Unravelling Chlamydia trachomatis diversity in Amhara, Ethiopia: MLVA-ompA sequencing as a molecular typing tool for trachoma.

Trachoma is the leading infectious cause of blindness worldwide and is now largely confined to around 40 low- and middle-income countries. It is caused by Chlamydia trachomatis (Ct), a contagious intracellular bacterium. The World Health Organization recommends mass drug administration (MDA) with azithromycin for treatment and control of ocular Ct infections, alongside improving facial cleanliness and environmental conditions to reduce transmission. To understand the molecular epidemiology of trachoma, especially in the context of MDA and transmission dynamics, the identification of Ct genotypes could be useful. While many studies have used the Ct major outer membrane protein gene (ompA) for genotyping, it has limitations. Our study applies a typing system novel to trachoma, Multiple Loci Variable Number Tandem Repeat Analysis combined with ompA (MLVA-ompA). Ocular swabs were collected post-MDA from four trachoma-endemic zones in Ethiopia between 2011-2017. DNA from 300 children with high Ct polymerase chain reaction (PCR) loads was typed using MLVA-ompA, utilizing 3 variable number tandem repeat (VNTR) loci within the Ct genome. Results show that MLVA-ompA exhibited high discriminatory power (0.981) surpassing the recommended threshold for epidemiological studies. We identified 87 MLVA-ompA variants across 26 districts. No significant associations were found between variants and clinical signs or chlamydial load. Notably, overall Ct diversity significantly decreased after additional MDA rounds, with a higher proportion of serovar A post-MDA. Despite challenges in sequencing one VNTR locus (CT1299), MLVA-ompA demonstrated cost-effectiveness and efficiency relative to whole genome sequencing, providing valuable information for trachoma control programs on local epidemiology. The findings suggest the potential of MLVA-ompA as a reliable tool for typing ocular Ct and understanding transmission dynamics, aiding in the development of targeted interventions for trachoma control.

Efficacy of Single-Dose Azithromycin for Ocular Chlamydial Infection: A Longitudinal Study.

Millions of doses of azithromycin are distributed each year for trachoma, yet the treatment efficacy of a single dose of azithromycin for ocular Chlamydia infection has not been well characterized. In this study, four villages in Niger received a mass azithromycin distribution for trachoma. All 426 children aged 0-5 years residing in the study villages were offered conjunctival swabbing every 6 months to test for ocular Chlamydia trachomatis. Among the children infected with ocular Chlamydia before treatment, 6% (95% CI: 2-15%) tested positive for ocular Chlamydia infection 6 months later, and 15% (95% CI: 7-28%) tested positive 12 months later. The most important predictor of post-treatment ocular Chlamydia infection was pretreatment ocular Chlamydia infection (relative risk: 3.5, 95% CI: 1.3-9.4). Although the 6-monthly monitoring schedule was suboptimal for testing the treatment efficacy of an antibiotic, these findings are nonetheless consistent with high treatment efficacy of a single dose of azithromycin and suggest that additional interventions might be most effective if targeted to those children infected prior to treatment.

Wait and watch: A trachoma surveillance strategy from Amhara region, Ethiopia.

