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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.

Background: Biannual distribution of azithromycin to children 1-59 months old reduced mortality by 14% in a cluster-randomized trial. The World Health Organization has proposed targeting this intervention to the subgroup of children 1-11 months old to reduce selection for antimicrobial resistance. Here, we describe a trial designed to determine the impact of age-based targeting of biannual azithromycin on mortality and antimicrobial resistance., Methods: AVENIR is a cluster-randomized, placebo-controlled, double-masked, response-adaptive large simple trial in Niger. During the 2.5-year study period, 3350 communities are targeted for enrollment. In the first year, communities in the Dosso region will be randomized 1:1:1 to 1) azithromycin 1-11: biannual azithromycin to children 1-11 months old with placebo to children 12-59 months old, 2) azithromycin 1-59: biannual azithromycin to children 1-59 months old, or 3) placebo: biannual placebo to children 1-59 months old. Regions enrolled after the first year will be randomized with an updated allocation based on the probability of mortality in children 1-59 months in each arm during the preceding study period. A biannual door-to-door census will be conducted to enumerate the population, distribute azithromycin and placebo, and monitor vital status. Primary mortality outcomes are defined as all-cause mortality rate (deaths per 1000 person-years) after 2.5 years from the first enrollment in 1) children 1-59 months old comparing the azithromycin 1-59 and placebo arms, 2) children 1-11 months old comparing the azithromycin 1-11 and placebo arm, and 3) children 12-59 months in the azithromycin 1-11 and azithromycin 1-59 arms. In the Dosso region, 50 communities from each arm will be followed to monitor antimicrobial resistance. Primary resistance outcomes will be assessed after 2 years of distributions and include 1) prevalence of genetic determinants of macrolide resistance in nasopharyngeal samples from children 1-59 months old, and 2) load of genetic determinants of macrolide resistance in rectal samples from children 1-59 months old., Discussion: As high-mortality settings consider this intervention, the results of this trial will provide evidence to support programmatic and policy decision-making on age-based strategies for azithromycin distribution to promote child survival., Trial Registration: This trial was registered on January 13, 2020 (clinicaltrials.gov: NCT04224987 ).

Background: Mass distributions of azithromycin for trachoma have been associated with secondary benefits, including reductions in child mortality., Methods: In the Partnership for the Rapid Elimination of Trachoma cluster-randomized trial in Niger, 24 communities were randomized to annual treatment of everyone and 24 communities were randomized to biannual treatment of children under 12 for 3 years (clinicaltrials.gov, NCT00792922). Treatment was a single dose of directly observed oral azithromycin (20 mg/kg up to 1 g in adults). Vital status was assessed during annual census and monitoring visits. In this prespecified secondary analysis, we compared the mortality rate among children 6 months to less than 5 years of age by treatment arm using negative binomial regression., Results: Among children 6 months to less than 5 years of age, 404 deaths occurred during the study period. The mortality rate was 35.6 deaths per 1000 person-years (231 deaths, 95% CI: 30.9-40.9) in the annual arm and 29.0 deaths per 1000 person-years (173 deaths, 95% CI: 24.8-33.8) in the biannual arm. The mortality rate ratio comparing children in the biannual arm to the annual arm was 0.81 (95% CI: 0.66-1.00, P = 0.07; primary outcome). The mortality rate ratio comparing children who died from infectious causes in the biannual arm to the annual arm was 0.73 (95% CI: 0.57-0.94; P = 0.02). No adverse events were reported., Conclusions: This secondary analysis of a cluster-randomized trial found a nonsignificant 19% decrease in mortality among children 6 months to less than 5 years of age who received biannual azithromycin compared with children who received annual azithromycin. This study was conducted in a high mortality, trachoma-endemic area; thus, results may be specific to this environment only. In addition, the trial was neither designed nor powered to detect a mortality effect, and we cannot rule out the possibility that mortality differences resulted from bias.

