Trachomatous Scarring Research Articles

The link between ocular infection with non-chlamydial bacteria and trachomatous eye changes

Introduction Globally, C. trachomatis is the leading infectious cause of blindness. There is evidence to suggest that trachomatous inflammation may be linked to ocular infection with other pathogenic organisms. Methods Conjunctival swab samples from 472 Tanzanian children who participated in a 4-year longitudinal study were analysed using optimised duplex qPCR assays to assess carriage of H. influenzae, CNS, S. pneumoniae and Adenovirus spp. in each sample. The presence of C. trachomatis (Ct) in the conjunctiva had previously been recorded. Logistic regression analysis, adjusted for age and sex, was performed to identify associations between the prevalence of bacterial infection and (1) progressive scarring trachoma, and (2) active trachoma (defined as the presence of follicular trachoma (TF) or trachomatous inflammation (TI)). Results Logistic regression identified no significant associations between (1) progressive scarring trachoma and Ct;and (2) progressive scarring trachoma and non-chlamydial bacterial infection. Active trachoma was only associated with conjunctival infection with H. influenzae. Logistic regression found that patients with ocular H. influenzae infection were more likely to demonstrate clinically-graded active trachoma (TF + TI) (OR = 1.96, 95% CI: 1.11 – 3.56, p = 0.023). Individual analyses of TF or TI and their associations with H. influenzae found (1) a strong association between ocular H. influenzae infection and TF (OR = 2.21, p = 0.0095); (2) no association between ocular H. influenzae infection and TI (OR = 2.19, p = 0.19). Conclusion These results indicate that H. influenzae might contribute to the TF phenotype. TF is widely used to assess population levels of trachoma.

Progress to Eliminate Trachoma as a Public Health Problem in Amhara National Regional State, Ethiopia: Results of 152 Population-Based Surveys.

.At baseline in 2006, Amhara National Regional State, Ethiopia, was the most trachoma-endemic region in the country. Trachoma impact surveys (TIS) were conducted in all districts between 2010 and 2015, following 3–5 years of intervention with the WHO-recommended SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy. A multistage cluster random sampling design was used to estimate the district-level prevalence of trachoma. In total, 1,887 clusters in 152 districts were surveyed, from which 208,265 individuals from 66,089 households were examined for clinical signs of trachoma. The regional prevalence of trachomatous inflammation-follicular (TF) and trachomatous inflammation-intense among children aged 1–9 years was 25.9% (95% CI: 24.9–26.9) and 5.5% (95% CI: 5.2–6.0), respectively. The prevalence of trachomatous scarring and trachomatous trichiasis among adults aged ≥ 15 years was 12.9% (95% CI: 12.2–13.6) and 3.9% (95% CI: 3.7–4.1), respectively. Among children aged 1–9 years, 76.5% (95% CI: 75.3–77.7) presented with a clean face; 66.2% (95% CI: 64.1–68.2) of households had access to water within 30 minutes round-trip, 48.1% (95% CI: 45.5–50.6) used an improved water source, and 46.2% (95% CI: 44.8–47.5) had evidence of a used latrine. Nine districts had a prevalence of TF below the elimination threshold of 5%. In hyperendemic areas, 3–5 years of implementation of SAFE is insufficient to achieve trachoma elimination as a public health problem; additional years of SAFE and several rounds of TIS will be required before trachoma is eliminated.

Conjunctival Microbiome-Host Responses Are Associated With Impaired Epithelial Cell Health in Both Early and Late Stages of Trachoma.

