Trial of Three Rounds of Mass Azithromycin Administration for Yaws Eradication

Abstract

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.)

Two Streptococcus pyogenes emm types and several anaerobic bacterial species are associated with idiopathic cutaneous ulcers in children after community-based mass treatment with azithromycin

“…The differences observed between the studies may be due to the different specimen collection periods or other technical differences. There was a large difference in sequencing depth between the studies, with this study having approximately 17x more depth than the previous study (11,418 median microorganism reads vs 678 median reads with species level identification in the CU specimens, respectively). Choice of annotation methods between the previous study (MEGAN and Kraken) and our study (MetaPhlAn3) may also explain some differences found in these two studies.…”

“…Since the overall prevalence of CU was still at 0.8% after 42 months, the trial was halted due to the failure to achieve the primary endpoint, eradication of yaws [ 10 ]. Another yaws eradication community-based trial in the Namatanai District of the New Ireland Province of Papua New Guinea used three rounds of MDA of azithromycin given every six months; however, this trial also failed to eradicate yaws [ 11 ].…”

“…Factors that could have contributed to these failures of prior attempts to eliminate yaws using MDA were the re-introduction of yaws in persons who were absent at the time of MDA, the emergence of azithromycin resistance in TP, environmental reservoirs of HD, and the consistent prevalence of IU throughout both trials [ 10 , 11 ]. The last observation suggests that azithromycin-resistant pathogen(s) could cause IU.…”

An integrated active case search for skin-NTDs in yaws endemic health districts in Cameroon, Côte d’Ivoire and Ghana

“…Areas of co-endemicity of skin-NTDs have undergone several investigations with treatment which have certainly reduced the incidence of yaws (10). The results of this study suggest that additional efforts are needed to control yaws in the three countries where the disease is endemic, in particular the number of rounds of MDA which can be reviewed to significantly reduce the incidence of the disease (51). More than 80% of yaws like ulcers were not yaws (542/3085), suggesting that proper identification and management of other cutaneous ulcers, such as H. ducreyi , is important to improve patient outcomes.…”

Diagnostics to support the eradication of yaws—Development of two target product profiles

“…A major concern has been the identification of a small number of cases of yaws which have developed resistance to azithromycin [5]. In Papua New Guinea, long term follow up studies have reported Azithromycin resistant yaws cases 24 months post MDA [6,7]. Two point mutations (A2059G and A2058G in the 23S ribosomal genes) are known to confer resistance to azithromycin in T.pallidum subsp pallidum, and both have now has been detected in T.pallidum subsp pertenue.…”