Trachoma: an underdiagnosed disease revealed by a survey carried out at Jaú, São Paulo.

BACKGROUND: Trachoma is a notifiable disease in the state of São Paulo- Brazil. However, in Jaú, a municipality located in this state, in the last 10 years there are no records of cases. This study purpose is to assess if there are cases of inflammatory trachoma in schoolchildren aged 1 to 9 years in the municipality of Jaú as well if it is possible to detect clusters areas of the disease to establish elimination programs. METHODS: An epidemiological study was performed in 2018, involving a stratified random sample of schoolchildren aged 1- to 9-year-old, from public day care centers and elementary schools in the municipality of Jaú. A trachoma screening following the criteria of the World Health Organization (WHO) and the distribution of cases was assessed using geoprocessing. RESULTS: Four thousand-six hundred-nineteen children from 44 elementary schools were examined, and 126 children with active trachoma were detected, with an adjusted prevalence rate of 2.65%. The prevalence was higher (3.01%) in children aged 6- to 9-year-old compared to children aged 1-to 5-year-old (2.42%). There were clusters with a higher concentration of positive cases of the disease in three schools located in the neighborhoods with lower socioeconomic conditions. CONCLUSION: Inflammatory trachoma still present in children aged 1- to 9-year-old in the city of Jaú. The positive cases were located mainly in areas with low socioeconomic conditions. Health promotion with active search and periodical treatment must be planned to fight this important blinding cause, that persists in our municipality.

Active trachoma and associated factors in children aged 1 to 9 years living in Sasiga rural districts, East Wallaga Zone, Ethiopia, in 2022: a community- based cross-sectional study.

BACKGROUND: Trachoma, caused by the bacteria Chlamydia trachomatous, is a contagious eye condition that frequently affects children and quickly spreads from child to child and from child to caregiver. The study aimed to assess the distribution of active trachoma and its associated risk factors among children 1-9 years aged in Households of Sasiga Rural District, Western Ethiopia, in 2022. METHODS: A community-based cross-sectional study was conducted among 577 randomly selected children from March to May 2022. A multistage sampling technique was used. Data was collected through an interviewer-based questionnaire, physical observation, and clinical eye examinations. Epi Data 3.1 was used for data entry. The data were analyzed with SPSS version 24. Bivariate and multivariate binary logistic regressions were performed. In multivariable logistic regression analysis, the adjusted odds ratio with a 95% confidence interval was used to identify factors associated with active trachoma. A P-value of 0.05 was considered statistically significant. RESULTS: The distribution of Active Trachoma among children 1-9 years aged in Households of the study area was 9.5%(95%CI:7.11,11.89). Being from a low-income household with a monthly income of less than 1500 ETB [AOR = 3.49, 95% CI: 1.39, 8.75], Households where the nearest water supply is more than 30 min away [AOR = 8.34, 95%CI: 1.89, 36.73], households with only one room [AOR = 2.98, 95%CI: 1.027, 8.68], and presence of feces in the compound of the households [AOR = 3.08, 95%CI: 1.41, 6.75] were associated with active trachoma in 1-9 years aged children living in the study setting. CONCLUSION: The distribution of Active Trachoma among children 1-9 years aged in Households of the study area was found to be high. Monthly income, the time it took to get water for home use, and the presence of feces in household compounds were all linked to active trachoma in children living in the study area. As a result, continuous sanitary education on trachoma transmission and prevention should be strengthened in the district.

Prevalence of trachoma in indigenous and non-indigenous areas, Northeastern Brazil, 2019-2021.

Objective: To estimate the prevalence of trachoma in indigenous and non-indigenous populations in selected areas of the state of Maranhão, in northeastern Brazil. Methods: This was a population-based survey with probabilistic sampling. For the diagnosis of trachoma, external ocular examination was performed using head magnifying loupes, at 2.5X magnification. The prevalence of trachomatous inflammation - follicular (TF) in children aged 1-9 years and the prevalence of trachomatous trichiasis (TT) in the population aged ≥15 years were estimated. Relative frequencies of sociodemographic and environmental characteristics were obtained. Results: The study included 7 971 individuals, 3 429 from non-indigenous populations and 4 542 from indigenous populations. The prevalence of TF in non-indigenous and indigenous populations was 0.1% and 2.9%, respectively, and the prevalence of TT among indigenous populations was 0.1%. Conclusions: The prevalence of TF and TT in the two evaluation units in the state of Maranhão were within the limits recommended for the elimination of trachoma as a public health problem. However, the prevalence of TF was higher in the indigenous evaluation unit, indicating a greater vulnerability of this population to the disease. The prevalence of TF of below 5.0% implies a reduction in transmission, which may have resulted from improved socioeconomic conditions and/or the implementation of the World Health Organization SAFE strategy.

