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HIGH FREQUENCY OF RECOMBINATION-DRIVEN ALLELIC DIVERSITY AND TEMPORAL VARIATION OF PLASMODIUM FALCIPARUM MSP1 IN TANZANIA

A major mechanism for the generation allelic diversity in the Plasmodium falciparum msp1 gene is meiotic recombination in the Anopheles mosquito. The frequency of recombination events is dependent on the intensity of transmission. Herein we investigate the frequency of recombination-driven allelic diversity and temporal variation of msp1 in Rufiji, eastern coastal Tanzania, where malaria transmission is intense. We identified 5' recombinant types, 3' sequence types, and msp1 haplotypes (unique associations of 5' recombinant types and 3' sequence types) to measure the extent and temporal variation of msp1 allelic diversity. The results show that msp1 haplotype diversity is higher in Tanzania as compared with areas with lower transmission rates. The frequencies of individual polymorphic regions/sites remained stable during the study period. However, the frequency distribution of msp1 haplotypes varied between 1993 and 1998. These results suggest that frequent recombination events between msp1 alleles intermittently generate novel alleles in high transmission areas.

Received October 31, 2006. Accepted for publication December 11, 2006.

Acknowledgments: The authors thank Richard Culleton for reading this manuscript and his comments. We are grateful to the villagers and the research team in Nyamisati who participated in this study.

Financial support: This study was supported by a Grant-in-Aid for Scientific Research on Priority Areas from The Japanese Ministry of Education, Culture, Sports, Science and Technology (18073013), Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (18390131, 18GS03140013), the Japanese Ministry of Health, Labor and Welfare (H17-Sinkou-ippan-019), and the Swedish International Development Agency.

^* Address correspondence to K. Tanabe, International Research Center of Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan. E-mail: kztanabe{at}biken.Osaka-u.ac.jp

Authors’ addresses: Kazuyuki Tanabe and Naoko Sakihama, Laboratory of Malariology, International Research Center of Infectious Diseases, Research Institute for Microbial Diseases Osaka University, 3-1, Yamada-Oka, Suita, 565-0871, Japan, Telephone: +81-6-6879-4260, Fax: +81-6-6879-4262, E-mail: kztanabe{at}biken.osaka-u.ac.jp. Ingegerd Rooth, Nyamisati Malaria Research Unit, P.O. Box, 663, Dar es Salaam, Tanzania. Anders Björkman and Anna Färnert, Unit of Infectious Diseases, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Solna, SE-17176 Stockholm, Sweden.

Reprint requests: Kazuyuki Tanabe, Laboratory of Malariology, International Research Center of Infectious Diseases, Research Institute for Microbial Diseases Osaka University, 3-1, Yamada-Oka, Suita, 565-0871, Japan. Telephone: +81-6-6879-4260, Fax: +81-6-6879-4262, E-mail: kztanabe{at}biken.osaka-u.ac.jp.