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The purpose of this study was to investigate the correlation between bacterial load of Chlamydia trachomatis as measured from quantitative polymerase chain reaction (qPCR) and the relative clinical severity of trachomatous inflammation. Individuals with trachoma from rural communities in Ethiopia had photographs taken as well as swabs obtained of the upper tarsal conjunctivas. Conjunctival swabs were processed with PCR assay, which provided quantitative results of ocular chlamydial load. A series of 125 conjunctival photographs were ranked from least to most severe according to clinical severity for follicular and papillary conjunctivitis. Higher intensity rankings of trachomatous inflammation were associated with higher chlamydial load for both follicular inflammation (Spearman's ρ = 0.43; P <0.001) and papillary inflammation (Spearman's ρ = 0.50; P <0.001). Rankings of trachomatous inflammation may be a clinically meaningful indicator of trachoma.

Objectives: A 6-week course of tetracycline eye ointment is an alternative to single -dose oral azithromycin in annual mass drug administration for trachoma control. Compliance with the recommended tetracycline eye ointment regimen has not been well characterised when administered as part of a trachoma control program., Methods: A routine mass drug administration for trachoma was carried out in 40 communities in the Amhara region of Ethiopia. Two tubes of tetracycline eye ointment, to be administered twice daily for 6 weeks, was offered to all children under 6 months of age, to pregnant women who declined to take azithromycin, and to all individuals with a macrolide allergy. Seven weeks following the mass drug administration, a treatment compliance survey was performed for all community members documented to have received tetracycline eye ointment during the mass drug administration., Results: Of the 491 individuals documented as having received tetracycline eye ointment from the treatment records, 367 completed the survey, of which 214 recalled being offered tetracycline eye ointment. A total of 105 (49%) respondents reported taking ≥1 daily dose of tetracycline eye ointment on most days of the week for at least the first week. Only 20 (9%) respondents reported taking at least 1 tetracycline eye ointment dose per week for 6 weeks. The most common reasons for low compliance included 'saving it for a future infection' and 'stopped because I (or my child) seemed healthy'. The odds of low compliance were greater for those who reported not having adequate counselling (e.g., odds ratio [OR] 5.3, 95% CI 2.5-28.9 when low compliance was defined as not taking a tetracycline eye ointment dose for most days of at least the first week)., Conclusions: Compliance with tetracycline eye ointment was low when administered by a trachoma program during a routine mass drug administration, especially for those reporting inadequate counselling. Further research with a larger sample size and varied settings is warranted to better understand and improve compliance., (© 2024 The Authors Tropical Medicine & International Health published by John Wiley & Sons Ltd.)

Trachoma is targeted for global elimination as a public health problem by 2030. Measurement of IgG antibodies in children is being considered for surveillance and programmatic decision-making. There are currently no guidelines for applications of serology, which represents a generalizable problem in seroepidemiology and disease elimination. We collated Chlamydia trachomatis Pgp3 and CT694 IgG measurements (63,911 children ages 1-9 years) from 48 serosurveys, including surveys across Africa, Latin America, and the Pacific Islands to estimate population-level seroconversion rates (SCR) along a gradient of trachoma endemicity. We propose a novel, generalizable approach to estimate the probability that population C. trachomatis transmission is below levels requiring ongoing programmatic action, or conversely is above levels that indicate ongoing interventions are needed. We provide possible thresholds for SCR at a specified level of certainty and illustrate how the approach could be used to inform trachoma program decision-making using serology., Competing Interests: KR, PJH, and PME are employees of, and EMHE receives salary support from, the International Trachoma Initiative, which receives an operating budget and research funds from Pfizer Inc., the manufacturers of Zithromax® (azithromycin). The other authors declare no competing interests. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated.