BACKGROUND: Trachoma recrudescence after elimination as a public health problem has been reached is a concern for control programs globally. Programs typically conduct district-level trachoma surveillance surveys (TSS) ≥ 2 years after the elimination threshold is achieved to determine whether the prevalence of trachomatous inflammation-follicular (TF) among children ages 1 to 9 years remains <5%. Many TSS are resulting in a TF prevalence ≥5%. Once a district returns to TF ≥5%, a program typically restarts costly mass drug administration (MDA) campaigns and surveys at least twice, for impact and another TSS. In Amhara, Ethiopia, most TSS which result in a TF ≥5% have a prevalence close to 5%, making it difficult to determine whether the result is due to true recrudescence or to statistical variability. This study's aim was to monitor recrudescence within Amhara by waiting to restart MDA within 2 districts with a TF prevalence ≥5% at TSS, Metema = 5.2% and Woreta Town = 5.1%. The districts were resurveyed 1 year later using traditional and alternative indicators, such as measures of infection and serology, a "wait and watch" approach. METHODS/PRINCIPAL FINDINGS: These post-surveillance surveys, conducted in 2021, were multi-stage cluster surveys whereby certified graders assessed trachoma signs. Children ages 1 to 9 years provided a dried blood spot and children ages 1 to 5 years provided a conjunctival swab. TF prevalence in Metema and Woreta Town were 3.6% (95% Confidence Interval [CI]:1.4-6.4) and 2.5% (95% CI:0.8-4.5) respectively. Infection prevalence was 1.2% in Woreta Town and 0% in Metema. Seroconversion rates to Pgp3 in Metema and Woreta Town were 0.4 (95% CI:0.2-0.7) seroconversions per 100 child-years and 0.9 (95% CI:0.6-1.5) respectively. CONCLUSIONS/SIGNIFICANCE: Both study districts had a TF prevalence <5% with low levels of Chlamydia trachomatis infection and transmission, and thus MDA interventions are no longer warranted. The wait and watch approach represents a surveillance strategy which could lead to fewer MDA campaigns and surveys and thus cost savings with reduced antibiotic usage.

Water, Sanitation, and Hygiene (WASH) Factors Influencing the Effectiveness of Mass Drug Administration to Eliminate Trachoma as a Public Health Problem in Malawi.

PURPOSE: Following a national population-based trachoma survey in Malawi one round of azithromycin mass drug administration (MDA) was carried out, with a post-MDA impact survey showing TF prevalence below 5% and considered eliminated as a public health problem. However, active trachoma was still present in over 200 children. We assessed whether water, sanitation, and hygiene (WASH) factors were associated with ongoing presence of TF in children aged 1-9 years following MDA. METHODS: A secondary analysis was performed on a sub-set of the post-MDA impact survey data for children aged 1-9 years. We used a logistic regression analysis, adjusted for clustering at the household and village level. RESULTS: Among 16,142 children aged 1-9 years, 209 (1.3%) had TF after MDA. Factors associated with a significantly lower odds of TF after MDA were living in a household with a handwashing facility (aOR: 0.37) and living in a household where water for washing is located further away from the home (30 min away aOR: 0.39, p = .034, or more than 1 h away aOR: 0.31, p = .018) compared with water in the yard. CONCLUSION: The inverse association between a domestic handwashing facility and TF is consistent with previous findings, but the association of increasing distance to collect water for washing with a reduced risk of TF was unexpected and may reflect the impact of drought and unmeasured behavioural factors related to water usage. A more comprehensive collection of sociodemographic and WASH factor information in population-based trachoma surveys will provide insight into achieving and maintaining low levels of trachoma.

Treatment coverage of mass administration of azithromycin among children aged 1-11 months in 21 districts of Kebbi state, Nigeria.

BACKGROUND: The WHO recommends mass drug administration (MDA) as a strategy to deliver safe and cost-effective medicines to prevent and treat diseases. The antibiotic, azithromycin, has been used during MDA for the treatment and prevention of trachoma in Nigeria. Azithromycin has recently been shown to reduce infant mortality in communities receiving it for trachoma-elimination purposes in sub-Saharan Africa. This article reports on the implementation strategies for the safety and antimicrobial resistance of mass administration of azithromycin to children aged 1-11 mo using the trachoma programme platform in Kebbi state. METHODS: The mass administration of azithromycin among 1-11-mo-olds in Kebbi was implemented in three phases: (i) the preimplementation phase, during which specific activities were conducted to achieve government and community buy-in, ownership and capacity building; (ii) the implementation phase, which included the mass administration of azithromycin carried out by community volunteers (also known as community-directed distributors [CDDs]), monitoring (by health workers and independent monitors) and reporting of the distribution by all personnel; and (iii) the postimplementation phase, which included the validation of community data, where each item of community summary data is verified and checked for completeness and accuracy before uploading to the District Health Information System platform, where data are visualised, analysed and stored. RESULTS: In total, 97% of the target population received treatment; the remaining 3% were not treated due to signs of ill health, history of allergy to antibiotics, parental refusal or absence at the time of MDA. Children aged 1-11 mo accounted for 17% of the under-5 population, with females constituting 56% of the target population. In communities that were monitored, reports showed that only 5% lacked distribution materials (scales, slings or registers), >80% correctly entered data into community registers and 5% of children were not treated due to inadequate azithromycin provided to the CDDs for distribution. CONCLUSION: The implementation of azithromycin MDA for children aged 1-11 mo in Kebbi, utilising the trachoma platform, exhibited commendable coverage due to existing programme platform, healthcare and community structures, intensive advocacy and social mobilisation, real-time monitoring and progress-tracking strategies. It also demonstrated that the trachoma platform is suitable for implementing public health interventions, even after the elimination of trachoma in previously endemic districts.