Background: Trachoma, a neglected tropical disease, is the leading infectious cause of blindness and visual impairment worldwide. Host responses to ocular chlamydial infection resulting in chronic inflammation and expansion of non-chlamydial bacteria are hypothesized risk factors for development of active trachoma and conjunctival scarring.Methods: Ocular swabs from trachoma endemic populations in The Gambia were selected from archived samples for 16S sequencing and host conjunctival gene expression. We recruited children with active trachoma and adults with conjunctival scarring, alongside corresponding matched controls.Findings: In children, active trachoma was not associated with significant changes in the ocular microbiome. Haemophilus enrichment was associated with antimicrobial responses but not linked to active trachoma. Adults with scarring trachoma had a reduced ocular bacterial diversity compared to controls, with increased relative abundance of Corynebacterium. Increased abundance of Corynebacterium in scarring disease was associated with innate immune responses to the microbiota, dominated by altered mucin expression and increased matrix adhesion.Interpretation: In the absence of current Chlamydia trachomatis infection, changes in the ocular microbiome associate with differential expression of antimicrobial and inflammatory genes that impair epithelial cell health. In scarring trachoma, expansion of non-pathogenic bacteria such as Corynebacterium and innate responses are coincident, warranting further investigation of this relationship. Comparisons between active and scarring trachoma supported the relative absence of type-2 interferon responses in scarring, whilst highlighting a common suppression of re-epithelialization with altered epithelial and bacterial adhesion, likely contributing to development of scarring pathology.

Progression of scarring trachoma in Tanzanian children: A four-year cohort study.

BackgroundTrachoma is a progressive blinding disease initiated by infection of the conjunctiva with Chlamydia trachomatis. Repeated infections are thought to cause chronic inflammation, which drives scarring, leading to in-turning of the eyelids. The relationship between C. trachomatis, clinical inflammation and scarring development in children is not fully understood due to a paucity of longitudinal studies with infection data at frequent follow-up.Methods and findingsThis longitudinal cohort study took place in northern Tanzania. Children aged 6–10 years at baseline were eligible for inclusion. Participants were visited every three months for four years. Clinical signs and conjunctival swabs for C. trachomatis detection by qPCR were collected at each time-point. Conjunctival photographs from baseline and final time-points were graded and compared side-by-side to determine scarring incidence and progression.Of the 666 children enrolled in the study, outcome data were obtained for 448. Scarring progression was detected in 103/448 (23%) children; 48 (11%) of which had incident scarring and 55 (12%) had progression of existing scarring. Scarring was strongly associated with increasing episodes of trachomatous papillary inflammation (TP). Weaker associations were found between episodes of C. trachomatis infection and follicular trachoma (TF) with scarring progression in unadjusted models, which were absent in multivariable analysis after adjusting for inflammation (multivariable results: C. trachomatis p = 0.44, TF p = 0.25, TP p = <0.0001, age p = 0.13, female sex p = 0.05). Individuals having TP at 30% or more of the time-points they were seen had an odds ratio of 7.5 (95%CI = 2.7–20.8) for scarring progression relative to individuals without any TP detected during the study period.ConclusionsThese data suggest that the effect of infection on scarring progression is mediated through papillary inflammation, and that other factors contributing to the development of inflammation, in addition to C. trachomatis infection, may be important in driving conjunctival scarring progression in children. The addition of TP as a measure in trachoma control programs would provide an indication of the future risk of developing scarring sequelae.

Ocular immune responses, Chlamydia trachomatis infection and clinical signs of trachoma before and after azithromycin mass drug administration in a treatment naïve trachoma-endemic Tanzanian community.

