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.

When the Neighboring Village is Not Treated: Role of Geographic Proximity to Communities Not Receiving Mass Antibiotics for Trachoma.

BACKGROUND: Mass administration of azithromycin is an established strategy for decreasing the prevalence of trachoma in endemic areas. However, nearby untreated communities could serve as a reservoir that may increase the chances of chlamydia reinfection in treated communities. METHODS: As part of a cluster-randomized trial in Ethiopia, 60 communities were randomized to receive mass azithromycin distributions and 12 communities were randomized to no treatments until after the first year. Ocular chlamydia was assessed from a random sample of children per community at baseline and month 12. Distances between treated and untreated communities were assessed from global positioning system coordinates collected for the study. RESULTS: The pretreatment prevalence of ocular chlamydia among 0 to 9 year olds was 43% (95% confidence interval [CI], 39%-47%), which decreased to 11% (95% CI, 9%-14%) at the 12-month visit. The posttreatment prevalence of chlamydia was significantly higher in communities that were closer to an untreated community after adjusting for baseline prevalence and the number of mass treatments during the year (odds ratio, 1.12 [95% CI, 1.03-1.22] for each 1 km closer to an untreated community). CONCLUSIONS: Mass azithromycin distributions to wide, contiguous geographic areas may reduce the likelihood of continued ocular chlamydia infection in the setting of mass antibiotic treatments.

Longer-Term Assessment of Azithromycin for Reducing Childhood Mortality in Africa.

BACKGROUND: The MORDOR I trial (Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance) showed that in Niger, mass administration of azithromycin twice a year for 2 years resulted in 18% lower postneonatal childhood mortality than administration of placebo. Whether this benefit could increase with each administration or wane owing to antibiotic resistance was unknown. METHODS: In the Niger component of the MORDOR I trial, we randomly assigned 594 communities to four twice-yearly distributions of either azithromycin or placebo to children 1 to 59 months of age. In MORDOR II, all these communities received two additional open-label azithromycin distributions. All-cause mortality was assessed twice yearly by census workers who were unaware of participants' original assignments. RESULTS: In the MORDOR II trial, the mean (±SD) azithromycin coverage was 91.3±7.2% in the communities that received twice-yearly azithromycin for the first time (i.e., had received placebo for 2 years in MORDOR I) and 92.0±6.6% in communities that received azithromycin for the third year (i.e., had received azithromycin for 2 years in MORDOR I). In MORDOR II, mortality was 24.0 per 1000 person-years (95% confidence interval [CI], 22.1 to 26.3) in communities that had originally received placebo in the first year and 23.3 per 1000 person-years (95% CI, 21.4 to 25.5) in those that had originally received azithromycin in the first year, with no significant difference between groups (P = 0.55). In communities that had originally received placebo, mortality decreased by 13.3% (95% CI, 5.8 to 20.2) when the communities received azithromycin (P = 0.007). In communities that had originally received azithromycin and continued receiving it for an additional year, the difference in mortality between the third year and the first 2 years was not significant (-3.6%; 95% CI, -12.3 to 4.5; P = 0.50). CONCLUSIONS: We found no evidence that the effect of mass administration of azithromycin on childhood mortality in Niger waned in the third year of treatment. Childhood mortality decreased when communities that had originally received placebo received azithromycin. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT02047981.).

Forecasting Trachoma Control and Identifying Transmission-Hotspots.

BACKGROUND: Tremendous progress towards elimination of trachoma as a public health problem has been made. However, there are areas where the clinical indicator of disease, trachomatous inflammation-follicular (TF), remains prevalent. We quantify the progress that has been made, and forecast how TF prevalence will evolve with current interventions. We also determine the probability that a district is a transmission-hotspot based on its TF prevalence (ie, reproduction number greater than one). METHODS: Data on trachoma prevalence come from the GET2020 global repository organized by the World Health Organization and the International Trachoma Initiative. Forecasts of TF prevalence and the percent of districts with local control is achieved by regressing the coefficients of a fitted exponential distribution for the year-by-year distribution of TF prevalence. The probability of a district being a transmission-hotspot is extrapolated from the residuals of the regression. RESULTS: Forecasts suggest that with current interventions, 96.5% of surveyed districts will have TF prevalence among children aged 1-9 years <5% by 2030 (95% CI: 86.6%-100.0%). Districts with TF prevalence < 20% appear unlikely to be transmission-hotspots. However, a district having TF prevalence of over 28% in 2016-2019 corresponds to at least 50% probability of being a transmission-hotspot. CONCLUSIONS: Sustainable control of trachoma appears achievable. However there are transmission-hotspots that are not responding to annual mass drug administration of azithromycin and require enhanced treatment in order to reach local control.

Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa.

BACKGROUND: We hypothesized that mass distribution of a broad-spectrum antibiotic agent to preschool children would reduce mortality in areas of sub-Saharan Africa that are currently far from meeting the Sustainable Development Goals of the United Nations. METHODS: In this cluster-randomized trial, we assigned communities in Malawi, Niger, and Tanzania to four twice-yearly mass distributions of either oral azithromycin (approximately 20 mg per kilogram of body weight) or placebo. Children 1 to 59 months of age were identified in twice-yearly censuses and were offered participation in the trial. Vital status was determined at subsequent censuses. The primary outcome was aggregate all-cause mortality; country-specific rates were assessed in prespecified subgroup analyses. RESULTS: A total of 1533 communities underwent randomization, 190,238 children were identified in the census at baseline, and 323,302 person-years were monitored. The mean (±SD) azithromycin and placebo coverage over the four twice-yearly distributions was 90.4±10.4%. The overall annual mortality rate was 14.6 deaths per 1000 person-years in communities that received azithromycin (9.1 in Malawi, 22.5 in Niger, and 5.4 in Tanzania) and 16.5 deaths per 1000 person-years in communities that received placebo (9.6 in Malawi, 27.5 in Niger, and 5.5 in Tanzania). Mortality was 13.5% lower overall (95% confidence interval [CI], 6.7 to 19.8) in communities that received azithromycin than in communities that received placebo (P<0.001); the rate was 5.7% lower in Malawi (95% CI, -9.7 to 18.9), 18.1% lower in Niger (95% CI, 10.0 to 25.5), and 3.4% lower in Tanzania (95% CI, -21.2 to 23.0). Children in the age group of 1 to 5 months had the greatest effect from azithromycin (24.9% lower mortality than that with placebo; 95% CI, 10.6 to 37.0). Serious adverse events occurring within a week after administration of the trial drug or placebo were uncommon, and the rate did not differ significantly between the groups. Evaluation of selection for antibiotic resistance is ongoing. CONCLUSIONS: Among postneonatal, preschool children in sub-Saharan Africa, childhood mortality was lower in communities randomly assigned to mass distribution of azithromycin than in those assigned to placebo, with the largest effect seen in Niger. Any implementation of a policy of mass distribution would need to strongly consider the potential effect of such a strategy on antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation; MORDOR ClinicalTrials.gov number, NCT02047981 .).

Ocular Chlamydia trachomatis Infection Under the Surgery, Antibiotics, Facial Cleanliness, and Environmental Improvement Strategy in Amhara, Ethiopia, 2011-2015.

Background: World Health Organization (WHO) recommendations for starting and stopping mass antibiotic distributions are based on a clinical sign of trachoma, which is indirectly related to actual infection with the causative agent, Chlamydia trachomatis. Methods: This study aimed to understand the effect of SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) interventions on ocular chlamydia in Amhara, Ethiopia, by describing the infection prevalence in a population-based sample of children aged 1-5 years. Trachoma surveys were conducted in all districts of Amhara, from 2011 to 2015 following approximately 5 years of SAFE. Ocular swabs were collected from randomly selected children to estimate the zonal prevalence of chlamydial infection. The Abbott RealTime polymerase chain reaction assay was used to detect C. trachomatis DNA. Results: A total of 15632 samples were collected across 10 zones of Amhara. The prevalence of chlamydial infection in children aged 1-5 years was 5.7% (95% confidence interval, 4.2%-7.3%; zonal range, 1.0%-18.5%). Chlamydial infection and trachomatous inflammation-intense (TI) among children aged 1-9 years were highly correlated at the zonal level (Spearman correlation [r] = 0.93; P < .001), while chlamydial infection and trachomatous inflammation-follicular were moderately correlated (r = 0.57; P = .084). Conclusions: After 5 years of SAFE, there is appreciable chlamydial infection in children aged 1-5 years, indicating that transmission has not been interrupted and that interventions should continue. The sign TI was highly correlated with chlamydial infection and can be used as a proxy indicator of infection.

