Research update: Immunological basis of scarring trachoma

30 Apr 2018
A researcher performs In Vivo Confocal Microscopy on the conjunctiva of a man with trachoma. Credit: Matthew Burton.

Trachoma remains the world's leading cause of preventable blindness. Repeated conjunctival infection by Chlamydia trachomatis during childhood can trigger a poorly understood and chronic inflammatory-scarring response in the eyelids. The eyelids eventually roll inwards (trichiasis) so that the eyelashes scratch and scar the surface of the cornea.

A team from LSHTM is seeking to identify why some people are more likely to develop chronic inflammation as a result from ocular C. trachomatis infection and also identify the key disease pathways that result in scarring of the eye. Dr Tamsyn Derrick explains how this research may help us to develop treatments or vaccines to interrupt transmission and ultimately eliminate the disease. 

A longitudinal cohort study was established in three trachoma-endemic villages in northern Tanzania. Over 600 children aged 6-10 years were enrolled and visited every three months for four years. Eyes were examined for clinical signs of trachoma and swabs were collected for the molecular detection of C. trachomatis and assessment of the expression of 46 immuno-fibrogenic genes. Dried blood spots were collected at the final timepoint for measurement of antibodies to key chlamydial antigens.

Progressive scarring trachoma was determined by comparison of conjunctival photographs at baseline and the final timepoint.

Why is this research necessary?

Current trachoma control strategies focus on reducing the burden of C. trachomatis infection within endemic communities through the use of repeated mass antibiotic distribution and improved hygiene and sanitation.

However, there are challenges with compliance to these interventions and their long-term effectiveness in halting the progression of scarring trachoma is unknown. Conjunctival inflammation often persists and new cases of scarring and trichiasis continue to develop in formerly endemic communities long after C. trachomatis becomes undetectable. There is currently no treatment to halt scarring progression. 

In some areas, the prevalence of trachoma remains high despite many years of antibiotic distribution. A considerable amount of effort is being put into the development of an anti-chlamydial vaccine, which offers the hope that repeated mass antibiotic treatment of endemic populations would no longer be necessary.

These efforts to develop a suitable vaccine are being held back by a limited understanding of how the pathological consequences of chlamydial infection develop.

Progress update

Sample collection and laboratory analyses have been completed and the team are currently in the process of analysing our results and writing them up for publication. Thus far, the data suggests that mass drug administration with Azithromycin for trachoma control has an anti-inflammatory effect on gene expression in the conjunctiva, detectable three months post treatment.

Preliminary analysis shows that four-year progression of scarring trachoma was linked to the frequency of inflammatory episodes but, interestingly, not the frequency of C. trachomatis infections. Together these results might suggest that the immunomodulatory effect of Azithromycin treatment has a beneficial role in resolving conjunctival inflammation.

Analyses to characterise inflammatory gene expression profiles associated with four-year disease progression are ongoing, alongside microbiological investigations to understand the factors driving pathological inflammation.

What is the research impact?

The primary outcome of this project is to identify the host immune responses involved in resolution of chlamydial infection and those associated with pathological scarring.

This will have substantial importance for the development of a vaccine that can prevent chlamydial infection without provoking immunopathology. It might also enable targeted treatment to halt scarring progression.

This project will also describe the association between chlamydial infection frequency and progressive scarring trachoma, for which there is a significant lack of longitudinal data. In addition, the use of specific antichlamydial antibodies for trachoma surveillance will be evaluated. These data will be particularly relevant to trachoma control programmes in order to move towards the elimination of blinding trachoma.

Further reading