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Abstract Background Infectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro rose bengal photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates (Atalay HT et al., Curr Eye Res 43:1322–5, 2018, Arboleda A et al. Am J Ophthalmol 158:64-70, 2014). In one published series, RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthamoeba keratitis not responsive to medical therapy. Methods This international, randomized, sham and placebo controlled 2-arm clinical trial randomizes patients with smear positive fungal and acanthamoeba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) topical antimicrobial plus sham RB-PDT or 2) topical antimicrobial plus RB-PDT. Discussion We anticipate that RB-PDT will improve best spectacle-corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via ClinicalTrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request. Trial registration NCT, NCT05110001 , Registered on November 5, 2021.

Background: Trachoma programs use the indicator trachomatous inflammation--follicular (TF) to monitor indication for and response to treatment for trachoma at the district level. Alternative indicators, including serologic markers, are increasingly being evaluated for trachoma surveillance. We evaluated seroprevalence of IgG antibodies to the Pgp3 antigen in two districts in Maradi, Niger thought to have low TF prevalence., Methods: Data were collected as part of the baseline assessment of the Azithromycin Reduction to Reach Elimination of Trachoma (ARRET) trial in September 2021. A random sample of 80 communities was selected from Mayahi and Guidan Roumdji districts, both of which had TF prevalence <20% at their most recent trachoma impact survey in 2018. A random sample of 50 children per community was sampled. We collected field grades, conjunctival swabs for processing PCR for ocular Chlamydia trachomatis, and dried blood spots for serologic assessment., Results: Of 3,994 children sampled in 80 communities, 49% were female and median age was 4 years. Overall TF prevalence was 4.6% (95% CI 3.5 to 5.8%) and trachomatous inflammation-intense (TI) prevalence was 0.6% (95% 0.3 to 0.9%). The prevalence of ocular chlamydia was 0.03% (95% CI 0.08%). Seroprevalence for Pgp3 antibodies was 6.3% (95% CI 5.5 to 7.1%) in 1-9-year-olds and 3.7% (95% CI 2.9 to 4.4%) in 1-5-year-olds. TF and Pgp3 seroprevalence were better correlated in 1-5-year-olds (correlation coefficient 0.29) compared to 1-9-year-olds (correlation coefficient 0.09)., Conclusions: In this low trachoma prevalence setting in Niger, seroprevalence of antibodies to Pgp3 were consistent with little ongoing transmission of C. trachomatis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: The risk of antibiotic resistance is complicated by the potential for spillover effects from one treated population to another. Azithromycin mass drug administration programs report higher rates of antibiotic resistance among treatment arms in targeted groups. This study aimed to understand the risk of spillover of antibiotic resistance to nontarget groups in these programs., Methods: Data were used from a cluster-randomized trial comparing the effects of biannual azithromycin and placebo distribution to children 1-59 months old on child mortality rates. Nasopharyngeal samples from untreated children 7-12 years old were tested for genetic determinants of macrolide resistance (primary outcome) and resistance to other antibiotic classes (secondary outcomes). Linear regression was used to compare the community-level mean difference in prevalence by arm at the 24-month time point, adjusting for baseline prevalence., Results: A total of 1103 children 7-12 years old in 30 communities were included in the analysis (15 azithromycin, 15 placebo). The adjusted mean differences in the prevalence of resistance determinants for macrolides, β-lactams, and tetracyclines were 3.4% (95% confidence interval, -4.1% to 10.8%; P = .37), -1.2% (-7.9% to 5.5%; P = .72), and -3.3% (-9.5% to 2.8%; P = .61), respectively., Conclusions: We were unable to demonstrate a statistically significant increase in macrolide resistance determinants in untreated groups in an azithromycin mass drug administration program. While the result might be consistent with a small spillover effect, this study was not powered to detect such a small difference. Larger studies are warranted to better quantify the potential for spillover effects within these programs., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Children with acute malnutrition are at high risk of morality. Mass azithromycin distribution reduces all-cause mortality among children aged 1-59 months, and effects may be greater in underweight infants. Here, we evaluate the efficacy of azithromycin for reducing all-cause mortality in children aged 6-59 months with acute malnutrition (mid-upper arm circumference, MUAC, < 12.5 cm). Communities in Nouna District, Burkina Faso were 1:1 randomized to biannual mass distribution of single dose azithromycin or placebo to all children aged 1-59 months. Mortality was assessed during each census and treatment round. MUAC measurements were collected for all children. We evaluated the effect of azithromycin on mortality in subgroups of children aged 6-59 months defined by acute malnutrition (MUAC < 12.5 cm versus MUAC ≥ 12.5 cm). In children with MUAC < 12.5 cm, mortality rates were 51% lower among those living in azithromycin communities compared to placebo (incidence rate ratio 0.49, 95% confidence interval, CI, 0.25 to 0.99; incidence rate difference -18.1 deaths per 1,000 person-years, 95% CI -37.0 to -0.01), which was greater than the reduction in mortality among children with MUAC ≥ 12.5 cm (P-value for interaction on the relative scale = 0.09; P-value for interaction of the additive scale = 0.03). Children with acute malnutrition may benefit from single dose azithromycin above and beyond those without acute malnutrition. Trial registration: ClinicalTrials.gov NCT03676764; https://clinicaltrials.gov/study/NCT03676764., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sié 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.)

Mozambique is making progress towards elimination of trachoma as a public health problem, but in some districts trachomatous inflammation-follicular (TF) prevalence remains above the 5% elimination threshold despite years of various interventions, including antibiotic mass drug administration. To characterize transmission in four districts, we incorporated testing of ocular infection and serology into routine trachoma impact surveys (TIS) in August 2022. We examined residents aged ≥ 1 year for trachoma and collected information on household water, sanitation, and hygiene. Among children aged 1-9 years, we tested conjunctival swabs for Chlamydia trachomatis nucleic acid and dried blood spots for C. trachomatis antibodies. We modeled age-dependent seroprevalence to estimate seroconversion rate (SCR). We examined 4841 children aged 1-9 years. TF prevalence ranged between 1.1 and 6.0% with three districts below the 5% threshold. PCR-confirmed infection prevalence ranged between 1.1 and 4.8%, and Pgp3 seroprevalence ranged between 8.8 and 24.3%. Pgp3 SCR was 1.9 per 100 children per year in the district with the lowest TF prevalence. Two other districts with TF < 5% had SCR of 5.0 and 4.7. The district with TF ≥ 5% had a SCR of 6.0. This enhanced TIS furthered understanding of transmission in these districts and provides information on additional indicators for monitoring trachoma programs., (© 2024. The Author(s).)

Purpose: The diagnosis and management of dry eye disease (DED) could be complicated by the discordance between DED-related symptoms and signs. We performed a cross-sectional study to investigate the factors of and develop predictive models for the discrepancy in DED symptomatology., Methods: We used data from 3455 participants, 21 to 89 years old, from the Sjögren's International Collaborative Clinical Alliance study. We performed a multivariable stepwise linear regression model with backward elimination and Bayesian information criteria to select predictors for the discordance in DES symptomatology, which was defined as the difference between the rank score of Ocular Surface Disease Index 6 (OSDI-6) and the rank score of ocular staining score (OSS)., Results: Ten predictors, such as "vitality," "immunomodulating drugs," sensory symptoms," and "ethnicity," remained in the final models, achieving an adjusted R2 (aR2) of 0.35 (95% confidence interval [CI], 0.32-0.39). Specifically, medication use explained 19% (95% CI, 0.17-0.22) of the variance in the outcome, followed by medical history (aR2 = 0.18; 95% CI, 0.15-0.21). Health-related quality of life contributed 16% to the variance in the outcome (95% CI, 0.13-0.19), and, last, demographics contributed 11% (95% CI, 0.09-0.13)., Conclusions: Our results suggest that individuals of Asian descent and those using immunomodulating medications often present with severe ocular signs that necessitate regular ophthalmological evaluations, even in the absence of proportionate ocular symptoms. Additionally, ocular symptoms, when accompanied by abnormal sensations in other parts of the body, could indicate systemic conditions that require further investigation and medical care.

