Progression of scarring trachoma in Tanzanian children: A four-year cohort study

Background: Trachoma is a progressive blinding disease initiated by infection of the conjunctiva with Chlamydia trachomatis. Repeated infections are thought to cause chronic inflammation, which drives scarring, leading to in-turning of the eyelids. The relationship between C. trachomatis, clinical inflammation and scarring development in children is not fully understood due to a paucity of longitudinal studies with infection data at frequent follow-up. Methods and findings: This longitudinal cohort study took place in northern Tanzania. Children aged 6–10 years at baseline were eligible for inclusion. Participants were visited every three months for four years. Clinical signs and conjunctival swabs for C. trachomatis detection by qPCR were collected at each time-point. Conjunctival photographs from baseline and final time-points were graded and compared side-by-side to determine scarring incidence and progression. Conclusions: These data suggest that the effect of infection on scarring progression is mediated through papillary inflammation, and that other factors contributing to the development of inflammation, in addition to C. trachomatis infection, may be important in driving conjunctival scarring progression in children. The addition of TP as a measure in trachoma control programs would provide an indication of the future risk of developing scarring sequelae. Author summary: Trachoma is the leading cause of preventable blindness worldwide and is targeted for elimination as a public health problem by 2020. The natural history of trachoma is not completely understood however. We conducted a four-year longitudinal study in a trachoma-endemic area of northern Tanzania with detailed follow up every three months. In the four-year study period, nearly one quarter of children developed progression of conjunctival scarring, despite three rounds of annual mass drug administration (MDA) for trachoma control. Disease progression was strongly associated with increasing proportion of episodes with conjunctival papillary inflammation (TP), and only weakly associated with Chlamydia trachomatis infection and trachomatous inflammation–follicular (TF). Analysis revealed that associations between infection and TF with scarring progression were mediated through TP, and that other factors causing individual differences in TP were also contributing to scarring progression. These data have significant implications for trachoma control. We hypothesise that in individuals who have previously experienced ocular C. trachomatis infection, TP is the primary driver of scarring progression. The addition of TP to trachoma surveillance programs would provide an indicator for active disease progression in the community and a more accurate guide to the need for future trichiasis interventions.