Background Medical male circumcision (MMC) reduces the risk of HIV acquisition by ∼60%, in part by reducing genital ulcer disease (GUD) and HSV-2. In the Ugandan and Kenyan trials, PCR did not find a sexually transmissible agent in 50–60% of GUD specimens, and MMC did not protect against HSV-2 in the Kenyan trial. We sought to better define the aetiology of GUD in the Kenyan trial and examine how MMC affects GUD aetiology.
Methods We defined GUD of unknown aetiology 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. In 59 GUD specimens from 59 men, 23 (39%) had unknown aetiology. We identified bacterial microbiota in all 59 specimens using multitag pyrosequencing of the 16S rRNA gene, and compared results by unknown vs STI aetiology. Statistical analysis employed exact methods.
Results Overall, 83 distinct genera were detected. Prevotella spp. was most abundant, accounting for 18% of microbiota on average, and present in 75% of specimens. Bacterial diversity was greater in GUD of unknown aetiology than STI associated GUD (median number of genera 13 [range 7–20] vs 11 [range 3–20], p=0.06). Fusobacterium spp., Sneathia spp. and Anaerococcus spp. were more abundant in GUD of unknown aetiology (7.7%, 7.6%, and 7.3%, respectively) than in GUD of STI aetiology (4.6%, 5.0%, and 5.4%). Fusobacteriales (Fusobacterium spp. or Sneathia spp.) [OR=4.7; 95% CI: 1.3 to 19.9] and Anaerococcus spp. [OR=4.6; 95% CI: 1.2 to 22.5] were more likely to be recovered in GUD of unknown aetiology than STI associated GUD. Fusobacteriales were more often recovered from uncircumcised men than circumcised men (62% vs 22%, p=0.04), and Anaerococcus spp. was present in 22% of circumcised vs 70% of uncircumcised men (p=0.010). Reported penile coital injuries were more common among men with Anaerococcus spp. (85% vs 57%, p=0.01), and condom use was less common (50% vs 71%, p=0.11). There was no difference in these bacteria by ulcer location.
Conclusions Fusobacteriales and Anaerococcus spp. may colonise genital ulcers that develop from a mechanism related to circumcision status. Many such “ulcers” may be epithelial disruptions that are traumatic in origin. These bacteria have cytotoxic properties that may ulcerate or exacerbate pre-existing minor epithelial disruptions. MMC may reduce GUD through a reduction in these anaerobic bacteria.
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