Seroreversion to Chlamydia trachomatis Pgp3 antigen among children in a hyperendemic region of Amhara, Ethiopia.

Monitoring trachoma transmission with antibody data requires characterization of decay in IgG to Chlamydia trachomatis antigens. In a three-year longitudinal cohort in a high transmission setting, we estimated a median IgG half-life of 3 years and a seroreversion rate of 2.5 (95% CI: 1.6, 3.5) per 100 person-years.

Targeted Mass Azithromycin Distribution for Trachoma: A Community-Randomized Trial (TANA II).

BACKGROUND: Current guidelines recommend annual community-wide mass administration of azithromycin for trachoma. Targeting treatments to those most likely to be infected could reduce the amount of unnecessary antibiotics distributed. METHODS: In a cluster-randomized trial conducted from 1 November 2010 through 8 November 2013, 48 Ethiopian communities previously treated with annual mass azithromycin distributions for trachoma were randomized in equal numbers to (1) annual azithromycin distributions targeted to children aged 0-5 years, (2) annual azithromycin distributions targeted to households with a child aged 0-5 years found to have clinically active trachoma, (3) continued annual mass azithromycin distributions to the entire community, or (4) cessation of treatment. The primary outcome was the community prevalence of ocular chlamydia infection among children aged 0-9 years at month 36. Laboratory personnel were masked to treatment allocation. RESULTS: The prevalence of ocular chlamydia infection among children aged 0-9 years increased from 4.3% (95% confidence interval [CI], .9%-8.6%) at baseline to 8.7% (95% CI, 4.2%-13.9%) at month 36 in the age-targeted arm, and from 2.8% (95% CI, .8%-5.3%) at baseline to 6.3% (95% CI, 2.9%-10.6%) at month 36 in the household-targeted arm. After adjusting for baseline chlamydia prevalence, the 36-month prevalence of ocular chlamydia was 2.4 percentage points greater in the age-targeted group (95% CI, -4.8% to 9.6%; P = .50; prespecified primary analysis). No adverse events were reported. CONCLUSIONS: Targeting azithromycin treatment to preschool children was no different than targeting azithromycin to households with a child with clinically active trachoma. Neither approach reduced ocular chlamydia over the 3-year study. CLINICAL TRIALS REGISTRATION: NCT01202331.

When the Neighboring Village is Not Treated: Role of Geographic Proximity to Communities Not Receiving Mass Antibiotics for Trachoma.

BACKGROUND: Mass administration of azithromycin is an established strategy for decreasing the prevalence of trachoma in endemic areas. However, nearby untreated communities could serve as a reservoir that may increase the chances of chlamydia reinfection in treated communities. METHODS: As part of a cluster-randomized trial in Ethiopia, 60 communities were randomized to receive mass azithromycin distributions and 12 communities were randomized to no treatments until after the first year. Ocular chlamydia was assessed from a random sample of children per community at baseline and month 12. Distances between treated and untreated communities were assessed from global positioning system coordinates collected for the study. RESULTS: The pretreatment prevalence of ocular chlamydia among 0 to 9 year olds was 43% (95% confidence interval [CI], 39%-47%), which decreased to 11% (95% CI, 9%-14%) at the 12-month visit. The posttreatment prevalence of chlamydia was significantly higher in communities that were closer to an untreated community after adjusting for baseline prevalence and the number of mass treatments during the year (odds ratio, 1.12 [95% CI, 1.03-1.22] for each 1 km closer to an untreated community). CONCLUSIONS: Mass azithromycin distributions to wide, contiguous geographic areas may reduce the likelihood of continued ocular chlamydia infection in the setting of mass antibiotic treatments.