BackgroundTrachoma, caused by Chlamydia trachomatis, remains the leading infectious cause of blindness worldwide. Persistence and progression of the resulting clinical disease appears to be an immunologically mediated process. Azithromycin, which is distributed at the community level for trachoma control, has immunomodulatory properties. We investigated the impact of one round of oral azithromycin on conjunctival immune responses, C. trachomatis infection and clinical signs three- and six- months post treatment relative to three pre-treatment time-points.MethodologyA cohort of children aged 6 to 10 years were recruited from a trachoma endemic region of northern Tanzania and were visited five times in a 12-month period. They were examined for clinical signs of trachoma and conjunctival swabs were collected for laboratory analysis. C. trachomatis infection was detected and the expression of 46 host genes was quantified using quantitative PCR. All community members were offered azithromycin treatment immediately after the six-month timepoint according to international guidelines.FindingsThe prevalence of C. trachomatis infection and inflammatory disease signs were significantly reduced three- and six- months post-mass drug administration (MDA). C. trachomatis infection was strongly associated with clinical signs at all five time-points. A profound anti-inflammatory effect on conjunctival gene expression was observed 3 months post-MDA, however, gene expression had largely returned to pre-treatment levels of variation by 6 months. This effect was less marked, but still observed, after adjusting for C. trachomatis infection and when the analysis was restricted to individuals who were free from both infection and clinical disease at all five time-points. Interestingly, a modest effect was also observed in individuals who did not receive treatment.ConclusionConjunctival inflammation is the major clinical risk factor for progressive scarring trachoma, therefore, the reduction in inflammation associated with azithromycin treatment may be beneficial in limiting the development of potentially blinding disease sequelae. Future work should seek to determine whether this effect is mediated directly through inhibition of pro-inflammatory intracellular signalling molecules, through reductions in concurrent, sub-clinical infections, and/or through reduction of infection exposure.

Prevalence of Trachoma in 47 Administrative Districts of Zambia: Results of 32 Population-Based Prevalence Surveys

ABSTRACTPurpose: A number of previous administrative-district-level baseline trachoma prevalence estimates in Zambia required verification. We used methodologies and systems for trachoma surveys considered to represent international best practice in order to generate reliable estimates of the prevalence of trachoma.Methods: Between March 2016 and July 2017, we undertook 32 population-based prevalence surveys covering 47 administrative districts. In each of the 32 evaluation units (EUs), we selected 31 households in each of 24 clusters. In selected households, trained, certified graders examined all residents aged 1 year and above for evidence of trachomatous inflammation—follicular (TF) and trichiasis. In eyes that had trichiasis, the presence or absence of trachomatous scarring (TS) was recorded, and the subject was asked about previous trichiasis management recommendations from health workers.Results: Five EUs (encompassing seven administrative districts) had prevalence estimates of trichiasis+TS unknown to the health system in ≥15-year-olds of ≥0.2%, and require public-health-level implementation of trichiasis surgery services. Eleven EUs (encompassing 16 administrative districts) had TF prevalence estimates in 1–9-year-olds of ≥5%. Intervention with the A, F and E components of the SAFE strategy for trachoma elimination is required for nearly 1.5 million people.Conclusion: Trachoma is a public health problem in some parts of Zambia. The Ministry of Health will continue to partner with other stakeholders to implement the multi-sectoral SAFE strategy. Consideration should be given to re-surveying other suspected-endemic administrative districts in which surveys using older methodologies returned TF prevalence estimates ≥5%.

Pathway-Wide Genetic Risks in Chlamydial Infections Overlap between Tissue Tropisms: A Genome-Wide Association Scan

Chlamydia trachomatis is the most commonly diagnosed bacterial sexually transmitted infection and can lead to tubal factor infertility, a disease characterised by fibrosis of the fallopian tubes. Genetic polymorphisms in molecular pathways involving G protein-coupled receptor signalling, the Akt/PI3K cascade, the mitotic cell cycle, and immune response have been identified in association with the development of trachomatous scarring, an ocular form of chlamydia-related fibrotic pathology. In this case-control study, we performed genome-wide association and pathways-based analysis in a sample of 71 Dutch women who attended an STI clinic who were seropositive for Chlamydia trachomatis antibodies and 169 high-risk Dutch women who sought similar health services but who were seronegative. We identified two regions of within-gene SNP association with Chlamydia trachomatis serological response and found that GPCR signalling and cell cycle pathways were also associated with the trait. These pathway-level associations appear to be common to immunological sequelae of chlamydial infections in both ocular and urogenital tropisms. These pathways may be central mediators of human refractoriness to chlamydial diseases.