Purpose: Trachoma surveys are used to estimate the prevalence of trachomatous inflammation-follicular (TF) to guide mass antibiotic distribution. These surveys currently rely on human graders, introducing a significant resource burden and potential for human error. This study describes the development and evaluation of machine learning models intended to reduce cost and improve reliability of these surveys., Methods: Fifty-six thousand seven hundred twenty-five everted eyelid photographs were obtained from 11,358 children of age 0 to 9 years in a single trachoma-endemic region of Ethiopia over a 3-year period. Expert graders reviewed all images from each examination to determine the estimated number of tarsal conjunctival follicles and the degree of trachomatous inflammation-intense. The median estimate of the 3 grader groups was used as the ground truth to train a MobileNetV3 large deep convolutional neural network to detect cases with TF., Results: The classification model predicted a TF prevalence of 32%, which was not significantly different from the human consensus estimate (30%; 95% confidence interval of difference, -2 to +4%). The model had an area under the receiver operating characteristic curve of 0.943, F1 score of 0.923, 88% accuracy, 83% sensitivity, and 91% specificity. The area under the receiver operating characteristic curve increased to 0.995 when interpreting nonborderline cases of TF., Conclusions: Deep convolutional neural network models performed well at classifying TF and detecting the number of follicles evident in conjunctival photographs. Implementation of similar models may enable accurate, efficient, large-scale trachoma screening. Further validation in diverse populations with varying TF prevalence is needed before implementation at scale., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Monitoring trachoma transmission with antibody data requires characterization of decay in IgG to Chlamydia trachomatis antigens. In a 3-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 per 100 person-years (95% confidence interval, 1.6-3.5). Clinical Trials Registration NCT02754583., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Promotion of facial cleanliness is recommended for the elimination of blinding trachoma, largely because of observational studies that have found an association between various measures of facial uncleanliness and trachoma. However, when a field grader assesses both facial cleanliness and trachoma, associations may be biased. Assessment of photographs of the face and conjunctiva by masked graders may provide a less biased estimate of the relationship between facial cleanliness and trachoma., Methods: Face photographs, conjunctival photographs, and conjunctival swabs were obtained on a random sample of 0-9-year-old children from each of 40 communities in Amhara region, Ethiopia. Face photographs were assessed for the presence of seven measures of an unclean face (i.e., wet nasal discharge, dry nasal discharge, wet ocular discharge, dry ocular discharge, food, dust/dirt, and flies) by three independent masked photo-graders. Conjunctival photographs were similarly graded in a masked fashion for signs of clinically active trachoma. Conjunctival swabs were processed for Chlamydia trachomatis DNA., Results: Of 2073 children with complete data, 808 (39%) had evidence of clinically active trachoma, 150 (7%) had evidence of ocular chlamydia infection, and 2524 (91%) had at least one measure of an unclean face. Dry ocular discharge had the strongest association with clinically active trachoma (age- and sex-adjusted prevalence ratio [PR] 1.4, 95% CI 1.2-1.6) and ocular chlamydia infection (PR 1.9, 95%CI 1.3-2.9), although significant associations were observed between each of the measures of facial uncleanliness and trachoma., Conclusions: Masked assessment of face and conjunctival photographs confirmed prior observational studies that have noted associations between various measures of facial uncleanliness and trachoma. The causal relationship between facial uncleanliness and trachoma is unclear since many features used to measure facial cleanliness (e.g., ocular discharge, nasal discharge, and flies) could be consequences of antecedent ocular chlamydia infection., Trial Registration: NCT02754583, clinicaltrials.gov., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Caleon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: CONFLICT OF INTEREST The authors report no conflicts of interest. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the National Institutes of Health or the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the Public Health Service or by the U.S. Department of Health and Human Services.

Trachoma, caused by ocular Chlamydia trachomatis infection, is targeted for global elimination as a public health problem by 2030. To provide evidence for use of antibodies to monitor C. trachomatis transmission, we collated IgG responses to Pgp3 antigen, PCR positivity, and clinical observations from 19,811 children aged 1-9 years in 14 populations. We demonstrate that age-seroprevalence curves consistently shift along a gradient of transmission intensity: rising steeply in populations with high levels of infection and active trachoma and becoming flat in populations near elimination. Seroprevalence (range: 0-54%) and seroconversion rates (range: 0-15 per 100 person-years) correlate with PCR prevalence (r: 0.87, 95% CI: 0.57, 0.97). A seroprevalence threshold of 13.5% (seroconversion rate 2.75 per 100 person-years) identifies clusters with any PCR-identified infection at high sensitivity ( >90%) and moderate specificity (69-75%). Antibody responses in young children provide a robust, generalizable approach to monitor population progress toward and beyond trachoma elimination., (© 2023. The Author(s).)