Global Trends in Blindness and Vision Impairment Resulting from Corneal Opacity 1984-2020: A Meta-analysis.

TOPIC: We provide global estimates of the prevalence of corneal blindness and vision impairment in adults 40 years of age and older and examine the burden by age, sex, and geographic region from 1984 through 2020. CLINICAL RELEVANCE: Corneal opacities (COs) are among the top 5 causes of blindness worldwide, yet the global prevalence, regional differences, and risk factors are unclear. METHODS: Abstracted data from the published literature and surveys were obtained from the Global Burden of Disease Vision Loss Expert Group. We supplemented this by an independent systematic literature search of several databases. Studies that provided CO vision impairment data based on population-based surveys for those 40 years of age or older were included, for a total of 244. For each of the 4 outcomes of blindness and moderate to severe vision impairment (MSVI) caused by trachomatous and nontrachomatous CO (NTCO), time trends and differences in prevalence by region, age, and sex were evaluated using a Poisson log-linear model with a generalized estimating equation method. Age-standardized estimates of global prevalence of blindness and MSVI were calculated using the 2015 United Nations standard populations. RESULTS: The global prevalence of blindness resulting from NTCO in those 40 years and older was 0.081% (95% confidence interval [CI], 0.049%-0.315%); that of MSVI was 0.130% (95% CI, 0.087%-0.372%). A significant increase with age was found (prevalence rate ratio, 2.15; 95% CI, 1.99-2.32). Latin America and Europe showed the lowest rates, with 2- to 8-fold higher rates of blindness or MSVI in other regions. The global prevalence of blindness resulting from trachomatous CO in those 50 years and older was 0.0094% (95% CI, 0%-0.0693%); that from MSVI was 0.012% (95% CI, 0%-0.0761%). Blindness resulting from trachomatous CO and MSVI increased with age and female sex, and rates were significantly higher in the African regions. A decrease in trachomatous blindness rates over time was found (prevalence rate ratio, 0.91; 95% CI, 0.86-0.96). DISCUSSION: An estimated 5.5 million people worldwide are bilaterally blind or have MSVI resulting from CO, with an additional 6.2 million unilaterally blind. Blindness resulting from trachomatous CO is declining over time, likely because of the massive scaleup of the global trachoma elimination program and overall socioeconomic development. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Perceptions of ophthalmologists on the impact of trachoma in Egypt: a mixed-methods, nationwide survey.

PURPOSE: Understanding the perception and practices of ophthalmologists for trachoma is important to develop interventions aimed at disease elimination in Egypt. The survey investigated: (1) the views and practice patterns of Egyptian ophthalmologists for trachoma and (2) the influence of geographic location, setting, and years of practice on ophthalmologists' perceptions. METHODS: A questionnaire sent to ophthalmologists currently working in Egypt collected information on: (1) demographics, (2) caseload and practice patterns for trachoma, (3) 13 Likert scale questions regarding the current state of trachoma, and (4) two open-ended written response questions. RESULTS: Of the 500 recipients, 194 ophthalmologists participated. 98% of the respondents reported seeing trachoma patients in their practice. 28.8% agreed that trachoma is currently an active health problem in Egypt, with ophthalmologists in public practice having significantly higher agreement scores compared to private practitioners (p = 0.030). Rural ophthalmologists were significantly more likely to agree that a targeted trachoma control program is needed in their location of practice compared to their urban counterparts (p < 0.001). Open-ended questions revealed recurrent themes, including the rural distribution of trachoma patients and the high volume of patients with corneal opacity. CONCLUSION: Ophthalmologists' experiences with trachoma in Egypt differed based on practice setting, years in practice, and location, and the overall perception of the impact of the disease remains low. However, there was widespread agreement that trachoma is present in communities across the country. Practitioners in rural areas and in the public sector shared a disproportionate burden of the trachoma caseload. The perspectives of such ophthalmologists must be emphasized in decision-making related to trachoma interventions.

Cost and community acceptability of enhanced antibiotic distribution approaches for trachoma in the Republic of South Sudan: enhancing the A in SAFE (ETAS) study protocol.