Mass azithromycin distribution for hyperendemic trachoma following a cluster-randomized trial: A continuation study of randomly reassigned subclusters (TANA II).

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: This study was prospectively registered at clinicaltrials.gov (clinicaltrials.gov NCT01202331).

Active trachoma and community use of sanitation, Ethiopia.

OBJECTIVE: To investigate, in Amhara, Ethiopia, the association between prevalence of active trachoma among children aged 1-9 years and community sanitation usage. METHODS: Between 2011 and 2014, prevalence of trachoma and household pit latrine usage were measured in five population-based cross-sectional surveys. Data on observed indicators of latrine use were aggregated into a measure of community sanitation usage calculated as the proportion of households with a latrine in use. All household members were examined for clinical signs, i.e. trachomatous inflammation, follicular and/or intense, indicative of active trachoma. Multilevel logistic regression was used to estimate prevalence odds ratios (OR) and 95% confidence intervals (CI), adjusting for community, household and individual factors, and to evaluate modification by household latrine use and water access. FINDINGS: In surveyed areas, prevalence of active trachoma among children was estimated to be 29% (95% CI: 28-30) and mean community sanitation usage was 47% (95% CI: 45-48). Despite significant modification (p < 0.0001), no pattern in stratified ORs was detected. Summarizing across strata, community sanitation usage values of 60 to < 80% and ≥ 80% were associated with lower prevalence odds of active trachoma, compared with community sanitation usage of < 20% (OR: 0.76; 95% CI: 0.57-1.03 and OR: 0.67; 95% CI: 0.48-0.95, respectively). CONCLUSION: In Amhara, Ethiopia, a negative correlation was observed between community sanitation usage and prevalence of active trachoma among children, highlighting the need for continued efforts to encourage higher levels of sanitation usage and to support sustained use throughout the community, not simply at the household level.

Evidence for clonal expansion after antibiotic selection pressure: pneumococcal multilocus sequence types before and after mass azithromycin treatments.

BACKGROUND: A clinical trial of mass azithromycin distributions for trachoma created a convenient experiment to test the hypothesis that antibiotic use selects for clonal expansion of preexisting resistant bacterial strains. METHODS: Twelve communities in Ethiopia received mass azithromycin distributions every 3 months for 1 year. A random sample of 10 children aged 0-9 years from each community was monitored by means of nasopharyngeal swab sampling before mass azithromycin distribution and after 4 mass treatments. Swab specimens were tested for Streptococcus pneumoniae, and isolates underwent multilocus sequence typing. RESULTS: Of 82 pneumococcal isolates identified before treatment, 4 (5%) exhibited azithromycin resistance, representing 3 different sequence types (STs): 177, 6449, and 6494. The proportion of isolates that were classified as one of these 3 STs and were resistant to azithromycin increased after 4 mass azithromycin treatments (14 of 96 isolates [15%]; P = .04). Using a classification index, we found evidence for a relationship between ST and macrolide resistance after mass treatments (P < .0001). The diversity of STs-as calculated by the unbiased Simpson index-decreased significantly after mass azithromycin treatment (P = .045). CONCLUSIONS: Resistant clones present before mass azithromycin treatments increased in frequency after treatment, consistent with the theory that antibiotic selection pressure results in clonal expansion of existing resistant strains.

Estimation of insecticide persistence, biological activity and mosquito resistance to PermaNet® 2 long-lasting insecticidal nets over three to 32 months of use in Ethiopia.

