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Mass oral azithromycin distributions have dramatically reduced the prevalence of the ocular strains of chlamydia that cause trachoma. Assessing efficacy of the antibiotic in an individual is important in planning trachoma elimination. However, the efficacy

Trachoma programs have dramatically reduced the prevalence of the ocular chlamydia that cause the disease. Some have hypothesized that immunity to the infection may be reduced because of program success in reducing the incidence of infection, and transmiss

Background: Control programs for trachoma use mass antibiotic distributions to treat ocular Chlamydia trachomatis in an effort to eliminate this disease worldwide. To determine whether children infected with ocular Chlamydia are more likely to present late

Background:Trachoma, caused by ocular Chlamydia trachomatis infection, is the leading infectious cause of blindess, but its prevalence is now falling in many countries. As the prevalence falls, an increasing proportion of individuals with clinical signs of

Antimicrobials are used primarily to treat infectious disease, but they have other effects. Here, we assess anthropometry measurements in children 6-60 months in 24 communities randomized to one or two mass azithromycin distributions over a 1-year period i

Background:The World Health Organization recommends at least 3 annual antibiotic mass drug administrations (MDA) where the prevalence of trachoma is >10% in children ages 1-9 years, with coverage at least at 80%. However, the additional value of higher cov

Summary Objective: To determine the impact after 2 years of a water and health education (W/HE) programme on ocular Chlamydia trachomatis infection and trachoma.Methods: We randomized 12 trachoma-endemic communities in Maradi, Niger 1:1 to W/HE intervention and control arms and collected data on 10 of the 12 villages. In the intervention villages, at least one clean water well was constructed, and a 3 month, modest health education programme was provided immediately prior to the 2 year survey. We censused all households, and 557 children ages 1-5 years were randomly selected as sentinel children and examined at baseline and at one and 2 years from baseline. Trachoma was clinically assessed and a swab taken and analyzed for C. trachomatis. Tetracycline eye ointment was provided to all children in either arm during the surveys who had signs of trachoma.Results: Infection with C. trachomatis declined slightly, and not significantly, in the children in the control villages over the 2 years, from 15% to 11%. The decline in infection was more pronounced, and significant, in the children in the intervention villages, from 26% to 15%. However, the change in infection rates in the intervention villages was not significantly different from the change in infection rates in the control villages (P = 0.39, and 0.11 for change from baseline to 1 year and 2 year, respectively). There was also no difference in the change in overall trachoma rates between the two arms.Conclusion: These data suggest that the provision of water plus a modest health education programme did not result in a significant difference in trachoma or ocular C. trachomatis infection in endemic communities in Niger. A more substantial health education intervention is likely necessary to produce change. [ABSTRACT FROM AUTHOR]

Objectives: The prevalence rate of diabetes is probably higher in Hispanics than in Caucasians, although there is controversy about differences in the risk of diabetic retinopathy. The purpose of the study is to determine the prevalence rates of diabetes and diabetic retinopathy in a population-based study of Hispanics aged > or = 40 years.Research Design and Methods: Proyecto VER is a random sample of Hispanic populations aged > or = 40 years in Arizona. A total of 4,774 individuals (71.6% of the eligible sample) completed the examinations. Diabetes was defined as self-report of a physician diagnosis or HbA(1c) value of > or = 7.0%. Diabetic retinopathy was assessed on stereo fundus photographs of fields 1, 2, and 4.Results: The prevalence rate of diabetes in the Hispanic community (individuals > or = 40 years of age) was 22%. The prevalence rate of diabetic retinopathy (DR) was 48%; 32% had moderate to severe nonproliferative and proliferative retinopathy. DR increased with increasing duration of diabetes and increasing level of HbA(1c). The prevalence rate of DR-like changes in the sample of individuals without diabetic retinopathy was 15% and was not associated with hypertension, systolic blood pressure, or diastolic blood pressure.Conclusions: The prevalence rate of diabetes in this population of Hispanics is high, almost twice that of Caucasians. The prevalence rate of DR is high but similar to reports in a Caucasian population. The prevalence rate of 9% moderate to severe retinopathy in the newly diagnosed group suggests that efforts to improve detection and treatment of diabetes in Hispanics may be warranted. [ABSTRACT FROM AUTHOR]

One criterion for validation of trachoma elimination is the management of Trachomatous Trichiasis (TT) after Trachoma inflammation-follicular (TF) is eliminated in children ages 1-9 years at district level. No data exist on how long countries must have dedicated TT programs, as the timeline for progression to TT from trachomatous scarring is unknown. We used eight years of longitudinal data in women in Kongwa Tanzania to model progression from no scarring (S0) through grades of scarring severity (S1-S4) to TT. Markov models were used, with age, community prevalence of TF (CPTF), and household characteristics as co-variates. Adjusted for covariates, the incidence of S1 was estimated at 4∙7% per year, and the risk increased by 26% if the CPTF was between 5-10% and by 48% if greater than 10%. The transition from S4 to TT was estimated at 2∙6% per year. Districts, even after elimination of TF, may have some communities with TF ≥ 5% and increased risk of incident scarring. Once scarring progresses to S2, further progression is not dependent on CPTF. These data suggest that, depending on the district level of scarring and degree of heterogeneity in CPTF at the time of elimination, incident TT will still be an issue for decades., (© 2024. The Author(s).)

Trachoma is the world-leading infectious cause of preventable blindness and is caused by the bacteria Chlamydia trachomatis . In developing countries, diagnosis is usually based on clinical evaluation. Serological-based tests are cheaper than molecular-based ones, but the latter are more sensitive and specific. The present study developed a new duplex qPCR which concomitantly detects the C. trachomatis cryptic plasmid and the human 18S rRNA gene, with an LOD95% for C. trachomatis DNA of 13.04 genome equivalents per reaction. The new qPCR was tested using 50 samples from an endemic area and 12 from a non-endemic area that were previously characterized using direct immunofluorescence assay (DFA) and clinical evaluation. Among the 50 endemic samples, 3 were found to be positive by clinical evaluation (6%), 18 were found to be positive by DFA (36%), and 48 were found to be positive by qPCR (96%). Next, the new duplex qPCR was validated using 50 samples previously characterized by qPCR. Validation was carried out on a benchtop instrument (ABI7500) or on a portable point-of-care instrument (Q3-Plus), showing 95% specificity and 100% sensitivity. The ubiquitous presence of C. trachomatis DNA in samples from the endemic region confirms that constant monitoring is of paramount importance for the effective measurement of the elimination of trachoma. The newly developed duplex qPCR presented in this study, along with its validation in a portable qPCR system, constitutes important tools toward achieving this goal.

