Background: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans, primarily affecting rural populations in west and central Africa. Between 2004 and 2023, reported Buruli ulcer cases declined sharply across the continent from 5871 to 1573. Determining whether this decline reflects real epidemiological change or surveillance artifacts is crucial for global Buruli ulcer control. We aimed to quantify the incidence of Buruli ulcer in Benin, to analyse observed epidemiological changes, and to relate them to environmental and climate changes. Methods: We did a nationwide, retrospective, observational study using data recorded by Benin's National Buruli Ulcer Control Programme at four specialised health-care centres in southern Benin over 16 years (2008-24). Data were collected prospectively at the time of patient care. 2568 patients with PCR-confirmed Buruli ulcer were included. Annual incidence trends were examined by age, sex, municipality, and clinical form of the lesion. Environmental and climatic variables, including water surface area, temperature, urbanisation, and land use, were integrated with patient data to assess ecological associations. In parallel, a large-scale environmental survey investigated the presence of M ulcerans DNA in aquatic ecosystems. Data census and population projections were obtained from the National Institute of Statistics and Demography of Benin; environmental variables were derived from spatial analyses conducted using open-access geospatial databases. Findings: The incidence of Buruli ulcer decreased by nearly 80% during the study period, from 1·37 per 10 000 inhabitants (SD 0·21 per 10 000 inhabitants) in 2010-16 to 0·24 per 10 000 inhabitants in 2024, with the steepest decrease in children aged 15 years and younger. Historical age and sex differences in incidence largely disappeared over the period. The decrease in incidence coincided with a 25-30% reduction in open water surfaces and a more than 1°C rise in mean air temperature. M ulcerans DNA was undetectable in 122 aquatic sites sampled between 2021 and 2024. Interpretation: To our knowledge, this study provides the first comprehensive, country-wide evidence of a sustained decline in Buruli ulcer incidence in Africa. Environmental changes, particularly climate warming and water surface reduction, might have contributed to this trend. Continued surveillance is essential to confirm whether Buruli ulcer foci are disappearing and to ensure early detection of potential re-emergence.

Background: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans, primarily affecting rural populations in west and central Africa. Between 2004 and 2023, reported Buruli ulcer cases declined sharply across the continent from 5871 to 1573. Determining whether this decline reflects real epidemiological change or surveillance artifacts is crucial for global Buruli ulcer control. We aimed to quantify the incidence of Buruli ulcer in Benin, to analyse observed epidemiological changes, and to relate them to environmental and climate changes. Methods: We did a nationwide, retrospective, observational study using data recorded by Benin's National Buruli Ulcer Control Programme at four specialised health-care centres in southern Benin over 16 years (2008-24). Data were collected prospectively at the time of patient care. 2568 patients with PCR-confirmed Buruli ulcer were included. Annual incidence trends were examined by age, sex, municipality, and clinical form of the lesion. Environmental and climatic variables, including water surface area, temperature, urbanisation, and land use, were integrated with patient data to assess ecological associations. In parallel, a large-scale environmental survey investigated the presence of M ulcerans DNA in aquatic ecosystems. Data census and population projections were obtained from the National Institute of Statistics and Demography of Benin; environmental variables were derived from spatial analyses conducted using open-access geospatial databases. Findings: The incidence of Buruli ulcer decreased by nearly 80% during the study period, from 1·37 per 10 000 inhabitants (SD 0·21 per 10 000 inhabitants) in 2010-16 to 0·24 per 10 000 inhabitants in 2024, with the steepest decrease in children aged 15 years and younger. Historical age and sex differences in incidence largely disappeared over the period. The decrease in incidence coincided with a 25-30% reduction in open water surfaces and a more than 1°C rise in mean air temperature. M ulcerans DNA was undetectable in 122 aquatic sites sampled between 2021 and 2024. Interpretation: To our knowledge, this study provides the first comprehensive, country-wide evidence of a sustained decline in Buruli ulcer incidence in Africa. Environmental changes, particularly climate warming and water surface reduction, might have contributed to this trend. Continued surveillance is essential to confirm whether Buruli ulcer foci are disappearing and to ensure early detection of potential re-emergence.