BACKGROUND: The World Health Organization targeted trachoma for global elimination as a public health problem by 2030. Reaching elimination thresholds by the year 2030 in the Republic of South Sudan will be a considerable challenge, as the country currently has many counties considered hyper-endemic (> 30% trachomatous inflammation-follicular [TF]) that have yet to receive interventions. Evidence from randomized trials, modeling, and population-based surveys suggests that enhancements may be needed to the standard-of-care annual mass drug administration (MDA) to reach elimination thresholds in a timely manner within highly endemic areas. We describe a protocol for a study to determine the cost and community acceptability of enhanced antibiotic strategies for trachoma in South Sudan. METHODS: The Enhancing the A in SAFE (ETAS) study is a community randomized intervention costing and community acceptability study. Following a population-based trachoma prevalence survey in 1 county, 30 communities will be randomized 1:1 to receive 1 of 2 enhanced MDA interventions, with the remaining communities receiving standard-of-care annual MDA. The first intervention strategy will consist of a community-wide MDA followed by 2 rounds of targeted treatment to children ages 6 months to 9 years, 2 weeks and 4 weeks after the community MDA. The second strategy will consist of a community-wide biannual MDA approximately 6 to 8 months apart. The costing analysis will use a payer perspective and identify the total cost of the enhanced interventions and annual MDA. Community acceptability will be assessed through MDA coverage monitoring and mixed-methods research involving community stakeholders. A second trachoma-specific survey will be conducted 12 months following the original survey. DISCUSSION: ETAS has received ethical clearance and is expected to be conducted between 2022 and 2023. Results will be shared through subsequent manuscripts. The study's results will provide information to trachoma programs on whether enhanced interventions are affordable and acceptable to communities. These results will further help in the design of future trachoma-specific antibiotic efficacy trials. Enhanced MDA approaches could help countries recover from delays caused by conflict or humanitarian emergencies and could also assist countries such as South Sudan in reaching trachoma elimination as a public health problem by 2030. TRIAL REGISTRATION: This trial was registered on December 1st, 2022 (clinicaltrails.org: NCT05634759).

Assessment of the status of improved F&E trachoma control practices among children of agro-pastoralists in Southern Ethiopia: a mixed design survey using theory of triadic influences.

BACKGROUND: Ethiopia is one of the countries with heavy trachoma burdens states globally. More than 75 million people in Ethiopia live in the trachoma endemic zones. Most populations with neglected tropical diseases (NTDs) live in hard-to-reach residences because of landscape and socio-cultural variances. This survey assessed the status of improved Face hygiene and Environmental cleanliness (F&E) trachoma control practices in children 1-9 years of age. METHODS: A mixed-method study design was applied concurrently. Enumeration was done through interviews using the standard tool and observational technique. Focus Group discussions (FGDs) and Key informant Interviews (KIIs) were used to conduct the qualitative arm. Confounders were controlled by modeling with multivariable logistic regression. RESULTS: For the Quantitative survey: The response rate was 99.8% of participants. The proportion with improved practice was 8%. About 13.9% of a child washed their faces and were visibly clean. About 15.2% of the households had an observable clean environment. High Wealth index, Perceived ability, knowledge about trachoma transmission from person to person, and stance toward preventive behavior were associated with improved practices. The odds of having improved F&E practice were 67% lower for those who reported positive normative preventive behavior than negatives. Qualitative arm: Some key informants reported village dwellers' shortage of basic knowledge; attitude and behavioral change for improved hygienic practices are the challenges. Inhabitants, including elder children, are aware of the hygiene issue though they do not practice it or have no intention to practice it. CONCLUSIONS: Improved F&E practices were much lower in the study region than the regional plan to achieve.

A Virtual Reading Center Model Using Crowdsourcing to Grade Photographs for Trachoma: Validation Study.