Background: The Alliance for the Global Elimination of Trachoma (GET) endorses the full SAFE strategy to eliminate trachoma; Surgery (for trichiasis), Antibiotics (to reduce the community pool of infection, Facial cleanliness, and Environmental improvement (to decrease transmission). There is no accepted measure of facial cleanliness. This study compared two possible metrics for facial cleanliness., Method/findings: Metric one: Clean face was defined as observed absence of ocular and nasal discharge on the face. Metric two: observing a grade of dirtiness (scale 10 = lightest to 0 = darkest) on a standard facial wipe. The reliability of grading a child's face or grading a facial wipe was determined in children in Kongwa Tanzania. We also observed both measurements in a cohort of 202 children ages 1 to <7years prior to face cleaning, immediately afterwards, and 4 hours afterwards. Fifty of the children did not have face cleaning and were controls. Intra-and interobserver reliability was similar for both measures, the latter = 0.53 for observing a clean face and 0.52 for grading a facial wipe. There was no correlation between the two. Both measures detected facial cleaning, compared to control children who were not cleaned, immediately after cleaning; control children with 53% clean faces and wipe score of 6.7 compared to cleaned children with 88% clean faces and wipe score of 8 (p = .0001, p = < .0001, respectively). Both measures also detected face washing 4 hours previously compared to controls., Conclusions: The two metrics were equally reliable, and both measured the behavior of face washing. They measure different aspects of a clean face; one measures the amount of dirt on wiped area and the other measures ocular and nasal discharge. Both measurements appear to capture the behavior of facial cleaning, and the choice of metric would appear to rest on the measurement that captures the stated objective of the behavior, consideration of costs, training, logistics, and implementation., Competing Interests: None of the authors report any competing interests that could be perceived to bias this work., (Copyright: © 2024 West 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.)

Background: Trachoma is a chronic conjunctivitis caused by the bacterium Chlamydia trachomatis. Repeated infections lead to trachomatous conjunctival scarring which can progress to potentially blinding trachomatous trichiasis (TT). In trachoma hyperendemic conditions, women compared to men have an increased risk of scarring and TT, which can progress to blinding corneal opacification. This study determined if there were gender differences in scarring prevalence and severity when trachoma prevalence approaches elimination, in a formerly trachoma hyperendemic region., Methodology/principal Findings: A cross-sectional prevalence study was conducted amongst adults age 15 years and older in Kongwa district, Tanzania in 2019. 3168 persons over age 15 years agreed to be examined and had at least one eye with a gradable image. Ocular photographs were graded for scarring according to a published four-step severity scale. Overall, about half of all study participants had scarring. However, more females (52.3%) had any scarring compared to males (47.2%), OR = 1.22 (95% CI = 1.05-1.43). For every year increase in age, there was a 6.5% increase in the odds of having more severe scarring (95% CI: 5.8%, 7.2%). Women were more likely than men to have severe scarring, OR 2.36 (95% CI: 1.84-3.02). Residence in a community with TF≥10% was associated with a 1.6-fold increased odds of any scarring., Conclusions/significance: Overall scarring prevalence and more severe scarring prevalence was higher in females compared to males, even adjusting for age and community TF prevalence. The data suggest that processes occur that lead to women preferentially progressing towards more severe scarring compared to men., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wolle 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.)

Background: The purpose was to assess an expansion of a previously published photographic four-step severity grading scale for trachomatous scarring (TS)., Methods: Images of everted eyelids of adult women in Tanzania were graded for the presence and severity of TS. The previous S3 grade was subdivided into two categories: S3A, one-third to <50% of the upper eyelid conjunctiva scarred; and S3B, 50% to <90%. The reliability and ease of use were evaluated. This new categorisation was then applied to images taken of the same women 5 y prior to evaluate whether it could help detect previously undetected progression., Results: In total, 142 eyes at baseline and 418 eyes at follow-up after 5 y were graded as S3. Interobserver agreement using the expanded scarring grading scale was a kappa of 0.86. At baseline, 51 (35.9%) eyes were S3A and 91 (64.1%) were S3B. At follow-up after 5 y, 36.6% of the eyes that were previously documented as not having progressed were now detected as having progressed from S3A to S3B. S3B images were more likely to progress to S4 compared with S3A (OR 4.6, 95% CI 2.1 to 9.9)., Conclusions: Adding S3A and S3B is reliable and detects more scarring progression. It will be beneficial for future studies analysing TS in photographs., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: There is an increasing demand for photography for trachoma prevalence surveys. In previous studies, digital single lens reflex (DSLR) images were superior to smartphone images, but newer-model smartphones and/or lens attachments may be able to bridge this gap. This study compares the image quality and ability to detect trachomatous inflammation - follicular (TF) of three camera types: a DSLR Nikon camera, an iPhone SE and an iPhone 13 Pro with a cell scope., Methods: We surveyed 62 children ages 1-7 y from two Tanzanian communities. Upper tarsal conjunctiva images of both eyes were graded for TF by two standardized graders. The McNemar's test and a logistic regression model were used for analyses., Results: The DSLR camera malfunctioned during the study, thus the iPhone SE and iPhone 13 Pro with cell scope were both more likely to take high-quality, gradable photographs (88% and 86%, respectively) compared with the DSLR camera (69%) (p<0.001 and p=0.02, respectively). TF was detected in gradable images from the iPhone SE (8.8%) and iPhone 13 Pro with cell scope (9.0%) at the same rate (p=1.0) as images from the DSLR camera (9.7%)., Conclusion: Smartphones with high-quality image capture, like the iPhone SE/13 Pro, have the potential for use in trachoma surveys if the proportion of gradable images can be improved., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

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: 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., (©Christopher J Brady, R Chase Cockrell, Lindsay R Aldrich, Meraf A Wolle, Sheila K West. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 06.04.2023.)

Background: Though significant progress in disease elimination has been made over the past decades, trachoma is the leading infectious cause of blindness globally. Further efforts in trachoma elimination are paradoxically being limited by the relative rarity of the disease, which makes clinical training for monitoring surveys difficult. In this work, we evaluate the plausibility of an Artificial Intelligence model to augment or replace human image graders in the evaluation/diagnosis of trachomatous inflammation-follicular (TF)., Methods: We utilized a dataset consisting of 2300 images with a 5% positivity rate for TF. We developed classifiers by implementing two state-of-the-art Convolutional Neural Network architectures, ResNet101 and VGG16, and applying a suite of data augmentation/oversampling techniques to the positive images. We then augmented our data set with additional images from independent research groups and evaluated performance., Results: Models performed well in minimizing the number of false negatives, given the constraint of the low numbers of images in which TF was present. The best performing models achieved a sensitivity of 95% and positive predictive value of 50-70% while reducing the number images requiring skilled grading by 66-75%. Basic oversampling and data augmentation techniques were most successful at improving model performance, while techniques that are grounded in clinical experience, such as highlighting follicles, were less successful., Discussion: The developed models perform well and significantly reduce the burden on graders by minimizing the number of false negative identifications. Further improvements in model skill will benefit from data sets with more TF as well as a range in image quality and image capture techniques used. While these models approach/meet the community-accepted standard for skilled field graders (i.e., Cohen's Kappa >0.7), they are insufficient to be deployed independently/clinically at this time; rather, they can be utilized to significantly reduce the burden on skilled image graders., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Socia 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.)

