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.

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.

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.

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.

Twelve-Year Longitudinal Trends in Trachoma Prevalence among Children Aged 1-9 Years in Amhara, Ethiopia, 2007-2019.

Trachoma control in the Amhara region of Ethiopia, where all districts were once endemic, began in 2001 and attained full scale-up of the Surgery, Antibiotics, Facial cleanliness, and Environmental improvement (SAFE) strategy by 2010. Since scaling up, the program has distributed approximately 14 million doses of antibiotic per year, implemented village- and school-based health education, and promoted latrine construction. This report aims to provide an update on the prevalence of trachoma among children aged 1-9 years as of the most recent impact or surveillance survey in all 160 districts of Amhara. As of 2019, 45 (28%) districts had a trachomatous inflammation-follicular (TF) prevalence below the 5% elimination threshold. There was a statistically significant relationship between TF prevalence observed at the first impact survey (2010-2015) and eventual achievement of TF < 5% (2015-2019). Of the 26 districts with a first impact survey < 10% TF, 20 (76.9%) had < 5% TF at the most recent survey. Of the 75 districts with a first survey between 10% and 29.9% TF, 21 (28.0%) had < 5% TF at the most recent survey. Finally, among 59 districts ≥ 30% TF at the first survey, four (6.8%) had < 5% TF by 2019. As of 2019, 30 (18.8%) districts remained with TF ≥ 30%. Amhara has seen considerable reductions of trachoma since the start of the program. A strong commitment to the SAFE strategy coupled with data-driven enhancements to that strategy is necessary to facilitate timely elimination of trachoma as a public health problem regionally in Amhara and nationwide in Ethiopia.

Population-Based Prevalence of Chlamydia trachomatis Infection and Antibodies in Four Districts with Varying Levels of Trachoma Endemicity in Amhara, Ethiopia.

The Trachoma Control Program in Amhara region, Ethiopia, scaled up the surgery, antibiotics, facial cleanliness, and environmental improvement (SAFE) strategy in all districts starting in 2007. Despite these efforts, many districts still require additional years of SAFE. In 2017, four districts were selected for the assessment of antibody responses against Chlamydia trachomatis antigens and C. trachomatis infection to better understand transmission. Districts with differing endemicity were chosen, whereby one had a previous trachomatous inflammation-follicular (TF) prevalence of ≥ 30% (Andabet), one had a prevalence between 10% and 29.9% (Dera), one had a prevalence between 5% and 10% (Woreta town), and one had a previous TF prevalence of < 5% (Alefa) and had not received antibiotic intervention for 2 years. Survey teams assessed trachoma clinical signs and took conjunctival swabs and dried blood spots (DBS) to measure infection and antibody responses. Trachomatous inflammation-follicular prevalence among children aged 1-9 years was 37.0% (95% CI: 31.1-43.3) for Andabet, 14.7% (95% CI: 10.0-20.5) for Dera, and < 5% for Woreta town and Alefa. Chlamydia trachomatis infection was only detected in Andabet (11.3%). Within these districts, 2,195 children provided DBS. The prevalence of antibody responses to the antigen Pgp3 was 36.9% (95% CI: 29.0-45.6%) for Andabet, 11.3% (95% CI: 5.9-20.6%) for Dera, and < 5% for Woreta town and Alefa. Seroconversion rate for Pgp3 in Andabet was 0.094 (95% CI: 0.069-0.128) events per year. In Andabet district, where SAFE implementation has occurred for 11 years, the antibody data support the finding of persistently high levels of trachoma transmission.

Ocular Chlamydia trachomatis infection and infectious load among pre-school aged children within trachoma hyperendemic districts receiving the SAFE strategy, Amhara region, Ethiopia.

BACKGROUND: After approximately 5 years of SAFE (surgery, antibiotics, facial cleanliness, environmental improvement) interventions for trachoma, hyperendemic (trachomatous inflammation-follicular (TF) ≥30%) districts remained in Amhara, Ethiopia. This study's aim was to characterize the epidemiology of Chlamydia trachomatis (Ct) infection and load among pre-school aged children living under the SAFE strategy. METHODS: Conjunctival swabs from a population-based sample of children aged 1-5 years collected between 2011 and 2015 were assayed to provide Ct infection data from 4 endemic zones (comprised of 58 districts). Ct load was determined using a calibration curve. Children were graded for TF and trachomatous inflammation-intense (TI). RESULTS: 7,441 children were swabbed in 4 zones. TF and TI prevalence were 39.9% (95% confidence Interval [CI]: 37.5%, 42.4%), and 9.2% (95% CI: 8.1%, 10.3%) respectively. Ct infection prevalence was 6.0% (95% CI: 5.0%, 7.2%). Infection was highest among children aged 2 to 4 years (6.6%-7.0%). Approximately 10% of infection occurred among children aged 1 year. Ct load decreased with age (P = 0.002), with the highest loads observed in children aged 1 year (P = 0.01) vs. aged 5 years. Participants with TF (P = 0.20) and TI (P<0.01) had loads greater than individuals without active trachoma. CONCLUSIONS: In this hyperendemic setting, it appears that the youngest children may contribute in meaningful ways towards persistent active trachoma.

Self-Reported Side Effects following Mass Administration of Azithromycin to Eliminate Trachoma in Amhara, Ethiopia: Results from a Region-Wide Population-Based Survey.

A region-wide population-based post-mass drug administration (MDA) coverage survey was conducted 3 weeks following the 2016 trachoma MDA in Amhara, Ethiopia. The prevalence of self-reported side effects was assessed among those who self-reported receiving azithromycin. A total of 16,773 individuals from 5,129 households reported taking azithromycin during the 2016 MDA in Amhara. The regional prevalence of any self-reported side effect was 9.6% (95% CI: 8.3-11.2%) and ranged from 3.9% to 12.4% among the 10 zones. The most common reported side effects were abdominal pain (53.1%), nausea (21.7%), vomiting (12.8%), and diarrhea (12.5%). Side-effect prevalence among female members was higher than in male members (11.6% versus 7.6%; P < 0.001) and increased with age. After an average of 8 years of annual MDA, the prevalence of self-reported side effects was less than 10% in this population.

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.

Trachoma prevalence remains below threshold in five districts after stopping mass drug administration: results of five surveillance surveys within a hyperendemic setting in Amhara, Ethiopia.

Background: The World Health Organization (WHO) recommends conducting trachoma surveillance surveys in districts where the elimination targets have been met and following a minimum 2-year period after cessation of mass drug administration (MDA) in order to determine the sustainability of low trachoma levels. Methods: In 2015, population-based surveillance surveys were conducted in five districts of Amhara, Ethiopia. All five districts had a prior trachomatous inflammation-follicular (TF) prevalence among children 1-9 y of age of <5% determined by an impact survey and had not received MDA for ≥2 y. Surveys included examinations for trachoma clinical signs and conjunctival swabbing to determine Chlamydia trachomatis infection prevalence. Results: Approximately 1000 children 1-9 y of age were examined for TF and 200 children 1-5 y of age were swabbed per district. All five surveillance districts had a TF prevalence of <5% and infection was only detected in one district. The prevalence of trachomatous trichiasis in adults ≥15 y of age was ≥1% in all districts. Conclusions: In a trachoma hyperendemic region, a TF prevalence <5% was successfully maintained in five districts for ≥2 years after stopping MDA. MDA is still not warranted for these districts, however, the S, F and E components of the SAFE strategy should continue.