Azithromycin for Child Survival in Niger: Mortality and Resistance Trial (AVENIR)

Aktiv komparator: Azithro 1-11

Toårlig vekt- eller høydebasert dose av oral azitromycinsuspensjon til barn 1-11 måneder gamle og oral placebo eller ingen intervensjon til barn 12-59 måneder gamle

Legemiddel: Azitromycin

Azitromycin vil bli administrert som en direkte observert dose i oral suspensjonsform for barn:

1. Enkeltdose på 20 mg/kg til barn (opptil maksimal voksendose på 1 g)
2. For barn i alderen 1-11 måneder vil vekt- eller aldersbasert dosering bli brukt
3. For barn i alderen 12-59 måneder vil høydebasert dosering bli brukt via tilnærming til høydestokken slik det for tiden utføres av Nigers trakomprogram

Andre navn:

• Zithromax

Annen: Placebo

Placebo vil bli administrert som en direkte observert dose i oral suspensjonsform for barn:

1. Enkeltdose på 20 mg/kg til barn (opptil maksimal voksendose på 1 g)
2. For barn i alderen 1-11 måneder vil vektbasert dosering brukes
3. For barn i alderen 12-59 måneder vil høydebasert dosering bli brukt via tilnærming til høydestokken slik det for tiden utføres av Nigers trakomprogram

Aktiv komparator: Azithro 1-59

Halvårlig alder, vekt- eller høydebasert dose av oral azitromycinsuspensjon til barn 1-59 måneder gamle

Legemiddel: Azitromycin

Azitromycin vil bli administrert som en direkte observert dose i oral suspensjonsform for barn:

1. Enkeltdose på 20 mg/kg til barn (opptil maksimal voksendose på 1 g)
2. For barn i alderen 1-11 måneder vil vekt- eller aldersbasert dosering bli brukt
3. For barn i alderen 12-59 måneder vil høydebasert dosering bli brukt via tilnærming til høydestokken slik det for tiden utføres av Nigers trakomprogram

Andre navn:

• Zithromax

Placebo komparator: Placebo

Halvårlig vekt- eller høydebasert dose av oral placebo til barn 1-59 måneder gamle

Annen: Placebo

Placebo vil bli administrert som en direkte observert dose i oral suspensjonsform for barn:

1. Enkeltdose på 20 mg/kg til barn (opptil maksimal voksendose på 1 g)
2. For barn i alderen 1-11 måneder vil vektbasert dosering brukes
3. For barn i alderen 12-59 måneder vil høydebasert dosering bli brukt via tilnærming til høydestokken slik det for tiden utføres av Nigers trakomprogram

Dødelighet av alle årsaker (1-59 måneder gammel)

Dødeligheten (dødsfall per 1000 årsverk i fare) blant barn 1-59 måneders alder, og sammenlignet azitro 1-59 og placebo-armer.

Dødelighet av alle årsaker (1-11 måneder gammel)

Dødelighetsraten (dødsfall per 1000 årsverk i fare) blant barn 1-11 måneders alder, og sammenligner azitro 1-11 og placebo-armer.

All-årsak dødelighet (12-59 måneder gammel)

Dødeligheten (dødsfall per 1000 årsverk i fare) blant barn 12-59 måneders alder med priser sammenlignet mellom azitro 1-11 og azitro 1-59 samfunn.

Prevalence of Resistance to Macrolides - Nasopharyngeal Swabs (1-59 Months Old)

Prevalence of macrolide resistance among pneumococcus-positive nasopharyngeal swabs collected from children aged 1-59 months after 4 distributions. Resistance was assessed among culture-positive pneumococcal isolates from nasopharyngeal swabs.

Load of Genetic Determinants of Resistance to Macrolides - Rectal Swabs (1-59 Months Old)

Community-level load of macrolide antimicrobial resistance determinants in pooled rectal swabs collected from children aged 1-59 months after four biannual distributions. Rectal swabs from each community were pooled and analyzed using metagenomic DNA sequencing. Nonhost sequencing reads were aligned to an antimicrobial resistance reference database, and reads matching macrolide resistance determinants were summed and normalized to the total number of nonhost reads in the pooled sample. Values are reported as matched resistance reads per million nonhost reads (rM). Higher values indicate a greater abundance of macrolide resistance determinants. The values presented in the table are untransformed normalized counts.

Mortality Rate by Weight-for-age Z-score Subgroup Among Infants Aged 1-11 Months

All-cause mortality incidence rate among children aged 1-11 months who had weight measured during at least one census round and had a valid weight-for-age z-score calculated using the World Health Organization Child Growth Standards. Nutritional status was assessed at the beginning of each census interval. This measure reports the overall mortality rate for this analysis population by randomized treatment arm and is not stratified by weight-for-age z-score subgroup. Mortality rates are reported as deaths per 1,000 person-years.

Load of Genetic Determinants of Resistance to Macrolides in Nasopharyngeal Swabs From Guardians

Community-level loads of macrolide antimicrobial resistance determinants in nasopharyngeal swabs collected from guardians of children eligible for treatment after four biannual distributions. Nasopharyngeal swabs from each community were pooled and analyzed using DNA sequencing. Nonhost sequencing reads were aligned to an antimicrobial resistance reference database, and reads matching macrolide resistance determinants were summed and normalized to the total number of nonhost reads in the pooled sample. Values are reported as matched resistance reads per million nonhost reads (rM). Higher values indicate a greater abundance of macrolide resistance determinants. The values presented in the table are untransformed normalized counts; log-transformed values were used only for inferential statistical analyses.

Program Costs Per Dose Delivered

Program cost per dose delivered was estimated using routine administrative data and micro-costing activities. Costs were calculated per dose delivered and were not stratified by randomized treatment arm.

Load of Genetic Determinants of Resistance to Macrolides in Nasopharyngeal Swabs From Children Aged 7-12 Years

Community-level loads of macrolide antimicrobial resistance determinants in nasopharyngeal swabs collected from children aged 7-12 years after four biannual distributions. Nasopharyngeal swabs from each community were pooled and analyzed using DNA sequencing. Nonhost sequencing reads were aligned to an antimicrobial resistance reference database, and reads matching macrolide resistance determinants were summed and normalized to the total number of nonhost reads in the pooled sample. Values are reported as matched resistance reads per million nonhost reads (rM). Higher values indicate a greater abundance of macrolide resistance determinants. The values presented in the table are untransformed normalized counts; log-transformed values were used only for inferential statistical analyses.