Cost and community acceptability of enhanced antibiotic distribution approaches for trachoma in the Republic of South Sudan: enhancing the A in SAFE (ETAS) study protocol.

BACKGROUND: The World Health Organization targeted trachoma for global elimination as a public health problem by 2030. Reaching elimination thresholds by the year 2030 in the Republic of South Sudan will be a considerable challenge, as the country currently has many counties considered hyper-endemic (> 30% trachomatous inflammation-follicular [TF]) that have yet to receive interventions. Evidence from randomized trials, modeling, and population-based surveys suggests that enhancements may be needed to the standard-of-care annual mass drug administration (MDA) to reach elimination thresholds in a timely manner within highly endemic areas. We describe a protocol for a study to determine the cost and community acceptability of enhanced antibiotic strategies for trachoma in South Sudan. METHODS: The Enhancing the A in SAFE (ETAS) study is a community randomized intervention costing and community acceptability study. Following a population-based trachoma prevalence survey in 1 county, 30 communities will be randomized 1:1 to receive 1 of 2 enhanced MDA interventions, with the remaining communities receiving standard-of-care annual MDA. The first intervention strategy will consist of a community-wide MDA followed by 2 rounds of targeted treatment to children ages 6 months to 9 years, 2 weeks and 4 weeks after the community MDA. The second strategy will consist of a community-wide biannual MDA approximately 6 to 8 months apart. The costing analysis will use a payer perspective and identify the total cost of the enhanced interventions and annual MDA. Community acceptability will be assessed through MDA coverage monitoring and mixed-methods research involving community stakeholders. A second trachoma-specific survey will be conducted 12 months following the original survey. DISCUSSION: ETAS has received ethical clearance and is expected to be conducted between 2022 and 2023. Results will be shared through subsequent manuscripts. The study's results will provide information to trachoma programs on whether enhanced interventions are affordable and acceptable to communities. These results will further help in the design of future trachoma-specific antibiotic efficacy trials. Enhanced MDA approaches could help countries recover from delays caused by conflict or humanitarian emergencies and could also assist countries such as South Sudan in reaching trachoma elimination as a public health problem by 2030. TRIAL REGISTRATION: This trial was registered on December 1st, 2022 (clinicaltrails.org: NCT05634759).

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.

Serological Responses to Trachoma Antigens prior to the Start of Mass Drug Administration: Results from Population-Based Baseline Surveys, North Darfur, Sudan.

After years of programmatic inaccessibility, in 2019-2020 the Sudan Federal Ministry of Health Trachoma Control Program conducted population-based trachoma surveys in three localities (districts) in North Darfur state, Sudan. These baseline surveys were to determine the prevalence of trachomatous inflammation-follicular (TF) among children aged 1-9 years and to further use serological markers to understand the historical trachoma burden within this mass drug administration (MDA)-naive area. Trained and certified graders collected trachoma clinical data, and trained nurses collected dried blood spot (DBS) samples. The DBSs were assayed on a multiplex bead array for antibody responses to the Chlamydia trachomatis antigens Pgp3 and CT694. Across the three localities, 3,613 individuals aged 1-9 years and 3,542 individuals aged ≥15 years were examined for clinical signs, and 8,322 DBSs were collected. The prevalence of TF among children aged 1-9 years was endemic (≥5%) in two localities (El Seraif, 15.6%, and Saraf Omrah, 11.0%) and below the TF elimination threshold (<5%) in the third (Kotom, 1.4%). The Pgp3 seroprevalence among children aged 1-9 years was 34.1% in El Seraif, 35.0% in Saraf Omrah, and 11.0% in Kotom. Locality prevalence results were similar for Pgp3 and CT694. Seroprevalence increased with age in all three localities. Serological data collected within these surveys demonstrate that all three localities have had a long history of exposure to Chlamydia trachomatis and that two of the three localities require MDA to reach elimination as a public health problem threshold.

Integrated Serosurveillance for Onchocerciasis, Lymphatic Filariasis, and Schistosomiasis in North Darfur, Sudan.

