District-Level Forecast of Achieving Trachoma Elimination as a Public Health Problem By 2030: An Ensemble Modelling Approach.

Assessing the feasibility of 2030 as a target date for global elimination of trachoma, and identification of districts that may require enhanced treatment to meet World Health Organization (WHO) elimination criteria by this date are key challenges in operational planning for trachoma programmes. Here we address these challenges by prospectively evaluating forecasting models of trachomatous inflammation-follicular (TF) prevalence, leveraging ensemble-based approaches. Seven candidate probabilistic models were developed to forecast district-wise TF prevalence in 11 760 districts, trained using district-level data on the population prevalence of TF in children aged 1-9 years from 2004 to 2022. Geographical location, history of mass drug administration treatment, and previously measured prevalence data were included in these models as key predictors. The best-performing models were included in an ensemble, using weights derived from their relative likelihood scores. To incorporate the inherent stochasticity of disease transmission and challenges of population-level surveillance, we forecasted probability distributions for the TF prevalence in each geographic district, rather than predicting a single value. Based on our probabilistic forecasts, 1.46% (95% confidence interval [CI]: 1.43-1.48%) of all districts in trachoma-endemic countries, equivalent to 172 districts, will exceed the 5% TF control threshold in 2030 with the current interventions. Global elimination of trachoma as a public health problem by 2030 may require enhanced intervention and/or surveillance of high-risk districts.

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.

Using model-based geostatistics for assessing the elimination of trachoma.

BACKGROUND: Trachoma is the commonest infectious cause of blindness worldwide. Efforts are being made to eliminate trachoma as a public health problem globally. However, as prevalence decreases, it becomes more challenging to precisely predict prevalence. We demonstrate how model-based geostatistics (MBG) can be used as a reliable, efficient, and widely applicable tool to assess the elimination status of trachoma. METHODS: We analysed trachoma surveillance data from Brazil, Malawi, and Niger. We developed geostatistical Binomial models to predict trachomatous inflammation-follicular (TF) and trachomatous trichiasis (TT) prevalence. We proposed a general framework to incorporate age and gender in the geostatistical models, whilst accounting for residual spatial and non-spatial variation in prevalence through the use of random effects. We also used predictive probabilities generated by the geostatistical models to quantify the likelihood of having achieved the elimination target in each evaluation unit (EU). RESULTS: TF and TT prevalence varied considerably by country, with Brazil showing the lowest prevalence and Niger the highest. Brazil and Malawi are highly likely to have met the elimination criteria for TF in each EU, but, for some EUs, there was high uncertainty in relation to the elimination of TT according to the model alone. In Niger, the predicted prevalence varied significantly across EUs, with the probability of having achieved the elimination target ranging from values close to 0% to 100%, for both TF and TT. CONCLUSIONS: We demonstrated the wide applicability of MBG for trachoma programmes, using data from different epidemiological settings. Unlike the standard trachoma prevalence survey approach, MBG provides a more statistically rigorous way of quantifying uncertainty around the achievement of elimination prevalence targets, through the use of spatial correlation. In addition to the analysis of existing survey data, MBG also provides an approach to identify areas in which more sampling effort is needed to improve EU classification. We advocate MBG as the new standard method for analysing trachoma survey outputs.

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.

Evaluation of facial cleanliness and environmental improvement activities: Lessons learned from Malawi, Tanzania, and Uganda.

The World Health Organization promotes the SAFE (Surgery, Antibiotics, Facial cleanliness, and Environmental improvements) strategy for trachoma control and prevention. The F&E components of the strategy focus on promotion of healthy hygiene and sanitation behaviors. In order to monitor F&E activities implemented across villages and schools in Malawi, Tanzania, and Uganda, an F&E Monitoring and Evaluation (FEME) framework was developed to track quarterly program outputs and to provide the basis for a pre and post evaluation of the activities. Results showed an increase in knowledge at the school and household levels, and in some cases, an increase in presence of hand/face washing stations. However, this did not always result in a change in trachoma prevention behaviors such as facial cleanliness or keeping compounds free of human feces. The results highlight that the F&E programs were effective in increasing awareness of trachoma prevention but not able to translate that knowledge into changes in behavior during the time between pre and post-surveys. This study also indicates the potential to improve the data collection and survey design and notes that the period of intervention was not long enough to measure significant changes.

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.

Pgp3 seroprevalence and associations with active trachoma and ocular Chlamydia trachomatis infection in Malawi: cross-sectional surveys in six evaluation units.

