Browsing by Author "Harris VC"

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Drivers of informal sector and non-prescription medication use in pediatric populations in a low- and middle-income setting: A prospective cohort study in Zambia.
(2023) Wildbret S; Stuck L; Luchen CC; Simuyandi M; Chisenga C; Schultsz C; Harris VC; Department of Global Health, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands.; Department of Medical Microbiology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands.; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, The Netherlands.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of Infectious Diseases, Department of Internal Medicine, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Obtaining medication from the informal sector is common in low- and middle- income countries. Informal sector use increases the risk for inappropriate medication use, including inappropriate antibiotic usage. Infants are at the highest risk of complications from inappropriate medication use, yet there is insufficient knowledge about the risk factors driving caregivers to obtain medication from the informal sector for young children. We aimed to define infant and illness characteristics associated with use of medication purchased in the informal sector for infants up to fifteen months of age in Zambia. We used data from, a prospective cohort study (ROTA-biotic) conducted among 6 weeks to 15 months old children in Zambia, which is nested within an ongoing phase III rotavirus vaccine trial (Clinicaltrial.gov NCT04010448). Weekly in-person surveys collected information about illness episodes and medication usage for the trial population and for a community control cohort. The primary outcome for this study was whether medication was purchased in the formal sector (hospital or clinic) or informal sector (pharmacy, street vendor, friend/relative/neighbor, or chemical shop) per illness episode. Descriptive analyses were used to describe the study population, and the independent and medication use variables stratified by the outcome. A mixed-effects logistic regression model with a participant-level random intercept was used to identify independent variables associated with the outcome. The analysis included 439 participants accounting for 1927 illness episodes over fourteen months in time. Medication was purchased in the informal sector for 386 (20.0%) illness episodes, and in the formal sector for 1541 (80.0%) illness episodes. Antibiotic usage was less common in the informal sector than in the formal sector (29.3% vs 56.2%, p < 0.001, chi-square). Most medications purchased in the informal sector were orally administered (93.4%), and non-prescribed (78.8%). Increased distance from the closest study site (OR: 1.09; 95% CI: 1.01, 1.17), being included in the community cohort site (OR: 3.18; 95% CI: 1.86, 5.46), illnesses with general malaise fever, or headache (OR: 2.62; 95% CI: 1.75, 3.93), and wound/skin disease (OR: 0.36; 95% CI: 0.18, 0.73) were associated with use of medication from the informal sector. Sex, socioeconomic status, and gastrointestinal disease were not associated with use of medication from the informal sector. Informal sector medication use is common and, in this study, risk factors for obtaining medications in the informal sector included a long distance to a formal clinic, type of illness, and not being enrolled in a clinical trial. Continued research on medication use from the informal sector is crucial and should include generalizable study populations, information on severity of disease, emphasis on qualitative research, and a move towards testing interventions that aim to improve access to formal health care settings. Our findings suggest that improved access to formal health care services may decrease reliance on medication from the informal sector for infants.
Impact of antibiotics on gut microbiome composition and resistome in the first years of life in low- to middle-income countries: A systematic review.
