@article {931, title = {Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger.}, journal = {Nat Commun}, volume = {13}, year = {2022}, month = {2022 02 21}, pages = {976}, abstract = {

The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5\% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1-59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29\% (hazard ratio = 0.71, 95\% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger.

}, issn = {2041-1723}, doi = {10.1038/s41467-022-28565-5}, author = {Arzika, Ahmed M and Maliki, Ramatou and Goodhew, E Brook and Rogier, Eric and Priest, Jeffrey W and Lebas, Elodie and O{\textquoteright}Brien, Kieran S and Le, Victoria and Oldenburg, Catherine E and Doan, Thuy and Porco, Travis C and Keenan, Jeremy D and Lietman, Thomas M and Martin, Diana L and Arnold, Benjamin F} } @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} } @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} }