Importance: Because transmission of ocular strains of Chlamydia trachomatis is greatest among preschool-aged children, limiting azithromycin distributions to this age group may conserve resources and result in less antimicrobial resistance, which is a potential advantage in areas with hypoendemic trachoma and limited resources., Objective: To determine the efficacy of mass azithromycin distributions to preschool-aged children as a strategy for trachoma elimination in areas with hypoendemic disease., Design, Setting, and Participants: In this cluster randomized clinical trial performed from November 23, 2014, until July 31, 2017, thirty rural communities in Niger were randomized at a 1:1 ratio to biannual mass distributions of either azithromycin or placebo to children aged 1 to 59 months. Participants and study personnel were masked to treatment allocation. Data analyses for trachoma outcomes were performed from October 19, 2021, through June 10, 2022., Interventions: Every 6 months, a single dose of either oral azithromycin (20 mg/kg using height-based approximation for children who could stand or weight calculation for small children) or oral placebo was provided to all children aged 1 to 59 months., Main Outcomes and Measures: Trachoma was a prespecified outcome of the trial, assessed as the community-level prevalence of trachomatous inflammation-follicular and trachomatous inflammation-intense through masked grading of conjunctival photographs from a random sample of 40 children per community each year during the 2-year study period. A secondary outcome was the seroprevalence of antibodies to C trachomatis antigens., Results: At baseline, 4726 children in 30 communities were included; 1695 children were enrolled in 15 azithromycin communities and 3031 children were enrolled in 15 placebo communities (mean [SD] proportions of boys, 51.8% [4.7%] vs 52.0% [4.2%]; mean [SD] age, 30.8 [2.8] vs 30.6 [2.6] months). The mean coverage of study drug for the 4 treatments was 79% (95% CI, 75%-83%) in the azithromycin group and 82% (95% CI, 79%-85%) in the placebo group. The mean prevalence of trachomatous inflammation-follicular at baseline was 1.9% (95% CI, 0.5%-3.5%) in the azithromycin group and 0.9% (95% CI, 0-1.9%) in the placebo group. At 24 months, trachomatous inflammation-follicular prevalence was 0.2% (95% CI, 0-0.5%) in the azithromycin group and 0.8% (95% CI, 0.2%-1.6%) in the placebo group (incidence rate ratio adjusted for baseline: 0.18 [95% CI, 0.01-1.20]; permutation P = .07)., Conclusions and Relevance: The findings of this trial do not show that biannual mass azithromycin distributions to preschool-aged children were more effective than placebo, although the underlying prevalence of trachoma was low. The sustained absence of trachoma even in the placebo group suggests that trachoma may have been eliminated as a public health problem in this part of Niger., Trial Registration: ClinicalTrials.gov Identifier: NCT02048007.

Background: There is evidence of the occurrence of trachoma in Peru, and studies have shown that soil-transmitted helminthiases (STH) are affecting rural communities in the Amazon basin in Loreto Department. This study was done to estimate trachoma prevalence, STH prevalence, and the associated factors for both diseases in children aged 1-9 years in rural communities of Peru., Methodology: A population-based cross-sectional survey was carried out in rural communities of Loreto. A standardized survey questionnaire with individual and household risk factors related to both diseases was used. Ocular examination was done for all participants aged one year and above, and eye swab samples were collected from children with follicular trachoma (TF). Anthropometric measurements, stool samples for STH, and blood samples for hemoglobin measurement were taken from children., Principal Findings: TF prevalence was 7.74% (95% CI 5.08-11.63%), STH prevalence was 49.49% (95% CI 25.00-52.43%), and prevalence of co-occurrence of both diseases was 5.06% (95% CI 2.80-8.98%) in children aged 1-9 years. Being at age 3-8 years old (AOR = 6.76; 95% CI 1.346-33.947), have an unclean face (AOR = 24.64; 95% CI 6.787-89.444), and having been dewormed in the last six months (AOR = 2.47; 95% CI 1.106-5.514), were risk factors of TF. Being a female (AOR = 0.22; 95% CI 0.103-0.457) was associated with decreased odds of TF. Having been dewormed in the last six months (AOR = 0.30; 95% CI 0.139-0.628) was a preventative factor for STH. Risk factors for children with both diseases mirrored the findings for risk factors for individual diseases., Conclusions: Neglected tropical diseases and associated risk factors overlap in communities living in vulnerable conditions in the Amazon basin of Peru. These findings support the need to implement integrated interventions, including mass drug administration, water, sanitation, and hygiene for both diseases in the study area., Competing Interests: The authors have declared that no competing interests exist.

