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| Name | Class |
|---|---|
| Centre de Recherche en Sante de Nouna, Burkina Faso | OTHER_GOV |
| Heidelberg University | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Azithromycin | Active Comparator | Comparison of nasopharyngeal and rectal microbiome in children receiving Azithromycin versus children receiving placebo Children aged 6 months to 59 months will be measured and weighed then, they will be randomized to one of the study arm and treated for 5 days. Children will receive treatment everyday, once a day as is: Azithromycin: 10 mg/kg once daily on Day 1, then 5 mg/kg once daily Days 2-5 |
|
| Amoxicillin | Active Comparator | Comparison of nasopharyngeal and rectal microbiome in children receiving Amoxicillin versus children receiving placebo Children aged 6 months to 59 months will be measured and weighed then, they will be randomized to one of the study arm. Children will receive treatment everyday, twice a day as is: Amoxicillin: 25 mg/kg/day, divided into twice daily doses for Days 1-5 |
|
| Cotrimoxazole | Active Comparator | Comparison of nasopharyngeal and rectal microbiome in children receiving Cotri-moxazole versus children receiving placebo Children aged 6 months to 59 months will be measured and weighed then, they will be randomized to one of the study arm. Children will receive treatment everyday, once a day as is: Co-trimoxazole: 240 mg daily for Days 1-5 |
|
| Placebo | Placebo Comparator | Comparison of nasopharyngeal and rectal microbiome in children receiving placebo versus children receiving antibiotics Children aged 6 months to 59 months will be measured and weighed then, they will be randomized to one of the study arm. Children will receive Placebo everyday, once a day. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Azithromycin | Drug | Children in this arm will receive Azithromycin once a day. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | The primary outcome of the study was pre-specified as α-diversity (inverse Simpson's) at the genus level, expressed in effective number. Simpson's Alpha Diversity were obtained at Baseline and Post-treatment in this study. The minimum of Simpson's index of diversity is 0, there is no maximum. Higher Simpson's index of diversity means more diverse. There are no subscales. | Baseline and Day 9 |
| Measure | Description | Time Frame |
|---|---|---|
| Simpson's Index of Diversity (Alpha Diversity) in Microbiome | Direct and indirect effect of antibiotics on alpha diversity from rectal samples | Day 9 |
| Weight-for-height Z-score | Nutritional status as determined by weight-for-height Z-score vs. Placebo household Weight-for-height Z-score in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Weight-for-height Z (WHZ) scores were calculated based on the 2006 World Health Organization (WHO) standards. The mean of the 2006 population standards is 0. Lower standard deviations = worse outcomes. A cutoff of < -2 means moderately wasted (WHZ). A cutoff of < -3 means wasted (WHZ). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas M Lietman, MD | UCSF F.I. Proctor Foundation | Principal Investigator |
| Catherine E Oldenburg, ScD | UCSF F.I. Proctor Foundation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Proctor Foundation | San Francisco | California | 94143 | United States | ||
| Centre de Recherche en Santé de Nouna |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32556194 | Derived | 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. | |
| 31362969 | Derived |
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| ID | Title | Description |
|---|---|---|
| FG000 | Amoxicillin Households | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Children will receive treatment everyday, twice a day as is: Amoxicillin: 25 mg/kg/day, divided into twice daily doses for Days 1-5 Amoxicillin Households - Antibiotic: Children in this arm will receive Amoxicillin twice a day. |
| FG001 | Azithromycin Households | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Children will receive treatment everyday, once a day as is: Azithromycin: 10 mg/kg once daily on Day 1, then 5 mg/kg once daily Days 2-5 Azithromycin Households - Antibiotic: Children in this arm will receive Azithromycin once a day. |
| FG002 | Cotrimoxazole Households | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Children will receive treatment everyday, once a day as is: Co-trimoxazole: 240 mg daily for Days 1-5 Cotrimoxazole: Children in this arm will receive co-trimoxazole once a day. |
| FG003 | Placebo | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. In placebo households, both children received placebo. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Children between 6 and 59 months of age and with parental consent. Data were only collected from children. In each arm, one children was given Antibiotic and one children was given Placebo. The baseline characteristics were reported separately in analysis and papers.