Background/objectives: Tablet-based perimetry could be used to test for glaucomatous visual field defects in settings without easy access to perimeters, although few studies have assessed diagnostic accuracy of tablet-based tests. The goal of this study was to determine the diagnostic accuracy of iPad perimetry using the visualFields Easy application., Subjects/methods: This was a prospective, cross-sectional study of patients undergoing their first Humphrey Field Analyser (HFA) visual field test at a glaucoma clinic in India. Participants underwent 24-2 SITA Standard HFA testing and iPad-based perimetry with the visualFields Easy application. Reference standards for both visual field loss and suspected glaucoma were determined by ophthalmologist review of HFA results and optic disc photographs. Receiver operating characteristic curves were constructed to assess diagnostic accuracy at various test thresholds., Results: 203 eyes from 115 participants were included, with 82 eyes classified as moderate or worse glaucoma. iPad perimetry had an area under the receiver operating characteristic (AUROC) curve of 0.64 (95% CI 0.57 to 0.71) for detection of any visual field defect relative to HFA and an AUROC of 0.68 (0.59 to 0.76) for detection of moderate or worse glaucoma relative to ophthalmologist examination. At a set specificity of 90%, the sensitivity of iPad perimetry for detection of moderate or worse glaucoma was 35% (22-48%)., Conclusions: iPad perimetry using the visualFields Easy application had inadequate diagnostic accuracy to be used as a screening tool for glaucoma in this South Indian population., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Trachoma, caused by ocular Chlamydia trachomatis infection, is targeted for global elimination as a public health problem by 2030. To provide evidence for use of antibodies to monitor C. trachomatis transmission, we collated IgG responses to Pgp3 antigen, PCR positivity, and clinical observations from 19,811 children aged 1- 9 years in 14 populations. We demonstrate that age-seroprevalence curves consistently shift along a gradient of transmission intensity: rising steeply in populations with high levels of infection and active trachoma and becoming flat in populations near elimination. Seroprevalence (range: 0-54%) and seroconversion rates (range: 0-15 per 100 person-years) correlate with PCR prevalence (r: 0.87, 95% CI: 0.57, 0.97). A seroprevalence threshold of 13.5% (seroconversion rate 2.75 per 100 person-years) identifies clusters with any PCR-identified infection at high sensitivity (>90%) and moderate specificity (69-75%). Antibody responses in young children provide a robust, generalizable approach to monitor population progress toward and beyond trachoma elimination.

