Child Development
Conditions
Keywords
infection, azithromycin, amoxicillin, co-trimoxazole, trachoma, mass 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.
Interventions
DRUGAzithromycin
Children in this arm will receive Azithromycin once a day.
DRUGAmoxicillin
Children in this arm will receive Amoxicillin twice a day.
DRUGCotrimoxazole
Children in this arm will receive co-trimoxazole once a day.
DRUGPlacebo
Children in this arm will receive Placebo once a day.
Sponsors
Centre de Recherche en Sante de Nouna, Burkina Faso
Heidelberg University
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double blind
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
Eligibility
Sex/Gender
ALL
Age
6 Months to 59 Months
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Baseline and Day 9 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight-for-height Z-score | Day 35 | 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). |
| Height-for-age Z-score | Day 35 | 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). |
| Weight-for-age Z-score | Day 35 | 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). |
| Mid-upper Arm Circumference | Day 35 | 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). |
| Shannon's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Baseline and Day 9 (Post- Treatment) | 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. |
| Shannon's Index of Diversity (Alpha Diversity) in Nasopharyngeal Microbiome | Day 9 | Direct and indirect effects of antibiotics on Shannon's index of bacterial diversity |
| Simpson's Index of Diversity (Alpha Diversity) in Microbiome | Day 9 | Direct and indirect effect of antibiotics on alpha diversity from rectal samples |
| L1-norm Distance on Bacterial Reads (Nasopharyngeal) | Day 9 | L1-norm distance on bacterial reads (nasopharyngeal) |
| L2-norm Distance on Bacterial Reads (Intestinal) | Baseline and Day 9 (Post- Treatment) | 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. |
| L2-norm Distance on Bacterial Reads (Nasopharyngeal) | Day 9 | L2-norm distance on bacterial reads (nasopharyngeal) |
| Number of Participants With Macrolide Resistance Genes | 2 years | Prevalence of macrolide resistance genes measured using DNA-seq from rectal swabs. |
| Alpha Diversity in the Intestinal Microbiome | 2 years | Alpha diversity in the intestinal microbiome using DNA-seq from rectal swabs |
| L1-norm Distance on Bacterial Reads (Intestinal) | Baseline and Day 9 (Post- Treatment) | 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. |
Countries
Burkina Faso, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 31 |
| 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. | 31 |
| 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. | 31 |
| 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. | 31 |
| 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. | 31 |
| 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. | 31 |
| 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. | 62 |
| Total | 248 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Had invalid anthropometric measurements | 5 | 3 | 4 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 | 2 | 2 |
Baseline characteristics
| Characteristic | Total | Amoxicillin Households - Placebo | Azithromycin Households - Antibiotic | Azithromycin Households - Placebo | Cotrimoxazole Households - Antibiotic | Cotrimoxazole Households - Placebo | Placebo | Amoxicillin Households - Antibiotic |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 37 months | 36 months | 29 months | 42 months | 37 months | 40 months | 38 months | 35 months |
| Race and Ethnicity Not Collected | 0 Participants | — | — | — | — | — | — | — |
| Sex: Female, Male Female | 125 Participants | 18 Participants | 18 Participants | 12 Participants | 20 Participants | 19 Participants | 24 Participants | 14 Participants |
| Sex: Female, Male Male | 123 Participants | 13 Participants | 13 Participants | 19 Participants | 11 Participants | 12 Participants | 38 Participants | 17 Participants |
| Stunted | 52 Participants | 7 Participants | 8 Participants | 7 Participants | 4 Participants | 11 Participants | 7 Participants | 8 Participants |
| Underweight | 35 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 10 Participants | 6 Participants | 5 Participants |
| Visited healthcare facility in past 30 days | 42 Participants | 2 Participants | 4 Participants | 2 Participants | 6 Participants | 8 Participants | 14 Participants | 6 Participants |
| Wasted | 25 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 7 Participants | 6 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 31 | 0 / 31 | 0 / 31 | 0 / 31 | 0 / 31 | 0 / 60 |
| other Total, other adverse events | 5 / 31 | 0 / 31 | 3 / 31 | 5 / 31 | 3 / 31 | 3 / 31 | 7 / 60 |
| serious Total, serious adverse events | 0 / 31 | 0 / 31 | 0 / 31 | 0 / 31 | 0 / 31 | 0 / 31 | 0 / 60 |
Outcome results
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.