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| ID | Title | Description |
|---|---|---|
| BG000 | Amoxicillin Households - Antibiotic | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Children will receive treatment everyday, twice a day as is: Amoxicillin: 25 mg/kg/day, divided into twice daily doses for Days 1-5 Amoxicillin Households - Antibiotic: Children in this arm will receive Amoxicillin twice a day. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | The primary outcome of the study was pre-specified as α-diversity (inverse Simpson's) at the genus level, expressed in effective number. Simpson's Alpha Diversity were obtained at Baseline and Post-treatment in this study. The minimum of Simpson's index of diversity is 0, there is no maximum. Higher Simpson's index of diversity means more diverse. There are no subscales. | 248 children in 124 households were enrolled and randomized to 1 of the 3 antibiotic regimens or placebo. Of these, 124 children were randomized within their household to receive treatment and are included in this analysis. Of these children, 9 children were lost to follow-up. The samples from Amoxicillin Households - Placebo, Azithromycin Households - Placebo, Cotrimoxazole Households - Placebo and half of placebo (31 participants) were not collected and analyzed, due to limited budget. | Posted | Mean | 95% Confidence Interval | Index score | Baseline and Day 9 |
|
days 1-5
On each day of treatment, caregivers were asked if the child had any symptoms since the previous day, including gastrointestinal symptoms, respiratory symptoms, a rash, or any other symptoms. Four days after the last treatment dose, caregivers were asked if their child had had three or more loose or watery stools over a 24-hour period, consistent with the WHO definition of diarrhea,21 and if the child currently had a cough or difficulty breathing.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Amoxicillin Households - Antibiotic | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Children will receive treatment everyday, twice a day as is: Amoxicillin: 25 mg/kg/day, divided into twice daily doses for Days 1-5 Amoxicillin Households - Antibiotic: Children in this arm will receive Amoxicillin twice a day. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting, days 1-5 | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Thomas Lietman | F.I. Proctor Foundation, University of Califonia, San Francisco | 415-502-2662 | tom.lietman@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 19, 2017 | Sep 17, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 1, 2017 | Sep 17, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D007239 | Infections |
| D014141 | Trachoma |
| ID | Term |
|---|---|
| D003234 | Conjunctivitis, Bacterial |
| D015818 | Eye Infections, Bacterial |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
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| ID | Term |
|---|---|
| D017963 | Azithromycin |
| D000658 | Amoxicillin |
| D015662 | Trimethoprim, Sulfamethoxazole Drug Combination |
| ID | Term |
|---|---|
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 |
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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
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double blind
|
| Amoxicillin | Drug | Children in this arm will receive Amoxicillin twice a day. |
|
| Cotrimoxazole | Drug | Children in this arm will receive co-trimoxazole once a day. |
|
| Placebo | Drug | Children in this arm will receive Placebo once a day. |
|
| Day 35 |
| Height-for-age Z-score | Nutritional status as determined by height-for-age Z-score Height-for-age Z-score in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Height-for-age Z (HAZ) score were calculated based on the 2006 World Health Organization (WHO) standards. The mean of the 2006 population standards is 0. Lower standard deviations = worse outcomes. A cutoff of < -2 means moderately stunted (HAZ). A cutoff of < -3 means severely stunted (HAZ). | Day 35 |
| Weight-for-age Z-score | Nutritional status as determined by weight-for-age Z-score vs. Placebo household Weight-for-age Z-score in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Weight-for-age Z-score (WAZ) scores were calculated based on the 2006 World Health Organization (WHO) standards. The mean of the 2006 population standards is 0. Lower standard deviations = worse outcomes. A cutoff of < -2 means moderately underweight (WAZ). A cutoff of < -3 means severely underweight (WAZ). | Day 35 |
