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

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

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

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

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

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

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

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

Population coverage and factors associated with participation following a mass drug administration of azithromycin for trachoma elimination in Amhara, Ethiopia.

OBJECTIVES: Mass drug administration (MDA) with azithromycin is a core component of the WHO-recommended strategy to eliminate trachoma as a public health problem, but low participation rates in MDA campaigns may undermine the effectiveness of this intervention. We explored factors associated with individual MDA participation at the individual, head of household and household levels in Amhara, Ethiopia. METHODS: We conducted four district-level, multilevel cluster random coverage surveys to collect data on self-reported MDA participation and predictors. Random-effects logistic regression modelling was used to identify correlates of MDA participation while adjusting for nesting of individuals at the household and village level. RESULTS: The district-level self-reported participation in the trachoma MDA ranged from 78.5% to 86.9%. Excellent and fair health status (Odds ratio [OR] = 5.77; 95% Confidence interval [CI]: 3.04, 10.95; OR = 7.08; 95% CI: 3.47, 14.46), advanced knowledge of the MDA campaign (OR = 2.93; 95% CI: 2.04, 4.21) and knowledge of trachoma (OR = 1.60; 95% CI: 1.17, 2.19) were all positively associated with MDA participation. When excluding heads of household from the model, correlates retained similar positive associations to participation, in addition to the head of household participation (OR = 3.34; 95% CI: 2.46, 4.54). CONCLUSIONS: To increase the impact of MDA campaigns, MDA mobilisation strategies-including comprehensive trachoma and azithromycin messaging and MDA campaign awareness-should target heads of household, those in poorer health and older age groups.

OBJECTIFS: La distribution en masse de médicaments (DMM) avec l'azithromycine est un élément central de la stratégie recommandée par l'OMS pour éliminer le trachome en tant que problème de santé publique, mais le faible taux de participation aux campagnes de DMM pourrait nuire à l'efficacité de cette intervention. Nous avons exploré les facteurs associés à la participation individuelle à la DMM au niveau de l'individu, du chef de ménage et du ménage à Amhara, en Ethiopie. MÉTHODES: Nous avons mené 4 surveillances de la couverture par grappes, aléatoire, à plusieurs niveaux au niveau du district afin de collecter des données sur la participation auto-déclarée à la DMM et les prédicteurs. Une modélisation par régression logistique à effets aléatoires a été utilisée pour identifier les corrélats de la participation à la DMM tout en ajustant la nidification des individus au niveau du ménage et du village. RÉSULTATS: La participation auto-déclarée au niveau du district à la DMM contre le trachome variait de 78,5% à 86,9%. L'état de santé excellent et passable (rapport de cotes [OR] = 5,77; intervalle de confiance à 95% [IC]: 3,04 -10,95 et OR = 7,08; IC95%: 3,47-14,46), la connaissance poussée sur la campagne de DMM (OR = 2,93; IC95%: 2,04, 4,21) et la connaissance sur le trachome (OR = 1,60; IC95%: 1,17, 2,19) étaient tous positivement associés à la participation à la DMM. En excluant les chefs de ménage du modèle, les corrélats ont conservé des associations positives similaires à la participation, en plus de la participation du chef de ménage (OR = 3,34; IC95%: 2,46, 4,54). CONCLUSIONS: Pour accroître l'impact des campagnes de DMM, les stratégies de mobilisation de la DMM, y compris le message complet sur le trachome et l'azithromycine, et la sensibilisation à la campagne de DMM, devraient cibler les chefs de famille, les personnes en mauvaise santé et les groupes de personnes plus âgées.

Ocular Chlamydia trachomatis Infection Under the Surgery, Antibiotics, Facial Cleanliness, and Environmental Improvement Strategy in Amhara, Ethiopia, 2011-2015.

