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Background Great progress has been made toward the elimination of trachoma as a public-health problem. Mathematical and statistical models have been used to forecast when the program will attain the goal of the elimination of active trachoma, defined as prevalence of trachomatous inflammation-follicular in 1-9 year olds (TF.sub.1-9) <5%. Here we use program data to create an empirical model predicting the year of attaining global elimination of TF.sub.1-9. Methodology/Principal findings We calculated the mean number of years (95% CI) observed for an implementation unit (IU) to move from a baseline TF.sub.1-9 prevalence [greater than or equal to]5% to the elimination threshold, based on the region (Ethiopia vs. non-Ethiopia) and baseline prevalence category. Ethiopia IUs had significantly different rates of reaching the TF.sub.1-9 elimination threshold after a trachoma impact survey (TIS) compared to non-Ethiopia IUs across all baseline categories. We used those estimates to predict when remaining active trachoma-endemic IUs (TF.sub.1-9 [greater than or equal to]5%) would have their last round of mass drug administration (MDA) based on the mean number of years required and number of MDA rounds already completed. Our model predicts that elimination of TF.sub.1-9 will be achieved in 2028 in Ethiopia (95% CI: 2026-2033) and 2029 outside of Ethiopia (95% CI: 2023-2034), with some IUs in East Africa predicted to be the last requiring MDA globally. Conclusions/Significance Our empirical estimate is similar to those resulting from previous susceptible-infectious-susceptible (SIS) and mathematical models, suggesting that the forecast achievement of TF.sub.1-9 elimination is realistic with the caveat that although disease elimination progress can be predicted for most IUs, there is an important minority of IUs that is not declining or has not yet started trachoma elimination activities. These IUs represent an important barrier to the timely global elimination of active trachoma.

Soil-transmitted helminth (STH) infections remain a public health problem in Uganda despite biannual national deworming campaigns implemented since the early 2000s. Recent surveys have indicated a heterogeneous STH infection prevalence, suggesting that the current blanket deworming strategy may no longer be cost-effective. This study identified infection predictors, estimated the geographic distribution of STH infection prevalence by species, and calculated deworming needs for school-age children (SAC). Bayesian geostatistical models were applied to STH survey data (2021-2023) for each species (i.e., Ascaris lumbricoides, hookworm, and Trichuris trichiura). Climatic, environmental, and socioeconomic predictors were obtained from remote sensing sources, model-based databases, and demographic and health surveys. Prevalence was predicted on a 1 × 1 km2 grid across Uganda, and district-level estimates were used to classify each district into treatment frequency categories and to determine its deworming tablet requirements. The national prevalence of A. lumbricoides, T. trichiura, and hookworm was estimated at 5.0% (95% Bayesian credible interval [BCI]: 0.8-11.8%), 3.5% (0.7-9.3%), and 7.2% (5.7-11.1%), respectively. The overall prevalence of any STH infection was 14.3% (9.6-21.8%). High intra-district variation in prevalence was observed. Of 146 implementation units (136 districts and 10 cities), 49 require twice-year treatment, 34 once-yearly treatment, 61 every other year treatment, and 2 had a prevalence <2%, indicating treatment suspension or event-based treatment. Approximately 17 million tablets will be needed for preventive chemotherapy aimed at SAC in 2025. The prevalence of STH infection has declined considerably across Uganda compared to the early 2000s. However, deworming needs remain heterogeneous across districts. Through geostatistical modeling, districts were classified according to the latest World Health Organization's (WHO) treatment guidelines. This approach optimizes treatment distribution and allows for prioritization of populations with the greatest needs. We estimated that tablet requirements are approximately 40% lower compared to the current twice-a-year deworming regimen, which contributes towards WHO's goal of halving the number of tablets required for preventive chemotherapy by 2030.

