Trachoma pathogenesis and scarring

Examining children for active trachoma, Tanzania.

Strengthen the understanding of trachoma and identify early markers for progressive disease

Trachoma is the leading infectious cause of blindness worldwide. Chlamydia trachomatis infection triggers a poorly understood inflammatory response, which leads to conjunctival scarring and blinding complications. It is unknown whether current control measures, including antibiotic treatment, will halt this process as scarring takes many years to develop. Currently trachoma control programmes rely on the implementation of the SAFE strategy. Unfortunately, due to our limited understanding of the pathogenesis of trachoma and its long natural history, it is currently unknown to what extent these strategies to control C. trachomatis infection will prevent or halt the development of blinding complications.

Aims and methods

This project supported the aims of VISION 2020 in several ways. Firstly, by strengthening understanding of the pathogenesis of blinding trachoma, which is necessary for the rational development of blindness prevention measures. Secondly, by developing and validating research tools to monitor progressive trachomatous scarring. Finally, these tools were used to investigate whether current and future interventions, such as mass antibiotic distribution, result in a reduction in factors associated with progressive scarring. The project  followed people with conjunctival scarring for two years to measure their immunological and scarring responses to infection and other stimulants to identify biomarkers for progression. It examined the impact of mass antibiotic treatment on these biomarkers.

Acknowledgements

We gratefully acknowledge the funders of this research:

Selected publications

  • Mabey DC, Hu V, Bailey RL, Burton MJ, Holland MJ. Towards a safe and effective chlamydial vaccine: lessons from the eye.  Vaccine. 2014 Mar 20;32(14):1572-8.  Article
  • Nguena MB, van den Tweel JG, Makupa W, Hu VH, Weiss HA, Gichuhi S, Burton MJ. Diagnosing ocular surface squamous neoplasia in East Africa: case-control study of clinical and in vivo confocal microscopy assessment. Ophthalmology. 2014 Feb;121(2):484-91. Article
  • Hu VH, Holland MJ, Cree IA, Pullin J, Weiss HA, Massae P, Makupa W, Mabey DC, Bailey RL, Burton MJ, Luthert P. In vivo confocal microscopy and histopathology of the conjunctiva in trachomatous scarring and normal tissue: a systematic comparison. Br J Ophthalmol. 2013 October; 97(10): 1333–1337. Article
  • Hu VH, Holland MJ, Burton MJ. Trachoma: Protective and Pathogenic Ocular Immune Responses to Chlamydia trachomatis. PLoS Negl Trop Dis. 2013 Feb;7(2):e2020. Article
  • Hu VH, Weiss HA, Ramadhani AM, Tolbert SB, Massae P, Mabey DC, Holland MJ, Bailey RL, Burton MJ. Innate immune responses and modified extracellular matrix regulation characterize bacterial infection and cellular/connective tissue changes in scarring trachoma. Infect Immun. 2012 Jan;80(1):121-30. Article
  • Hu VH, Weiss HA, Massae P, Courtright P, Makupa W, Mabey DC, Bailey RL, Burton MJ. In vivo confocal microscopy in scarring trachoma. Ophthalmology. 2011 Nov;118(11):2138-46. Epub 2011 Sep 13. Article
  • Burton MJ, Hu VH, Massae P, Burr SE, Chevallier C, Afwamba IA, Courtright P, Weiss HA, Mabey DC, Bailey RL. What is causing active trachoma? The role of non-chlamydial bacterial pathogens in a low prevalence setting. Invest Ophthalmol Vis Sci. 2011 Jul 29;52(8):6012-7. Article
  • Hu VH, Massae P, Weiss HA, Chevallier C, Onyango JJ, Afwamba IA, Mabey DC, Bailey RL, Burton MJ. Bacterial infection in scarring trachoma. Invest Ophthalmol Vis Sci. 2011 April; 52(5): 2181–2186. Article
  • Hu VH, Massae P, Weiss HA, Cree IA, Courtright P, Mabey DC, Bailey RL, Burton MJ. In vivo confocal microscopy of trachoma in relation to normal tarsal conjunctiva. Ophthalmology. 2011 Apr;118(4):747-54. Article
  • Hu VH, Harding-Esch EM, Burton MJ, Bailey RL, Kadimpeul J, Mabey DC. Epidemiology and control of trachoma: systematic review Trop Med Int Health. 2010 Jun;15(6):673-91. Abstract

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Image credit: Examining children for active trachoma, Tanzania. ICEH/LSHTM

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