Non-Chlamydial Bacterial Infection and Progression of Conjunctival Scarring in Trachoma.

PurposeThe purpose of this study was to assess whether non-chlamydial bacterial infection is associated with progression of trachomatous scarring in adults.MethodsThis was a cohort study involving 800 participants in northern Tanzania who underwent clinical examination, photography, and conjunctival swab collection for microbiology over a 24-month period. Samples for microbiology were inoculated onto blood and chocolate agar, and Chlamydia trachomatis was detected by PCR. Progression was determined by comparison of baseline to 24-month photographs.ResultsC. trachomatis was detected in only four participants at baseline. At 24 months, 617 participants (77.1%) were followed up. Of those seen at 24 months, 452 could be reliably assessed. Definite scarring progression (progressors) was seen in 345 (55.9%); there was no progression (nonprogressors) in 107 (17.3%). Using combined baseline and 12-month microbiology results, progressors had significantly higher levels of commensal and pathogenic bacterial organisms detected compared with nonprogressors. After adjusting for age, baseline scarring, and ethnicity, there was weak evidence (P = 0.07) that the bacteria category was associated with scarring progression (commensal organisms only: odds ratio [OR] = 1.61; 95% confidence interval [CI]: 0.90 to 2.89; pathogenic organisms either with or without commensal: OR = 2.39; 95% CI: 1.10 to 5.16).ConclusionThe findings were consistent with the possibility that trachomatous scarring in adults is associated with the presence of non-chlamydial bacterial organisms, particularly pathogenic organisms. C. trachomatis was detected very infrequently and may not be an important factor in the pathogenesis of scarring progression in adults. This has implications for trachoma control programs, which largely concentrate on reducing C. trachomatis levels and transmission.

Trachoma in Yunnan province of southwestern China: findings from trachoma rapid assessment

BackgroundTo understand the situation of active trachoma among children aged 6 to 8 years old and scarring trachoma among those aged 15 and over in Yunnan Province, South-western China.MethodsA rapid assessment of trachoma was conducted to determine the presence or absence of trachoma in Yunnan. Through risk assessment, 9 sites in 8 suspected trachoma epidemic counties were selected. Trachoma Rapid Assessment was conducted in these areas afterwards. Within each sites, 50 students from grade one in local primary school and adults aged 15 and above with suspected scarring trachoma were examined by survey teams.ResultsA total of 450 children aged 6–8 years and 160 adults aged 15 and above were screened in 9 sites of 8 counties. Only 1 case of active trachoma was found. Detection rate of active trachoma in children was 0.2%(1/450) in all sites and 2% (1/50)in Pingbian County. Out of 150 adults only 1 case of TT and 1 case of CO were found in all the highest at risk communities. People with scarring trachoma were aged over 60 years.ConclusionsThe active trachoma was rarely seen and trachoma is unlikely to be a significant public health problem in Yunnan Province, South-western China.

Risk factors for incidence of trachomatous scarring in a cohort of women in low endemic district

Background/aimsTo determine the incidence of scarring in women in a trachoma low endemic district of rural Tanzania and to determine the effects of lifetime cooking fire exposure and markers of...

Trachomatous scarring among children in a formerly hyper-endemic district of Tanzania.

