District-Level Forecast of Achieving Trachoma Elimination as a Public Health Problem By 2030: An Ensemble Modelling Approach.

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.

Prolonged mass azithromycin distributions and macrolide resistance determinants among preschool children in Niger: A sub-study of a cluster-randomized trial (MORDOR).

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.

Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution.

BACKGROUND: Mass distribution of azithromycin to preschool children twice yearly for 2 years has been shown to reduce childhood mortality in sub-Saharan Africa but at the cost of amplifying macrolide resistance. The effects on the gut resistome, a reservoir of antimicrobial resistance genes in the body, of twice-yearly administration of azithromycin for a longer period are unclear. METHODS: We investigated the gut resistome of children after they received twice-yearly distributions of azithromycin for 4 years. In the Niger site of the MORDOR trial, we enrolled 30 villages in a concurrent trial in which they were randomly assigned to receive mass distribution of either azithromycin or placebo, offered to all children 1 to 59 months of age every 6 months for 4 years. Rectal swabs were collected at baseline, 36 months, and 48 months for analysis of the participants' gut resistome. The primary outcome was the ratio of macrolide-resistance determinants in the azithromycin group to those in the placebo group at 48 months. RESULTS: Over the entire 48-month period, the mean (±SD) coverage was 86.6±12% in the villages that received placebo and 83.2±16.4% in the villages that received azithromycin. A total of 3232 samples were collected during the entire trial period; of the samples obtained at the 48-month monitoring visit, 546 samples from 15 villages that received placebo and 504 from 14 villages that received azithromycin were analyzed. Determinants of macrolide resistance were higher in the azithromycin group than in the placebo group: 7.4 times as high (95% confidence interval [CI], 4.0 to 16.7) at 36 months and 7.5 times as high (95% CI, 3.8 to 23.1) at 48 months. Continued mass azithromycin distributions also selected for determinants of nonmacrolide resistance, including resistance to beta-lactam antibiotics, an antibiotic class prescribed frequently in this region of Africa. CONCLUSIONS: Among villages assigned to receive mass distributions of azithromycin or placebo twice yearly for 4 years, antibiotic resistance was more common in the villages that received azithromycin than in those that received placebo. This trial showed that mass azithromycin distributions may propagate antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02047981.).

Impact of Biannual Mass Azithromycin Treatment on Enteropathogen Carriage in Children <5 Years Old in Niger.

We analyzed samples obtained at baseline and 24 months in a mass azithromycin administration trial in Niger using quantitative polymerase chain reaction. In villages randomized to azithromycin, Shigella was the only pathogen reduced at 24 months (prevalence ratio, 0.36 [95% confidence interval: .17-.79]; difference in log quantity, -.42 [-.75 to -.10]).

Gut Resistome of Preschool Children After Prolonged Mass Azithromycin Distribution: A Cluster-randomized Trial.

We evaluated the gut resistome of children from communities treated with 10 twice-yearly azithromycin distributions. Although the macrolide resistance remained higher in the azithromycin arm, the selection of non-macrolide resistance observed at earlier time points did not persist. Longitudinal resistance monitoring should be a critical component of mass distribution programs. CLINICAL TRIALS REGISTRATION: NCT02047981.

Influence of Distance and Near Visual Impairment on Self-Reported Near Visual Functioning in a Multinational Study.

PURPOSE: To assess the influence of distance and near visual impairment on self-reported near visual functioning (VF) in a multinational study. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Participants aged 35 years or older were selected randomly with cluster sampling at 7 sites: rural sites in Nepal (Kaski) and India (Madurai), a semirural site in China (Shunyi), semiurban sites in South Africa (Durban) and Niger (Dosso), and urban sites in the United States (Los Angeles) and China (Guangzhou). METHODS: Binocular presenting distance and near visual acuity (VA) were measured with a logarithm of the minimum angle of resolution tumbling E chart at 4 m and 40 cm, respectively. A 12-item near VF questionnaire interview was administered by trained local interviewers, with responses scored from 100 to 0 as visual disability increased. Multiple linear regression was used to investigate the association of age, gender, education, and VA with overall eyesight, difficulty with activities, and social functioning subscale scores. MAIN OUTCOME MEASURES: Visual functioning subscale scores. RESULTS: The study sample consisted of 6851 questionnaire respondents. The VF subscale scores decreased significantly with worse distance and near VA, and even mildly impaired VA could result in reduced VF. Lower VF subscale scores were associated with older age at 4 sites, female gender at 3 sites, and greater education at 2 sites. The influence of near VA was greater than distance VA at 3 sites, and at 1 site, distance VA was more influential than near VA. With study site included in the regression modeling, lower scores for the overall eyesight subscale (compared with the Shunyi reference site) were found in Guangzhou, Kaski, and Durban; lower difficulty in activities scores were found in Kaski and Durban, but better scores were found in Guangzhou and Madurai; and social functioning scores were lower in Kaski, Durban, and Dosso. CONCLUSIONS: Along the entire VA spectrum, lower levels of distance and near VA led to significant reductions in VF subscale scores, with wide variation both within and between study sites. The impact of near vision on VF should receive greater emphasis with further investigation in various socioeconomic and cultural settings.

