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.

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).

Genomics of Ocular Chlamydia trachomatis After 5 Years of SAFE Interventions for Trachoma in Amhara, Ethiopia.

BACKGROUND: To eliminate trachoma as a public health problem, the World Health Organization recommends the SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy. As part of the SAFE strategy in the Amhara Region, Ethiopia, the Trachoma Control Program distributed >124 million doses of antibiotics between 2007 and 2015. Despite this, trachoma remained hyperendemic in many districts and a considerable level of Chlamydia trachomatis (Ct) infection was evident. METHODS: We utilized residual material from Abbott m2000 Ct diagnostic tests to sequence 99 ocular Ct samples from Amhara and investigated the role of Ct genomic variation in continued transmission of Ct. RESULTS: Sequences were typical of ocular Ct at the whole-genome level and in tissue tropism-associated genes. There was no evidence of macrolide resistance in this population. Polymorphism around the ompA gene was associated with village-level trachomatous inflammation-follicular prevalence. Greater ompA diversity at the district level was associated with increased Ct infection prevalence. CONCLUSIONS: We found no evidence for Ct genomic variation contributing to continued transmission of Ct after treatment, adding to evidence that azithromycin does not drive acquisition of macrolide resistance in Ct. Increased Ct infection in areas with more ompA variants requires longitudinal investigation to understand what impact this may have on treatment success and host immunity.

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.

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.

Targeted Antibiotics for Trachoma: A Cluster-Randomized Trial.

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.

Conjunctival Scarring, Corneal Pannus, and Herbert's Pits in Adolescent Children in Trachoma-endemic Populations of the Solomon Islands and Vanuatu.

BACKGROUND: In the Solomon Islands and Vanuatu, the sign trachomatous inflammation-follicular (TF) is common, but ocular infection with Chlamydia trachomatis is not. It is therefore debatable whether azithromycin mass drug administration (MDA), the recommended antibiotic treatment strategy for trachoma's elimination as a public health problem, is necessary in this setting. We set out to estimate what proportion of adolescents were at risk of progression of trachomatous scarring. METHODS: A cross-sectional survey was undertaken of all children aged 10-14 years resident in communities identified as high-TF clusters during previous population-based mapping. Graders examined children for clinical evidence of trachomatous scarring, pannus, and Herbert's pits (HPs) or limbal follicles in both eyes. A dried blood spot was collected from each child and tested for antibodies to C. trachomatis. RESULTS: A total of 492 children in 24 villages of the Solomon Islands and Vanuatu were examined. In total, 35/492 (7%) of children had limbal signs (pannus and/or HPs) plus any conjunctival scarring. And 9/492 (2%) had limbal signs and moderate or severe conjunctival scarring; 22% of children were anti-Pgp3 seropositive. CONCLUSIONS: Few adolescents here are at risk of future complications from trachoma, supporting the conclusion that further antibiotic MDA is not currently required for trachoma elimination purposes in these settings.

Azithromycin Reduction to Reach Elimination of Trachoma (ARRET): study protocol for a cluster randomized trial of stopping mass azithromycin distribution for trachoma.

BACKGROUND: The World Health Organization (WHO) recommends annual mass azithromycin distribution until districts drop below 5% prevalence of trachomatous inflammation-follicular (TF). Districts with very low TF prevalence may have little or no transmission of the ocular strains of Chlamydia trachomatis that cause trachoma, and additional rounds of mass azithromycin distribution may not be useful. Here, we describe the protocol for a randomized controlled trial designed to evaluate whether mass azithromycin distribution can be stopped prior to the current WHO guidelines. METHODS: The Azithromycin Reduction to Reach Elimination of Trachoma (ARRET) study is a 1:1 community randomized non-inferiority trial designed to evaluate whether mass azithromycin distribution can be stopped in districts with baseline prevalence of TF under 20%. Communities in Maradi, Niger are randomized after baseline assessment either to continued annual mass azithromycin distribution or stopping annual azithromycin distribution over a 3-year period. We will compare the prevalence of ocular C. trachomatis (primary outcome), TF and other clinical signs of trachoma, and serologic markers of trachoma after 3 years. We hypothesize that stopping annual azithromycin distribution will be non-inferior to continued annual azithromycin distributions for all markers of trachoma prevalence and transmission. DISCUSSION: The results of this trial are anticipated to provide potentially guideline-changing evidence for when mass azithromycin distributions can be stopped in low TF prevalence areas. TRIAL REGISTRATION NUMBER: This study is registered at clinicaltrials.gov ( NCT04185402 ). Registered December 4, 2019; prospectively registered pre-results.

