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.

Gender differences in the surgical management of trachomatous trichiasis: an exploratory analysis of global trachoma survey data, 2015-2019.

BACKGROUND: Trachomatous trichiasis (TT) is a painful, potentially blinding eye condition that can be managed through epilation or surgery. Women are affected by TT approximately twice as often as men and are believed to face gendered barriers to receiving surgical care to prevent vision loss. METHODS: We used data from 817 cross-sectional surveys conducted during 2015-2019 in 20 African countries to estimate the prevalence difference (PD) between female and male eyes for four outcomes potentially indicating gender-related differences in TT management: (1) received surgery and developed postoperative TT (PTT), (2) never offered surgery, (3) offered surgery but declined it, and (4) offered epilation but never offered surgery. RESULTS: The prevalence was modestly elevated among female eyes compared with male eyes for having PTT (PD:1.8 [95% confidence limits (CL): 0.6, 3.0]) and having declined surgery for the eye (PD: 6.2 [95% CL: 1.8, 10.7]). The proportion offered epilation was similar by gender (PD:0.5 [95% CL: -0.4, 1.3]), while never having been offered surgery was somewhat more prevalent among male eyes (PD: -2.1 [95% CL: -3.5, -0.7]). CONCLUSIONS: Our results suggest potential gender differences in TT management. More research is needed to determine the causes and implications of the observed differences.

Exploring water, sanitation, and hygiene coverage targets for reaching and sustaining trachoma elimination: G-computation analysis.

BACKGROUND: Trachoma is the leading infectious cause of blindness. To reduce transmission, water, sanitation, and hygiene (WaSH) improvements are promoted through a comprehensive public health strategy. Evidence supporting the role of WaSH in trachoma elimination is mixed and it remains unknown what WaSH coverages are needed to effectively reduce transmission. METHODS/FINDINGS: We used g-computation to estimate the impact on the prevalence of trachomatous inflammation-follicular among children aged 1-9 years (TF1-9) when hypothetical WaSH interventions raised the minimum coverages from 5% to 100% for "nearby" face-washing water (<30 minutes roundtrip collection time) and adult latrine use in an evaluation unit (EU). For each scenario, we estimated the generalized prevalence difference as the TF1-9 prevalence under the intervention scenarios minus the observed prevalence. Data from 574 cross-sectional surveys conducted in 16 African and Eastern Mediterranean countries were included. Surveys were conducted from 2015-2019 with support from the Global Trachoma Mapping Project and Tropical Data. When modeling interventions among EUs that had not yet met the TF1-9 elimination target, increasing nearby face-washing water and latrine use coverages above 30% was generally associated with consistent decreases in TF1-9. For nearby face-washing water, we estimated a ≥25% decrease in TF1-9 at 65% coverage, with a plateau upon reaching 85% coverage. For latrine use, the estimated decrease in TF1-9 accelerated from 80% coverage upward, with a ≥25% decrease in TF1-9 by 85% coverage. Among EUs that had previously met the elimination target, results were inconclusive. CONCLUSIONS: Our results support Sustainable Development Goal 6 and provide insight into potential WaSH-related coverage targets for trachoma elimination. Targets can be tested in future trials to improve evidence-based WaSH guidance for trachoma.

Trachoma Prevalence in Four Localities of Darfur Region, Sudan, following One Round of Antibiotic Mass Drug Administration.