| Mid-upper Arm Circumference | Nutritional status as determined by mid-upper arm circumference in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Mid-upper arm circumference (MUAC) in each antibiotic group compared with placebo 4 weeks after last antibiotic dose. MUAC is a measure to assess nutritional status. It is measured on a straight left arm, mid-way between the tip of the shoulder and the tip of the elbow. It identifies acute malnutrition and is commonly used in children 6-59 months of age as well as pregnant women. MUAC less than 115 mm indicates severe wasting or severe acute malnutrition (SAM). MUAC greater than or equal to 115 mm and less than 125 mm indicates moderate wasting or moderate acute malnutrition (MAM). | Day 35 |
| Shannon's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Shannon's Alpha Diversity at Baseline and Post-treatment. combines richness and diversity. Shannon's index of diversity (alpha diversity) measures both the number of species and the inequality between species abundances. A large value is given by the presence of many species with well balanced abundances. | Baseline and Day 9 (Post- Treatment) |
| Shannon's Index of Diversity (Alpha Diversity) in Nasopharyngeal Microbiome | Direct and indirect effects of antibiotics on Shannon's index of bacterial diversity | Day 9 |
| L1-norm Distance on Bacterial Reads (Intestinal) | L1-norm distance on bacterial reads (intestinal) - L1 norm is equivalent to Shannon's diversity. Shannon's Alpha Diversity combines richness and diversity. Shannon's index of diversity (alpha diversity) measures both the number of species and the inequality between species abundances. A large value is given by the presence of many species with well balanced abundances. | Baseline and Day 9 (Post- Treatment) |
| L1-norm Distance on Bacterial Reads (Nasopharyngeal) | L1-norm distance on bacterial reads (nasopharyngeal) | Day 9 |
| L2-norm Distance on Bacterial Reads (Intestinal) | L2-norm distance on bacterial reads (intestinal) - L2 norm is equivalent to Simpson's diversity. Simpson's Alpha Diversity were obtained at Baseline and Post-treatment in this study. The minimum of Simpson's index of diversity is 0, there is no maximum. Higher Simpson's index of diversity means more diverse. There are no subscales. | Baseline and Day 9 (Post- Treatment) |
| L2-norm Distance on Bacterial Reads (Nasopharyngeal) | L2-norm distance on bacterial reads (nasopharyngeal) | Day 9 |
| Number of Participants With Macrolide Resistance Genes | Prevalence of macrolide resistance genes measured using DNA-seq from rectal swabs. | 2 years |
| Alpha Diversity in the Intestinal Microbiome | Alpha diversity in the intestinal microbiome using DNA-seq from rectal swabs | 2 years |
| Nouna |
| Burkina Faso |
| 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. |
| 30895203 | Derived | 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. |
| 30515431 | Derived | 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. |
| 30014828 | Derived | 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. |
| Had invalid anthropometric measurements |
|
| BG001 | Amoxicillin Households - Placebo | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Amoxicillin Households - Placebo: Children in this arm will receive Placebo. |
| BG002 | Azithromycin Households - Antibiotic | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Children will receive treatment everyday, once a day as is: Azithromycin: 10 mg/kg once daily on Day 1, then 5 mg/kg once daily Days 2-5 Azithromycin Households - Antibiotic: Children in this arm will receive Azithromycin once a day. |
| BG003 | Azithromycin Households - Placebo | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Azithromycin Households - Placebo: Children in this arm will receive Placebo. |
| BG004 | Cotrimoxazole Households - Antibiotic | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Children will receive treatment everyday, once a day as is: Co-trimoxazole: 240 mg daily for Days 1-5 Cotrimoxazole: Children in this arm will receive co-trimoxazole once a day. |
| BG005 | Cotrimoxazole Households - Placebo | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Cotrimoxazole Households - Placebo: Children in this arm will receive Placebo. |
| BG006 | Placebo | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. In placebo households, both children received placebo. |
| BG007 | Total | Total of all reporting groups |
| months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Wasted | Defined as Weight-for-height Z-score (WHZ) < -2 SD. | Count of Participants | Participants |