Understanding hard-to-reach communities: local perspectives and experiences of trachoma control among the pastoralist Maasai in northern Tanzania.

As progress to eliminate trachoma is made, addressing hard-to-reach communities becomes of greater significance. Areas in Tanzania, inhabited by the Maasai, remain endemic for trachoma. This study assessed the effectiveness of Mass Drug Administration (MDA) through an ethnographic study of trachoma amongst a Maasai community. The MDA experience in the context of the livelihoods of the Maasai in a changing political economy was explored using participant observation and household interviews. Factors influencing MDA effectiveness within five domains were analysed. 1) Terrain of intervention: Human movement hindered MDA, including seasonal migration, domestic chores, grazing and school. Encounters with wildlife were significant. 2) Socio-cultural factors and community agency: Norms around pregnancy led women to accept the drug but hide refusal to swallow the drug. Timing of Community Drug Distributor (CDD) visits conflicted with livestock grazing. Refusals occurred among the ilmurrani age group and older women. Mistrust significantly hindered uptake of drugs. 3) Strategies and motivation of drug distributors: Maa-speaking CDDs were critical to effective drug delivery. Maasai CDDs, whilst motivated, faced challenges of distances, encounters with wildlife and compensation. 4) Socio-materiality of technology: Decreases in side-effects over years have improved trust in the drug. Restrictions to swallowing drugs and/or water were relevant to post-partum women and the ilmurrani. 5) History and health governance: Whilst perceptions of the programme were positive, communities questioned government priorities for resources for hospitals, medicines, clean water and roads. They complained of a lack of information and involvement of community members in health care services. With elimination in sight, hard-to-reach communities are paramount as these are probably the last foci of infection. Effective delivery of MDA programmes in such communities requires a critical understanding of community experiences and responses that can inform tailored approaches to trachoma control. Application of a critical social science perspective should be embedded in planning and evaluation of all NTD programmes.

Trachoma Prevalence After Discontinuation of Mass Azithromycin Distribution.

BACKGROUND: As the World Health Organization seeks to eliminate trachoma by 2020, countries are beginning to control the transmission of trachomatous inflammation-follicular (TF) and discontinue mass drug administration (MDA) with oral azithromycin. We evaluated the effect of MDA discontinuation on TF1-9 prevalence at the district level. METHODS: We extracted from the available data districts with an impact survey at the end of their program cycle that initiated discontinuation of MDA (TF1-9 prevalence <5%), followed by a surveillance survey conducted to determine whether TF1-9 prevalence remained below the 5% threshold, warranting discontinuation of MDA. Two independent analyses were performed, 1 regression based and 1 simulation based, that assessed the change in TF1-9 from the impact survey to the surveillance survey. RESULTS: Of the 220 districts included, TF1-9 prevalence increased to >5% from impact to surveillance survey in 9% of districts. Regression analysis indicated that impact survey TF1-9 prevalence was a significant predictor of surveillance survey TF1-9 prevalence. The proportion of simulations with >5% TF1-9 prevalence in the surveillance survey was 2%, assuming the survey was conducted 4 years after MDA. CONCLUSION: An increase in TF1-9 prevalence may represent disease resurgence but could also be due to measurement error. Improved diagnostic tests are crucial to elimination of TF1-9 as a public health problem.

Antimicrobial Resistance Following Azithromycin Mass Drug Administration: Potential Surveillance Strategies to Assess Public Health Impact.

The reduction in childhood mortality noted in trials investigating azithromycin mass drug administration (MDA) for trachoma control has been confirmed by a recent large randomized controlled trial. Population-level implementation of azithromycin MDA may lead to selection of multiresistant pathogens. Evidence suggests that repeated azithromycin MDA may result in a sustained increase in macrolide and other antibiotic resistance in gut and respiratory bacteria. Current evidence comes from standard microbiological techniques in studies focused on a time-limited intervention, while MDA implemented for mortality benefits would likely repeatedly expose the population over a prolonged period and may require a different surveillance approach. Targeted short-term and long-term surveillance of resistance emergence to key antibiotics, especially those from the World Health Organization Access group, is needed throughout any implementation of azithromycin MDA, focusing on a genotypic approach to overcome the limitations of resistance surveillance in indicator bacteria.

