Genetic susceptibility to scarring trachoma

Trachoma is the leading infectious cause of blindness worldwide. Repeated conjunctival infection by Chlamydia trachomatis throughout childhood triggers a poorly understood inflammatory-driven scarring response in the eyelids, which continues throughout the lives of some individuals even in the absence of detectable infection.

Conjunctival scarring causes the eyelids to role inwards so that the eyelashes scratch the surface of the cornea. Eventually blinding corneal opacification develops. Current efforts to develop a trachoma vaccine are being held back by a limited understanding of how the pathological consequences of chlamydial infection develop.

This study aims to identify the genetic determinants associated with the development of scarring trachoma subsequent to ocular infection with C. trachomatis. This will enable us to identify the key genes and biological pathways that contribute to the pathogenesis of this disease.

We are using two separate cohort designs. Firstly, a case-control design comparing adults with trachomatous conjunctival scarring to age, sex and location matched controls. Secondly, a nested longitudinal cohort, in which we identify younger individuals and compare their disease progression over time.

In total we will collect buccal mucosal swab samples from 6000 Tanzanians for host genomic DNA extraction to perform a SNP based GWAS. In parallel we will perform genotyping of highly polymorphic immune response genes that are not amenable to genome wide SNP genotyping.

These studies in Tanzania will serve as both discovery and validation studies of case-control studies performed in The Gambia, and are an essential step in determining the causal and common pathways to scarring disease that might inform vaccine design.