Chlamydia trachomatis: quest for an eye-opening vaccine breakthrough.

INTRODUCTION: Chlamydia trachomatis, commonly referred to as chlamydia (a bacterium), is a common sexually transmitted infection, and if attended to early, it can be treatable. However, if left untreated it can lead to serious consequences. C. trachomatis infects both females and males although its occurrence in females is more common, and it can spread to the eyes causing disease and in some case blindness. AREA COVERED: With ongoing attempts in the most impoverished regions of the country, trachoma will be eradicated as a blinding disease by the year 2022. A prophylactic vaccine candidate with established safety and efficacy is a cogent tool to achieve this goal. This manuscript covers the vaccine development programs for chlamydial infection. EXPERT OPINION: Currently, the Surgery Antibiotics Facial Environmental (SAFE) program is being implemented in endemic countries in order to reduce transmission and control of the disease. Vaccines have been shown over the years to protect against infectious diseases. Charge variant-based adjuvant can also be used for the successful delivery of chlamydial specific antigen for efficient vaccine delivery through nano delivery platform. Thus, a vaccine against C. trachomatis would be of great public health benefit.

Population-Based Prevalence of Chlamydia trachomatis Infection and Antibodies in Four Districts with Varying Levels of Trachoma Endemicity in Amhara, Ethiopia.

The Trachoma Control Program in Amhara region, Ethiopia, scaled up the surgery, antibiotics, facial cleanliness, and environmental improvement (SAFE) strategy in all districts starting in 2007. Despite these efforts, many districts still require additional years of SAFE. In 2017, four districts were selected for the assessment of antibody responses against Chlamydia trachomatis antigens and C. trachomatis infection to better understand transmission. Districts with differing endemicity were chosen, whereby one had a previous trachomatous inflammation-follicular (TF) prevalence of ≥ 30% (Andabet), one had a prevalence between 10% and 29.9% (Dera), one had a prevalence between 5% and 10% (Woreta town), and one had a previous TF prevalence of < 5% (Alefa) and had not received antibiotic intervention for 2 years. Survey teams assessed trachoma clinical signs and took conjunctival swabs and dried blood spots (DBS) to measure infection and antibody responses. Trachomatous inflammation-follicular prevalence among children aged 1-9 years was 37.0% (95% CI: 31.1-43.3) for Andabet, 14.7% (95% CI: 10.0-20.5) for Dera, and < 5% for Woreta town and Alefa. Chlamydia trachomatis infection was only detected in Andabet (11.3%). Within these districts, 2,195 children provided DBS. The prevalence of antibody responses to the antigen Pgp3 was 36.9% (95% CI: 29.0-45.6%) for Andabet, 11.3% (95% CI: 5.9-20.6%) for Dera, and < 5% for Woreta town and Alefa. Seroconversion rate for Pgp3 in Andabet was 0.094 (95% CI: 0.069-0.128) events per year. In Andabet district, where SAFE implementation has occurred for 11 years, the antibody data support the finding of persistently high levels of trachoma transmission.

Prevalence of trachoma and associated factors in the rural area of the department of Vaupés, Colombia.

OBJECTIVES: The objectives of the study were to estimate the prevalence of different clinical signs of trachoma and identify possible factors associated with TF. METHODOLOGY: Following the approval of the study protocol by the ethics committee, a cross-sectional study was conducted in Vaupés, a department of the Colombian Amazon, between the years 2012 and 2013 in two districts. Based on the records obtained from a standardized format for the clinical evaluation of the participants and the factors associated with follicular trachoma, an excel database was built and debugged, which was analyzed using IBM SPSS, Statistics Version 23 and Stata STATA (Version 14, 2015, StataCorp LLC, Texas, USA). RESULTS: The records of 13,091 individuals was collected from 216 rural indigenous communities, of which 12,080 were examined (92.3%); 7,274 in the Western and 4,806 in the Eastern districts. A prevalence of trachomatous inflammation-follicular (TF) of 21.7% (n = 599; 95% CI 20.2-23.3) in the Western and 24.9% (n = 483; 95% CI 23.1-26.9) in the Eastern district was found in children aged 1 to 9 years. Regarding trachomatous trichiasis (TT), 77 cases were found, of which 14 belonged to the Western district (prevalence 0.3%, CI 95% 0.2-0.5) and 63 to the Eastern district (1.8%, CI 95% 1.4-2.4). Children aged between 1 to 9 years were significantly more likely to have TF when there was the presence of secretions on the face (OR: 3.2; 95% CI: 2.6-3.9). CONCLUSIONS: Trachoma is a public health problem in Vaupés that requires the implementation of the SAFE strategy (S = Surgery, A = Antibiotics, F = Face Washing, E = Environment) in the Eastern and Western districts, for at least 3 consecutive years, in accordance with WHO recommendations.

