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

Abstract

Background In yaws-endemic areas, two-thirds of exudative cutaneous ulcers (CU) are associated with Treponema pallidum subsp. pertenue (TP) and Haemophilus ducreyi (HD); one-third are classified as idiopathic ulcers (IU). A yaws eradication campaign on Lihir Island in Papua New Guinea utilizing mass drug administration (MDA) of azithromycin initially reduced but failed to eradicate yaws; IU rates remained constant throughout the study. Using 16S rRNA gene sequencing, we previously determined that Streptococcus pyogenes was associated with some cases of IU. Here, we applied shotgun metagenomics to the same samples we analyzed previously by 16S rRNA sequencing to verify this result, identify additional IU-associated microorganisms, and determine why S. pyogenes-associated IU might have persisted after MDA of azithromycin. Methodology/Principal findings We sequenced DNA extracted from 244 CU specimens separated into four groups based upon microorganism-specific PCR results (HD+, TP+, TP+HD+, and TP-HD- or IU). S. pyogenes was enriched in IU (24.71% relative abundance [RA]) specimens compared to other ulcer sub-groups, confirming our prior results. We bioinformatically identified the emm (M protein gene) types found in the S. pyogenes IU specimens and found matches to emm156 and emm166. Only ~39% of IU specimens contained detectable S. pyogenes, suggesting that additional organisms could be associated with IU. In the sub-set of S. pyogenes-negative IU specimens, Criibacterium bergeronii, a member of the Peptostreptococcaceae, and Fusobacterium necrophorum (7.07% versus 0.00% RA and 2.18% versus 0.00% RA, respectively), were enriched compared to the S. pyogenes-positive sub-set. Although a broad range of viruses were detected in the CU specimens, none were specifically associated with IU. Conclusions/Significance Our observations confirm the association of S. pyogenes with IU in yaws-endemic areas, and suggest that additional anaerobic bacteria, but not other microorganisms, may be associated with this syndrome. Our results should aid in the design of diagnostic tests and selective therapies for CU.

Mycobacterium ulcerans-Bordetella trematum chronic tropical cutaneous ulcer: A four-case series, Côte d’Ivoire

“…Present study offers one more example of polymicrobial chronic tropical ulcer: our study echoes previous microscopic observations of mixed spirochetes and fusobacteria in tropical ulcers in four different tropical countries (Zambia, Gambia, southern India and Papua New Guinea); recently complemented by metagenomic confirmation of Fusobacterium necrophorum in samples from Papua New Guinea [48,49]. Understanding microbial diversity in tropical ulcers may offer valuable insights into the diagnosis and management of Buruli ulcer, particularly in cases where co-infections may play a role.…”

Prevalence and risk factors associated with Haemophilus ducreyi cutaneous ulcers in Cameroon

“…While our research has primarily focused on HD and to a lesser extent to TPE , it is worth noting that other pathogens, including Streptococcus pyogenes [ 42 ], Streptococcus dysgalactiae , Arcanobacterium haemolyticum , Corynebacterium diphtheriae [ 43 ], Fuso-bacterium , Bacillus fusiformis , Treponema vincentii [ 8 ] have also been described to be associated with approximately one-third of cutaneous encountered in yaws-endemic communities.…”

Tackling Infectious Diseases with Rapid Molecular Diagnosis and Innovative Prevention

“…It is not clear if it has a pathologic role. It was later shown by other researchers to be found in the vagina of women with gynecologic cancer [ 72 ], and to be associated in large numbers with idiopathic cutaneous ulcers in children treated with azithromycin [ 73 ].…”