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PRJEB42363 ERP126206

Azithromycin MDA and gut resistome in Malawi children

Impact of azithromycin mass drug administration on the antibiotic resistant gut microbiome: a randomized, controlled trial

181 faecal samples from children in a Malawi trachoma MDA site, studying azithromycin's effect on gut macrolide resistance and microbiome composition, in a randomized controlled trial (azithromycin vs placebo). machine-written summary

181 samples · 181 runs · ZA, MW · Infant / toddler · 2021 · 2.65 Gbp / sample

Sources
○Sequence archive✓Abstract / description 185○Full text✓Supplementary tables 708–External resources–User contribution–Human verified

Checked this project's papers and archive records yourself? Mark it human-verified.

what each source gave
○ Sequence archiverecords read; no usable sample values
✓ Abstract / description185 sample values (country, location site)
○ Full textread; no usable statement or table · PMC10269646, PMC12769767
✓ Supplementary tables708 sample values (country, feeding mode, subject id, timepoint)
– External resourcesnot covered by the external resources we ingest
– User contributionnothing uploaded yet · share metadata
– Human verifiednot yet checked by a person · I checked this project — verify it
Interventions

intervention — arms not resolved

Antibiotic given as the study intervention (incl. eradication therapy design randomized_controlled_trial · population healthy_control · Azithromycin mass drug administration vs placebo in children, 4 rounds

“half receiving azithromycin and half placebo” — bioproject.description (study level; per-sample arms are in the intervention column below)

Samples at a glance
2 countries
Age
unknown181
Country
ZA177
MW4
Body site
primary181
Sequencing depth per sample · this project all projects
all projects, 0–0.03 Gbp: 25,080 samples (4 %)this project, 0–0.03 Gbp: 4 samplesall projects, 0.03–0.1 Gbp: 17,066 samples (3 %)all projects, 0.1–0.3 Gbp: 29,179 samples (5 %)all projects, 0.3–1 Gbp: 47,044 samples (8 %)all projects, 1–3 Gbp: 124,983 samples (22 %)this project, 1–3 Gbp: 129 samplesall projects, 3–10 Gbp: 253,728 samples (44 %)this project, 3–10 Gbp: 48 samplesall projects, 10–30 Gbp: 72,533 samples (13 %)all projects, 30–100 Gbp: 3,024 samples (1 %)all projects, 100–300 Gbp: 106 samples (0 %)all projects, ≥ 300 Gbp: 9 samples (0 %)project median 2.65 Gbp per sample0130Gbp
Sampling design and relatedness

longitudinal — not resolvedcommunity — not resolved

4 of 173 people sampled more than once (8 samples; median 2, up to 2 per person).

Children from 30 MORDOR Malawi communities (40 per community per visit); no per-sample community id in archive.

How longitudinal and relatedness information is derived

Community composition
Prevotella 33.0%Bifidobacterium 5.7%Bacteroides 3.2%Faecalibacterium 2.9%Escherichia 2.9%Ruminococcoides 2.7%Streptococcus 2.6%Roseburia 2.5%Alloprevotella 1.9%Ligilactobacillus 1.5%Veillonella 1.5%Vescimonas 1.3%not assigned to a genus 5.2%other genera 33.1%

Genera, mean relative abundance over 160 profiled gut samples of this project (Sandpiper SingleM profiles, GTDB R232; low-depth and non-metagenome profiles left out).

Field coverage
fieldsamplescoverageR1R2R3R4
age_category0 0%
country181 100%1774
health_condition0 0%
subject_id177 98%177
detailed_location181 100%
location_site181 100%181
feeding_mode177 98%177
timepoint_label177 98%177
Papers (2)
  • Exploring Molecular Interactions between Human Milk Hormone Insulin and Bifidobacteria. PMID 37191543 PMC10269646 curated
  • Compiling an early life human gut microbiome atlas and identification of key microbial drivers. PMID 41350579 PMC12769767 curated
Details
Archive description

