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Pathogenesis of Progressive Scarring Trachoma in Ethiopia and Tanzania and Its Implications for Disease Control: Two Cohort Studies
BACKGROUND: Trachoma causes blindness through a conjunctival scarring process initiated by ocular Chlamydia trachomatis infection; however, the rates, drivers and pathophysiological determinants are poorly understood. We investigated progressive scarring and its relationship to conjunctival infectio...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430253/ https://www.ncbi.nlm.nih.gov/pubmed/25970613 http://dx.doi.org/10.1371/journal.pntd.0003763 |
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author | Burton, Matthew J. Rajak, Saul N. Hu, Victor H. Ramadhani, Athumani Habtamu, Esmael Massae, Patrick Tadesse, Zerihun Callahan, Kelly Emerson, Paul M. Khaw, Peng T. Jeffries, David Mabey, David C. W. Bailey, Robin L. Weiss, Helen A. Holland, Martin J. |
author_facet | Burton, Matthew J. Rajak, Saul N. Hu, Victor H. Ramadhani, Athumani Habtamu, Esmael Massae, Patrick Tadesse, Zerihun Callahan, Kelly Emerson, Paul M. Khaw, Peng T. Jeffries, David Mabey, David C. W. Bailey, Robin L. Weiss, Helen A. Holland, Martin J. |
author_sort | Burton, Matthew J. |
collection | PubMed |
description | BACKGROUND: Trachoma causes blindness through a conjunctival scarring process initiated by ocular Chlamydia trachomatis infection; however, the rates, drivers and pathophysiological determinants are poorly understood. We investigated progressive scarring and its relationship to conjunctival infection, inflammation and transcript levels of cytokines and fibrogenic factors. METHODOLOGY/PRINCIPAL FINDINGS: We recruited two cohorts, one each in Ethiopia and Tanzania, of individuals with established trachomatous conjunctival scarring. They were followed six-monthly for two years, with clinical examinations and conjunctival swab sample collection. Progressive scarring cases were identified by comparing baseline and two-year photographs, and compared to individuals without progression. Samples were tested for C. trachomatis by PCR and transcript levels of S100A7, IL1B, IL13, IL17A, CXCL5, CTGF, SPARCL1, CEACAM5, MMP7, MMP9 and CD83 were estimated by quantitative RT-PCR. Progressive scarring was found in 135/585 (23.1%) of Ethiopian participants and 173/577 (30.0%) of Tanzanian participants. There was a strong relationship between progressive scarring and increasing inflammatory episodes (Ethiopia: OR 5.93, 95%CI 3.31–10.6, p<0.0001. Tanzania: OR 5.76, 95%CI 2.60–12.7, p<0.0001). No episodes of C. trachomatis infection were detected in the Ethiopian cohort and only 5 episodes in the Tanzanian cohort. Clinical inflammation, but not scarring progression, was associated with increased expression of S100A7, IL1B, IL17A, CXCL5, CTGF, CEACAM5, MMP7, CD83 and reduced SPARCL1. CONCLUSIONS/SIGNIFICANCE: Scarring progressed in the absence of detectable C. trachomatis, which raises uncertainty about the primary drivers of late-stage trachoma. Chronic conjunctival inflammation appears to be central and is associated with enriched expression of pro-inflammatory factors and altered expression of extracellular matrix regulators. Host determinants of scarring progression appear more complex and subtle than the features of inflammation. Overall this indicates a potential role for anti-inflammatory interventions to interrupt progression and the need for trichiasis disease surveillance and surgery long after chlamydial infection has been controlled at community level. |
format | Online Article Text |