BACKGROUND: As trachoma is eliminated, skilled field graders become less adept at correctly identifying active disease (trachomatous inflammation-follicular [TF]). Deciding if trachoma has been eliminated from a district or if treatment strategies need to be continued or reinstated is of critical public health importance. Telemedicine solutions require both connectivity, which can be poor in the resource-limited regions of the world in which trachoma occurs, and accurate grading of the images. OBJECTIVE: Our purpose was to develop and validate a cloud-based "virtual reading center" (VRC) model using crowdsourcing for image interpretation. METHODS: The Amazon Mechanical Turk (AMT) platform was used to recruit lay graders to interpret 2299 gradable images from a prior field trial of a smartphone-based camera system. Each image received 7 grades for US $0.05 per grade in this VRC. The resultant data set was divided into training and test sets to internally validate the VRC. In the training set, crowdsourcing scores were summed, and the optimal raw score cutoff was chosen to optimize kappa agreement and the resulting prevalence of TF. The best method was then applied to the test set, and the sensitivity, specificity, kappa, and TF prevalence were calculated. RESULTS: In this trial, over 16,000 grades were rendered in just over 60 minutes for US $1098 including AMT fees. After choosing an AMT raw score cut point to optimize kappa near the World Health Organization (WHO)-endorsed level of 0.7 (with a simulated 40% prevalence TF), crowdsourcing was 95% sensitive and 87% specific for TF in the training set with a kappa of 0.797. All 196 crowdsourced-positive images received a skilled overread to mimic a tiered reading center and specificity improved to 99%, while sensitivity remained above 78%. Kappa for the entire sample improved from 0.162 to 0.685 with overreads, and the skilled grader burden was reduced by over 80%. This tiered VRC model was then applied to the test set and produced a sensitivity of 99% and a specificity of 76% with a kappa of 0.775 in the entire set. The prevalence estimated by the VRC was 2.70% (95% CI 1.84%-3.80%) compared to the ground truth prevalence of 2.87% (95% CI 1.98%-4.01%). CONCLUSIONS: A VRC model using crowdsourcing as a first pass with skilled grading of positive images was able to identify TF rapidly and accurately in a low prevalence setting. The findings from this study support further validation of a VRC and crowdsourcing for image grading and estimation of trachoma prevalence from field-acquired images, although further prospective field testing is required to determine if diagnostic characteristics are acceptable in real-world surveys with a low prevalence of the disease.

The 100 most cited articles on trachoma: a bibliometric analysis.

OBJECTIVE: Trachoma is the cause of blindness or visual impairment in 1.9 million people. Few bibliometric studies have been carried out, but none explore the characteristics of the 100 most cited articles on trachoma. METHODS: A keyword-based search without time restriction was performed in September 2022 using the Scopus database. Search keywords include the following: "trachoma; trachome; tracoma; trachomatis." Two authors independently screened the literature and extracted data. The search result was obtained to classify the 100 articles according to their number of citations. RESULTS: The Top 100 articles were published between 1957 and 2015 with a total of 11,102 citations (range 56-689). The country with the most significant contribution was the USA (n = 56). The Lancet was the most active journal (n = 15). Bailey RL was the author with the highest number of publications (n = 30). The Edna McConnell Clark Foundation (n = 26) was the most prominent funding entity. The type of original article was the most published (n = 83), in addition, the most frequent thematic area was prevention (n = 33). The most popular keywords were trachoma (n = 93), chlamydia trachomatis (n = 55), and azithromycin (n = 34). CONCLUSIONS: The study provides new insight into trachoma research, information that may help healthcare providers, researchers, and stakeholders better understand trends and influential contributions. It highlights under-researched areas that could be the basis for future research.

Genomics of Ocular Chlamydia trachomatis After 5 Years of SAFE Interventions for Trachoma in Amhara, Ethiopia.

BACKGROUND: To eliminate trachoma as a public health problem, the World Health Organization recommends the SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy. As part of the SAFE strategy in the Amhara Region, Ethiopia, the Trachoma Control Program distributed >124 million doses of antibiotics between 2007 and 2015. Despite this, trachoma remained hyperendemic in many districts and a considerable level of Chlamydia trachomatis (Ct) infection was evident. METHODS: We utilized residual material from Abbott m2000 Ct diagnostic tests to sequence 99 ocular Ct samples from Amhara and investigated the role of Ct genomic variation in continued transmission of Ct. RESULTS: Sequences were typical of ocular Ct at the whole-genome level and in tissue tropism-associated genes. There was no evidence of macrolide resistance in this population. Polymorphism around the ompA gene was associated with village-level trachomatous inflammation-follicular prevalence. Greater ompA diversity at the district level was associated with increased Ct infection prevalence. CONCLUSIONS: We found no evidence for Ct genomic variation contributing to continued transmission of Ct after treatment, adding to evidence that azithromycin does not drive acquisition of macrolide resistance in Ct. Increased Ct infection in areas with more ompA variants requires longitudinal investigation to understand what impact this may have on treatment success and host immunity.