Introduction: It remains uncertain whether Descemet membrane endothelial keratoplasty (DMEK) or Descemet stripping only (DSO) yields better outcomes in patients with symptomatic Fuchs endothelial corneal dystrophy (FECD). This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial II (DETECT II), a multicentre, outcome-masked, randomised, placebo-controlled, clinical trial comparing DMEK to DSO with ripasudil (DSO-R) for this patient population., Methods and Analysis: A total of 60 patients with endothelial dysfunction due to symptomatic FECD will be enrolled from seven participating sites in the USA. The patients will be randomly assigned in a 1:1 ratio to one of the following treatment groups: group 1-DMEK plus topical placebo and group 2-DSO plus topical ripasudil 0.4%. The enrolment period is 24 months. The primary outcome is best spectacle-corrected visual acuity at 12 months. Secondary outcomes include peripheral and central endothelial cell density, visual acuity, vision-related quality of life and Pentacam Scheimpflug tomography. Study outcomes will be analysed using mixed effects linear regression. Adverse events, including rebubble procedures, endothelial failure and graft rejection, will be documented and analysed using appropriate statistical methods. DETECT II aims to provide evidence on the comparative effectiveness of DMEK and DSO-R. The results of this trial will contribute to optimising the treatment of FECD, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation., Ethics and Dissemination: A data and safety monitoring committee has been empanelled by the National Eye Institute. All study protocols will be subject to review and approval by WCG IRB as the single IRB of record. This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request., Trial Registration Number: NCT05275972., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Purpose: The purpose of this study was to identify conjunctival transcriptome differences in patients with Acanthamoeba keratitis compared with keratitis with no known associated pathogen., Methods: The host conjunctival transcriptome of 9 patients with Acanthamoeba keratitis (AK) is compared with the host conjunctival transcriptome of 13 patients with pathogen-free keratitis. Culture and/or confocal confirmed Acanthamoeba in 8 of 9 participants with AK who underwent metagenomic RNA sequencing as the likely pathogen. Cultures were negative in all 13 cases where metagenomic RNA sequencing did not identify a pathogen., Results: Transcriptome analysis identified 36 genes differently expressed between patients with AK and patients with presumed sterile, or pathogen-free, keratitis. Gene enrichment analysis revealed that some of these genes participate in several biologic pathways important for cellular signaling, ion transport and homeostasis, glucose transport, and mitochondrial metabolism. Notable relatively differentially expressed genes with potential relevance to Acanthamoeba infection included CPS1 , SLC35B4 , STEAP2 , ATP2B2 , NMNAT3 , and AKAP12 ., Conclusions: This research suggests that the local transcriptome in Acanthamoeba keratitis may be sufficiently robust to be detected in the conjunctiva and that corneas infected with Acanthamoeba may be distinguished from the inflamed cornea where no pathogen was identified. Given the low sensitivity for corneal cultures, identification of differentially expressed genes may serve as a suggestive transcriptional signature allowing for a complementary diagnostic technique to identify this blinding parasite. Knowledge of differentially expressed genes may also direct investigation of disease pathophysiology and suggest novel pathways for therapeutic targets., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Although community randomized trials have found a reduction in all-cause child mortality in communities receiving mass azithromycin distribution compared with placebo, individually randomized trials have not found similar protective effects. If a direct effect of azithromycin for prevention of child mortality exists, it is likely due to reduction in infectious mortality. Here, we assessed cause-specific mortality in a large randomized controlled trial of azithromycin administered during well-infant visits in Burkina Faso for prevention of mortality. Among 32,877 enrolled infants, the most common causes of death by 6 months of age were malaria, acute respiratory infections, and diarrheal disease. We found no evidence of a difference in the distribution of cause of death by randomized treatment assignment (P = 0.42) or in any infectious-specific cause of death. The results of this analysis are consistent with no direct effect of azithromycin on infant mortality when administered during well-infant visits.

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.)

Importance: Infectious conjunctivitis can lead to corneal involvement and result in ocular morbidity. The identification of biomarkers associated with corneal involvement has the potential to improve patient care., Objective: To identify biomarkers in patients with acute infectious conjunctivitis., Design, Setting, and Participants: This cross-sectional study took place from December 2016 to March 2024. Analyses were performed in 3 phases. First, logistic regression and machine learning algorithms were used to predict the probability of demonstrating corneal involvement in patients with presumed infectious conjunctivitis. Second, quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to confirm the most important biomarker gene identified by the algorithm. Third, the biomarker gene was validated in prospectively collected conjunctival samples of adult patients from 3 outpatient centers in Thailand and 1 in India. Patients with signs and symptoms of infectious conjunctivitis and onset within less than 14 days were eligible. Exclusion criteria were the inability to consent, presumed toxicity, or allergic conjunctivitis., Exposures: Acute infectious conjunctivitis., Main Outcomes and Measures: The identification and validation of ocular surface gene expression associated with corneal findings on slitlamp examination., Results: Thirteen genes exhibited a 1.5-log2 fold change in expression in patients with corneal involvement compared to patients without corneal involvement. Using the 13 genes to train and cross validate, logistic regression produced the highest mean area under the receiver operating characteristic curve (AUROC; 0.85; 95% CI, 0.84-0.86) for corneal involvement. The removal of apolipoprotein E (APOE) from the gene ensemble led to a decline in predictive performance of the logistic regression classifier (from mean AUROC 0.85 [95% CI, 0.84-0.86] to 0.74 [95% CI, 0.73-0.75]; adjusted P = .001 [Tukey test]). Orthogonal testing of APOE expression level with RT-qPCR showed that APOE expression was higher in patients with corneal involvement compared to patients without (median [IQR], 0.23 [0.04-0.47] vs 0.04 [0.02-0.06]; P = .004 [Mann-Whitney U test]). Using a Youden index of 0.23 Δ threshold cycle, APOE had a sensitivity of 56% (95% CI, 33-77) and a specificity of 88% (95% CI, 79-93) in 106 samples with conjunctivitis at Aravind, India (P < .001 [Fisher exact test]). When applied to a different patient population in Thailand, the same criteria could discriminate between disease states (58 samples; sensitivity, 47%; 95% CI, 30-64 and specificity, 93%; 95% CI, 77-99; P = .001 [Fisher exact test])., Conclusions and Relevance: The results from this study suggest that the host conjunctival immune response can be meaningfully interrogated to identify biomarkers for ocular surface diseases.

Objectives: To determine the associated pathogen during the 2023 conjunctivitis outbreak in Vietnam METHODS: RNA-sequencing was used to identify pathogens before and during the outbreak., Results: 24 patients with infectious conjunctivitis between March and October 2023 from Hai Yen Vision Institute in Vietnam were swabbed. Coxsackievirus A24v was the most common pathogen identified. Phylogenetic analysis of these strains demonstrates similarities to the Coxsackievirus identified in the 2022 India outbreak. Human adenovirus D was also circulating. Ocular findings of tearing, purulence, and itching were common in this outbreak., Conclusions: Multiple viruses can co-circulate during conjunctivitis outbreaks. Hemorrhagic conjunctivitis, commonly associated with coxsackievirus conjunctivitis, was not a common clinical sign in this outbreak. Repeat genetic surveillance, with the notable inclusion of RNA virus detection strategies, is important for outbreak detection., Competing Interests: Declarations of competing interest The authors have no relevant financial or non-financial competing interests to report., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The Steroids and Cross-linking for Ulcer Treatment Trial is an NIH-funded international, randomized, double-masked, sham and placebo-controlled clinical trial to determine the benefit of adjunctive corneal cross-linking with riboflavin and/or topical difluprednate in addition to topical antibiotic drops for treatment of smear-positive bacterial ulcers. The purpose of this study was to explore the baseline characteristics for infection of patients enrolled, and the ocular comorbidities of patients screened for inclusion., Methods: Of the 2005 patients with smear-positive bacterial ulcers screened, 280 patients were enrolled. Descriptive statistics were used to summarize and characterize the data., Results: Eligible patients in India had baseline factors associated with agricultural work (N = 132; 47%) and manual labor (N = 54; 19%), whereas patients in the United States were associated with contact lens wear (N = 11; 69%) (P <0.001). Nearly, 10% of patients with unilateral infectious keratitis are at risk of bilateral blindness because of preexisting visual disability in their other eye and thus ineligible for inclusion. India had higher rates of exclusionary factors for blindness in the other eye such as cataract (N = 48; 27%) and glaucoma (N = 24; 13) compared with the United States (N = 0; 0%) (P <0.001)., Conclusions: While corneal ulceration is an important cause of disability in technologically advanced countries, it occurs more frequently in low and middle-income countries, and the implications on these populations should be considered. These baseline factors can be evaluated to address such health care disparities., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Infectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro rose bengal photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates (Atalay HT et al., Curr Eye Res 43:1322-5, 2018, Arboleda A et al. Am J Ophthalmol 158:64-70, 2014). In one published series, RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthamoeba keratitis not responsive to medical therapy., Methods: This international, randomized, sham and placebo controlled 2-arm clinical trial randomizes patients with smear positive fungal and acanthamoeba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) topical antimicrobial plus sham RB-PDT or 2) topical antimicrobial plus RB-PDT., Discussion: We anticipate that RB-PDT will improve best spectacle-corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via ClinicalTrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request., Trial Registration: NCT, NCT05110001 , Registered on November 5, 2021., (© 2024. The Author(s).)

