Which Members of a Community Need Antibiotics to Control Trachoma? Conjunctival<i>Chlamydia trachomatis</i>Infection Load in Gambian Villages

Burton, Matthew J.; Holland, Martin J.; Faal, Nkoyo; Aryee, Esther A. N.; Alexander, Neal; Bah, Momodou; Faal, Hannah; West, Sheila K.; Foster, Allen; Johnson, Gordon J.; Mabey, David; Bailey, Robin L.

doi:10.1167/iovs.03-0107

Cited by 129 publications

(128 citation statements)

References 16 publications

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“…41,42 Our study gives limited support to the idea that genetically determined reductions in the transcription efficiency of IFNg, which may permit greater multiplication of C. trachomatis following infection, are associated with an increased risk of scarring. Studies using quantitative PCR estimates of bacterial load have found that high bacterial loads in the conjunctiva are associated with intense disease, 43,44 and there is Cytokine SNPs linked to risk of severe trachoma A Natividad et al evidence linking intensity of conjunctival inflammation with scarring in later life. 45 Distal and proximal promoter variants thought to affect IL10 production were genotyped.…”

Section: Discussionmentioning

confidence: 99%

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci

et al. 2005

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Experimental evidence implicates interferon gamma (IFNg) in protection from and resolution of chlamydial infection. Conversely, interleukin 10 (IL10) is associated with susceptibility and persistence of infection and pathology. We studied genetic variation within the IL10 and IFNg loci in relation to the risk of developing severe complications of human ocular Chlamydia trachomatis infection. A total of 651 Gambian subjects with scarring trachoma, of whom 307 also had potentially blinding trichiasis and pair-matched controls with normal eyelids, were screened for associations between single-nucleotide polymorphisms (SNPs), SNP haplotypes and the risk of disease. MassEXTEND (Sequenom) and MALDI-TOF mass spectrometry were used for detection and analysis of SNPs and the programs PHASE and SNPHAP used to infer haplotypes from population genetic data. Multivariate conditional logistic regression analysis identified IL10 and IFNg SNP haplotypes associated with increased risk of both trachomatous scarring and trichiasis. SNPs in putative IFNg and IL10 regulatory regions lay within the disease-associated haplotypes. The IFNg þ 874A allele, previously linked to lower IFNg production, lies in the IFNg risk haplotype and was more common among cases than controls, but not significantly so. The promoter IL10-1082G allele, previously associated with high IL10 expression, is in both susceptibility and resistance haplotypes.

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Section: Discussionmentioning

confidence: 99%

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci

et al. 2005

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“…were designated commensal organisms and excluded from the analysis of bacterial pathogens. To detect C. trachomatis, DNA was extracted from the dry swab using the QIAamp DNA minikit (Qiagen, Crawley, United Kingdom) and tested using the Amplicor CT/NG kit (Roche Molecular Systems, Branchburg, NJ), with previously described modifications (8,24).…”

Section: Methodsmentioning

confidence: 99%

“…The principal driver for this inflammatory scarring process in communities where trachoma is endemic is thought to be infection with Chlamydia trachomatis, although direct evidence is limited (59). The signs of inflammation and the detection of chlamydial infection may show only a relatively weak correlation, particularly in low-prevalence settings (8,9,60). This relationship weakens after the introduction of antibiotic treatment (28).…”

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confidence: 99%

Active Trachoma Is Associated with Increased Conjunctival Expression ofIL17Aand Profibrotic Cytokines