BackgroundAssociations between repeated ocular infections with Chlamydia trachomatis in childhood and conjunctival scarring in adulthood are well established. Trachomatous scarring (TS) in children has also been observed in hyper-endemic areas, but data are scant regarding childhood scarring in areas where trachoma has been reduced to hypo-endemic levels.Methods/Principle findingsIn this cross-sectional study, a random sample of children, ages 1–9 years, were selected from 38 communities in the formerly hyper-endemic district of Kongwa, Tanzania. Each participant received an ocular examination and eye-swab test for C. trachomatis infection. Conjunctival photographs were taken and analyzed at 5x magnification to determine scarring presence and severity. Community-level case clustering was assessed using intra-class correlation coefficients, and associations between TS presence and demographic/clinical factors were assessed using contingency table analyses. 1,496 children (78% of eligible) participated in this study. The mean age was 5.5 years and 51% were female. Scarring prevalence was 2.1% (95% CI: 1.5%– 3.0%). The prevalence of follicular trachoma and ocular C. trachomatis infection were 3.2% and 6.5%, respectively. Most TS cases (68.7%) fell into the mildest category, grade S1. 18.7% were grade S2; 12.6% were grade S3. No significant associations were seen between TS presence and age, sex, follicular trachoma, or active ocular C. trachomatis infection (p-values: 0.14, 0.48, 0.27, 0.15, respectively). Thirty communities (78.9%) had 0–1 TS cases, and the most seen in any single community was four cases. Three years ago, follicular trachoma prevalence averaged 4.9% in communities with 0–1 TS cases, but 7.6% in communities with 2–4 TS cases (p-value: 0.08).ConclusionsIn this formerly hyper-endemic district of Tanzania, TS was rare in 1–9 year-olds and usually mild when present. Communities with higher rates of follicular trachoma in the past were more likely to have ≥2 cases of scarring, but the association was not statistically significant.

Immunofibrogenic Gene Expression Patterns in Tanzanian Children with Ocular Chlamydia trachomatis Infection, Active Trachoma and Scarring: Baseline Results of a 4-Year Longitudinal Study.

Trachoma, caused by Chlamydia trachomatis, is the world's leading infectious cause of blindness and remains a significant public health problem. Much of trachomatous disease pathology is thought to be caused indirectly by host cellular and immune responses, however the immune response during active trachoma and how this initiates progressive scarring is not clearly understood. Defining protective vs. pathogenic immune response to C. trachomatis is important for vaccine design and evaluation. This study reports the baseline results of a longitudinal cohort of Tanzanian children, who were monitored for 4 years in order to determine the immunofibrogenic and infectious correlates of progressive scarring trachoma. In this cohort baseline, 506 children aged 6–10 years were assessed for clinical signs, infection status and the expression of 91 genes of interest prior to mass azithromycin administration for trachoma control. C. trachomatis was detected using droplet digital PCR and gene expression was measured using quantitative real-time PCR. The prevalence of follicles, papillary inflammation and scarring were 33.6, 31.6, and 28.5%, respectively. C. trachomatis was detected in 78/506 (15.4%) individuals, 62/78 of whom also had follicles. C. trachomatis infection was associated with a strong upregulation of IFNG and IL22, the enrichment of Th1 and NK cell pathways and Th17 cell-associated cytokines. In individuals with inflammation in the absence of infection the IFNG/IL22 and NK cell response was reduced, however, pro-inflammatory, growth and matrix factors remained upregulated and mucins were downregulated. Our data suggest that, strong IFNG/IL22 responses, probably related to Th1 and NK cell involvement, is important for clearance of C. trachomatis and that the residual pro-inflammatory and pro-fibrotic phenotype that persists after infection might contribute to pathological scarring. Interestingly, females appear more susceptible to developing papillary inflammation and scarring than males, even at this young age, despite comparable levels of C. trachomatis infection. Females also had increased expression of a number of IFNγ pathway related genes relative to males, suggesting that overexpression of this pathway in response to infection might contribute to more severe scarring. Longitudinal investigation of these factors will reveal their relative contributions to protection from C. trachomatis infection and development of scarring complications.

Trachomatous Scarring and Infection With Non-Chlamydia Trachomatis Bacteria in Women in Kongwa, Tanzania.

