Gut Resistome After Oral Antibiotics in Preschool Children in Burkina Faso: A Randomized, Controlled Trial.
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ABSTRACT:
SUBMITTER: Oldenburg CE
PROVIDER: S-EPMC7456340 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Gut Resistome After Oral Antibiotics in Preschool Children in Burkina Faso: A Randomized, Controlled Trial.
Oldenburg Catherine E CE Hinterwirth Armin A Sié Ali A Coulibaly Boubacar B Ouermi Lucienne L Dah Clarisse C Tapsoba Charlemagne C Cummings Susie L SL Zhong Lina L Chen Cindi C Sarkar Samarpita S Bärnighausen Till T Lietman Thomas M TM Keenan Jeremy D JD Doan Thuy T
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20200101 3
We evaluated the effect of systemic antibiotics (azithromycin, amoxicillin, cotrimoxazole, or placebo) on the gut resistome in children aged 6 to 59 months. Azithromycin and cotrimoxazole led to an increase in macrolide and sulfonamide resistance determinants. Resistome expansion can be induced with a single course of antibiotics. ...[more]
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Project description:BackgroundExposure to antibiotics may result in alterations to the composition of intestinal microbiota. However, few trials have been conducted, and observational studies are subject to confounding by indication. We conducted a randomized controlled trial to determine the effect of 3 commonly used pediatric antibiotics on the intestinal microbiome in healthy preschool children.MethodsChildren aged 6-59 months were randomized (1:1:1:1) to a 5-day course of 1 of 3 antibiotics, including amoxicillin (25 mg/kg/d twice-daily doses), azithromycin (10 mg/kg dose on day 1 and then 5 mg/kg once daily for 4 days), cotrimoxazole (240 mg once daily), or placebo. Rectal swabs were obtained at baseline and 5 days after the last dose and were processed using 16S rRNA gene sequencing. The prespecified primary outcome was inverse Simpson's α-diversity index.ResultsPost-treatment Simpson's diversity was significantly different across the 4 arms (P = .003). The mean Simpson's α-diversity among azithromycin-treated children was significantly lower than in placebo-treated children (6.6; 95% confidence interval [CI], 5.5-7.8; vs 9.8; 95% CI, 8.7-10.9; P = .0001). Diversity in children treated with amoxicillin (8.3; 95% CI, 7.0-9.6; P = .09) or cotrimoxazole (8.3; 95% CI, 8.2-9.7; P = .08) was not significantly different than placebo.ConclusionsAzithromycin affects the composition of the pediatric intestinal microbiome. The effect of amoxicillin and cotrimoxazole on microbiome composition was less clear.Clinical trials registrationclinicaltrials.gov NCT03187834.
| S-EPMC6262116 | biostudies-literature
Project description:There is a lack of empirical, prospective human data on the gut microbiome and its relationship with growth, especially in low- and middle-income countries. We prospectively assessed the association between gut microbial diversity and short-term growth in a cohort of preschool children in Burkina Faso to better characterize whether there is any evidence that changes in gut microbial diversity may affect growth. Data were obtained from a randomized controlled trial evaluating the effect of antibiotic administration on gut microbial diversity in preschool children. We followed up the enrolled children for 35 days, with anthropometric measurements at baseline and day 35 and microbial diversity measured at baseline and day 9 (analytic sample, N = 155). We estimated linear mixed-effects regression models with household random intercepts to assess the association of Simpson's and Shannon's alpha diversity with measures of change in anthropometry (e.g., ponderal growth since baseline) and absolute anthropometric measurements (e.g., day 35 weight). We did not find evidence that alpha gut microbial diversity was associated with growth or absolute anthropometric measurements after adjusting for confounding variables. Effect estimates were close to the null (P ≥ 0.15 for all fully adjusted comparisons), with the association between Simpson's alpha diversity and day 35 height (cm) farthest from the null (coefficient = -0.03, 95% CI: -0.07, 0.01). The change in gut microbial diversity also was not associated with the change in anthropometry in crude or adjusted models. Future research is needed to explore whether gut diversity has an impact on growth over a longer time period, in both healthy and malnourished children.