Background: Azithromycin has modest efficacy against malaria, and previous cluster randomized trials have suggested that mass azithromycin distribution for trachoma control may play a role in malaria control. We evaluated the effect of annual versus biannual mass azithromycin distribution over a 3-year period on malaria prevalence during the peak transmission season in a region with seasonal malaria transmission in Niger., Methods: Twenty-four communities in Matameye, Niger, were randomized to annual mass azithromycin distribution (3 distributions to the entire community during the peak transmission season) or biannual-targeted azithromycin distribution (6 distributions to children <12 years of age, including 3 in the peak transmission season and 3 in the low transmission season). Malaria indices were evaluated at 36 months during the high transmission season., Results: Parasitemia prevalence was 42.6% (95% confidence interval: 31.7%-53.6%) in the biannual distribution arm compared with 50.6% (95% confidence interval: 40.3%-60.8%) in the annual distribution arm (P = 0.29). There was no difference in parasite density or hemoglobin concentration in the 2 treatment arms., Conclusions: Additional rounds of mass azithromycin distribution during low transmission may not have a significant impact on malaria parasitemia measured during the peak transmission season.

Background/aims: The WHO recommends 3-5 years of annual mass azithromycin distribution with at least 80% treatment coverage to districts with active trachoma prevalence over 10% among children. Here, we assess the efficacy of expanding the coverage target to at least 90% for trachoma control in a mesoendemic region of Niger., Methods: Twenty-four communities were randomised to a single day of azithromycin distribution with a coverage target of 80% of the community or up to 4 days of treatment, aiming for greater than 90% coverage. Distributions were annual and individuals above 6 months of age were treated. Children under 5 years of age were monitored for ocular chlamydia infection and active trachoma., Results: At baseline, ocular chlamydia prevalence was 20.5% (95% CI 9.8% to 31.2%) in the standard coverage arm and 21.9% (95% CI 11.3% to 32.5%) in the enhanced coverage arm, which reduced to 4.6% (95% CI 0% to 9.5%, p=0.008) and 7.1% (95% CI 2.7% to 11.4%, p<0.001) at 36 months, respectively. There was no significant difference in 36-month ocular chlamydia prevalence between the two arms (p=0.21). There was no difference in the rate of decline in ocular chlamydia between the two arms in a repeated measures model (p=0.80)., Conclusions: For annual mass azithromycin distribution programme to an entire community, there may be no additional benefit of increasing antibiotic coverage above the WHO's 80% target., Trial Registration Number: NCT00792922, post-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The World Health Organization recommends annual treatment of entire trachoma-endemic communities, although children typically have a higher load, longer duration, and greater likelihood of infection., Methods: Forty-eight communities in Matameye, Niger, were randomized to annual oral azithromycin treatment of the entire community or biannual treatment of children aged 0-12 years only. Both children and adults were monitored for ocular chlamydial infection by polymerase chain reaction., Results: The prevalence of childhood infection was reduced in the annually treated arm from 21.2% (95% confidence interval [CI], 15.2%-28.0%) at baseline to 5.8% (95% CI, 3.2%-9.0%) at 36 months (P < .001) and in the biannual arm from 20.2% (95% CI, 15.5%-25.3%) to 3.8% (95% CI, 2.2%-6.0%; P < .001). Adult infection in the annual arm was reduced from 1.7% (95% CI, .9%-2.7%) to 0.3% (95% CI, .0%-.7%) and in the biannual arm from 1.2% (95% CI, .5%-2.2%) to 0.0% (95% CI, .0%-.7%; P = .005). The effect of biannual treatment of children compared with annual treatment of the entire community in both children (95% CI, -.04% to .02%) and adults (95% CI, .9%-2.7%) excluded the prespecified noninferiority threshold of 6% (P = .003 and P < .001, respectively)., Conclusions: Periodic distribution of antibiotics to children in trachoma-endemic communities reduces chlamydial infection in both children and untreated adults, suggesting a form of herd protection. Biannual treatment of children was comparable to (specifically, noninferior to) annual treatment of the entire community, and may offer lower antibiotic use and other logistical advantages., Clinical Trials Registration: NCT00792922., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com)

