Bacterial Isolates and Antibiotic Sensitivity among Gambian Children with Severe Acute Malnutrition

Background. Establishing the pattern of infection and antimicrobial sensitivities in the local environment is critical to rational use of antibiotics and the development of management algorithms. Methods. Morbidity history and physical examination of 140 children with severe acute malnutrition were recorded. Their blood, stool, and urine samples were cultured and antibiotic sensitivity patterns determined for any bacterial pathogens isolated. Results. Thirty-eight children had a pathogen isolated from blood culture, 60% of which were considered contaminants. Coagulase negative staphylococcus was the predominant contaminant, while the major causes of bacteraemia were nontyphoidal Salmonella (13%), S. pneumoniae (10%), and E. coli (8%). E. coli accounted for 58% of the urinary isolates. No pathogen was isolated from stool. In vitro sensitivity by disk diffusion showed that 87.5% of the isolates were sensitive to ampicillin and/or gentamicin and 84.4% (27/32) to penicillin and/or gentamicin. Conclusions. A combination of ampicillin and gentamicin provides adequate antibiotic cover for severely malnourished children in The Gambia

Timeliness of routine childhood vaccination in low- and middle-income countries, 1978-2021: Protocol for a scoping review to map methodologic gaps and determinants.

The literature on the timeliness of childhood vaccination (i.e. vaccination at the earliest appropriate age) in low-and middle-income countries has important measurement and methodological issues that may limit their usefulness and cross comparison. We aim to conduct a comprehensive scoping review to map the existing literature with a key focus on how the literature on vaccination timeliness has evolved, how it has been defined or measured, and what determinants have been explored in the period spanning the last four decades. This scoping review protocol was developed based on the guidance for scoping reviews from the Joanna Briggs Institute. We will include English and French language peer-reviewed publications and grey literature on the timeliness of routine childhood vaccination in low-and middle-income countries published between January 1978 through to 2021. A three-step search strategy that involves an initial search of two databases to refine the keywords, a full search of all included electronic databases, and screening of references of previous studies for relevant articles missing from our full search will be employed. The search will be conducted in five electronic databases: MEDLINE, EMBASE, Global Health, CINAHL and Web of Science. Google search will also be conducted to identify relevant grey literature on vaccination timeliness. All retrieved titles from the search will be imported into Endnote X9.3.3 (Clarivate Analytics) and deduplicated. Two reviewers will screen the titles, abstracts and full texts of publications for eligibility using Rayyan-the web based application for screening articles for systematic reviews. Using a tailored data extraction template, we will extract relevant information from eligible studies. The study team will analyse the extracted data using descriptive statistical methods and thematic analysis. The results will be presented using tables, while charts and maps will be used to aid the visualisation of the key findings and themes. The proposed review will generate evidence on key methodological gaps in the literature on timeliness of childhood vaccination. Such evidence would shape the direction of future research, and assist immunisation programme managers and country-level stakeholders to address the needs of their national immunisation system

Timeliness of routine childhood vaccination among 12-35 months old children in The Gambia: Analysis of national immunisation survey data, 2019-2020.

The Gambia's routine childhood vaccination programme is highly successful, however, many vaccinations are delayed, with potential implications for disease outbreaks. We adopted a multi-dimensional approach to determine the timeliness of vaccination (i.e., timely, early, delayed, and untimely interval vaccination). We utilised data for 3,248 children from The Gambia 2019-2020 Demographic and Health Survey. Nine tracer vaccines administered at birth and at two, three, four, and nine months of life were included. Timeliness was defined according to the recommended national vaccination windows and reported as both categorical and continuous variables. Routine coverage was high (above 90%), but also a high rate of untimely vaccination. First-dose pentavalent vaccine (PENTA1) and oral polio vaccine (OPV1) had the highest timely coverage that ranged from 71.8% (95% CI = 68.7-74.8%) to 74.4% (95% CI = 71.7-77.1%). Delayed vaccination was the commonest dimension of untimely vaccination and ranged from 17.5% (95% CI = 14.5-20.4%) to 91.1% (95% CI = 88.9-93.4%), with median delays ranging from 11 days (IQR = 5, 19.5 days) to 28 days (IQR = 11, 57 days) across all vaccines. The birth-dose of Hepatitis B vaccine had the highest delay and this was more common in the 24-35 months age group (91.1% [95% CI = 88.9-93.4%], median delays = 17 days [IQR = 10, 28 days]) compared to the 12-23 months age-group (84.9% [95% CI = 81.9-87.9%], median delays = 16 days [IQR = 9, 26 days]). Early vaccination was the least common and ranged from 4.9% (95% CI = 3.2-6.7%) to 10.7% (95% CI = 8.3-13.1%) for all vaccines. The Gambia's childhood immunization system requires urgent implementation of effective strategies to reduce untimely vaccination in order to optimize its quality, even though it already has impressive coverage rates