Background: Twice-yearly mass distribution of azithromycin to children is a promising intervention to reduce childhood mortality in sub-Saharan Africa. The World Health Organization recommended restricting distribution to infants 1 to 11 months of age to mitigate antimicrobial resistance, although this more limited treatment had not yet been tested., Methods: We randomly assigned rural communities in Niger to four twice-yearly distributions of azithromycin for children 1 to 59 months of age (child azithromycin group), four twice-yearly distributions of azithromycin for infants 1 to 11 months of age and placebo for children 12 to 59 months of age (infant azithromycin group), or placebo for children 1 to 59 months of age. Census workers who were not aware of the group assignments monitored mortality twice yearly over the course of 2 years. We assessed three primary community-level mortality outcomes (deaths per 1000 person-years), each examining a different age group and pairwise group comparison., Results: A total of 1273 communities were randomly assigned to the child azithromycin group (1229 were included in the analysis), 773 to the infant azithromycin group (751 included in the analysis), and 954 to the placebo group (929 included in the analysis). Among 382,586 children, 419,440 person-years and 5503 deaths were recorded. Lower mortality among children 1 to 59 months of age was observed in the child azithromycin group (11.9 deaths per 1000 person-years; 95% confidence interval [CI], 11.3 to 12.6) than in the placebo group (13.9 deaths per 1000 person-years; 95% CI, 13.0 to 14.8) (representing 14% lower mortality with azithromycin; 95% CI, 7 to 22; P<0.001). Mortality among infants 1 to 11 months of age was not significantly lower in the infant azithromycin group (22.3 deaths per 1000 person-years; 95% CI, 20.0 to 24.7) than in the placebo group (23.9 deaths per 1000 person-years; 95% CI, 21.6 to 26.2) (representing 6% lower mortality with azithromycin; 95% CI, -8 to 19). Five serious adverse events were reported: three in the placebo group, one in the infant azithromycin group, and one in the child azithromycin group., Conclusions: Azithromycin distributions to children 1 to 59 months of age significantly reduced mortality and was more effective than treatment of infants 1 to 11 months of age. Antimicrobial resistance must be monitored. (Funded by the Bill and Melinda Gates Foundation; AVENIR ClinicalTrials.gov number, NCT04224987.)., (Copyright © 2024 Massachusetts Medical Society.)

Purpose: To identify weather variables associated with pathogens contributing to infectious conjunctivitis globally., Methods: Sample collection and pathogen identification from patients with acute infectious conjunctivitis was performed from 2017 to 2023. We linked pathogens identified from 13 sites across 8 countries with publicly available weather data by geographic coordinates. Mixed effects logistic regression analysis was performed to estimate the associations between temperature, precipitation, and relative humidity exposures, and the prevalence of infection types (RNA virus, DNA virus, bacteria, and fungus)., Results: 498 cases from the United States, India, Nepal, Thailand, Burkina Faso, Niger, Vietnam, and Israel were included in the analysis. 8-day average precipitation (mm) was associated with increased odds of RNA virus infection (odds ratio (OR)=1.47, 95% confidence interval (CI): 1.12 to 1.93, P=0.01) and decreased odds of DNA infection (OR=0.62, 95% CI: 0.46 to 0.82, P<0.001). Relative humidity (%) was associated with increased odds of RNA virus infections (OR=2.64, 95% CI: 1.51 to 4.61, P<0.001), and fungal infections (OR=2.35, 95% CI: 1.19 to 4.66, P=0.01), but decreased odds of DNA virus (OR=0.58, 95%CI: 0.37 to 0.90, P=0.02) and bacterial infections (OR=0.42, 95% CI: 0.25 to 0.71, P<0.001). Temperature (°C) was not associated with ocular infections for any pathogen type., Conclusions: This study suggests that weather factors affect pathogens differently. Particularly, humidity and precipitation were predictors for pathogens contributing to conjunctivitis worldwide. Additional work is needed to clarify the effects of shifts in weather and environmental factors on ocular infectious diseases., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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.)

Single-dose azithromycin is being considered by the WHO as an intervention for prevention of child mortality. However, concerns have emerged related to longer term unintended consequences of early life antibiotic use, particularly among infants. We conducted a long-term follow-up in a random sample of children who had been enrolled in a trial of neonatal azithromycin versus placebo for prevention of mortality to assess whether neonatal azithromycin exposure led to differences in child growth up to 4 years of age. We found no evidence of a difference in any anthropometric outcome among children who had received a single oral dose of azithromycin compared with placebo during the neonatal period. These results do not support long-term growth-promoting or deleterious effects of early life azithromycin exposure.

Infectious keratitis is a leading cause of corneal blindness worldwide with little information known about causative etiologies in Malawi, Africa. This area is resource-limited with ophthalmologist and microbiology services. The Department of Ophthalmology at the Kamuzu College of Health Sciences in Blantyre, Malawi, is a participating site of an international corneal ulcer consortium, capriCORN (Comprehensive Analysis of Pathogens, Resistomes, and Inflammatory-markers in the CORNea). In this study, 50 patients with corneal ulcers were swabbed for pathogen identification using RNA-sequencing. Corneal trauma was reported in 41% and 19% of the patients worked in agriculture. A pathogen was identified in 58% of the cases. Fungal pathogens predominated, followed by viruses and bacteria. Aspergillus, Fusarium, HSV-1, and Gardnerella were the most common pathogens detected. 50% of patients reported treatment with an antibiotic before presentation. Pathogens unusual for infectious keratitis, such as Subramaniula asteroids, Aureobasidium pullulans, and Gardnerella vaginalis, were also detected.

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.)