Clinical signs of trachoma and laboratory evidence of ocular Chlamydia trachomatis infection in a remote Queensland community: a serial cross-sectional study.

OBJECTIVES: To compare the findings of standard clinical assessments and of complementary clinical and laboratory methods for determining whether community-wide treatment for trachoma is warranted in a remote Queensland community. DESIGN: Three cross-sectional screening surveys, 2019-2021, complemented by laboratory pathology testing. SETTING: Small community in northwest Queensland with geographic and cultural ties to Northern Territory communities where trachoma persists. PARTICIPANTS: Children aged 1-14 years; opportunistic screening of people aged 15 years or more. MAIN OUTCOME MEASURES: Prevalence of clinical signs of trachoma, Chlamydia trachomatis infection, ocular non-chlamydial infections, and seropositivity for antibodies to the C. trachomatis Pgp3 protein. RESULTS: During the three surveys, 73 examinations of 58 children aged 1-4 years, 309 of 171 aged 5-9 years, and 142 of 105 aged 10-14 years for trachoma were undertaken, as were 171 examinations of 164 people aged 15 years or more; 691 of 695 examinations were of Aboriginal or Torres Strait Islander people (99%), 337 were of girls or young women (48%). Clinical signs consistent with trachomatous inflammation-follicular were identified in 5-9-year-old children 23 times (7%), including in eleven with non-chlamydial infections and one with a C. trachomatis infection. One child (10-14 years) met the criteria for trachomatous scarring. Two of 272 conjunctival swab samples (all ages) were polymerase chain reaction-positive for C. trachomatis (0.7%). Two of 147 people aged 15 years or more examined in 2019 had trichiasis, both aged 40 years or more. Seven of 53 children aged 1-9 years in 2019 and seven of 103 in 2021 were seropositive for anti-Pgp3 antibodies. CONCLUSIONS: Despite the prevalence of clinical signs consistent with trachomatous inflammation-follicular among 5-9-year-old children exceeding the 5% threshold for community-wide treatment, laboratory testing indicated that childhood exposure to ocular C. trachomatis is rare in this community. Laboratory testing should be integrated into Australian trachoma guidelines.

Forecasting Trachoma Control and Identifying Transmission-Hotspots.

BACKGROUND: Tremendous progress towards elimination of trachoma as a public health problem has been made. However, there are areas where the clinical indicator of disease, trachomatous inflammation-follicular (TF), remains prevalent. We quantify the progress that has been made, and forecast how TF prevalence will evolve with current interventions. We also determine the probability that a district is a transmission-hotspot based on its TF prevalence (ie, reproduction number greater than one). METHODS: Data on trachoma prevalence come from the GET2020 global repository organized by the World Health Organization and the International Trachoma Initiative. Forecasts of TF prevalence and the percent of districts with local control is achieved by regressing the coefficients of a fitted exponential distribution for the year-by-year distribution of TF prevalence. The probability of a district being a transmission-hotspot is extrapolated from the residuals of the regression. RESULTS: Forecasts suggest that with current interventions, 96.5% of surveyed districts will have TF prevalence among children aged 1-9 years <5% by 2030 (95% CI: 86.6%-100.0%). Districts with TF prevalence < 20% appear unlikely to be transmission-hotspots. However, a district having TF prevalence of over 28% in 2016-2019 corresponds to at least 50% probability of being a transmission-hotspot. CONCLUSIONS: Sustainable control of trachoma appears achievable. However there are transmission-hotspots that are not responding to annual mass drug administration of azithromycin and require enhanced treatment in order to reach local control.

Targeted Antibiotics for Trachoma: A Cluster-Randomized Trial.

