Trachoma is a chronic ocular infection caused by Chlamydia trachomatis and is the leading cause of preventable blindness in the world. Over 500 million people are infected of whom 100 million have serious visual impairment, 9 million are blind. Blinding trachoma is predicted to increase to 12 million cases by the year 2020. Appropriate public health interventions and an effective vaccine rely on an understanding of behavioral risk factors, the organism's antigenic potential and capacity for change, its mode of transmission, and the pathogenesis of disease progression. The investigators will address the latter in this research proposal. Disease progression results in trichiasis and entropion which occur concomitantly from conjunctival scarring and are the sequelae of trachoma that lead to blindness. There are few studies that address pathogenesis. Some have evaluated local and systemic immune responses or peripheral blood mononuclear cells in proliferation assays among individuals with conjunctival scarring. Others have conducted short term studies in animal models. Still others have looked at in vitro assays of chlamydial antigens and their pathogenic effect in various cell lines and tissues. However, there are no studies examining conjunctival tissue from patients with trichiasis/entropion for latent chlamydial organisms, chlamydial hsp60, and MOMP antigens, cell types, and cytokine profiles that may contribute to the immunopathogenesis of disease. Further, no studies have prospectively looked at conjunctival mucosal reinfection rates, cytokine profiles, and chlamydial hsp60 responses at multiple time points, and correlated these with progression of clinical disease. The investigators propose to study trachoma trichiasis/entropion patients from two villages compared with age, sex, and ethnically matched, non-trachomatis scarred controls who require surgery for other reasons, and study the remaining individuals in both villages.
Specific Aims : 1) Determine whether the chronic sequelae of trachoma result from latent infection and how infection correlates with cell mediated immune (CMI) responses; 2) Identify the immune mediators of trichiasis/entropion by determining cell types, hsp60 and MOMP antigens, inflammation, and cytokines present in conjunctival biopsy material; and 3) Evaluate the role of chlamydial hsp60 and CMI responses in the pathogenesis of scarring disease among trachoma patients. A greater understanding of the pathogenesis of trachoma will aid in developing public health interventions and a vaccine that can be implemented in trachoma endemic areas throughout the world.
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