Background: Infectious conjunctivitis is common in Nepal., Materials and Methods: This prospective study recruited 60 patients with presumed acute infectious conjunctivitis from the B.P. Koirala Lions Center for Ophthalmic Studies in Kathmandu, Nepal. Swabs from the conjunctiva and anterior nares were processed for metagenomic RNA deep sequencing (RNA-seq)., Results: Pathogens were identified in 55% of cases. RNA viruses were the most common pathogen class identified. Severe acute respiratory syndrome coronavirus 2 was the most common RNA virus identified., Conclusions: Acute infectious conjunctivitis varies by location. Contrary to expectations, RNA viruses predominated. Repeat surveillance may be useful and RNA-seq allows for detection of the unexpected pathogen including RNA viruses., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Randomized controlled trials found that twice-yearly mass azithromycin administration (MDA) reduces childhood mortality, presumably by reducing infection burden. World Health Organization (WHO) issued conditional guidelines for mass azithromycin administration in high-mortality settings in sub-Saharan Africa given concerns for antibiotic resistance. While prolonged twice-yearly MDA has been shown to increase antibiotic resistance in small randomized controlled trials, the objective of this study was to determine if macrolide and non-macrolide resistance in the gut increases with the duration of azithromycin MDA in a larger setting., Methods and Findings: The Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study was conducted in Niger from December 2014 to June 2020. It was a cluster-randomized trial of azithromycin (A) versus placebo (P) aimed at evaluating childhood mortality. This is a sub-study in the MORDOR trial to track changes in antibiotic resistance after prolonged azithromycin MDA. A total of 594 communities were eligible. Children 1 to 59 months in 163 randomly chosen communities were eligible to receive treatment and included in resistance monitoring. Participants, staff, and investigators were masked to treatment allocation. At the conclusion of MORDOR Phase I, by design, all communities received an additional year of twice-yearly azithromycin treatments (Phase II). Thus, at the conclusion of Phase II, the treatment history (1 letter per 6-month period) for the participating communities was either (PP-PP-AA) or (AA-AA-AA). In Phase III, participating communities were then re-randomized to receive either another 3 rounds of azithromycin or placebo, thus resulting in 4 treatment histories: Group 1 (AA-AA-AA-AA-A, N = 51), Group 2 (PP-PP-AA-AA-A, N = 40), Group 3 (AA-AA-AA-PP-P, N = 27), and Group 4 (PP-PP-AA-PP-P, N = 32). Rectal swabs from each child (N = 5,340) were obtained 6 months after the last treatment. Each child contributed 1 rectal swab and these were pooled at the community level, processed for DNA-seq, and analyzed for genetic resistance determinants. The primary prespecified outcome was macrolide resistance determinants in the gut. Secondary outcomes were resistance to beta-lactams and other antibiotic classes. Communities recently randomized to azithromycin (groups 1 and 2) had significantly more macrolide resistance determinants than those recently randomized to placebo (groups 3 and 4) (fold change 2.18, 95% CI 1.5 to 3.51, Punadj < 0.001). However, there was no significant increase in macrolide resistance in communities treated 4.5 years (group 1) compared to just the most recent 2.5 years (group 2) (fold change 0.80, 95% CI 0.50 to 1.00, Padj = 0.010), or between communities that had been treated for 3 years in the past (group 3) versus just 1 year in the past (group 4) (fold change 1.00, 95% CI 0.78 to 2.35, Padj = 0.52). We also found no significant differences for beta-lactams or other antibiotic classes. The main limitations of our study were the absence of phenotypic characterization of resistance, no complete placebo arm, and no monitoring outside of Niger limiting generalizability., Conclusions: In this study, we observed that mass azithromycin distribution for childhood mortality among preschool children in Niger increased macrolide resistance determinants in the gut but that resistance may plateau after 2 to 3 years of treatment. Co-selection to other classes needs to be monitored., Trial Registration: NCT02047981 https://classic.clinicaltrials.gov/ct2/show/NCT02047981., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Arzika 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.)

Assessing the feasibility of 2030 as a target date for global elimination of trachoma, and identification of districts that may require enhanced treatment to meet World Health Organization (WHO) elimination criteria by this date are key challenges in operational planning for trachoma programmes. Here we address these challenges by prospectively evaluating forecasting models of trachomatous inflammation-follicular (TF) prevalence, leveraging ensemble-based approaches. Seven candidate probabilistic models were developed to forecast district-wise TF prevalence in 11 760 districts, trained using district-level data on the population prevalence of TF in children aged 1-9 years from 2004 to 2022. Geographical location, history of mass drug administration treatment, and previously measured prevalence data were included in these models as key predictors. The best-performing models were included in an ensemble, using weights derived from their relative likelihood scores. To incorporate the inherent stochasticity of disease transmission and challenges of population-level surveillance, we forecasted probability distributions for the TF prevalence in each geographic district, rather than predicting a single value. Based on our probabilistic forecasts, 1.46% (95% confidence interval [CI]: 1.43-1.48%) of all districts in trachoma-endemic countries, equivalent to 172 districts, will exceed the 5% TF control threshold in 2030 with the current interventions. Global elimination of trachoma as a public health problem by 2030 may require enhanced intervention and/or surveillance of high-risk districts., Competing Interests: Potential conflicts of interest. A. V. reports funding for this supplement provided by the BMGF via INV-030046 to the NTD Modelling Consortium, funding for this supplement provided by the Li Ka Shing Foundation via Professor Hollingsworth research funding, and funding for this project provided by Children's Investment Foundation (CIFF) Accelerate Trachoma Elimination funding. T. D. H. reports that the study was funded by the Bill & Melinda Gates Foundation via grant number INV-030046 to the NTD Modelling Consortium: Informing program decision-making. T. P. reports funding from the NEI, NIH (NIH NEI grant number R01EY025350) and funding from CIFF and the Bill & Melinda Gates Foundation (grant number INV-030046). T. L. reports funding from the NEI and NIH (grant number R01EY025350) and funding from CIFF and the Bill & Melinda Gates Foundation (grant number INV-030046). S. B. is also supported by the National Institute of General Medical Sciences [NIH NIGMS R35GM147702] and the National Eye Institute [NIH NEI K12 EY031372] at the NIH. P. J. H. reports salary and travel support from Pfizer, Inc., through a grant to The Task Force for Global Health and a donation of the antibiotic azithromycin from Pfizer through The Task Force for Global Health for global trachoma elimination purposes. K. K. R. reports being an employee of the International Trachoma Initiative, a program of The Task Force for Global Health, which receives an operating budget and research funds from Pfizer Inc, the manufacturers of Zithromax (azithromycin). B. F. A. reports funding to their institution from NIH National Institute of Allergy and Infectious Diseases (NIAID), payments to cover airfare and hotel to attend scientific meetings in Baltimore and Atlanta from the Bill & Melinda Gates Foundation, and honoraria payments for serving on a trial DSMB from the NIH. All other authors report no potential 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) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Most evidence supporting screening for undernutrition is for children aged 6-59 months. However, the highest risk of mortality and highest incidence of wasting occurs in the first 6 months of life. We evaluated relationships between neonatal anthropometric indicators, including birth weight, weight-for-age Z -score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z -score (LAZ) and mid-upper arm circumference (MUAC) and mortality and growth at 6 months of age among infants in Burkina Faso., Design: Data arose from a randomised controlled trial evaluating neonatal azithromycin administration for the prevention of child mortality. We evaluated relationships between baseline anthropometric measures and mortality, wasting (WLZ < -2), stunting (LAZ < -2) and underweight (WAZ < -2) at 6 months of age were estimated using logistic regression models adjusted for the child's age and sex., Setting: Five regions of Burkina Faso., Participants: Infants aged 8-27 d followed until 6 months of age., Results: Of 21 832 infants enrolled in the trial, 7·9 % were low birth weight (<2500 g), 13·3 % were wasted, 7·7 % were stunted and 7·4 % were underweight at enrolment. All anthropometric deficits were associated with mortality by 6 months of age, with WAZ the strongest predictor (WAZ < -2 to ≥ -3 at enrolment v . WAZ ≥ -2: adjusted OR, 3·91, 95 % CI, 2·21, 6·56). Low WAZ was also associated with wasting, stunting, and underweight at 6 months., Conclusions: Interventions for identifying infants at highest risk of mortality and growth failure should consider WAZ as part of their screening protocol.