Background: World Health Organization (WHO) recommendations for starting and stopping mass antibiotic distributions are based on a clinical sign of trachoma, which is indirectly related to actual infection with the causative agent, Chlamydia trachomatis. Methods: This study aimed to understand the effect of SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) interventions on ocular chlamydia in Amhara, Ethiopia, by describing the infection prevalence in a population-based sample of children aged 1-5 years. Trachoma surveys were conducted in all districts of Amhara, from 2011 to 2015 following approximately 5 years of SAFE. Ocular swabs were collected from randomly selected children to estimate the zonal prevalence of chlamydial infection. The Abbott RealTime polymerase chain reaction assay was used to detect C. trachomatis DNA. Results: A total of 15632 samples were collected across 10 zones of Amhara. The prevalence of chlamydial infection in children aged 1-5 years was 5.7% (95% confidence interval, 4.2%-7.3%; zonal range, 1.0%-18.5%). Chlamydial infection and trachomatous inflammation-intense (TI) among children aged 1-9 years were highly correlated at the zonal level (Spearman correlation [r] = 0.93; P < .001), while chlamydial infection and trachomatous inflammation-follicular were moderately correlated (r = 0.57; P = .084). Conclusions: After 5 years of SAFE, there is appreciable chlamydial infection in children aged 1-5 years, indicating that transmission has not been interrupted and that interventions should continue. The sign TI was highly correlated with chlamydial infection and can be used as a proxy indicator of infection.

Mass azithromycin distribution for hyperendemic trachoma following a cluster-randomized trial: A continuation study of randomly reassigned subclusters (TANA II).

BACKGROUND: The World Health Organization recommends annual mass azithromycin administration in communities with at least 10% prevalence of trachomatous inflammation-follicular (TF) in children, with further treatment depending on reassessment after 3-5 years. However, the effect of stopping mass azithromycin distribution after multiple rounds of treatment is not well understood. Here, we report the results of a cluster-randomized trial where communities that had received 4 years of treatments were then randomized to continuation or discontinuation of treatment. METHODS AND FINDINGS: In all, 48 communities with 3,938 children aged 0-9 years at baseline in northern Ethiopia had received 4 years of annual or twice yearly mass azithromycin distribution as part of the TANA I trial. We randomized these communities to either continuation or discontinuation of treatment. Individuals in the communities in the continuation arm were offered either annual or twice yearly distribution of a single directly observed dose of oral azithromycin. The primary outcome was community prevalence of ocular chlamydial infection in a random sample of children aged 0-9 years, 36 months after baseline. We also assessed the change from baseline to 36 months in ocular chlamydia prevalence within each arm. We compared 36-month ocular chlamydia prevalence in communities randomized to continuation versus discontinuation in a model adjusting for baseline ocular chlamydia prevalence. A secondary prespecified analysis assessed the rate of change over time in ocular chlamydia prevalence between arms. In the continuation arm, mean antibiotic coverage was greater than 90% at all time points. In the discontinuation arm, the mean prevalence of infection in children aged 0-9 years increased from 8.3% (95% CI 4.2% to 12.4%) at 0 months to 14.7% (95% CI 8.7% to 20.8%, P = 0.04) at 36 months. Ocular chlamydia prevalence in communities where mass azithromycin distribution was continued was 7.2% (95% CI 3.3% to 11.0%) at baseline and 6.6% (95% CI 1.1% to 12.0%, P = 0.64) at 36 months. The 36-month prevalence of ocular chlamydia was significantly lower in communities continuing treatment compared with those discontinuing treatment (P = 0.03). Limitations of the study include uncertain generalizability outside of trachoma hyperendemic regions. CONCLUSIONS: In this study, ocular chlamydia infection rebounded after 4 years of periodic mass azithromycin distribution. Continued distributions did not completely eliminate infection in all communities or meet WHO control goals, although they did prevent resurgence. TRIAL REGISTRATION: This study was prospectively registered at clinicaltrials.gov (clinicaltrials.gov NCT01202331).

