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.

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.

Severity of Trachomatous Scarring among Adults in Trachoma-Endemic Amhara Region of Ethiopia.

Trachomatous scarring has been shown to progress regardless of active ocular Chlamydia trachomatis infection, indicating that scarring drivers may be unrelated to ongoing transmission. Although scarring prevalence is commonly associated with older age and female sex, less is known about other potential contributors to its development. This study identified and assessed risk factors associated with scarring magnitude in a trachoma-endemic setting, utilizing a five-point photographic scale (S0-S4). During 2017 trachoma surveys of Amhara, Ethiopia, photographers captured left and right conjunctival images of adults (ages 15 years and older) from 10 districts. Subsequently, two graders independently assessed photographs for scarring, with discrepancies adjudicated by an expert grader. Scarring scores for 729 individuals were aggregated from the eye level to the participant level, excluding 17 participants because of poor photograph quality. Among those with scarring, most cases (20.4%) were severe (S4, comprising more than 90% of the tarsal conjunctiva) compared with the prevalence of moderate S3-A/B (11.2%), S2 (8.3%), and mild S1 (19.2%). The youngest group (ages 15-19 years) exhibited all scarring stages. Older participants (60 years and older) experienced a greater burden of severe scarring (S4 prevalence: 32.6%) than their younger (15-19 years) counterparts (6.2%). Multivariate ordinal logistic regression models indicated female sex, increasing age, and district-level trachomatous follicular-inflammation prevalence were significant predictors of scarring severity. Trachomatous scarring and its progression to trichiasis, may prove a barrier to meeting WHO timelines for trachoma elimination and will necessitate ongoing surveillance and interventions after elimination thresholds have been met.

Impact of a School Trachoma Program Emphasizing Facial Cleanliness and Environmental Improvement in Amhara, Ethiopia.

The SAFE (Surgery, Antibiotics, Facial cleanliness, Environmental improvement) strategy is the WHO's endorsed approach for eliminating trachoma as a public health problem; however, not all components have been treated equally. Historically, the F and E components have not been prioritized owing to their perceived complexity. With school enrollment increasing in Ethiopia, development of a national school health program that is focused on the F and E components represents an opportunity to strengthen the SAFE strategy in the country. In 2016, the Trachoma Control Program in Amhara, Ethiopia, along with its partners, developed a School Trachoma Program (STP) that offers grade-specific lessons to improve sanitation and hygiene knowledge and practices among primary school-aged children. To assess its impact, schools were sampled before implementation and then up to 1 year after STP rollout. The aim of this report is to detail STP outcomes and the associations between outcomes and school-level variables. By 2018, adoption of an STP was strong within Amhara, with 85% of the 137 surveyed schools completing their quarterly reports and nearly 80% having at least one teacher trained in the STP. By the end of the third quarter, nearly all schools (86%) had access to a latrine, and 89% of students had a clean face. A schoolwide orientation was associated with increased STP lessons and activities (P = 0.01). Development of an STP, with buy-in from principals and teachers, represents a promising approach for the adoption of a new F- and E-specific curriculum and may help advance efforts to eliminate trachoma.

Unravelling Chlamydia trachomatis diversity in Amhara, Ethiopia: MLVA-ompA sequencing as a molecular typing tool for trachoma.

Trachoma is the leading infectious cause of blindness worldwide and is now largely confined to around 40 low- and middle-income countries. It is caused by Chlamydia trachomatis (Ct), a contagious intracellular bacterium. The World Health Organization recommends mass drug administration (MDA) with azithromycin for treatment and control of ocular Ct infections, alongside improving facial cleanliness and environmental conditions to reduce transmission. To understand the molecular epidemiology of trachoma, especially in the context of MDA and transmission dynamics, the identification of Ct genotypes could be useful. While many studies have used the Ct major outer membrane protein gene (ompA) for genotyping, it has limitations. Our study applies a typing system novel to trachoma, Multiple Loci Variable Number Tandem Repeat Analysis combined with ompA (MLVA-ompA). Ocular swabs were collected post-MDA from four trachoma-endemic zones in Ethiopia between 2011-2017. DNA from 300 children with high Ct polymerase chain reaction (PCR) loads was typed using MLVA-ompA, utilizing 3 variable number tandem repeat (VNTR) loci within the Ct genome. Results show that MLVA-ompA exhibited high discriminatory power (0.981) surpassing the recommended threshold for epidemiological studies. We identified 87 MLVA-ompA variants across 26 districts. No significant associations were found between variants and clinical signs or chlamydial load. Notably, overall Ct diversity significantly decreased after additional MDA rounds, with a higher proportion of serovar A post-MDA. Despite challenges in sequencing one VNTR locus (CT1299), MLVA-ompA demonstrated cost-effectiveness and efficiency relative to whole genome sequencing, providing valuable information for trachoma control programs on local epidemiology. The findings suggest the potential of MLVA-ompA as a reliable tool for typing ocular Ct and understanding transmission dynamics, aiding in the development of targeted interventions for trachoma control.