Infectious conjunctivitis outbreaks remain a public health burden. This study focuses on the pathogen and antimicrobial resistance (AMR) profiles identified in Niger. Sixty-two patients with acute infectious conjunctivitis who presented to health posts were enrolled from December 2021 to May 2022. Nasal and conjunctival swabs were obtained from each patient. Unbiased RNA deep sequencing (RNA-seq) was used to identify associated pathogens. A pathogen was identified in 39 patients (63%; 95% CI, 50-74). Of those, an RNA virus was detected in 23 patients (59%; 95% CI, 43-73). RNA viruses were diverse and included human coronaviruses (HCoVs): SARS-CoV-2, HCoV-229E, HCoV-HKU1, and HCoV-OC43. A DNA virus was identified in 11 patients (28%; 95% CI, 17-44). Of those, four patients had a coinfection with an RNA virus and two patients had a coinfection with both an RNA virus and a bacterium. DNA viruses were predominantly human herpesvirus (cytomegalovirus, Epstein-Barr virus, human herpesvirus 8) and human adenovirus species B, C, and F. Eighteen patients (46%; 95% CI, 32-61) had a bacteria-associated infection that included Haemophilus influenza, Haemophilus aegyptius, Staphylococcus aureus, Streptococcus pneumoniae, and Moraxella spp. Antimicrobial resistance determinants were detected in either the conjunctiva or nasal samples of 20 patients (32%; 95% CI, 22-45) and were found to be more diverse in the nose (Shannon alpha diversity, 1.12 [95% CI, 1.05-1.26] versus 1.02 [95% CI, 1.00-1.05], P = 0.01). These results suggest the potential utility of leveraging RNA-seq to surveil pathogens and AMR for ocular infections.

BackgroundThe 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.MethodsThe 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.DiscussionThe 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.

Purpose: The clinical sign trachomatous inflammation - follicular (TF) is used to monitor indication for and response to mass azithromycin distribution in trachoma-endemic communities. Here, we assess the relationship between TF, trachomatous inflammation - intense (TI), and infection with ocular Chlamydia trachomatis over time during annual mass azithromycin distribution. Methods: We used data from a cluster-randomized trial of mass azithromycin distribution for trachoma control in a mesoendemic region of Niger. This study includes 24 communities that received 3 years of annual mass azithromycin distribution. TF, TI, and ocular chlamydia infection were monitored among children aged 0-5 years. We assessed the correlation between the prevalence of ocular chlamydia infection and 1) TF and 2) TI prevalence over time. Results: At baseline, ocular chlamydia prevalence was 21.2% (95% CI 14.3-28.1%), TF prevalence was 27.7% (95% CI 21.2-34.2%), and TI prevalence was 8.3% (95% CI 5.2-11.5%). The prevalence of all three measures decreased significantly over time (P < 0.001). At baseline, ocular chlamydia infection prevalence was strongly correlated with both TF (rho = 0.78, P < 0.0001) and TI (rho = 0.76, P < 0.0001). The correlation between ocular chlamydia infection and both TF and TI was weak at months 12 and 24. At 36 months, when TF prevalence had dropped below 10%, ocular chlamydia infection and TF were moderately correlated (rho = 0.70, P= 0.0002). Conclusions: Both TF and TI are good indicators of infection prevalence prior to mass azithromycin distribution. However, this relationship may be affected by repeated rounds of mass azithromycin distribution.

Repeated oral azithromycin distribution targeted only to children has proven effective in reducing the ocular Chlamydia that causes trachoma. Here, we assess whether an enhanced coverage target of at least 90% of children is superior to the World Health Organization recommendation of at least 80%. Twenty-four trachoma-endemic communities in Matamèye, Niger, were randomized to a single day of azithromycin distribution aiming for at least 80% coverage or up to 4 days of treatment and > 90% coverage of children under age 12. All distributions were biannual. Children < 5 years of age and adults > 15 years were monitored for ocular Chlamydia infection by polymerase chain reaction every 6 months for 36 months in children and at baseline and 36 months in adults. Ocular Chlamydia prevalence in children decreased from 24.9% (95% confidence interval [CI] 15.9-33.8%) to 4.4% (95% CI 0.6-8.2%, P < 0.001) at 36 months in the standard coverage arm and from 15.6% (95% CI 10.0-21.2%) to 3.3% (95% CI 1.0-5.5%; P < 0.001) in the enhanced coverage arm. Enhanced coverage reduced ocular Chlamydia prevalence in children more quickly over time compared with standard (P = 0.04). There was no difference between arms at 36 months in children (2.4% lower with enhanced coverage, 95% CI 7.7-12.5%; P = 0.60). No infection was detected in adults at 36 months. Increasing antibiotic coverage among children from 80% to 90% may yield only short term improvements for trachoma control programs. Targeting treatment to children alone may be sufficient for trachoma control in this setting.