|
| Stunted | Defined as Height-for-age Z-score (HAZ) < -2 SD. | Count of Participants | Participants |
|
| Underweight | Defined as Weight-for-age Z-score (WAZ) < -2 SD. | Count of Participants | Participants |
|
| Visited healthcare facility in past 30 days | Count of Participants | Participants |
|
| Amoxicillin |
Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Children will receive treatment everyday, twice a day as is: Amoxicillin: 25 mg/kg/day, divided into twice daily doses for Days 1-5 Amoxicillin Households - Antibiotic: Children in this arm will receive Amoxicillin twice a day. |
| OG001 | Azithromycin | Comparison of nasopharyngeal and rectal microbiome in children receiving Azithromycin versus children receiving placebo Children aged 6 months to 59 months will be measured and weighed then, they will be randomized to one of the study arm and treated for 5 days. Children will receive treatment everyday, once a day as is: Azithromycin: 10 mg/kg once daily on Day 1, then 5 mg/kg once daily Days 2-5 Azithromycin: Children in this arm will receive Azithromycin once a day. |
| OG002 | Cotrimoxazole | Comparison of nasopharyngeal and rectal microbiome in children receiving Cotri-moxazole versus children receiving placebo Children aged 6 months to 59 months will be measured and weighed then, they will be randomized to one of the study arm. Children will receive treatment everyday, once a day as is: Co-trimoxazole: 240 mg daily for Days 1-5 Cotrimoxazole: Children in this arm will receive co-trimoxazole once a day. |
| OG003 | Placebo | Comparison of nasopharyngeal and rectal microbiome in children receiving placebo versus children receiving antibiotics Children aged 6 months to 59 months will be measured and weighed then, they will be randomized to one of the study arm. Children will receive Placebo everyday, once a day. Placebo: Children in this arm will receive Placebo once a day. |
|
|
| Secondary | Simpson's Index of Diversity (Alpha Diversity) in Microbiome | Direct and indirect effect of antibiotics on alpha diversity from rectal samples | rectal samples were not analyzed due to limited budget - samples were collected but not analyzed and never will be analyzed | Posted | Day 9 |
|
|
| Secondary | Weight-for-height Z-score | Nutritional status as determined by weight-for-height Z-score vs. Placebo household Weight-for-height Z-score in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Weight-for-height Z (WHZ) scores were calculated based on the 2006 World Health Organization (WHO) standards. The mean of the 2006 population standards is 0. Lower standard deviations = worse outcomes. A cutoff of < -2 means moderately wasted (WHZ). A cutoff of < -3 means wasted (WHZ). | In Amoxicillin, Azithromycin, Cotrimoxazole households, children assigned to receive antibiotic and placebo were analyzed separately, showed in different row below. | Posted | Mean | Standard Deviation | z score | Day 35 |
|
|
|
| Secondary | Height-for-age Z-score | Nutritional status as determined by height-for-age Z-score Height-for-age Z-score in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Height-for-age Z (HAZ) score were calculated based on the 2006 World Health Organization (WHO) standards. The mean of the 2006 population standards is 0. Lower standard deviations = worse outcomes. A cutoff of < -2 means moderately stunted (HAZ). A cutoff of < -3 means severely stunted (HAZ). | In Amoxicillin, Azithromycin, Cotrimoxazole households, children assigned to receive antibiotic and placebo were analyzed separately, showed in different row below. | Posted | Mean | Standard Deviation | z score | Day 35 |
|
|
|
| Secondary | Weight-for-age Z-score | Nutritional status as determined by weight-for-age Z-score vs. Placebo household Weight-for-age Z-score in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Weight-for-age Z-score (WAZ) scores were calculated based on the 2006 World Health Organization (WHO) standards. The mean of the 2006 population standards is 0. Lower standard deviations = worse outcomes. A cutoff of < -2 means moderately underweight (WAZ). A cutoff of < -3 means severely underweight (WAZ). | In Amoxicillin, Azithromycin, Cotrimoxazole households, children assigned to receive antibiotic and placebo were analyzed separately, showed in different row below. | Posted | Mean | Standard Deviation | Z score | Day 35 |
|
|
|
