@article {1391, title = {Assessment of spillover of antimicrobial resistance to untreated children 7 to 12 years old after mass drug administration of azithromycin for child survival in Niger: a secondary analysis of the MORDOR cluster-randomized trial.}, journal = {Clin Infect Dis}, year = {2024}, month = {2024 May 13}, abstract = {

BACKGROUND: The risk of antibiotic resistance is complicated by the potential for spillover effects from one treated population to another. Azithromycin mass drug administration programs report higher rates of antibiotic resistance among treatment arms in targeted groups. This study aims to understand the risk of spillover of antibiotic resistance to non-target groups in these programs.

METHODS: Data was used from a cluster-randomized trial comparing the effect of biannual azithromycin and placebo distribution to children 1-59 months on child mortality. Nasopharyngeal samples from untreated children 7-12 years old were tested for genetic determinants of macrolide resistance (primary outcome) and resistance to other antibiotic classes (secondary outcomes). Linear regression was used to compare the community-level mean difference in prevalence by arm at the 24-month timepoint adjusting for baseline prevalence.

RESULTS: 1,103 children 7-12 years old in 30 communities were included in the analysis (15 azithromycin, 15 placebo). Adjusted mean differences in prevalence of resistance determinants for macrolides, beta-lactams and tetracyclines were 3.4\% (95\% CI -4.1\% to 10.8\%, P-value 0.37), -1.2\% (95\% CI -7.9\% to 5.5\%, P-value 0.72), and -3.3\% (95\% CI -9.5\% to 2.8\%, P-value 0.61), respectively.

CONCLUSIONS: We were unable to demonstrate a statistically significant increase in macrolide resistance determinants in untreated groups in an azithromycin mass drug administration program. While the result might be consistent with a small spillover effect, this study was not powered to detect such a small difference. Larger studies are warranted to better understand the potential for spillover effects within these programs.

}, issn = {1537-6591}, doi = {10.1093/cid/ciae267}, author = {Peterson, Brittany and Arzika, Ahmed M and Amza, Abdou and Maliki, Ramatou and Mankara Karamba, Alio and Moussa, Mariama and Kemago, Mariama and Liu, Zijun and Houpt, Eric and Liu, Jie and Pholwat, Suporn and Doan, Thuy and Porco, Travis and Keenan, Jeremy D and Lietman, Thomas M and O{\textquoteright}Brien, Kieran S} } @article {1361, title = {Gut Microbiome Diversity and Antimicrobial Resistance After a Single Dose of Oral Azithromycin in Children: A Randomized Placebo-Controlled Trial.}, journal = {Am J Trop Med Hyg}, year = {2024}, month = {2024 Jan 16}, abstract = {

Mass antibiotic distribution to preschool children resulted in alterations of the gut microbiome months after distribution. This individually randomized, placebo-controlled trial evaluated changes in the gut microbiome and resistome in children aged 8 days to 59 months after one dose of oral azithromycin in Burkina Faso. A total of 450 children were randomized in a 1:1 ratio to either placebo or azithromycin. Rectal samples were collected at baseline, 2 weeks, and 6 months after randomization and subjected to DNA deep sequencing. Gut microbiome diversity and normalized antimicrobial resistance determinants for different antibiotic classes were evaluated. Azithromycin decreased gut bacterial diversity (Shannon P < 0.0001; inverse Simpson P < 0.001) 2 weeks after treatment relative to placebo. Concurrently, the normalized abundance of macrolide resistance genetic determinants was 243-fold higher (95\% CI: 76-fold to 776-fold, P < 0.0001). These alterations did not persist at 6 months, suggesting that disruptions were transient. Furthermore, we were unable to detect resistance changes in other antibiotic classes, indicating that co-resistance with a single course of azithromycin when treated at the individual level was unlikely.

}, issn = {1476-1645}, doi = {10.4269/ajtmh.23-0651}, author = {Doan, Thuy and Liu, Zijun and Sie, Ali and Dah, Clarisse and Bountogo, Mamadou and Ouattara, Mamadou and Coulibaly, Boubacar and Kiemde, Dramane and Zonou, Guillaume and Nebie, Eric and Brogdon, Jessica and Lebas, Elodie and Hinterwirth, Armin and Zhong, Lina and Chen, Cindi and Zhou, Zhaoxia and Porco, Travis and Arnold, Benjamin F and Oldenburg, Catherine E and Lietman, Thomas M} } @article {1411, title = {Pathogen Profiles of Infectious Conjunctivitis in Ho Chi Minh City, Vietnam.}, journal = {Cornea Open}, volume = {2}, year = {2023}, month = {2023 Dec}, abstract = {

PURPOSE: Conjunctivitis epidemics and pandemics remain a global burden. This study aims to comprehensively identify pathogens associated with conjunctivitis in Vietnam.

METHODS: Patients with acute conjunctivitis presented to an outpatient clinic in Ho Chi Minh City, Vietnam, were enrolled from September 2022 to March 2023. Swabs were obtained from conjunctiva and anterior nares of all patients. Unbiased RNA deep sequencing (RNA-seq) was used to identify any replicating pathogens in the samples.