BACKGROUND: Information is needed on the expected durability of insecticidal nets under operational conditions. The persistence of insecticidal efficacy is important to estimate the median serviceable life of nets under field conditions and to plan for net replacement. METHODS: Deltamethrin residue levels were evaluated by the proxy method of X-ray fluorescence spectrometry on 189 nets used for three to six months from nine sites, 220 nets used for 14-20 months from 11 sites, and 200 nets used for 26-32 months from ten sites in Ethiopia. A random sample of 16.5-20% of nets from each time period (total 112 of 609 nets) were tested by bioassay with susceptible mosquitoes, and nets used for 14-20 months and 26-32 months were also tested with wild caught mosquitoes. RESULTS: Mean insecticide levels estimated by X-ray fluorescence declined by 25.9% from baseline of 66.2 (SD 14.6) mg/m2 at three to six months to 44.1 (SD 21.2) mg/m2 at 14-20 months and by 30.8% to 41.1 (SD 18.9) mg/m2 at 26-32 months. More than 95% of nets retained greater than 10 mg/m2 of deltamethrin and over 79% had at least 25 mg/m2 at all time periods. By bioassay with susceptible Anopheles, mortality averaged 89.0% on 28 nets tested at three to six months, 93.3% on 44 nets at 14-20 months and 94.1% on 40 nets at 26-32 months. With wild caught mosquitoes, mortality averaged 85.4% (range 79.1 to 91.7%) at 14-20 months but had dropped significantly to 47.2% (39.8 to 54.7%) at 26-32 months. CONCLUSIONS: Insecticide residue level, as estimated by X-ray fluorescence, declined by about one third between three and six months and 14-20 months, but remained relatively stable and above minimum requirements thereafter up to 26-32 months. The insecticidal activity of PermaNet® 2.0 long-lasting insecticidal nets in the specified study area may be considered effective to susceptible mosquitoes at least for the duration indicated in this study (32 months). However, results indicated that resistance in the wild population is already rendering nets with optimum insecticide concentrations less effective in practice.

Malaria prevalence, anemia and baseline intervention coverage prior to mass net distributions in Abia and Plateau States, Nigeria.

BACKGROUND: Nigeria suffers the world's largest malaria burden, with approximately 51 million cases and 207,000 deaths annually. As part of the country's aim to reduce by 50% malaria-related morbidity and mortality by 2013, it embarked on mass distribution of free long-lasting insecticidal nets (LLINs). METHODS: Prior to net distribution campaigns in Abia and Plateau States, Nigeria, a modified malaria indicator survey was conducted in September 2010 to determine baseline state-level estimates of Plasmodium prevalence, childhood anemia, indoor residual spraying (IRS) coverage and bednet ownership and utilization. RESULTS: Overall age-adjusted prevalence of Plasmodium infection by microscopy was similar between Abia (36.1%, 95% CI: 32.3%-40.1%; n = 2,936) and Plateau (36.6%, 95% CI: 31.3%-42.3%; n = 4,209), with prevalence highest among children 5-9 years. P. malariae accounted for 32.0% of infections in Abia, but only 1.4% of infections in Plateau. More than half of children ≤10 years were anemic, with anemia significantly higher in Abia (76.9%, 95% CI: 72.1%-81.0%) versus Plateau (57.1%, 95% CI: 50.6%-63.4%). Less than 1% of households in Abia (n = 1,305) or Plateau (n = 1,335) received IRS in the 12 months prior to survey. Household ownership of at least one bednet of any type was 10.1% (95% CI: 7.5%-13.4%) in Abia and 35.1% (95% CI: 29.2%-41.5%) in Plateau. Ownership of two or more bednets was 2.1% (95% CI: 1.2%-3.7%) in Abia and 14.5% (95% CI: 10.2%-20.3%) in Plateau. Overall reported net use the night before the survey among all individuals, children <5 years, and pregnant women was 3.4%, 6.0% and 5.7%, respectively in Abia and 14.7%, 19.1% and 21.0%, respectively in Plateau. Among households owning nets, 34.4% of children <5 years and 31.6% of pregnant women in Abia used a net, compared to 52.6% of children and 62.7% of pregnant women in Plateau. CONCLUSIONS: These results reveal high Plasmodium prevalence and childhood anemia in both states, low baseline coverage of IRS and LLINs, and sub-optimal net use-especially among age groups with highest observed malaria burden.