| S-EPMC7695110 | biostudies-literature
Project description:A broad-spectrum antibiotic, typically amoxicillin, is included in many country guidelines as part of the management of uncomplicated severe acute malnutrition (SAM) in children without overt clinical symptoms of infection. Alternative antibiotics may be beneficial for children with SAM without increasing selection for beta-lactam resistance. We conducted a 1:1 randomized controlled trial of single dose azithromycin versus a 7-day course of amoxicillin for SAM. Children 6-59 months of age with uncomplicated SAM (mid-upper arm circumference < 11.5 cm and/or weight-for-height Z-score < -3) were enrolled in Boromo District, Burkina Faso, from June through October 2020. Rectal swabs were collected at baseline and 8 weeks after treatment and processed using DNA-Seq. We compared the resistome at the class level in children randomized to azithromycin compared with amoxicillin. We found no evidence of a difference in the distribution of genetic antibiotic resistance determinants to any antibiotic class 8 weeks after treatment. There was no difference in genetic macrolide resistance determinants (65% azithromycin, 65% placebo, odds ratio, OR, 1.00, 95% confidence interval, CI, 0.43-2.34) or beta-lactam resistance determinants (82% azithromycin, 83% amoxicillin, OR 0.94, 95% CI, 0.33-2.68) at 8 weeks. Although presence of genetic antibiotic resistance determinants to macrolides and beta-lactams was common, we found no evidence of a difference in the gut resistome 8 weeks after treatment. If there are earlier effects of antibiotics on selection for genetic antibiotic resistance determinants, the resistome may normalize by 8 weeks.
| S-EPMC9294673 | biostudies-literature
Project description:Antibiotics improve both weight and height gain in randomized trials of preschool children with preexisting morbidity. Here, we assess the effect of a short course of three different antibiotics (amoxicillin, azithromycin, and cotrimoxazole) on short-term linear and ponderal growth in a population-based sample of preschool children in rural Burkina Faso. We randomized households with at least two children in the Nouna district, Burkina Faso, to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic-randomized household, one child was randomly assigned to receive the antibiotic and the other to receive the placebo. Weight and height measurements were taken at baseline and 30 days following the last study medication dose. Weight-for-height Z (WHZ), height-for-age Z (HAZ), and weight-for-age Z (WAZ) scoreswere calculated based on the 2006 World Health Organization standards. Of the 124 households and 248 children enrolled, 229 had anthropometry measurements at 1 month and were analyzed. Children randomized to amoxicillin gained significantly more weight compared with both the placebo household (mean difference 317 g, 95% confidence interval [CI]: 115-519 g) and placebo sibling (mean difference 315 g, 95% CI: 147-482 g) controls. Growth velocity in g/kg/day, and WHZ and WAZ scores were higher in amoxicillin-treated children compared with placebo households and siblings. There were no differences in weight gain in children randomized to azithromycin or cotrimoxazole compared with placebo households or placebo siblings. There were no differences in height gain or HAZ across any of the study arms. Amoxicillin may have short-term growth-promoting effects in healthy children.
