The etiology of exudative cutaneous ulcers in a yaws-endemic community prior to receipt of antimicrobials is similar to that found in communities after mass treatment with azithromycin

Mass drug administration (MDA) of azithromycin (AZ) and case finding and treatment of children with cutaneous ulcers (CU) has been trialed as a strategy to eliminate yaws. Metagenomic sequencing of CU swabs obtained from children 3 to 4 years after initiation of a yaws elimination campaign on Lihir Island showed enrichment of Treponema pallidum subsp. pertenue (TPE), Haemophilus ducreyi (HD), Streptococcus pyogenes (SP) and several anaerobic bacteria. Whether these results were influenced by AZ pressure or are generalizable to other populations is unknown. Here, we performed quantitative PCR (qPCR) for TPE, HD, and SP DNAs and metagenomic sequencing on 260 CU specimens collected from children on New Britain Island, whose inhabitants had not received MDA of AZ. Based on qPCR results, specimens were classified as containing no, single, or multiple pathogens. 31.9% of the specimens contained SP, 28.1% HD and 25.4% TPE DNAs; mixed infections with 2 or 3 pathogen DNAs occurred in 16.5% of cases. No pathogen DNA was detected in 31.5% of the specimens, which were defined as idiopathic ulcers (IU). In most of the categories, the same pathogen(s) used to classify the ulcers by qPCR were the most abundant taxa present in the specimens. In IU, the most abundant taxon was Arcanobacterium haemolyticum; however, its relative abundance was similar across all groups, suggesting that this organism may adapt to the CU environment rather than represent a cause of IU. These data indicate that TPE, HD and SP are the primary causes of CU in this untreated population.