Prevalence and associated factors of active trachoma among 1-9 years old children in Deguatemben, Tigray, Ethiopia, 2018: community cross-sectional study.

BACKGROUND: Trachoma is a contagious infection of the eye. World Health Organization recommended three rounds of mass drug administration in districts where the prevalence of trachomatous follicular (TF) is ≥10% in children aged 1-9 years. Mass drug distribution was given to residents for three consecutive years with more than 90% coverage. However, the prevalence and associated factors of active trachoma in the study community after the intervention was not yet determined. Thus, this deals with the prevalence and associated factors of active trachoma among children aged 1-9 years. METHODS: We conducted a Community based cross-sectional study among 502 children aged 1-9 in March 2018 in Deguatemben. A multi-stage sampling technique was applied. Selected children were examined for trachoma using 2.5x binocular loupe and graded based on the WHO simplified grading system. Mothers were interviewed for factors associated with trachoma using a structured questionnaire. Data was entered on Epi-Info and exported to SPSS for analysis. Both descriptive and inferential analyses were done with 95% confidence intervals (CIs) at a p-value < 0.05 for the final model. RESULTS: The prevalence of active trachoma was found 21.5% (95% CI: 17.8-25.1%). Being 1 to 4 years old [AOR (95% CI) = 6.81(2.00-23.11)], not washing face [AOR (95% CI) =9.31(1.13-77.66)], not using soap [AOR (95% CI) =5.84(1.87-18.21)], unclean face [AOR(95% CI) = 18.22(4.93-69.32)] and mother's knowledge [AOR (95% CI) =0.06(0.02-0.19)] were found as independent predictors. CONCLUSION: The prevalence declined from the baseline, but it is still a public health problem in the district. Personal-related factors were found to be associated with the disease. Health education of "Facial cleanness" and related factors is recommended to increase knowledge of the mothers on their children's care in addition to the provision of antibiotics.

Milestones in the fight to eliminate trachoma.

PURPOSE: Trachoma, a chronic conjunctivitis that can result in vision loss from trichiasis, is targeted for global elimination by 2020. Several milestones in the long process towards elimination are noteworthy for the impact they have had on changing or accelerating progress. The purpose of this review is to describe the milestones and the impact they have had both for trachoma elimination and beyond. FINDINGS: Eight milestones are presented. They are discovery of the causative agent; development of a clinical grading scheme; establishment of the World Health Organization Alliance for the Global Elimination of Trachoma by 2020; setting targets that define elimination; building an evidence base for trichiasis surgery; azithromycin donation programme; use of the SAFE strategy (Surgery, Antibiotics, Facial cleanliness, and Environmental improvement); and The Global Trachoma Mapping Project. SUMMARY: These milestones have significantly pushed the progress towards elimination. Despite challenges to achieving the goal of elimination by 2020, there is continued commitment into the future to ensure that this preventable cause of blindness is no longer a threat.

Mass Oral Azithromycin for Childhood Mortality: Timing of Death After Distribution in the MORDOR Trial.

In a large community-randomized trial, biannual azithromycin distributions significantly reduced postneonatal childhood mortality in sub-Saharan African sites. Here, we present a prespecified secondary analysis showing that much of the protective effect was in the first 3 months postdistribution. Distributing more frequently than biannually could be considered if logistically feasible. Clinical Trials Registration. NCT02047981.

Impact of mass drug administration of azithromycin for trachoma elimination on prevalence and azithromycin resistance of genital Mycoplasma genitalium infection.

