Kobe J. Med. Sci., Vol. 49, No. 6, pp. 143-151, 2003 Phone: 81-78-382-5111(ext. 5681) Fax: 81-78-382-5715 E-mail: mkawabat@med.kobe-u.ac.jp 143 Effects of Mefloquine Usage on Genetic Polymorphism of Plasmodium Falciparum in Thai-Myanmarese Border TOSHIAKI MATSUO 1 , TOSHIRO SHIRAKAWA 1 , PRATAP SINGHASIVANON 2 , SORNCHAI LOOAREESUWAN 2 , and MASATO KAWABATA 1 International Center for Medical Research, Kobe University School of Medicine, Kobe 650-0017, Japan 1 ; Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand 2 Received 16 December 2003/ Accepted 23 February 2004 Key words: Plasmodium falciparum, genetic polymorphism, msp-1, mefloquine resistance, Thailand We studied the polymorphism of msp-1, which encodes a major surface protein on the merozoite, isolated from blood samples from western Thailand in 1999. Our study area was a low-transmission area for malaria, where mefloquine has been used as an antimalarial drug since 1994. Forty-nine patients were confirmed to have contracted falciparum malaria twice within 24 weeks. The number of detected haplotypes in 49 patients was 89 at the first diagnosis and 68 at the second diagnosis. The mean number of haplotypes per patient significantly decreased from 1.82 to 1.39 but the frequency distributions of msp-1 haplotypes did not change significantly with the use of mefloquine. Our study strongly suggests that the antigenic diversity of Plasmodium falciparum is retained during mefloquine therapy in low-transmission areas. Falciparum malaria is an infectious disease caused by Plasmodium falciparum, and unless diagnosed and treated early, is often fatal. Approximately three hundred million clinical cases of malaria occur worldwide each year and over one million people die (22). The burden of this disease in disability-adjusted life years (DALYs) accounts for approximately 3% of all disease (23). Moreover, multidrug-resistant malaria has been a severe problem since about 1960 when chloroquine-resistant malaria was first reported in the Thai-Cambodian border regions, Colombia, and Venezuela (24). Repetition of infection and a difficulty in acquiring immunity are characteristic of malaria. Antigenic diversity is also known to play a role in its characteristics and the immune response is believed to be strain-specific (1) (3). It is also reported that exposure to different antigens is more specifically important for acquiring immunity of malaria (2). Thus, it is important to examine the antigenic diversity of malaria parasites in malaria-endemic areas. Currently, many kinds of antimalarial drugs are used for therapy, and the rate of expansion of multidrug-resistant malaria strains is known to differ between regions (4). It is believed that the use of antimalarial drugs decreases the degree of polymorphism and indirectly influences the immunological situation of a given area. However, little is known about the effects of drug therapy on antigenic diversity. It is reported that therapy with pyrimethamine/sulfadoxine and chlorproguanil/dapsone did not affect the number of clones of Plasmodium falciparum per individual (multiplicity) or the polymorphism of Plasmodium