INTRODUCTION: The prevalence of trachomatous inflammation-follicular (TF) in 1-9-year-olds and of trachomatous trichiasis (TT) in ≥15-year-olds in four endemic evaluation units (EUs) of Darfur region, Sudan, was measured more than a year after the required single round of antibiotic mass drug administration (MDA). METHODS: Surveys were conducted using highly standardised, World Health Organization-recommended methodologies. Individuals aged ≥1 year, resident in selected households, were chosen for the survey using a two-stage cluster sampling process. Consenting adults and children were examined for the signs TF and TT by graders trained to international standards. Prevalence of disease in key indicator groups was calculated and weighted to the underlying population structure. RESULTS: A mean of 1,415 (range: 1,253-1,611) children aged 1-9 years were examined in each EU. The age-adjusted prevalence of TF in 1-9-year-olds in each of the four surveyed EUs was <5%. A mean of 1,139 people aged ≥15 years (range: 1,080-1,201) were examined in each EU. The estimated age- and gender-adjusted prevalence of TT in ≥15-year-olds was <0.2% in all four EUs. In general, the proportion of households with access to improved WASH facilities was generally lower in this study than in corresponding baseline studies. CONCLUSIONS: No further MDA should be conducted in these four EUs for the next 2 years, at which point they should be re-surveyed to determine whether the prevalence of TF in 1-9-year-olds has remained <5%. Active TT case-finding is also not indicated. Environmental improvement and promotion of facial cleanliness measures should continue to be implemented to prevent disease recrudescence.

Global progress toward the elimination of active trachoma: an analysis of 38 countries.

BACKGROUND: Global elimination of trachoma as a public health problem was targeted for 2020. We reviewed progress towards the elimination of active trachoma by country and geographical group. METHODS: In this retrospective analysis of national survey and implementation data, all countries ever known to be endemic for trachoma that had either implemented at least one trachoma impact survey shown in the publicly available Trachoma Atlas, or are in Africa were invited to participate in this study. Scale-up was described according to the number of known endemic implementation units and mass drug administration implementation over time. The prevalence of active trachoma-follicular among children aged 1-9 years (TF1-9) from baseline, impact, and surveillance surveys was categorised and used to show programme progress towards reaching the elimination threshold (TF1-9 <5%) using dot maps, spaghetti plots, and boxplots. FINDINGS: We included data until Nov 10, 2021, for 38 countries, representing 2097 ever-endemic implementation units. Of these, 1923 (91·7%) have had mass drug administration. Of 1731 implementation units with a trachoma impact survey, the prevalence of TF1-9 had reduced by at least 50% in 1465 (84·6%) implementation units and 1182 (56·4%) of 2097 ever-endemic implementation units had reached the elimination threshold. 2 years after reaching a TF1-9 prevalence below 5%, most implementation units sustained this target; however, 58 (56·3%) of 103 implementation units in Ethiopia showed recrudescence. INTERPRETATION: Global elimination of trachoma as a public health problem by 2020 was not possible, but this finding masks the great progress achieved. Implementation units in high baseline categories and recrudescent TF1-9 might prolong the attainment of elimination of active trachoma. Elimination is delayed but, with an understanding of the patterns and timelines to reaching elimination targets and a commitment toward meeting future targets, global elimination can still be achieved by 2030. FUNDING: None.

Comparison of genovars and Chlamydia trachomatis infection loads in ocular samples from children in two distinct cohorts in Sudan and Morocco.

Trachoma is a blinding disease caused by repeated conjunctival infection with different Chlamydia trachomatis (Ct) genovars. Ct B genovars have been associated with more severe trachoma symptoms. Here, we investigated associations between Ct genovars and bacterial loads in ocular samples from two distinct geographical locations in Africa, which are currently unclear. We tested ocular swabs from 77 Moroccan children (28 with trachomatous inflammation-follicular (TF) and 49 healthy controls), and 96 Sudanese children (54 with TF and 42 healthy controls) with a Ct-specific real-time polymerase chain reaction (PCR) assay. To estimate bacterial loads, Ct-positive samples were further processed by multiplex real-time qPCR to amplify the chromosomal outer membrane complex B and plasmid open reading frame 2 of Ct. Genotyping was performed by PCR-based amplification of the outer membrane protein A gene (~1120 base pairs) of Ct and Sanger sequencing. Ct-positivities among the Moroccan and Sudanese patient groups were 60·7% and 31·5%, respectively. Significantly more Sudanese patients than Moroccan patients were genovar A-positive. In contrast, B genovars were significantly more prevalent in Moroccan patients than in Sudanese patients. Significantly higher Ct loads were found in samples positive for B genovars (598596) than A genovar (51005). Geographical differences contributed to the distributions of different ocular Ct genovars. B genovars may induce a higher bacterial load than A genovars in trachoma patients. Our findings emphasize the importance of conducting broader studies to elucidate if the noted difference in multiplication abilities are genovar and/or endemicity level dependent.

