BACKGROUND: Persistent trachoma is increasingly recognized as a serious concern for the global trachoma program. Persistent trachoma is defined as those districts that have had two or more trachoma impact surveys in which the trachomatous inflammation-follicular (TF) prevalence has never been <
5%, the elimination threshold for TF. Enhanced tools such as infection and serological monitoring elucidate long-term transmission patterns within persistent districts. This study aimed to clarify trachoma intensity via both traditional indicators and Chlamydia trachomatis (Ct) infection and serologic markers in four districts experiencing persistent trachoma with >
10 years of interventions. METHODOLOGY: Population-based surveys were conducted in 2019 in four trachoma persistent districts. Children ages 1-9 years were examined for trachoma clinical signs and children 1-5 years were swabbed for Ct infection. Antibodies to the trachoma antigens Pgp3 and CT694 were measured for all individuals ≥1 year, assessed by multiplex bead assay. Seroconversion rates (SCRs) to both antigens were estimated for children and for individuals of all ages. RESULTS: One district, Ebinat, remained highly endemic, with a TF prevalence and infection prevalence (ages 1-5 years) of 42.5% and 7.1% respectively. Indicators were lower in the other three districts ranging from 10.7%-17.9% TF and 0%-1.7% infection. The Pgp3 SCR among children ages 1-9 years was considerably higher in Ebinat with 10.8 seroconversions per 100 child-years, (95% Confidence Interval [CI]: 8.2, 14.4) compared to the other three districts (SCR range: 0.9-3.9). All-age Pgp3 SCR estimates detected a significant decline in seroprevalence in Machakel district at approximately 12 years prior to 2019. CONCLUSIONS: Infection and serology may be useful tools for clarifying transmission, particularly among persistent districts, and ongoing interventions likely helped push these hyperendemic districts towards the elimination threshold. However, districts such as Ebinat may require more intense interventions to reach elimination within acceptable timelines.