Background: Serologic testing for chlamydial antibodies is one potential tool for trachoma monitoring. Understanding the dynamics of seroconversion and seroreversion in low endemic districts is critical for determining the value of using serology., Methodology/principal Findings: We surveyed a random sample of 2536 children aged 1-9 years in Kongwa, Tanzania, over three years; 1719 (67.8%) participants had all three follow-ups. Surveys assessed trachomatous inflammation-follicular (TF), Chlamydia trachomatis infection, and anti-pgp3 antibodies. Mass drug administration occurred immediately after the first and second follow-up surveys. The cohort was classified into trajectories of change in serostatus, and risk factors were evaluated for seroconversion and seroreversion. We found that 86.2% of seropositives remained seropositive throughout the study, whereas 12.1% seroreverted. Seroreverters were younger (Odds Ratio [OR] = 0.88 for every one-year increase in age, 95% CI = 0.79-0.99). 84.5% of seronegatives remained seronegative, and 13.0% seroconverted. Seroconverters were also younger (OR = 0.92, 95% CI = 0.87-0.98). Seroconversion and seroreversion were not explained by indeterminate values for the intensity of antibody response. Less than 1% of the cohort had unstable changes in serostatus, mostly explained by values in the indeterminate range. TF and infection in the cohort declined over time, while seropositivity increased from 31.5% to 36.4%., Conclusions/significance: Antibody status is relatively stable over time. Both seroconversion and seroreversion occurred over the three years in this low endemic district, especially in younger children. Modeling seroreversion is important for accurate determination of seroconversion. The use of serology as a monitoring tool should target the younger aged children as they will most likely capture recent changes in serostatus., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Graded images can be used for trachoma prevalence surveys, but there is concern for mismatch between image and field grades of the upper tarsal conjunctiva. We aimed to determine if poor photograph quality and/or inflammation may contribute to differential grading of trachomatous inflammation-follicular (TF) between field and photograph graders., Methods: We developed a simplified and expanded image quality grading tool. Agreement was assessed using kappa statistic. We included 5417 eyes with both field and image grades for TF. Eyes where the field and adjudicated photograph TF grades did not match were identified (mismatched) and assigned an image quality (IQ) score and a potential mismatch reason. We also assigned IQ scores to a stratified random sample of 60 eyes with matching field and photograph TF grades (matched)., Results: There were 5240 eyes that had matching grades, whereas 177 eyes (3.3%) were mismatched. Overall quality was high, even in mismatched eyes. There was no difference in overall or specific IQ metrics between eyes with matching grades and eyes with mismatched grades (P = 0.59). Mismatched eyes had worse inflammation compared to matched eyes (P = 0.048). The primary reason for calling TF in the field but not in the photographs appeared to be the number of follicles observed., Conclusions: Image quality did not explain mismatch between field grades and image grades from this prevalence survey. Inflammation made mismatch more likely., Translational Relevance: Our quality grading scheme rapidly identifies image quality issues for training. Standardizing TF grading in the presence of inflammation will improve field and photograph grading.

Background: Unintentional falls among older adults are associated with an ensuing decline in physical activity. Our objective is to evaluate the associations between fall status and changes in excursions after a fall., Methods: Prospective cohort study of older adults with glaucoma or suspected glaucoma who reported falls for 1 year and wore a GPS device for 1-week at the baseline and 1 year later. GPS data were quantified into average: daily excursions, daily time away from home, and time per excursion. Fall status was categorized as fallers, injurious fallers, recurrent fallers, and recurrent injurious fallers. Multivariable negative binomial regression and generalized estimating equations models were employed to evaluate relationship between excursion parameters and fall status., Results: A total of 192 eligible participants were included in the analyses. Approximately half were males (50.5%) with a mean age of 70.1 years and one-fourth were Black (28.1%). There were no significant associations between fall status and end-of-study excursion parameters (p > 0.06 for all), and visual field damage did not modify these relationships (p > 0.07 for all). For instance, patients with multiple falls during a one-year study period did not demonstrate more daily excursions (incident rate ratio [IRR] = 1.16, 95% confidence interval [CI] = 0.85 to 1.57), longer time per excursion (IRR = 0.79, 95% CI =0.59 to 1.06), or more average daily time away (IRR = 1.05, 95% CI = 0.84 to 1.30) conducted at the end-of-the study. Excursion parameters at the final assessment were not significantly different from those at baseline (p > 0.09 for all) and the changes did not vary by fall status (p > 0.23 for all)., Conclusions: Older adults with glaucoma did not modify their travel away from home after experiencing a fall. Additional research is necessary to understand how often maintenance of travel outside the home after a fall reflects proper compensation for greater fall risk or continued activity despite the risk of falling., (© 2022. The Author(s).)

Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations., Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists., Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity., Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges., Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission., Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section., Competing Interests: MJB reports grants (in support of the work of the Lancet Global Health Commission) from The Wellcome Trust, The Queen Elizabeth Diamond Jubilee Trust, Sightsavers, The Fred Hollows Foundation, The British Council for the Prevention of Blindness, Moorfields Eye Charity, The Seva Foundation, and Christian Blind Mission during the conduct of the study. NC reports personal fees from Belkin Vision. DSF reports personal fees from W L Gore, Bausch and Lomb, Life Biosciences, Thea, and iDx outside of the submitted work; and is a member of the Board of Orbis International. TYW reports grants from Allergan, Bayer, Boehringer Ingelheim, Eden Ophthalmic, Genentech, Iveric Bio, Merck, Novartis, Oxurion (formerly ThromboGenics), Roche, Samsung, Shanghai Henlius, Zhaoke Pharmaceutical, and Aldropika Therapeutics, and is co-founder of start-up companies Plano and EyRiS. PTK reports stockholding for Radiance Therapeutics and Optceutics; personal fees from Aerie, Alcon, AstraZeneca, Bausch + Lomb, Genetech, Novartis, Pfizer, and Sanofi-Aventis outside of the submitted work; being a board member of Moorfields Eye Hospital; and having a patent pending for Biochannel Device. HT reports leadership roles for the International Council of Ophthalmology and the Ophthalmology Foundation (unpaid roles). SKW reports board membership (unpaid) of Christian Blind Mission-USA. All other authors declare no competing interests., (© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

Importance: Mass azithromycin distributions may decrease childhood mortality, although the causal pathway is unclear. The potential for antibiotics to function as growth promoters may explain some of the mortality benefit., Objective: To investigate whether biannual mass azithromycin distributions are associated with increased childhood growth., Design, Setting, and Participants: This cluster-randomized trial was performed from December 2014 until March 2020 among 30 rural communities in Boboye and Loga departments in Niger, Africa, with populations from 200 to 2000 individuals. Communities were randomized in a 1:1 ratio to biannual mass distributions of azithromycin or placebo for children ages 1 to 59 months. Participants, field-workers, and study personnel were masked to treatment allocation. Height and weight changes from baseline to follow-up at 4 years were compared between groups. Data were analyzed from June through November 2021., Interventions: Participants received azithromycin at 20 mg/kg using height-based approximation or by weight for children unable to stand every 6 months at the participants' households. Placebo contained the vehicle of the azithromycin suspension., Main Outcomes and Measures: Longitudinal anthropometric assessments were performed on a random sample of children before the first treatment and then annually for 5 years. Height and weight were the prespecified primary outcomes., Results: Among 3936 children enrolled from 30 communities, baseline characteristics were similar between 1299 children in the azithromycin group and 2637 children in the placebo group (mean 48.2% [95% CI, 45.5% to 50.8%] girls vs 48.0% [95% CI, 45.7% to 50.3%] girls; mean age, 30.8 months [95% CI, 29.5 to 32.0 months] vs 30.6 months [95% CI, 29.2 to 31.6 months]). Baseline anthropometric assessments were performed among 2230 children, including 985 children in the azithromycin group and 1245 children in the placebo group, of whom follow-up measurements were available for 789 children (80.1%) and 1063 children (85.4%), respectively. At the prespecified 4-year follow-up visit, children in the azithromycin group gained a mean 6.7 cm (95% CI, 6.5 to 6.8 cm) in height and 1.7 kg (95% CI, 1.7 to 1.8 kg) in weight per year and children in the placebo group gained a mean 6.6 cm (95% CI, 6.4 to 6.7 cm) in height and 1.7 kg (95% CI, 1.7 to 1.8 kg) in weight per year. Height at 4 years was not statistically significantly different between groups when adjusted for baseline height (0.08 cm [95% CI, -0.12 to 0.28 cm] greater in the azithromycin group; P = .45), and neither was weight when adjusted for height and baseline weight (0.02 kg [95% CI, -0.10 to 0.06 kg] less in the azithromycin group; P = .64). However, among children in the shortest quartile of baseline height, azithromycin was associated with a 0.4 cm (95% CI, 0.1 to 0.7 cm) increase in height compared with placebo., Conclusions and Relevance: This study did not find evidence of an association between mass azithromycin distributions and childhood growth, although subgroup analysis suggested some benefit for the shortest children. These findings suggest that the mortality benefit of mass azithromycin distributions is unlikely to be due solely to growth promotion., Trial Registration: ClinicalTrials.gov Identifier: NCT02048007.