PurposeTo assess for an association between conjunctival infection with nonchlamydial bacterial species and the presence of trachomatous scarring (TS) in women in central Tanzania.MethodsCross-sectional data were collected from a random sample of women ages 18 and older in 47 trachoma-endemic communities in Kongwa, Tanzania. Each participant completed a survey, provided a conjunctival swab sample, and received an ocular exam to assess for TS. Biologic samples were cultured for bacterial growth and speciation. Contingency tables were used to assess the associations between TS and bacterial carriage.ResultsComplete data was provided by 3882 women (80.7% of invitees). Of all samples, 14% resulted in a positive bacterial isolate. There was no association between TS and nonchlamydial bacterial carriage, whether assessed by species, pathogenicity, or in aggregate. There was a significant association between increasing age and TS severity, but not between age and bacterial carriage. No Corynebacterium was found in the swabs.ConclusionsThis study found no association between TS and nonchlamydial ocular infections, although associations with Corynebacterium cannot be ruled out.

Chlamydia trachomatis Infection Is Associated with E-Cadherin Promoter Methylation, Downregulation of E-Cadherin Expression, and Increased Expression of Fibronectin and α-SMA-Implications for Epithelial-Mesenchymal Transition.

Chlamydia trachomatis (Ct) can induce scarring disease of the ocular mucosa, known as trachoma, the most common infectious cause of blindness worldwide. We hypothesized that epithelial-mesenchymal transition (EMT) contributes to the fibrotic process in trachomatous scarring. Infection of human conjunctival epithelial cells (HCjE) with Ct activated signaling pathways involved in EMT induction, which was correlated with decreased expression of E-cadherin, guardian of the epithelial phenotype. In addition, Ct infection was associated with increased expression of two mesenchymal cell markers: fibronectin and α-SMA. The DNA methylation statuses of selected regions of E-cadherin, fibronectin, and α-SMA genes revealed that Ct infection was accompanied with changes in DNA methylation of the E-cadherin promoter, while the expression of the two mesenchymal markers was not related with this epigenetic event. Our data suggest that Ct infection of conjunctival epithelial cells induces EMT-like changes that go along with modification of the methylation profile of the E-cadherin promoter and could, as one of the earliest events, contribute to processes triggering conjunctival scarring.

Rapid assessment of children's active trachoma in rural area of Naxi district and Jiangyang district of Luzhou in China during 10 years

Background Trachoma is a serious blinding eye disease.At present, the incidence rate of trachoma in China has been greatly reduced with the unremitting efforts of World Health Orgnization (WHO) and Chinese government.However, in some economically underdeveloped areas, there is still active trachoma. Objective This study aimed to survey the prevalence of children's active trachoma in rural area of Naxi district and Jiangyang district of Luzhou city and assess the prevention and treatment outcome of trachoma during 10 years. Methods A cross-sectional study was performed in Naxi district and Jiangyang district of Luzhou city, the economic underdeveloping and water-starved regions in the year 2000.The active trachoma was screened in 214 school-age children with the male 113 and female 101 based on simplified trachoma grading system and trachoma rapid assessment survey standards and requirements of WHO.The symptoms of active trachoma were divided into trachomatous follicular (TF), trachomatous inflammation intense (TI), trachomatous scarring (TS), trachoma trichiasis (TT) and corneal opacities (CO). The epidemiological survey was re-assessed in 100 school-age children (with the male 58 and female 42) in these regions in the year 2013 to evaluate the prevalence change of children active trachoma during 10 years. Results In the year 2000, 214 children were screened in 4 villages of Naxi district and Jiangyang district, and the prevalence rate of TF was 49.07% (105/214) in the year 2000.The prevalence rate of TF was 49.05% (52/106) in the Naxi district and 49.07% (53/108) in the Jiangyang district, showing no significant difference between them (χ2=0.01, P=0.99). In the 100 school-age children who received survey in Naxi district and Jiangyang district in the year 2013, no TF, TF, TI, TS, TT and CO was found, showing no active trachoma. Conclusions The active trachoma has been controlled in rural areas of Luzhou city following the prevention and treatment of trachoma and the improvement of economic status in past decade. Key words: Trachoma/epidemiology; Trachomatous follicular; Prevalence; WHO simplified trachoma grading system; School-age children; Rural region; Corss-sectional studies; Trachoma rapid assessment

MiRNAs that associate with conjunctival inflammation and ocular Chlamydia trachomatis infection do not predict progressive disease.