Purpose: Portable perimetric testing could be useful for community-based glaucoma screening programs. Frequency-doubling technology (FDT) and the Moorfields motion displacement test (MDT) are portable perimeters that have shown promise as potential screening tools for glaucoma. This study's goal was to determine the diagnostic accuracy of FDT and MDT for visual field defects and glaucoma., Design: Prospective, cross-sectional, diagnostic accuracy study., Participants: A consecutive series of patients aged ≥ 50 years who presented to a glaucoma clinic in South India and had never undergone Humphrey field analyzer (HFA) visual field testing in the past., Methods: Participants underwent 24-2 Swedish Interactive Thresholding Algorithm (SITA) Standard HFA perimetry, FDT perimetry, MDT perimetry, and iPad perimetry using visualFields Easy in random order. Ophthalmologist grades of HFA and optic nerve head photographs were used as reference standards for glaucoma and field defect presence. Receiver operating characteristic curves were constructed to assess the diagnostic accuracy of various parameters for each test., Main Outcome Measures: Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC)., Results: Overall, 292 eyes from 173 participants were included, with 112 eyes classified as moderate or worse glaucoma. For moderate or worse glaucoma detection, the best parameter on FDT was mean deviation (MD) (AUROC, 0.84; 95% confidence interval [CI], 0.79-0.89) and the best parameter on MDT was global probability of true damage (GPTD) (AUROC, 0.87; 95% CI, 0.82-0.91). When specificity was set to 90%, the sensitivity for detection of moderate or worse glaucoma was 55% (95% CI, 39%-68%) for FDT MD and 62% (95% CI 52%-71%) for MDT GPTD., Conclusions: Frequency-doubling technology and MDT perimetry had fair diagnostic accuracy for glaucoma detection when administered to naïve test takers in this South Indian population. Although not appropriate for use as a sole glaucoma screening test, these perimetric tests may be useful as ancillary tests., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: As countries reach the trachoma elimination threshold and cases of trachomatous inflammation follicular (TF) become rare, it becomes difficult to train survey graders to recognize clinical signs. We assess the use of photography as a grading tool, the efficiency of an in-country grading center and the comparability of field and photographic grading., Methods: During January-February 2017 surveys in Amhara, Ethiopia, field graders assessed TF, trachomatous inflammation intense (TI) and trachomatous scarring (TS). Photographs were taken from each conjunctiva and later graded at the Gondar Grading Center (GGC) at the University of Gondar in Amhara. Two trained ophthalmology residents graded each set of photographs and a third grader provided an adjudicating grade when needed., Results: A total of 4953 photographs of 2477 conjunctivae from 1241 participants in 10 communities were graded over 5 d at the GGC. Six examined participants were not photographed. Agreement between field and photographic grades were for TF: percent agreement (PA) 96.7%, κ=0.70 (95% confidence interval [CI] 0.64 to 0.77; for TI: PA 94.7%, κ=0.32 (95% CI 0.20 to 0.43); and for TS: PA 83.5%, κ=0.22 (95% CI 0.15 to 0.29)., Conclusions: Conjunctival photography may be a solution for programs near the elimination threshold where there are few available community cases for training field graders., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Purpose: To determine the diagnostic accuracy of potential screening tests for moderate to advanced glaucoma., Design: Prospective diagnostic test accuracy study., Participants: The study enrolled a consecutive series of patients aged ≥50 years who presented to a glaucoma clinic in South India without ever having received automated visual field testing., Methods: All participants underwent 8 index tests: OCT of the peripapillary retinal nerve fiber layer, optic disc photography, Moorfield's Motion Displacement Test (MDT), frequency doubling technique perimetry, noncontact tonometry, pneumatonometry, presenting visual acuity, and best-corrected visual acuity. Participants also underwent stereoscopic photographs and Humphrey visual fields, which were used by 2 ophthalmologists to arrive at the reference standard diagnosis of moderate to advanced glaucoma., Main Outcome Measures: Sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio., Results: A total of 217 people were enrolled; 321 eyes from 180 participants had all tests performed. Of these, 127 eyes (40%) were classified as having moderate to advanced glaucoma. Among the 8 tests, OCT best optimized sensitivity (84%, 95% confidence interval [CI], 76-90) and specificity (75%, 95% CI, 68-81). Moorfield's Motion Displacement Test was the best perimetric test, with a sensitivity of 91% (95% CI, 