The global burden of trichiasis in 2016.

BACKGROUND: Trichiasis is present when one or more eyelashes touches the eye. Uncorrected, it can cause blindness. Accurate estimates of numbers affected, and their geographical distribution, help guide resource allocation. METHODS: We obtained district-level trichiasis prevalence estimates in adults for 44 endemic and previously-endemic countries. We used (1) the most recent data for a district, if more than one estimate was available; (2) age- and sex-standardized corrections of historic estimates, where raw data were available; (3) historic estimates adjusted using a mean adjustment factor for districts where raw data were unavailable; and (4) expert assessment of available data for districts for which no prevalence estimates were available. FINDINGS: Internally age- and sex-standardized data represented 1,355 districts and contributed 662 thousand cases (95% confidence interval [CI] 324 thousand-1.1 million) to the global total. Age- and sex-standardized district-level prevalence estimates differed from raw estimates by a mean factor of 0.45 (range 0.03-2.28). Previously non- stratified estimates for 398 districts, adjusted by ×0.45, contributed a further 411 thousand cases (95% CI 283-557 thousand). Eight countries retained previous estimates, contributing 848 thousand cases (95% CI 225 thousand-1.7 million). New expert assessments in 14 countries contributed 862 thousand cases (95% CI 228 thousand-1.7 million). The global trichiasis burden in 2016 was 2.8 million cases (95% CI 1.1-5.2 million). INTERPRETATION: The 2016 estimate is lower than previous estimates, probably due to more and better data; scale-up of trichiasis management services; and reductions in incidence due to lower active trachoma prevalence.

Unimproved water sources and open defecation are associated with active trachoma in children in internally displaced persons camps in the Darfur States of Sudan.

PURPOSE: To estimate the proportion of children with trachomatous inflammation-follicular (TF) and adults with trachomatous trichiasis (TT) in internally displaced persons (IDP) camps in the Darfur States of Sudan and to evaluate associated risk factors. METHODS: IDP camps were identified from government census data. We conducted a subanalysis of data collected in these camps during 2014-2015 as part of surveys covering 37 districts of the Darfur States within the Global Trachoma Mapping Project. A random-effects hierarchical model was used to evaluate factors associated with TF in children or TT in adults. RESULTS: Thirty-six IDP camps were represented in the survey data, in which 1926 children aged 1-9 y were examined, of whom 38 (8%) had TF. Poor sanitation, younger age and living in a household that purchased water from a vendor were associated with TF in children aged 1-9 y. Of 2139 individuals examined aged ≥15 y, 16 (0.7%) had TT. TT was strongly independently associated with being older and living alone. CONCLUSION: Trachoma is found at low levels in these camps, but still at levels where intervention is needed. Disease elimination in conflict-related settings presents a unique challenge for the trachoma community, and may require an innovative approach. Understanding how best to undertake trachoma elimination interventions in these areas should be prioritized.

Understanding the spatial distribution of trichiasis and its association with trachomatous inflammation-follicular.

