Effect of amoxicillin on the gut microbiome of children with severe acute malnutrition in Madarounfa, Niger: A retrospective metagenomic analysis of a placebo-controlled trial

BACKGROUND: Children with severe acute malnutrition are treated with antibiotics as outpatients. We aimed to determine the effect of 7 days of amoxicillin on acute and long-term changes to the gut microbiome and antibiotic resistome in children treated for severe acute malnutrition. METHODS: We conducted a secondary analysis of a randomised, double-blinded, placebo-controlled trial (NCT01613547) of amoxicillin in children (aged 6-59 months) with severe acute malnutrition treated as outpatients in Madarounfa, Niger. We randomly selected 161 children from the overall cohort (n=2399) for initial 12-week follow-up from Sept 23, 2013 to Feb 3, 2014. We selected a convenience sample of those 161 children, on the basis of anthropometric measures, for follow-up 2 years later (Sept 28 to Oct 27, 2015). Children provided faecal samples at baseline, week 1, week 4, week 8, week 12, and, for those in the 2-year follow-up cohort, week 104. We conducted metagenomic sequencing followed by microbiome and resistome profiling of faecal samples. 38 children without severe acute malnutrition and six children with severe acute malnutrition matching the baseline ages of the original cohort were used as reference controls. FINDINGS: In the 12-week follow-up group, amoxicillin led to an immediate decrease in gut microbiome richness from 37·6 species (95% CI 32·6-42·7) and Shannon diversity index (SDI) 2·18 (95% CI 1·97-2·39) at baseline to 27·7 species (95% CI 22·9-32·6) species and SDI 1·55 (95% CI 1·35-1·75) at week 1. Amoxicillin increased gut antibiotic resistance gene abundance to 6044 reads per kilobase million (95% CI 4704-7384) at week 1, up from 4800 (3391-6208) at baseline, which returned to baseline 3 weeks later. 35 children were included in the 2-year follow-up; the amoxicillin-treated children (n=22) had increased number of species in the gut microbiome compared with placebo-treated children (n=13; 60·7 [95% CI 54·7-66·6] vs 36·9 [29·4-44·3]). Amoxicillin-treated children had increased Prevotella spp and decreased Bifidobacterium spp relative to age-matched placebo-treated children, indicating a more mature, adult-like microbiome. INTERPRETATION: Amoxicillin treatment led to acute but not sustained increases in antimicrobial resistance genes and improved gut microbiome maturation 2 years after severe acute malnutrition treatment. FUNDING: Bill & Melinda Gates Foundation; Médecins sans Frontières Operational Center Paris; National Institute of Allergy and Infectious Diseases; National Institute of General Medical Sciences; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Edward Mallinckrodt Jr Foundation; Doris Duke Foundation

Exploring HIV infection and susceptibility to measles among older children and adults in Malawi: a facility-based study

SummaryBackgroundHIV infection increases measles susceptibility in infants, but little is known about this relationship among older children and adults. We conducted a facility-based study to explore whether HIV status and/or CD4 count were associated with either measles seroprotection and/or measles antibody concentration.MethodsA convenience sample was recruited comprising HIV-infected patients presenting for follow-up care, and HIV-uninfected individuals presenting for HIV testing at Chiradzulu District Hospital, Malawi, from January to September 2012. We recorded age, sex, and reported measles vaccination and infection history. Blood samples were taken to determine the CD4 count and measles antibody concentration.ResultsOne thousand nine hundred and thirty-five participants were recruited (1434 HIV-infected and 501 HIV-uninfected). The majority of adults and approximately half the children were seroprotected against measles, with lower odds among HIV-infected children (adjusted odds ratio 0.27, 95% confidence interval 0.10–0.69; p=0.006), but not adults. Among HIV-infected participants, neither CD4 count (p=0.16) nor time on antiretroviral therapy (p=0.25) were associated with measles antibody concentration, while older age (p<0.001) and female sex (p<0.001) were independently associated with this measure.ConclusionsWe found no evidence that HIV infection contributes to the risk of measles infection among adults, but HIV-infected children (including at ages older than previously reported), were less likely to be seroprotected in this sample

Intra-household use and acceptability of Ready-to-Use-Supplementary-Foods distributed in Niger between July and December 2010.

