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.

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.

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.

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.

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.

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.

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.

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.

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.

WASH Upgrades for Health in Amhara (WUHA): study protocol for a cluster-randomised trial in Ethiopia.

INTRODUCTION: Facial hygiene promotion and environmental improvements are central components of the global trachoma elimination strategy despite a lack of experimental evidence supporting the effectiveness of water, sanitation and hygiene (WASH) measures for reducing trachoma transmission. The objective of the WUHA (WASH Upgrades for Health in Amhara) trial is to evaluate if a comprehensive water improvement and hygiene education programme reduces the prevalence of ocular chlamydia infection in rural Africa. METHODS AND ANALYSIS: Forty study clusters, each of which had received at least annual mass azithromycin distributions for the 7 years prior to the start of the study, are randomised in a 1:1 ratio to the WASH intervention arm or a delayed WASH arm. The WASH package includes a community water point, community-based hygiene promotion workers, household wash stations, household WASH education books, household soap distribution and a primary school hygiene curriculum. Educational activities emphasise face-washing and latrine use. Mass antibiotic distributions are not provided during the first 3 years but are provided annually over the final 4 years of the trial. Annual monitoring visits are conducted in each community. The primary outcome is PCR evidence of ocular chlamydia infection among children aged 0-5 years, measured in a separate random sample of children annually over 7 years. A secondary outcome is improvement of the clinical signs of trachoma between the baseline and final study visits as assessed by conjunctival photography. Laboratory workers and photo-graders are masked to treatment allocation. ETHICS AND DISSEMINATION: Study protocols have been approved by human subjects review boards at the University of California, San Francisco, Emory University, the Ethiopian Food and Drug Authority, and the Ethiopian Ministry of Innovation and Technology. A data safety and monitoring committee oversees the trial. Results will be disseminated through peer-reviewed publications and presentations. TRIAL REGISTRATION NUMBER: (http://www.clinicaltrials.gov): NCT02754583; Pre-results.

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.

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.

Frequency of Mass Azithromycin Distribution for Ocular Chlamydia in a Trachoma Endemic Region of Ethiopia: A Cluster Randomized Trial.

PURPOSE: Annual mass azithromycin distribution significantly reduces the prevalence of ocular Chlamydia trachomatis, the causative organism of trachoma. However, in some areas a decade or more of treatment has not controlled infection. Here, we compared multiple treatment arms from a community-randomized trial to evaluate whether increasing frequency of azithromycin distribution decreases prevalence in the short term. METHODS: Seventy-two communities in Goncha Siso Enesie woreda in the Amhara region of Northern Ethiopia were randomized to 1 of 6 azithromycin distribution strategies: (1) delayed, (2) annual, (3) biannual, (4) quarterly to children only, (5) biennial, or (6) biennial plus latrine promotion. We analyzed data from the 60 communities in the delayed, annual, biannual, quarterly, and biennial distribution arms at the 12-month study visit. Communities in the annual and biennial distribution arm were combined, as they each had a single distribution before any 12-month retreatment. We assessed the effect of increased frequency of azithromycin distribution on ocular chlamydia prevalence. RESULTS: Ocular chlamydia prevalence was significantly different across azithromycin distribution frequency in children (P < .0001) and adults (P < .0001), with lower prevalence associated with higher frequency. Among children, quarterly azithromycin distribution led to a significantly greater reduction in ocular chlamydia prevalence than the World Health Organization-recommended annual treatment prevalence (mean difference -11.4%, 95% confidence interval -19.5 to -3.3%, P = .007). CONCLUSIONS: Increased frequency of azithromycin distribution leads to decreased ocular chlamydia prevalence over a short-term period. In some regions with high levels of ocular chlamydia prevalence, additional azithromycin distributions may help achieve local elimination of infection.

Associations between Water, Sanitation and Hygiene (WASH) and trachoma clustering at aggregate spatial scales, Amhara, Ethiopia.

BACKGROUND: Trachoma is the leading infectious cause of blindness globally. The WHO has recommended the SAFE (Surgery, Antibiotics, Facial cleanliness and Environmental improvements) strategy to eliminate trachoma as a public health problem. The F and E arms of the strategy will likely be important for sustained disease reductions, yet more evidence is needed detailing relationships between hygiene, sanitation and trachoma in areas with differing endemicity. This study addressed whether the regional differences in water, sanitation, and hygiene (WASH) variables were associated with the spatial distribution of trachomatous inflammation-follicular (TF) among children aged 1 to 9 years in the Amhara National Regional State of Ethiopia. METHODS: Data from 152 multi-stage cluster random trachoma surveys were used to understand the degree of clustering of trachoma on two spatial scales (district and village) in Amhara using a geographical information system and the Getis-Ord Gi* (d) statistic for local clustering. Trained and certified graders examined children for the clinical signs of trachoma using the WHO simplified system. Socio-demographic, community, and geoclimatic factors thought to promote the clustering of the disease were included as covariates in a logistic regression model. RESULTS: The mean district prevalence of TF among children aged 1 to 9 years in Amhara was 25.1% (standard deviation = 16.2%). The spatial distribution of TF was found to exhibit global spatial dependency with neighboring evaluation units at both district and village level. Specific clusters of high TF were identified at both the district and the village scale of analysis using weighted estimates of the prevalence of the disease. Increased prevalence of children without nasal and ocular discharge as well as increased prevalence of households with access to a water source within 30 minutes were statistically significantly negatively associated with clusters of high TF prevalence. CONCLUSIONS: Water access and facial cleanliness were important factors in the clustering of trachoma within this hyperendemic region. Intensified promotion of structural and behavioral interventions to increase WASH coverage may be necessary to eliminate trachoma as a public health problem in Amhara and perhaps other hyper-endemic settings.

Progress to Eliminate Trachoma as a Public Health Problem in Amhara National Regional State, Ethiopia: Results of 152 Population-Based Surveys.

At baseline in 2006, Amhara National Regional State, Ethiopia, was the most trachoma-endemic region in the country. Trachoma impact surveys (TIS) were conducted in all districts between 2010 and 2015, following 3-5 years of intervention with the WHO-recommended SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy. A multistage cluster random sampling design was used to estimate the district-level prevalence of trachoma. In total, 1,887 clusters in 152 districts were surveyed, from which 208,265 individuals from 66,089 households were examined for clinical signs of trachoma. The regional prevalence of trachomatous inflammation-follicular (TF) and trachomatous inflammation-intense among children aged 1-9 years was 25.9% (95% CI: 24.9-26.9) and 5.5% (95% CI: 5.2-6.0), respectively. The prevalence of trachomatous scarring and trachomatous trichiasis among adults aged ≥ 15 years was 12.9% (95% CI: 12.2-13.6) and 3.9% (95% CI: 3.7-4.1), respectively. Among children aged 1-9 years, 76.5% (95% CI: 75.3-77.7) presented with a clean face; 66.2% (95% CI: 64.1-68.2) of households had access to water within 30 minutes round-trip, 48.1% (95% CI: 45.5-50.6) used an improved water source, and 46.2% (95% CI: 44.8-47.5) had evidence of a used latrine. Nine districts had a prevalence of TF below the elimination threshold of 5%. In hyperendemic areas, 3-5 years of implementation of SAFE is insufficient to achieve trachoma elimination as a public health problem; additional years of SAFE and several rounds of TIS will be required before trachoma is eliminated.