| Secondary | Mid-upper Arm Circumference | Nutritional status as determined by mid-upper arm circumference in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Mid-upper arm circumference (MUAC) in each antibiotic group compared with placebo 4 weeks after last antibiotic dose. MUAC is a measure to assess nutritional status. It is measured on a straight left arm, mid-way between the tip of the shoulder and the tip of the elbow. It identifies acute malnutrition and is commonly used in children 6-59 months of age as well as pregnant women. MUAC less than 115 mm indicates severe wasting or severe acute malnutrition (SAM). MUAC greater than or equal to 115 mm and less than 125 mm indicates moderate wasting or moderate acute malnutrition (MAM). | In Amoxicillin, Azithromycin, Cotrimoxazole households, children assigned to receive antibiotic and placebo were analyzed separately, showed in different row below. | Posted | Mean | Standard Deviation | mm | Day 35 |
|
|
|
| Secondary | Shannon's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Shannon's Alpha Diversity at Baseline and Post-treatment. combines richness and diversity. Shannon's index of diversity (alpha diversity) measures both the number of species and the inequality between species abundances. A large value is given by the presence of many species with well balanced abundances. | 248 children in 124 households were enrolled and randomized to 1 of the 3 antibiotic regimens or placebo. Of these, 124 children were randomized within their household to receive treatment and are included in this analysis. Of these children, 9 children were lost to follow-up. The samples for children who received placebo in Amoxicillin Households, Azithromycin Households, Cotrimoxazole Households and half of placebo (31 participants) were not collected and analyzed, due to limited budget. | Posted | Mean | 95% Confidence Interval | Index score | Baseline and Day 9 (Post- Treatment) |
|
|
|
| Secondary | Shannon's Index of Diversity (Alpha Diversity) in Nasopharyngeal Microbiome | Direct and indirect effects of antibiotics on Shannon's index of bacterial diversity | Nasopharyngeal samples were not analyzed, due to limited budget - samples were collected but not analyzed and never will be analyzed | Posted | Day 9 |
|
|
| Secondary | L1-norm Distance on Bacterial Reads (Intestinal) | L1-norm distance on bacterial reads (intestinal) - L1 norm is equivalent to Shannon's diversity. Shannon's Alpha Diversity combines richness and diversity. Shannon's index of diversity (alpha diversity) measures both the number of species and the inequality between species abundances. A large value is given by the presence of many species with well balanced abundances. | 248 children in 124 households were enrolled and randomized to 1 of the 3 antibiotic regimens or placebo. Of these, 124 children were randomized within their household to receive treatment and are included in this analysis. Of these children, 9 children were lost to follow-up. The samples for children who received placebo in Amoxicillin Households, Azithromycin Households, Cotrimoxazole Households and half of placebo (31 participants) were not collected and analyzed, due to limited budget. | Posted | Mean | 95% Confidence Interval | Index score | Baseline and Day 9 (Post- Treatment) |
|
|
|
| Secondary | L1-norm Distance on Bacterial Reads (Nasopharyngeal) | L1-norm distance on bacterial reads (nasopharyngeal) | Nasopharyngeal samples were not analyzed due to limited budget- samples were collected but not analyzed and never will be analyzed | Posted | Day 9 |
|
|
| Secondary | L2-norm Distance on Bacterial Reads (Intestinal) | L2-norm distance on bacterial reads (intestinal) - L2 norm is equivalent to Simpson's diversity. Simpson's Alpha Diversity were obtained at Baseline and Post-treatment in this study. The minimum of Simpson's index of diversity is 0, there is no maximum. Higher Simpson's index of diversity means more diverse. There are no subscales. | 248 children in 124 households were enrolled and randomized to 1 of the 3 antibiotic regimens or placebo. Of these, 124 children were randomized within their household to receive treatment and are included in this analysis. Of these children, 9 children were lost to follow-up. Indirect effect (antibiotic household - placebo) was not analyzed. we will not analyzed these biological specimens because no funding are available for this. Only direct effect of treatment is analyzed. | Posted | Mean | 95% Confidence Interval | Index score | Baseline and Day 9 (Post- Treatment) |
|
|
|
