Agreement between novice and experienced trachoma graders improves after a single day of didactic training.

BACKGROUND/AIMS: Prevalence estimates and treatment decisions for trachoma are based entirely on ocular clinical examination. The aim of the current study is to demonstrate that ophthalmic assistants can be trained and certified to provide trachoma grading within a single day. METHODS: Conjunctival photographs from an area with endemic trachoma were randomised into two sets of 60 cases. Photographs were graded for trachomatous inflammation-follicular (TF) and trachomatous inflammation-intense (TI) by three experienced graders. Inter-rater reliability of eight ophthalmic assistants and three experienced graders were compared before and after training. RESULTS: The mean κ agreement between the ophthalmic assistants and the consensus grades of the experienced graders for TF was 0.38 (95% CI 0.18 to 0.58) before training, and increased to 0.60 (95% CI 0.42 to 0.78) after training (p=0.07). The mean κ agreement for TI was 0.16 (95% CI 0.02 to 0.30) before training, and increased to 0.39 (95% CI 0.20 to 0.58) after training (p=0.02). CONCLUSION: A single day of training improves agreement between prospective and experienced trachoma graders, and provides the basis for certification of workers who are able to accurately grade trachoma and generate reliable prevalence estimates.

The distribution of ocular Chlamydia prevalence across Tanzanian communities where trachoma is declining.

BACKGROUND: Mathematical models predict an exponential distribution of infection prevalence across communities where a disease is disappearing. Trachoma control programs offer an opportunity to test this hypothesis, as the World Health Organization has targeted trachoma for elimination as a public health concern by the year 2020. Local programs may benefit if a single survey could reveal whether infection was headed towards elimination. Using data from a previously-published 2009 survey, we test the hypothesis that Chlamydia trachomatis prevalence across 75 Tanzanian communities where trachoma had been documented to be disappearing is exponentially distributed. METHODS/FINDINGS: We fit multiple continuous distributions to the Tanzanian data and found the exponential gave the best approximation. Model selection by Akaike Information Criteria (AICc) suggested the exponential distribution had the most parsimonious fit to the data. Those distributions which do not include the exponential as a special or limiting case had much lower likelihoods of fitting the observed data. 95% confidence intervals for shape parameter estimates of those distributions which do include the exponential as a special or limiting case were consistent with the exponential. Lastly, goodness-of-fit testing was unable to reject the hypothesis that the prevalence data came from an exponential distribution. CONCLUSIONS: Models correctly predict that infection prevalence across communities where a disease is disappearing is best described by an exponential distribution. In Tanzanian communities where local control efforts had reduced the clinical signs of trachoma by 80% over 10 years, an exponential distribution gave the best fit to prevalence data. An exponential distribution has a relatively heavy tail, thus occasional high-prevalence communities are to be expected even when infection is disappearing. A single cross-sectional survey may be able to reveal whether elimination efforts are on-track.

Reliability of trachoma clinical grading--assessing grading of marginal cases.

BACKGROUND: Clinical examination of trachoma is used to justify intervention in trachoma-endemic regions. Currently, field graders are certified by determining their concordance with experienced graders using the kappa statistic. Unfortunately, trachoma grading can be highly variable and there are cases where even expert graders disagree (borderline/marginal cases). Prior work has shown that inclusion of borderline cases tends to reduce apparent agreement, as measured by kappa. Here, we confirm those results and assess performance of trainees on these borderline cases by calculating their reliability error, a measure derived from the decomposition of the Brier score. METHODS AND FINDINGS: We trained 18 field graders using 200 conjunctival photographs from a community-randomized trial in Niger and assessed inter-grader agreement using kappa as well as reliability error. Three experienced graders scored each case for the presence or absence of trachomatous inflammation-follicular (TF) and trachomatous inflammation-intense (TI). A consensus grade for each case was defined as the one given by a majority of experienced graders. We classified cases into a unanimous subset if all 3 experienced graders gave the same grade. For both TF and TI grades, the mean kappa for trainees was higher on the unanimous subset; inclusion of borderline cases reduced apparent agreement by 15.7% for TF and 12.4% for TI. When we assessed the breakdown of the reliability error, we found that our trainees tended to over-call TF grades and under-call TI grades, especially in borderline cases. CONCLUSIONS: The kappa statistic is widely used for certifying trachoma field graders. Exclusion of borderline cases, which even experienced graders disagree on, increases apparent agreement with the kappa statistic. Graders may agree less when exposed to the full spectrum of disease. Reliability error allows for the assessment of these borderline cases and can be used to refine an individual trainee's grading.

Dendritic cell-derived thrombospondin-1 is critical for the generation of the ocular surface Th17 response to desiccating stress.

TSP-1 is a physiologic activator of TGF-ß, a critical induction factor for Th17-mediated immunity. The purpose of this study was to investigate the role of TSP-1 in the induction of the Th17 ocular surface response to DS. TSP-1KO and WT mice were subjected to DS5 and DS10), and parameters of ocular surface disease, including corneal barrier function, conjunctival CD4(+) T cell infiltration, and GC density, were evaluated. TSP-1KO mice subjected to DS had less corneal barrier disruption, reduced loss of PAS+ GC, and decreased CD4(+) T cell infiltration in the conjunctiva. In contrast to WT, TSP-1KO mice failed to up-regulate MMP-3 and MMP-9 mRNA transcripts in the cornea and IL-17A mRNA transcripts in the conjunctiva. RAG-1KO recipients of adoptively transferred CD4(+) T cells isolated from TSP-1KO mice subjected to DS5 showed milder dry-eye phenotype and less conjunctival inflammation than recipients of CD4(+) T cells from DS5 WT control. Reconstitution of TSP-1KO mice with WT DCs prior to DS reversed the resistance of the TSP-1KO to DS-induced immunopathology. In conclusion, DC-derived TSP-1 is critical for generating the Th17 ocular surface response to DS.