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HIGH REINFECTION RATE AND TREATMENT FAILURES IN CHILDREN TREATED WITH AMODIAQUINE FOR FALCIPARUM MALARIA IN MUHEZA VILLAGES, NORTHEASTERN TANZANIA

In May 2003, we studied amodiaquine (AQ) efficacy in children < 5 years of age with uncomplicated falciparum malaria in Magoda and Mpapayu (with insecticide treated nets [ITNs]) and Mgome (without ITNs) in Muheza, Tanzania. The trial involved 28 days of follow-up, and data were adjusted by polymerase chain reaction (PCR) genotyping of msp1 and msp2 genes. Additionally, Pfcrt codon 72–76 polymorphisms were studied by PCR and sequence-specific oligonucleotide probe (SSOP) ELISA. In 54 cases with complete follow-up, a significant difference in late treatment failure (LTF) rates was seen (60.7% in ITN versus 88.5% in non-ITN villages, P = 0.02) before PCR correction. However, after PCR correction, 23 cases (60.5%) were confirmed as reinfections, giving a true LTF rate of 21.4% (6/28) and 34.6% (9/26) in the above settings, respectively. Frequency of Pfcrt CVIET haplotype mutation pretreatment was high (97.0%); the remaining samples were CVMNK. We conclude that AQ alone is no longer effective in the study area.

Received March 16, 2005. Accepted for publication March 6, 2006.

Acknowledgments: We thank Rehema Hussein and Batuli Luhanda from Teule hospital for assistance in the clinical component; the people of Magoda, Mpapayu, and Mgome for cooperation; and Julius K. Mhina, Juma A. Akida, Alban Machaga, and Zacharia X. Savael for technical assistance with the field and laboratory work in Tanzania. Dr. Omari Minzi and D. Hipolite Shewiyo assisted with quality check on the AQ tablets. Excellent laboratory assistance rendered by Jimmy Weng in the PCR analysis for Pfcrt, Msp1, and Msp2 is greatly appreciated. We also thank Rashidi Madebe and Alphaxado Manjurano for assisting Jimmy Weng at KCMC biotechnology laboratory. Prof. W. Nkya and Dr. Chris Drakeley are thanked for cooperation in providing facilities at the KCMC BL.

Financial support: This study received financial support from the Danish International Development Agency Grant 104.Dan.8L as part of Tanzanian-Danish collaboration under the Enhancement of Research Capacity program.

^* Address correspondence to Martha M. Lemnge, Tanga Medical Research Centre, PO Box 5004, Tanga, Tanzania. E-mail: mlemnge{at}amani.mimcom.net; marthalemnge{at}yahoo.com

Authors’ addresses: Martha Lemnge, Mwanaidi Kafuye, Method, Segeja, Samwel Gesase, Daniel Minja, and Julius Massaga, National Institute for Medical Research, Tanga Medical Research Centre, PO Box 5004, Tanga, Tanzania. Michael Alifrangis, Anita Rønn, and Ib Bygbjerg, Centre for Medical Parasitology at the Institute of Medical Microbiology and Immunology and Institute of Public Health, University of Copenhagen, Copenhagen, Denmark.

Reprint requests: Martha Lemnge, Tanga Medical Research Centre, PO Box 5004, Tanga, Tanzania. E-mail: mlemnge{at}amani.mimcom.net or marthalemnge{at}yahoo.com.