Mass drug administration (MDA) with azithromycin is the primary strategy for global trachoma control efforts. Numerous studies have reported secondary effects of MDA with azithromycin, including reductions in childhood mortality, diarrhoeal disease and malaria. Most recently, the MORDOR clinical trial demonstrated that treatment led to an overall reduction in all-cause childhood mortality in targeted communities. There is however considerable concern about the potential of increased antimicrobial resistance in treated communities.This study evaluated the impact of azithromycin MDA on prevalence of gastrointestinal carriage of macrolide-resistant bacteria in communities within the MORDOR Malawi study site, while additionally profiling changes in the gut microbiome after treatment. For faecal metagenomics, 60 children were sampled prior to treatment and 122 children after four rounds of MDA, half receiving azithromycin and half placebo.The proportion of bacteria carrying macrolide resistance increased after azithromycin treatment the effect was enhanced in children treated within six months of sampling. Diversity and global community structure of the gut was minimally impacted by treatment, however abundance of several individual species was altered by treatment. Notably, the putative human enteropathogen Escherichia albertii was more abundant after treatment.The impacts of MDA with azithromycin, including increased carriage of macrolide resistant bacteria, were enhanced in children treated more recently, suggesting effects may be transient. Increased abundance of enteropathogenic Escherichia species after treatment requires further, higher resolution investigation. Future studies should focus on the number of treatments and administration schedule to ensure clinical benefits continue to outweigh costs in antimicrobial resistance carriage.

How this project entered the registry

Classified as human gut / stool shotgun DNA metagenome of infant / toddler and child by deterministic_prior with confidence 0.90. Assay shotgun_dna.

  • host external_curation.infant_catalog · “infant triage verdict include”
  • body site study.title · “the antibiotic resistant gut microbiome: a randomized,”
  • body site study.description · “on prevalence of gastrointestinal carriage of macrolide-resistant”
  • life stage external_curation.infant_catalog · “infant triage verdict include (0-3 y scope)”
  • life stage study.description · “including reductions in childhood mortality, diarrhoeal disease”
Evidence examples (one per field × route)
samplefieldvaluerouteconf.sourcequote
SAMEA7766609countryZAR20.75paper.supp.tableGeography=Africa
SAMEA7766647countryMWR40.45study.descriptionMORDOR Malawi study site
SAMEA7766609feeding_modeexclusive_breastR20.75paper.supp.tableFeeding type=Breast Milk
SAMEA7766609location_siteMORDOR Malawi study siteR40.45ena.study_descriptioncommunities within the MORDOR Malawi study site
SAMEA7766609subject_idFE498542-8F63-40D6-8B7B-FDEC33678F3FR20.85paper.supp.13099_2021_478_MOESM1_ESM.xlsx[species!ParticipantID]SampleID 147529; ParticipantID FE498542-8F63-40D6-8B7B-FDEC33678F3F
SAMEA7766609timepoint_labelpre-weaningR20.75paper.supp.tableTime Group=pre-weaning
Sequencing

181 runs over 181 samples · mean 2.76 Gbp per run (median 2.65 Gbp, total 499.41 Gbp; 181 runs with a base count) · layout PAIRED 181 · platform ILLUMINA 181 · models NextSeq 500 (181) · 88% of runs with a Sandpiper profile · first public 2021-04-01

Authors (18)

Rizzo SM first · Alessandri G · Lugli GA · Fontana F · Tarracchini C · Mancabelli L · Viappiani A · Bianchi MG · Bussolati O · van Sinderen D · Ventura M · Turroni F last · Longhi G · Gennaioli E · Muscò A · Vitale SG · Angioni S · Milani C

Help complete this project

2 of the 4 core fields are below 50% coverage: age_category, health_condition. Share metadata

Downloads

PRJEB42363.csv.gz (10.1 KB) · parquet (89.2 KB) — all 181 samples, every field with route and confidence · PRJEB42363_determinations.csv.gz (12.2 KB) — 893 evidence rows

Samples (181 · every field this project has values for · hover a cell for its source)
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