The long-term goal of this study is to more precisely define the role of mass azithromycin treatments as an intervention for reducing childhood morbidity and increasing growth, and for the potential selection of antibiotic resistance. The investigators propose a set of 3 cluster-randomized trials comparing communities randomized to oral azithromycin with those randomized to placebo. To assess the generalizability of the intervention, investigators will monitor for antibiotic resistance, which could potentially limit adoption of mass antibiotic treatments. The investigators will also assess several measures of infectious diseases. The investigators hypothesize that mass azithromycin treatments will reduce childhood morbidity and will be accompanied by an acceptable level of antibiotic resistance.
Evaluating Impact of Azithromycin Mass Drug Administrations on Cause-specific Mortality and Antibiotic Resistance: Morbidity Study
The investigators will assess childhood infectious disease morbidity and macrolide resistance over two years, comparing communities where children aged 1-60 months receive biannual oral azithromycin to communities where the children receive biannual oral placebo. In Niger, a third arm - annual treatment of all persons 1 month and older - will also be included.
Randomization of Treatment Allocation. In each site, 30 communities within a contiguous area of 300,000 to 600,000 individuals will be randomized into the azithromycin or placebo arm. At the Niger site, an additional 15 communities will be randomized to the third arm (azithromycin for everyone). The investigators will use a simple random sample separately for each study site, but without stratification or block randomization within the site. These communities are being randomized from the same pool of communities eligible for a sister trial (Mortality Reduction After Oral Azithromycin (MORDOR) - Morbidity Study; clinicaltrials.gov OPP1032340-A).
Specific Aim 1: To assess whether macrolide resistance is greater in a population-based community sample of pre-school children, or in a clinic-based sample of ill pre-school children
Specific Aim 2: To assess whether biannual mass azithromycin treatments of pre-school children can eliminate ocular chlamydia in a hypoendemic area
Specific Aim 3: To assess the diversity of the microbiome of the nasopharynx, oropharynx, nares, conjunctiva, and gastrointestinal tract
The community leader consents to participation in the trial
The community's estimated population is between 200-2,000 people.
The community is not in an urban area.
Children-treated arms (all 3 sites): All children aged 1-60 months (up to but not including the 5th birthday), as assessed at the most recent biannual census
Everyone-treated arm (Niger only): All individuals aged 1 month and up, as assessed at the most recent biannual census
Individuals (Examination & Sample Collection):
All swabs, blood tests, and stool samples: A random sample of children aged 1-60 months (up to but not including the 5th birthday) based on the previous census
Anthropometric measurements: All children aged 1-60 months (up to but not including the 5th birthday) will have anthropometric measurements assessed.
Nasopharyngeal swabs in untreated children: A random sample of individuals aged 7 - 12 years (7th birthday up to but not including the 12th birthday), as assessed from the previous census
Clinic-based nasopharyngeal swabs: All children aged 1-60 months (up to but not including the 5th birthday) who present to a local health clinic in the study area and report symptoms of a respiratory infection
You CAN'T join if...
All those who are allergic to macrolides or azalides
Refusal of village chief (for village inclusion), or refusal of parent or guardian(for individual inclusion)
UCSF Proctor Foundationin progress, not accepting new patients San Francisco, California, 94143, USA
Johns Hopkins Universityin progress, not accepting new patients Baltimore, Maryland, 21205, USA
College of Medicine at the University of Malawi, Blantyreaccepting new patients Blantyre, Malawi
The Carter Center, Nigeraccepting new patients Niamey, Niger
Kongwa Trachoma Projectaccepting new patients Kongwa, Tanzania
London School of Hygiene & Tropical Medicinein progress, not accepting new patients London, United Kingdom