Acceptability and feasibility of tests for infection, serological testing, and photography to define need for interventions against trachoma.

BACKGROUND: 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. METHODOLOGY: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparison of annual versus twice-yearly mass azithromycin treatment for hyperendemic trachoma in Ethiopia: a cluster-randomised trial.

BACKGROUND: In trachoma control programmes, azithromycin is distributed to treat the strains of chlamydia that cause ocular disease. We aimed to compare the effect of annual versus twice-yearly distribution of azithromycin on infection with these strains. METHODS: We did a cluster-randomised trial in 24 subdistricts in northern Ethiopia, which we randomly assigned to receive annual or twice-yearly treatment for all residents of all ages. Random assignment was done with the RANDOM and SORT functions of Microsoft Excel. All individuals were offered their assigned treatment of a single, directly observed, oral dose of azithromycin. A 6 week course of topical 1% tetracycline ointment, applied twice daily to both eyes but not directly observed, was offered as an alternative to azithromycin in patients younger than 12 months, and in patients with self-reported pregnancy, with allergy, or who refused azithromycin. Our primary, prespecified outcome was the prevalence of ocular chlamydial infection in a random sample of children aged 0-9 years at baseline and every 6 months for a total of 42 months within sentinel villages. Our analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00322972. FINDINGS: Antibiotic coverage of children aged 1-9 years was greater than 80% (range 80·9 to 93·0) at all study visits. In the groups treated annually, the prevalence of infection in children aged 0-9 years was reduced from a mean 41·9% (95% CI 31·5 to 52·2) at baseline to 1·9% (0·3 to 3·5) at 42 months. In the groups treated twice yearly, the prevalence of infection was reduced from a mean 38·3% (29·0 to 47·6) at baseline to 3·2 % (0·0 to 6·5) at 42 months. The prevalence of ocular chlamydial infection in children aged 0-9 years in groups treated annually was not different from that of the groups treated twice yearly at 18, 30, and 42 months (pooled regression p>0·99, 95 % CI -0·06 to 0·06). The mean elimination time in the twice-yearly treatment group was 7·5 months earlier (2·3 to 17·3) than that of the annual group (p=0·10, Cox proportional hazards model). INTERPRETATION: After 42 months of treatment, the prevalence of ocular infection with chlamydia was similar in the groups treated annually and twice yearly. However, elimination of infection might have been more rapid in the groups of villages that received treatment twice yearly. FUNDING: National Institutes of Health (NEI U10 EY016214).

Physical durability of PermaNet 2.0 long-lasting insecticidal nets over three to 32 months of use in Ethiopia.

BACKGROUND: Ethiopia scaled up net distribution markedly starting in 2006. Information on expected net life under field conditions (physical durability and persistence of insecticidal activity) is needed to improve planning for net replacement. Standardization of physical durability assessment methods is lacking. METHODS: Permanet®2.0 long-lasting insecticidal bed nets (LLINs), available for distribution in early 2007, were collected from households at three time intervals. The number, size and location of holes were recorded for 189 nets used for three to six months from nine sites (2007) and 220 nets used for 14 to 20 months from 11 sites (2008). In 2009, a "finger/fist" sizing method classified holes in 200 nets used for 26 to 32 months from ten sites into small (<2 cm), medium (> = 2 to < =10 cm) and large (>10 cm) sizes. A proportionate hole index based on both hole number and area was derived from these size classifications. RESULTS: After three to six months, 54.5% (95% CI 47.1-61.7%) of 189 LLINs had at least one hole 0.5 cm (in the longest axis) or larger; mean holes per net was 4.4 (SD 8.4), median was 1.0 (Inter Quartile Range [IQR] 0-5) and median size was 1 cm (IQR 1-2). At 14 to 20 months, 85.5% (95% CI 80.1-89.8%) of 220 nets had at least one hole with mean 29.1 (SD 50.1) and median 12 (IQR 3-36.5) holes per net, and median size of 1 cm (IQR 1-2). At 26 to 32 months, 92.5% of 200 nets had at least one hole with a mean of 62.2 (SD 205.4) and median of 23 (IQR 6-55.5) holes per net. The mean hole index was 24.3, 169.1 and 352.8 at the three time periods respectively. Repairs were rarely observed. The majority of holes were in the lower half of the net walls. The proportion of nets in 'poor' condition (hole index >300) increased from 0% at three to six months to 30% at 26 to 32 months. CONCLUSIONS: Net damage began quickly: more than half the nets had holes by three to six months of use, with 40% of holes being larger than 2 cm. Holes continued to accumulate until 92.5% of nets had holes by 26 to 32 months of use. An almost complete lack of repairs shows the need for promoting proper use of nets and repairs, to increase LLIN longevity. Using the hole index, almost one third of the nets were classed as unusable and ineffective after two and a half years of potential use.

