In sub-Saharan Africa, men who have sex with men (MSM) have 2-4 times higher rates of sexually transmitted
infections (STIs) and HIV than the general male population. In our cohort of 700 MSM in Kisumu, Kenya, the
incidence of urethral and anorectal C. trachomatis (CT) and/or N. gonorrhoeae (NG) was 19.8 per 100 person
years (PY) over one year. These rates are 2-3 times the incidence we measured among heterosexual Kenyan
men. Our studies of MSM in Kisumu and Nairobi have identified specific rectal bacterial community structures
that are associated with inflammatory mucosal immune profiles. Inflammatory rectal microbiome profiles could
increase risk of STI acquisition and interfere with vaccine efficacy by skewing systemic T cell populations
toward an increased memory/decreased naïve lymphocyte ratios, and a higher state of basal immune
activation, as supported by our preliminary investigations. Inflammation could therefore undermine the partial
protective efficacy of STI vaccines ability to prime naïve lymphocytes required for optimal immunity, both by
decreasing the frequency of naïve lymphocytes, and by decreasing the efficiency in which the remaining naïve
T cells are primed. Objective: Over a one-year period, in a sample of 500 MSM in Kisumu (n=250) and Nairobi
(n=250), we will measure the penile and rectal microbiomes, mucosal immune profiles, socio-behavioral and
structural factors, and incidence of urethral and anorectal STIs (CT, NG). In Aim 1, we will characterize the
clinical history of STI infection from time of detection to time of treatment to treatment and clearance.
Samples will be collected from all men at baseline, 6- and 12- months to characterize penile and rectal
microbiome composition (via high throughput amplicon sequencing), mucosal immunology (broad measure of
pro-inflammatory, inflammatory, and anti-inflammatory cytokines and chemokines and measures of epithelial
barrier integrity), and test for STI by nucleic acid amplification assay. Accounting for loss to follow-up, we
expect 70-90 incident CT and/or NG infections, and for these men, microbiome composition, mucosal
immunology, and bacterial function will be assessed again when they present for antibiotic treatment, and 4
weeks subsequent to treatment. In Aim 2, we will quantify how penile and rectal microbiome composition are
associated with risk of incident urethral and rectal STIs, respectively. As a secondary outcome, we will identify
dominant mucosal immune profiles and examine how they change over time in relation to microbiome
composition. In Aim 3, we will in STI cases identify adaptive immune mechanisms that link rectal microbiome,
host immunity, and symptomatic or asymptomatic STI incident infections. Therapeutic and preventive
implications: The impact of STI treatment on penile and rectal microbiome composition and bacterial function
is unknown and characterizing this aspect of clinical history of infection can identify novel treatment and
prevention pathways. Understanding factors that might undermine protective immunity to STIs could be critical
to informing the design of more effective vaccines that are required to achieve STI control.