(2023-Jun) Luchen CC; Chibuye M; Spijker R; Simuyandi M; Chisenga C; Bosomprah S; Chilengi R; Schultsz C; Mende DR; Harris VC; Amsterdam UMC, location University of Amsterdam, Department of Global Health, Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands.; Zambia National Public Health Institute, Ministry of Health, Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology, Amsterdam, the Netherlands.; Republic of Zambia State House, Lusaka, Zambia.; Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Amsterdam UMC, location University of Amsterdam, Department of Internal Medicine, Division of Infectious Diseases, Amsterdam, the Netherlands.; Amsterdam Institute of Infection and Immunity, Infectious Diseases, Amsterdam University Medical Center, Amsterdam, the Netherlands.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Inappropriate antimicrobial usage is a key driver of antimicrobial resistance (AMR). Low- and middle-income countries (LMICs) are disproportionately burdened by AMR and young children are especially vulnerable to infections with AMR-bearing pathogens. The impact of antibiotics on the microbiome, selection, persistence, and horizontal spread of AMR genes is insufficiently characterized and understood in children in LMICs. This systematic review aims to collate and evaluate the available literature describing the impact of antibiotics on the infant gut microbiome and resistome in LMICs. METHODS AND FINDINGS: In this systematic review, we searched the online databases MEDLINE (1946 to 28 January 2023), EMBASE (1947 to 28 January 2023), SCOPUS (1945 to 29 January 2023), WHO Global Index Medicus (searched up to 29 January 2023), and SciELO (searched up to 29 January 2023). A total of 4,369 articles were retrieved across the databases. Duplicates were removed resulting in 2,748 unique articles. Screening by title and abstract excluded 2,666 articles, 92 articles were assessed based on the full text, and 10 studies met the eligibility criteria that included human studies conducted in LMICs among children below the age of 2 that reported gut microbiome composition and/or resistome composition (AMR genes) following antibiotic usage. The included studies were all randomized control trials (RCTs) and were assessed for risk of bias using the Cochrane risk-of-bias for randomized studies tool. Overall, antibiotics reduced gut microbiome diversity and increased antibiotic-specific resistance gene abundance in antibiotic treatment groups as compared to the placebo. The most widely tested antibiotic was azithromycin that decreased the diversity of the gut microbiome and significantly increased macrolide resistance as early as 5 days posttreatment. A major limitation of this study was paucity of available studies that cover this subject area. Specifically, the range of antibiotics assessed did not include the most commonly used antibiotics in LMIC populations. CONCLUSION: In this study, we observed that antibiotics significantly reduce the diversity and alter the composition of the infant gut microbiome in LMICs, while concomitantly selecting for resistance genes whose persistence can last for months following treatment. Considerable heterogeneity in study methodology, timing and duration of sampling, and sequencing methodology in currently available research limit insights into antibiotic impacts on the microbiome and resistome in children in LMICs. More research is urgently needed to fill this gap in order to better understand whether antibiotic-driven reductions in microbiome diversity and selection of AMR genes place LMIC children at risk for adverse health outcomes, including infections with AMR-bearing pathogens.
Systematic review of associations between gut microbiome composition and stunting in under-five children.
(2024-May-23) Chibuye M; Mende DR; Spijker R; Simuyandi M; Luchen CC; Bosomprah S; Chilengi R; Schultsz C; Harris VC; Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.; The Zambia National Public Health Institute (ZNPHI), Lusaka, Zambia.; Division of Infectious Diseases, Department of Internal Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands. v.c.harris@amsterdamumc.nl.; Amsterdam Institute of Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, The Netherlands.; Department of Biostatistics, School of Public Health, University of Ghana, Legon, Accra, Ghana.; Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Amsterdam Institute of Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, The Netherlands. v.c.harris@amsterdamumc.nl.; Department of Medical Microbiology and Infection Control, Amsterdam University Medical Centers, Amsterdam, The Netherlands.; Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands. v.c.harris@amsterdamumc.nl.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Childhood stunting is associated with impaired cognitive development and increased risk of infections, morbidity, and mortality. The composition of the enteric microbiota may contribute to the pathogenesis of stunting. We systematically reviewed and synthesized data from studies using high-throughput genomic sequencing methods to characterize the gut microbiome in stunted versus non-stunted children under 5 years in LMICs. We included 14 studies from Asia, Africa, and South America. Most studies did not report any significant differences in the alpha diversity, while a significantly higher beta diversity was observed in stunted children in four out of seven studies that reported beta diversity. At the phylum level, inconsistent associations with stunting were observed for Bacillota, Pseudomonadota, and Bacteroidota phyla. No single genus was associated with stunted children across all 14 studies, and some associations were incongruent by specific genera. Nonetheless, stunting was associated with an abundance of pathobionts that could drive inflammation, such as Escherichia/Shigella and Campylobacter, and a reduction of butyrate producers, including Faecalibacterium, Megasphera, Blautia, and increased Ruminoccoccus. An abundance of taxa thought to originate in the oropharynx was also reported in duodenal and fecal samples of stunted children, while metabolic pathways, including purine and pyrimidine biosynthesis, vitamin B biosynthesis, and carbohydrate and amino acid degradation pathways, predicted linear growth. Current studies show that stunted children can have distinct microbial patterns compared to non-stunted children, which could contribute to the pathogenesis of stunting.