Distribution and treatment needs of soil-transmitted helminthiasis in Bangladesh: A Bayesian geostatistical analysis of 2017-2020 national survey data.

BACKGROUND: 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. METHODOLOGY: 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. PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

Ribosomal RNA evidence of ocular Chlamydia trachomatis infection following 3 annual mass azithromycin distributions in communities with highly prevalent trachoma.

Twelve trachoma-hyperendemic communities were treated with 3 annual mass azithromycin distributions. Children aged 0-9 years were monitored 1 year following the third treatment. An RNA-based test detected ocular chlamydial infection in more children than did a DNA-based test (6.9% vs 4.2%), and in a larger number of communities (8 vs 7).

Epilation for trachomatous trichiasis and the risk of corneal opacification.

PURPOSE: Eight million people have trachomatous trichiasis (TT). The World Health Organization (WHO) recommends entropion surgery for TT regardless of severity. However, epilation is widely practiced for treating minor TT (1-5 lashes touching the globe). We report the frequency and effectiveness of patient-initiated epilation and its relationship to corneal opacity. DESIGN: Cross-sectional baseline data of individuals recruited to 2 randomized, clinical trials. PARTICIPANTS: We included 2556 individuals (4310 eyes) with previously unoperated TT in ≥ 1 eye. METHODS: A single ophthalmologist examined all participants for signs of trachoma using WHO grading systems with additional assessment of entropion grading, location and number of trichiatic lashes, and evidence of epilation. A questionnaire enquired about epilation practices. MAIN OUTCOME MEASURES: The association between epilation and degree of corneal opacity. Epilation practices of TT patients. RESULTS: Central corneal scarring was present in 1436 (33%) eyes. Entropion was absent/mild in 2328 (54%) eyes, moderate in 1259 (29.2%), and severe in 723 (16.8%). The median number of lashes touching the eye was 2 (interquartile range, 1-5; range, 0-133). There was clinical evidence of epilation in 3018 (70%) eyes, of which 738 (24%) were successfully epilated (no lashes touching globe). Epilation was performed frequently (at least monthly in 3311 [76.8%] eyes), by someone other than the patient (92.8%), and using locally made forceps (88.9%). Controlling for age and degree of entropion, successful epilation was associated with less corneal opacity (odds ratio [OR], 0.61; 95% confidence interval [CI]. 0.43-0.88; P = 0.007). The association was only significant in patients with severe entropion (OR, 0.07; 95% CI, 0.02-0.25; P<0.005). CONCLUSIONS: We found an association between successful epilation and less central corneal opacity. This indicates the importance of preventing eyelashes from touching the cornea, particularly in individuals with severe entropion. This is a cross-sectional study; therefore, a causative relationship cannot be concluded. However, the results suggest that among patients who decline or are unable to access surgery, and perhaps in minor TT where the management remains controversial, the provision of high-quality forceps and epilation training may be beneficial. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Forecasting the elimination of active trachoma: An empirical model.

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 (TF1-9) <5%. Here we use program data to create an empirical model predicting the year of attaining global elimination of TF1-9. METHODOLOGY/PRINCIPAL FINDINGS: We calculated the mean number of years (95% CI) observed for an implementation unit (IU) to move from a baseline TF1-9 prevalence ≥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 TF1-9 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 (TF1-9 ≥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 TF1-9 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 TF1-9 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.

Safety of integrated preventive chemotherapy for neglected tropical diseases.

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.