85-96) and specificity of 53% (95% CI, 44-61). Pressure and vision tests were not sensitive (e.g., sensitivity of 16%, 95% CI, 9-23 for noncontact tonometry and 23%, 95% CI, 15-31 for best-corrected visual acuity). Moorfield's Motion Displacement Test identified 16 of 127 eyes (13%) with glaucoma that were not captured by OCT, but also had false-positive results in 65 of 194 eyes (34%) without glaucoma that OCT correctly classified as negative., Conclusions: OCT had moderate sensitivity and fair specificity for diagnosing moderate to advanced glaucoma and should be prioritized during an initial assessment for glaucoma., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Trachoma is an infectious disease characterized by repeated exposures to Chlamydia trachomatis (Ct) that may ultimately lead to blindness. Efficient identification of communities with high infection burden could help target more intensive control efforts. We hypothesized that IgG seroprevalence in combination with geospatial layers, machine learning, and model-based geostatistics would be able to accurately predict future community-level ocular Ct infections detected by PCR. We used measurements from 40 communities in the hyperendemic Amhara region of Ethiopia to assess this hypothesis. Median Ct infection prevalence among children 0-5 years old increased from 6% at enrollment, in the context of recent mass drug administration (MDA), to 29% by month 36, following three years without MDA. At baseline, correlation between seroprevalence and Ct infection was stronger among children 0-5 years old (ρ = 0.77) than children 6-9 years old (ρ = 0.48), and stronger than the correlation between active trachoma and Ct infection (0-5y ρ = 0.56; 6-9y ρ = 0.40). Seroprevalence was the strongest concurrent predictor of infection prevalence at month 36 among children 0-5 years old (cross-validated R2 = 0.75, 95% CI: 0.58-0.85), though predictive performance declined substantially with increasing temporal lag between predictor and outcome measurements. Geospatial variables, a spatial Gaussian process, and stacked ensemble machine learning did not meaningfully improve predictions. Serological markers among children 0-5 years old may be an objective tool for identifying communities with high levels of ocular Ct infections, but accurate, future prediction in the context of changing transmission remains an open challenge., Competing Interests: The authors have declared that no competing interests exist.

Background: WHO promotes the SAFE strategy for the elimination of trachoma as a public health programme, which promotes surgery for trichiasis (ie, the S component), antibiotics to clear the ocular strains of chlamydia that cause trachoma (the A component), facial cleanliness to prevent transmission of secretions (the F component), and environmental improvements to provide water for washing and sanitation facilities (the E component). However, little evidence is available from randomised trials to support the efficacy of interventions targeting the F and E components of the strategy. We aimed to determine whether an integrated water, sanitation, and hygiene (WASH) intervention prevents the transmission of trachoma., Methods: The WASH Upgrades for Health in Amhara (WUHA) was a two-arm, parallel-group, cluster-randomised trial in 40 rural communities in Wag Hemra Zone (Amhara Region, Ethiopia) that had been treated with 7 years of annual mass azithromycin distributions. The randomisation unit was the school catchment area. All households within a 1·5 km radius of a potential water point within the catchment area (as determined by the investigators) were eligible for inclusion. Clusters were randomly assigned (at a 1:1 ratio) to receive a WASH intervention either immediately (intervention) or delayed until the conclusion of the trial (control), in the absence of concurrent antibiotic distributions. Given the nature of the intervention, participants and field workers could not be masked, but laboratory personnel were masked to treatment allocation. The WASH intervention consisted of both hygiene infrastructure improvements (namely, construction of a community water point) and hygiene promotion by government, school, and community leaders, which were implemented at the household, school, and community levels. Hygiene promotion focused on two simple messages: to use soap and water to wash your or your child's face, and to always use a latrine for defecation. The primary outcome was the cluster-level prevalence of ocular chlamydia, measured annually using conjunctival swabs in a random sample of children aged 0-5 years from each cluster at 12, 24, and 36 month timepoints. Analyses were done in an intention-to-treat manner. This trial is ongoing and is registered at ClinicalTrials.gov, NCT02754583., Findings: Between Nov 9, 2015, and March 5, 2019, 40 of 44 clusters assessed for eligibility