Identification of pyrimethamine- and chloroquine-resistant Plasmodium falciparum in Africa between 1984 and 1998: genotyping of archive blood samples

Malaria Journal

Research

Toshihiro Mita¹  Yumiko Saito-Nakano²  Kazuyuki Tanabe³ 

[1] Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan;Department of Parasitology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan;Laboratory of Malariology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan;

关键词: Plasmodium falciparum;    Drug resistance;    Chloroquine;    pfcrt;    Pyrimethamine;    dhfr;    Africa;    Archive sample;   

DOI  :  10.1186/1475-2875-10-388

 received in 2011-09-27, accepted in 2011-12-31,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundUnderstanding the geographical distribution of drug resistance of Plasmodium falciparum is important for the effective treatment of malaria. Drug resistance has previously been inferred mainly from records of clinical resistance. However, clinical resistance is not always consistent with the parasite's genetic resistance. Thus, molecular identification of the parasite's drug resistance is required. In Africa, clinical resistance to pyrimethamine (Pyr) and chloroquine (CQ) was evident before 1980 but few studies investigating the genetic resistance to these drugs were conducted before the late 1990s. In this study, genotyping of genes involved in resistance to Pyr and CQ was performed using archive blood samples from Africa between 1984 and 1998.MethodsParasite DNA was extracted from P. falciparum-infected blood smears collected from travellers returning to Japan from Africa between 1984 and 1998. Genotypes of the dihydrofolate reductase gene (dhfr) and CQ-resistance transporter gene (pfcrt) were determined by polymerase chain reaction amplification and sequencing.ResultsGenotyping of dhfr and pfcrt was successful in 59 and 80 samples, respectively. One wild-type and seven mutant dhfr genotypes were identified. Three dhfr genotypes lacking the S108N mutation (NR SI, I CSI, IR SI; amino acids at positions 51, 59, 108, and 164 with mutations underlined) were highly prevalent before 1994 but reduced after 1995, accompanied by an increase in genotypes with the S108N mutation. The dhfrIRN I genotype was first identified in Nigeria in 1991 in the present samples, and its frequency gradually increased. However, two double mutants (I CN I and NRN I), the latter of which was exclusively found in West Africa, were more frequent than the IRN I genotype. Only two pfcrt genotypes were found, the wild-type and a Southeast Asian type (CVIET; amino acids at positions 72-76 with mutations underlined). The CVIET genotype was already present as early as 1984 in Tanzania and Nigeria, and appeared throughout Africa between 1984 and 1998.ConclusionsThis study is the first to report the molecular identification of Pyr- and CQ-resistant genotypes of P. falciparum in Africa before 1990. Genotyping of dhfr and pfcrt using archive samples has revealed new aspects of the evolutionary history of Pyr- and CQ-resistant parasites in Africa.

【 授权许可】

CC BY   
© Saito-Nakano et al; licensee BioMed Central Ltd. 2011