Predictors of Trachomatous Trichiasis Surgery Outcome.

PURPOSE: Unfavorable outcomes after trachomatous trichiasis (TT) surgery are undermining the global trachoma elimination effort. This analysis investigates predictors of postoperative TT (PTT), eyelid contour abnormalities (ECAs), and granuloma in the 2 most common TT surgery procedures: posterior lamellar tarsal rotation (PLTR) and bilamellar tarsal rotation (BLTR). DESIGN: Secondary data analysis from a randomized, controlled, single-masked clinical trial. PARTICIPANTS: A total of 1000 patients with TT, with lashes touching the eye or evidence of epilation, in association with tarsal conjunctival scarring. METHODS: Participants were randomly allocated and received BLTR (n = 501) or PLTR (n = 499) surgery. Disease severity at baseline, surgical incisions, sutures, and corrections were graded during and immediately after surgery. Participants were examined at 6 and 12 months by assessors masked to allocation. MAIN OUTCOME MEASURES: Predictors of PTT, ECA, and granuloma. RESULTS: Data were available for 992 (99.2%) trial participants (496 in each arm). There was strong evidence that performing more peripheral dissection with scissors in PLTR (odd ratio [OR], 0.70; 95% confidence interval [CI], 0.54-0.91; P = 0.008) and BLTR (OR, 0.83; 95% CI, 0.72-0.96; P = 0.01) independently protected against PTT. Baseline major trichiasis and mixed location lashes and immediate postoperative central undercorrection independently predicted PTT in both surgical procedures. Peripheral lashes in PLTR (OR, 5.91; 95% CI, 1.48-23.5; P = 0.01) and external central incision height ≥4 mm in BLTR (OR, 2.89; 95% CI, 1.55-5.41; P = 0.001) were independently associated with PTT. Suture interval asymmetry of >2 mm (OR, 3.18; 95% CI, 1.31-7.70; P = 0.01) in PLTR and baseline conjunctival scarring in BLTR (OR, 1.72; 95% CI, 1.06-2.81; P = 0.03) were independently associated with ECA. Older age was independently associated with ECA in both PLTR (P value for trend < 0.0001) and BLTR (P value for trend = 0.03). There was substantial intersurgeon variability in ECA rates for both PLTR (range, 19.0%-36.2%) and BLTR (range, 6.1%-28.7%) procedures. In PLTR surgery, irregular posterior lamellar incision at the center of the eyelid (OR, 6.72; 95% CI, 1.55-29.04; P = 0.01) and ECA (OR, 3.08; 95% CI, 1.37-6.94; P = 0.007) resulted in granuloma formation. CONCLUSIONS: Poor postoperative outcomes in TT surgery were associated with inadequate peripheral dissection, irregular incision, asymmetric suture position and tension, inadequate correction, and lash location. Addressing these will improve TT surgical outcomes.

Active trachoma and community use of sanitation, Ethiopia.

OBJECTIVE: To investigate, in Amhara, Ethiopia, the association between prevalence of active trachoma among children aged 1-9 years and community sanitation usage. METHODS: Between 2011 and 2014, prevalence of trachoma and household pit latrine usage were measured in five population-based cross-sectional surveys. Data on observed indicators of latrine use were aggregated into a measure of community sanitation usage calculated as the proportion of households with a latrine in use. All household members were examined for clinical signs, i.e. trachomatous inflammation, follicular and/or intense, indicative of active trachoma. Multilevel logistic regression was used to estimate prevalence odds ratios (OR) and 95% confidence intervals (CI), adjusting for community, household and individual factors, and to evaluate modification by household latrine use and water access. FINDINGS: In surveyed areas, prevalence of active trachoma among children was estimated to be 29% (95% CI: 28-30) and mean community sanitation usage was 47% (95% CI: 45-48). Despite significant modification (p < 0.0001), no pattern in stratified ORs was detected. Summarizing across strata, community sanitation usage values of 60 to < 80% and ≥ 80% were associated with lower prevalence odds of active trachoma, compared with community sanitation usage of < 20% (OR: 0.76; 95% CI: 0.57-1.03 and OR: 0.67; 95% CI: 0.48-0.95, respectively). CONCLUSION: In Amhara, Ethiopia, a negative correlation was observed between community sanitation usage and prevalence of active trachoma among children, highlighting the need for continued efforts to encourage higher levels of sanitation usage and to support sustained use throughout the community, not simply at the household level.