id | pubmed-4430253 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44302532015-05-21 Pathogenesis of Progressive Scarring Trachoma in Ethiopia and Tanzania and Its Implications for Disease Control: Two Cohort Studies Burton, Matthew J. Rajak, Saul N. Hu, Victor H. Ramadhani, Athumani Habtamu, Esmael Massae, Patrick Tadesse, Zerihun Callahan, Kelly Emerson, Paul M. Khaw, Peng T. Jeffries, David Mabey, David C. W. Bailey, Robin L. Weiss, Helen A. Holland, Martin J. PLoS Negl Trop Dis Research Article BACKGROUND: Trachoma causes blindness through a conjunctival scarring process initiated by ocular Chlamydia trachomatis infection; however, the rates, drivers and pathophysiological determinants are poorly understood. We investigated progressive scarring and its relationship to conjunctival infection, inflammation and transcript levels of cytokines and fibrogenic factors. METHODOLOGY/PRINCIPAL FINDINGS: We recruited two cohorts, one each in Ethiopia and Tanzania, of individuals with established trachomatous conjunctival scarring. They were followed six-monthly for two years, with clinical examinations and conjunctival swab sample collection. Progressive scarring cases were identified by comparing baseline and two-year photographs, and compared to individuals without progression. Samples were tested for C. trachomatis by PCR and transcript levels of S100A7, IL1B, IL13, IL17A, CXCL5, CTGF, SPARCL1, CEACAM5, MMP7, MMP9 and CD83 were estimated by quantitative RT-PCR. Progressive scarring was found in 135/585 (23.1%) of Ethiopian participants and 173/577 (30.0%) of Tanzanian participants. There was a strong relationship between progressive scarring and increasing inflammatory episodes (Ethiopia: OR 5.93, 95%CI 3.31–10.6, p<0.0001. Tanzania: OR 5.76, 95%CI 2.60–12.7, p<0.0001). No episodes of C. trachomatis infection were detected in the Ethiopian cohort and only 5 episodes in the Tanzanian cohort. Clinical inflammation, but not scarring progression, was associated with increased expression of S100A7, IL1B, IL17A, CXCL5, CTGF, CEACAM5, MMP7, CD83 and reduced SPARCL1. CONCLUSIONS/SIGNIFICANCE: Scarring progressed in the absence of detectable C. trachomatis, which raises uncertainty about the primary drivers of late-stage trachoma. Chronic conjunctival inflammation appears to be central and is associated with enriched expression of pro-inflammatory factors and altered expression of extracellular matrix regulators. Host determinants of scarring progression appear more complex and subtle than the features of inflammation. Overall this indicates a potential role for anti-inflammatory interventions to interrupt progression and the need for trichiasis disease surveillance and surgery long after chlamydial infection has been controlled at community level. Public Library of Science 2015-05-13 /pmc/articles/PMC4430253/ /pubmed/25970613 http://dx.doi.org/10.1371/journal.pntd.0003763 Text en © 2015 Burton et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Burton, Matthew J. Rajak, Saul N. Hu, Victor H. Ramadhani, Athumani Habtamu, Esmael Massae, Patrick Tadesse, Zerihun Callahan, Kelly Emerson, Paul M. Khaw, Peng T. Jeffries, David Mabey, David C. W. Bailey, Robin L. Weiss, Helen A. Holland, Martin J. Pathogenesis of Progressive Scarring Trachoma in Ethiopia and Tanzania and Its Implications for Disease Control: Two Cohort Studies |
title | Pathogenesis of Progressive Scarring Trachoma in Ethiopia and Tanzania and Its Implications for Disease Control: Two Cohort Studies |
title_full | Pathogenesis of Progressive Scarring Trachoma in Ethiopia and Tanzania and Its Implications for Disease Control: Two Cohort Studies |
title_fullStr | Pathogenesis of Progressive Scarring Trachoma in Ethiopia and Tanzania and Its Implications for Disease Control: Two Cohort Studies |
title_full_unstemmed | Pathogenesis of Progressive Scarring Trachoma in Ethiopia and Tanzania and Its Implications for Disease Control: Two Cohort Studies |
title_short | Pathogenesis of Progressive Scarring Trachoma in Ethiopia and Tanzania and Its Implications for Disease Control: Two Cohort Studies |
title_sort | pathogenesis of progressive scarring trachoma in ethiopia and tanzania and its implications for disease control: two cohort studies |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430253/ https://www.ncbi.nlm.nih.gov/pubmed/25970613 http://dx.doi.org/10.1371/journal.pntd.0003763 |
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