Purpose: This study sought to identify the sources of differential performance and misclassification error among local (Indian) and external (non-Indian) corneal specialists in identifying bacterial and fungal keratitis based on corneal photography., Methods: This study is a secondary analysis of survey data assessing the ability of corneal specialists to identify acute bacterial versus fungal keratitis by using corneal photography. One-hundred images of 100 eyes from 100 patients with acute bacterial or fungal keratitis in South India were previously presented to an international cohort of cornea specialists for interpretation over the span of April to July 2021. Each expert provided a predicted probability that the ulcer was either bacterial or fungal. Using these data, we performed multivariable linear regression to identify factors predictive of expert performance, accounting for primary practice location and surrogate measures to infer local fungal ulcer prevalence, including locality, latitude, and dew point. In addition, Brier score decomposition was used to determine experts' reliability ("calibration") and resolution ("boldness") and were compared between local (Indian) and external (non-Indian) experts., Results: Sixty-six experts from 16 countries participated. Indian practice location was the only independently significant predictor of performance in multivariable linear regression. Resolution among Indian experts was significantly better (0.08) than among non-Indian experts (0.01; P < 0.001), indicating greater confidence in their predictions. There was no significant difference in reliability between the two groups ( P = 0.40)., Conclusion: Local cornea experts outperformed their international counterparts independent of regional variability in tropical risk factors for fungal keratitis. This may be explained by regional characteristics of infectious ulcers with which local corneal specialists are familiar., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Background: South Asia is experiencing rapid urbanization, which may be changing the risk factor profile for ocular trauma. The objective of this study was to compare risk factors for traumatic corneal abrasions in rural versus urban Nepal, and to assess if any risk factors were associated with a poor outcome., Methods: In a prospective, cross-sectional, community-based study performed as part of a cluster-randomized trial, community health workers from Nepal were trained to diagnose and treat traumatic corneal abrasions. Participants with an abrasion were invited to complete a risk factor survey. The main exposure variable was the object of eye injury, stratified by rural-urban residence. The main outcome measure was a lack of corneal healing after a three-day course of antimicrobials., Results: Of 3657 participants diagnosed with a corneal abrasion, 2265 completed a survey. Eye trauma occurred most frequently during agricultural activities. The most common object of injury was vegetative matter, accounting for approximately 40% of injuries in rural, peri-urban, and urban communities. Wood injuries were more common in rural communities (24%) compared with urban or peri-urban communities (13%). Eye injury from an animal was more likely to result in a non-healing corneal abrasion after 3 days of treatment compared with other types of trauma (prevalence ratio 2.59, 95%CI 1.16-5.76)., Conclusions: Health promotion activities for prevention of corneal ulcers in Nepal should focus on agricultural trauma in both rural and urban areas. Community members experiencing eye trauma from an animal may benefit from early referral to an eye clinic., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Millions of doses of azithromycin are distributed each year for trachoma, yet the treatment efficacy of a single dose of azithromycin for ocular Chlamydia infection has not been well characterized. In this study, four villages in Niger received a mass azithromycin distribution for trachoma. All 426 children aged 0-5 years residing in the study villages were offered conjunctival swabbing every 6 months to test for ocular Chlamydia trachomatis. Among the children infected with ocular Chlamydia before treatment, 6% (95% CI: 2-15%) tested positive for ocular Chlamydia infection 6 months later, and 15% (95% CI: 7-28%) tested positive 12 months later. The most important predictor of post-treatment ocular Chlamydia infection was pretreatment ocular Chlamydia infection (relative risk: 3.5, 95% CI: 1.3-9.4). Although the 6-monthly monitoring schedule was suboptimal for testing the treatment efficacy of an antibiotic, these findings are nonetheless consistent with high treatment efficacy of a single dose of azithromycin and suggest that additional interventions might be most effective if targeted to those children infected prior to treatment.

Purpose: This study aims to explore the potential subgroups of sarcoidosis-associated uveitis (SAU) within a multicenter cohort of uveitis participants., Design: Cross-sectional study., Participants: A cohort of 826 uveitis patients from a uveitis registry from 19 clinical centers in 12 countries between January 2011 and April 2015., Methods: We employed a latent class analysis (LCA) incorporating recommended tests and clinical signs from the revised International Workshop on Ocular Sarcoidosis (IWOS) to identify potential SAU subgroups within the multicenter uveitis cohort. Additionally, we assessed the performance of the individual tests and clinical signs in classifying the potential subclasses., Main Outcome Measures: Latent subtypes of SAU., Results: Among 826 participants included in this analysis, the 2-class LCA model provided a best fit, with the lowest Bayesian information criteria of 7218.7 and an entropy of 0.715. One class, consisting of 548 participants, represented the non-SAU, whereas the second class, comprised of 278 participants, was most representative of SAU. Snowballs/string of pearls vitreous opacities had the best test performance for classification, followed by bilaterality and bilateral hilar lymphadenopathy (BHL). The combination of 4 tests with the highest classification importance, including snowballs/string of pearls vitreous opacities, periphlebitis and/or macroaneurysm, bilaterality, and BHL, demonstrated a sensitivity of 84.8% and a specificity of 95.4% in classifying the SAU subtypes. In the exploratory analysis of the 3-class LCA model, which had comparable fit indices as the 2-class model, we identified a candidate non-SAU subtype, candidate SAU subtype with pulmonary involvement, and a candidate SAU with less pulmonary involvement., Conclusions: Latent class modeling, incorporating tests and clinical signs from the revised IWOS criteria, effectively identified a subset of participants with clinical features indicative of SAU. Though the sensitivity of individual ocular signs or tests was not perfect, using a combination of tests provided a satisfactory performance in classifying the SAU subclasses identified by the 2-class LCA model. Notably, the classes identified by the 3-class LCA model, including a non-SAU subtype, an SAU subtype with pulmonary involvement, and an SAU subtype with less pulmonary involvement, may have potential implication for clinical practice, and hence should be validated in further research., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Background: Previous work suggests that Google searches could be useful in identifying conjunctivitis epidemics. Content-based assessment of social media content may provide additional value in serving as early indicators of conjunctivitis and other systemic infectious diseases., Objective: We investigated whether large language models, specifically GPT-3.5 and GPT-4 (OpenAI), can provide probabilistic assessments of whether social media posts about conjunctivitis could indicate a regional outbreak., Methods: A total of 12,194 conjunctivitis-related tweets were obtained using a targeted Boolean search in multiple languages from India, Guam (United States), Martinique (France), the Philippines, American Samoa (United States), Fiji, Costa Rica, Haiti, and the Bahamas, covering the time frame from January 1, 2012, to March 13, 2023. By providing these tweets via prompts to GPT-3.5 and GPT-4, we obtained probabilistic assessments that were validated by 2 human raters. We then calculated Pearson correlations of these time series with tweet volume and the occurrence of known outbreaks in these 9 locations, with time series bootstrap used to compute CIs., Results: Probabilistic assessments derived from GPT-3.5 showed correlations of 0.60 (95% CI 0.47-0.70) and 0.53 (95% CI 0.40-0.65) with the 2 human raters, with higher results for GPT-4. The weekly averages of GPT-3.5 probabilities showed substantial correlations with weekly tweet volume for 44% (4/9) of the countries, with correlations ranging from 0.10 (95% CI 0.0-0.29) to 0.53 (95% CI 0.39-0.89), with larger correlations for GPT-4. More modest correlations were found for correlation with known epidemics, with substantial correlation only in American Samoa (0.40, 95% CI 0.16-0.81)., Conclusions: These findings suggest that GPT prompting can efficiently assess the content of social media posts and indicate possible disease outbreaks to a degree of accuracy comparable to that of humans. Furthermore, we found that automated content analysis of tweets is related to tweet volume for conjunctivitis-related posts in some locations and to the occurrence of actual epidemics. Future work may improve the sensitivity and specificity of these methods for disease outbreak detection., (©Michael S Deiner, Natalie A Deiner, Vagelis Hristidis, Stephen D McLeod, Thuy Doan, Thomas M Lietman, Travis C Porco. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 01.03.2024.)

Purpose: To assess the diagnostic accuracy of anterior segment OCT (AS-OCT) screening for detecting gonioscopically narrow angles., Design: Population-based cross-sectional study., Participants: A stratified random sample of individuals aged ≥ 60 years, selected from a door-to-door census performed in low-lying Nepal., Testing: Participants underwent AS-OCT, posterior segment OCT, and intraocular pressure (IOP) testing in the community. Those meeting referral criteria in either eye were invited to have a comprehensive eye examination including gonioscopy. Referral criteria included (i) the lowest 2.5% of AS-OCT measurements, (ii) retinal OCT results suggestive of glaucomatous optic neuropathy, diabetic retinopathy, or age-related macular degeneration, and (iii) elevated IOP., Main Outcome Measures: Sensitivity and specificity of 5 semiautomated AS-OCT parameters relative to gonioscopically narrow angles, defined as the absence of visible trabecular meshwork for ≥ 180° on nonindentation gonioscopy., Results: Of 17 656 people aged ≥ 60 years enumerated from 102 communities, 12 633 (71.6%) presented for AS-OCT testing. Referral was recommended for 697 participants based on AS-OCT criteria and 2419 participants based on other criteria, of which 858 had gonioscopy performed by a glaucoma specialist. Each of the 5 AS-OCT parameters offered good diagnostic information for predicting eyes with gonioscopically narrow angles, with areas under the receiver operating characteristic curve ranging from 0.85 to 0.89. The angle opening distance at 750 μm from the scleral spur (AOD750) provided the most diagnostic information, providing an optimal sensitivity of 87% (95% confidence interval [CI], 75%-96%) and specificity of 77% (71%-83%) at a cutpoint of 367 μm, and a sensitivity of 65% (95% CI, 54%-74%) when specificity was constrained to 90% (cutpoint, 283 μm)., Conclusions: On AS-OCT, the AOD750 parameter detected approximately two-thirds of cases of gonioscopically narrow angles when test specificity was set to 90%. Although such a sensitivity may not be sufficient when screening solely for narrow angles, AS-OCT requires little additional effort if posterior segment OCT is already being performed and thus could provide incremental benefit when performing OCT-based screening., Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions., Objective: To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention., Design, Setting, and Participants: This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities., Interventions: Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023., Main Outcomes and Measures: The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census., Results: A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months., Conclusions and Relevance: Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference., Trial Registration: ClinicalTrials.gov Identifier: NCT03676764.