Age-related prevalence and met need for correctable and uncorrectable near vision impairment in a multi-country study.

PURPOSE: To estimate the prevalence, potential determinants, and proportion of met need for near vision impairment (NVI) correctable with refraction approximately 2 years after initial examination of a multi-country cohort. DESIGN: Population-based, prospective cohort study. PARTICIPANTS: People aged ≥35 years examined at baseline in semi-rural (Shunyi) and urban (Guangzhou) sites in China; rural sites in Nepal (Kaski), India (Madurai), and Niger (Dosso); a semi-urban site (Durban) in South Africa; and an urban site (Los Angeles) in the United States. METHODS: Near visual acuity (NVA) with and without current near correction was measured at 40 cm using a logarithm of the minimum angle of resolution near vision tumbling E chart. Participants with uncorrected binocular NVA ≤20/40 were tested with plus sphere lenses to obtain best-corrected binocular NVA. MAIN OUTCOME MEASURES: Prevalence of total NVI (defined as uncorrected NVA ≤20/40) and NVI correctable and uncorrectable to >20/40, and current spectacle wearing among those with bilateral NVA ≤20/63 improving to >20/40 with near correction (met need). RESULTS: Among 13 671 baseline participants, 10 533 (77.2%) attended the follow-up examination. The prevalence of correctable NVI increased with age from 35 to 50-60 years and then decreased at all sites. Multiple logistic regression modeling suggested that correctable NVI was not associated with gender at any site, whereas more educated persons aged >54 years were associated with a higher prevalence of correctable NVI in Nepal and India. Although near vision spectacles were provided free at baseline, wear among those who could benefit was <40% at all but 2 centers (Guangzhou and Los Angeles). CONCLUSIONS: Prevalence of correctable NVI is greatest among persons of working age, and rates of correction are low in many settings, suggesting that strategies targeting the workplace may be needed.

Efficacy of Single-Dose Azithromycin for Ocular Chlamydial Infection: A Longitudinal Study.

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.

Temporal Trends in Phenotypic Macrolide and Nonmacrolide Resistance for Streptococcus pneumoniae Nasopharyngeal Samples Up to 36 Months after Mass Azithromycin Administration in a Cluster-Randomized Trial in Niger.

Azithromycin mass drug administration decreases child mortality but also selects for antibiotic resistance. Herein, we evaluate macrolide resistance of nasopharyngeal Streptococcus pneumoniae after azithromycin MDA. In a cluster-randomized trial, children 1-59 months received azithromycin or placebo biannually. Fifteen villages from each arm were randomly selected for antimicrobial resistance testing, and 10-15 randomly selected swabs from enrolled children at each village were processed for S. pneumoniae isolation and resistance testing. The primary prespecified outcome was macrolide resistance fraction for azithromycin versus placebo villages at 36 months. Secondary non-prespecified outcomes were comparisons of azithromycin and placebo for: 1) macrolide resistance at 12, 24, and 36 months; 2) nonmacrolide resistance at 36 months; and 3) suspected-erm mutation. At 36 months, 423 swabs were obtained and 322 grew S. pneumoniae, (azithromycin: 146/202, placebo: 176/221). Mean resistance prevalence was non-significantly higher in treatment than placebo (mixed-effects model: 14.6% vs. 8.9%; OR = 2.0, 95% CI: 0.99-3.97). However, when all time points were evaluated, macrolide resistance prevalence was significantly higher in the azithromycin group (ß = 0.102, 95% CI: 0.04-0.167). For all nonmacrolides, resistance prevalence at 36 months was not different between the two groups. Azithromycin and placebo were not different for suspected-erm mutation prevalence. Macrolide resistance was higher in the azithromycin group over all time points, but not at 36 months. Although this suggests resistance may not continue to increase after biannual MDA, more studies are needed to clarify when MDA can safely decrease mortality and morbidity in lower- and middle-income countries.