BACKGROUND: Following one to five years of antibiotic mass drug administration (MDA) for the elimination of trachoma as a public health problem, programmes must conduct impact surveys to inform decisions on whether MDA is still needed. These decisions are currently based on the prevalence of trachomatous inflammation-follicular (TF), which, after MDA, correlates poorly with prevalence of ocular Chlamydia trachomatis infection. METHODOLOGY/PRINCIPAL FINDINGS: Impact surveys in six evaluation units (EUs) of Malawi were used as a platform to explore associations between the prevalence of TF, ocular C. trachomatis infection and anti-Pgp3 antibodies one year after the third annual round of MDA. Participants were examined for trachoma using the World Health Organization simplified grading system. Ocular swabs and dried blood spots (DBS) were collected from children aged 1-9 years. Swabs were tested for C. trachomatis DNA using GeneXpert. DBS were assayed for anti-Pgp3 antibodies using ELISA. EU-level prevalence of TF in children aged 1-9 years ranged from 4.7% (95% CI 3.4-6.3) to 7.2% (95% CI 5.8-8.9). Prevalence of C. trachomatis infection in children ranged from 0.1% (95% CI 0.0-0.6) to 0.7% (95% CI 0.3-1.3) while Pgp3 seroprevalence ranged from 6.9% (95% CI 5.4-8.6) to 12.0% (95% CI 10.1-14.0) and increased with age. CONCLUSIONS/SIGNIFICANCE: Based on current global policy, the prevalence of TF indicates that a further year of antibiotic MDA is warranted in four of six EUs yet the very low levels of infection cast doubt on the universal applicability of TF-based cut-offs for antibiotic MDA. Pgp3 seroprevalence was similar to that reported following MDA in other settings that have reached the elimination target however the predictive value of any particular level of seropositivity with respect to risk of subsequent infection recrudescence is, as yet, unknown.

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.

One round of azithromycin MDA adequate to interrupt transmission in districts with prevalence of trachomatous inflammation-follicular of 5.0-9.9%: Evidence from Malawi.

BACKGROUND: As highly trachoma-endemic countries approach elimination, some districts will have prevalences of trachomatous inflammation-follicular in 1-9-year-olds (TF1-9) of 5.0-9.9%. The World Health Organization (WHO) previously recommended that in such districts, TF prevalence be assessed in each sub-district (groupings of at least three villages), with three rounds of azithromycin treatment offered to any sub-district in which TF≥10%. Given the large number of endemic districts worldwide and the human and financial resources required to conduct surveys, this recommendation may not be practical. In a group of 8 Malawi districts with baseline TF prevalences of 5.0-9.9%, the Malawi Ministry of Health administered one round of azithromycin mass treatment, to the whole of each district, achieving mean coverage of ~80%. Here, we report impact surveys conducted after that treatment. METHODS: We undertook population-based trachoma surveys in 18 evaluation units of the 8 treated districts, at least 6 months after the MDA. The standardized training package and survey methodologies of Tropical Data, which conform to WHO recommendations, were used. RESULTS: Each of the 18 evaluation units had a TF1-9 prevalence <5.0%. CONCLUSION: The study demonstrates that in Malawi districts with TF of 5.0-9.9%, one round of azithromycin MDA with ~80% coverage associates with a reduction in TF prevalence to <5%. Further evidence for this approach should be collected elsewhere.

Completion of Baseline Trachoma Mapping in Malawi: Results of Eight Population-Based Prevalence Surveys Conducted with the Global Trachoma Mapping Project.

PURPOSE: Following a first phase of trachoma mapping in Malawi with the Global Trachoma Mapping Project, we identified and mapped trachoma districts previously suspected to be non-endemic, although adjacent to districts with estimated trachoma prevalences indicating a public health problem. METHODS: We conducted population-based surveys in eight evaluation units (EUs) comprising eight districts in Malawi (total population 3,230,272). A 2-stage cluster random sampling design allowed us to select 30 households from each of 30 clusters per EU; all residents aged 1 year and older in selected households were examined for evidence of trachomatous inflammation-follicular (TF) and trachomatous trichiasis (TT). RESULTS: None of the eight EUs had a TF prevalence in 1-9-year-olds ≥10%, one district (Dedza) had a TF prevalence between 5.0% and 9.9%, and only one district (Karonga) had a trichiasis prevalence in adults ≥0.2%. CONCLUSION: The prevalence of TF and TT in six of eight EUs surveyed was consistent with an original categorization of trachoma being unlikely to be a public health problem. In the absence of formal surveys, health management information system data and other locally available information about trachoma is likely to be useful in predicting areas where public health interventions against trachoma are required.

Baseline Trachoma Mapping in Malawi with the Global Trachoma Mapping Project (GTMP).

PURPOSE: To determine the prevalence of trachoma in all suspected endemic districts in Malawi. METHODS: A population-based survey conducted in 16 evaluation units from 12 suspected endemic districts in Malawi (population 6,390,517), using the standardized Global Trachoma Mapping Project (GTMP) protocol. A 2-stage cluster-random sampling design selected 30 households from each of 30 clusters per evaluation unit; all residents aged 1 year and older in selected households were examined for evidence of follicular trachoma (TF), intense trachomatous inflammation (TI), and trachomatous trichiasis (TT). RESULTS: Four of the 16 evaluation units were found to be endemic for trachoma, with a prevalence range of 10.0-13.5% for TF and 0.2-0.6% for TT. Nine evaluation units had a TF prevalence between 5.0% and 9.9% while three evaluation units had a TF prevalence <5.0%. CONCLUSION: The prevalence rates of active trachoma in Malawi were not uniform among suspected endemic evaluation units, with rates higher than the World Health Organization (WHO) threshold for implementation of community-based control measures (TF ≥ 10.0%) in only 4 of the 16 evaluation units. Trachoma remains a disease of public health importance in some parts of Malawi and adjoining (unmapped) districts should be prioritized for mapping. According to the survey, an additional 3,169,362 people require intervention to reduce active disease and 1557 trichiasis surgeries are needed to reduce the prevalence of TT below WHO recommended thresholds.