Few studies have looked at consumption of Ready-to-Use-Supplementary-Foods (RUSFs) during a nutritional emergency. Here, we describe the use and acceptability of RUSF within households in four districts of the region of Maradi, Niger during large scale preventive distributions with RUSF in 2010 targeted at children 6-35months of age. Our study comprised both quantitative and qualitative components to collect detailed information and to allow in-depth interviews. We performed a cross-sectional survey in 16 villages between two monthly distributions of RUSF (October-November 2010). All households with at least one child who received RUSF were included and a total of 1842 caregivers were interviewed using a structured questionnaire. Focus groups and individual interviews of 128 caregivers were conducted in eight of the selected villages. On average, 24.7% of households reported any sharing of RUSF within the household. Sharing practices outside the household remained rare. Most of the sharing reported occurred among children under 5years of age living in the household. On average, 91% of caregivers in all districts rated the child's appreciation of the products as good or very good. Program planning may need to explicitly accounting for the sharing of products among children under 5 within household

Preventive Effects of Long-Term Supplementation with 2 Nutritious Food Supplements in Young Children in Niger

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Carriage prevalence and serotype distribution of Streptococcus pneumoniae prior to 10-valent pneumococcal vaccine introduction: A population-based cross-sectional study in South Western Uganda, 2014.

BACKGROUND: Information on Streptococcus pneumoniae nasopharyngeal (NP) carriage before the pneumococcal conjugate vaccine (PCV) introduction is essential to monitor impact. The 10-valent PCV (PCV10) was officially introduced throughout Ugandan national childhood immunization programs in 2013 and rolled-out countrywide during 2014. We aimed to measure the age-specific Streptococcus pneumoniae carriage and serotype distribution across all population age groups in the pre-PCV10 era in South Western Uganda. METHODS: We conducted a two-stage cluster, age-stratified, cross-sectional community-based study in Sheema North sub-district between January and March 2014. One NP swab was collected and analyzed for each participant in accordance with World Health Organization guidelines. RESULTS: NP carriage of any pneumococcal serotype was higher among children <2years old (77%; n=387) than among participants aged ≥15years (8.5%; n=325) (chi2 p<0.001). Of the 623 positive cultures, we identified 49 serotypes among 610 (97.9%) isolates; thirteen (2.1%) isolates were non-typeable. Among <2years old, serotypes 6A, 6B, 14, 15B, 19F and 23F accounted for half of all carriers. Carriage prevalence with PCV10 serotypes was 29.4% among individuals aged <2years (n=387), 23.4% in children aged 2-4years (n=217), 11.4% in 5-14years (n=417), and 0.4% among individuals ≥15years of age (n=325). The proportion of carried pneumococci serotypes contained in PCV10 was 38.1% (n=291), 32.8% (n=154), 29.4% (n=156), and 4.4% (n=22) among carriers aged <2years, 2-4years, 5-14years and ≥15years, respectively. DISCUSSION: In Sheema district, the proportion of PCV10 serotypes was low (<40%), across all age groups, especially among individuals aged 15years or older (<5%). PCV10 introduction is likely to impact transmission among children and to older individuals, but less likely to substantially modify pneumococcal NP ecology among individuals aged 15years or older

Diagnostic et prise en charge des échecs thérapeutiques aux antirétroviraux (perception des barrières et défis majeurs dans des centres de référence d'Abidjan (Côte d'Ivoire))

LYON1-BU Santé (693882101) / SudocSudocFranceF

Prescribing practices in the treatment of wasting: secondary analysis from a randomised trial