In our view, the integrated and holistic SAFE strategy to eliminate trachoma-a strategy based on surgical correction of misplaced lashes, the mass distribution of donated antibiotics, and the promotion of water, sanitation, and hygiene (WASH)-makes the program the most compelling of the neglected tropical disease (NTD) elimination programs. An annual dose of azithromycin increases child survivorship by reducing mortality from common ailments like malaria, bacterial respiratory tract infections, and diarrhea, the three of which remain the primary killers of children living in poverty-children who do not have routine access to antibiotics [2, 3]. Scaling up the donation program When the World Health Assembly adopted the elimination of trachoma in 1998, the geographical distribution of the disease and numbers affected could only be estimated. Without a clear understanding of the scale of the problem, the pharmaceutical company Pfizer Inc. agreed to an initial donation of 10 million doses of its antibiotic azithromycin through the International Trachoma Initiative as a proof of concept after it was demonstrated that a single oral dose was as effective as the current standard treatment of six weeks of topical ophthalmic tetracycline [4]. [...]the donation was quickly increased to 35 million doses. [...]we were not shooting in the dark, new financial resources were made available (largely from the United States and United Kingdom governments and the Queen Elizabeth Diamond Jubilee Trust), and Pfizer Inc. once again doubled the size of its donation to over 100 million doses a year in 2016 (Fig 1). The global program remains...

The World Health Organization recommends annual mass azithromycin administration in communities with at least 10% prevalence of trachomatous inflammation-follicular (TF) in children, with further treatment depending on reassessment after 3-5 years. However, the effect of stopping mass azithromycin distribution after multiple rounds of treatment is not well understood. Here, we report the results of a cluster-randomized trial where communities that had received 4 years of treatments were then randomized to continuation or discontinuation of treatment. In all, 48 communities with 3,938 children aged 0-9 years at baseline in northern Ethiopia had received 4 years of annual or twice yearly mass azithromycin distribution as part of the TANA I trial. We randomized these communities to either continuation or discontinuation of treatment. Individuals in the communities in the continuation arm were offered either annual or twice yearly distribution of a single directly observed dose of oral azithromycin. The primary outcome was community prevalence of ocular chlamydial infection in a random sample of children aged 0-9 years, 36 months after baseline. We also assessed the change from baseline to 36 months in ocular chlamydia prevalence within each arm. We compared 36-month ocular chlamydia prevalence in communities randomized to continuation versus discontinuation in a model adjusting for baseline ocular chlamydia prevalence. A secondary prespecified analysis assessed the rate of change over time in ocular chlamydia prevalence between arms. In the continuation arm, mean antibiotic coverage was greater than 90% at all time points. In the discontinuation arm, the mean prevalence of infection in children aged 0-9 years increased from 8.3% (95% CI 4.2% to 12.4%) at 0 months to 14.7% (95% CI 8.7% to 20.8%, P = 0.04) at 36 months. Ocular chlamydia prevalence in communities where mass azithromycin distribution was continued was 7.2% (95% CI 3.3% to 11.0%) at baseline and 6.6% (95% CI 1.1% to 12.0%, P = 0.64) at 36 months. The 36-month prevalence of ocular chlamydia was significantly lower in communities continuing treatment compared with those discontinuing treatment (P = 0.03). Limitations of the study include uncertain generalizability outside of trachoma hyperendemic regions. In this study, ocular chlamydia infection rebounded after 4 years of periodic mass azithromycin distribution. Continued distributions did not completely eliminate infection in all communities or meet WHO control goals, although they did prevent resurgence. This study was prospectively registered at clinicaltrials.gov (clinicaltrials.gov NCT01202331).