Background: Trachoma, a chronic conjunctivitis caused by Chlamydia trachomatis, is the leading infectious cause of blindness worldwide. Trachoma has been targeted for elimination as a public health problem which includes reducing trachomatous inflammation-follicular prevalence in children and reducing trachomatous trichiasis prevalence in adults. The rate of development of trachomatous trichiasis, the potentially blinding late-stage trachoma sequelae, depends on the rate of trachomatous scarring development and progression. Few studies to date have evaluated the progression of trachomatous scarring in communities that have recently transitioned to a low trachomatous inflammation-follicular prevalence., Methodology/principal Findings: Women aged 15 and older were randomly selected from households in 48 communities within Kongwa district, Tanzania and followed over 3.5 years for this longitudinal study. Trachomatous inflammation-follicular prevalence was 5% at baseline and at follow-up in children aged 1-9 in Kongwa, Tanzania. 1018 women aged 15 and older had trachomatous scarring at baseline and were at risk for trachomatous scarring progression; 691 (68%) completed follow-up assessments. Photographs of the upper tarsal conjunctiva were obtained at baseline and follow-up and graded for trachomatous scarring using a previously published four-step severity scale. The overall cumulative 3.5-year progression rate of scarring was 35.3% (95% CI 31.6-39.1). The odds of TS progression increased with an increase in age in women younger than 50, (OR 1.03, 95% CI 1.01-1.05, p = 0.005) as well as an increase in the household poverty index (OR 1.29, 95% CI 1.13-1.48, p = 0.0002)., Conclusions/significance: The 3.5-year progression of scarring among women in Kongwa, a formerly hyperendemic now turned hypoendemic district in central Tanzania, was high despite a low active trachoma prevalence. This suggests that the drivers of scarring progression are likely not related to on-going trachoma transmission in this district., Competing Interests: The authors have declared that no competing interests exist.

Background: As the prevalence of trachoma declines worldwide, it is becoming increasingly expensive and challenging to standardize graders in the field for surveys to document elimination. Photography of the tarsal conjunctiva and remote interpretation may help alleviate these challenges. The purpose of this study was to develop, and field test an Image Capture and Processing System (ICAPS) to acquire hands-free images of the tarsal conjunctiva for upload to a virtual reading center for remote grading., Methodology/principal Findings: This observational study was conducted during a district-level prevalence survey for trachomatous inflammation-follicular (TF) in Chamwino, Tanzania. The ICAPS was developed using a Samsung Galaxy S8 smartphone, a Samsung Gear VR headset, a foot pedal trigger and customized software allowing for hands-free photography. After a one-day training course, three trachoma graders used the ICAPS to collect images from 1305 children ages 1-9 years, which were expert-graded remotely for comparison with field grades. In our experience, the ICAPS was successful at scanning and assigning barcodes to images, focusing on the everted eyelid with adequate examiner hand visualization, and capturing images with sufficient detail to grade TF. The percentage of children with TF by photos and by field grade was 5%. Agreement between grading of the images compared to the field grades at the child level was kappa = 0.53 (95%CI = 0.40-0.66). There were ungradable images for at least one eye in 199 children (9.1%), with more occurring in children ages 1-3 (18.5%) than older children ages 4-9 (4.2%) (χ2 = 145.3, p<0.001)., Conclusions/significance: The prototype ICAPS device was robust, able to image 1305 children in a district level survey and transmit images from rural Tanzania to an online grading platform. More work is needed to improve the percentage of ungradable images and to better understand the causes of disagreement between field and photo grading., Competing Interests: The authors have declared that no competing interests exist.

Background: Having a clean face is protective against trachoma. In the past, long distances to water were associated with unclean faces and increased trachoma. Other environmental factors have not been extensively explored. We need improved clarity on the environmental factors associated with facial cleanliness and trachoma prevalence, especially when the disease burden is low., Methodology/principle Findings: A cross-sectional survey focusing on household environments was conducted in all 92 villages in Kongwa, Tanzania, in a random selection of 1798 households. Children aged 0-5 years in these households were examined for facial cleanliness. In each of the 50 randomly-selected villages, 50 children aged 1-9 years were randomly selected and examined for trachoma. In a multivariate model adjusting for child age, we found that children were more likely to have clean faces if the house had a clean yard (OR 1.62, 95% CI 1.37-1.91), an improved latrine (OR 1.11, 95% CI 1.01-1.22), and greater water storage capacity (OR 1.02, 95% CI 1.00-1.04), and if there were clothes washed and drying around the house (OR 1.30, 95% CI 1.09-1.54). However, measures of crowding, wealth, time spent on obtaining water, or the availability of piped water was not associated with clean faces. Using a cleanliness index (clean yard, improved latrine, washing clothes, ≥1 child in the household having a clean face), the community prevalence of trachoma decreased with an increase in the average value of the index (OR 2.28, 95% CI 1.17-4.80)., Conclusions/significance: Access to water is no longer a significant limiting factor in children's facial cleanliness in Kongwa. Instead, water storage capacity and the way that water is utilized are more important in facial cleanliness. A household cleanliness index with a holistic measure of household environment is associated with reduced community prevalence of trachoma., Competing Interests: The authors have declared that no competing interests exist.