Potential mitigating role of ivermectin on the spread of Chlamydia trachomatis by Musca sorbens.

Trachoma is the world's most frequent cause of blindness from an infectious agent. The disease caused by infection is associated with lack of access to sanitation and low hygiene standards. Trachoma is controlled through the Surgery, Antibiotics, Facial cleanliness, and Environmental improvement (SAFE) strategy, which delivers azithromycin (AZM) mass drug administration (MDA) in endemic areas. The putative vector Musca sorbens principally reproduce in human faecal matter left in the environment due to open defecation. Ivermectin (IVM) is on the WHO's essential medicines list and is administered as preventative chemotherapy against two neglected tropical diseases (NTDs)-onchocerciasis, as an annual or bi-annual treatment, and lymphatic filariasis, as an annual treatment in combination with albendazole. Ivermectin has a known inhibitive effect on insects that reproduce in dung. To assess if IVM could be a viable vector control tool against M. sorbens, this study evaluates existing data from trachoma, onchocerciasis and lymphatic filariasis mass drug administration (MDA) operations in Ethiopia. Persistent and recrudescent trachoma in evaluation units (EUs) were examined for whether AZM MDA in EUs was accompanied by IVM MDA, and whether co-administration was associated with greater likelihood of trachoma control. Results show an association suggesting that EUs that received both IVM and AZM MDA benefit from improved control of trachoma in persistent or recrudescent areas, when compared to EUs that received AZM MDA. This initial investigation supports the potential for ivermectin's use to support SAFE. Findings warrant further work to validate ivermectin's impact on M. sorbens reproduction through controlled lab and field-based studies.

Changes in trachoma indicators in Kiribati with two rounds of azithromycin mass drug administration, measured in serial population-based surveys.

Baseline mapping in the two major population centers of Kiribati showed that trachoma was a public health problem in need of programmatic interventions. After conducting two annual rounds of antibiotic mass drug administration (MDA), Kiribati undertook trachoma impact surveys in 2019, using standardized two-stage cluster surveys in the evaluation units of Kiritimati Island and Tarawa. In Kiritimati, 516 households were visited and in Tarawa, 772 households were visited. Nearly all households had a drinking water source and access to an improved latrine. The prevalence of trachomatous trichiasis remained above the elimination threshold (0.2% in ≥15-year-olds) and was virtually unchanged from baseline. The prevalence of trachomatous inflammation-follicular (TF) in 1-9-year-olds decreased by approximately 40% from baseline in both evaluation units but remained above the 5% TF prevalence threshold for stopping MDA. TF prevalence at impact survey was 11.5% in Kiritimati and 17.9% in Tarawa. Infection prevalence in 1-9-year-olds by PCR was 0.96% in Kiritimati and 3.3% in Tarawa. Using a multiplex bead assay to measure antibodies to the C. trachomatis antigen Pgp3, seroprevalence in 1-9-year-olds was 30.2% in Kiritimati and 31.4% in Tarawa. The seroconversion rate, in seroconversion events/100 children/year, was 9.0 in Kiritimati and 9.2 in Tarawa. Seroprevalence and seroconversion rates were both assessed by four different assays, with strong agreement between tests. These results show that, despite decreases in indicators associated with infection at impact survey, trachoma remains a public health problem in Kiribati, and provide additional information about changes in serological indicators after MDA.