| S-EPMC6169163 | biostudies-literature
Project description:BackgroundAzithromycin is a broad-spectrum antibiotic that has moderate antimalarial activity and has been shown to reduce all-cause mortality when biannually administered to children under five in high mortality settings in sub-Saharan Africa. One potential mechanism for this observed reduction in mortality is via a reduction in malaria transmission.MethodsWe evaluated whether a single oral dose of azithromycin reduces malaria positivity by rapid diagnostic test (RDT). We conducted an individually randomized placebo-controlled trial in Burkina Faso during the high malaria transmission season in August 2020. Children aged 8 days to 59 months old were randomized to a single oral dose of azithromycin (20 mg/kg) or matching placebo. At baseline and 14 days following treatment, we administered a rapid diagnostic test (RDT) to detect Plasmodium falciparum and measured tympanic temperature for all children. Caregiver-reported adverse events and clinic visits were recorded at the day 14 visit.ResultsWe enrolled 449 children with 221 randomized to azithromycin and 228 to placebo. The median age was 32 months and 48% were female. A total of 8% of children had a positive RDT for malaria at baseline and 11% had a fever (tympanic temperature ≥ 37.5 °C). In the azithromycin arm, 8% of children had a positive RDT for malaria at 14 days compared to 7% in the placebo arm (P = 0.65). Fifteen percent of children in the azithromycin arm had a fever ≥ 37.5 °C compared to 21% in the placebo arm (P = 0.12). Caregivers of children in the azithromycin group had lower odds of reporting fever as an adverse event compared to children in the placebo group (OR 0.41, 95% CI 0.18-0.96, P = 0.04). Caregiver-reported clinic visits were uncommon, and there were no observed differences between arms (P = 0.32).ConclusionsWe did not find evidence that a single oral dose of azithromycin reduced malaria positivity during the high transmission season. Caregiver-reported fever occurred less often in children receiving azithromycin compared to placebo, indicating that azithromycin may have some effect on non-malarial infections. Trial registration Clinicaltrials.gov NCT04315272, registered 19/03/2020.
| S-EPMC8957146 | biostudies-literature
Project description:We evaluated the gut resistome of children from communities treated with 10 twice-yearly azithromycin distributions. Although the macrolide resistance remained higher in the azithromycin arm, the selection of non-macrolide resistance observed at earlier time points did not persist. Longitudinal resistance monitoring should be a critical component of mass distribution programs.Clinical trials registrationNCT02047981.
| S-EPMC8492121 | biostudies-literature
Project description:BackgroundAntibiotic use by one individual may affect selection for antimicrobial resistance in close contacts. Here we evaluated whether oral antibiotic treatment of one child within a household affected the gut resistome of an untreated cohabiting child.MethodsHouseholds with at least two children <5 y of age were randomized in a 1:1 fashion to a 5d course of azithromycin or placebo. To evaluate indirect effects of azithromycin treatment on the gut resistome, we randomly assigned one child in the house to azithromycin and one to placebo. In placebo households, each child received placebo. We performed DNA sequencing of rectal swabs collected 5 d after the last antibiotic dose. We estimated risk ratios for the presence of genetic resistance determinants at the class level using modified Poisson models for children in azithromycin households compared with placebo households and assessed the composition of the resistome using permutational analysis of variance (PERMANOVA).ResultsOf 58 children (n = 30 azithromycin households, n = 28 placebo households) with post-treatment rectal swabs, genetic resistance determinants were common but there was no significant difference at the class (p = 0.54 for macrolides) or gene (p = 0.94 for structure by PERMANOVA, p = 0.94 for diversity) level between untreated children in azithromycin households compared with placebo households.ConclusionsThe results are encouraging that one child's antibiotic use may not influence the resistome of another child. Trial registration: ClinicalTrials.gov NCT03187834.
| S-EPMC7902679 | biostudies-literature
Project description:ObjectivesNutrition has profound effects on children's health outcomes and is linked to weight gain and cognitive development. We used data from a randomised controlled trial to evaluate the prospective associations between dietary, socioeconomic and demographic factors and short-term weight gain during the lean season in a rural area of Burkina Faso.DesignProspective cohort data arising from a randomised controlled trial of the effect of antibiotic distribution on child growth and intestinal microbial diversity.SettingTwo rural communities in Nouna District, Burkina Faso.Participants246 children aged 6-59 months living in the study communities were enrolled in the study.Primary and secondary outcome measuresAnthropometric measurements, including weight and height, were obtained at baseline and 1 month.ResultsOf 246 children, the median weight for wasted children at baseline (weight-for-height z-score <-2) was 9.7 kg (IQR 8.65-10.8) and the weight of non-wasted children was 12.8 kg (IQR 10.9-14.75). Food insecurity was significantly associated with decreased weight gain velocity (mean difference -0.03 g/kg/day, 95% CI -0.06 to -0.006, p=0.04).ConclusionExperiences of household food insecurity before the beginning of the lean season were associated with decreased weight gain in children in rural Burkina Faso during the lean season, although the mean difference was small. Understanding the relationship between timing of food insecurity and anthropometric outcomes may help to develop policies and health programme that address both of these issues.Trial registration numberNCT03187834.