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.

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.

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.

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 Performance of Immunoassays to Measure Antibodies to the Chlamydia trachomatis Antigen Pgp3 in Different Epidemiological Settings for Trachoma.

Programs to eliminate trachoma as a public health problem use prevalence of the clinical sign trachomatous inflammation-follicular (TF) in 1- to 9-year-olds in endemic districts to make decisions to begin or end mass drug administration with azithromycin. Trachomatous inflammation-follicular is used as a proxy for transmission of ocular Chlamydia trachomatis infection. Long-term monitoring of previously endemic districts for recrudescence of ocular C. trachomatis infection would benefit from a simple blood test that could be integrated with other public health programs. In this study, we evaluated multiple tests to measure antibodies against the C. trachomatis antigen Pgp3-a multiplex bead assay (MBA), an ELISA, and two versions of a lateral flow assay (LFA)-in four districts of the Amhara region of Ethiopia with varying levels of TF. Seroprevalence and seroconversion rate (SCR) results were proportional to TF prevalence by district for most tests, with the notable exception of the LFA using colloidal gold as the developing reagent. Changing the test developing reagent to black latex improved agreement between serological measures and TF prevalence and in inter-rater agreement. Seroconversion rate estimates using data derived from the LFA-gold assay were inconsistent with the shape of the age-seroprevalence curve, which did not increase in older ages. These data revealed potential complications with using SCR that will need further evaluation. Data from MBA, ELISA, and LFA with the black test line showed good agreement with each other and proportionality to TF estimates, providing further data that serology has potential utility for trachoma surveillance.

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.

A cost-analysis of conducting population-based prevalence surveys for the validation of the elimination of trachoma as a public health problem in Amhara, Ethiopia.

BACKGROUND: Trachoma prevalence surveys, including impact surveys (TIS) and surveillance surveys (TSS), provide information to program managers on the impact of the SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy and current burden of disease, and they provide a crucial component of the evidence base necessary for the validation of the elimination of trachoma as a public health problem. The prevalence surveys included in this analysis are multi-level cluster random surveys that provide population-based estimates for program planning. This study conducted an analysis of the cost of 8 rounds of TIS/TSS executed in Amhara, Ethiopia, 2012-2016, comprising 232,357 people examined over 1,828 clusters in 187 districts. METHODOLOGY AND FINDINGS: Cost data were collected retrospectively from accounting and procurement records from the implementing partner, The Carter Center, and coded by survey activity (i.e. training and field work) and input category (i.e. personnel, transportation, supplies, venue rental, and other). Estimates of staff time were obtained from The Carter Center Ethiopia. Data were analyzed by activity and input category. The mean total cost per cluster surveyed was $752 (standard deviation $101). Primary cost drivers were personnel (39.6%) and transportation (49.2%), with costs increasing in the last 3 rounds of TIS/TSS. CONCLUSION: Despite the considerable cost of conducting TIS and TSS, these surveys provide necessary information for program managers. Limited options are available to reduce the costs of TIS/TSS and gain economies of scale, as the surveys must be designed to achieve their designated sample size. However, surveys must also be designed in a way that is possible to be executed given the financial resources, personnel, and time required. Program managers can use these findings to improve estimates of the total cost of a survey and its components to ensure that sufficient resources are budgeted accordingly.

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.