Purpose: The aim of this study was to validate the C-DU(KE) calculator as a predictor of treatment outcomes on a data set derived from patients with culture-positive ulcers., Methods: C-DU(KE) criteria were compiled from a data set consisting of 1063 cases of infectious keratitis from the Steroids for Corneal Ulcer Trial (SCUT) and Mycotic Ulcer Treatment Trial (MUTT) studies. These criteria include corticosteroid use after symptoms, visual acuity, ulcer area, fungal etiology, and elapsed time to organism-sensitive therapy. Univariate analysis was performed followed by multivariable logistic regressions on culture-exclusive and culture-inclusive models to assess for associations between the variables and outcome. The predictive probability of treatment failure, defined as the need for surgical intervention, was calculated for each study participant. Discrimination was assessed using the area under the curve for each model., Results: Overall, 17.9% of SCUT/MUTT participants required surgical intervention. Univariate analysis showed that decreased visual acuity, larger ulcer area, and fungal etiology had a significant association with failed medical management. The other 2 criteria did not. In the culture-exclusive model, 2 of 3 criteria, decreased vision [odds ratio (OR) = 3.13, P < 0.001] and increased ulcer area (OR = 1.03, P < 0.001), affected outcomes. In the culture-inclusive model, 3 of 5 criteria, decreased vision (OR = 4.9, P < 0.001), ulcer area (OR = 1.02, P < 0.001), and fungal etiology (OR = 9.8, P < 0.001), affected results. The area under the curves were 0.784 for the culture-exclusive model and 0.846 for the culture-inclusive model which were comparable to the original study., Conclusions: The C-DU(KE) calculator is generalizable to a study population from large international studies primarily taking place in India. These results support its use as a risk stratification tool assisting ophthalmologists in patient management., Competing Interests: V.L. Perez has financial relationships with Alcon, Dompe, EyeGate, Kala, Trefoil, Novartis, and Oculis. The remaining authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: It remains uncertain which endothelial keratoplasty (EK) technique yields the best outcomes while maintaining safety, particularly in eyes with coexisting ocular conditions. Moreover, the impact of endothelial cell loss (ECL) on long-term graft survival requires further investigation. Adjuvant ripasudil, a rho kinase inhibitor, may address the challenge of ECL in corneal transplantation. This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial 1 (DETECT 1), a multicentre, outcome-masked, randomised, placebo-controlled, four-arm clinical trial., Methods: A total of 160 eligible patients with endothelial dysfunction will be enrolled from five participating sites in the USA. The patients will be randomly assigned in a 2×2 factorial design to one of the following treatment groups: group 1-ultrathin Descemet stripping endothelial keratoplasty (UT-DSAEK) plus topical ripasudil 0.4%; group 2-UT-DSAEK plus topical placebo; group 3-Descemet membrane endothelial keratoplasty (DMEK) plus topical ripasudil 0.4% and group 4-DMEK plus topical placebo. Primary outcomes include the best spectacle-corrected visual acuity at 12 months and ECL at 12 months. Secondary outcomes include visual acuity at different time points, vision-related quality of life, endothelial cell morphology and cost-effectiveness., Results: The study outcomes will be analysed using mixed effects linear regression models, taking into account the treatment arms and relevant covariates. Adverse events, including rebubble procedures, graft failure and graft rejection, will be documented and analysed using appropriate statistical methods., Conclusion: DETECT I aims to provide evidence on the comparative effectiveness of UT-DSAEK and DMEK, as well as the potential benefits of adjuvant topical ripasudil in reducing ECL. The results of this trial will contribute to optimising corneal transplantation techniques and improving long-term graft survival, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation., Ethics and Dissemination: A data and safety monitoring committee (DSMC) has been empaneled by the NEI.All study protocols will be subject to review and approval by WCG IRB as the single IRB of record.This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Antibiotic use during early infancy has been linked to childhood obesity in high-income countries. We evaluated whether a single oral dose of azithromycin administered during infant-well visits led to changes in infant growth outcomes at 6 months of age in a setting with a high prevalence of undernutrition in rural Burkina Faso., Methods and Findings: Infants were enrolled from September 25, 2019, until October 22, 2022, in a randomized controlled trial designed to evaluate the efficacy of a single oral dose of azithromycin (20 mg/kg) compared to placebo when administered during well-child visits for prevention of infant mortality. The trial found no evidence of a difference in the primary endpoint. This paper presents prespecified secondary anthropometric endpoints including weight gain (g/day), height change (mm/day), weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ), and mid-upper arm circumference (MUAC). Infants were eligible for the trial if they were between 5 and 12 weeks of age, able to orally feed, and their families were planning to remain in the study area for the duration of the study. Anthropometric measurements were collected at enrollment (5 to 12 weeks of age) and 6 months of age. Among 32,877 infants enrolled in the trial, 27,298 (83%) were followed and had valid anthropometric measurements at 6 months of age. We found no evidence of a difference in weight gain (mean difference 0.03 g/day, 95% confidence interval (CI) -0.12 to 0.18), height change (mean difference 0.004 mm/day, 95% CI -0.05 to 0.06), WAZ (mean difference -0.004 SD, 95% CI -0.03 to 0.02), WLZ (mean difference 0.001 SD, 95% CI -0.03 to 0.03), LAZ (mean difference -0.005 SD, 95% CI -0.03 to 0.02), or MUAC (mean difference 0.01 cm, 95% CI -0.01 to 0.04). The primary limitation of the trial was that measurements were only collected at enrollment and 6 months of age, precluding assessment of shorter-term or long-term changes in growth., Conclusions: Single-dose azithromycin does not appear to affect weight and height outcomes when administered during early infancy., Trial Registration: ClinicalTrials.gov NCT03676764., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sié 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: Mass distribution of azithromycin to children 1 to 59 months of age has been shown to reduce childhood all-cause mortality in some sub-Saharan African regions, with the largest reduction seen among infants younger than 12 months of age. Whether the administration of azithromycin at routine health care visits for infants would be effective in preventing death is unclear., Methods: We conducted a randomized, placebo-controlled trial of a single dose of azithromycin (20 mg per kilogram of body weight) as compared with placebo, administered during infancy (5 to 12 weeks of age). The primary end point was death before 6 months of age. Infants were recruited at routine vaccination or other well-child visits in clinics and through community outreach in three regions of Burkina Faso. Vital status was assessed at 6 months of age., Results: Of the 32,877 infants enrolled from September 2019 through October 2022, a total of 16,416 infants were randomly assigned to azithromycin and 16,461 to placebo. Eighty-two infants in the azithromycin group and 75 infants in the placebo group died before 6 months of age (hazard ratio, 1.09; 95% confidence interval [CI], 0.80 to 1.49; P = 0.58); the absolute difference in mortality was 0.04 percentage points (95% CI, -0.10 to 0.21). There was no evidence of an effect of azithromycin on mortality in any of the prespecified subgroups, including subgroups defined according to age, sex, and baseline weight, and no evidence of a difference between the two trial groups in the incidence of adverse events., Conclusions: In this trial conducted in Burkina Faso, we found that administration of azithromycin to infants through the existing health care system did not prevent death. (Funded by the Bill and Melinda Gates Foundation; CHAT ClinicalTrials.gov number, NCT03676764.)., (Copyright © 2024 Massachusetts Medical Society.)