Oral activated charcoal prevents experimental cerebral malaria in mice and in a randomized controlled clinical trial in man did not interfere with the pharmacokinetics of parenteral artesunate.

BACKGROUND: Safe, cheap and effective adjunct therapies preventing the development of, or reducing the mortality from, severe malaria could have considerable and rapid public health impact. Oral activated charcoal (oAC) is a safe and well tolerated treatment for acute poisoning, more recently shown to have significant immunomodulatory effects in man. In preparation for possible efficacy trials in human malaria, we sought to determine whether oAC would i) reduce mortality due to experimental cerebral malaria (ECM) in mice, ii) modulate immune and inflammatory responses associated with ECM, and iii) affect the pharmacokinetics of parenteral artesunate in human volunteers. METHODS/PRINCIPAL FINDINGS: We found that oAC provided significant protection against P. berghei ANKA-induced ECM, increasing overall survival time compared to untreated mice (p<0.0001; hazard ratio 16.4; 95% CI 6.73 to 40.1). Protection from ECM by oAC was associated with reduced numbers of splenic TNF(+) CD4(+) T cells and multifunctional IFNgamma(+)TNF(+) CD4(+) and CD8(+) T cells. Furthermore, we identified a whole blood gene expression signature (68 genes) associated with protection from ECM. To evaluate whether oAC might affect current best available anti-malarial treatment, we conducted a randomized controlled open label trial in 52 human volunteers (ISRCTN NR. 64793756), administering artesunate (AS) in the presence or absence of oAC. We demonstrated that co-administration of oAC was safe and well-tolerated. In the 26 subjects further analyzed, we found no interference with the pharmacokinetics of parenteral AS or its pharmacologically active metabolite dihydroartemisinin. CONCLUSIONS/SIGNIFICANCE: oAC protects against ECM in mice, and does not interfere with the pharmacokinetics of parenteral artesunate. If future studies succeed in establishing the efficacy of oAC in human malaria, then the characteristics of being inexpensive, well-tolerated at high doses and requiring no sophisticated storage would make oAC a relevant candidate for adjunct therapy to reduce mortality from severe malaria, or for immediate treatment of suspected severe malaria in a rural setting. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN64793756

Mapping the timeliness of routine childhood vaccination in The Gambia: A spatial modelling study.

INTRODUCTION: Timeliness of routine vaccination shapes childhood infection risk and thus is an important public health metric. Estimates of indicators of the timeliness of vaccination are usually produced at the national or regional level, which may conceal epidemiologically relevant local heterogeneities and makeitdifficultto identify pockets of vulnerabilities that could benefit from targeted interventions. Here, we demonstrate the utility of geospatial modelling techniques in generating high-resolution maps of the prevalence of delayed childhood vaccination in The Gambia. To guide local immunisation policy and prioritize key interventions, we also identified the districts with a combination of high estimated prevalence and a significant population of affected infants. METHODS: We used the birth dose of the hepatitis-B vaccine (HepB0), third-dose of the pentavalent vaccine (PENTA3), and the first dose of measles-containing vaccine (MCV1) as examples to map delayed vaccination nationally at a resolution of 1 × 1-km2 pixel. We utilized cluster-level childhood vaccination data from The Gambia 2019-20 Demographic and Health Survey. We adopted a fully Bayesian geostatistical model incorporating publicly available geospatial covariates to aid predictive accuracy. The model was implemented using the integrated nested Laplace approximation-stochastic partial differential equation (INLA-SPDE) approach. RESULTS: We found significant subnational heterogeneity in delayed HepB0, PENTA3 and MCV1 vaccinations. Specificdistricts in the central and eastern regions of The Gambia consistentlyexhibited the highest prevalence of delayed vaccination, while the coastal districts showed alower prevalence forallthree vaccines. We also found that districts in the eastern, central, as well as in coastal parts of The Gambia had a combination of high estimated prevalence of delayed HepB0, PENTA3 and MCV1 and a significant population of affected infants. CONCLUSIONS: Our approach provides decision-makers with a valuable tool to better understand local patterns of untimely childhood vaccination and identify districts where strengthening vaccine delivery systems could have the greatest impact

Impact of the COVID-19 pandemic on the coverage and timeliness of routine childhood vaccinations in the Gambia, 2015-2021

INTRODUCTION: The COVID-19 pandemic caused widespread morbidity and mortality and resulted in the biggest setback in routine vaccinations in three decades. Data on the impact of the pandemic on immunisation in Africa are limited, in part, due to low-quality routine or administrative data. This study examined coverage and timeliness of routine childhood immunisation during the pandemic in The Gambia, a country with an immunisation system considered robust. METHODS: We obtained prospective birth cohort data of 57 286 children in over 300 communities in two health and demographic surveillance system sites, including data from the pre-pandemic period (January 2015-February 2020) and the three waves of the pandemic period (March 2020-December 2021). We determined monthly coverage and timeliness (early and delayed) of the birth dose of hepatitis B vaccine (HepB0) and the first dose of pentavalent vaccine (Penta1) during the different waves of the pandemic relative to the pre-pandemic period. We implemented a binomial interrupted time-series regression model. RESULT: We observed no significant change in the coverage of HepB0 and Penta1 vaccinations from the pre-pandemic period up until the periods before the peaks of the first and second waves of the pandemic in 2020. However, there was an increase in HepB0 coverage before as well as after the peak of the third wave in 2021 compared with the pre-pandemic period (pre-third wave peak OR = 1.83, 95% CI 1.06 to 3.14; post-third wave period OR=2.20, 95% CI 1.23 to 3.92). There was some evidence that vaccination timeliness changed during specific periods of the pandemic. Early Penta1 vaccination decreased by 70% (OR=0.30, 95% CI 0.12 to 0.78) in the period before the second wave, and delayed HepB0 vaccination decreased by 47% (OR=0.53, 95% CI 0.29 to 0.97) after the peak of the third wave in 2021. CONCLUSION: Despite the challenges of the COVID-19 pandemic, The Gambia's routine vaccination programme has defied the setbacks witnessed in other settings and remained resilient, with coverage increasing and timeliness improving during the second and third waves. These findings highlight the importance of having adequate surveillance systems to monitor the impact of large shocks to vaccination coverage and timeliness

Maternal colonization and early-onset neonatal bacterial sepsis in the Gambia, West Africa: a genomic analysis of vertical transmission

OBJECTIVES: To define bacterial aetiology of neonatal sepsis and estimate the prevalence of neonatal infection from maternal genital tract bacterial carriage among mother-newborn pairs. METHODS: We carried out a cross-sectional study of newborns with clinical sepsis admitted to three hospitals in the Gambia neonatal wards. Neonatal blood cultures and maternal genital swabs were obtained at recruitment. We used whole-genome sequencing to explore vertical transmission for neonates with microbiologically confirmed bloodstream infection by comparing phenotypically-matched paired neonatal blood cultures and maternal genital tract bacterial isolates. RESULTS: We enrolled 203 maternal-newborn pairs. Two-thirds (67%; 137/203) of neonates presented with early-onset sepsis (days 0-6 after birth) of which 26% (36/137) were because of a clinically-significant bacterial pathogen. Blood culture isolates from newborns with early-onset sepsis because of Staphylococcus aureus (n = 5), Klebsiella pneumonia (n = 2), and Enterococcus faecalis (n = 1), phenotypically matched their maternal genital tract isolates. Pairwise single-nucleotide variants comparisons showed differences of 12 to 52 single-nucleotide variants only between maternal and newborn S. aureus isolates, presumably representing vertical transmission with a transmission rate of 14% (5/36). CONCLUSIONS: We found a low prevalence of vertical transmission of maternal genital tract colonization in maternal-newborn pairs for early-onset neonatal sepsis in the West African context. Identifying infection acquisition pathways among newborns is essential to prioritize preventive interventions, which could be targeted at the mother or infection control in the hospital environment, depending on the major pathways of transmission

