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

Abstract

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. Of the 666 children enrolled in the study, outcome data were obtained for 448. Scarring progression was detected in 103/448 (23%) children; 48 (11%) of which had incident scarring and 55 (12%) had progression of existing scarring. Scarring was strongly associated with increasing episodes of trachomatous papillary inflammation (TP). Weaker associations were found between episodes of C . trachomatis infection and follicular trachoma (TF) with scarring progression in unadjusted models, which were absent in multivariable analysis after adjusting for inflammation (multivariable results: C . trachomatis p = 0.44, TF p = 0.25, TP p = <0.0001, age p = 0.13, female sex p = 0.05). Individuals having TP at 30% or more of the time-points they were seen had an odds ratio of 7.5 (95%CI = 2.7–20.8) for scarring progression relative to individuals without any TP detected during the study period. 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.

Immunopathogenesis of Progressive Scarring Trachoma: Results of a 4-Year Longitudinal Study in Tanzanian Children

“…A detailed description of the longitudinal study design and primary outcomes has been published elsewhere (4,9,10). Briefly, of the 666 eligible children, 616 were enrolled in the cohort study.…”

“…Prior analysis of the cohort data set indicated that the marginal association between C. trachomatis infection and 4-year scarring progression was mediated through TP, suggesting that an individual's response to infection-rather than simply the presence or absence of infection alone-determines their risk of scarring sequelae (9). In order to investigate this further, random effects regression models were performed for each gene in turn; these included an interaction term between scarring progression status and C. trachomatis infection in order to determine whether scarring progressors responded differently to infection relative to nonprogressors.…”

“…We recently reported the results of a cohort study that investigated the association between conjunctival C. trachomatis infection and clinically visible inflammatory episodes with scarring progression in children over a 4-year period (9). The study took place from 2012 to 2016 in a region of northern Tanzania where trachoma is endemic.…”

DjinniChip: Evaluation of a novel molecular rapid diagnostic device for the detection of Chlamydia trachomatis in trachoma-endemic areas

“…Conjunctival swabs were collected as previously described using sterile polyester-tipped swabs [7,8]. The rst swab was collected into 250µl RNA later and was used elsewhere [7][8][9], whilst the second swab was collected dry and stored at -80°C until used in this study. 0.5% of swabs collected were 'air' control swabs in order to test for eld and laboratory contamination.…”

DjinniChip: Evaluation of a novel molecular rapid diagnostic device for the detection of Chlamydia trachomatis in trachoma-endemic areas

“…Conjunctival swabs were collected as previously described using sterile polyester-tipped swabs [7,8]. The rst swab was collected into 250 ml RNA later and was used elsewhere [7][8][9], whilst the second swab was collected dry and stored at -80 °C until used in this study. 0.5% of swabs collected were 'air' control swabs in order to test for eld-and laboratory contamination.…”