Background Preventive chemotherapy (PC) is a central strategy for control and elimination of neglected tropical diseases (NTDs). Increased emphasis has been given to \"integration\" of NTD programs within health systems and coadministration of NTD drugs offers significant programmatic benefits. Guidance from the World Health Organization (WHO) reflects current evidence for safe drug coadministration and highlights measures to prevent choking of young children during PC. Methodology To understand how coadministration of NTD drugs might affect PC safety, we reviewed literature on choking risk in young children and safety of coadministered NTD drugs. To understand current practices of drug coadministration, we surveyed 15 NTD program managers and implementing partners. Principal findings In high-income countries, choking on medication is an infrequent cause of death in young children. In low-resource settings, data are limited, but age-appropriate drug formulations are less available. During PC, fatal choking, although infrequent, occurs primarily in young children; forcing them to swallow tablets appears to be the major risk factor. The WHO currently recommends 6 drugs and 5 possible drug combinations for use in PC. Of 105 nations endemic for the 5 PC-NTDs, 72 (68.6%) are co-endemic for 2 or more diseases and could benefit from drug coadministration during PC. All 15 survey respondents reported coadministering medications during PC. Reported responses to a child refusing to take medicine included: not forcing the child to do so (60.0%), encouraging the child (46.7%), bringing the child back later (26.7%), offering powder for oral suspension (POS) for azithromycin (13.3%), and having parents or community members intervene to calm the child (6.7%). Conclusions Coadministration of NTD drugs during PC appears to be increasingly common. Safety of coadministered PC drugs requires attention to choking prevention, use of approved drug combinations, and increased access to age-appropriate drug formulations.

Large cross-sectional household surveys are common for measuring indicators of neglected tropical disease control programs. As an alternative to standard paper-based data collection, we utilized novel paperless technology to collect data electronically from over 12,000 households in Ethiopia. We conducted a needs assessment to design an Android-based electronic data collection and management system. We then evaluated the system by reporting results of a pilot trial and from comparisons of two, large-scale surveys; one with traditional paper questionnaires and the other with tablet computers, including accuracy, person-time days, and costs incurred. The electronic data collection system met core functions in household surveys and overcame constraints identified in the needs assessment. Pilot data recorders took 264 (standard deviation (SD) 152 sec) and 260 sec (SD 122 sec) per person registered to complete household surveys using paper and tablets, respectively (P = 0.77). Data recorders felt a lack of connection with the interviewee during the first days using electronic devices, but preferred to collect data electronically in future surveys. Electronic data collection saved time by giving results immediately, obviating the need for double data entry and cross-correcting. The proportion of identified data entry errors in disease classification did not differ between the two data collection methods. Geographic coordinates collected using the tablets were more accurate than coordinates transcribed on a paper form. Costs of the equipment required for electronic data collection was approximately the same cost incurred for data entry of questionnaires, whereas repeated use of the electronic equipment may increase cost savings. Conducting a needs assessment and pilot testing allowed the design to specifically match the functionality required for surveys. Electronic data collection using an Android-based technology was suitable for a large-scale health survey, saved time, provided more accurate geo-coordinates, and was preferred by recorders over standard paper-based questionnaires.

In Bangladesh, preventive chemotherapy targeting soil-transmitted helminth (STH) infections in school-age children has been implemented since 2008. To evaluate the success of this strategy, surveys were conducted between 2017 and 2020 in 10 out of 64 districts. We estimate the geographic distribution of STH infections by species at high spatial resolution, identify risk factors, and estimate treatment needs at different population subgroups. Bayesian geostatistical models were fitted to prevalence data of each STH species. Climatic, environmental, and socioeconomic predictors were extracted from satellite images, open-access, model-based databases, and demographic household surveys, and used to predict the prevalence of infection over a gridded surface at 1 x 1 km spatial resolution across the country, via Bayesian kriging. These estimates were combined with gridded population data to estimate the number of required treatments for different risk groups. The population-adjusted prevalence of Ascaris lumbricoides, Trichuris trichiura, and hookworm across all ages is estimated at 9.9% (95% Bayesian credible interval: 8.0-13.0%), 4.3% (3.0-7.3%), and 0.6% (0.4-0.9%), respectively. There were 24 out of 64 districts with an estimated population-adjusted STH infection prevalence above 20%. The proportion of households with improved sanitation showed a statistically important, protective association for both, A. lumbricoides and T. trichiura prevalence. Precipitation in the driest month of the year was negatively associated with A. lumbricoides prevalence. High organic carbon concentration in the soil's fine earth fraction was related to a high hookworm prevalence. Furthermore, we estimated that 30.5 (27.2; 36.0) million dosages of anthelmintic treatments for school-age children were required per year in Bangladesh. For each of the STH species, the prevalence was reduced by at least 80% since treatment was scaled up more than a decade ago. The current number of deworming dosages could be reduced by up to 61% if the treatment strategy was adapted to the local prevalence.