et al. 2011

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The immunological basis of scarring trachoma is not well understood. It is unclear whether it is driven primarily through cell-mediated adaptive or epithelial-cell-derived innate responses. The purpose of this study was to investigate the expression of the inflammatory and fibrogenic mediators which may be involved. We conducted a cross-sectional survey of children living in an untreated trachoma-endemic community in Tanzania. The children were examined for signs of trachoma, and swabs were collected for bacteriological culture and RNA and DNA isolation. Chlamydia trachomatis was detected by the Amplicor PCR test. The expression of the following genes was measured by quantitative reverse transcription-PCR (RT-PCR): S100A7, IL1B, IL17A, IL23A, CXCL5, CCL18, TLR2, NLRP3, KLRD1, CTGF, and MMP9. Four hundred seventy children under the age of 10 years were included. Follicular trachoma (TF) was detected in 65 children (14%), C. trachomatis was detected in 25 (5%), and bacterial pathogens were cultured in 161 (34%). TF was associated with significantly increased expression of S100A7, IL17A, CCL18, CXCL5, and CTGF. Expression was increased further in the presence of papillary inflammation. Nonchlamydial bacterial infection was associated with increased expression of IL17A, CXCL5, CCL18, and KLRD1. IL17A expression was associated with increased expression of S100A7, CXCL5, CCL18, KLRD1, and CTGF. These data are consistent with a role for IL-17A in orchestrating the proinflammatory response in trachoma. Its activity may be promoted either as part of the cell-mediated response or through innate pathways. It may drive a range of proinflammatory factors leading to excessive tissue damage and repair involving fibrosis.

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“…All samples were checked for inhibition of PCR and DNA integrity by amplification of the ␤2-microglobulin gene. Template DNA was prepared by extraction and purification of DNA from conjunctival swabs as described elsewhere (6). Two to 10 ng of genomic DNA in 2 l of H 2 O was added to 23 l of a standard hot-start PCR mixture (QIAGEN Ltd., Crawley, United Kingdom) containing primers and cycled under the conditions described in Table 1, footnote a.…”

Section: Subjectsmentioning

confidence: 99%

The Frequency ofChlamydia trachomatisMajor Outer Membrane Protein-Specific CD8⁺T Lymphocytes in Active Trachoma Is Associated with Current Ocular Infection

et al. 2006

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Chlamydia-specific cytotoxic T lymphocytes are able to control model infections but may be implicated in disease pathogenesis. HLA-A2 peptide tetramers to Chlamydia trachomatis major outer membrane protein 258-266 (MOMP258-266) and MOMP260-268 were used to characterize HLA class I-restricted CD8 ؉ T cells in Gambian children aged 4 to 15 years with clinical signs of active trachoma and/or infection with C. trachomatis. The frequencies of circulating HLA-A2 tetramer binding cells (TBC) were determined in whole blood samples by flow cytometric analysis. Initial screening of subjects with an anti-HLA-A2 antibody confirmed the presence of either HLA-A2 or HLA-A28. These were subsequently further divided by molecular subtyping. The C. trachomatis-specific HLA-A2 peptide tetramers were able to bind T cells with receptors from subjects which were restricted by either the HLA-A2 or the HLA-A28 restriction element. In this population, the median value of C. trachomatis-specific CD8 ؉ T cells was 0.02%, with frequencies of up to 3.71% of CD8 ؉ T cells reactive with a single tetramer in a minority of subjects. TBC were detected more often in subjects who were infected at the ocular surface, and their presence was associated with infection episodes of longer duration. Detection of C. trachomatis-specific TBC was not associated with the presence of disease or with the estimated load of ocular C. trachomatis infection at the time of sample collection. High frequencies of C. trachomatis-specific cells did not predict subsequent appearance or resolution of the clinical disease signs of active trachoma.

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Which Members of a Community Need Antibiotics to Control Trachoma? ConjunctivalChlamydia trachomatisInfection Load in Gambian Villages

Cited by 129 publications

References 16 publications

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci

Active Trachoma Is Associated with Increased Conjunctival Expression ofIL17Aand Profibrotic Cytokines

The Frequency ofChlamydia trachomatisMajor Outer Membrane Protein-Specific CD8⁺T Lymphocytes in Active Trachoma Is Associated with Current Ocular Infection

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Which Members of a Community Need Antibiotics to Control Trachoma? ConjunctivalChlamydia trachomatisInfection Load in Gambian Villages

Cited by 129 publications

References 16 publications

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci

Active Trachoma Is Associated with Increased Conjunctival Expression ofIL17Aand Profibrotic Cytokines

The Frequency ofChlamydia trachomatisMajor Outer Membrane Protein-Specific CD8+T Lymphocytes in Active Trachoma Is Associated with Current Ocular Infection

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The Frequency ofChlamydia trachomatisMajor Outer Membrane Protein-Specific CD8⁺T Lymphocytes in Active Trachoma Is Associated with Current Ocular Infection