BACKGROUND: Current guidelines recommend community-wide mass azithromycin for trachoma, but a targeted treatment strategy could reduce the volume of antibiotics required. METHODS: In total, 48 Ethiopian communities were randomized to mass, targeted, or delayed azithromycin distributions. In the targeted arm, only children aged 6 months to 5 years with evidence of ocular chlamydia received azithromycin, distributed thrice over the following year. The primary outcome was ocular chlamydia at months 12 and 24, comparing the targeted and delayed arms (0-5 year-olds, superiority analysis) and the targeted and mass azithromycin arms (8-12 year-olds, noninferiority analysis, 10% noninferiority margin). RESULTS: At baseline, the mean prevalence of ocular chlamydia in the 3 arms ranged from 7% to 9% among 0-5 year-olds and from 3% to 9% among 8-12 year-olds. Averaged across months 12-24, the mean prevalence of ocular chlamydia among 0-5 year-olds was 16.7% (95% confidence interval [CI]: 9.0%-24.4%) in the targeted arm and 22.3% (95% CI: 11.1%-33.6%) in the delayed arm (P = .61). The final mean prevalence of ocular chlamydia among 8-12 year-olds was 13.5% (95% CI: 7.9%-19.1%) in the targeted arm and 5.5% (95% CI: 0.3%-10.7%) in the mass treatment arm (adjusted risk difference 8.5 percentage points [pp] higher in the targeted arm, 95% CI: 0.9 pp-16.1 pp higher). CONCLUSIONS: Antibiotic treatments targeted to infected preschool children did not result in significantly less ocular chlamydia infections compared with untreated communities and did not meet noninferiority criteria relative to mass azithromycin distributions. Targeted approaches may require treatment of a broader segment of the population in areas with hyperendemic trachoma.

Conjunctival Scarring, Corneal Pannus, and Herbert's Pits in Adolescent Children in Trachoma-endemic Populations of the Solomon Islands and Vanuatu.

BACKGROUND: In the Solomon Islands and Vanuatu, the sign trachomatous inflammation-follicular (TF) is common, but ocular infection with Chlamydia trachomatis is not. It is therefore debatable whether azithromycin mass drug administration (MDA), the recommended antibiotic treatment strategy for trachoma's elimination as a public health problem, is necessary in this setting. We set out to estimate what proportion of adolescents were at risk of progression of trachomatous scarring. METHODS: A cross-sectional survey was undertaken of all children aged 10-14 years resident in communities identified as high-TF clusters during previous population-based mapping. Graders examined children for clinical evidence of trachomatous scarring, pannus, and Herbert's pits (HPs) or limbal follicles in both eyes. A dried blood spot was collected from each child and tested for antibodies to C. trachomatis. RESULTS: A total of 492 children in 24 villages of the Solomon Islands and Vanuatu were examined. In total, 35/492 (7%) of children had limbal signs (pannus and/or HPs) plus any conjunctival scarring. And 9/492 (2%) had limbal signs and moderate or severe conjunctival scarring; 22% of children were anti-Pgp3 seropositive. CONCLUSIONS: Few adolescents here are at risk of future complications from trachoma, supporting the conclusion that further antibiotic MDA is not currently required for trachoma elimination purposes in these settings.

Trachoma, Anti-Pgp3 Serology, and Ocular Chlamydia trachomatis Infection in Papua New Guinea.

BACKGROUND: In Melanesia, the prevalence of trachomatous inflammation-follicular (TF) suggests that public health-level interventions against active trachoma are needed. However, the prevalence of trachomatous trichiasis is below the threshold for elimination as a public health problem and evidence of conjunctival infection with trachoma's causative organism (Chlamydia trachomatis [CT]) is rare. Here, we examine the prevalence of ocular infection with CT and previous exposure to CT in three evaluation units (EUs) of Papua New Guinea. METHODS: All individuals aged 1-9 years who were examined for clinical signs of trachoma in 3 Global Trachoma Mapping Project EUs were eligible to take part in this study (N = 3181). Conjunctival swabs were collected from 349 children with TF and tested by polymerase chain reaction to assess for ocular CT infection. Dried blood spots were collected from 2572 children and tested for anti-Pgp3 antibodies using a multiplex assay. RESULTS: The proportion of children with TF who had CT infection was low across all 3 EUs (overall 2%). Anti-Pgp3 seroprevalence was 5.2% overall and there was no association between anti-Pgp3 antibody level and presence of TF. In 2 EUs, age-specific seroprevalence did not increase significantly with increasing age in the 1- to 9-year-old population. In the third EU, there was a statistically significant change with age but the overall seroprevalence and peak age-specific seroprevalence was very low. CONCLUSIONS: Based on these results, together with similar findings from the Solomon Islands and Vanuatu, the use of TF to guide antibiotic mass drug administration decisions in Melanesia should be reviewed.