Distance to Health Centers and Effectiveness of Azithromycin Mass Administration for Children in Niger: A Secondary Analysis of the MORDOR Cluster Randomized Trial.

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.

Tropical Data: Approach and Methodology as Applied to Trachoma Prevalence Surveys.

PURPOSE: Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys. METHODS: Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported. RESULTS: Between 29th February 2016 and 24th April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma. CONCLUSION: This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets.

Case series about physiological astigmatism and the impact of pterygium surgery.

Introduction: Pterygium is a benign conjunctival fibrovascular neoformation progressively encroaching on the cornea, it can cause corneal distortion and induce astigmatism, or aggravate pre-existing physiological astigmatism, which is defined as ≤ 0.50 D and not requiring optical correction. The radical treatment of pterygium is purely surgical, with conjunctivo-limbal grafting and conjunctival autografting emerging as the surgical techniques of choice. The main objective of the study was to investigate whether pterygium surgery does not worsen the preoperative physiological astigmatism. Material and methods: This is a prospective cohort study conducted in the ophthalmology department of the Mohammed V Military Hospital in Rabat over a period of 12 months, including 43 stage II/III/IV pterygia that were operated on by conjunctival autograft by the same surgeon. First, we looked for an association between pterygium surgery and variations in astigmatism. For quantitative variables we used the Wilcoxon test. In a second step we split the file into two distinct groups according to the value of preoperative astigmatism≤ 0.5 D or >0.5 D in order to detect the impact of pterygium surgery on physiological astigmatism. Statistical analysis of the data was performed by comparing the distribution of these characteristics. Results: The median astigmatism was 1 D (0.25; 2.50). 35% of our population had preoperative astigmatism ≤0.5 D. The Wilcoxon test showed that there was a statistically significant difference between preoperative and postoperative astigmatism (p = 0.001). The paired sample T-test showed no statistically significant difference between the preoperative and postoperative outcome in the physiological astigmatism population (p = 0.53). Conclusion: Many studies have shown the benefits of pterygium excision on astigmatism, but few studies have specified the impact of this surgery on physiological astigmatism. Our study showed that pterygium surgery does not alter physiological astigmatism.

Effect of Biannual Mass Azithromycin Distributions to Preschool-Aged Children on Trachoma Prevalence in Niger: A Cluster Randomized Clinical Trial.

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

Simplified dosing of oral azithromycin for children 1-11 months old in child survival programmes: age-based and height-based dosing protocols.

BACKGROUND: To facilitate mass distribution of azithromycin, trachoma control programmes use height instead of weight to determine dose for children 6 months to 15 years old. WHO has recommended azithromycin distribution to children 1-11 months old to reduce mortality in high mortality settings under carefully monitored conditions. Weight was used to determine dose in children 1-5 months old in studies of azithromycin distribution for child survival, but a simplified approach using age or height for all aged 1-11 months old could increase programme efficiency in real-world settings. METHODS: This secondary analysis used data from two cluster randomised trials of azithromycin distribution for child mortality in Niger and Burkina Faso. An exhaustive search algorithm was developed to determine the optimal dose for different age groups, using tolerance limits of 10-20 mg/kg for children 1-2 months old and 15-30 mg/kg for children 3-11 months old. Height-based dosing was evaluated against the existing trachoma dosing pole and with a similar exhaustive search. RESULTS: The optimal two-tiered age-based approach suggested a dose of 80 mg (2 mL) for children 1-2 months old and 160 mg (4 mL) for children 3-11 months old. Under this schedule, 89%-93% of children would have received doses within tolerance limits in both study populations. Accuracy was 93%-94% with a three-tiered approach, which resulted in doses of 80 mg (2 mL), 120 mg (3 mL) and 160 mg (4 mL) for children 1-2, 3-4 and 5-11 months old, respectively. For children 1-5 months old, the existing height pole would result in 70% of doses within tolerance limits. The optimisation identified height-based dosing options with 95% accuracy, although this would require changes to the existing dosing pole as well as additional training to measure infants lying flat. CONCLUSIONS: Overall, an age-based approach with two age tiers resulted in high accuracy while considering both concerns about overdosing in this young population and simplicity of field operations.

Effect of Mass Azithromycin Distributions on Childhood Growth in Niger: A Cluster-Randomized Trial.

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

How much is not enough? A community randomized trial of a Water and Health Education programme for Trachoma and Ocular C. trachomatis infection in Niger.

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

The global burden of trichiasis in 2016.