The Epidemiology of Ocular Chlamydia trachomatis Infection within Districts Persistently Endemic for Trachoma in Amhara, Ethiopia.

Persistent trachoma is a growing concern to trachoma control programs globally and programs serving Ethiopia specifically. Persistent trachoma is defined as a district with two or more trachoma impact surveys (TISs) at which the prevalence of trachomatous inflammation-follicular (TF) among children ages 1-9 years is ≥5%, the elimination threshold. Because the global target for trachoma elimination as a public health problem is 2030, research is needed to better characterize persistent trachoma. This study described the epidemiology of ocular Chlamydia trachomatis infection, the causative bacteria of trachoma, in seven contiguous districts experiencing persistent trachoma. In 2019, multistage cluster random sampling TISs were conducted in the seven districts after 10 years of interventions. All individuals ages ≥1 year were examined for trachoma clinical signs by certified graders, and conjunctival swabs were collected from children ages 1-5 years to test for C. trachomatis infection. The district TF prevalence ranged from 11.8% (95% CI:7.6-16.0%) to 36.1% (95% CI:27.4-44.3%). The range of district-level C. trachomatis infection prevalence was between 2.7% and 34.4%. Statistically significant spatial clustering of high-infection communities was observed in the study districts, and children with infection were more likely than those without to be found in households with clinical signs of trachoma and those without latrines. These seven districts appear to constitute a persistent hotspot in Amhara, where an additional 3-5 years or more of interventions will be required. The global program will need to strengthen and enhance intervention strategies within persistent districts if elimination by 2030 is to be achieved.

Wait and watch: A trachoma surveillance strategy from Amhara region, Ethiopia.

BACKGROUND: Trachoma recrudescence after elimination as a public health problem has been reached is a concern for control programs globally. Programs typically conduct district-level trachoma surveillance surveys (TSS) ≥ 2 years after the elimination threshold is achieved to determine whether the prevalence of trachomatous inflammation-follicular (TF) among children ages 1 to 9 years remains <5%. Many TSS are resulting in a TF prevalence ≥5%. Once a district returns to TF ≥5%, a program typically restarts costly mass drug administration (MDA) campaigns and surveys at least twice, for impact and another TSS. In Amhara, Ethiopia, most TSS which result in a TF ≥5% have a prevalence close to 5%, making it difficult to determine whether the result is due to true recrudescence or to statistical variability. This study's aim was to monitor recrudescence within Amhara by waiting to restart MDA within 2 districts with a TF prevalence ≥5% at TSS, Metema = 5.2% and Woreta Town = 5.1%. The districts were resurveyed 1 year later using traditional and alternative indicators, such as measures of infection and serology, a "wait and watch" approach. METHODS/PRINCIPAL FINDINGS: These post-surveillance surveys, conducted in 2021, were multi-stage cluster surveys whereby certified graders assessed trachoma signs. Children ages 1 to 9 years provided a dried blood spot and children ages 1 to 5 years provided a conjunctival swab. TF prevalence in Metema and Woreta Town were 3.6% (95% Confidence Interval [CI]:1.4-6.4) and 2.5% (95% CI:0.8-4.5) respectively. Infection prevalence was 1.2% in Woreta Town and 0% in Metema. Seroconversion rates to Pgp3 in Metema and Woreta Town were 0.4 (95% CI:0.2-0.7) seroconversions per 100 child-years and 0.9 (95% CI:0.6-1.5) respectively. CONCLUSIONS/SIGNIFICANCE: Both study districts had a TF prevalence <5% with low levels of Chlamydia trachomatis infection and transmission, and thus MDA interventions are no longer warranted. The wait and watch approach represents a surveillance strategy which could lead to fewer MDA campaigns and surveys and thus cost savings with reduced antibiotic usage.