Targeted Mass Azithromycin Distribution for Trachoma: A Community-Randomized Trial (TANA II).

BACKGROUND: Current guidelines recommend annual community-wide mass administration of azithromycin for trachoma. Targeting treatments to those most likely to be infected could reduce the amount of unnecessary antibiotics distributed. METHODS: In a cluster-randomized trial conducted from 1 November 2010 through 8 November 2013, 48 Ethiopian communities previously treated with annual mass azithromycin distributions for trachoma were randomized in equal numbers to (1) annual azithromycin distributions targeted to children aged 0-5 years, (2) annual azithromycin distributions targeted to households with a child aged 0-5 years found to have clinically active trachoma, (3) continued annual mass azithromycin distributions to the entire community, or (4) cessation of treatment. The primary outcome was the community prevalence of ocular chlamydia infection among children aged 0-9 years at month 36. Laboratory personnel were masked to treatment allocation. RESULTS: The prevalence of ocular chlamydia infection among children aged 0-9 years increased from 4.3% (95% confidence interval [CI], .9%-8.6%) at baseline to 8.7% (95% CI, 4.2%-13.9%) at month 36 in the age-targeted arm, and from 2.8% (95% CI, .8%-5.3%) at baseline to 6.3% (95% CI, 2.9%-10.6%) at month 36 in the household-targeted arm. After adjusting for baseline chlamydia prevalence, the 36-month prevalence of ocular chlamydia was 2.4 percentage points greater in the age-targeted group (95% CI, -4.8% to 9.6%; P = .50; prespecified primary analysis). No adverse events were reported. CONCLUSIONS: Targeting azithromycin treatment to preschool children was no different than targeting azithromycin to households with a child with clinically active trachoma. Neither approach reduced ocular chlamydia over the 3-year study. CLINICAL TRIALS REGISTRATION: NCT01202331.

Cost and community acceptability of enhanced antibiotic distribution approaches for trachoma in the Republic of South Sudan: enhancing the A in SAFE (ETAS) study protocol.

BACKGROUND: The World Health Organization targeted trachoma for global elimination as a public health problem by 2030. Reaching elimination thresholds by the year 2030 in the Republic of South Sudan will be a considerable challenge, as the country currently has many counties considered hyper-endemic (> 30% trachomatous inflammation-follicular [TF]) that have yet to receive interventions. Evidence from randomized trials, modeling, and population-based surveys suggests that enhancements may be needed to the standard-of-care annual mass drug administration (MDA) to reach elimination thresholds in a timely manner within highly endemic areas. We describe a protocol for a study to determine the cost and community acceptability of enhanced antibiotic strategies for trachoma in South Sudan. METHODS: The Enhancing the A in SAFE (ETAS) study is a community randomized intervention costing and community acceptability study. Following a population-based trachoma prevalence survey in 1 county, 30 communities will be randomized 1:1 to receive 1 of 2 enhanced MDA interventions, with the remaining communities receiving standard-of-care annual MDA. The first intervention strategy will consist of a community-wide MDA followed by 2 rounds of targeted treatment to children ages 6 months to 9 years, 2 weeks and 4 weeks after the community MDA. The second strategy will consist of a community-wide biannual MDA approximately 6 to 8 months apart. The costing analysis will use a payer perspective and identify the total cost of the enhanced interventions and annual MDA. Community acceptability will be assessed through MDA coverage monitoring and mixed-methods research involving community stakeholders. A second trachoma-specific survey will be conducted 12 months following the original survey. DISCUSSION: ETAS has received ethical clearance and is expected to be conducted between 2022 and 2023. Results will be shared through subsequent manuscripts. The study's results will provide information to trachoma programs on whether enhanced interventions are affordable and acceptable to communities. These results will further help in the design of future trachoma-specific antibiotic efficacy trials. Enhanced MDA approaches could help countries recover from delays caused by conflict or humanitarian emergencies and could also assist countries such as South Sudan in reaching trachoma elimination as a public health problem by 2030. TRIAL REGISTRATION: This trial was registered on December 1st, 2022 (clinicaltrails.org: NCT05634759).