RESULTS: Samples from 35 patients were analyzed. A pathogen was identified in 80\% of the patients. 72\% (95\% confidence interval: 54\% to 85\%) were infected with either HAdV-D or HAdV-B. RNA viruses detected were rhinoviruses and human coronavirus 229E. Bacteria etiologies included , , and One patient had co-infection of rhinovirus A and HAdV-B. , a fungus, was identified in one patient. Corneal sub-epithelial infiltrates, pseudomembranes, or pre-auricular lymphadenopathy were not reported in any patient.

CONCLUSIONS: Human adenoviruses are the common circulating pathogens associated with infectious conjunctivitis in Vietnam. HAdV species, however, appear to vary between geographic locations within Vietnam. Other under-recognized pathogens identified in this study, such as RNA viruses, suggest broader pathogen surveillance may be beneficial.

}, issn = {2833-6992}, doi = {10.1097/coa.0000000000000025}, author = {Tran, Huy and Hoang, Linh and Tran, Yen and Hạ, Thảo and Ruder, Kevin and Zhong, Lina and Chen, Cindi and Yu, Danny and Liu, YuHeng and Abraham, Thomas and Hinterwirth, Armin and Deiner, Michael and Porco, Travis and Lietman, Thomas M and Seitzman, Gerami D and Doan, Thuy} } @article {821, title = {Gut resistome of preschool children after prolonged mass azithromycin distribution: a cluster-randomized trial.}, journal = {Clin Infect Dis}, year = {2021}, month = {2021 May 26}, abstract = {

We evaluated the gut resistome of children from communities treated with 10 twice-yearly azithromycin distributions. While the macrolide resistance remained higher in the azithromycin arm, the selection of non-macrolide resistance observed at earlier time points did not persist. Longitudinal resistance monitoring should be a critical component of mass distribution programs.

}, issn = {1537-6591}, doi = {10.1093/cid/ciab485}, author = {Arzika, Ahmed M and Maliki, Ramatou and Abdou, Amza and Mankara, Alio K and Harouna, Abdoul N and Cook, Catherine and Hinterwirth, Armin and Worden, Lee and Zhong, Lina and Chen, Cindi and Ruder, Kevin and Zhou, Zhaoxia and Lebas, Elodie and O{\textquoteright}Brien, Kieran S and Oldenburg, Catherine E and Le, Victoria and Arnold, Benjamin F and Porco, Travis and Keenan, Jeremy D and Lietman, Thomas M and Doan, Thuy} } @article {131, title = {Neonatal azithromycin administration to prevent infant mortality: study protocol for a randomised controlled trial.}, journal = {BMJ Open}, volume = {9}, year = {2019}, month = {2019 09 04}, pages = {e031162}, abstract = {

INTRODUCTION: Biannual mass azithromycin distribution to children aged 1-59 months has been shown to reduce all-cause mortality. Children under 28 days of age were not treated in studies evaluating mass azithromycin distribution for child mortality due to concerns related to infantile hypertrophic pyloric stenosis (IHPS). Here, we report the design of a randomised controlled trial to evaluate the efficacy and safety of administration of a single dose of oral azithromycin during the neonatal period.

METHODS AND ANALYSIS: The (NAITRE) study is a double-masked randomised placebo-controlled trial designed to evaluate the efficacy of a single dose of azithromycin (20 mg/kg) for the prevention of child mortality. Newborns (n=21 712) aged 8-27 days weighing at least 2500 g are 1:1 randomised to a single, directly observed, oral dose of azithromycin or matching placebo. Participants are followed weekly for 3 weeks after treatment to screen for adverse events, including IHPS. The primary outcome is all-cause mortality at the 6-month study visit.

ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Boards at the University of California, San Francisco in San Francisco, USA (Protocol $\#$18-25027) and the Comit{\'e} National d{\textquoteright}Ethique pour la Recherche in Ouagadougou, Burkina Faso (Protocol $\#$2018-10-123). The findings of this trial will be presented at local, regional and international meetings and published in open access peer-reviewed journals.

TRIAL REGISTRATION NUMBER: NCT03682653; Pre-results.

}, keywords = {Anti-Bacterial Agents, Azithromycin, Body Size, Body Weight, Child Development, Double-Blind Method, Humans, Infant, Infant Mortality, Infant, Newborn, Randomized Controlled Trials as Topic}, issn = {2044-6055}, doi = {10.1136/bmjopen-2019-031162}, author = {Sie, Ali and Bountogo, Mamadou and Nebie, Eric and Ouattara, Mamadou and Coulibaly, Boubacar and Bagagnan, Cheik and Zabre, Pascal and Lebas, Elodie and Brogdon, Jessica and Godwin, William W and Lin, Ying and Porco, Travis and Doan, Thuy and Lietman, Thomas M and Oldenburg, Catherine E} }