Introduction Current guidelines for the outpatient treatment of severe acute malnutrition (SAM) recommend the provision of routine medications to all children at admission and prescribed medications as clinically indicated thereafter. The objective of this study was to describe the amount and purpose of medications prescribed during outpatient SAM treatment and explore the effect of routine antibiotics at admission on subsequent medication prescription.Methods Medications prescribed during outpatient treatment were described by medication category, time from admission, and diagnoses among children with SAM in a placebo-controlled, double-blind trial of 7-day amoxicillin use. Total medications were compared by parent trial intervention arm (amoxicillin vs placebo) and differences assessed using Χ2 and two-sample t-tests.Results Of the 2399 children enrolled, 74.6% of children received ≥1 prescribed medication during outpatient treatment. Antipyretics/analgesics (44.1% of children), antimalarials (56.6%) and antibiotics (30.0%) were prescribed most frequently. Children who received placebo in the parent trial received fewer total medications (mean difference: −0.80, 95% CI: −0.96 to –0.65) and oral antibiotics (mean difference: −0.96, 95% CI: −0.99 to –0.92) during treatment compared with children who received routine amoxicillin.Conclusions We found high rates of medication prescription during outpatient treatment for SAM, but fewer total medications and oral antibiotics prescribed to children receiving placebo in the parent trial. Our findings underscore the role of outpatient treatment programmes as an important source of medicine prescription and suggest that provision of antibiotics on a clinically indicated basis for outpatient SAM cases may be a strategy to support prudent antibiotic use in certain settings.Trial registration number ClinicalTrials.gov Registry (NCT01613547; https://clinicaltrials.gov/ct2/show/NCT01613547)

Diagnostic accuracy of VIKIA® Rota-Adeno and Premier™ Rotaclone® tests for the detection of rotavirus in Niger

Abstract Objective We conducted a parallel evaluation of the diagnostic accuracy of VIKIA® Rota-Adeno, a rapid diagnostic test (RDT) and Premier™ Rotaclone® an enzyme immunoassay (EIA) using reverse transcription polymerase chain reaction (RT-PCR) as the reference standard. The study was part of a rotavirus surveillance project in Niger. Results The sensitivity of both tests was 80.7%. After exclusion of one indeterminate result by visual reading, the specificity of the Premier™ Rotaclone® was 100% by visual or optical density readings and that of VIKIA® Rota-Adeno test was 95.5%. Inter-reader agreement was excellent for both tests (kappa = 1). Our results showed almost similar performance of the EIA and RDT when compared to RT-PCR. Hence, the VIKIA® Rota-Adeno could be a good alternative for use in peripheral health centres where laboratory capacity is limited

Post-traumatic osteomyelitis in Middle East war-wounded civilians: resistance to first-line antibiotics in selected bacteria over the decade 2006–2016

Abstract Background War-wounded civilians in Middle East countries are at risk of post-traumatic osteomyelitis (PTO). We aimed to describe and compare the bacterial etiology and proportion of first-line antibiotics resistant bacteria (FLAR) among PTO cases in civilians from Syria, Iraq and Yemen admitted to the reconstructive surgical program of Médecins Sans Frontières (MSF) in Amman, Jordan, and to identify risk factors for developing PTO with FLAR bacteria. Methods We retrospectively analyzed the laboratory database of the MSF program. Inclusion criteria were: patients from Iraq, Yemen or Syria, admitted to the Amman MSF program between October 2006 and December 2016, with at least one bone biopsy sample culture result. Only bone samples taken during first orthopedic surgery were included in the analysis. To assess factors associated with FLAR infection, logistic regression was used to estimate odds ratio (ORs) and 95% confidence intervals (CI). Results 558 (76.7%) among 727 patients included had ≥1 positive culture results. 318 were from Iraq, 140 from Syria and 100 from Yemen. Median time since injury was 19 months [IQR 8–40]. Among the 732 different bacterial isolates, we identified 228 Enterobacteriaceae (31.5%), 193 Staphylococcus aureus (26.3%), 99 Pseudomonas aeruginosa (13.5%), and 21 Acinetobacter baumanii (2.8%). Three hundred and sixty four isolates were FLAR: 86.2% of Enterobacteriaceae, 53.4% of Pseudomonas aeruginosa, 60.5% of S. aureus and 45% of Acinetobacter baumannii. There was no difference in bacterial etiology or proportion of FLAR according to the country of origin. In multivariate analysis, a FLAR infection was associated with an infection of the lower extremity, with a time since the injury ≤12 months compared with time > 30 months and with more than 3 previous surgeries. Conclusions Enterobacteriaceae were frequently involved in PTO in war wounded civilians from Iraq, Yemen and Syria between 2006 and 2016. Proportion of FLAR was high, particularly among Enterobacteriaceae, regardless of country of origin