03877nas a2200397 4500000000100000008004100001260003400042653002100076653001700097100001200114700001400126700001400140700001400154700001200168700001300180700001500193700001200208700001300220700002100233700001300254700001200267700002300279700001300302700001400315700001300329700001500342700001200357700001800369700001300387245008300400856007300483300001000556490000800566520288000574022002503454 2022 d bMassachusetts Medical Society10aGeneral Medicine10aAzithromycin1 aJohn LN1 aBeiras CG1 aHouinei W1 aMedappa M1 aSabok M1 aKolmau R1 aJonathan E1 aMaika E1 aWangi JK1 aPospíšilová P1 aŠmajs D1 aOuchi D1 aGalván-Femenía I1 aBeale MA1 aGiacani L1 aClotet B1 aMooring EQ1 aMarks M1 aVall-Mayans M1 aMitjà O00aTrial of Three Rounds of Mass Azithromycin Administration for Yaws Eradication uhttps://www.nejm.org/doi/pdf/10.1056/NEJMoa2109449?articleTools=true a47-560 v3863 a

BACKGROUND

Treponema pallidum subspecies pertenue causes yaws. Strategies to better control, eliminate, and eradicate yaws are needed.

METHODS

In 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.

RESULTS

Of 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.

CONCLUSIONS

The 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. opens in new tab.)

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