Ocular Chlamydia trachomatis infection and infectious load among pre-school aged children within trachoma hyperendemic districts receiving the SAFE strategy, Amhara region, Ethiopia.

BACKGROUND: After approximately 5 years of SAFE (surgery, antibiotics, facial cleanliness, environmental improvement) interventions for trachoma, hyperendemic (trachomatous inflammation-follicular (TF) ≥30%) districts remained in Amhara, Ethiopia. This study's aim was to characterize the epidemiology of Chlamydia trachomatis (Ct) infection and load among pre-school aged children living under the SAFE strategy. METHODS: Conjunctival swabs from a population-based sample of children aged 1-5 years collected between 2011 and 2015 were assayed to provide Ct infection data from 4 endemic zones (comprised of 58 districts). Ct load was determined using a calibration curve. Children were graded for TF and trachomatous inflammation-intense (TI). RESULTS: 7,441 children were swabbed in 4 zones. TF and TI prevalence were 39.9% (95% confidence Interval [CI]: 37.5%, 42.4%), and 9.2% (95% CI: 8.1%, 10.3%) respectively. Ct infection prevalence was 6.0% (95% CI: 5.0%, 7.2%). Infection was highest among children aged 2 to 4 years (6.6%-7.0%). Approximately 10% of infection occurred among children aged 1 year. Ct load decreased with age (P = 0.002), with the highest loads observed in children aged 1 year (P = 0.01) vs. aged 5 years. Participants with TF (P = 0.20) and TI (P<0.01) had loads greater than individuals without active trachoma. CONCLUSIONS: In this hyperendemic setting, it appears that the youngest children may contribute in meaningful ways towards persistent active trachoma.

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.

Achieving the endgame: Integrated NTD case searches.

Trachoma and Guinea Worm Disease (GWD) are neglected tropical diseases (NTD) slated for elimination as a public health problem and eradication respectively by the World Health Organization. As these programs wind down, uncovering the last cases becomes an urgent priority. In 2010, Ghana Health Services, along with The Carter Center, Sightsavers, and other partners, conducted integrated case searches for both GWD and the last stage of trachoma disease, trachomatous trichiasis (TT), as well as providing surgical treatment for TT to meet elimination (and eradication targets). House to house case searches for both diseases were conducted and two case management strategies were explored: a centralized referral to services method and a Point of Care (POC) delivery method. 835 suspected TT cases were discovered in the centralized method, of which 554 accepted surgery. 482 suspected TT cases were discovered in the POC method and all TT cases accepted surgery. The cost per TT case examined was lower in the POC searches compared to the centralized searches ($19.97 in the POC searches and $20.85 in the centralized searches). Both strategies resulted in high surgical uptake for TT surgery, with average uptakes of 72.4% and 83.9% for the centralized and POC searches respectively. We present here that house to house case searches offering services at POC are feasible and a potential tool for elimination and eradication programs nearing their end.

Baseline trachoma prevalence in Guinea: Results of national trachoma mapping in 31 health districts.