were enrolled and randomly allocated to the trial groups (20 clusters each, with 7636 people from 1751 households in the intervention group and 9821 people from 2211 households in the control group at baseline). At baseline, ocular chlamydia prevalence among children aged 0-5 years was 11% (95% CI 6 to 16) in the WASH group and 11% (5 to 18) in the control group. At month 36, ocular chlamydia prevalence had increased in both groups, to 32% (24 to 41) in the WASH group and 31% (21 to 41) in the control group (risk difference across three annual monitoring visits, after adjustment for prevalence at baseline: 3·7 percentage points; 95% CI -4·9 to 12·4; p=0·40). No adverse events were reported in either group., Interpretation: An integrated WASH intervention addressing the F and E components of the SAFE strategy did not prevent an increase in prevalence of ocular chlamydia following cessation of antibiotics in an area with hyperendemic trachoma. The impact of WASH in the presence of annual mass azithromycin distributions is currently being studied in a follow-up trial of the 40 study clusters. Continued antibiotic distributions will probably be important in areas with persistent trachoma., Funding: National Institutes of Health-National Eye Institute., Translation: For the Amharic translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests BA reports financial support to attend global health meetings from the Bill & Melinda Gates Foundation. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine whether a water, sanitation and hygiene intervention could change hygiene behaviours thought to be important for trachoma control., Methods: We conducted a cluster-randomized trial in rural Ethiopia from 9 November 2015 to 5 March 2019. We randomized 20 clusters to an intervention consisting of water and sanitation infrastructure and hygiene promotion and 20 clusters to no intervention. All intervention clusters received a primary-school hygiene curriculum, community water point, household wash station, household soap and home visits from hygiene promotion workers. We assessed intervention fidelity through annual household surveys., Findings: Over the 3 years, more wash stations, soap and latrines were seen at households in the intervention clusters than the control clusters: risk difference 47 percentage points (95% confidence interval, CI: 41-53) for wash stations, 18 percentage points (95% CI: 12-24) for soap and 12 percentage points (95% CI: 5-19) for latrines. A greater proportion of people in intervention clusters reported washing their faces with soap (e.g. risk difference 21 percentage points; 95% CI: 15-27 for 0-5 year-old children) and using a latrine (e.g. risk difference 9 percentage points; 95% CI: 2-15 for 6-9 year-old children). Differences between the intervention and control arms were not statistically significant for many indicators until the programme had been implemented for at least a year; they did not decline during later study visits., Conclusion: The community- and school-based intervention was associated with improved hygiene access and behaviours, although changes in behaviour were slow and required several years of the intervention., ((c) 2021 The authors; licensee World Health Organization.)

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., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose : Previous studies have used subjective assessments to implicate darker skin color as a risk factor for glaucoma. This study used objective measurements to determine whether skin melanin is a risk factor for glaucoma. Methods: In a case-control study conducted at a tertiary eye hospital in Nepal, patients aged 40 years or older from the glaucoma clinic were enrolled as cases and age-matched patients without glaucoma from other clinics at the eye hospital were enrolled as controls. A colorimeter was used to capture melanin measurements in triplicate from the inner arm and forehead of each participant. The exposure variable of interest was the median skin melanin value, in arbitrary units. The outcome of interest was the presence of glaucoma. Results: 100 glaucoma cases and 100 matched controls were enrolled. Agreement between the triplicate melanin measurements was high, with an intra-class correlation of 0.99 (95% CI, 0.99-0.99) for inner arm measurements and 0.97 (95% CI 0.96-0.98) for forehead measurements. Mean inner arm melanin values were 604 units (standard deviation [SD] 177) in cases and 602 units (SD 179) in controls; forehead values were 650 (SD 146) in cases and 652 (SD 152) in controls. After adjusting for sex and country of residence, skin melanin was not associated with the presence of glaucoma (odds ratio 1.04, 95%CI 0.78-1.38 for inner arm values and 0.97, 95%CI 0.70-1.35 for forehead values). Conclusion: This study failed to find a significant association between skin pigmentation and glaucoma.

