Newcrest Mining Company.

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SummaryBackgroundTo achieve yaws eradication, the use of the new WHO strategy of initial mass treatment with azithromycin and surveillance twice a year needs to be extended everywhere the disease occurs. However, the geographic scope of the disease is unknown. We aimed to synthesise published and unpublished work to update the reported number of people with yaws at national and subnational levels and to estimate at-risk populations.MethodsWe searched PubMed and WHO databases to identify published data for prevalence of active and latent yaws from Jan 1, 1990, to Dec 31, 2014. We also searched for ongoing or recently completed unpublished studies from the WHO yaws surveillance network. We estimated yaws prevalence (and 95% CIs). We collected yaws incidence data from official national surveillance programmes at the first administrative level from Jan 1, 2010, to Dec 31, 2013, and we used total population data at the second administrative level to estimate the size of at-risk populations.FindingsWe identified 103 records, of which 23 published articles describing 27 studies and four unpublished studies met the inclusion criteria. Prevalence of active disease ranged from 0·31% to 14·54% in yaws-endemic areas, and prevalence of latent yaws ranged from 2·45% to 31·05%. During 2010–13, 256 343 yaws cases were reported to WHO from 13 endemic countries, all of which are low-income and middle-income countries. 215 308 (84%) of 256 343 cases reported to WHO were from three countries—Papua New Guinea, Solomon Islands, and Ghana. We estimated that, in 2012, over 89 million people were living in yaws-endemic districts.InterpretationPapua New Guinea, Solomon Islands, and Ghana should be the focus of initial efforts at implementing the WHO yaws eradication strategy. Community-based mapping and active surveillance must accompany the implementation of yaws eradication activities.FundingNone.

Background In a longitudinal study assessing the WHO strategy for yaws eradication using mass azithromycin treatment, we observed resurgence of yaws cases with dominance of a single JG8 sequence type and emergence of azithromycin-resistant Treponema pallidum subspecies pertenue (T p pertenue). Here, we analyse genomic changes in the bacterial population using samples collected during the study. MethodsWe did whole bacterial genome sequencing directly on DNA extracted from 37 skin lesion swabs collected from patients on Lihir Island, Papua New Guinea, between April 1, 2013, and Nov 1, 2016. We produced phylogenies and correlated these with spatiotemporal information to investigate the source of new cases and the emergence of five macrolide-resistant cases. We used deep amplicon sequencing of surveillance samples to assess the presence of minority macrolide-resistant populations.Findings We recovered 20 whole T p pertenue genomes, and phylogenetic analysis showed that the re-emerging JG8 sequence type was composed of three bacterial sublineages characterised by distinct spatiotemporal patterns. Of five patients with resistant T p pertenue, all epidemiologically linked, we recovered genomes from three and found no variants. Deep sequencing showed that before treatment, the index patient had fixed macrolide-sensitive T p pertenue, whereas the post-treatment sample had a fixed resistant genotype, as did three of four contact cases.Interpretation In this study, re-emergence of yaws cases was polyphyletic, indicating multiple epidemiological sources. However, given the genomic and epidemiological linkage of resistant cases and the rarity of resistance alleles in the general population, azithromycin resistance is likely to have evolved only once in this study, followed by onward dissemination.Funding Wellcome and Provincial Deputation of Barcelona.