BACKGROUND: Based on previous studies, historical records and risk factors, trachoma was suspected to be endemic in 31 health districts (HDs) in Guinea. To facilitate planning for the elimination of trachoma as a public health problem, national trachoma surveys were conducted between 2011 and 2016 to determine the prevalence of trachomatous inflammation-follicular (TF) and trachomatous trichiasis (TT) in all 31 endemic HDs. METHODOLOGY/PRINCIPAL FINDINGS: A total of 27 cross-sectional surveys were conducted, each using two-stage cluster sampling (one survey in 2011 covered five HDs). Children aged 1-9 years and adults aged ≥15 years were examined for TF and TT, respectively, using the World Health Organization (WHO) simplified grading system. Indicators of household access to water, sanitation and hygiene (WASH) were also collected. A total of 100,051 people from 13,725 households of 556 clusters were examined, of whom 44,899 were male and 55,152 were female. 44,209 children aged 1-9-years and 48,745 adults aged ≥15 years were examined. The adjusted prevalence of TF varied between 1.0% (95%CI: 0.6-1.5%) to 41.8% (95%CI: 39.4-44.2%), while the adjusted prevalence of TT ranged from 0.0% (95%CI: 0.0-0.2%) to 2.8% (95%CI: 2.3-3.5%) in the 27 surveys. In all, 18 HDs had a TF prevalence ≥5% in children aged 1-9 years and 21 HDs had a TT prevalence ≥0.2% in adults aged ≥15 years. There were an estimated 32,737 (95% CI: 19,986-57,811) individuals with TT living in surveyed HDs at the time of surveys. CONCLUSIONS/SIGNIFICANCE: Trachoma is a public health problem in Guinea. 18 HDs required intervention with at least one round of mass drug administration and an estimated 32,737 persons required TT surgery in the country. The results provided clear evidence for Guinea to plan for national trachoma elimination.

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.

Chlamydial eye infections: Current perspectives.

Chlamydia trachomatis, an obligate intraocular bacteria causing trachoma, adult and neonatal inclusion conjunctivitis, was the leading cause of blindness in the last century worldwide. Improvement in socioeconomic and living conditions, availability of antibiotics, and introduction of National Trachoma Control Programmes reduced the prevalence in developed countries, but it persisted in resource-poor settings of Africa and Asia, including India. In 2016, as per the WHO report, trachoma is restricted to 42 countries, causing blindness/visual impairment in ~1.9 million people. India is one of the five countries with nearly half of total active trachoma patients. Introduction of Global Elimination of Trachoma 2020 program by the WHO, using SAFE strategy (surgery for trachomatous trichiasis; Antibiotics for C. trachomatis; Facial cleanliness; and environmental improvement) greatly reduced the prevalence, but trachoma still persists in India. Global increase in the reproductive tract infection by C. trachomatis urogenital serotypes (D-K) has led to concurrent increase in C. trachomatis eye infections. Therefore, kerato eye infections due to chlamydial infections continue to be seen in hospitals. Over the years, there have been advances in laboratory diagnostics, in understanding the pathogenesis, tissue tropism, C. trachomatis genomics, and treatment modalities. Due attention and research is still needed for the study of C. trachomatis eye infections.

Australian trachoma surveillance annual report, 2013.

Australia remains the only developed country to have endemic levels of trachoma (a prevalence of 5% or greater among children) in some regions. Endemic trachoma in Australia is found predominantly in remote and very remote Aboriginal communities. The Australian Government funds the National Trachoma Surveillance and Reporting Unit to collate, analyse and report trachoma prevalence data and document trachoma control strategies in Australia through an annual surveillance report. This report presents data collected in 2013. Data are collected from Aboriginal and Torres Strait Island communities designated at-risk for endemic trachoma within New South Wales, the Northern Territory, South Australia and Western Australia. The World Health Organization grading criteria were used to diagnose cases of trachoma in Aboriginal children, with jurisdictions focusing screening activities on the 5-9 years age group; but some children in the 1-4 and 10-14 years age groups were also screened. The prevalence of trachoma within a community was used to guide treatment strategies as a public health response. Aboriginal adults aged 40 years or over were screened for trichiasis. Screening coverage for the estimated population of children aged 5-9 years and adults aged 40 years or over in at-risk communities required to be screened in 2013 was 84% and 30%, respectively. There was a 4% prevalence of trachoma among children aged 5-9 years who were screened. Of communities screened, 50% were found to have no cases of active trachoma and 33% were found to have endemic levels of trachoma. Treatment was required in 75 at-risk communities screened. Treatment coverage for active cases and their contacts varied between jurisdictions from 79% to 100%. Trichiasis prevalence was 1% within the screened communities.

