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Pathogenesis of progressive scarring trachoma in Ethiopia and Tanzania and its implications for disease control: two cohort studies.

Burton MJ, Rajak SN, Hu VH, Ramadhani A, Habtamu E, Massae P, Tadesse Z, Callahan K, Emerson PM, Khaw PT, Jeffries D, Mabey DC, Bailey RL, Weiss HA, Holland MJ - PLoS Negl Trop Dis (2015)

Bottom Line: Clinical inflammation, but not scarring progression, was associated with increased expression of S100A7, IL1B, IL17A, CXCL5, CTGF, CEACAM5, MMP7, CD83 and reduced SPARCL1.Chronic conjunctival inflammation appears to be central and is associated with enriched expression of pro-inflammatory factors and altered expression of extracellular matrix regulators.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.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London (UCL) Institute of Ophthalmology, London, United Kingdom; Department of Ophthalmology, Kilimanjaro Christian Medical Centre, Moshi, Tanzania.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Examples of paired photographs from individuals showing signs of increasing upper tarsal conjunctival scarring between baseline and 24-months.
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pntd.0003763.g003: Examples of paired photographs from individuals showing signs of increasing upper tarsal conjunctival scarring between baseline and 24-months.

Mentions: Between baseline and 24-months there was visible progression of the upper tarsal conjunctival scarring in 135 / 585 (23.1%) of the Ethiopian participants (Fig 1 and Fig 3). There was no association between scarring progression and age, gender or BMI (Table 1). Progressors had slightly less marked baseline scarring than Non-Progressors (Table 1). There was an association between the presence of clinical inflammation (P2/P3) on each occasion and progression of scarring by 24-months (Table 1). Clinical inflammation was present on at least one occasion in 71.9% of Progressors and 42.7% of Non-Progressors (p<0.0001). There was a strong relationship between progressive scarring and an increasing proportion of occasions (from none to all) when clinical inflammation was observed (OR 5.93, 95%CI 3.31–10.6, p<0.0001).


Pathogenesis of progressive scarring trachoma in Ethiopia and Tanzania and its implications for disease control: two cohort studies.

Burton MJ, Rajak SN, Hu VH, Ramadhani A, Habtamu E, Massae P, Tadesse Z, Callahan K, Emerson PM, Khaw PT, Jeffries D, Mabey DC, Bailey RL, Weiss HA, Holland MJ - PLoS Negl Trop Dis (2015)

Examples of paired photographs from individuals showing signs of increasing upper tarsal conjunctival scarring between baseline and 24-months.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430253&req=5

pntd.0003763.g003: Examples of paired photographs from individuals showing signs of increasing upper tarsal conjunctival scarring between baseline and 24-months.
Mentions: Between baseline and 24-months there was visible progression of the upper tarsal conjunctival scarring in 135 / 585 (23.1%) of the Ethiopian participants (Fig 1 and Fig 3). There was no association between scarring progression and age, gender or BMI (Table 1). Progressors had slightly less marked baseline scarring than Non-Progressors (Table 1). There was an association between the presence of clinical inflammation (P2/P3) on each occasion and progression of scarring by 24-months (Table 1). Clinical inflammation was present on at least one occasion in 71.9% of Progressors and 42.7% of Non-Progressors (p<0.0001). There was a strong relationship between progressive scarring and an increasing proportion of occasions (from none to all) when clinical inflammation was observed (OR 5.93, 95%CI 3.31–10.6, p<0.0001).

Bottom Line: Clinical inflammation, but not scarring progression, was associated with increased expression of S100A7, IL1B, IL17A, CXCL5, CTGF, CEACAM5, MMP7, CD83 and reduced SPARCL1.Chronic conjunctival inflammation appears to be central and is associated with enriched expression of pro-inflammatory factors and altered expression of extracellular matrix regulators.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.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London (UCL) Institute of Ophthalmology, London, United Kingdom; Department of Ophthalmology, Kilimanjaro Christian Medical Centre, Moshi, Tanzania.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus