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Trachoma is an infectious disease characterized by repeated exposures to Chlamydia trachomatis (Ct) that may ultimately lead to blindness. Efficient identification of communities with high infection burden could help target more intensive control efforts. We hypothesized that IgG seroprevalence in combination with geospatial layers, machine learning, and model-based geostatistics would be able to accurately predict future community-level ocular Ct infections detected by PCR. We used measurements from 40 communities in the hyperendemic Amhara region of Ethiopia to assess this hypothesis. Median Ct infection prevalence among children 0–5 years old increased from 6% at enrollment, in the context of recent mass drug administration (MDA), to 29% by month 36, following three years without MDA. At baseline, correlation between seroprevalence and Ct infection was stronger among children 0–5 years old (ρ = 0.77) than children 6–9 years old (ρ = 0.48), and stronger than the correlation between active trachoma and Ct infection (0-5y ρ = 0.56; 6-9y ρ = 0.40). Seroprevalence was the strongest concurrent predictor of infection prevalence at month 36 among children 0–5 years old (cross-validated R2 = 0.75, 95% CI: 0.58–0.85), though predictive performance declined substantially with increasing temporal lag between predictor and outcome measurements. Geospatial variables, a spatial Gaussian process, and stacked ensemble machine learning did not meaningfully improve predictions. Serological markers among children 0–5 years old may be an objective tool for identifying communities with high levels of ocular Ct infections, but accurate, future prediction in the context of changing transmission remains an open challenge. Author summary: Trachoma, one of the leading infectious causes of blindness globally, is targeted for elimination as a public health problem by 2030. District-level estimates of active trachoma among children 1–9 years old are currently used to guide control programs and assess elimination. However, active trachoma, based on diagnosis of clinical signs, is a subjective indicator. Serological markers present an objective, scalable alternative that could be measured in integrated platforms. In a hyperendemic region, community-level seroprevalence aligned more closely with concurrent infection prevalence than active trachoma. The correlation between seroprevalence and infection prevalence was stronger among 0–5-year-olds compared to 6–9-year-olds and was consistent over a three-year period of increasing transmission. Serosurveillance among children 0–5 years old may be a promising monitoring strategy to identify communities with the highest burdens of ocular chlamydial infection. [ABSTRACT FROM AUTHOR]

Background Current guidelines recommend community-wide mass azithromycin for trachoma, but a targeted treatment strategy could reduce the volume of antibiotics required. Methods In total, 48 Ethiopian communities were randomized to mass, targeted, or delayed azithromycin distributions. In the targeted arm, only children aged 6 months to 5 years with evidence of ocular chlamydia received azithromycin, distributed thrice over the following year. The primary outcome was ocular chlamydia at months 12 and 24, comparing the targeted and delayed arms (0–5 year-olds, superiority analysis) and the targeted and mass azithromycin arms (8–12 year-olds, noninferiority analysis, 10% noninferiority margin). Results At baseline, the mean prevalence of ocular chlamydia in the 3 arms ranged from 7% to 9% among 0–5 year-olds and from 3% to 9% among 8–12 year-olds. Averaged across months 12–24, the mean prevalence of ocular chlamydia among 0–5 year-olds was 16.7% (95% confidence interval [CI]: 9.0%–24.4%) in the targeted arm and 22.3% (95% CI: 11.1%–33.6%) in the delayed arm (P  = .61). The final mean prevalence of ocular chlamydia among 8–12 year-olds was 13.5% (95% CI: 7.9%–19.1%) in the targeted arm and 5.5% (95% CI: 0.3%–10.7%) in the mass treatment arm (adjusted risk difference 8.5 percentage points [pp] higher in the targeted arm, 95% CI: 0.9 pp–16.1 pp higher). Conclusions Antibiotic treatments targeted to infected preschool children did not result in significantly less ocular chlamydia infections compared with untreated communities and did not meet noninferiority criteria relative to mass azithromycin distributions. Targeted approaches may require treatment of a broader segment of the population in areas with hyperendemic trachoma. [ABSTRACT FROM AUTHOR]

