The Clinical History of Rectal and Urethral Sexually Transmitted Infections among Men who have Sex with Men: Characterizing microbiome host immune interactions for diagnostic and vaccine advances

The Mbili Pamoja Study

Start:                  March 2024

Status:                Recruiting

Design:               Clinical Trial

Study Sites:        Anza Mapema Centre of Excellence and PHDA SWOP Clinics in Nairobi

Sponsor:             National Institutes of Health  

IRB:                      Jaramogi Oginga Odinga Teaching and Referral Hospital ISERC

Purpose:             We propose to analyse the host microbiome and immune response to elucidate the clinical history of incident urethral and rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in a prospective cohort study of men who have sex with men (MSM).

Design:               Over a one-year period, in a prospective cohort study 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). After informed consent process, the following will be collected at baseline, 6 months, and 12 months from all participants: (1) Socio-behavioural, dietary, network, and psychosocial survey; (2) Clinician-conducted medical history and physical examination for clinical outcomes; (3) Clinician-collected penile and rectal swabs for microbiome and mucosal immunology characterization; (4) Bacterial community functional profiling through metatranscriptomic analysis; (5) Mucosal cytokine measurement; (6) Systemic memory and activation markers; (7) STI testing, with detection of CT, NG, and HPV; (8) schistosomiasis testing (Kisumu only). The AIM and ICS assays, and TCR profiling will be done on cases pre- and post-STI. Participants will be compensated 750 Kenyan shillings (~$5.00 USD) for time and travel to take part in the study. Study procedures are expected to take 1.5 to 2 hours at each study visit. 

Population:        MSM who report being assigned male at birth, aged 18-39, and report sexual activity with another man or transgender/non-binary person assigned male at birth in the past 3 months and living in the study catchment area.

Study Size:          We target a desired sample size of 75 incident STI infections. With expected STI incidence of 18 per 100 PY, we need to enrol 417 men. Follow-up in our cohorts ranges 72-95%. Estimating 85% follow-up rate, we seek to enrol 491 men, and round this to 500.

Study Aims:        Aim 1: Describe the clinical history of STIs from (1) time of detection, to (2) time of treatment, to (3) post-treatment. Based on our prior studies, in a cohort of 500 MSM in Kisumu (n=250) and Nairobi (n=250), we expect 70-80 incident CT and NG infections over one year of follow-up. At baseline (prevalent infection) and one year (incident infection), we will characterize the clinical history of CT and NG infection in terms of bacterial community composition and function, and host immunology from: time of detection, to time of treatment, to 4 weeks post treatment.

Aim 2: Identify microbiome community composition and specific taxa associated with STI incidence and symptomatic infection. We hypothesize that bacterial communities and dominant taxa with more inflammatory profiles will be associated with increased risk of STI acquisition. We will additionally examine host immune profile as an intermediate outcome, characterizing the associations between microbiome composition and inflammatory profile over time.

Aim 3: Identify adaptive immune mechanisms that link microbiome, STI infection, and host immunity. We hypothesize that more inflammatory microbiome profiles will be associated with increased risk of incident STI infection, and that this will be mediated by gut microbiota-linked systemic inflammation that impedes successful mounting of natural NG- and CT-specific B and T cell responses. We will also examine the frequency, phenotype, and clonality of antigen-specific T cell subsets that may mediate vaccine efficacy, and how these are impacted by baseline gut microbiota and inflammation.