Time frame: Baseline and Day 9
Population: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Amoxicillin | Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Baseline | 10.2 Index score |
| Amoxicillin | Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Post-treatment | 8.3 Index score |
| Azithromycin | Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Post-treatment | 6.6 Index score |
| Azithromycin | Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Baseline | 8.8 Index score |
| Cotrimoxazole | Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Baseline | 9.7 Index score |
| Cotrimoxazole | Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Post-treatment | 8.3 Index score |
| Placebo | Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Baseline | 9.6 Index score |
| Placebo | Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Post-treatment | 9.8 Index score |
Secondary
Alpha Diversity in the Intestinal Microbiome
Alpha diversity in the intestinal microbiome using DNA-seq from rectal swabs
Time frame: 2 years
Population: The intestinal microbiome in rectal swabs were not analyzed due to limited budget. these samples were collected but will not be analyzed
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).
Time frame: Day 35
Population: In Amoxicillin, Azithromycin, Cotrimoxazole households, children assigned to receive antibiotic and placebo were analyzed separately, showed in different row below.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin | Height-for-age Z-score | Children who received Placebo | -0.73 z score | Standard Deviation 1.11 |
| Amoxicillin | Height-for-age Z-score | Children who received Antibiotic | -0.80 z score | Standard Deviation 1.19 |
| Azithromycin | Height-for-age Z-score | Children who received Placebo | -1.16 z score | Standard Deviation 1.34 |
| Azithromycin | Height-for-age Z-score | Children who received Antibiotic | -0.92 z score | Standard Deviation 1.13 |
| Cotrimoxazole | Height-for-age Z-score | Children who received Antibiotic | -0.69 z score | Standard Deviation 1 |
| Cotrimoxazole | Height-for-age Z-score | Children who received Placebo | -1.38 z score | Standard Deviation 0.94 |
| Placebo | Height-for-age Z-score | Children who received Placebo | -0.59 z score | Standard Deviation 1.08 |
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.
Time frame: Baseline and Day 9 (Post- Treatment)
Population: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Amoxicillin | L1-norm Distance on Bacterial Reads (Intestinal) | Baseline | 16.6 Index score |
| Amoxicillin | L1-norm Distance on Bacterial Reads (Intestinal) | Post-treatment | 13.9 Index score |
| Azithromycin | L1-norm Distance on Bacterial Reads (Intestinal) | Post-treatment | 11.0 Index score |
| Azithromycin | L1-norm Distance on Bacterial Reads (Intestinal) | Baseline | 14.6 Index score |
| Cotrimoxazole | L1-norm Distance on Bacterial Reads (Intestinal) | Baseline | 15.6 Index score |
| Cotrimoxazole | L1-norm Distance on Bacterial Reads (Intestinal) | Post-treatment | 13.5 Index score |
| Placebo | L1-norm Distance on Bacterial Reads (Intestinal) | Baseline | 15.4 Index score |
| Placebo | L1-norm Distance on Bacterial Reads (Intestinal) | Post-treatment | 16.0 Index score |
Secondary
L1-norm Distance on Bacterial Reads (Nasopharyngeal)
L1-norm distance on bacterial reads (nasopharyngeal)
Time frame: Day 9
Population: Nasopharyngeal samples were not analyzed due to limited budget- samples were collected but not analyzed and never will be analyzed
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.
Time frame: Baseline and Day 9 (Post- Treatment)
Population: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Amoxicillin | L2-norm Distance on Bacterial Reads (Intestinal) | Baseline | 10.2 Index score |
| Amoxicillin | L2-norm Distance on Bacterial Reads (Intestinal) | Post-treatment | 8.3 Index score |
| Azithromycin | L2-norm Distance on Bacterial Reads (Intestinal) | Post-treatment | 6.6 Index score |
| Azithromycin | L2-norm Distance on Bacterial Reads (Intestinal) | Baseline | 8.8 Index score |
| Cotrimoxazole | L2-norm Distance on Bacterial Reads (Intestinal) | Baseline | 9.7 Index score |
| Cotrimoxazole | L2-norm Distance on Bacterial Reads (Intestinal) | Post-treatment | 8.3 Index score |
| Placebo | L2-norm Distance on Bacterial Reads (Intestinal) | Baseline | 9.6 Index score |
| Placebo | L2-norm Distance on Bacterial Reads (Intestinal) | Post-treatment | 9.8 Index score |
Secondary
L2-norm Distance on Bacterial Reads (Nasopharyngeal)
L2-norm distance on bacterial reads (nasopharyngeal)
Time frame: Day 9
Population: Nasopharyngeal samples were not analyzed due to limited budget. these samples were collected but won't be analyzed.
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).
