Abstract

We measured the microbial community structure of genital ulcers in women. Swabs from clinically detected ulcers were tested for HSV-2 and Treponema pallidum by polymerase chain reaction (PCR). HSV-2 and T. pallidum were detected by serum antibody testing. Microbial community structure was characterized by high-throughput 16 s rRNA gene amplicon sequencing. Multiple group testing and Elastic net and Lasso regressions identified taxa associated with differences in factors of interest. Among 49 ulcer specimens from 49 HSV-2 seropositive women, by PCR HSV-2 was recovered from 28 (57%) specimens and T. pallidum from none; one woman showed serologic evidence of syphilis. Overall, 63% of women were HIV-positive and 49% had an uncircumcised male sex partner. By both multiple group testing and regression, Porphyromonas (FDR p-value = 0.02), Prevotella (FDR p-value = 0.03), Anaerococcus (FDR p-value = 0.07), and Dialister (FDR p-value = 0.09) were detected at higher relative abundance in HSV-2 PCR-positive than negative ulcers. The presence of HSV-2 in a lesion was associated with presumed bacterial agents of Bacterial vaginosis. Differences in bacterial communities may contribute to HSV-2 ulcer pathogenesis, severity, or prolonged healing. If these results are confirmed, future studies may consider the influence of BV treatment on women’s GUD and HSV-2 incidence and recurrence.

Highlights

  • Medical male circumcision (MMC) reduces the risk of heterosexual HIV acquisition in African men by ~60%1–3

  • One serologically negative subject had an operational taxonomic units (OTU) annotated as Treponema (30/47,102 sequences before rarefaction) with HSV-2 recovered from the ulcer

  • This study was conducted as response to our previous finding that 55% of men with clinically detected genital ulcers were serologically negative for HSV-2 and syphilis, and 39% had no HSV-2 or T. pallidum recovered by PCR8

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Summary

Introduction

Medical male circumcision (MMC) reduces the risk of heterosexual HIV acquisition in African men by ~60%1–3. Fusobacteria and Sneathia had nearly 6-fold greater odds of recovery from clinically detected non-herpetic and non-syphilitic GUD compared to STI-associated GUD8. These two BV-associated anaerobes are more common among uncircumcised men[4,8]. Bacteria from these genera have inflammatory and tissue destructive properties causing oral mucosal ulcers[9,10,11] In light of this novel yet plausible mechanism by which anaerobic bacteria might contribute to genital ulcer pathogenesis, and the relationships between male circumcision status, penile microbiome, GUD, and HIV, we sought to describe the bacterial community structure of GUD in women and whether that differed by ulcer recovery of HSV-2, HIV status, male partner’s circumcision status, and clinical presentation

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