| S-EPMC6677972 | biostudies-literature
Project description:BackgroundSchistosomiasis remains a major public health concern in sub-Saharan Africa. Although schistosomiasis is well documented in school-aged children in Burkina Faso, prevalence data among preschool-aged children (PSAC) are limited and outdated, and its risk factors in this group remain poorly documented. The main objective of this study was to assess the prevalence and risk factors associated with Schistosoma (S.) mansoni infection among PSAC from Panamasso village, western Burkina Faso.MethodologyA cross-sectional study was carried out among 228 children under 6 years old from Panamasso village. Sociodemographic and water contact data were collected using a structured questionnaire. Kato-Katz and formol-ether concentration techniques were used to detect S. mansoni eggs in stool samples. Urine samples were subjected to a point-of-care circulating cathodic antigen (POC-CCA) cassette test and a centrifugation method to check for both S. mansoni and S. haematobium infection, respectively. Potential risk factors for S. mansoni infection were explored using multivariable logistic regression.ResultsThe mean age of children was 40.2 ± 15.0 months. The prevalence of S. mansoni infection as determined by Kato-Katz, formol-ether concentration and POC-CCA was 42.1%, 39.5% and 80.7%, respectively. Based on the combined results of the three methods, the overall prevalence of S. mansoni infection was 81.1%. No case of S. haematobium infection was found. The geometric mean intensity of S. mansoni infection was 107.2 eggs per gram of feces with 54.2%, 33.3% and 12.5% of the children having light, moderate and heavy infections, respectively. Girls (AOR = 2.9, 95% CI 1.3-6.1), a household located within 500 m from the pond (AOR = 3.0, 95% CI 1.0-8.6) or between 500 and 1000 m from the pond (AOR = 3.0, 95% CI 1.2-7.2), and the child's history of going to the pond (AOR = 5.0, 95% CI 1.7-14.3) were the variables significantly associated with S. mansoni infection.ConclusionS. mansoni was the sole species infecting a high proportion of PSAC in the study area. A mass drug administration program with praziquantel is therefore urgently required for those below 6 years old. Other control strategies should include increased community-awareness and provision of safe water.
| S-EPMC8017716 | biostudies-literature
Project description:ObjectiveTo determine whether an intervention to involve the male partners of pregnant women in maternity care influenced care-seeking, healthy breastfeeding and contraceptive practices after childbirth in urban Burkina Faso.MethodsIn a non-blinded, multicentre, parallel-group, superiority trial, 1144 women were assigned by simple randomization to two study arms: 583 entered the intervention arm and 561 entered the control arm. All women were cohabiting with a male partner and had a low-risk pregnancy. Recruitment took place at 20 to 36 weeks' gestation at five primary health centres in Bobo-Dioulasso. The intervention comprised three educational sessions: (i) an interactive group session during pregnancy with male partners only, to discuss their role; (ii) a counselling session during pregnancy for individual couples; and (iii) a postnatal couple counselling session. The control group received routine care only. We followed up participants at 3 and 8 months postpartum.FindingsThe follow-up rate was over 96% at both times. In the intervention arm, 74% (432/583) of couples or men attended at least two study sessions. Attendance at two or more outpatient postnatal care consultations was more frequent in the intervention than the control group (risk difference, RD: 11.7%; 95% confidence interval, CI: 6.0 to 17.5), as was exclusive breastfeeding 3 months postpartum (RD: 11.4%; 95% CI: 5.8 to 17.2) and effective modern contraception use 8 months postpartum (RD: 6.4%; 95% CI: 0.5 to 12.3).ConclusionInvolving men as supportive partners in maternity care was associated with better adherence to recommended healthy practices after childbirth.
| S-EPMC6022615 | biostudies-literature