BACKGROUND: Mass drug administration (MDA) of 20 mg/kg (maximum 1 g in adults) azithromycin for ocular Chlamydia trachomatis (CT) infection is a key component of the WHO trachoma elimination strategy. However, this dose may be suboptimal in Mycoplasma genitalium infection and may encourage emergence of antimicrobial resistance (AMR) to azithromycin. OBJECTIVES: To determine the effect of MDA for trachoma elimination on M. genitalium prevalence, strain type and azithromycin resistance. METHODS: A secondary analysis of CT-negative vulvovaginal swabs from three outpatient antenatal clinics (Honiara, Solomon Islands) from patients recruited either pre-MDA, or 10 months post-MDA in two cross-sectional surveys was carried out. Swabs were tested for M. genitalium infection using Fast Track Diagnostics Urethritis Plus nucleic acid amplification assay. M. genitalium-positive samples were subsequently tested for azithromycin resistance by sequencing domain V of the 23S rRNA DNA region of M. genitalium and underwent phylogenetic analysis by dual locus sequence typing. RESULTS: M. genitalium prevalence was 11.9% (28/236) in women pre-MDA and 10.9% (28/256) 10 months post-MDA (p=0.7467). Self-reported receipt of azithromycin as part of MDA was 49.2% in women recruited post-MDA and 17.9% (5/28) in those who tested M. genitalium positive. Of samples sequenced (21/28 pre-MDA, 22/28 post-MDA), all showed a macrolide susceptible genotype. Strain typing showed that sequence types diverged into two lineages, with a suggestion of strain replacement post-MDA. CONCLUSION: A single round of azithromycin MDA in an island population with high baseline M. genitalium prevalence did not appear to impact on either prevalence or azithromycin resistance, in contrast to reported decreased genital CT prevalence in the same population. This may be due to limitations such as sample size, including CT-negative samples only, and low MDA coverage. Further investigation of the impact of multiple rounds of MDA on M. genitalium azithromycin AMR in antibiotic experienced and naïve populations is warranted.

Population coverage and factors associated with participation following a mass drug administration of azithromycin for trachoma elimination in Amhara, Ethiopia.

OBJECTIVES: Mass drug administration (MDA) with azithromycin is a core component of the WHO-recommended strategy to eliminate trachoma as a public health problem, but low participation rates in MDA campaigns may undermine the effectiveness of this intervention. We explored factors associated with individual MDA participation at the individual, head of household and household levels in Amhara, Ethiopia. METHODS: We conducted four district-level, multilevel cluster random coverage surveys to collect data on self-reported MDA participation and predictors. Random-effects logistic regression modelling was used to identify correlates of MDA participation while adjusting for nesting of individuals at the household and village level. RESULTS: The district-level self-reported participation in the trachoma MDA ranged from 78.5% to 86.9%. Excellent and fair health status (Odds ratio [OR] = 5.77; 95% Confidence interval [CI]: 3.04, 10.95; OR = 7.08; 95% CI: 3.47, 14.46), advanced knowledge of the MDA campaign (OR = 2.93; 95% CI: 2.04, 4.21) and knowledge of trachoma (OR = 1.60; 95% CI: 1.17, 2.19) were all positively associated with MDA participation. When excluding heads of household from the model, correlates retained similar positive associations to participation, in addition to the head of household participation (OR = 3.34; 95% CI: 2.46, 4.54). CONCLUSIONS: To increase the impact of MDA campaigns, MDA mobilisation strategies-including comprehensive trachoma and azithromycin messaging and MDA campaign awareness-should target heads of household, those in poorer health and older age groups.

OBJECTIFS: La distribution en masse de médicaments (DMM) avec l'azithromycine est un élément central de la stratégie recommandée par l'OMS pour éliminer le trachome en tant que problème de santé publique, mais le faible taux de participation aux campagnes de DMM pourrait nuire à l'efficacité de cette intervention. Nous avons exploré les facteurs associés à la participation individuelle à la DMM au niveau de l'individu, du chef de ménage et du ménage à Amhara, en Ethiopie. MÉTHODES: Nous avons mené 4 surveillances de la couverture par grappes, aléatoire, à plusieurs niveaux au niveau du district afin de collecter des données sur la participation auto-déclarée à la DMM et les prédicteurs. Une modélisation par régression logistique à effets aléatoires a été utilisée pour identifier les corrélats de la participation à la DMM tout en ajustant la nidification des individus au niveau du ménage et du village. RÉSULTATS: La participation auto-déclarée au niveau du district à la DMM contre le trachome variait de 78,5% à 86,9%. L'état de santé excellent et passable (rapport de cotes [OR] = 5,77; intervalle de confiance à 95% [IC]: 3,04 -10,95 et OR = 7,08; IC95%: 3,47-14,46), la connaissance poussée sur la campagne de DMM (OR = 2,93; IC95%: 2,04, 4,21) et la connaissance sur le trachome (OR = 1,60; IC95%: 1,17, 2,19) étaient tous positivement associés à la participation à la DMM. En excluant les chefs de ménage du modèle, les corrélats ont conservé des associations positives similaires à la participation, en plus de la participation du chef de ménage (OR = 3,34; IC95%: 2,46, 4,54). CONCLUSIONS: Pour accroître l'impact des campagnes de DMM, les stratégies de mobilisation de la DMM, y compris le message complet sur le trachome et l'azithromycine, et la sensibilisation à la campagne de DMM, devraient cibler les chefs de famille, les personnes en mauvaise santé et les groupes de personnes plus âgées.