| Secondary | L2-norm Distance on Bacterial Reads (Nasopharyngeal) | L2-norm distance on bacterial reads (nasopharyngeal) | Nasopharyngeal samples were not analyzed due to limited budget. these samples were collected but won't be analyzed. | Posted | Day 9 |
|
|
| Secondary | Number of Participants With Macrolide Resistance Genes | Prevalence of macrolide resistance genes measured using DNA-seq from rectal swabs. | The outcome is limited to children randomized to placebo in azithromycin households and to the placebo-treated child control in placebo households. A direct effect of antibiotics on the resistome was only observed among children receiving azithromycin compared with placebo; we were unable to process samples from the other study arms due to cost constraints. According to study design, only placebo treated children in these two arms were analyzed. | Posted | Count of Participants | Participants | 2 years |
|
|
|
| Secondary | Alpha Diversity in the Intestinal Microbiome | Alpha diversity in the intestinal microbiome using DNA-seq from rectal swabs | The intestinal microbiome in rectal swabs were not analyzed due to limited budget. these samples were collected but will not be analyzed | Posted | 2 years |
|
|
| 0 |
| 31 |
| 0 |
| 31 |
| 5 |
| 31 |
| EG001 | Amoxicillin Households - Placebo | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Amoxicillin Households - Placebo: Children in this arm will receive Placebo. | 0 | 31 | 0 | 31 | 0 | 31 |
| EG002 | Azithromycin Households - Antibiotic | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Children will receive treatment everyday, once a day as is: Azithromycin: 10 mg/kg once daily on Day 1, then 5 mg/kg once daily Days 2-5 Azithromycin Households - Antibiotic: Children in this arm will receive Azithromycin once a day. | 0 | 31 | 0 | 31 | 3 | 31 |
| EG003 | Azithromycin Households - Placebo | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Azithromycin Households - Placebo: Children in this arm will receive Placebo. | 0 | 31 | 0 | 31 | 5 | 31 |
| EG004 | Cotrimoxazole Households - Antibiotic | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Children will receive treatment everyday, once a day as is: Co-trimoxazole: 240 mg daily for Days 1-5 Cotrimoxazole: Children in this arm will receive co-trimoxazole once a day. Cotrimoxazole: Children in this arm will receive co-trimoxazole once a day. | 0 | 31 | 0 | 31 | 3 | 31 |
| EG005 | Cotrimoxazole Households - Placebo | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. Cotrimoxazole Households - Placebo: Children in this arm will receive Placebo. | 0 | 31 | 0 | 31 | 3 | 31 |
| EG006 | Placebo | Households were randomized in a 1:1:1:1 fashion to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic household, one child was randomly assigned to receive placebo. In placebo households, both children received placebo. | 0 | 60 | 0 | 60 | 7 | 60 |
| Nausea, days 1-5 | Gastrointestinal disorders | Systematic Assessment |
|
| Fever, days 1-5 | General disorders | Systematic Assessment |
|
| Cough, Days 1-5 | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Cough, Day 9 | Reproductive system and breast disorders | Systematic Assessment |
|
| Diarrhea, days 1-5 | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea, day 9 | Gastrointestinal disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D002690 | Chlamydia Infections |
| D002694 | Chlamydiaceae Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D015817 | Eye Infections |
| D003231 | Conjunctivitis |
| D003229 | Conjunctival Diseases |
| D005128 | Eye Diseases |
| D003316 | Corneal Diseases |
| Organic Chemicals |
| D000667 | Ampicillin |
| D010400 | Penicillin G |
| D010406 | Penicillins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D013420 | Sulfamethoxazole |
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D013424 | Sulfanilamides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D014295 | Trimethoprim |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| Male |
|
| Title | Measurements |
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| Children who received Placebo |
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| Children who received Placebo |
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| Children who received Placebo |
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| Children who received Placebo |
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| Post-treatment |
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| Post-treatment |
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| Post-treatment |
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