Prevalência de Tracoma em crianças em idade escolar no município de Turmalina, MG / Trachoma prevalence among schoolchildren in the municipality of Turmalina, Minas Gerais state

RESUMO O tracoma, tido equivocadamente como erradicado em nosso meio, encontra-se na lista de doenças negligenciadas. Trata-se da maior causa de cegueira evitável do mundo, sendo encontrado predominantemente nos países subdesenvolvidos. Diversos trabalhos têm demonstrado que esta doença atualmente se faz presente em todas as regiões do Brasil, o que evidencia que tanto o governo (nas esferas federal, estadual e municipal), quanto a academia devem continuar a considerar o tracoma entre as causas de cegueira em nosso meio. Neste trabalho, procurou-se levantar a prevalência de tracoma entre as crianças de sete a quinze anos matriculadas nas escolas da rede pública do município de Turmalina, MG. A pesquisa foi realizada neste município, situado no Vale do Jequitinhonha, considerando que existem nele regiões com populações em situação de alta vulnerabilidade social, portanto com características propícias para o surgimento da doença. Participaram da pesquisa seis médicos e onze enfermeiros com atuação na atenção primária, capacitados e padronizados para tal. Os profissionais de saúde realizaram o exame de 635 estudantes entre 7 a 15 anos nas escolas públicas de Turmalina, MG. Os estudantes com diagnóstico clínico de tracoma foram submetidos à raspagem de conjuntiva com swab e o material enviado para análise laboratorial. Todos os estudantes diagnosticados com tracoma foram tratados no Sistema Único de Saúde (SUS). Os dados coletados foram analisados com auxílio do software Statistical Package for Social Sciences, IBM Inc., USA - SPSS, versão 22.0. Entre os estudantes foi encontrada uma prevalência do tracoma de 4,7%, com predomínio nas áreas rurais.

ABSTRACT Trachoma has been mistakenly assumed as having been eradicated, but is on the list of neglected diseases. It is the leading cause of preventable blindness in the world, being found predominantly in developing countries. Several studies have shown that this disease is currently present in all regions of Brazil, which shows that both the government (at the federal, state and municipal levels) and academia must continue to treat trachoma as one of the causes of blindness. In this study, we sought to identify the prevalence of trachoma among schoolchildren aged between seven and 15 years from public schools in the municipality of Turmalina, Minas Gerais state. The survey was conducted in this municipality, located in the Jequitinhonha Valley, a region that contains populations who live in situations of high social vulnerability, and thus display the characteristics that are conducive to the emergence of the disease. The participants were six doctors and 11 nurses working in primary healthcare, trained and standardized to do so. Health professionals examined 635 students aged 7-15 years in the public schools of Turmalina. Students with a clinical diagnosis of trachoma underwent conjunctiva scraping with a swab and the material was sent for laboratory analysis. All school children diagnosed with trachoma were treated at the Unified Health System (SUS). The collected data were analyzed using the Statistical Package for Social Sciences software, IBM Inc., USA - SPSS, version 22.0. Among the students, a 4.7% prevalence rate of trachoma was found, predominantly in rural areas.

Etiological characteristics of chlamydia trachoma conjunctivitis of Primary Boarding School students in the Qinghai Tibetan area.