The MORDOR study, a masked, community-level randomized clinical trial conducted in Niger, Malawi and Tanzania (2015 to 2017), showed that biannual administration of single-dose azithromycin to preschool children reduced all-cause mortality. We sought to evaluate its impact on causes of death in children aged 1-59 months in Tanzania. A random sampling of 614 communities was conducted in Kilosa District, Tanzania, with simple random assignment of communities to receive either azithromycin or placebo. In these communities, a census was carried out every 6 months and children aged 1-59 months received biannual (every 6 months), single-dose azithromycin (~20mg/kg) or placebo depending on community assignment, over a 2-year period. Mortality was determined at the time of the biannual census. For child deaths, a verbal autopsy was performed to ascertain the cause using a standardized diagnostic classification. A total of 190- (0.58 /100 person-years) and 200 deaths (0.59/100 person-years) were reported in the azithromycin and placebo arms, respectively. Malaria, pneumonia and diarrhea, accounted for 71% and 68% of deaths in the respective arms. Overall, the mortality was not different by treatment arm, nor were the distribution of causes of death after adjusting for community clustering. The cause-specific mortality for diarrhea/pneumonia was no different over time. In children aged 1-5 months, 32 deaths occurred in the placebo arm and 25 deaths occurred in the azithromycin arm; 20 (62.5%) deaths in the placebo- and 10 (40%) in the azithromycin arm were attributed to diarrhea or pneumonia. Neither differences in the number of deaths nor the diarrhea/pneumonia attribution was statistically significant after adjusting for community clustering. In conclusion, azithromycin was not associated with a significant decline in deaths by specific causes compared to placebo. The non-significant lower rates of diarrhea or pneumonia in children <6 months who received azithromycin merit further investigation in high-mortality settings. Trial registration: NCT02048007., Competing Interests: The authors have no relevant conflicts of interest to disclose.

Background: Visually impaired older adults have a greater risk of falling, making them particularly susceptible to fall-related health consequences and restricted physical activity. Unclear however, is the relationship between having falls and longitudinal changes in daily patterns of objectively measured physical activity in older adults with visual impairments., Methods: We created a three-year prospective cohort study (Falls in Glaucoma Study) of older adults with primary or suspected glaucoma at the Johns Hopkins Wilmer Eye Institute from 2013 to 2015. Cumulative incidence of falls was determined through self-reported fall calendars over 12 months. Participants were then classified into one of three groups: multiple fallers (≥2 falls), single fallers (1 fall), and non-fallers (0). Daily physical activity was measured over 1 week using a waist-bound accelerometer during baseline and three-year follow-ups. Activity fragmentation was defined as the reciprocal of the mean activity bout length, with higher fragmentation reflecting shorter, more fractured bouts of continuous activity. Multivariate linear mixed-effects models were used to assess three-year longitudinal changes in: 1) activity fragmentation, and 2) accumulation of activity across six three-hour intervals from 5 AM to 11 PM., Findings: In adjusted models accounting for visual field damage and other factors, multiple fallers demonstrated greater annual declines (per year) in daily active bouts (-1.79 bouts/day, 95% confidence interval [CI]: -3.35, -0.22), daily active minutes (-17.15 min/day, 95% CI: -26.35, -7.94), and increased fragmentation (1%, 95% CI: 0, 2%) over the three-year follow-up period as compared to non-fallers; no such changes were seen when comparing single fallers and non-fallers. In time-of-day analyses, multiple fallers experienced greater annual declines in average hourly steps over all periods of the day, though the rate of decline was only significant between 5 PM and 8 PM (-27.07 steps/hour, 95% CI: -51.15, -2.99) compared to non-fallers., Interpretation: In an older population with visual impairment, multiple falls over 12 months were associated with more transient and fragmented activity over a subsequent three-year period, and activity declines during evening hours, compared to non-fallers. These findings suggest that multiple fallers with visual impairment may be at high risk for a decline in physical capacity and endurance, warranting clinical interventions., Funding: The research was supported in part by National Institutes of Health Grant EY022976., Competing Interests: AM and PR reported grants from the National Institutes of Health. JS reported grants from the National Institute on Aging. TL reported grants from the National Eye Institute. No other disclosures were reported., (© 2021 The Authors.)

Understanding periods of the year associated with higher risk for falling and less physical activity may guide fall prevention and activity promotion for older adults. We examined the relationship between weather and seasons on falls and physical activity in a three-year cohort of older adults with glaucoma. Participants recorded falls information via monthly calendars and participated in four one-week accelerometer trials (baseline and per study year). Across 240 participants, there were 406 falls recorded over 7569 person-months, of which 163 were injurious (40%). In separate multivariable regression models incorporating generalized estimating equations, temperature, precipitation, and seasons were not significantly associated with the odds of falling, average daily steps, or average daily active minutes. However, every 10 °C increase in average daily temperature was associated with 24% higher odds of a fall being injurious, as opposed to non-injurious ( p = 0.04). The odds of an injurious fall occurring outdoors, as opposed to indoors, were greater with higher average temperatures (OR per 10 °C = 1.46, p = 0.03) and with the summer season (OR = 2.69 vs. winter, p = 0.03). Falls and physical activity should be understood as year-round issues for older adults, although the likelihood of injury and the location of fall-related injuries may change with warmer season and temperatures.

Objective: Knowledge of a patient's emotional health status and using patient-centred communication may be key to providing early intervention and referral to appropriate treatment/support services for ophthalmology patients. This study aims to determine if and how ophthalmologists use anxiety and depression scores to determine clinical care of patients with chronic eye disease., Methods and Analysis: This cross-sectional study included 10 ophthalmologists and a convenience sample of 100 of their patients (>18 years). The Patient Health Questionnaire (PHQ-9) for depression and the Generalised Anxiety Disorder (GAD-7) tool were administered to patients. Scores from these instruments were provided to ophthalmologists just prior to the clinic visit. After the visit, ophthalmologists were given a questionnaire to assess self-reported change in clinical practice and whether knowledge of scores impacted their communication style, treatment plan and follow-up protocol., Results: Of these patients (mean age=63), 27% reported mild-moderate anxiety or depression as their worst score, while 2% reported suicidal thoughts; 20% reported neither anxiety nor depression. Ophthalmologists' response to patients with mild or worse anxiety or depression was to change clinical approach (28%) and communication style (31%), both metrics increasing with severity of symptoms (Fisher's exact p<0.05). None reported changing their choice of treatment or modifying follow-up protocols; referral to social work/psychiatry services was 60%, 3.7% and 0% for patients with moderately severe or worse, mild-to-moderate, or minimal scores, respectively., Conclusion: Providing ophthalmologists with knowledge of the emotional health of their patients may change the clinical approach and referral pattern., 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.)

