Table 1.
Ongoing Studies Addressing Research Questions of Antimicrobial Resistance After Macrolide Mass Treatment
| NCT Number | Country | Target Disease | Part of MORDOR | Type of Study | Target Age Group | Number of AZM Doses/ Course | Number of AZM Courses | Microbiology Endpoints | Genotypic Methods Used |
|---|---|---|---|---|---|---|---|---|---|
| NCT03683667 | Bangladesh | Malnutrition/ stunting | No | cRCT | 6-12-mo-old children | 1 | 2 (6 and 9 mo) | Enteropathogen burden (7× at age 6–18 mo), gut microbiota composition (as above), AMR of E. coli and S. pneumoniae at 6, 9, 12, 15, and 18 mo of age in participating children | qPCR, 16S ribosomal RNA sequencing |
| NCT03682653 | Burkina Faso | Mortality | Yes | RCT | 8-27-d-old children | 1 | 1 (during newborn period) | None specified | … |
| NCT03676764 | Burkina Faso | Mortality | Yes | cRCT | 1-60-mo-old children and those receiving first DTP vaccine (5-8-wk-old children) | 1 | 1 and 2×/y for older children | Carriage of S. pneumoniae and nasopharyngeal macrolide resistance at 36 mo postexposure, proportion of E. coli resistant to macrolides and other key antibiotics at 36 mo postexposure, microbial diversity in the nasopharyngeal and intestinal microbiome at 36 mo postexposure | Next-generation sequencing (not further specified) |
| NCT03676751 | Burkina Faso | Growth and development | Yes | RCT | 8-d to 59-mo-old children | 1 | 1 | Intestinal microbial diversity at 6 mo postexposure | Targeted PCR and next-generation sequencing (not further specified) |
| NCT03676140 | Papua New Guinea | Trachoma/NTD | No | cRCT | Persons older than 5 y of age in randomized communities | 1 | 1 | None specified | … |
| NCT03570814 | Ethiopia | Trachoma/NTD | No | cRCT | Persons older than 5 y of age in randomized communities | 1 | 1 | None specified | … |
| NCT03568643 | Niger | Malnutrition/ stunting | No | RCT | 6–59-mo-old children | 1 | 1 | None specified | … |
| NCT03564652 | Pakistan | Malnutrition/stunting | No | RCT | Pregnant women, infants 42 d of age | 1 | 1 | Enteropathogen burden at 40–42 and 56 d of age | Multiplex PCR and metagenomics (not further specified) |
| NCT03523156 | Ethiopia | Trachoma | No | cRCT | 6-mo- to 9-y-old children | 1 | 1 (MDA annual) or 3 (MDA annual plus 2× targeted) | None specified beyond chlamydial infections (not AMR) | … |
| NCT03490123 | Papua New Guinea | Yaws | No | cRCT | Older than 6 mo | 1 | 3 | Macrolide resistance in T.p. pertenue | … |
| NCT03474276 | Madagascar, Niger, CAR, Senegal | Malnutrition/stunting | No | RCT | 6–24-mo-old children | 3 | 1 | Comparison of OTU composition of stool according to nutritional status (at baseline and 3 and 6 mo postexposure) | Next-generation sequencing (detailed description) |
| NCT03338244 | Original MORDOR sites | Mortality | Yes | cRCT | 1–60 mo of age | 1 | 2×/y | Macrolide resistance 18 mo postexposure in nasopharyngeal and rectal swabs, microbial composition of stool at 18 mo, enteropathogen burden at 18 mo | Metagenomic deep sequencing for microbial composition; resistance detected by standard phenotypic methods |
| NCT03335072 | Ethiopia | Trachoma | No | cRCT | All persons in randomized communities eligible for MDA according to WHO guideline | 1 | 4×/y | None specified beyond chlamydial infections (not AMR) | … |
| NCT03268902 | Tanzania | Malnutrition/stunting | No | RCT | Up to 14 d old | 1 | 6, 9, 12, and 15 mo | Enteropathogen burden (5× between 6 and 18 mo), intestinal microbiota composition (4× between 6 and 18 mo) | Not specified |
| NCT03199547 | The Gambia and Burkina Faso | Neonatal sepsis | No | RCT | Women in labor | 1 | 1 | EONS (culture confirmed) and LONS (culture confirmed) | … |
| NCT03187834 | Burkina Faso | Growth and development | No | cRCT (households) | 6–59-mo-old children | 5 | 1 | Nasopharyngeal and intestinal microbiome (day 9 postexposure) | DNA sequencing (not further specified) |
| NCT03032042 | Ethiopia | Helminthic infection | No | RCT | 1–60 mo of age | 1 | 1 | Microbial diversity in intestinal microbiome 7 d postexposure | … |
| NCT02754583 | Ethiopia | Trachoma | No | RCT | All persons in randomized communities | 1 (MDA, annual), 1 (targeted) | 1 (MDA, annual), 4 (quarterly) | Nasopharyngeal pneumococcal macrolide resistance (12, 24, 36 mo postexposure), intestinal microbiome at 12 mo postexposure (substudy) | Not specified |
| NCT02414399 | Kenya | Mortality | No | RCT | 1–59 mo of age | 5 | 1 | Prevalence of enteric pathogen and pneumococcal carriage (6 mo postexposure), proportion of β-lactam or macrolide resistance or both (6 mo postexposure) | … |
| NCT02048007 | Malawi, Niger, and Tanzania | Mortality | Yes | cRCT | 1–60 mo of age | 1 | 2×/y | Pneumococcal macrolide resistance at 24 and 48 mo, macrolide resistance (genetic) in stool and nasopharynx at 24 and 48 mo, carriage of resistant pneumococcus at 6 to 24 mo, proportion of rectal/stool isolates and E. coli isolates resistant to macrolides and other antibiotics at 6 to 24 mo, MRSA (NP) at 24 mo, carriage of S. aureus resistant to macrolides and other antibiotics at 6 to 24 mo, various deep-sequencing endpoints | Metagenomics (not further specified) |
Abbreviations: AMR, antimicrobial resistance; AZM, azithromycin; CAR, Central African Republic; cRCT, cluster-randomized controlled trials; DTP, diphtheria, pertussis, tetanus vaccine; E. coli, Escherichia coli; EONS, early onset neonatal sepsis, LONS, late-onset neonatal sepsis; MDA, mass drug administration; MORDOR, Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance; MRSA, methicillin-resistant Staphylococcus aureus; NCT, national clinical trial; NP, nasopharynx; NTD, neglected tropical disease; OTU, Operational Taxonomic Unit; PCR, polymerase chain reaction; qPCR, quantitative polymerase chain reaction; RCT, randomized controlled trial; S. aureus, Staphylococcus aureus; S. pneumoniae, Streptococcus pneumoniae; T.p. pertenue, Treponema pallidum ssp. pertenue; WHO, World Health Organization.