We previously showed that conjunctival miR-147b and miR-1285 were upregulated in Gambian adults with inflammatory scarring trachoma, and miR-155 and miR-184 expression was strongly associated with conjunctival inflammation and ocular Chlamydia trachomatis infection in children from Guinea-Bissau. We investigated whether the single or combined expression of miR-147b, miR-1285, miR-155 and miR-184 was able to identify individuals with increased risk of incident or progressive scarring trachoma. Conjunctival swab samples were collected from 506 children between the ages of 4 and 12 living in northern Tanzania. These 506 samples formed the baseline sample set of a 4-year longitudinal study. Chlamydia trachomatis infection was diagnosed by droplet digital PCR and expression of miR-155, miR-184, miR-1285 and miR-147b was tested by qPCR. Individuals were assessed for incidence and progression of conjunctival scarring by comparison of conjunctival photographs taken at baseline and 4 years later. miR-184 and miR-155 were strongly associated with inflammation and infection at baseline; however, no miR was associated with 4-year scarring incidence or progression. miR-184 expression was more strongly downregulated during inflammation in non-progressors relative to progressors, suggesting that a disequilibrium in the efficiency of wound healing is a significant determinant of progressive conjunctival fibrosis.

Use of in-vivo confocal microscopy to assess the association of dendritiform cells with progressive trachomatous conjunctival scarring

BackgroundTrachoma is the most common infectious cause of blindness worldwide. In-vivo confocal microscopy (IVCM) provides high-resolution images of the ocular surface. We have previously reported a grading system for the quantitative assessment of these images in scarring trachoma. We found that the presence of trachomatous scarring was strongly associated with the presence of dendritiform cells (DFCs). The present study assessed whether there is an association between DFCs and clinical progression in scarring. MethodsParticipants with trachomatous scarring in northern Tanzania were examined at baseline and 24 months (clinical assessment, photography, and IVCM of the upper tarsal conjunctiva). IVCM images were graded according to a validated grading system. Two independent observers identified scarring progression by comparing photographs taken at baseline and 24 months. Findings800 participants were assessed clinically at baseline and 617 of them were re-examined at 24 months. There were 465 individuals who had photographs that could be confidently graded as having either progression or scarring, or not having progression. Progression was found to occur in 113 (24%) of the 465 individuals. IVCM images were obtained in 344 of these participants at baseline and 24 months, and 29 (8·4%) had DFCs present at baseline. The presence of DFCs at baseline was significantly associated with scarring progression (p=0·01), including adjustment for age and sex (p=0·03). InterpretationThe presence of DFCs on IVCM images is associated with progressive trachomatous conjunctival scarring. DFCs are thought to represent dendritic cells, which have a central role in mediating the immune response and potentially in the pathogenesis of trachomatous scarring. The nature of these cells warrants further investigation, potentially as a novel antifibrotic therapeutic target. FundingWellcome Trust senior research fellowship (to MB). National Institute for Health and Research academic clinical fellowship (to JH).

Eyelash Epilation in the Absence of Trichiasis: Results of a Population-Based Prevalence Survey in the Western Division of Fiji.