Trachoma causes blindness due to repeated conjunctival infection by Chlamydia trachomatis (Ct). Transmission intensity is estimated, for programmatic decision-making, by prevalence of the clinical sign trachomatous inflammation-follicular (TF) in children aged 1-9 years. Research into complementary indicators to field-graded TF includes work on conjunctival photography, tests for ocular Ct infection, and serology. The perceived acceptability and feasibility of these indicators among a variety of stakeholders is unknown. Focus group discussions (FGDs) with community members and in-depth interviews (IDIs) with public health practitioners in Tanzania were conducted. FGDs explored themes including participants' experience with, and thoughts about, different diagnostic approaches. The framework method for content analysis was used. IDIs yielded lists of perceived strengths of, and barriers to, implementation for programmatic use of each indicator. These were used to form an online quantitative survey on complementary indicators distributed to global stakeholders via meetings, mailing lists, and social media posts. Sixteen FGDs and 11 IDIs were conducted in October-November 2022. In general, all proposed sample methods were deemed acceptable by community members. Common themes included not wanting undue discomfort and a preference for tests perceived as accurate. Health workers noted the importance of community education for some sample types. The online survey was conducted in April-May 2023 with 98 starting the questionnaire and 81 completing it. Regarding barriers to implementing diagnostics, the highest agreement items related to feasibility, rather than acceptability. No evidence of significant differences was found in responses pertaining to community acceptability based on participant characteristics. All of the indicators included were generally deemed acceptable by all stakeholders in Tanzania, although community education around the benefits and risks of different sample types, as well as addressing issues around feasibility, will be key to successful, sustainable integration of these indicators into trachoma programs.

Trachoma causes blindness through a conjunctival scarring process initiated by ocular Chlamydia trachomatis infection; however, the rates, drivers and pathophysiological determinants are poorly understood. We investigated progressive scarring and its relationship to conjunctival infection, inflammation and transcript levels of cytokines and fibrogenic factors. We recruited two cohorts, one each in Ethiopia and Tanzania, of individuals with established trachomatous conjunctival scarring. They were followed six-monthly for two years, with clinical examinations and conjunctival swab sample collection. Progressive scarring cases were identified by comparing baseline and two-year photographs, and compared to individuals without progression. Samples were tested for C. trachomatis by PCR and transcript levels of S100A7, IL1B, IL13, IL17A, CXCL5, CTGF, SPARCL1, CEACAM5, MMP7, MMP9 and CD83 were estimated by quantitative RT-PCR. Progressive scarring was found in 135/585 (23.1%) of Ethiopian participants and 173/577 (30.0%) of Tanzanian participants. There was a strong relationship between progressive scarring and increasing inflammatory episodes (Ethiopia: OR 5.93, 95%CI 3.31-10.6, p<0.0001. Tanzania: OR 5.76, 95%CI 2.60-12.7, p<0.0001). No episodes of C. trachomatis infection were detected in the Ethiopian cohort and only 5 episodes in the Tanzanian cohort. Clinical inflammation, but not scarring progression, was associated with increased expression of S100A7, IL1B, IL17A, CXCL5, CTGF, CEACAM5, MMP7, CD83 and reduced SPARCL1. Scarring progressed in the absence of detectable C. trachomatis, which raises uncertainty about the primary drivers of late-stage trachoma. Chronic conjunctival inflammation appears to be central and is associated with enriched expression of pro-inflammatory factors and altered expression of extracellular matrix regulators. Host determinants of scarring progression appear more complex and subtle than the features of inflammation. Overall this indicates a potential role for anti-inflammatory interventions to interrupt progression and the need for trichiasis disease surveillance and surgery long after chlamydial infection has been controlled at community level.