Background: Post-surgical follow-up is a challenge in low- and middle-income countries. Understanding barriers to trachomatous trichiasis (TT) surgical follow-up can inform program improvements. In this study, patient perceived barriers and enabling factors to follow-up after TT surgery are identified., Methods: A longitudinal study was carried out in a community-based cohort of persons who received TT surgery in Bahi district, Tanzania. Questionnaires were administered before TT surgery and again after the scheduled 6-month follow-up. Those who did not return were examined at their homes., Results: At baseline, 852 participants were enrolled. Of these, 633 (74%) returned at 6 months and 128 (15%) did not and were interviewed at home. Prior to surgery, attenders were more likely to report familiarity with a community health worker (CHW) (22% vs. 14%; p = 0.01) and less likely to state that time constraints are a potential reason for failure to follow-up (66% vs. 74%; p = .04). At follow-up, non-attenders were more likely to endorse barriers pertaining to knowledge about the need for follow-up, lack of transportation, and satisfaction with surgery. There was no difference in post-operative TT between attenders and non-attenders (23% vs. 18% respectively; p = 0.25)., Conclusions: The outcome of surgery was not a barrier to follow-up. However, better integration of CHWs into their communities and work at coordinating post-surgical care may improve follow-up rates. Moreover, provision of transportation and implementation of effective reminder systems may address patient-perceived barriers to improve follow-up., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Posttreatment Lyme disease (PTLD) is marked by neurologic symptoms, cognitive impairment, and significant symptom burden, including fatigue and ocular complaints. The purpose of this study was to determine whether contrast sensitivity (CS) is altered in patients with PTLD compared with healthy controls and, second, whether CS is associated with cognitive and/or neurologic deficits., Methods: CS was measured using a Pelli-Robson chart with forced-choice procedures, and the total number of letters read was recorded for each eye. CS impairment was defined for age <60 years as logCS of 1.80 (36 letters or fewer) and for those age ≥60 years as logCS of 1.65 (33 letters or fewer). Participants self-administered a questionnaire to assess presence of ocular symptoms and underwent a neurologic exam and battery of neurocognitive tests., Results: CS impairment was associated with an increased odds of being in the PTLD group that was 2.6 times as high as those without CS impairment (odds ratio, 2.6; 95% confidence interval, 1.3-5.2). Neither cases nor controls had significant distance acuity impairment. CS impairment was not associated with any of the ocular complaints in cases but was borderline associated with neurologic abnormalities and cognitive impairment., Conclusions: CS impairment in patients with PTLD is linked to signs of cognitive and neurologic impairment and may be a marker of illness severity., Translational Relevance: Further investigation into the value of testing CS impairment in PTLD cases is warranted, especially if it is an indicator of cognitive or neurologic manifestations.

Purpose: To evaluate the importance of central versus far peripheral visual field (VF) loss in assessing disability in glaucoma., Methods: In total, 231 patients with glaucoma or suspected glaucoma completed 24-2 VF testing and automated peripheral VFs using the suprathreshold 30- to 60-degree pattern. Questionnaires assessed fear of falling (FoF), quality of life (QOL), instrumental activities of daily living (IADLs), and driving habits; nonsedentary time, reading speed, and gait were objectively measured. Multivariable regression models analyzed the effect of central VF and/or peripheral VF damage on each outcome., Results: In models including both central and peripheral VF damage (independent effects), greater central, but not peripheral, VF damage was associated with greater FoF, worse QOL, fewer daily steps, and difficulty with IADLs (P < 0.02 for central; P > 0.5 for peripheral). For gait measures, greater peripheral, but not central, damage was associated with shorter steps and shorter strides, as well as greater variability in step length (P < 0.03 for peripheral; P > 0.14 for central). Model R2 values were not substantially higher (less than 5% additional explained variability) for models including both central and peripheral VF damage as compared to the best models incorporating only one region of VF damage (i.e., central or peripheral)., Conclusions: The relative importance of central 24 degrees versus more peripheral VF damage differs across functional domains in patients with glaucoma. Central damage is more strongly associated with most disability outcomes, although peripheral damage is more associated with specific gait measures. Studies examining the relative importance of various VF regions should assess functional domain separately and eschew integrated measures of quality of life/activity limitation.

Background: Trachoma is the leading infectious cause of blindness. Repeated or persistent ocular infection with Chlamydia trachomatis in childhood leads to conjunctival scarring, usually in adulthood but often earlier in areas with greater disease burden. There are limited longitudinal data examining change in scarring in children, especially where trachoma rates are low., Methodology/principal Findings: A cohort of children, ages 1-9 years, were randomly selected at baseline from 38 communities in Kongwa, Tanzania and followed for 2 years. Rates of trachomatous inflammation-follicular (TF) were <5% over the survey period. At baseline, 1,496 children were recruited and 1,266 (85%) were followed-up. Photographs were obtained at baseline and follow-up and graded for the presence and severity of scarring using a four-point scale ranging between S1-S4. In children without scarring at baseline, 1.6% (20/1,246) were found to have incident scarring, and incident scarring was more common among girls compared to boys. Among children with scarring at baseline, 21% (4/19) demonstrated progression., Conclusions/significance: In this formerly hyper-endemic district, the incidence of new scarring in children ages 1-9 years is low, although 21% of those who had scarring at baseline progressed in severity over the 2-year follow-up period. These data provide support for the thesis that while incident scarring more closely reflects ongoing exposure, progression may involve factors independent of ongoing transmission of trachoma., Competing Interests: The authors have declared that no competing interests exist.

A simplified grading system for trachoma was published by the World Health Organization (WHO) in 1987. Intended for use by non-specialist personnel working at community level, the system includes five signs, each of which can be present or absent in any eye: (i) trachomatous trichiasis; (ii) corneal opacity; (iii) trachomatous inflammation-follicular; (iv) trachomatous inflammation-intense; and (v) trachomatous scarring. Though neither perfectly sensitive nor perfectly specific for trachoma, these signs have been essential tools for identifying populations that need interventions to eliminate trachoma as a public health problem. In 2018, at WHO's 4th global scientific meeting on trachoma, the definition of one of the signs, trachomatous trichiasis, was amended to exclude trichiasis that affects only the lower eyelid. This paper presents the amended system, updates its presentation, offers notes on its use and identifies areas of ongoing debate., ((c) 2020 The authors; licensee World Health Organization.)

Competing Interests: The authors have declared that no competing interests exist.

