Introduction: The WHO recommends mass administration of azithromycin 30 mg/kg to eradicate yaws and 20 mg/kg to eliminate trachoma. We evaluated the effectiveness of azithromycin at 20 and 30 mg/Kg, and the number of cycles of mass administration on the treatment and interruption of yaws transmission in the Mba？ki health district in the Central African Republic. Methods: Following a yaws prevalence survey, azithromycin was administered as a mass treatment in four yaws endemic communities in the Mba？ki health district. Azithromycin 30 mg/kg was administered in one cycle in Kenengué and three cycles spaced three months apart in Bambou. In Kapou and Bangui-Bouchia, azithromycin was administered at a dose of 20 mg/kg in one cycle and three cycles, respectively, spaced three months apart. Before the mass treatment round, confirmed yaw cases were selected and followed for seven months. The primary endpoint was serological cure seven months after the first treatment cycle. Secondary endpoints were clinical cure at four weeks after the first treatment cycle and serological cure at four months after the first treatment cycle. A non-inferiority margin (？) of 10% was used. Results: A total of 92 participants aged 1 to 90 years, including 52 men, were included in the study. The frequently encountered skin lesions were ulcers (65.22%) and were localized to the lower limbs (59.78%). Clinical cure was not obtained in Bangui-Bouchia and Kapou (？ = 17.1% and 30.8%). Serological cure at four and seven months was not obtained in Kapou (？ equal to 17.9% and 13.8% respectively). Conclusion: This study confirms the effectiveness of azithromycin 30 mg/kg in a single dose for the treatment of yaws. However, the study suggests that for yaws eradication programs, two to three cycles of mass administration of azithromycin at 20 or 30 mg/kg spaced three months apart, with therapeutic coverage greater than 90% are essential.
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