Trachoma, caused by Chlamydia trachomatis, is the world's leading infectious cause of blindness and remains a significant public health problem. Much of trachomatous disease pathology is thought to be caused indirectly by host cellular and immune responses, however the immune response during active trachoma and how this initiates progressive scarring is not clearly understood. Defining protective vs. pathogenic immune response to C. trachomatis is important for vaccine design and evaluation. This study reports the baseline results of a longitudinal cohort of Tanzanian children, who were monitored for 4 years in order to determine the immunofibrogenic and infectious correlates of progressive scarring trachoma. In this cohort baseline, 506 children aged 6–10 years were assessed for clinical signs, infection status and the expression of 91 genes of interest prior to mass azithromycin administration for trachoma control. C. trachomatis was detected using droplet digital PCR and gene expression was measured using quantitative real-time PCR. The prevalence of follicles, papillary inflammation and scarring were 33.6, 31.6, and 28.5%, respectively. C. trachomatis was detected in 78/506 (15.4%) individuals, 62/78 of whom also had follicles. C. trachomatis infection was associated with a strong upregulation of IFNG and IL22, the enrichment of Th1 and NK cell pathways and Th17 cell-associated cytokines. In individuals with inflammation in the absence of infection the IFNG/IL22 and NK cell response was reduced, however, pro-inflammatory, growth and matrix factors remained upregulated and mucins were downregulated. Our data suggest that, strong IFNG/IL22 responses, probably related to Th1 and NK cell involvement, is important for clearance of C. trachomatis and that the residual pro-inflammatory and pro-fibrotic phenotype that persists after infection might contribute to pathological scarring. Interestingly, females appear more susceptible to developing papillary inflammation and scarring than males, even at this young age, despite comparable levels of C. trachomatis infection. Females also had increased expression of a number of IFNγ pathway related genes relative to males, suggesting that overexpression of this pathway in response to infection might contribute to more severe scarring. Longitudinal investigation of these factors will reveal their relative contributions to protection from C. trachomatis infection and development of scarring complications.

In order to maximize the effectiveness of “Seek, Test, and Treat” strategies for curbing the HIV epidemic, new approaches are needed to increase the uptake of HIV testing services, particularly among high-risk groups. Low HIV testing rates among such groups suggests that current testing services may not align well with the testing preferences of these populations. Female bar workers and male mountain porters have been identified as two important high-risk groups in the Kilimanjaro Region of Tanzania. We used conventional survey methods and a Discrete Choice Experiment (DCE), a preference elicitation method increasingly applied by economists and policy makers to inform health policy and services, to analyze trade-offs made by individuals and quantify preferences for HIV testing services. Compared to 486 randomly selected community members, 162 female bar workers and 194 male Kilimanjaro porters reported 2 to 3 times as many lifetime sexual partners (p<0.001), but similar numbers of lifetime HIV tests (median 1–2 across all groups). Bivariate descriptive statistics were used to analyze differences in survey responses across groups. For the DCE, participants’ stated choices across 11,178 hypothetical HIV testing scenarios (322 female and 299 male participants × 9 choice tasks × 2 alternatives) were analyzed using gender-specific mixed logit models. Direct assessments and the DCE data demonstrated that barworkers were less likely to prefer home testing and were more concerned about disclosure issues compared with their community counterparts. Male porters preferred testing in venues where antiretroviral therapy was readily available. Both high-risk groups were less averse to traveling longer distances to test compared to their community counterparts. These results expose systematic differences in HIV testing preferences across high-risk populations compared to their community peers. Tailoring testing options to the preferences of high-risk populations should be evaluated as a means of improving uptake of testing in these populations.

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.