A serologic test for antibodies to chlamydia may be a useful tool for trachoma surveillance. However, little is known about the longitudinal stability of antibody status, especially following Mass Drug Administration (MDA), which is critical to understanding serostatus in trachoma-endemic areas. A longitudinal cohort of 1908 children ages 1-9 years in Tanzania from 50 communities were followed at baseline and for 6 months after MDA. They were evaluated for clinical trachoma, conjunctival swabs were tested for chlamydial infection using GeneXpert platform, and blood spots were collected on filter paper and dried to test for antibodies to Chlamydia trachomatis pgp3 using the Luminex platform. 6.3% of children in the study had infection, and coverage with MDA was 97%. 670 (35%) were sero-positive for pgp3 antibodies at baseline, and 4.0% of these seroreverted to negative following MDA. Of those seronegative at baseline, 3.6% seroconverted. The individual change in log median fluorescence intensity(MFI-BG) values was -0.15 overall (p < .001). Seroconversion rates were lower following MDA and seroreversion rates were slightly higher compared to rates in this same cohort in the absence of MDA. MDA has a small effect on reduction of MFI-BG.

Background: Biannual azithromycin distribution has been shown to reduce child mortality as well as increase antimicrobial resistance. Targeting distributions to vulnerable subgroups such as malnourished children is one approach to reaching those at the highest risk of mortality while limiting selection for resistance. The objective of this analysis was to assess whether the effect of azithromycin on mortality differs by nutritional status., Methods and Findings: A large simple trial randomized communities in Niger to receive biannual distributions of azithromycin or placebo to children 1-59 months old over a 2-year timeframe. In exploratory subgroup analyses, the effect of azithromycin distribution on child mortality was assessed for underweight subgroups using weight-for-age Z-score (WAZ) thresholds of -2 and -3. Modification of the effect of azithromycin on mortality by underweight status was examined on the additive and multiplicative scale. Between December 2014 and August 2017, 27,222 children 1-11 months of age from 593 communities had weight measured at their first study visit. Overall, the average age among included children was 4.7 months (interquartile range [IQR] 3-6), 49.5% were female, 23% had a WAZ < -2, and 10% had a WAZ < -3. This analysis included 523 deaths in communities assigned to azithromycin and 661 deaths in communities assigned to placebo. The mortality rate was lower in communities assigned to azithromycin than placebo overall, with larger reductions among children with lower WAZ: -12.6 deaths per 1,000 person-years (95% CI -18.5 to -6.9, P < 0.001) overall, -17.0 (95% CI -28.0 to -7.0, P = 0.001) among children with WAZ < -2, and -25.6 (95% CI -42.6 to -9.6, P = 0.003) among children with WAZ < -3. No statistically significant evidence of effect modification was demonstrated by WAZ subgroup on either the additive or multiplicative scale (WAZ < -2, additive: 95% CI -6.4 to 16.8, P = 0.34; WAZ < -2, multiplicative: 95% CI 0.8 to 1.4, P = 0.50, WAZ < -3, additive: 95% CI -2.2 to 31.1, P = 0.14; WAZ < -3, multiplicative: 95% CI 0.9 to 1.7, P = 0.26). The estimated number of deaths averted with azithromycin was 388 (95% CI 214 to 574) overall, 116 (95% CI 48 to 192) among children with WAZ < -2, and 76 (95% CI 27 to 127) among children with WAZ < -3. Limitations include the availability of a single weight measurement on only the youngest children and the lack of power to detect small effect sizes with this rare outcome. Despite the trial's large size, formal tests for effect modification did not reach statistical significance at the 95% confidence level., Conclusions: Although mortality rates were higher in the underweight subgroups, this study was unable to demonstrate that nutritional status modified the effect of biannual azithromycin distribution on mortality. Even if the effect were greater among underweight children, a nontargeted intervention would result in the greatest absolute number of deaths averted., Trial Registration: The MORDOR trial is registered at clinicaltrials.gov NCT02047981., Competing Interests: The authors have declared that no competing interests exist.

Mass azithromycin distribution has been shown to reduce all-cause mortality in preschool children in sub-Saharan Africa. However, substantial heterogeneity in the apparent effect has been noted across geographic settings, suggesting a greater relative benefit in higher mortality settings. Here, we evaluated the relationship between the underlying mortality rate and the efficacy of azithromycin for the prevention of child mortality using data from multiple sites in Ethiopia, Malawi, Niger, and Tanzania. Between regions, we find no strong evidence of effect modification of the efficacy of azithromycin distribution for the prevention of child mortality by the underlying mortality rate ( P = 0.12), although a modest effect is consistent with our findings. Higher mortality settings could be prioritized, however, because of the larger number of deaths which could be averted with azithromycin distribution.

We examined whether baseline mortality risk, as a function of child age and site, modified the azithromycin mortality-reduction effect in the Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) clinical trial. We used the Cox proportional hazards model with an interaction term. Three models were examined representing three sources for the baseline-risk covariate: two using sources external to MORDOR and the third leveraging data within MORDOR. All three models provided moderate evidence for the effect becoming stronger with increasing baseline mortality ( P = 0.02, 0.02, and 0.07, respectively) at the rate of approximately 6-12% additional mortality reduction per doubling of baseline mortality. Etiological and programmatic implications of these findings are discussed.

The Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance study showed that administration of biannual, single-dose azithromycin to preschool children reduces mortality. We sought to evaluate its impact on azithromycin resistance. Thirty randomly selected communities in Kilosa district, Tanzania, were randomized to receive 6-monthly single-dose azithromycin (∼20 mg/kg) versus placebo treatment of children aged 1-59 months. From each community, 40 children (aged 1-59 months) were randomly selected at baseline, 12 and 24 months. Isolation and resistance testing of Streptococcus pneumoniae and Escherichia coli were evaluated using nasopharyngeal and rectal swabs, respectively. The carriage prevalence and the proportion of azithromycin-resistant isolates were determined using disk diffusion. At baseline, the characteristics of the randomly selected children were similar by treatment arms. Both at baseline and in annual cross-sectional surveys, rates of S. pneumoniae and E. coli isolation between treatment arms were similar. The proportions of azithromycin-resistant S. pneumoniae isolates in the children in communities treated with azithromycin versus placebo at baseline, 12 months, and 24 months were 26.5% (18.1%; P = 0.26), 26.8% (16.5%; P = 0.29), and 13.4% (17.0%; P = 0.57), respectively. The proportions of azithromycin-resistant E. coli isolates at baseline, 12 months, and 24 months in the azithromycin (versus placebo) arms were 14.9% (18.9%; P = 0.16), 21.5% (16.6%; P = 0.10), and 14.9% (14.7%; P = 0.95), respectively. Over the 24 months, the mean treatment coverage for the azithromycin and placebo was 76.9% and 74.8%, respectively ( P = 0.49). Biannual administration of single-dose azithromycin to children did not appear to result in excess azithromycin resistance in S. pneumoniae and E. coli isolates over 24 months of follow-up.