Comparison of annual versus twice-yearly mass azithromycin treatment for hyperendemic trachoma in Ethiopia: a cluster-randomised trial.

BACKGROUND: In trachoma control programmes, azithromycin is distributed to treat the strains of chlamydia that cause ocular disease. We aimed to compare the effect of annual versus twice-yearly distribution of azithromycin on infection with these strains. METHODS: We did a cluster-randomised trial in 24 subdistricts in northern Ethiopia, which we randomly assigned to receive annual or twice-yearly treatment for all residents of all ages. Random assignment was done with the RANDOM and SORT functions of Microsoft Excel. All individuals were offered their assigned treatment of a single, directly observed, oral dose of azithromycin. A 6 week course of topical 1% tetracycline ointment, applied twice daily to both eyes but not directly observed, was offered as an alternative to azithromycin in patients younger than 12 months, and in patients with self-reported pregnancy, with allergy, or who refused azithromycin. Our primary, prespecified outcome was the prevalence of ocular chlamydial infection in a random sample of children aged 0-9 years at baseline and every 6 months for a total of 42 months within sentinel villages. Our analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00322972. FINDINGS: Antibiotic coverage of children aged 1-9 years was greater than 80% (range 80·9 to 93·0) at all study visits. In the groups treated annually, the prevalence of infection in children aged 0-9 years was reduced from a mean 41·9% (95% CI 31·5 to 52·2) at baseline to 1·9% (0·3 to 3·5) at 42 months. In the groups treated twice yearly, the prevalence of infection was reduced from a mean 38·3% (29·0 to 47·6) at baseline to 3·2 % (0·0 to 6·5) at 42 months. The prevalence of ocular chlamydial infection in children aged 0-9 years in groups treated annually was not different from that of the groups treated twice yearly at 18, 30, and 42 months (pooled regression p>0·99, 95 % CI -0·06 to 0·06). The mean elimination time in the twice-yearly treatment group was 7·5 months earlier (2·3 to 17·3) than that of the annual group (p=0·10, Cox proportional hazards model). INTERPRETATION: After 42 months of treatment, the prevalence of ocular infection with chlamydia was similar in the groups treated annually and twice yearly. However, elimination of infection might have been more rapid in the groups of villages that received treatment twice yearly. FUNDING: National Institutes of Health (NEI U10 EY016214).

Prevalence of Ocular Chlamydia trachomatis Infection in Amhara Region, Ethiopia, after 8 Years of Trachoma Control Interventions.

Although trachoma mass drug administration (MDA) programs target ocular Chlamydia trachomatis, the global trachoma control program does not monitor infection as a measure of impact but instead relies on monitoring clinical indicators. This study aimed to monitor the prevalence of ocular C. trachomatis among a population-based sample of children ages 1-5 years throughout Amhara, Ethiopia, a region that has received approximately 8 years of annual MDA as part of trachoma control. Between 2014 and 2021, trachoma impact surveys and surveillance surveys were conducted in all 156 districts of Amhara using a multistage cluster randomized methodology. Certified graders assessed individuals ages ≥ 1 year for trachomatous inflammation-follicular (TF), and a random subset of children ages 1-5 years also provided a conjunctival swab. Polymerase chain reaction was used to test for C. trachomatis. A total of 28,410 conjunctival swabs were collected from children ages 1-5 years across Amhara. The regional C. trachomatis infection prevalence was 4.7% (95% uncertainty interval: 4.3-5.1%). Infection was detected in all 10 zones of the region and ranged from 0.2% in Awi Zone to 11.9% in Waghemra Zone. Infection was detected in 17 (26%) districts with a TF prevalence < 10% and in 7 (21%) districts with a TF prevalence < 5%. Through programmatic monitoring of C. trachomatis infection, this study demonstrated that considerable infection remained throughout Amhara despite approximately 8 years of trachoma interventions and that enhanced interventions such as more frequent than annual MDA will be needed if elimination thresholds are to be reached.