The transmission of trachoma, caused by repeat infections with Chlamydia trachomatis, and many enteropathogens are linked to water quantity. We hypothesized that children living further from a water source would have higher exposure to C. trachomatis and enteric pathogens as determined by antibody responses. We used a multiplex bead assay to measure IgG antibody responses to C. trachomatis, Giardia intestinalis, Cryptosporidium parvum, Entamoeba histolytica, Salmonella enterica, Campylobacter jejuni, enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae in eluted dried blood spots collected from 2267 children ages 0–9 years in 40 communities in rural Ethiopia in 2016. Linear distance from the child's house to the nearest water source was calculated. We derived seroprevalence cutoffs using external negative control populations, if available, or by fitting finite mixture models. We used targeted maximum likelihood estimation to estimate differences in seroprevalence according to distance to the nearest water source. Seroprevalence among 1–9-year-olds was 43% for C. trachomatis, 28% for S. enterica, 70% for E. histolytica, 54% for G. intestinalis, 96% for C. jejuni, 76% for ETEC and 94% for C. parvum. Seroprevalence increased with age for all pathogens. Median distance to the nearest water source was 473 meters (IQR 268, 719). Children living furthest from a water source had a 12% (95% CI: 2.6, 21.6) higher seroprevalence of S. enterica and a 12.7% (95% CI: 2.9, 22.6) higher seroprevalence of G. intestinalis compared to children living nearest. Seroprevalence for C. trachomatis and enteropathogens was high, with marked increases for most enteropathogens in the first two years of life. Children living further from a water source had higher seroprevalence of S. enterica and G. intestinalis indicating that improving access to water in the Ethiopia's Amhara region may reduce exposure to these enteropathogens in young children. Author summary: Trachoma, an infection of the eye caused by the bacteria Chlamydia trachomatis, and many diarrhea-causing infections are associated with access to water for washing hands and faces. Measuring these different pathogens in a population is challenging and rarely are multiple infections measured at the same time. Here, we used an integrated approach to simultaneously measure antibody responses to C. trachomatis, Giardia intestinalis, Cryptosporidium parvum, Entamoeba histolytica, Salmonella enterica, Campylobacter jejuni, enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae among young children residing in rural Ethiopia. We found that the seroprevalence of all pathogens increased with age and that seropositivity to more than one pathogen was common. Children living further from a water source were more likely to be exposed to S. enterica and G. intestinalis. Integrated sero-surveillance is a promising avenue to explore the complexities of multi-pathogen exposure as well as to investigate associations between water, sanitation, and hygiene related exposures and disease transmission. [ABSTRACT FROM AUTHOR]

Objective To determine whether a water, sanitation and hygiene intervention could change hygiene behaviours thought to be important for trachoma control. Methods We conducted a cluster-randomized trial in rural Ethiopia from 9 November 2015 to 5 March 2019. We randomized 20 clusters to an intervention consisting of water and sanitation infrastructure and hygiene promotion and 20 clusters to no intervention. All intervention clusters received a primary-school hygiene curriculum, community water point, household wash station, household soap and home visits from hygiene promotion workers. We assessed intervention fidelity through annual household surveys. Findings Over the 3 years, more wash stations, soap and latrines were seen at households in the intervention clusters than the control clusters: risk difference 47 percentage points (95% confidence interval, CI: 41--53) for wash stations, 18 percentage points (95% CI: 12--24) for soap and 12 percentage points (95% CI: 5--19) for latrines. A greater proportion of people in intervention clusters reported washing their faces with soap (e.g. risk difference 21 percentage points; 95% CI: 15--27 for 0--5 year-old children) and using a latrine (e.g. risk difference 9 percentage points; 95% CI: 2--15 for 6--9 year-old children). Differences between the intervention and control arms were not statistically significant for many indicators until the programme had been implemented for at least a year; they did not decline during later study visits. Conclusion The community- and school-based intervention was associated with improved hygiene access and behaviours, although changes in behaviour were slow and required several years of the intervention. [ABSTRACT FROM AUTHOR]