BackgroundThe WHO definition of trachomatous trichiasis (TT) is “at least one eyelash touching the globe, or evidence of recent epilation of in-turned eyelashes”, reflecting the fact that epilation is used as a self-management tool for TT. In Fiji’s Western Division, a high TT prevalence (8.7% in those aged ≥15 years) was reported in a 2012 survey, yet a 2013 survey found no TT and Fijian ophthalmologists rarely see TT cases. Local anecdote suggests that eyelash epilation is a common behaviour, even in the absence of trichiasis. Epilators may have been identified as TT cases in previous surveys.MethodsWe used a preliminary focus group to design an interview questionnaire, and subsequently conducted a population-based prevalence survey to estimate the prevalence of epilation in the absence of trichiasis, and factors associated with this behaviour, in the Western Division of Fiji.ResultsWe sampled 695 individuals aged ≥15 years from a total of 457 households in 23 villages. 125 participants (18%) reported epilating their eyelashes at least once within the past year. Photographs were obtained of the eyes of 121/125 (97%) individuals who epilated, and subsequent analysis by an experienced trachoma grader found no cases of trachomatous conjunctival scarring or trichiasis. The age- and sex- adjusted prevalence of epilation in those aged ≥15 years was 8.6% (95% CI 5.7–11.3%). iTaukei ethnicity, female gender, and a higher frequency of drinking kava root were independently associated with epilation.ConclusionEpilation occurs in this population in the absence of trichiasis, with sufficient frequency to have markedly inflated previous estimates of local TT prevalence. Individuals with epilated eyelashes should be confirmed as having epilated in-turned eyelashes in an eye with scarring of the conjunctiva before being counted as cases of TT.

Fibroblasts profiling in scarring trachoma identifies IL-6 as a functional component of a fibroblast-macrophage pro-fibrotic and pro-inflammatory feedback loop.

Trachoma is a conjunctiva scarring disease, which is the leading infectious cause of blindness worldwide. Yet, the molecular mechanisms underlying progressive fibrosis in trachoma are unknown. To investigate the contribution of local resident fibroblasts to disease progression, we isolated conjunctival fibroblasts from patients with scarring trachoma and matching control individuals, and compared their gene expression profiles and functional properties in vitro. We show that scarring trachoma fibroblasts substantially differ from control counterparts, displaying pro-fibrotic and pro-inflammatory features matched by an altered gene expression profile. This pro-inflammatory signature was exemplified by increased IL-6 expression and secretion, and a stronger response to macrophage-mediated stimulation of contraction. We further demonstrate that scarring trachoma fibroblasts can promote Akt phosphorylation in macrophages in an IL-6 –dependent manner. Overall this work has uncovered a distinctive molecular fingerprint for scarring trachoma fibroblasts, and identified IL-6- as a potential contributor to the chronic conjunctival fibrosis, mediating reciprocal pro-fibrotic/pro-inflammatory interactions between macrophages and fibroblasts.

Increased Epithelial Expression of CTGF and S100A7 with Elevated Subepithelial Expression of IL-1β in Trachomatous Trichiasis.

PurposeTo characterize the histological appearance and expression of pro-inflammatory mediators, growth factors, matrix metalloproteinases and biomarkers of epithelial-mesenchymal transition (EMT) in healthy control and trachomatous trichiasis (TT) conjunctival tissue.MethodsConjunctival biopsies were taken from 20 individuals with TT and from 16 individuals with healthy conjunctiva, which served as controls. Study participants were of varying ethnicity and were living in a trachoma-endemic region of northern Tanzania. Formalin-fixed paraffin-embedded tissue sections were stained using hematoxylin and eosin or by immunohistochemistry using antibodies against: IL-1β, IL-6, IL-17A, IL-22, CXCL5, S100A7, cleaved caspase 1 (CC1), PDGF, CTGF, TGFβ2, MMP7, MMP9, E-cadherin, vimentin, and αSMA.ResultsTissue from TT cases had a greater inflammatory cell infiltrate relative to controls and greater disruption of collagen structure. CTGF and S100A7 were more highly expressed in the epithelium and IL-1β was more highly expressed in the substantia propria of TT cases relative to controls. Latent TGFβ2 was slightly more abundant in the substantia propria of control tissue. No differences were detected between TT cases and controls in the degree of epithelial atrophy, the number of myofibroblasts or expression of EMT biomarkers.ConclusionsThese data indicate that the innate immune system is active in the immunopathology of trachoma, even in the absence of clinical inflammation. CTGF might provide a direct link between inflammation and fibrosis and could be a suitable target for therapeutic treatment to halt the progression of trachomatous scarring.