BACKGROUND: Whilst previous work has identified clustering of the active trachoma sign "trachomatous inflammation-follicular" (TF), there is limited understanding of the spatial structure of trachomatous trichiasis (TT), the rarer, end-stage, blinding form of disease. Here we use community-level TF prevalence, information on access to water and sanitation, and large-scale environmental and socio-economic indicators to model the spatial variation in community-level TT prevalence in Benin, Cote d'Ivoire, DRC, Guinea, Ethiopia, Malawi, Mozambique, Nigeria, Sudan and Uganda. METHODS: We fit binomial mixed models, with community-level random effects, separately for each country. In countries where spatial correlation was detected through a semi-variogram diagnostic check we then fitted a geostatistical model to the TT prevalence data including TF prevalence as an explanatory variable. RESULTS: The estimated regression relationship between community-level TF and TT was significant in eight countries. We estimate that a 10% increase in community-level TF prevalence leads to an increase in the odds for TT ranging from 20 to 86% when accounting for additional covariates. CONCLUSION: We find evidence of an association between TF and TT in some parts of Africa. However, our results also suggest the presence of additional, country-specific, spatial risk factors which modulate the variation in TT risk.

The Epidemiology of Trachoma in Darfur States and Khartoum State, Sudan: Results of 32 Population-Based Prevalence Surveys.

PURPOSE: To complete the baseline trachoma map of Sudan by estimating the prevalence of trachoma and associated risk factors in the five Darfur States and Khartoum State. METHODS: Using a standardized methodology developed for the Global Trachoma Mapping Project, we undertook a cross sectional, community-based survey in each of 32 evaluation units (EUs) covering all accessible districts. RESULTS: We enumerated a total of 84,568 individuals, with 73,489 people (86.9%) examined from 20,242 households in 908 villages. The highest prevalence of trachomatous inflammation - follicular (TF) in children was found in El Fashir district (18.7%), and the lowest in El Malha district (0.0%). Five districts (El Fashir, Zalinji, Azoom, Maleet, and El Koma) were in the three EUs that had TF prevalences above the 10% threshold at which the World Health Organization recommends mass treatment with azithromycin, together with facial clean3liness and environmental improvement interventions, for at least 3 years. The highest trachomatous trichiasis prevalence in adults was found in the EU composed of Forbranga and Habillah (1.2%), and the lowest in the EU composed of As-salam and Belale districts in South Darfur (0.0%). TF in children was independently associated with younger age, unimproved sanitation in the household, having ≥5 children in the household, outside annual maximum temperatures <40°C, and living in an internally displaced persons camp. CONCLUSION: We found a high prevalence of trachoma in some areas of Darfur, but in general the prevalence throughout Darfur and Khartoum was low.

The prevalence of blinding trachoma in northern states of Sudan.

BACKGROUND: Despite historical evidence of blinding trachoma, there have been no widespread contemporary surveys of trachoma prevalence in the northern states of Sudan. We aimed to conduct district-level surveys in this vast region in order to map the extent of the problem and estimate the need for trachoma control interventions to eliminate blinding trachoma. METHODS AND FINDINGS: Separate, population based cross-sectional surveys were conducted in 88 localities (districts) in 12 northern states of Sudan between 2006 and 2010. Two-stage cluster random sampling with probability proportional to size was used to select the sample. Trachoma grading was done using the WHO simplified grading system. Key prevalence indicators were trachomatous inflammation-follicular (TF) in children aged 1-9 years and trachomatous trichiasis (TT) in adults aged 15 years and above. The sample comprised 1,260 clusters from which 25,624 households were surveyed. A total of 106,697 participants (81.6% response rate) were examined for trachoma signs. TF prevalence was above 10% in three districts and between 5% and 9% in 11 districts. TT prevalence among adults was above 1% in 20 districts (which included the three districts with TF prevalence >10%). The overall number of people with TT in the population was estimated to be 31,072 (lower and upper bounds = 26,125-36,955). CONCLUSION: Trachoma mapping is complete in the northern states of Sudan except for the Darfur States. The survey findings will facilitate programme planning and inform deployment of resources for elimination of trachoma from the northern states of Sudan by 2015, in accordance with the Sudan Federal Ministry of Health (FMOH) objectives.