• Lucy N John, Camila G Beiras, Wendy Houinei, Monica Medappa, Maria Sabok, Reman Kolmau, Eunice Jonathan, Edward Maika, James K Wangi, Petra Pospíšilová, David Šmajs, Dan Ouchi, Iván Galván-Femenía, Mathew A Beale, Lorenzo Giacani, Bonaventura Clotet, Eric Q Mooring, Michael Marks, Martí Vall-Mayans, and Oriol Mitjà.
• From the National Department of Health, Aopi Centre (L.N.J., W.H.), the School of Medicine and Health Sciences, University of Papua New Guinea (L.N.J., O.M.), and the World Health Organization Representative Office in Papua New Guinea (J.K.W.), Port Moresby, the New Ireland Provincial Health Authority, Kavieng (M.S., E.J., E.M.), and Lihir Medical Center, International SOS, Lihir Island (R.K., O.M.) - all in Papua New Guinea; the Infectious Diseases Department and Fight AIDS and Infectious Diseases Foundation, Hospital Universitari Germans Trias i Pujol (L.N.J., C.G.B., D.O., B.C., M.V.-M., O.M.), the Genomes for Life-Genomes of Catalonia Lab Group, Institute for Health Science Research Germans Trias i Pujol (I.G.-F.), and the IrsiCaixa AIDS Research Institute (B.C.), Badalona, the Barcelona Institute for Global Health, Faculty of Medicine, University of Barcelona (L.N.J.), and the Institute for Research in Biomedicine, Barcelona Institute of Science and Technology (I.G.-F.), Barcelona, and Universitat de Vic-Universitat Central de Catalunya, Vic (B.C., O.M.) - all in Spain; the Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic (M. Medappa, P.P., D.Š.); the Parasites and Microbes Programme, Wellcome Sanger Institute, Hinxton (M.A.B.), and the Clinical Research Department, London School of Hygiene and Tropical Medicine, and the Hospital for Tropical Diseases, University College London Hospitals, London (M. Marks) - all in the United Kingdom; the Department of Medicine, Division of Allergy and Infectious Diseases, and the Department of Global Health, University of Washington, Seattle (L.G.); and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston (E.Q.M.).
• N. Engl. J. Med. 2022 Jan 6; 386 (1): 475647-56.

BackgroundTreponema pallidum subspecies pertenue causes yaws. Strategies to better control, eliminate, and eradicate yaws are needed.MethodsIn an open-label, cluster-randomized, community-based trial conducted in a yaws-endemic area of Papua New Guinea, we randomly assigned 38 wards (i.e., clusters) to receive one round of mass administration of azithromycin followed by two rounds of target treatment of active cases (control group) or three rounds of mass administration of azithromycin (experimental group); round 1 was administered at baseline, round 2 at 6 months, and round 3 at 12 months. The coprimary end points were the prevalence of active cases of yaws, confirmed by polymerase-chain-reaction assay, in the entire trial population and the prevalence of latent yaws, confirmed by serologic testing, in a subgroup of asymptomatic children 1 to 15 years of age; prevalences were measured at 18 months, and the between-group differences were calculated.ResultsOf the 38 wards, 19 were randomly assigned to the control group (30,438 persons) and 19 to the experimental group (26,238 persons). A total of 24,848 doses of azithromycin were administered in the control group (22,033 were given to the participants at round 1 and 207 and 2608 were given to the participants with yaws-like lesions and their contacts, respectively, at rounds 2 and 3 [combined]), and 59,852 doses were administered in the experimental group. At 18 months, the prevalence of active yaws had decreased from 0.46% (102 of 22,033 persons) at baseline to 0.16% (47 of 29,954 persons) in the control group and from 0.43% (87 of 20,331 persons) at baseline to 0.04% (10 of 25,987 persons) in the experimental group (relative risk adjusted for clustering, 4.08; 95% confidence interval [CI], 1.90 to 8.76). The prevalence of other infectious ulcers decreased to a similar extent in the two treatment groups. The prevalence of latent yaws at 18 months was 6.54% (95% CI, 5.00 to 8.08) among 994 children in the control group and 3.28% (95% CI, 2.14 to 4.42) among 945 children in the experimental group (relative risk adjusted for clustering and age, 2.03; 95% CI, 1.12 to 3.70). Three cases of yaws with resistance to macrolides were found in the experimental group.ConclusionsThe reduction in the community prevalence of yaws was greater with three rounds of mass administration of azithromycin at 6-month intervals than with one round of mass administration of azithromycin followed by two rounds of targeted treatment. Monitoring for the emergence and spread of antimicrobial resistance is needed. (Funded by Fundació "la Caixa" and others; ClinicalTrials.gov number, NCT03490123.).Copyright © 2022 Massachusetts Medical Society.

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