Azithromycin Reduction to Reach Elimination of Trachoma (ARRET): study protocol for a cluster randomized trial of stopping mass azithromycin distribution for trachoma.

BACKGROUND: The World Health Organization (WHO) recommends annual mass azithromycin distribution until districts drop below 5% prevalence of trachomatous inflammation-follicular (TF). Districts with very low TF prevalence may have little or no transmission of the ocular strains of Chlamydia trachomatis that cause trachoma, and additional rounds of mass azithromycin distribution may not be useful. Here, we describe the protocol for a randomized controlled trial designed to evaluate whether mass azithromycin distribution can be stopped prior to the current WHO guidelines. METHODS: The Azithromycin Reduction to Reach Elimination of Trachoma (ARRET) study is a 1:1 community randomized non-inferiority trial designed to evaluate whether mass azithromycin distribution can be stopped in districts with baseline prevalence of TF under 20%. Communities in Maradi, Niger are randomized after baseline assessment either to continued annual mass azithromycin distribution or stopping annual azithromycin distribution over a 3-year period. We will compare the prevalence of ocular C. trachomatis (primary outcome), TF and other clinical signs of trachoma, and serologic markers of trachoma after 3 years. We hypothesize that stopping annual azithromycin distribution will be non-inferior to continued annual azithromycin distributions for all markers of trachoma prevalence and transmission. DISCUSSION: The results of this trial are anticipated to provide potentially guideline-changing evidence for when mass azithromycin distributions can be stopped in low TF prevalence areas. TRIAL REGISTRATION NUMBER: This study is registered at clinicaltrials.gov ( NCT04185402 ). Registered December 4, 2019; prospectively registered pre-results.

The population-based prevalence of trachomatous scarring in a trachoma hyperendemic setting: results from 152 impact surveys in Amhara, Ethiopia.

BACKGROUND: Trachomatous scarring (TS) results from repeated infection with the bacterium Chlamydia trachomatis. Pronounced scarring is an underlying cause of trachomatous trichiasis (TT) that can lead to blindness. Since the condition is irreversible, TS in adults has been considered a marker of past exposure to trachoma infection. The aim of this report was to estimate the population-based prevalence of TS within Amhara, Ethiopia, a region with a historically high burden of trachoma. METHODS: District-level multi-stage cluster surveys were conducted in all districts between 2010 and 2015 to monitor the impact of approximately 5 years of trachoma interventions. Approximately 40 households were sampled per cluster and all participants ages ≥ 1 year were graded for the 5 World Health Organization simplified signs. Before each survey round, trachoma graders participated in a 7-day training and reliability exam that included cases of TS. TS prevalence estimates were weighted to account for sampling design and adjusted for age and sex using post-stratification weighting. RESULTS: Across the 152 districts in Amhara, 208,510 individuals ages 1 year and older were examined for the signs of trachoma. Region-wide, the prevalence of TS was 8.2 %, (95 % Confidence Interval [CI]: 7.7-8.6 %), and the prevalence among individuals ages 15 years and older (n = 110,137) was 12.6 % (95 % CI: 12.0-13.3 %). District-level TS prevalence among individuals ages 15 years and older ranged from 0.9 to 36.9 % and was moderately correlated with district prevalence of TT (r = 0.31; P < 0.001). The prevalence of TS increased with age, reaching 22.4 % among those ages 56 to 60 years and 24.2 % among those ages 61 to 65 years. Among children ages 1 to 15 years TS prevalence was 2.2 % (95 % CI: 1.8-2.8 %), increased with age (P < 0.001), and 5 % of individuals with TS also had trachomatous inflammation-intense (TI). CONCLUSIONS: These results suggest that Amhara has had a long history of trachoma exposure and that a large population remains at risk for developing TT. It is promising, however, that children, many born after interventions began, have low levels of TS compared to other known trachoma-hyperendemic areas.