research

Sugeng Riyanto¹  Yoes P Dachlan²  Haruki Uemura³  Sukmawati Basuki⁴ 

[1] Department of Health of Banjar District, Jl Jend A Yani KM 100, 70611, Martapura, South Kalimantan Province, Indonesia;Department of Medical Parasitology, Faculty of Medicine, Universitas Airlangga, Jl Mayjen Prof Dr Moestopo 47, 60131, Surabaya, Indonesia;Tropical Infectious Diseases Hospital, Kampus C Universitas Airlangga, Kampus C Jl Mulyorejo, 60115, Surabaya, Indonesia;Department of Protozoology, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan;Medical Science, Graduate School, Faculty of Medicine, Universitas Airlangga, Jl Mayjen Prof Dr Moestopo 47, 60131, Surabaya, Indonesia;Department of Medical Parasitology, Faculty of Medicine, Universitas Airlangga, Jl Mayjen Prof Dr Moestopo 47, 60131, Surabaya, Indonesia;Malaria Study Group/Laboratory of Malaria, Institute of Tropical Disease, Universitas Airlangga, Kampus C Jl Mulyorejo, 60115, Surabaya, Indonesia;

关键词: Plasmodium falciparum;    Sulphadoxine-pyrimethamine;    pfdhfr;    pfdhps;   

DOI  :  10.1186/1475-2875-13-135

 received in 2013-12-23, accepted in 2014-03-25,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundMutations in pfdhfr and pfdhps genes have been shown to associate with sulphadoxine-pyrimethamine (SP) resistance of Plasmodium falciparum parasites. However, pfdhfr, pfdhps genotypes and the correlations to SP treatment outcome in Indonesia has not yet been well analysed.MethodsAfter obtaining informed consent, 61 uncomplicated falciparum malaria patients were recruited in Banjar district, South Kalimantan Province, Indonesia, from October 2009 to August 2010. They were treated by a single oral dose of SP and its effects on clinical and parasitological status were followed until day 28 after treatment. Occasionally, a thick smear blood film for microscopy observation and blood spot on a filter paper for pfdhfr and pfdhps genotype analysis were collected.ResultsPfdhfr and pfdhps genotypes from 24 P. falciparum-infected patients consisting of adequate clinical parasitological response (ACPR) (n = 6; 25.0%) and early treatment failure (ETF) (n = 10; 41.7%) or late parasitological failure (LPF) (n = 8; 33.3%) were obtained by sequencing. Two novel mutations of pfdhps gene, K540T and I588F, were determined in ten and five isolates, respectively. These mutations were present in the pfdhfr/pfdhps combined haplotypes of ANRN I/SGTG A (n = 6), ANRNL/SGTG A (n = 4), and ANRN I/SGE AA(588F) (n = 5), (mutation codons are bold typed); these haplotypes were mostly belonging to parasitological failure (ETF or LPF). The parasites acquiring five mutations in pfdhfr/pfdhps haplotypes and four mutations with additional I588F did not respond adequately to SP treatment.ConclusionMany of Plasmodium falciparum infected patients in Banjar district, South Kalimantan, Indonesia did not respond adequately to SP treatment and these low ineffectiveness of SP in this area was associated with two novel mutations of pfdhps, K540T and I588F.

【 授权许可】

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© Basuki 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.