@article {1561, title = {Azithromycin to Reduce Mortality - An Adaptive Cluster-Randomized Trial.}, journal = {N Engl J Med}, volume = {391}, year = {2024}, month = {2024 Aug 22}, pages = {699-709}, abstract = {

BACKGROUND: Twice-yearly mass distribution of azithromycin to children is a promising intervention to reduce childhood mortality in sub-Saharan Africa. The World Health Organization recommended restricting distribution to infants 1 to 11 months of age to mitigate antimicrobial resistance, although this more limited treatment had not yet been tested.

METHODS: We randomly assigned rural communities in Niger to four twice-yearly distributions of azithromycin for children 1 to 59 months of age (child azithromycin group), four twice-yearly distributions of azithromycin for infants 1 to 11 months of age and placebo for children 12 to 59 months of age (infant azithromycin group), or placebo for children 1 to 59 months of age. Census workers who were not aware of the group assignments monitored mortality twice yearly over the course of 2 years. We assessed three primary community-level mortality outcomes (deaths per 1000 person-years), each examining a different age group and pairwise group comparison.

RESULTS: A total of 1273 communities were randomly assigned to the child azithromycin group (1229 were included in the analysis), 773 to the infant azithromycin group (751 included in the analysis), and 954 to the placebo group (929 included in the analysis). Among 382,586 children, 419,440 person-years and 5503 deaths were recorded. Lower mortality among children 1 to 59 months of age was observed in the child azithromycin group (11.9 deaths per 1000 person-years; 95\% confidence interval [CI], 11.3 to 12.6) than in the placebo group (13.9 deaths per 1000 person-years; 95\% CI, 13.0 to 14.8) (representing 14\% lower mortality with azithromycin; 95\% CI, 7 to 22; P\<0.001). Mortality among infants 1 to 11 months of age was not significantly lower in the infant azithromycin group (22.3 deaths per 1000 person-years; 95\% CI, 20.0 to 24.7) than in the placebo group (23.9 deaths per 1000 person-years; 95\% CI, 21.6 to 26.2) (representing 6\% lower mortality with azithromycin; 95\% CI, -8 to 19). Five serious adverse events were reported: three in the placebo group, one in the infant azithromycin group, and one in the child azithromycin group.

CONCLUSIONS: Azithromycin distributions to children 1 to 59 months of age significantly reduced mortality and was more effective than treatment of infants 1 to 11 months of age. Antimicrobial resistance must be monitored. (Funded by the Bill and Melinda Gates Foundation; AVENIR ClinicalTrials.gov number, NCT04224987.).

}, author = {O{\textquoteright}Brien, Kieran S and Arzika, Ahmed M and Amza, Abdou and Maliki, Ramatou and Aichatou, Bawa and Bello, Ismael Mamane and Beidi, Diallo and Galo, Nasser and Harouna, Naser and Karamba, Alio M and Mahamadou, Sani and Abarchi, Moustapha and Ibrahim, Almou and Lebas, Elodie and Peterson, Brittany and Liu, Zijun and Le, Victoria and Colby, Emily and Doan, Thuy and Keenan, Jeremy D and Oldenburg, Catherine E and Porco, Travis C and Arnold, Benjamin F and Lietman, Thomas M and AVENIR Study Group} } @article {1351, title = {Comprehensive Profile of Pathogens and Antimicrobial Resistance in Conjunctivitis Cases from Niger.}, journal = {Am J Trop Med Hyg}, volume = {109}, year = {2023}, month = {2023 Dec 06}, pages = {1333-1338}, abstract = {

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.

}, issn = {1476-1645}, doi = {10.4269/ajtmh.23-0498}, author = {Amza, Abdou and Nassirou, Beido and Kadri, Boubacar and Ali, Saley and Mariama, Boubacar and Ibrahim, Ciss{\'e} Mamadou and Roufaye, Lamine Aboubacar and Lebas, Elodie and Colby, Emily and Zhong, Lina and Chen, Cindi and Ruder, Kevin and Yu, Danny and Liu, YuHeng and Abraham, Thomas and Chang, Aaron and Mai, Lina and Hinterwirth, Armin and Seitzman, Gerami D and Lietman, Thomas M and Doan, Thuy} } @article {1281, title = {Wastewater-Based Surveillance of Antimicrobial Resistance in Niger: An Exploratory Study.}, journal = {Am J Trop Med Hyg}, year = {2023}, month = {2023 Aug 28}, abstract = {