The aim of this study was to investigate the etiological characteristics of Chlamydia trachomatis conjunctivitis among resident students at primary schools in the Qinghai Tibetan area in order to understand the distribution of C. trachomatis and other pathogenic microorganisms, to detect the isolation rate of infectious pathogens, and to provide an evidence for further targeted efforts in the prevent of sporadic trachoma efforts. From two primary schools in Qinghai Province, ocular samples from 35 students who were clinically diagnosed as trachoma cases and 60 normal controls were obtained by swabbing their upper eyelids and lower conjunctival sacs. Samples were preserved at 4°C and airlifted to Beijing Tongren Hospital within 24 h. Real- time polymerase chain reaction (RT-PCR) was used to screen for C. trachomatis, and nested PCR was used to amplify a fragment of the ompA gene for serotype confirmation. Bacterial cultivation and sensitivity tests were conducted based on the 2015 version of the Clinical and Laboratory Standards Institute. Adenovirus, herpes simplex virus, cytomegalovirus, and Epstein-Barr virus were screened by RT-PCR. Among the 35 students with trachoma, 8 came from the Jianshetang Primary School and 27 came from the Central Primary School. Two novel C. trachomatis B serotypes (GenBank accession numbers KU737520 and KU737521) were detected based on a sequence analysis of the ompA gene. Single C. trachomatis infections accounted for 42.86% (9/21) of the cases, and infections with multiple bacteria, particularly Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, and Streptococcus pneumoniae, accounted for the remaining 57.14% (12/21). Of the 14 C. trachomatis-negative samples, one was positive for adenoviral infection (serotype D) and 13 were positive for bacterial infections (H. influenzae, M. catarrhalis, S. pneumoniae, S. aureus, streptococci other than S. pneumoniae, Staphylococcus epidermidis, Corynebacterium, and Arthrobacterium). In addition to C. trachomatis, the other bacteria and virus that were detected in the boarding students of primary schools in the Qinghai Tibetan area should be emphasized in trachoma prevention and control.

Corneal Sensitivity and Presence of Pathogenic Organisms Among Participants Who Have Undergone Trichiasis Surgery Differ by Surgical Outcome.

PURPOSE: To explore the potential association between reduced corneal sensation and/or conjunctival bacterial colonization and postoperative trichiasis and eyelid contour abnormalities after corrective eyelid surgery among participants with a history of trachomatous trichiasis. METHODS: As an ancillary study to the Partnership for Rapid Elimination of Trachoma (PRET) Surgery Trial in southern Tanzania, we collected data on 580 PRET participants who had undergone trichiasis surgery 1 year earlier and 200 age-group-matched individuals without trichiasis. Assessments included eyelid status evaluation (presence and severity of postoperative trichiasis and/or eyelid contour abnormality), corneal sensitivity by Cochet-Bonnet aesthesiometer, a questionnaire on symptoms of ocular irritation, and conjunctival microbiology. We divided PRET participants based on their eyelid status and compared results across PRET groups and versus normals. RESULTS: PRET participants had reduced corneal sensitivity compared with age-matched normals (mean sensitivity ranged from 2.8 to 3.8 cm in PRET participants vs. 5.9 cm in normals), and increasing severity of postoperative trichiasis was associated in a stepwise fashion with reduced corneal sensitivity (mean = 3.5 cm for mild and 2.6 cm for severe postoperative trichiasis). Conjunctival colonization with pathogenic bacteria was also associated with more severe postoperative trichiasis (Cochran-Armitage trend test P = 0.001) and with reduced corneal sensitivity (trend test P < 0.0001). Symptoms of ocular irritation were not associated with previous trichiasis surgery, postoperative trichiasis, or eyelid contour abnormality. CONCLUSIONS: These findings indicate that reduced corneal sensitivity accompanies trachomatous trichiasis and suggest that reduced corneal sensitivity may play an important role in the harboring of pathogenic bacteria on the ocular surface.

Mass drug administration of azithromycin for trachoma reduces the prevalence of genital Chlamydia trachomatis infection in the Solomon Islands.

