A Trial of Three Rounds of Mass Drug Administration with Azithromycin for Yaws

BACKGROUND: Treponema pallidum subsp. pertenue causes yaws. Strategies to better control and hopefully eliminate yaws are needed. METHODS: We conducted an open-label cluster-randomized community trial in a yaws-endemic area of Papua New Guinea. Thirty-eight wards were randomized to receive either one mass drug administration (MDA) round followed by two target treatment of active cases rounds (control arm) or three MDA rounds (experimental arm) at 6-month intervals. The difference in the prevalence of active and latent yaws were measured at 18-month surveys. RESULTS: Nineteen wards (30,438 individuals) were randomized to the control arm and 19 (26,238 individuals) to the experimental arm. 24,848 azithromycin doses were administered in the control arm (22,033 at baseline, 207 participants with yaws-like lesions and 2,608 contacts at 6-month and 12-month), compared to 59,852 doses in the experimental arm. At 18 months, the prevalence of active yaws had decreased from 0.46% (102/22,033) to 0.16% (47/29,954) in the control arm and from 0.43% (87/20,331) to 0.04% (10/25,987) in the experimental arm (RR 3.54; 95%CI 1.72–7.27). The prevalence of other infectious ulcers decreased to a similar extent in the two study arms. The prevalence of latent yaws at 18 months, assessed in 994 and 945 children in the control and experimental arms, was 6.54% (5.00–8.08) and 3.28% (2.14–4.42), respectively (RR 2.03; 1.12–3.7). Three cases with resistance to macrolides were found in the experimental arm. CONCLUSIONS: These data show that three rounds of azithromycin MDA 6 months apart are better than one round of azithromycin MDA with two rounds of targeted treatment for decreasing the community prevalence of yaws. Monitoring for the emergence and spread of antimicrobial resistance is needed. (ClinicalTrials.gov number, NCT03490123.)