Mass antibiotic distribution to preschool children resulted in alterations of the gut microbiome months after distribution. This individually randomized, placebo-controlled trial evaluated changes in the gut microbiome and resistome in children aged 8 days to 59 months after one dose of oral azithromycin in Burkina Faso. A total of 450 children were randomized in a 1:1 ratio to either placebo or azithromycin. Rectal samples were collected at baseline, 2 weeks, and 6 months after randomization and subjected to DNA deep sequencing. Gut microbiome diversity and normalized antimicrobial resistance determinants for different antibiotic classes were evaluated. Azithromycin decreased gut bacterial diversity (Shannon P < 0.0001; inverse Simpson P < 0.001) 2 weeks after treatment relative to placebo. Concurrently, the normalized abundance of macrolide resistance genetic determinants was 243-fold higher (95% CI: 76-fold to 776-fold, P < 0.0001). These alterations did not persist at 6 months, suggesting that disruptions were transient. Furthermore, we were unable to detect resistance changes in other antibiotic classes, indicating that co-resistance with a single course of azithromycin when treated at the individual level was unlikely.

Purpose: Combining cataract surgery with endothelial keratoplasty (triple EK) is a common practice and may be safer because it commits the patient to only one surgery. This study aimed to determine whether outcomes of pseudophakic endothelial keratoplasty and triple EK have similar outcomes., Methods: This was a non-prespecified secondary analysis of a multicenter, double-masked, randomized, controlled clinical trial. Enrollment centers included the Casey Eye Institute at Oregon Health and Sciences University and the Byers Eye Institute at Stanford University. Patients with damaged or diseased endothelium and were considered good candidates for either Descemet membrane endothelial keratoplasty or ultrathin Descemet stripping automated endothelial keratoplasty were randomized to one of the two surgeries 1-2 days prior to surgery. If the patient had a cataract, they underwent simultaneous cataract surgery. The primary outcome was visual acuity at 6 months. Visual acuity at 3, 12, and 24 months, 3, 6, 12, and 24 month endothelial cell density and intraoperative and postoperative complications were also recorded., Results: Those who had pseudophakic EK generally were older, more likely to be male, and more likely to have worse baseline vision with higher corneal densitometry values. After controlling for baseline visual acuity and type of keratoplasty, those that underwent Triple-EK had 0.09 better LogMAR lines better visual acuity at 6 (95% CI -0.17 to -0.10; P = 0.02) and 12 months (95% CI -0.21 to -0.07; P = 0.03). Although those receiving Triple- EK had nearly one-half LogMAR line better visual acuity at 24 months, it was no longer statistically significant (95% CI -0.20 to -0.05; P = 0.36). There was no statistically significant difference in ECD between groups at any timepoint. Those undergoing triple EK were more likely to have at least one adverse event (P = 0.02)., Conclusions: Earlier intervention with Triple-EK may improve visual acuity outcomes after endothelial keratoplasty compared with staged procedures, but may also increase the risks of adverse events including the need for re-bubble., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: The MORDOR (Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance) trial demonstrated that mass azithromycin administration reduced mortality by 18% among children aged 1 to 59 months in Niger. The identification of high-risk subgroups to target with this intervention could reduce the risk of antimicrobial resistance., Objective: To evaluate whether distance to the nearest primary health center modifies the effect of azithromycin administration to children aged 1 to 59 months on child mortality., Design, Setting, and Participants: The MORDOR cluster randomized trial was conducted from December 1, 2014, to July 31, 2017; this post hoc secondary analysis was conducted in 2023 among 594 clusters (communities or grappes) in the Boboye and Loga departments in Niger. All children aged 1 to 59 months in eligible communities were evaluated., Interventions: Biannual (twice-yearly) administration of a single dose of oral azithromycin or matching placebo over 2 years., Main Outcomes and Measures: A population-based census was used to monitor mortality and person-time at risk (trial primary outcome). Community distance to a primary health center was calculated as kilometers between the center of each community and the nearest health center. Negative binomial regression was used to evaluate the interaction between distance and the effect of azithromycin on the incidence of all-cause mortality among children aged 1 to 59 months., Results: Between December 1, 2014, and July 31, 2017, a total of 594 communities were enrolled, with 76 092 children (mean [SD] age, 31 [2] months; 39 022 [51.3%] male) included at baseline, for a mean (SD) of 128 (91) children per community. Median (IQR) distance to the nearest primary health center was 5.0 (3.2-7.1) km. Over 2 years, 145 693 person-years at risk were monitored and 3615 deaths were recorded. Overall, mortality rates were 27.5 deaths (95% CI, 26.2-28.7 deaths) per 1000 person-years at risk in the placebo arm and 22.5 deaths (95% CI, 21.4-23.5 deaths) per 1000 person-years at risk in the azithromycin arm. For each kilometer increase in distance in the placebo arm, mortality increased by 5% (adjusted incidence rate ratio, 1.05; 95% CI, 1.03-1.07; P < .001). The effect of azithromycin on mortality varied significantly by distance (interaction P = .02). Mortality reduction with azithromycin compared with placebo was 0% at 0 km from the health center (95% CI, -19% to 17%), 4% at 1 km (95% CI, -12% to 17%), 16% at 5 km (95% CI, 7% to 23%), and 28% at 10 km (95% CI, 17% to 38%)., Conclusions and Relevance: In this secondary analysis of a cluster randomized trial of mass azithromycin administration for child mortality, children younger than 5 years who lived farthest from health facilities appeared to benefit the most from azithromycin administration. These findings may help guide the allocation of resources to ensure that those with the least access to existing health resources are prioritized in program implementation., Trial Registration: ClinicalTrials.gov Identifier: NCT02047981.

Importance: Acute infectious conjunctivitis is a common ocular condition with major public health consequences., Objective: To assess regional variations and microbial etiologies of acute infectious conjunctivitis to guide treatment., Design, Setting, and Participants: In this cross-sectional study, patients with presumed acute infectious conjunctivitis were enrolled in the study at 5 sites (Honolulu, Hawaii; Los Angeles, San Francisco, and San Diego, California; and Petah-Tikva, Israel) from March 2021 to March 2023. Patients with allergic or toxic conjunctivitis were excluded., Main Outcomes and Measures: Pathogens were identified by unbiased RNA deep sequencing., Results: In all, 52 patients (mean [range] age, 48 [7-80] years; 31 females [60%]) were enrolled at 5 sites (6 patients from Honolulu, 9 from San Diego, 11 from Los Angeles, 13 from San Francisco, and 13 from Petah-Tikva). RNA deep sequencing detected human adenovirus species D in one-quarter of patients (13 of 52). A wide range of pathogens, including human coronavirus 229E, SARS-CoV-2, and herpes simplex virus type 1, was also identified, as well as several bacteria and fungi. Moreover, 62% (32 of 52) of patients presented with purulent discharge, while only 8% (4 of 52) of patients had confirmed bacterial pathogens., Conclusion and Relevance: In this cross-sectional study, pathogens associated with acute infectious conjunctivitis varied between all 5 sites in the US and Israel. Purulent discharge was a common presenting sign in this study, with a low specificity for bacteria-associated conjunctivitis, suggesting that further diagnostic workup may be necessary to inform antibiotic stewardship. Additional research on cost-effectiveness of using RNA deep sequencing is needed to ascertain whether it is better to monitor patients clinically until resolution of disease.