Wastewater-based surveillance is increasingly recognized as an important approach to monitoring population-level antimicrobial resistance (AMR). In this exploratory study, we examined the use of metagenomics to evaluate AMR using untreated wastewater samples routinely collected by the Niger national polio surveillance program. Forty-eight stored samples from two seasons each year over 4 years (2016-2019) in three regions were selected for inclusion in this study and processed using unbiased DNA deep sequencing. Normalized number of reads of genetic determinants for different antibiotic classes were compared over time, by season, and by location. Correlations in resistance were examined among classes. Changes in reads per million per year were demonstrated for several classes, including decreases over time in resistance determinants for phenicols (-3.3, 95\% CI: -8.7 to -0.1, P = 0.029) and increases over time for aminocoumarins (3.8, 95\% CI: 0.0 to 11.4, P = 0.043), fluoroquinolones (6.8, 95\% CI: 0.0 to 20.5, P = 0.048), and beta-lactams (0.85, 95\% CI: 0.1 to 1.7, P = 0.006). Sulfonamide resistance was higher in the post-rainy season compared with the dry season (5.2-fold change, 95\% CI: 3.4 to 7.9, P < 0.001). No differences were detected when comparing other classes by season or by site for any antibiotic class. Positive correlations were identified in genetic determinants of resistance among several antibiotic classes. These results demonstrate the potential utility of leveraging existing wastewater sample collection in this setting for AMR surveillance.

}, issn = {1476-1645}, doi = {10.4269/ajtmh.23-0204}, author = {Ousmane, Sani and Kollo, Issifi A and Jambou, Ronan and Boubacar, Rakia and Arzika, Ahmed M and Maliki, Ramatou and Amza, Abdou and Liu, Zijun and Lebas, Elodie and Colby, Emily and Zhong, Lina and Chen, Cindi and Hinterwirth, Armin and Doan, Thuy and Lietman, Thomas M and O{\textquoteright}Brien, Kieran S} } @article {891, title = {Deep sequencing analysis of acute conjunctivitis in Burkina Faso, Africa.}, journal = {Int Health}, year = {2022}, month = {2022 Jan 24}, abstract = {

BACKGROUND: Seasonal and epidemic conjunctivitis (pink eye) infections are highly contagious and impose a significant economic burden worldwide. Long-term visual impairment can occur.

METHODS: This study used metagenomic deep sequencing to evaluate pathogens causing acute infectious conjunctivitis in Burkina Faso.

RESULTS: We found that pathogens causing conjunctivitis in Burkina Faso are diverse, with human adenoviruses responsible for a small fraction of the samples tested.

CONCLUSIONS: These results are unexpected and suggest the importance of regional surveillance.

}, issn = {1876-3405}, doi = {10.1093/inthealth/ihac001}, author = {Bountogo, Mamadou and Sie, Ali and Coulibaly, Boubacar and Ruder, Kevin and Chen, Cindi and Zhong, Lina and Colby, Emily and Lebas, Elodie and Deiner, Michael and Hinterwirth, Armin and Lietman, Thomas M and Seitzman, Gerami D and Doan, Thuy} } @article {911, title = {Age-based targeting of biannual azithromycin distribution for child survival in Niger: an adaptive cluster-randomized trial protocol (AVENIR).}, journal = {BMC Public Health}, volume = {21}, year = {2021}, month = {2021 04 29}, pages = {822}, abstract = {

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 ).

}, keywords = {Anti-Bacterial Agents, Azithromycin, Child, Child, Preschool, Drug Resistance, Bacterial, Humans, Infant, Macrolides, Mass Drug Administration, Niger, Randomized Controlled Trials as Topic}, issn = {1471-2458}, doi = {10.1186/s12889-021-10824-7}, author = {O{\textquoteright}Brien, Kieran S and Arzika, Ahmed M and Amza, Abdou and Maliki, Ramatou and Ousmane, Sani and Kadri, Boubacar and Nassirou, Beido and Mankara, Alio Karamba and Harouna, Abdoul Naser and Colby, Emily and Lebas, Elodie and Liu, Zijun and Le, Victoria and Nguyen, William and Keenan, Jeremy D and Oldenburg, Catherine E and Porco, Travis C and Doan, Thuy and Arnold, Benjamin F and Lietman, Thomas M} }