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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012219-02
Application #
6384748
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Fisher, Richard S
Project Start
2000-05-01
Project End
2005-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
2
Fiscal Year
2001
Total Cost
$309,400
Indirect Cost
Name
Children's Hospital & Res Ctr at Oakland
Department
Type
DUNS #
City
Oakland
State
CA
Country
United States
Zip Code
94609
Skwor, Troy; Kandel, Ram Prasad; Basravi, Sunniya et al. (2010) Characterization of humoral immune responses to chlamydial HSP60, CPAF, and CT795 in inflammatory and severe trachoma. Invest Ophthalmol Vis Sci 51:5128-36
Dean, Deborah; Bruno, William J; Wan, Raymond et al. (2009) Predicting phenotype and emerging strains among Chlamydia trachomatis infections. Emerg Infect Dis 15:1385-94
Somboonna, Naraporn; Mead, Sally; Liu, Jessica et al. (2008) Discovering and differentiating new and emerging clonal populations of Chlamydia trachomatis with a novel shotgun cell culture harvest assay. Emerg Infect Dis 14:445-53
Skwor, Troy A; Atik, Berna; Kandel, Raj Prasad et al. (2008) Role of secreted conjunctival mucosal cytokine and chemokine proteins in different stages of trachomatous disease. PLoS Negl Trop Dis 2:e264
Dean, Deborah; Kandel, Ram P; Adhikari, Him K et al. (2008) Multiple Chlamydiaceae species in trachoma: implications for disease pathogenesis and control. PLoS Med 5:e14
Gomes, Joao P; Hsia, Ru-ching; Mead, Sally et al. (2005) Immunoreactivity and differential developmental expression of known and putative Chlamydia trachomatis membrane proteins for biologically variant serovars representing distinct disease groups. Microbes Infect 7:410-20
Zhang, Hui; Kandel, Ram P; Sharma, Bassant et al. (2004) Risk factors for recurrence of postoperative trichiasis: implications for trachoma blindness prevention. Arch Ophthalmol 122:511-6
Gomes, Joao P; Bruno, William J; Borrego, Maria J et al. (2004) Recombination in the genome of Chlamydia trachomatis involving the polymorphic membrane protein C gene relative to ompA and evidence for horizontal gene transfer. J Bacteriol 186:4295-306
Millman, Kim; Black, Carolyn M; Johnson, Robert E et al. (2004) Population-based genetic and evolutionary analysis of Chlamydia trachomatis urogenital strain variation in the United States. J Bacteriol 186:2457-65
Frick, Kevin D; Colchero, M Arantxa; Dean, Deborah (2004) Modeling the economic net benefit of a potential vaccination program against ocular infection with Chlamydia trachomatis. Vaccine 22:689-96

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