Pathogenesis of Progressive Scarring Trachoma in Ethiopia and Tanzania and Its Implications for Disease Control: Two Cohort Studies

Matthew J. Burton, Saul N. Rajak, Victor H. Hu, Athumani Ramadhani, Esmael Habtamu, Patrick Massae, Zerihun Tadesse, Kelly Callahan, Paul M. Emerson, Peng T. Khaw, David Jeffries, David C. W. Mabey, Robin L. Bailey, Helen A. Weiss, Martin J. Holland
Publication year: 


Trachoma causes blindness through a conjunctival scarring process initiated by ocularChlamydia 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 Ctrachomatis by PCR and transcript levels ofS100A7IL1BIL13IL17ACXCL5CTGFSPARCL1CEACAM5MMP7MMP9 and CD83were 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 Ctrachomatis 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 S100A7IL1BIL17ACXCL5CTGFCEACAM5MMP7CD83and reduced SPARCL1.


Scarring progressed in the absence of detectable Ctrachomatis, 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.