OBJECTIVES: Chlamydia trachomatis is the most common bacterial sexually transmitted infection and is frequently asymptomatic; ocular C. trachomatis strains cause trachoma. Mass drug administration (MDA) of azithromycin for trachoma might also reduce the prevalence of genital C. trachomatis. In a survey conducted in the Solomon Islands in 2014, prior to MDA, the prevalence of genital C. trachomatis was 20.3% (95% CI 15.9% to 25.4%). We conducted a survey to establish the impact of MDA with azithromycin on genital C. trachomatis. METHODS: Women attending three community outpatient clinics, predominantly for antenatal care, 10 months after MDA with azithromycin given for trachoma elimination, were enrolled in this survey. Self-taken high vaginal swabs were for C. trachomatis and Neisseria gonorrhoeae using the BD Probetec strand displacement assay. RESULTS: 298 women were enrolled. C. trachomatis infection was diagnosed in 43 women (14.4%, 95% CI 10.6% to 18.9%) and N. gonorrhoeae in 9 (3%, 95% CI 1.4% to 5.7%). The age-adjusted OR for C. trachomatis infection was consistent with a significant decrease in the prevalence of C. trachomatis following MDA (OR 0.58, 95% CI 0.37 to 0.94, p=0.027). There was no change in the prevalence of N. gonorrhoeae between following MDA (OR 0.51, 95% CI 0.22 to 1.22, p=0.13). CONCLUSIONS: This study demonstrated a 40% reduction in the age-adjusted prevalence of genital C. trachomatis infection following azithromycin MDA for trachoma elimination.

Chlamydia trachomatis from Australian Aboriginal people with trachoma are polyphyletic composed of multiple distinctive lineages.

Chlamydia trachomatis causes sexually transmitted infections and the blinding disease trachoma. Current data on C. trachomatis phylogeny show that there is only a single trachoma-causing clade, which is distinct from the lineages causing urogenital tract (UGT) and lymphogranuloma venerum diseases. Here we report the whole-genome sequences of ocular C. trachomatis isolates obtained from young children with clinical signs of trachoma in a trachoma endemic region of northern Australia. The isolates form two lineages that fall outside the classical trachoma lineage, instead being placed within UGT clades of the C. trachomatis phylogenetic tree. The Australian trachoma isolates appear to be recombinants with UGT C. trachomatis genome backbones, in which loci that encode immunodominant surface proteins (ompA and pmpEFGH) have been replaced by those characteristic of classical ocular isolates. This suggests that ocular tropism and association with trachoma are functionally associated with some sequence variants of ompA and pmpEFGH.

The TNF-α-308G/A Polymorphism is Not Associated with Ocular Chlamydia trachomatis Infection in Han Chinese Children.

OBJECTIVE: To investigate the association between the TNF-α-308G/A polymorphism and ocular chlamydia trachomatis (C. Trachomatis) infection among Han Chinese children. METHODS: 248 patients and 162 matched healthy controls were recruited. The diagnosis of ocular C. Trachomatis infection was given after clinical observation and latex immunochromatography tests. The TNF-α-308G/A polymorphism was genotyped by sequencing. RESULTS: No association was found between the TNF-α-308G/A polymorphism and ocular C. Trachomatis infection. CONCLUSIONS: The TNF-α-308A polymorphism is unlikely to play a major role in the risk for ocular C. Trachomatis in the Chinese population.

Population-Based Study of Trachoma in Guatemala.

PURPOSE: A prevalence survey for active trachoma in children aged under 10 years and trichiasis in women aged 40 years and older was carried out in four districts in the Sololá region in Guatemala, which is suspected of still having a trachoma problem. METHODS: Population-based surveys were undertaken in three districts, within 15 randomly selected communities in each district. In addition, in a fourth district that borders the third district chosen, we surveyed the small northern sub-district, by randomly selecting three communities in each community, 100 children aged under 10 years were randomly selected, and all females over 40 years. Five survey teams were trained and standardized. Trachoma was graded using the World Health Organization simplified grading scheme and ocular swabs were taken in cases of clinical follicular or inflammatory trachoma. Prevalence estimates were calculated at district and sub-district level. RESULTS: Trachoma rates at district level varied from 0-5.1%. There were only two sub-districts where active trachoma approached 10% (Nahualá Costa, 8.1%, and Santa Catarina Costa, 7.3%). Trichiasis rates in females aged 40 years and older varied from 0-3%. Trachoma was likely a problem in the past. CONCLUSIONS: Trachoma is disappearing in the Sololá region in Guatemala. Health leadership may consider further mapping of villages around the areas with an especially high rate of trachoma and infection, and instituting trichiasis surgery and active trachoma intervention where needed.

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 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.