Prevalence of Ocular Chlamydia trachomatis Infection in Amhara Region, Ethiopia, after 8 Years of Trachoma Control Interventions.

Although trachoma mass drug administration (MDA) programs target ocular Chlamydia trachomatis, the global trachoma control program does not monitor infection as a measure of impact but instead relies on monitoring clinical indicators. This study aimed to monitor the prevalence of ocular C. trachomatis among a population-based sample of children ages 1-5 years throughout Amhara, Ethiopia, a region that has received approximately 8 years of annual MDA as part of trachoma control. Between 2014 and 2021, trachoma impact surveys and surveillance surveys were conducted in all 156 districts of Amhara using a multistage cluster randomized methodology. Certified graders assessed individuals ages ≥ 1 year for trachomatous inflammation-follicular (TF), and a random subset of children ages 1-5 years also provided a conjunctival swab. Polymerase chain reaction was used to test for C. trachomatis. A total of 28,410 conjunctival swabs were collected from children ages 1-5 years across Amhara. The regional C. trachomatis infection prevalence was 4.7% (95% uncertainty interval: 4.3-5.1%). Infection was detected in all 10 zones of the region and ranged from 0.2% in Awi Zone to 11.9% in Waghemra Zone. Infection was detected in 17 (26%) districts with a TF prevalence < 10% and in 7 (21%) districts with a TF prevalence < 5%. Through programmatic monitoring of C. trachomatis infection, this study demonstrated that considerable infection remained throughout Amhara despite approximately 8 years of trachoma interventions and that enhanced interventions such as more frequent than annual MDA will be needed if elimination thresholds are to be reached.

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.

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

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

The conjunctival microbiome before and after azithromycin mass drug administration for trachoma control in a cohort of Tanzanian children.

Background: Trachoma, caused by ocular infection with Chlamydia trachomatis, is a neglected tropical disease that can lead to blinding pathology. Current trachoma control programmes have successfully used mass drug administration (MDA) with azithromycin to clear C. trachomatis infection and reduce transmission, alongside promoting facial cleanliness for better personal hygiene and environmental improvement. In areas of low-trachoma endemicity, the relationship between C. trachomatis infection and trachomatous disease weakens, and non-chlamydial bacteria have been associated with disease signs. Methods: We enrolled a cohort of children aged 6-10 years from three adjacent trachoma endemic villages in Kilimanjaro and Arusha regions, Northern Tanzania. Children were divided into four clinical groups based on the presence or absence of ocular C. trachomatis infection and clinical signs of trachomatous papillary inflammation (TP). To determine the impact of treatment on the ocular microbiome in these clinical groups, we performed V4-16S rRNA sequencing of conjunctival DNA from children 3-9 months pre-MDA (n = 269) and 3 months post-MDA (n = 79). Results: Chlamydia trachomatis PCR-negative, no TP children had the highest pre-MDA ocular microbiome alpha diversity, which was reduced in C. trachomatis infected children and further decreased in those with TP. Pre-MDA, Haemophilus and Staphylococcus were associated with C. trachomatis infection with and without concurrent TP, while Helicobacter was increased in those with TP in the absence of current C. trachomatis infection. Post-MDA, none of the studied children had ocular C. trachomatis infection or TP. MDA increased ocular microbiome diversity in all clinical groups, the change was of greater magnitude in children with pre-MDA TP. MDA effectively reduced the prevalence of disease causing pathogenic non-chlamydial bacteria, and promoted restoration of a normal, healthy conjunctival microbiome. Conclusion: We identified Helicobacter as a non-chlamydial bacterium associated with the clinical signs of TP. Further investigation to determine its relevance in other low-endemicity communities is required. MDA was shown to be effective at clearing C. trachomatis infection and other non-chlamydial ocular pathogens, without any detrimental longitudinal effects on the ocular microbiome. These findings suggest that azithromycin MDA may be valuable in trachoma control even in populations where the relationship between clinical signs of trachoma and the prevalence of current ocular C. trachomatis infection has become dissociated.

Simplified dosing of oral azithromycin for children 1-11 months old in child survival programmes: age-based and height-based dosing protocols.

