Molecular characterisation of drug-resistant Plasmodium falciparum from Thailand

doi:10.1186/1475-2875-1-12

Malaria Journal

Volume 1

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Lopes D
Rungsihirunrat K
Nogueira F
Seugorn A
Gil JP
do Rosário VE
Cravo P

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Rungsihirunrat K
Nogueira F
Seugorn A
Gil JP
do Rosário VE
Cravo P
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Research

Molecular characterisation of drug-resistant Plasmodium falciparum from Thailand

Dinora Lopes¹ , Kanchana Rungsihirunrat² , Fátima Nogueira¹ , Aree Seugorn² , José Pedro Gil¹^,3 , Virgilio E do Rosário¹ and Pedro Cravo¹

¹Centro de Malária e Outras Doenças Tropicais/IHMT/UNL, Rua da Junqueira, 96, 1349-008, Lisbon, Portugal

²Malaria Research Unit, Institute of Health Research, Chulalongkorn University, Bangkok 10330, Thailand

³Present address: Malaria Research Laboratory, Division of Infectious Diseases, Institutionen för Medicin, Karolinska Institutet, Karolinska Sjukhuset, Malaria Research Laboratory L7, Plan 3, 17176 Stockholm, Sweden

author email corresponding author email

Malaria Journal 2002, 1:12doi:10.1186/1475-2875-1-12


Published:	14 October 2002

Abstract

Background

The increasing levels of Plasmodium falciparum resistance to chloroquine (CQ) in Thailand have led to the use of alternative antimalarials, which are at present also becoming ineffective. In this context, any strategies that help improve the surveillance of drug resistance, become crucial in overcoming the problem.

Methods

In the present study, we have established the in vitro sensitivity to CQ, mefloquine (MF), quinine (QUIN) and amodiaquine (AMQ) of 52 P. falciparum isolates collected in Thailand, and assessed the prevalence of four putative genetic polymorphisms of drug resistance, pfcrt K76T, pfmdr1 N86Y, pfmdr1 D1042N and pfmdr1 Y1246D, by PCR-RFLP.

Results

The percentage of isolates resistant to CQ, MF, and AMQ was 96% (50/52), 62% (32/52), and 58% (18/31), respectively, while all parasites were found to be sensitive to QUIN. In addition, 41 (79%) of the isolates assayed were resistant simultaneously to more than one drug; 25 to CQ and MF, 9 to CQ and AMQ, and 7 to all three drugs, CQ, MF and AMQ. There were two significant associations between drug sensitivity and presence of particular molecular markers, i) CQ resistance / pfcrt 76T (P = 0.001), and ii) MF resistance / pfmdr1 86N (P < 0.001)

Conclusions

i) In Thailand, the high levels of CQ pressure have led to strong selection of the pfcrt 76T polymorphism and ii) pfmdr1 86N appears to be a good predictor of in vitro MF resistance.