Photographic grading for trachoma diagnosis within trachoma impact surveys in Amhara region, Ethiopia.

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

Optimizing cluster survey designs for estimating trachomatous inflammation-follicular within trachoma control programs.

OBJECTIVES: The World Health Organization recommends mass drug administration (MDA) with azithromycin to eliminate trachoma as a public health problem. MDA decisions are based on prevalence estimates from two-stage cluster surveys. There is a need to mathematically evaluate current trachoma survey designs. Our study aimed to characterize the effects of the number of units sampled on the precision and cost of trachomatous inflammation-follicular (TF) estimates. METHODS: A population of 30 districts was simulated to represent the breadth of possible TF distributions in Amhara, Ethiopia. Samples of varying numbers of clusters (14-34) and households (10-60) were selected. Sampling schemes were evaluated based on precision, proportion of incorrect and low MDA decisions made, and estimated cost. RESULTS: The number of clusters sampled had a greater impact on precision than the number of households. The most efficient scheme depended on the underlying TF prevalence in a district. For lower prevalence areas (< 10%) the most cost-efficient design (providing adequate precision while minimizing cost) was 20 clusters of 20-30 households. For higher prevalence areas (> 10%), the most efficient design was 15-20 clusters of 20-30 households. CONCLUSIONS: For longer-running programs, using context-specific survey designs would allow for practical precision while reducing survey costs. Sampling 15 clusters of 20-30 households in suspected moderate-to-high prevalence districts and 20 clusters of 20-30 households in districts suspected to be near the 5% threshold appears to be a balanced approach.

Surgical output within the Fast Track Initiative against trachoma in Amhara region, Ethiopia.

INTRODUCTION: Trachomatous trichiasis (TT) is the advanced stage of trachoma where lashes touch the globe of the eye causing permanent damage. Without eyelid surgery, TT can lead to irreversible blindness. In 2015 the Ethiopian Ministry of Health launched the Fast Track Initiative with the aim of enhancing the provision of surgical services for TT. The aims of this study were to determine the productivity of individual surgeons during the 2017 Initiative, to compare this productivity with the Ministry's annual target indicator of ≥ 200 surgeries, and to assess the factors associated with surgical output. METHODOLOGY: This retrospective cross-sectional study utilized programmatic data on surgical output from 140 surgeons active from January 2017 through December 2017 in the eastern half of Amhara region, Ethiopia. Data were collected from a surgery monitoring dataset, analyzed, and compared to the performance targets set by the Ministry. RESULTS: The mean annual number of surgeries carried out per surgeon was 169 (standard deviation: 111) for a total of 23,616 surgeries. Among the 140 surgeons, 38% achieved the target set by the Ministry. Location of surgical training site and estimated surgical backlog were signficantly associated with a higher surgery output. CONCLUSIONS: An increase in surgical output was observed compared to productivity prior to the Initiative, although the average annual output during the 2017 Fast Track Initiative was lower than the Ministry's target. Using data driven approaches to setting annual productivity goals should be considered, particularly in light of fewer remaining TT cases as a result of the successful Initiative.

Effect of Azithromycin on the Ocular Surface Microbiome of Children in a High Prevalence Trachoma Area.