BACKGROUND: To facilitate mass distribution of azithromycin, trachoma control programmes use height instead of weight to determine dose for children 6 months to 15 years old. WHO has recommended azithromycin distribution to children 1-11 months old to reduce mortality in high mortality settings under carefully monitored conditions. Weight was used to determine dose in children 1-5 months old in studies of azithromycin distribution for child survival, but a simplified approach using age or height for all aged 1-11 months old could increase programme efficiency in real-world settings. METHODS: This secondary analysis used data from two cluster randomised trials of azithromycin distribution for child mortality in Niger and Burkina Faso. An exhaustive search algorithm was developed to determine the optimal dose for different age groups, using tolerance limits of 10-20 mg/kg for children 1-2 months old and 15-30 mg/kg for children 3-11 months old. Height-based dosing was evaluated against the existing trachoma dosing pole and with a similar exhaustive search. RESULTS: The optimal two-tiered age-based approach suggested a dose of 80 mg (2 mL) for children 1-2 months old and 160 mg (4 mL) for children 3-11 months old. Under this schedule, 89%-93% of children would have received doses within tolerance limits in both study populations. Accuracy was 93%-94% with a three-tiered approach, which resulted in doses of 80 mg (2 mL), 120 mg (3 mL) and 160 mg (4 mL) for children 1-2, 3-4 and 5-11 months old, respectively. For children 1-5 months old, the existing height pole would result in 70% of doses within tolerance limits. The optimisation identified height-based dosing options with 95% accuracy, although this would require changes to the existing dosing pole as well as additional training to measure infants lying flat. CONCLUSIONS: Overall, an age-based approach with two age tiers resulted in high accuracy while considering both concerns about overdosing in this young population and simplicity of field operations.

Clinical signs of trachoma and laboratory evidence of ocular Chlamydia trachomatis infection in a remote Queensland community: a serial cross-sectional study.

OBJECTIVES: To compare the findings of standard clinical assessments and of complementary clinical and laboratory methods for determining whether community-wide treatment for trachoma is warranted in a remote Queensland community. DESIGN: Three cross-sectional screening surveys, 2019-2021, complemented by laboratory pathology testing. SETTING: Small community in northwest Queensland with geographic and cultural ties to Northern Territory communities where trachoma persists. PARTICIPANTS: Children aged 1-14 years; opportunistic screening of people aged 15 years or more. MAIN OUTCOME MEASURES: Prevalence of clinical signs of trachoma, Chlamydia trachomatis infection, ocular non-chlamydial infections, and seropositivity for antibodies to the C. trachomatis Pgp3 protein. RESULTS: During the three surveys, 73 examinations of 58 children aged 1-4 years, 309 of 171 aged 5-9 years, and 142 of 105 aged 10-14 years for trachoma were undertaken, as were 171 examinations of 164 people aged 15 years or more; 691 of 695 examinations were of Aboriginal or Torres Strait Islander people (99%), 337 were of girls or young women (48%). Clinical signs consistent with trachomatous inflammation-follicular were identified in 5-9-year-old children 23 times (7%), including in eleven with non-chlamydial infections and one with a C. trachomatis infection. One child (10-14 years) met the criteria for trachomatous scarring. Two of 272 conjunctival swab samples (all ages) were polymerase chain reaction-positive for C. trachomatis (0.7%). Two of 147 people aged 15 years or more examined in 2019 had trichiasis, both aged 40 years or more. Seven of 53 children aged 1-9 years in 2019 and seven of 103 in 2021 were seropositive for anti-Pgp3 antibodies. CONCLUSIONS: Despite the prevalence of clinical signs consistent with trachomatous inflammation-follicular among 5-9-year-old children exceeding the 5% threshold for community-wide treatment, laboratory testing indicated that childhood exposure to ocular C. trachomatis is rare in this community. Laboratory testing should be integrated into Australian trachoma guidelines.

Effect of Biannual Mass Azithromycin Distributions to Preschool-Aged Children on Trachoma Prevalence in Niger: A Cluster Randomized Clinical Trial.