Antibiotics for trachoma.

BACKGROUND: Trachoma is the world's leading infectious cause of blindness. In 1996, WHO launched the Alliance for the Global Elimination of Trachoma by the year 2020, based on the 'SAFE' strategy (surgery, antibiotics, facial cleanliness, and environmental improvement). OBJECTIVES: To assess the evidence supporting the antibiotic arm of the SAFE strategy by assessing the effects of antibiotics on both active trachoma (primary objective), Chlamydia trachomatis infection of the conjunctiva, antibiotic resistance, and adverse effects (secondary objectives). SEARCH METHODS: We searched relevant electronic databases and trials registers. The date of the last search was 4 January 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that satisfied either of two criteria: (a) trials in which topical or oral administration of an antibiotic was compared to placebo or no treatment in people or communities with trachoma, (b) trials in which a topical antibiotic was compared with an oral antibiotic in people or communities with trachoma. We also included studies addressing different dosing strategies in the population.  DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We identified 14 studies where individuals with trachoma were randomised and 12 cluster-randomised studies. Any antibiotic versus control (individuals)Nine studies (1961 participants) randomised individuals with trachoma to antibiotic or control (no treatment or placebo). All of these studies enrolled children and young people with active trachoma. The antibiotics used in these studies included topical (oxy)tetracycline (5 studies), doxycycline (2 studies), and sulfonamides (4 studies). Four studies had more than two study arms. In general these studies were poorly reported, and it was difficult to judge risk of bias.These studies provided low-certainty evidence that people with active trachoma treated with antibiotics experienced a reduction in active trachoma at three months (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.69 to 0.89; 1961 people; 9 RCTs; I2 = 73%) and 12 months (RR 0.74, 95% CI 0.55 to 1.00; 1035 people; 4 RCTs; I2 = 90%). Low-certainty evidence was available for ocular infection at three months (RR 0.81, 95% CI 0.63 to 1.04; 297 people; 4 RCTs; I2 = 0%) and 12 months (RR 0.25, 95% CI 0.08 to 0.78; 129 people; 1 RCT). None of these studies assessed antimicrobial resistance. In those studies that reported harms, no serious adverse effects were reported (low-certainty evidence).Oral versus topical antibiotics (individuals)Eight studies (1583 participants) compared oral and topical antibiotics. Only one study included people older than 21 years of age. Oral antibiotics included azithromycin (5 studies), sulfonamides (2 studies), and doxycycline (1 study). Topical antibiotics included (oxy)tetracycline (6 studies), azithromycin (1 study), and sulfonamide (1 study). These studies were poorly reported, and it was difficult to judge risk of bias.There was low-certainty evidence of little or no difference in effect between oral and topical antibiotics on active trachoma at three months (RR 0.97, 95% CI 0.81 to 1.16; 953 people; 6 RCTs; I2 = 63%) and 12 months (RR 0.93, 95% CI 0.75 to 1.15; 886 people; 5 RCTs; I2 = 56%). There was very low-certainty evidence for ocular infection at three or 12 months. Antimicrobial resistance was not assessed. In those studies that reported adverse effects, no serious adverse effects were reported; one study reported abdominal pain with azithromycin; one study reported a couple of cases of nausea with azithromycin; and one study reported three cases of reaction to sulfonamides (low-certainty evidence).Oral azithromycin versus control (communities)Four cluster-randomised studies compared antibiotic with no or delayed treatment. Data were available on active trachoma at 12 months from two studies but could not be pooled because of reporting differences. One study at low risk of bias found a reduced prevalence of active trachoma 12 months after a single dose of azithromycin in communities with a high prevalence of infection (RR 0.58, 95% CI 0.52 to 0.65; 1247 people). The other, lower quality, study in low-prevalence communities reported similar median prevalences of infection at 12 months: 9.3% in communities treated with azithromycin and 8.2% in untreated communities. We judged this moderate-certainty evidence for a reduction in active trachoma with treatment, downgrading one level for inconsistency between the two studies. Two studies reported ocular infection at 12 months and data could be pooled. There was a reduction in ocular infection (RR 0.36, 0.31 to 0.43; 2139 people) 12 months after mass treatment with a single dose compared with no treatment (moderate-certainty evidence). There was high-certainty evidence of an increased risk of resistance of Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli to azithromycin, tetracycline, and clindamycin in communities treated with azithromycin, with approximately 5-fold risk ratios at 12 months. The evidence did not support increased resistance to penicillin or trimethoprim-sulfamethoxazole. None of the studies measured resistance to C trachomatis. No serious adverse events were reported. The main adverse effect noted for azithromycin (˜10%) was abdominal pain, vomiting, and nausea.Oral azithromycin versus topical tetracycline (communities)Three cluster-randomised studies compared oral azithromycin with topical tetracycline. The evidence was inconsistent for active trachoma and ocular infection at three and 12 months (low-certainty evidence) and was not pooled due to considerable heterogeneity. Antimicrobial resistance and adverse effects were not reported.Different dosing strategiesSix studies compared different strategies for dosing. There were: mass treatment at different dosing intervals; applying cessation or stopping rules to mass treatment; strategies to increase mass treatment coverage. There was no strong evidence to support any variation in the recommended annual mass treatment. AUTHORS' CONCLUSIONS: Antibiotic treatment may reduce the risk of active trachoma and ocular infection in people infected with C trachomatis, compared to no treatment/placebo, but the size of the treatment effect in individuals is uncertain. Mass antibiotic treatment with single dose oral azithromycin reduces the prevalence of active trachoma and ocular infection in communities. There is no strong evidence to support any variation in the recommended periodicity of annual mass treatment. There is evidence of an increased risk of antibiotic resistance at 12 months in communities treated with antibiotics.