PURPOSE: The aim of this study was to evaluate the effect of the 4 times per year mass azithromycin distributions on the ocular surface microbiome of children in a trachoma endemic area. METHODS: In this cluster-randomized controlled trial, children aged 1 to 10 years in rural communities in the Goncha Seso Enesie district of Ethiopia were randomized to either no treatment or treatment with a single dose of oral azithromycin (height-based dosing to approximate 20 mg/kg) every 3 months for 1 year. Post hoc analysis of ocular surface Chlamydia trachomatis load, microbial community diversity, and macrolide resistance determinants was performed to evaluate differences between treatment arms. RESULTS: One thousand two hundred fifty-five children from 24 communities were included in the study. The mean azithromycin coverage in the treated communities was 80% (95% CI: 73%-86%). The average age was 5 years (95% CI: 4-5). Ocular surface C. trachomatis load was reduced in children treated with the 4 times per year azithromycin ( P = 0.0003). Neisseria gonorrhoeae , Neisseria lactamica , and Neisseria meningitidis were more abundant in the no-treatment arm compared with the treated arm. The macrolide resistance gene ermB was not different between arms ( P = 0.63), but mefA / E was increased ( P = 0.04) in the azithromycin-treated arm. CONCLUSIONS: We found a reduction in the load of C. trachomatis and 3 Neisseria species in communities treated with azithromycin. These benefits came at the cost of selection for macrolide resistance.

Childhood mortality in a cohort treated with mass azithromycin for trachoma.

BACKGROUND: Mass azithromycin distributions are used to clear ocular strains of chlamydia that cause trachoma, but treatments may also affect respiratory infections, diarrhea, and malaria. Here, we monitor a large cohort in which almost 90% of individuals received azithromycin. We assess whether receiving treatment is associated with reduced all-cause and infectious childhood mortality. METHODS: As part of a clinical trial for trachoma, a census was conducted in 24 communities in rural Ethiopia. All individuals ≥1 year of age were eligible for single-dose oral azithromycin, although antibiotic coverage was not universal. A follow-up census was performed 26 months after treatment to estimate all-cause mortality among children 1-5 years of age, and verbal autopsies were performed to identify infectious mortality. RESULTS: The cohort included 35,052 individuals ≥1 year of age and 5507 children 1-5 years of age, of whom 4914 received a dose of azithromycin. All-cause mortality was significantly lower among those 1-5-year-old children who received azithromycin (odds ratio [OR]=0.35 [95% confidence interval {CI}, 0.17-0.74]), as was infectious mortality (OR=0.20 [95% CI, 0.07-0.58]). When individuals were compared only with members of the same household, azithromycin treatment was still associated with reduced all-cause mortality in children 1-5 years of age (OR=0.40 [95% CI, 0.16-0.96]), although this relationship was not statistically significant for infectious mortality (OR=0.35 [95% CI, 0.10-1.28]). CONCLUSIONS: This study demonstrated an association between mass oral azithromycin treatment and reduced all-cause and infectious childhood mortality. This relationship could not be attributed to bias at the level of the household. Mass azithromycin distributions may have benefits unrelated to trachoma.

Population-Based Prevalence of Ocular Chlamydia trachomatis Infection among Infants in the Trachoma Endemic Amhara Region, Ethiopia.

Infants ages < 6 months do not receive azithromycin as part of trachoma control and thus may serve as an infection reservoir in persistently endemic districts. The aim of this study was to determine the population-based Chlamydia trachomatis infection prevalence and infectious load among infants ages 1-12 months in persistently trachoma endemic districts in Amhara, Ethiopia. Across six districts, 475 infants were enumerated, and of these 464 (97.7%) were swabbed for infection testing. The C. trachomatis infection prevalence in the study area among infants was 0.2% (95% CI: 0.0-1.5). Among children ages 0-5 years positive for C. trachomatis, the median load was 31 elementary bodies (EB) (Inter quartile range: 7-244 EB), and the infection-positive infant had a load of 7,755 EB. While it is worth reconsidering azithromycin treatment recommendations for the potential mortality benefits, these results do not support lowering the treatment age for trachoma control.

Community Hand-Dug Wells for Trachoma: A Cluster-Randomized Trial.

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