Importance: Because transmission of ocular strains of Chlamydia trachomatis is greatest among preschool-aged children, limiting azithromycin distributions to this age group may conserve resources and result in less antimicrobial resistance, which is a potential advantage in areas with hypoendemic trachoma and limited resources. Objective: To determine the efficacy of mass azithromycin distributions to preschool-aged children as a strategy for trachoma elimination in areas with hypoendemic disease. Design, Setting, and Participants: In this cluster randomized clinical trial performed from November 23, 2014, until July 31, 2017, thirty rural communities in Niger were randomized at a 1:1 ratio to biannual mass distributions of either azithromycin or placebo to children aged 1 to 59 months. Participants and study personnel were masked to treatment allocation. Data analyses for trachoma outcomes were performed from October 19, 2021, through June 10, 2022. Interventions: Every 6 months, a single dose of either oral azithromycin (20 mg/kg using height-based approximation for children who could stand or weight calculation for small children) or oral placebo was provided to all children aged 1 to 59 months. Main Outcomes and Measures: Trachoma was a prespecified outcome of the trial, assessed as the community-level prevalence of trachomatous inflammation-follicular and trachomatous inflammation-intense through masked grading of conjunctival photographs from a random sample of 40 children per community each year during the 2-year study period. A secondary outcome was the seroprevalence of antibodies to C trachomatis antigens. Results: At baseline, 4726 children in 30 communities were included; 1695 children were enrolled in 15 azithromycin communities and 3031 children were enrolled in 15 placebo communities (mean [SD] proportions of boys, 51.8% [4.7%] vs 52.0% [4.2%]; mean [SD] age, 30.8 [2.8] vs 30.6 [2.6] months). The mean coverage of study drug for the 4 treatments was 79% (95% CI, 75%-83%) in the azithromycin group and 82% (95% CI, 79%-85%) in the placebo group. The mean prevalence of trachomatous inflammation-follicular at baseline was 1.9% (95% CI, 0.5%-3.5%) in the azithromycin group and 0.9% (95% CI, 0-1.9%) in the placebo group. At 24 months, trachomatous inflammation-follicular prevalence was 0.2% (95% CI, 0-0.5%) in the azithromycin group and 0.8% (95% CI, 0.2%-1.6%) in the placebo group (incidence rate ratio adjusted for baseline: 0.18 [95% CI, 0.01-1.20]; permutation P = .07). Conclusions and Relevance: The findings of this trial do not show that biannual mass azithromycin distributions to preschool-aged children were more effective than placebo, although the underlying prevalence of trachoma was low. The sustained absence of trachoma even in the placebo group suggests that trachoma may have been eliminated as a public health problem in this part of Niger. Trial Registration: ClinicalTrials.gov Identifier: NCT02048007.

Secondary Effects from Mass Azithromycin Administration: A Systematic Review and Meta-analysis.

The effects of azithromycin mass drug administration (MDA) on trachoma and yaws have been addressed. However, the secondary effects of azithromycin MDA remain unclear. This study aimed to explore the secondary effects of azithromycin MDA. PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from conception to January 5, 2022. Studies on secondary effects of azithromycin MDA were included. A total of 34 studies were included. Six of them reported on child mortality, 10 on malaria, and 20 on general morbidity and condition. Azithromycin MDA reduced child mortality, and quarterly MDA may be most beneficial for reducing child mortality. The effect of azithromycin MDA on malaria was weak. No association was observed between azithromycin MDA and malaria parasitemia (rate ratio: 0.71, 95% confidence interval: 0.43-1.15). Azithromycin MDA was associated with a lower risk of respiratory tract infections and diarrhea. Additionally, it was associated with a lower risk of fever, vomiting, and headache. The carriage of pathogenic organisms such as Streptococcus pneumoniae and gut Campylobacter species was reduced. However, these secondary effects of azithromycin MDA appeared to last only a few weeks. Moreover, no association was observed between azithromycin MDA and nutritional improvement in children. In conclusion, azithromycin MDA had favorable secondary effects on child mortality and morbidity. However, the effects were short term.

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.