Clinical trial NCT03187834: Antibiotic Resistance and Microbiome in Children Aged 6-59 Months in Nouna, Burkina Faso
Official title: Antibiotic Resistance and Microbiome in Children Aged 6-59 Months in Nouna, Burkina Faso
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Child Development
Keywords: infection
azithromycin
amoxicillin
co-trimoxazole
trachoma
mass treatment
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Centre de Recherche en Sante de Nouna, Burkina Faso
name: Heidelberg University
First posted: 2017-06-15
Enrollment: 252
Sex: ALL
Minimum age (years): 6
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Households will be randomized to one of four treatment arms (azithromycin, cotrimoxazole, amoxicillin, or placebo), and each child age 6-59 months in the household will receive 5 days of treatment. One child within each of the antibiotic households will be randomly selected to receive placebo instead of the antibiotc, to allow for study of indirect effects of antibiotic use
Primary purpose: TREATMENT

Brief summary: The use of antibiotics has saved millions of human lives, however consumption of antibiotics can select for antibiotic resistant organisms and may lead to changes in commensal microbiome. This study is designed to estimate the effect of antibiotic consumption on microbiome in a rural region of rural Burkina Faso. Changes in the intestinal and nasopharyngeal microbiome and resistome following a short course of antibiotics will be measured.

Detailed description: This study is designed to better understand the effect of a short course of antibiotics on changes in intestinal and nasopharyngeal microbiome on treated children and untreated household contacts. The investigators hypothesize that a short course of antibiotics will lead to decreased bacterial diversity shortly after completion of the antibiotic course, and higher probability of identification of bacterial resistance genes in rectal and nasopharyngeal samples. The investigators hypothesize that a 5-day course of antibiotics (azithromycin, amoxicillin, or co-trimoxazole) will lead to significantly decreased intestinal and nasopharyngeal bacterial diversity among children aged 6-59 months.

Specific Aim 1. Determine the effect of treatment with antibiotics on microbiome diversity in children aged 6-59 months following a 5-day course of antibiotics.

Specific Aim 1A. Determine the direct effect of a 5-day course of azithromycin, amoxicillin, or co-trimoxazole on intestinal and nasopharyngeal bacterial diversity in children aged 6-59 months compared to no treatment.

Specific Aim 1B. Determine the indirect effect of antibiotic treatment of children in a household on intestinal and nasopharyngeal bacterial diversity in an untreated child aged 6-59 months.

Specific Aim 1C. Assess the association between intestinal bacterial diversity and anthropometry in a population-based sample of children.

Eligibility criteria: Inclusion Criteria:

* Households will be eligible for inclusion in the study if they have 2 or more children aged 6 months to 59 months currently residing in the household. Children from the household will be eligible if they are 6-59 months of age and are not currently receiving antibiotic treatment

Exclusion Criteria:

* Children who are allergic to any of the study antibiotics will be excluded. Individuals aged under 6 months and 5 years or older will be excluded. Children already receiving antibiotics for an ongoing disease will be excluded.

Primary outcomes:
measure: Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome
timeFrame: Baseline and Day 9
Secondary outcomes:
measure: Simpson's Index of Diversity (Alpha Diversity) in Microbiome
timeFrame: Day 9
measure: Weight-for-height Z-score
timeFrame: Day 35
measure: Height-for-age Z-score
timeFrame: Day 35
measure: Weight-for-age Z-score
timeFrame: Day 35
measure: Mid-upper Arm Circumference
timeFrame: Day 35
measure: Shannon's Index of Diversity (Alpha Diversity) in Intestinal Microbiome
timeFrame: Baseline and Day 9 (Post- Treatment)
measure: Shannon's Index of Diversity (Alpha Diversity) in Nasopharyngeal Microbiome
timeFrame: Day 9
measure: L1-norm Distance on Bacterial Reads (Intestinal)
timeFrame: Baseline and Day 9 (Post- Treatment)
measure: L1-norm Distance on Bacterial Reads (Nasopharyngeal)
timeFrame: Day 9
measure: L2-norm Distance on Bacterial Reads (Intestinal)
timeFrame: Baseline and Day 9 (Post- Treatment)
measure: L2-norm Distance on Bacterial Reads (Nasopharyngeal)
timeFrame: Day 9
measure: Number of Participants With Macrolide Resistance Genes
timeFrame: 2 years
measure: Alpha Diversity in the Intestinal Microbiome
timeFrame: 2 years
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Proctor Foundation
state: California
city: Nouna
country: Burkina Faso
facility: Centre de Recherche en Santé de Nouna
Study officials:
affiliation: UCSF F.I. Proctor Foundation
name: Thomas M Lietman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UCSF F.I. Proctor Foundation
name: Catherine E Oldenburg, ScD
role: STUDY_DIRECTOR
References:
citation: Oldenburg CE, Hinterwirth A, Worden L, Sie A, Dah C, Ouermi L, Coulibaly B, Zhong L, Chen C, Ruder K, Lietman TM, Keenan JD, Doan T. Indirect effect of oral azithromycin on the gut resistome of untreated children: a randomized controlled trial. Int Health. 2021 Feb 24;13(2):130-134. doi: 10.1093/inthealth/ihaa029.
citation: Dennis EG, Sie A, Ouermi L, Dah C, Tapsoba C, Zabre P, Barnighausen T, O'Brien KS, Lebas E, Keenan JD, Oldenburg CE. Short-term weight gain among preschool children in rural Burkina Faso: a secondary analysis of a randomised controlled trial. BMJ Open. 2019 Jul 29;9(7):e029634. doi: 10.1136/bmjopen-2019-029634.
citation: Oldenburg CE, Sie A, Coulibaly B, Ouermi L, Dah C, Tapsoba C, Barnighausen T, Lebas E, Arzika AM, Cummings S, Zhong L, Lietman TM, Keenan JD, Doan T. Indirect Effect of Azithromycin Use on the Intestinal Microbiome Diversity of Untreated Children: A Randomized Trial. Open Forum Infect Dis. 2019 Feb 6;6(3):ofz061. doi: 10.1093/ofid/ofz061. eCollection 2019 Mar.
citation: Oldenburg CE, Sie A, Coulibaly B, Ouermi L, Dah C, Tapsoba C, Barnighausen T, Ray KJ, Zhong L, Cummings S, Lebas E, Lietman TM, Keenan JD, Doan T. Effect of Commonly Used Pediatric Antibiotics on Gut Microbial Diversity in Preschool Children in Burkina Faso: A Randomized Clinical Trial. Open Forum Infect Dis. 2018 Nov 2;5(11):ofy289. doi: 10.1093/ofid/ofy289. eCollection 2018 Nov.
citation: Sie A, Dah C, Ouermi L, Tapsoba C, Zabre P, Barnighausen T, Lebas E, Arzika AM, Snyder BM, Porco TC, Lietman TM, Keenan JD, Oldenburg CE. Effect of Antibiotics on Short-Term Growth among Children in Burkina Faso: A Randomized Trial. Am J Trop Med Hyg. 2018 Sep;99(3):789-796. doi: 10.4269/ajtmh.18-0342. Epub 2018 Jul 12.