Time frame: Day 35
Population: In Amoxicillin, Azithromycin, Cotrimoxazole households, children assigned to receive antibiotic and placebo were analyzed separately, showed in different row below.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin | Mid-upper Arm Circumference | Children who received Placebo | 14.90 mm | Standard Deviation 1.1 |
| Amoxicillin | Mid-upper Arm Circumference | Children who received Antibiotic | 15.01 mm | Standard Deviation 0.92 |
| Azithromycin | Mid-upper Arm Circumference | Children who received Placebo | 15.15 mm | Standard Deviation 1.01 |
| Azithromycin | Mid-upper Arm Circumference | Children who received Antibiotic | 14.53 mm | Standard Deviation 1.11 |
| Cotrimoxazole | Mid-upper Arm Circumference | Children who received Antibiotic | 15.49 mm | Standard Deviation 0.98 |
| Cotrimoxazole | Mid-upper Arm Circumference | Children who received Placebo | 14.83 mm | Standard Deviation 1.36 |
| Placebo | Mid-upper Arm Circumference | Children who received Placebo | 15.23 mm | Standard Deviation 1.23 |
Secondary
Number of Participants With Macrolide Resistance Genes
Prevalence of macrolide resistance genes measured using DNA-seq from rectal swabs.
Time frame: 2 years
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Amoxicillin | Number of Participants With Macrolide Resistance Genes | 12 Participants |
| Azithromycin | Number of Participants With Macrolide Resistance Genes | 9 Participants |
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.
Time frame: Baseline and Day 9 (Post- Treatment)
Population: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Amoxicillin | Shannon's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Baseline | 16.6 Index score |
| Amoxicillin | Shannon's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Post-treatment | 13.9 Index score |
| Azithromycin | Shannon's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Post-treatment | 11.0 Index score |
| Azithromycin | Shannon's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Baseline | 14.6 Index score |
| Cotrimoxazole | Shannon's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Baseline | 15.6 Index score |
| Cotrimoxazole | Shannon's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Post-treatment | 13.5 Index score |
| Placebo | Shannon's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Baseline | 15.4 Index score |
| Placebo | Shannon's Index of Diversity (Alpha Diversity) in Intestinal Microbiome | Post-treatment | 16.0 Index score |
Secondary
Shannon's Index of Diversity (Alpha Diversity) in Nasopharyngeal Microbiome
Direct and indirect effects of antibiotics on Shannon's index of bacterial diversity
Time frame: Day 9
Population: Nasopharyngeal samples were not analyzed, due to limited budget - samples were collected but not analyzed and never will be analyzed
Secondary
Simpson's Index of Diversity (Alpha Diversity) in Microbiome
Direct and indirect effect of antibiotics on alpha diversity from rectal samples
Time frame: Day 9
Population: rectal samples were not analyzed due to limited budget - samples were collected but not analyzed and never will be analyzed
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).
Time frame: Day 35
Population: In Amoxicillin, Azithromycin, Cotrimoxazole households, children assigned to receive antibiotic and placebo were analyzed separately, showed in different row below.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin | Weight-for-age Z-score | Children who received Placebo | -0.78 Z score | Standard Deviation 0.89 |
| Amoxicillin | Weight-for-age Z-score | Children who received Antibiotic | -0.60 Z score | Standard Deviation 0.87 |
| Azithromycin | Weight-for-age Z-score | Children who received Placebo | -0.78 Z score | Standard Deviation 1.02 |
| Azithromycin | Weight-for-age Z-score | Children who received Antibiotic | -1.01 Z score | Standard Deviation 0.95 |
| Cotrimoxazole | Weight-for-age Z-score | Children who received Antibiotic | -0.58 Z score | Standard Deviation 0.94 |
| Cotrimoxazole | Weight-for-age Z-score | Children who received Placebo | -1.12 Z score | Standard Deviation 1.04 |
| Placebo | Weight-for-age Z-score | Children who received Placebo | -0.53 Z score | Standard Deviation 0.97 |
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).
Time frame: Day 35
Population: In Amoxicillin, Azithromycin, Cotrimoxazole households, children assigned to receive antibiotic and placebo were analyzed separately, showed in different row below.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin | Weight-for-height Z-score | Children who received Placebo | -0.52 z score | Standard Deviation 1.05 |
| Amoxicillin | Weight-for-height Z-score | Children who received Antibiotic | -0.24 z score | Standard Deviation 0.92 |
| Azithromycin | Weight-for-height Z-score | Children who received Placebo | -0.17 z score | Standard Deviation 0.85 |
| Azithromycin | Weight-for-height Z-score | Children who received Antibiotic | -0.71 z score | Standard Deviation 0.98 |
| Cotrimoxazole | Weight-for-height Z-score | Children who received Antibiotic | -0.27 z score | Standard Deviation 0.91 |
| Cotrimoxazole | Weight-for-height Z-score | Children who received Placebo | -0.49 z score | Standard Deviation 1.11 |
| Placebo | Weight-for-height Z-score | Children who received Placebo | -0.28 z score | Standard Deviation 1 |