Purpose: Conjunctivitis epidemics and pandemics remain a global burden. This study aims to comprehensively identify pathogens associated with conjunctivitis in Vietnam., Methods: Patients with acute conjunctivitis presented to an outpatient clinic in Ho Chi Minh City, Vietnam, were enrolled from September 2022 to March 2023. Swabs were obtained from conjunctiva and anterior nares of all patients. Unbiased RNA deep sequencing (RNA-seq) was used to identify any replicating pathogens in the samples., Results: Samples from 35 patients were analyzed. A pathogen was identified in 80% of the patients. 72% (95% confidence interval: 54% to 85%) were infected with either HAdV-D or HAdV-B. RNA viruses detected were rhinoviruses and human coronavirus 229E. Bacteria etiologies included Streptococcus pneumoniae , Hemophilus influenza , and Pseudomonas spp. One patient had co-infection of rhinovirus A and HAdV-B. Vittaforma corneae , a fungus, was identified in one patient. Corneal sub-epithelial infiltrates, pseudomembranes, or pre-auricular lymphadenopathy were not reported in any patient., Conclusions: Human adenoviruses are the common circulating pathogens associated with infectious conjunctivitis in Vietnam. HAdV species, however, appear to vary between geographic locations within Vietnam. Other under-recognized pathogens identified in this study, such as RNA viruses, suggest broader pathogen surveillance may be beneficial., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to disclose.

Background/aims: We aimed to examine risk factors for corneal ulcer in a rural and peri-urban setting in Nepal., Methods: This population-based matched case-control study was nested in a cluster randomised trial in 24 village development committees in Nepal. Incidence density sampling was used to match incident corneal opacity cases to controls, matching on time of opacity, age, sex and location. Cases and controls were invited to participate in a survey of risk factors for corneal ulcer. Risk factors were evaluated using conditional logistic regression to account for matching., Results: Of the 540 participants with incident opacities identified in the trial, 433 were willing to participate in this substudy and matched to a control. Compared with controls, cases had lower odds of having any education vs no education (adjusted OR, aOR 0.60, 95% CI 0.39 to 0.94), working in non-manual labour occupations vs manual labour occupations (aOR 0.64, 95% CI 0.42 to 0.95) and preferring medical shops for ocular trauma versus eye care system centres (aOR 0.58, 95% CI 0.37 to 0.92). Cases had higher odds of protective goggle use versus no protection (aOR 3.8, 95% CI 1.3 to 11.0) and having an ocular injury vs none (aOR 7.7, 95% CI 4.3 to 13.6) compared with controls., Conclusion: We found ocular injury, manual labour and lower education to be strongly associated with the development of corneal ulcer. Given the persistent burden of corneal blindness in this area, prevention efforts could target efforts to increase access to care in areas where these factors are common., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Recent evidence indicates mass azithromycin distribution reduces under-5 mortality. This intervention is being considered for child survival programs in high mortality sub-Saharan African settings. The delivery approach used in prior studies required a full-time census and distribution team, which is not feasible for most programs. To determine the optimal programmatic approach to delivery, this study aimed to compare treatment coverage, costs, and acceptability of different delivery approaches with existing community health workers (CHWs). This cluster-randomized trial included rural and peri-urban communities in Dosso, Niger (clinicaltrials.gov, NCT04774991). A random sample of 80 eligible communities was randomized 1:1 to biannual door-to-door or fixed-point delivery of oral azithromycin to children 1-59 months old over 1 year. Data analysts alone were masked given the nature of the intervention. The primary outcome was community-level treatment coverage defined as the number of children treated recorded by CHWs divided by the number of eligible children determined using a post-distribution census. Costs were monitored through routine administrative data collection and micro-costing. The census included survey questions on intervention acceptability among caregivers, community leaders, and CHWs. After randomization, 1 community was excluded due to inaccuracies in available administrative data, resulting in 39 communities receiving door-to-door delivery. At the second distribution, community-level mean treatment coverage was 105% (SD 44%) in the door-to-door arm and 92% (SD 20%) in the fixed-point arm (Mean difference 13%, 95% CI -2% to 28%, P-value = 0.08). The total cost per dose delivered was $1.91 in the door-to-door arm and $2.51 in the fixed-point arm. Indicators of acceptability were similar across stakeholder groups in both arms, with most respondents in each group indicating a preference for door-to-door. Overall, door-to-door delivery is the preferred approach to azithromycin distribution in this setting and might reach more children at a lower cost per dose delivered than fixed-point. Trial Registration: clinicaltrials.gov NCT04774991., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Arzika 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.)

Infectious conjunctivitis outbreaks remain a public health burden. This study focuses on the pathogen and antimicrobial resistance (AMR) profiles identified in Niger. Sixty-two patients with acute infectious conjunctivitis who presented to health posts were enrolled from December 2021 to May 2022. Nasal and conjunctival swabs were obtained from each patient. Unbiased RNA deep sequencing (RNA-seq) was used to identify associated pathogens. A pathogen was identified in 39 patients (63%; 95% CI, 50-74). Of those, an RNA virus was detected in 23 patients (59%; 95% CI, 43-73). RNA viruses were diverse and included human coronaviruses (HCoVs): SARS-CoV-2, HCoV-229E, HCoV-HKU1, and HCoV-OC43. A DNA virus was identified in 11 patients (28%; 95% CI, 17-44). Of those, four patients had a coinfection with an RNA virus and two patients had a coinfection with both an RNA virus and a bacterium. DNA viruses were predominantly human herpesvirus (cytomegalovirus, Epstein-Barr virus, human herpesvirus 8) and human adenovirus species B, C, and F. Eighteen patients (46%; 95% CI, 32-61) had a bacteria-associated infection that included Haemophilus influenza, Haemophilus aegyptius, Staphylococcus aureus, Streptococcus pneumoniae, and Moraxella spp. Antimicrobial resistance determinants were detected in either the conjunctiva or nasal samples of 20 patients (32%; 95% CI, 22-45) and were found to be more diverse in the nose (Shannon alpha diversity, 1.12 [95% CI, 1.05-1.26] versus 1.02 [95% CI, 1.00-1.05], P = 0.01). These results suggest the potential utility of leveraging RNA-seq to surveil pathogens and AMR for ocular infections.

Prcis: Intraocular pressure (IOP) decreased with age in a population-based study in Nepal, from a mean of 14.1 mm Hg among those 60-64 years old to 13.0 mm Hg among those 80 years old or older., Purpose: Few studies have assessed the distribution of IOP from the Indian subcontinent, despite its large population and high burden of glaucoma. The objective of this study was to assess the distribution of IOP measurements from adults living in a lowland region of Nepal., Methods: In a population-based cross-sectional study, all individuals aged 60 years and older from an area of lowland Nepal were invited for an IOP assessment with a rebound tonometer., Results: Of 160 communities (28,672 people aged ≥60 y) enrolled, 79 (13,808 people aged ≥60 y) were randomly selected for IOP testing. Of those eligible, 10,017 (72.5%) individuals underwent tonometry. Mean IOP decreased monotonically over 5-year age groups, from 14.1 mm Hg (SD: 3.6) among those aged 60-64 years to 13.0 mm Hg (SD: 4.2) among those 80 years or older. The 97.5th percentile IOP measurement was 21.0 mm Hg for all age groups. In adjusted analyses, younger age, self-reported diabetes, and higher population density were each associated with higher IOP, and self-reported cataract surgery was associated with lower IOP., Conclusions: Mean IOP was lower among older individuals in Nepal, consistent with many studies from East Asia and in contrast to many studies from western populations. These results suggest that ethnic background might be a consideration when diagnosing ocular hypertension., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The WHO guidelines on mass distribution of azithromycin for child survival recommend monitoring of mortality to evaluate effectiveness. Trials that contributed evidence to these guidelines used a population-based census to monitor vital status, requiring census workers to visit each household biannually (twice yearly). Birth history is an alternative to the census approach that may be more feasible because it decreases the time and labor needed for mortality monitoring. This study aimed to compare the population-based census (reference standard) and birth history (index test) approaches to estimating mortality among children 1 to 59 months old using data from the Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial. Sixteen communities that received 5 years of biannual census in the MORDOR trial were selected randomly also to receive birth history surveys. The census approach recorded more participants and households than birth history, with correlations more than 0.94 for each. The correlation between number of deaths in each community was 0.84 (95% CI, 0.59-0.94). A comparison of the mortality incidence rate estimated from the census against the under-5 mortality rate estimated from the birth history resulted in a correlation of 0.60 (95% CI, 0.15-0.84). Of the 47% of children who were linked individually to compare vital status from each method, the death status of children had a sensitivity of 80% (95% CI, 73-89) and a specificity of 98% (95% CI, 98-99), comparing birth history to census. Overall birth histories were found to be a reasonable alternative to biannual census for tracking vital status.