Models of Trachoma Transmission and Their Policy Implications: From Control to Elimination.

Despite great progress in eliminating trachoma from the majority of worldwide districts, trachoma control seems to have stalled in some endemic districts. Can mathematical models help suggest the way forward? We review specific achievements of models in trachoma control in the past. Models showed that, even with incomplete coverage, mass drug administration could eliminate disease through a spillover effect, somewhat analogous to how incomplete vaccine campaigns can eliminate disease through herd protection. Models also suggest that elimination can always be achieved if enough people are treated often enough with an effective enough drug. Other models supported the idea that targeting ages at highest risk or continued improvements in hygiene and sanitation can contribute meaningfully to trachoma control. Models of intensive targeting of a core group may point the way to final eradication even in areas with substantial transmission and within-community heterogeneity.

The Effect of Antibiotic Selection Pressure on the Nasopharyngeal Macrolide Resistome: A Cluster-randomized Trial.

Background: Frequent use of antibiotics is thought to create selection pressure by clearing susceptible bacteria and allowing resistant bacteria to spread in a community. A cluster-randomized trial comparing 2 different frequencies of mass azithromycin distributions for trachoma provided a convenient experiment for determining the causal relationship between antibiotic consumption and antibiotic resistance. Methods: Twenty-four communities were randomized to either annual or biannual mass azithromycin distributions for trachoma. Randomization was stratified on health catchment area and trachoma prevalence. Swabs were processed for the genetic macrolide resistance determinants ermB and mefA/E in a masked fashion from a random sample of 120 preschool children before treatment and another 120 children after 2 years of mass antibiotics. Results: Macrolide resistance determinants were similar in the 12 annually and 12 biannually treated communities before treatment, with a median prevalence among preschool children of 20% (interquartile range [IQR], 10%-40%) in each group. By 24 months, macrolide resistance determinants were found more commonly in the biannually treated communities (median, 60% [IQR, 50%-80%]) than the annually treated communities (median, 40% [IQR, 20%-40%]; P < .001). Adjusting for baseline, the 24-month prevalence of macrolide resistance determinants in the biannual group was 29.4% higher than that of the annual group (95% confidence interval, 10.5%-56.7%). Conclusions: This randomized trial used direct genetic methods to confirm the causal relationship of community antibiotic consumption and antibiotic resistance. Communities randomized to less frequent use of antibiotics had a significantly lower prevalence of genetic antibiotic resistance determinants. Clinical Trials Registration: NCT00792922.