Multiplex bead assays (MBAs) for serologic testing have become more prevalent in public health surveys, but few studies have assessed their test performance. As part of a trachoma study conducted in a rural part of Ethiopia in 2016, dried blood spots (DBS) were collected from a random sample of 393 children aged 0 to 9 years, with at least two separate 6-mm DBS collected on a filter card. Samples eluted from DBS were processed using an MBA on the Luminex platform for antibodies against 13 antigens of nine infectious organisms: Chlamydia trachomatis, Vibrio cholera, enterotoxigenic Escherichia coli, Cryptosporidium parvum, Entamoeba histolytica, Camplyobacter jejuni, Salmonella typhimurium Group B, Salmonella enteritidis Group D, and Giardia lamblia. Two separate DBS from each child were processed. The first DBS was run a single time, with the MBA set to read 100 beads per well. The second DBS was run twice, first at 100 beads per well and then at 50 beads per well. Results were expressed as the median fluorescence intensity minus background (MFI-BG), and classified as seropositive or seronegative according to external standards. Agreement between the three runs was high, with intraclass correlation coefficients of > 0.85 for the two Salmonella antibody responses and > 0.95 for the other 11 antibody responses. Agreement was also high for the dichotomous seropositivity indicators, with Cohen's kappa statistics exceeding 0.87 for each antibody assay. These results suggest that serologic testing on the Luminex platform had strong test performance characteristics for analyzing antibodies using DBS.

Purpose: Autorefractors allow non-specialists to quickly assess refractive error, and thus could be a useful component of large-scale vision screening programs. In order to better characterize the role of autorefraction for public health outreach programs in resource-limited settings, the diagnostic accuracy of two autorefractors was assessed relative to subjective refraction in an adult Indian population., Methods: An optometrist refracted a series of patients aged ≥50 years at an eye clinic in Bangalore, India using the Nidek ARK-900 autorefractor first, followed by the 3nethra Royal autorefractor, and then subjective refraction. The diagnostic accuracy of each autorefractor for myopia, hyperopia, and astigmatism was assessed using subjective refraction as the reference standard, and measures of agreement between refractions were calculated., Results: A total of 197 eyes in 104 individuals (mean age 63 ± 8 years, 52% female) were evaluated. Both autorefractors produced spherical equivalent estimates that were on average more hyperopic than subjective refraction, with a measurement bias of +0.16 D (95%CI +0.09 to +0.23D) for Nidek and +0.42 D (95%CI +0.28 to +0.54D) for 3nethra. When comparing pairs of measurements from autorefraction and subjective refraction, the limits of agreement were approximately ±1D for the Nidek autorefractor and ±1.75D for the 3Nethra autorefractor. The sensitivity and specificity of detecting ≥1 diopter of myopia were 94.6% (95%CI 86.8-100%) and 92.5% (95%CI 88.9-97.5%) for the Nidek, and 89.2% (95%CI 66.7-97.4) and 77.5% (95%CI 71.2-99.4%) for the 3Nethra. The accuracy of each autorefractor increased at greater levels of refractive error., Conclusions: The sensitivity and specificity of the Nidek autorefractor for diagnosing refractive error among adults ≥50 years in an urban Indian clinic was sufficient for screening for visually significant refractive errors, although the relatively wide limits of agreement suggest that subjective refinement of the eyeglasses prescription would still be necessary., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Facial hygiene promotion and environmental improvements are central components of the global trachoma elimination strategy despite a lack of experimental evidence supporting the effectiveness of water, sanitation and hygiene (WASH) measures for reducing trachoma transmission. The objective of the WUHA (WASH Upgrades for Health in Amhara) trial is to evaluate if a comprehensive water improvement and hygiene education programme reduces the prevalence of ocular chlamydia infection in rural Africa., Methods and Analysis: Forty study clusters, each of which had received at least annual mass azithromycin distributions for the 7 years prior to the start of the study, are randomised in a 1:1 ratio to the WASH intervention arm or a delayed WASH arm. The WASH package includes a community water point, community-based hygiene promotion workers, household wash stations, household WASH education books, household soap distribution and a primary school hygiene curriculum. Educational activities emphasise face-washing and latrine use. Mass antibiotic distributions are not provided during the first 3 years but are provided annually over the final 4 years of the trial. Annual monitoring visits are conducted in each community. The primary outcome is PCR evidence of ocular chlamydia infection among children aged 0-5 years, measured in a separate random