03893nas a2200589   4500000000100000008004100001653001500042653001300057653001300070653001800083653003000101653001600131653003100147653000900178653001900187653001700206653001100223653002400234653001100258653001300269653002400282653001400306653003600320653001600356653001900372653001300391653002600404653002900430653001400459653001000473100001300483700001200496700000900508700001600517700001400533700001300547700001400560700001500574700001400589700001200603700001500615700001200630700001300642700001300655700001500668245013700683856007800820300001300898490000600911520237200917022001403289       2015                            d10aTrichiasis10aTrachoma10aTanzania10aS100 Proteins10apolymerase chain reaction10aMiddle Aged10aMatrix Metalloproteinase 710aMale10aInterleukin-1710aInflammation10aHumans10aGPI-Linked Proteins10aFemale10aEthiopia10aDisease Progression10aCytokines10aConnective Tissue Growth Factor10aConjunctiva10aCohort Studies10aCicatrix10aChlamydia trachomatis10aCarcinoembryonic Antigen10aBlindness10aAdult1 aBurton M1 aRajak S1 aHu V1 aRamadhani A1 aHabtamu E1 aMassae P1 aTadesse Z1 aCallahan K1 aEmerson P1 aKhaw PT1 aJeffries D1 aMabey D1 aBailey R1 aWeiss HA1 aHolland MJ00aPathogenesis of progressive scarring trachoma in Ethiopia and Tanzania and its implications for disease control: two cohort studies.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430253/pdf/pntd.0003763.pdf  ae00037630 v93 a<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>METHODOLOGY/PRINCIPAL FINDINGS: </strong>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&lt;0.0001. Tanzania: OR 5.76, 95%CI 2.60-12.7, p&lt;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.</p>

<p><strong>CONCLUSIONS/SIGNIFICANCE: </strong>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.</p>
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