Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study

BACKGROUND: Yaws is an important cause of chronic disfiguring ulcers in children in the tropics. WHO’s newly adopted strategy for yaws eradication employs a single round of mass azithromycin treatment followed by targeted treatment programs, and data from pilot studies have shown a short-term significant reduction of yaws. We assessed the long-term efficacy of the WHO strategy for yaws eradication. METHODS: We conducted a longitudinal study on a Papua New Guinea island (16092 population) in which yaws was endemic. In the initial study, the participants were followed for 12 months; in this extended follow-up study, clinical, serological, and PCR surveys were continued 6-monthly for 3·5 years; genotyping and travel history were used to identify importation events. Active yaws confirmed by a Treponema pallidum specific PCR was the primary-outcome indicator. FINDINGS: Mass azithromycin treatment (coverage rate of 84%) followed by targeted treatment programs reduced the prevalence of active yaws from 1·8% to a minimum of 0·1% at 18 months (difference from baseline, −1·7%; P<0·0001), but the infection began to re-emerge after 24 months with a significant increase to 0·4% at 42 months (difference from 18 months, 0·3%; P<0·0001). At each time point after baseline, > 70% of the total community burden of yaws was found in persons absent from the mass treatment or as new infections in non-travelling residents. At months 36 and 42, five cases of active yaws, all from the same village, demonstrated clinical failure following azithromycin treatment with PCR detected mutations in the 23S ribosomal RNA genes conferring resistance to azithromycin. A sustained decrease in the prevalence of high titre latent yaws in asymptomatic children aged 1–5 years from 13.7% to <1.5%, and of genetic diversity of yaws strains from 0·139 to <0·046 between 24 and 42 months indicated a reduction in transmission of infection. INTERPRETATION: The implementation of the WHO strategy did not, in the long-term, achieve elimination in a high-endemic community mainly due to persons who were absent at the time of mass treatment in whom yaws reactivated; repeated mass treatment may be necessary to eliminate yaws. For the first time, we report the emergence of azithromycin-resistant T. p. pertenue and spread within one village. Communities’ surveillance should be strengthened to detect any possible treatment failure and biological markers of resistance.