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Dear Sirs,

Ashley et al. raise two main points. First, they agree with us that mefloquine monotherapy is failing at points along the Thai-Myanmar border and should be replaced by combination therapy. Secondly, they suggest that we lay too much stress on the low adequate clinico-parasitological response (ACPR) to the artesunate–mefloquine combination therapy because the sample size was low, because we did not use polymerase chain reaction (PCR) assays for correction to account for re-infections, and because we used a 2-day, rather than a 3-day artesunate–mefloquine regimen.

We did not use PCR correction for three reasons. First, as explained in the report, transmission intensity at the study site was very low. If 60% of our late recurrences were actually re-infections, as claimed by Ashley et al. at their site in Mae Sot, it would imply an attack rate of at least 10% per month in our population. This is very unlikely given the paucity of cases in the area and the tendency of subjects to remain in town during the follow-up period. Secondly, neither is PCR recommended according to the WHO guidelines for therapeutic efficacy monitoring in low transmission areas. Finally, PCR may falsely identify recrudescences as re-infections if a minor parasite population in the initial infection is missed by PCR and subsequently selected by drug treatment.

We used a 2-day rather than 3-day regimen because in practice compliance is easier, the regimen has remained effective in Tak and Chantaburi since 1995, and we are unaware of any published report of a randomized trial showing that the 3-day regimen is superior.

As reported in the September 2006 issue of the Journal, an artesunate–mefloquine efficacy monitoring conducted on the western border of Cambodia with Thailand in 2004 with the combination given over 3 days, 42 days of follow-up and PCR correction found a cure rate of 79.3% (46/58) (Mey Bouth et al. 2006).

We agree that the finding of reduced artemisinin-based combination therapy (ACT) effectiveness is preliminary and based on only two sites, both with relatively small samples. We hope that ACT will remain effective in other areas for many years. Nonetheless, the history of malaria therapy suggests that no treatment regimen will remain effective indefinitely.

Acknowledgements

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We thank William O. Rogers for his reviews and comments.

Disclaimer

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The views and opinions are those of the authors and do not purport to represent those of the U.S. Navy or Department of Defense.

References

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