Sudan is endemic for multiple neglected tropical diseases, including trachoma, onchocerciasis (OV), lymphatic filariasis (LF), and schistosomiasis (SCH). In 2019, dried blood spot samples were collected for a baseline trachoma serosurvey in three localities (El Seraif, Kotom, and Saraf Omrah) in North Darfur State. None were classified previously as OV- or LF-endemic, although low levels of SCH had been identified in all three. Approximately 30 households from 25 communities in each locality were selected by multistage cluster random sampling. Collections of DBSs were analyzed by multiplex bead assay for antibodies to multiple pathogens. This paper presents data on OV (Ov16), LF (Wb123, Bm14, Bm33), and SCH (soluble egg antigen [SEA], Sm25) antibodies among 8,322 individuals from 2,119 households. The survey-adjusted seroprevalence estimates for Ov16 were <0.3% in all localities. Lymphatic filariasis-antigen seroprevalences were discordant. Seroprevalence estimates ranged from 4.6-6.0% (Wb123), 0.99-1.4% (Bm14), and 29.2-33.3% (Bm33). Schistosomiasis seroprevalence estimates among school-aged children ranged from 2.7-8.0% (SEA) and 10.9-15.6% (Sm25). Ov16 seropositivity was low and supported the localities' classification as nonendemic. The results suggested LF exposure, but discordance between antigens, challenges defining seropositivity thresholds, and the absence of programmatic guidance based on antibody serology alone for Wuchereria bancrofti indicate a need for remapping surveys to confirm transmission. Schistosomiasis antibody levels were high enough to warrant further mapping to guide treatment decisions. The lack of gold standards limited interpretation of results, particularly for LF, but in resource-challenged areas, integrated serological surveillance offers the possibility of efficient monitoring of exposure to multiple diseases.

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.

Impact of Three to Five Rounds of Mass Drug Administration on Schistosomiasis and Soil-Transmitted Helminths in School-Aged Children in North-Central Nigeria.

Nasarawa and Plateau states of north-central Nigeria have implemented programs to control schistosomiasis (SCH) and soil-transmitted helminths (STH) in children since the 1990s. Statewide mapping surveys were conducted in 2013, when 11,332 school-aged children were sampled from 226 schools. The local government areas (LGAs) then received varying combinations of mass drug administration (MDA) for the next 5 years. We revisited 196 (87%) schools in 2018 plus an additional six (202 schools in total), sampling 9,660 children. We calculated overall prevalence and intensity of infection and evaluated associations with gender; age; behaviors; water, sanitation, and hygiene (WASH); and treatment regimen. Urine heme detection dipsticks were used for Schistosoma hematobium in both surveys, with egg counts added in 2018. Stool samples were examined by Kato-Katz for Ascaris lumbricoides, Trichuris trichiura, Schistosoma mansoni, and hookworm. Schistosomiasis prevalence among sampled students dropped from 12.9% (95% confidence interval [CI]: 11.1-14.9%) to 9.0% (95% CI: 7.5-10.9%), a statistically significant change (P < 0.05). In 2018, eight LGAs still had > 1% of children with heavy-intensity schistosome infections. Prevalence of STH infection did not significantly change, with 10.8% (95% CI: 9.36-12.5%) of children positive in 2013 and 9.4% (95% CI: 8.0-10.9%) in 2018 (P = 0.182). Heavy-intensity STH infections were found in < 1% of children with hookworm, and none in children with A. lumbricoides or T. trichiura in either study. The WASH data were collected in 2018, indicating 43.6% of schools had a latrine and 14.4% had handwashing facilities. Although progress is evident, SCH remains a public health problem in Nasarawa and Plateau states.

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.

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.

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.

Prevalence of trachoma within refugee camps serving South Sudanese refugees in White Nile State, Sudan: Results from population-based surveys.

BACKGROUND: The world is witnessing mass displacement of populations which could impact global efforts to eliminate neglected tropical diseases such as trachoma. On the African continent, South Sudan has experienced high levels of population displacement. Population based baseline trachoma surveys were conducted among refugee camps in two Sudanese localities hosting South Sudanese refugee populations to determine whether the SAFE strategy was warranted. METHODOLOGY/PRINCIPAL FINDINGS: Cross-sectional, multi-stage, cluster-random surveys were conducted within refugee camps in each of two Sudanese localities, Al Salam and Al Jabalain. For survey sampling, multiple camps within each locality were combined to form the sampling frame for that locality. Household water, sanitation and hygiene indicators were assessed, and trachoma signs were graded by trained and certified graders. The prevalence of trachomatous inflammation-follicular (TF) in children aged one to nine years was 15.7% (95%CI: 12.1-20.2) in Al Salam and 10.6% (95%CI: 7.9-14.0) in Al Jabalain. The prevalence of trachomatous trichiasis (TT) in those 15 years above was 2.9% (95%CI: 1.8-4.8) in Al Salam and 5.0% (95%CI: 3.8-6.6) in Al Jabalain. The presence of water and sanitation was high in both survey units. CONCLUSION/ SIGNIFICANCE: Sudan has made progress in reducing the prevalence of trachoma within the country; however, the presence of over one million refugees from a neighboring trachoma hyper-endemic country could impact this progress. These surveys were the first step in addressing this important issue. The results demonstrate that at least three years of mass drug administration with azithromycin and tetracycline is needed in addition to the provision of TT surgical services. Additionally, it highlights that non-endemic or formerly endemic localities may have to adopt new strategies to provide services for refugee populations originating from hyper-endemic regions to ensure elimination of trachoma as a public health problem for all populations.