sample of children annually over 7 years. A secondary outcome is improvement of the clinical signs of trachoma between the baseline and final study visits as assessed by conjunctival photography. Laboratory workers and photo-graders are masked to treatment allocation., Ethics and Dissemination: Study protocols have been approved by human subjects review boards at the University of California, San Francisco, Emory University, the Ethiopian Food and Drug Authority, and the Ethiopian Ministry of Innovation and Technology. A data safety and monitoring committee oversees the trial. Results will be disseminated through peer-reviewed publications and presentations., Trial Registration Number: (http://www.clinicaltrials.gov): NCT02754583; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The WHO recommends improving access to water as part of a comprehensive strategy for elimination of trachoma as a public health problem; however, this recommendation is not based on evidence from randomized trials. In a region of Ethiopia with hyperendemic trachoma, seven communities were randomized to a hand-dug well (HDW) and seven communities to no intervention to determine the impact of HDWs on the community prevalence of ocular chlamydia infection (primary prespecified outcome). All communities continued to receive government hygiene and sanitation services and outreach. Participants were not masked, given the nature of the intervention, but laboratory personnel were masked to treatment allocation. Hand-dug wells were successfully built in six of the seven communities; five of these wells were still functional at the conclusion of the trial. At the end of the trial, an average of 74% of households reported traveling < 30 minutes to collect water in the HDW arm, compared with 45% in the control arm, and the daily volume of water used for hygiene was similar (e.g., mean of 0.7 L per person in each arm). The pseudo-median prevalence of ocular chlamydia among 0- to 5-year old children at the 24-month visit was 23% in the HDW group and 13% in the control group (P > 0.99). This small cluster-randomized trial provided no evidence to suggest that simply constructing HDWs, in the absence of other hygiene promotion activities, is effective for reducing transmission of ocular chlamydia.

Pit latrines are promoted in resource-limited settings, but unpleasant odours may deter their use. In this study, latrines in rural Ethiopia were randomized to the addition of cooking ash, the addition of boiling water or neither. Study staff ranked odour on a 6-point scale before and approximately 24 h after intervention. Following intervention, odour grades were on average 0.2 points lower (95% confidence interval [CI] 0.7 lower to 0.3 higher) in ash-treated latrines and 0.4 points lower (95% CI 0.9 lower to 0.1 higher) in boiled water-treated latrines, although the difference between the three groups was not statistically significant (p = 0.21). Larger studies might detect a smaller difference., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

The transmission of trachoma, caused by repeat infections with Chlamydia trachomatis, and many enteropathogens are linked to water quantity. We hypothesized that children living further from a water source would have higher exposure to C. trachomatis and enteric pathogens as determined by antibody responses. We used a multiplex bead assay to measure IgG antibody responses to C. trachomatis, Giardia intestinalis, Cryptosporidium parvum, Entamoeba histolytica, Salmonella enterica, Campylobacter jejuni, enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae in eluted dried blood spots collected from 2267 children ages 0-9 years in 40 communities in rural Ethiopia in 2016. Linear distance from the child's house to the nearest water source was calculated. We derived seroprevalence cutoffs using external negative control populations, if available, or by fitting finite mixture models. We used targeted maximum likelihood estimation to estimate differences in seroprevalence according to distance to the nearest water source. Seroprevalence among 1-9-year-olds was 43% for C. trachomatis, 28% for S. enterica, 70% for E. histolytica, 54% for G. intestinalis, 96% for C. jejuni, 76% for ETEC and 94% for C. parvum. Seroprevalence increased with age for all pathogens. Median distance to the nearest water source was 473 meters (IQR 268, 719). Children living furthest from a water source had a 12% (95% CI: 2.6, 21.6) higher seroprevalence of S. enterica and a 12.7% (95% CI: 2.9, 22.6) higher seroprevalence of G. intestinalis compared to children living nearest. Seroprevalence for C. trachomatis and enteropathogens was high, with marked increases for most enteropathogens in the first two years of life. Children living further from a water source had higher seroprevalence of S. enterica and G. intestinalis indicating that improving access to water in the Ethiopia's Amhara region may reduce exposure to these enteropathogens in young children., Competing Interests: The authors have declared that no competing interests exist.