The Long-Term Natural History of Trachomatous Trichiasis in The Gambia

Burton, Matthew J.; Bowman, Richard; Faal, Hannah; Aryee, Esther A. N.; Ikumapayi, Usman N.; Alexander, Neal; Adegbola, Richard A.; Mabey, David; Foster, Allen; Johnson, Gordon J.; Bailey, Robin L.

doi:10.1167/iovs.05-0714

Cited by 51 publications

(59 citation statements)

References 17 publications

(38 reference statements)

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“…These genes also showed a clearly progressive increase in expression with increasing IVCM connective tissue organization grade. We found infection with C. trachomatis to be infrequent in these adults with conjunctival scarring, with a similar detection rate to previous studies of trachomatous trichiasis (8,11,13). While caution is needed in interpreting these data because of the small numbers, individuals infected with C. trachomatis had gene expression profiles characteristic of C. trachomatis infection in children (9,46).…”

Section: Discussionsupporting

confidence: 85%

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Innate Immune Responses and Modified Extracellular Matrix Regulation Characterize Bacterial Infection and Cellular/Connective Tissue Changes in Scarring Trachoma

Weiss

Ramadhani

et al. 2012

Infect Immun

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Trachoma is the most common infectious cause of blindness and a major public health problem in many developing countries. It is caused by recurrent ocular infection with Chlamydia trachomatis in childhood, with conjunctival scarring seen later in life. The pathogenesis of trachomatous scarring, however, is poorly understood, and this study was carried out to investigate the immunofibrogenic correlates of trachomatous conjunctival scarring. A case-control study of 363 cases with conjunctival scarring and 363 control participants was conducted. Investigations included in vivo confocal microscopy (IVCM) assessment, quantitative real-time PCR gene expression, C. trachomatis detection, and nonchlamydial bacterial culture. Trachomatous scarring was found to be strongly associated with a proinflammatory, innate immune response with increased expression of psoriasin, interleukin-1␤, tumor necrosis factor alpha, defensin-␤4A, chemokine ligand 5, and serum amyloid A1. There was also differential expression of various modifiers of the extracellular matrix, including metalloproteinases 7, 9, 10, and 12, tissue inhibitor of matrix metalloproteinase 1, and secreted protein acidic cystein-rich-like 1. The expression of many of these genes was also significantly associated with the presence of nonchlamydial bacterial infection. These infections had a marked effect on conjunctival immune processes, including an increased inflammatory infiltrate and edema seen with IVCM. This study supports the possibility that the immunofibrogenic response in scarring trachoma is partly stimulated by nonchlamydial bacterial infection, which is characterized by the expression of innate factors.

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Section: Discussionsupporting

confidence: 85%

“…Instead, proinflammatory mediators, particularly suggestive of innate immune responses and factors affecting extracellular matrix (ECM) remodeling, were prominent (14,29). A number of studies have also provided compelling evidence supporting the importance of conjunctival inflammation in the development of scarring and blinding complications (11,18,43,55,57).…”

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confidence: 99%

Innate Immune Responses and Modified Extracellular Matrix Regulation Characterize Bacterial Infection and Cellular/Connective Tissue Changes in Scarring Trachoma

Weiss

Ramadhani

et al. 2012

Infect Immun

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“…Both trichiasis and its recurrence after surgical correction have been associated with severe conjunctival inflammation. 34 TNF is highly expressed during episodes of conjunctival inflammation in these subjects with trichiasis (M Burton, personal communication) and may influence risk of disease progression in relation to the spectrum of TNF-inducible genes, such as matrix metalloprotease 9 that may be important in initiating fibrosis. 35,36 We studied SNPs capturing common genetic variation within 25 kb of genome within the MHC region.…”

Section: Discussionmentioning

confidence: 99%

Genetic variation at the TNF locus and the risk of severe sequelae of ocular Chlamydia trachomatis infection in Gambians

et al. 2007

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Tumor necrosis factor (TNF) is thought to be a key mediator of the inflammatory and fibrotic response to Chlamydia trachomatis (Ct) infection. A large matched-pair case-control study investigated putative functional single nucleotide polymorphisms (SNPs) across the major histocompatibility complex (MHC) class III region, including TNF and its immediate neighbors nuclear factor of k light polypeptide gene enhancer in B cells (IkBL), inhibitor like 1 and lymphotoxin alpha (LTA) in relation to the risk of scarring sequelae of ocular Ct infection. Haplotype and linkage disequilibrium analysis demonstrated two haplotypes, differing at position TNF-308, conferring an increased risk of trichiasis. The TNF-308A allele, and its bearing haplotype, correlated with increased TNF production in lymphocyte cultures stimulated with chlamydial elementary body antigen. Thus TNF-308A may determine directly, or be a marker of a high TNF producer phenotype associated with increased risk of sequelae of chlamydial infection. Multivariate analysis provided evidence for the presence of additional risk-associated variants near the TNF locus.

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“…3 It is known that the conjunctivae of eyes with trachomatous trichiasis are frequently colonized with bacteria. [4][5][6] Casecontrol studies have shown that conjunctival bacterial infection is associated with trichiasis and conjunctival scarring, although the significance of this bacterial growth is unclear. 7,8 Eyelashes touching the globe (i.e., trichiasis) could provide a direct route for environmental pathogens to gain entry to the conjunctiva or cornea.…”

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confidence: 99%

Association of Conjunctival Bacterial Infection and Female Sex in Cicatricial Trachoma

Cevallos¹,

Whitcher²,

Melese

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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In a region of Ethiopia with endemic trachoma, conjunctival bacterial growth was more common in females than that in males. S. pneumoniae and H. influenzae, both of which frequently colonize the nasopharynx of children, were more common in females, suggesting that the preponderance of infection in females may be attributable to close contact with children. This finding is consistent with the theory that childcare activities may preferentially expose females to ocular chlamydial infection. (ClinicalTrials.gov number, NCT00221364.).

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The Long-Term Natural History of Trachomatous Trichiasis in The Gambia

Cited by 51 publications

References 17 publications

Innate Immune Responses and Modified Extracellular Matrix Regulation Characterize Bacterial Infection and Cellular/Connective Tissue Changes in Scarring Trachoma

Innate Immune Responses and Modified Extracellular Matrix Regulation Characterize Bacterial Infection and Cellular/Connective Tissue Changes in Scarring Trachoma

Genetic variation at the TNF locus and the risk of severe sequelae of ocular Chlamydia trachomatis infection in Gambians

Association of Conjunctival Bacterial Infection and Female Sex in Cicatricial Trachoma

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