Monitoring trachoma transmission with antibody data requires characterization of decay in IgG to Chlamydia trachomatis antigens. In a 3-year longitudinal cohort in a high-transmission setting, we estimated a median IgG half-life of 3 years and a seroreversion rate of 2.5 per 100 person-years (95% confidence interval, 1.6-3.5). Clinical Trials Registration NCT02754583., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: WHO promotes the SAFE strategy for the elimination of trachoma as a public health programme, which promotes surgery for trichiasis (ie, the S component), antibiotics to clear the ocular strains of chlamydia that cause trachoma (the A component), facial cleanliness to prevent transmission of secretions (the F component), and environmental improvements to provide water for washing and sanitation facilities (the E component). However, little evidence is available from randomised trials to support the efficacy of interventions targeting the F and E components of the strategy. We aimed to determine whether an integrated water, sanitation, and hygiene (WASH) intervention prevents the transmission of trachoma., Methods: The WASH Upgrades for Health in Amhara (WUHA) was a two-arm, parallel-group, cluster-randomised trial in 40 rural communities in Wag Hemra Zone (Amhara Region, Ethiopia) that had been treated with 7 years of annual mass azithromycin distributions. The randomisation unit was the school catchment area. All households within a 1·5 km radius of a potential water point within the catchment area (as determined by the investigators) were eligible for inclusion. Clusters were randomly assigned (at a 1:1 ratio) to receive a WASH intervention either immediately (intervention) or delayed until the conclusion of the trial (control), in the absence of concurrent antibiotic distributions. Given the nature of the intervention, participants and field workers could not be masked, but laboratory personnel were masked to treatment allocation. The WASH intervention consisted of both hygiene infrastructure improvements (namely, construction of a community water point) and hygiene promotion by government, school, and community leaders, which were implemented at the household, school, and community levels. Hygiene promotion focused on two simple messages: to use soap and water to wash your or your child's face, and to always use a latrine for defecation. The primary outcome was the cluster-level prevalence of ocular chlamydia, measured annually using conjunctival swabs in a random sample of children aged 0-5 years from each cluster at 12, 24, and 36 month timepoints. Analyses were done in an intention-to-treat manner. This trial is ongoing and is registered at ClinicalTrials.gov, NCT02754583., Findings: Between Nov 9, 2015, and March 5, 2019, 40 of 44 clusters assessed for eligibility were enrolled and randomly allocated to the trial groups (20 clusters each, with 7636 people from 1751 households in the intervention group and 9821 people from 2211 households in the control group at baseline). At baseline, ocular chlamydia prevalence among children aged 0-5 years was 11% (95% CI 6 to 16) in the WASH group and 11% (5 to 18) in the control group. At month 36, ocular chlamydia prevalence had increased in both groups, to 32% (24 to 41) in the WASH group and 31% (21 to 41) in the control group (risk difference across three annual monitoring visits, after adjustment for prevalence at baseline: 3·7 percentage points; 95% CI -4·9 to 12·4; p=0·40). No adverse events were reported in either group., Interpretation: An integrated WASH intervention addressing the F and E components of the SAFE strategy did not prevent an increase in prevalence of ocular chlamydia following cessation of antibiotics in an area with hyperendemic trachoma. The impact of WASH in the presence of annual mass azithromycin distributions is currently being studied in a follow-up trial of the 40 study clusters. Continued antibiotic distributions will probably be important in areas with persistent trachoma., Funding: National Institutes of Health-National Eye Institute., Translation: For the Amharic translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests BA reports financial support to attend global health meetings from the Bill & Melinda Gates Foundation. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Multiplex bead assays (MBAs) for serologic testing have become more prevalent in public health surveys, but few studies have assessed their test performance. As part of a trachoma study conducted in a rural part of Ethiopia in 2016, dried blood spots (DBS) were collected from a random sample of 393 children aged 0 to 9 years, with at least two separate 6-mm DBS collected on a filter card. Samples eluted from DBS were processed using an MBA on the Luminex platform for antibodies against 13 antigens of nine infectious organisms: Chlamydia trachomatis, Vibrio cholera, enterotoxigenic Escherichia coli, Cryptosporidium parvum, Entamoeba histolytica, Camplyobacter jejuni, Salmonella typhimurium Group B, Salmonella enteritidis Group D, and Giardia lamblia. Two separate DBS from each child were processed. The first DBS was run a single time, with the MBA set to read 100 beads per well. The second DBS was run twice, first at 100 beads per well and then at 50 beads per well. Results were expressed as the median fluorescence intensity minus background (MFI-BG), and classified as seropositive or seronegative according to external standards. Agreement between the three runs was high, with intraclass correlation coefficients of > 0.85 for the two Salmonella antibody responses and > 0.95 for the other 11 antibody responses. Agreement was also high for the dichotomous seropositivity indicators, with Cohen's kappa statistics exceeding 0.87 for each antibody assay. These results suggest that serologic testing on the Luminex platform had strong test performance characteristics for analyzing antibodies using DBS.

The Trachoma Control Program in Amhara region, Ethiopia, scaled up the surgery, antibiotics, facial cleanliness, and environmental improvement (SAFE) strategy in all districts starting in 2007. Despite these efforts, many districts still require additional years of SAFE. In 2017, four districts were selected for the assessment of antibody responses against Chlamydia trachomatis antigens and C. trachomatis infection to better understand transmission. Districts with differing endemicity were chosen, whereby one had a previous trachomatous inflammation-follicular (TF) prevalence of ≥ 30% (Andabet), one had a prevalence between 10% and 29.9% (Dera), one had a prevalence between 5% and 10% (Woreta town), and one had a previous TF prevalence of < 5% (Alefa) and had not received antibiotic intervention for 2 years. Survey teams assessed trachoma clinical signs and took conjunctival swabs and dried blood spots (DBS) to measure infection and antibody responses. Trachomatous inflammation-follicular prevalence among children aged 1-9 years was 37.0% (95% CI: 31.1-43.3) for Andabet, 14.7% (95% CI: 10.0-20.5) for Dera, and < 5% for Woreta town and Alefa. Chlamydia trachomatis infection was only detected in Andabet (11.3%). Within these districts, 2,195 children provided DBS. The prevalence of antibody responses to the antigen Pgp3 was 36.9% (95% CI: 29.0-45.6%) for Andabet, 11.3% (95% CI: 5.9-20.6%) for Dera, and < 5% for Woreta town and Alefa. Seroconversion rate for Pgp3 in Andabet was 0.094 (95% CI: 0.069-0.128) events per year. In Andabet district, where SAFE implementation has occurred for 11 years, the antibody data support the finding of persistently high levels of trachoma transmission.