Microbial Diversity of Genital Ulcer Disease in Men Enrolled in a Randomized Trial of Male Circumcision in Kisumu, Kenya
journal contributionposted on 2013-11-12, 00:00 authored by Supriya D. Mehta, Stefan J. Green, Ian Maclean, Hong Hu, Robert C. Bailey, Patrick M. Gillevet, Greg T. Spear
Background: Medical male circumcision (MMC) reduces the risk of genital ulcer disease (GUD) in men by 50%. In Ugandan and Kenyan trials, a sexually transmissible agent was not identified in 50–60% of GUD specimens by polymerase chain reaction (PCR) assay. We sought to better define the etiology of GUD in men participating in the Kenyan trial and examine how MMC affects GUD etiology. Methods: We defined GUD of unknown etiology as negative for HSV (type 1 and type 2), T. pallidum, and H. ducreyi by PCR, and negative for HSV-2 and T. pallidum by serology. We identified bacterial microbiota in a subset of 59 GUD specimens using multitag pyrosequencing of the 16S rRNA gene, and compared results by unknown vs. STI-associated etiology. Statistical analysis employed Bray-Curtis similarity measure of bacterial community by etiology, hierarchical clustering and logistic regression. Results: In 59 GUD specimens from 59 men, 23 (39%) had unknown etiology. Bacterial diversity was greater in GUD of unknown than STI etiology (p = 0.01). Fusobacteria (Fusobacterium spp. and Sneathia spp.) were more commonly detected in men with GUD of unknown etiology [adjusted OR = 5.67; 95% CI: 1.63–19.8] as were Oxobacter spp. and Anaerovorax spp. [adjusted OR = 3.12; 95% CI: 0.83–11.7]. Sequences from these four anaerobic bacterial taxa were more often detected in uncircumcised men than circumcised men (p,0.05). Conclusions: Anaerobic bacteria are more common in genital ulcers of uncircumcised men. The specific anaerobic bacteria associated with GUD of unknown etiology have cytotoxic properties that can exacerbate epithelial disruptions leading to ulcer-like appearance. MMC may reduce GUD through a reduction in these anaerobic bacteria.
This analysis was supported by a pilot grant award from the Chicago Developmental Center for AIDS Research. The clinical trial in which the data were collected was supported by grant number AI50440 from the National Institute of Allergy and Infectious Diseases (NIAID), Division of AIDS, National Institutes of Health; and by grant number HCT 44180 from the Canadian Institutes of Health Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Statement© 2012 Mehta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PublisherPublic Library of Science