Progress toward Elimination of Trachoma as a Public Health Problem in Seven Localities in the Republic of Sudan: Results from Population-Based Surveys.

Trachoma is the leading cause of infectious blindness in the world. After baseline surveys demonstrated that Sudan was endemic for trachoma, the Sudan Federal Ministry of Health (FMOH) Trachoma Control Program conducted trachoma prevention and treatment interventions in endemic localities. The Sudan FMOH conducted population-based trachoma prevalence surveys between September 2016 and April 2017 in seven localities across five states of Sudan to document current trachoma prevalence estimates and measure water, sanitation, and hygiene (WASH) indicators. Children aged 1-9 years were examined for five clinical signs of trachoma, and participants of all ages were examined for trachomatous trichiasis (TT). A household questionnaire was administered to gather demographic and WASH-related information. The prevalence of trachomatous inflammation-follicular (TF) in children aged 1-9 years ranged from 0.4% (95% CI: 0.1-1.1%) to 6.4% (95% CI: 3.3-11.9%). Trachomatous trichiasis in those aged 15 years and older ranged from 0.1% (95% CI: 0.0-0.6%) to a high of 4.4% (95% CI: 2.1-9.1%). Of seven localities surveyed, four localities had achieved the elimination threshold of less than 5% TF in children aged 1-9 years. Six localities still required interventions to achieve less than 0.2% TT in those aged 15 years and older. The presence of latrine ranged from a low of 10.8% (95% CI: 5.2-21.1%) to 88.4% (CI: 81.5-93.0%) and clean face among children ranged between 69.5% (95% CI: 63.5-75.0%) and 87.5% (95% CI: 81.2-91.9%). These results demonstrate that Sudan is within reach of eliminating trachoma as a public health problem.

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.

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.

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.

Population-based coverage survey results following the mass drug administration of azithromycin for the treatment of trachoma in Amhara, Ethiopia.

BACKGROUND: Trachoma is the leading infectious cause of blindness worldwide. In communities where the district level prevalence of trachomatous inflammation-follicular among children ages 1-9 years is ≥5%, WHO recommends annual mass drug administration (MDA) of antibiotics with the aim of at least 80% coverage. Population-based post-MDA coverage surveys are essential to understand the effectiveness of MDA programs, yet published reports from trachoma programs are rare. METHODS: In the Amhara region of Ethiopia, a population-based MDA coverage survey was conducted 3 weeks following the 2016 MDA to estimate the zonal prevalence of self-reported drug coverage in all 10 administrative zones. Survey households were selected using a multi-stage cluster random sampling design and all individuals in selected households were presented with a drug sample and asked about taking the drug during the campaign. Zonal estimates were weighted and confidence intervals were calculated using survey procedures. Self-reported drug coverage was then compared with regional reported administrative coverage. RESULTS: Region-wide, 24,248 individuals were enumerated, of which, 20,942 (86.4%) individuals were present. The regional self-reported antibiotic coverage was 76.8% (95%Confidence Interval (CI):69.3-82.9%) in the population overall and 77.4% (95%CI = 65.7-85.9%) among children ages 1-9 years old. Zonal coverage ranged from 67.8% to 90.2%. Five out of 10 zones achieved a coverage >80%. In all zones, the reported administrative coverage was greater than 90% and was considerably higher than self-reported MDA coverage. Main reasons reported for MDA campaign non-attendance included being physically unable to get to MDA site (22.5%), traveling (20.6%), and not knowing about the campaign (21.0%). MDA refusal was low (2.8%) in this population. CONCLUSIONS: Although self-reported MDA coverage in Amhara was greater than 80% in some zones, programmatic improvements are warranted throughout Amhara to achieve higher coverage. These results will be used to enhance community mobilization and improve training for MDA distributors and supervisors to improve coverage in future MDAs.