BACKGROUND: Trichiasis is present when one or more eyelashes touches the eye. Uncorrected, it can cause blindness. Accurate estimates of numbers affected, and their geographical distribution, help guide resource allocation. METHODS: We obtained district-level trichiasis prevalence estimates in adults for 44 endemic and previously-endemic countries. We used (1) the most recent data for a district, if more than one estimate was available; (2) age- and sex-standardized corrections of historic estimates, where raw data were available; (3) historic estimates adjusted using a mean adjustment factor for districts where raw data were unavailable; and (4) expert assessment of available data for districts for which no prevalence estimates were available. FINDINGS: Internally age- and sex-standardized data represented 1,355 districts and contributed 662 thousand cases (95% confidence interval [CI] 324 thousand-1.1 million) to the global total. Age- and sex-standardized district-level prevalence estimates differed from raw estimates by a mean factor of 0.45 (range 0.03-2.28). Previously non- stratified estimates for 398 districts, adjusted by ×0.45, contributed a further 411 thousand cases (95% CI 283-557 thousand). Eight countries retained previous estimates, contributing 848 thousand cases (95% CI 225 thousand-1.7 million). New expert assessments in 14 countries contributed 862 thousand cases (95% CI 228 thousand-1.7 million). The global trichiasis burden in 2016 was 2.8 million cases (95% CI 1.1-5.2 million). INTERPRETATION: The 2016 estimate is lower than previous estimates, probably due to more and better data; scale-up of trichiasis management services; and reductions in incidence due to lower active trachoma prevalence.

The distribution of the prevalence of ocular chlamydial infection in communities where trachoma is disappearing.

Mathematical models predict that the prevalence of infection in different communities where an infectious disease is disappearing should approach a geometric distribution. Trachoma programs offer an opportunity to test this hypothesis, as the World Health Organization (WHO) has targeted trachoma to be eliminated as a public health concern by the year 2020. We assess the distribution of the community prevalence of childhood ocular chlamydia infection from periodic, cross-sectional surveys in two areas of Ethiopia. These surveys were taken in a controlled setting, where infection was documented to be disappearing over time. For both sets of surveys, the geometric distribution had the most parsimonious fit of the distributions tested, and goodness-of-fit testing was consistent with the prevalence of each community being drawn from a geometric distribution. When infection is disappearing, the single sufficient parameter describing a geometric distribution captures much of the distributional information found from examining every community. The relatively heavy tail of the geometric suggests that the presence of an occasional high-prevalence community is to be expected, and does not necessarily reflect a transmission hot spot or program failure. A single cross-sectional survey can reveal which direction a program is heading. A geometric distribution of the prevalence of infection across communities may be an encouraging sign, consistent with a disease on its way to eradication.

Prevalence and correction of near vision impairment at seven sites in China, India, Nepal, Niger, South Africa, and the United States.

PURPOSE: To estimate the prevalence of near vision impairment and use of corrective spectacles among middle-aged and older adults in different settings and ethnic groups. DESIGN: Population-based, cross-sectional study. METHODS: People aged ≥ 35 years were randomly selected with cluster sampling in 4 rural settings in Shunyi (China), Kaski (Nepal), Madurai (India), and Dosso (Niger); 1 semi-urban area in Durban (South Africa); and 2 urban settings in Guangzhou (China) and Los Angeles (USA). Near visual acuity (VA), with and without presenting near correction, was measured at 40 cm using a logMAR near vision tumbling E chart. Subjects with uncorrected binocular near VA ≤ 20/40 were tested with plus spheres to obtain the best-corrected binocular VA. RESULTS: A total of 17 734 persons aged ≥ 35 years were enumerated and 14 805 (83.5%) were examined. The age- and sex-standardized prevalence of uncorrected near vision impairment (VA ≤ 20/40) ranged from 49% in Dosso to 60% in Shunyi and Guangzhou, 65% in Kaski and Los Angeles, and 83% in Madurai and Durban. The prevalence of near vision impairment based on best-corrected visual acuity was less than 10% in Guangzhou, Kaski, Durban, and Los Angeles, but as high as 23% in Madurai. In multiple logistic regression models, uncorrected near vision impairment was associated with older age (odds ratio [OR] = 1.14, P < .001) and female sex (OR = 1.12, P = .027), but not with educational level (OR = 1.01, P = .812). Over 90% of people in need of near refractive correction in rural settings did not have the necessary spectacles. These rates were 40% in urban settings. CONCLUSIONS: By 50 years of age, the majority of people suffer from near vision impairment, most of which can be corrected optically. Over 90% of those in need of near refractive correction in rural settings do not have the necessary spectacles.