Intramuscular Artesunate for Severe Malaria in African Children: A Multicenter Randomized Controlled Trial.

BACKGROUND: Current artesunate (ARS) regimens for severe malaria are complex. Once daily intramuscular (i.m.) injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v.) or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%). METHODS AND FINDINGS: This randomized controlled trial included children (0.5-10 y) with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0, 12, 24, 48, and 72 h) (n = 348) or three injections of 4 mg/kg (at 0, 24, and 48 h) either i.m. (n = 348) or i.v. (n = 351), both of which were the intervention arms. The primary endpoint was the proportion of children with ≥ 99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan-Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7 g/dl 7 d or more after admission. The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333); 139 participants were lost to follow-up. In the three-dose i.m. arm, 265/338 (78%) children had a ≥ 99% reduction in parasitemia at 24 h compared to 263/331 (79%) receiving the five-dose i.m. regimen, showing non-inferiority of the simplified three-dose regimen to the conventional five-dose regimen (95% CI -7, 5; p = 0.02). In the three-dose i.v. arm, 246/333 (74%) children had ≥ 99% reduction in parasitemia at 24 h; hence, non-inferiority of this regimen to the five-dose control regimen was not shown (95% CI -12, 1; p = 0.24). Delayed parasite clearance was associated with the N86YPfmdr1 genotype. In a post hoc analysis, 192/885 (22%) children developed delayed anemia, an adverse event associated with increased leukocyte counts. There was no observed difference in delayed anemia between treatment arms. A potential limitation of the study is its open-label design, although the primary outcome measures were assessed in a blinded manner. CONCLUSIONS: A simplified three-dose i.m. regimen for severe malaria in African children is non-inferior to the more complex WHO-recommended regimen. Parenteral ARS is associated with a risk of delayed anemia in African children. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201102000277177

Neonatal admissions, quality of care and outcome: 4 years of inpatient audit data from The Gambia's teaching hospital.

BACKGROUND: National facility-based neonatal mortality audits are an important source of data to identify areas for improvement of service delivery and outcome of care. OBJECTIVES: To examine admissions to the neonatal unit, Edward Francis Small Teaching Hospital, Banjul, The Gambia and make recommendations for programme action to reduce mortality through improvements in the quality of care, particularly with respect to suspected neonatal infections. METHODS: Case notes were reviewed for all neonates admitted to the neonatal unit during a 5-year period (1 January 2009 to 31 December 2013) to assess outcome and quality of care. Data for 2009 were subsequently excluded because of the low proportion of records retrieved. RESULTS: Of the 4944 admissions between 1 January 2010 and 31 December 2013, 1734 infants (35%) died, with 57% of all deaths occurring within the first 48 hours of admission. There were 1267 early neonatal deaths (deaths occurring during the first 7 days of life), 67% of which occurred during the first 48 hours of life. Independent predictors of neonatal death in the multivariable analysis were; maternal lack of antenatal care, non-teaching hospital delivery, admission weight 6.9 mmol/L) and hypothermia (axillary temperature < 36.5 ˚C). Forty-eight per cent of newborns had point-of-admission hypothermia. Possible severe bacterial infection (pSBI) accounted for 44% (2166/4944) of admissions, prematurity/low birthweight for 27% (1340/4944) and intrapartum-related conditions for 20%. Only 5% (104/2166) of pSBI cases had at least one supportive investigation; 41 had a chest radiograph, 26 had a blood culture and 43 had a lumbar puncture. Although 94% of the newborns received intravenous antibiotics, 55% of those who did lacked clinical evidence of pSBI and had no diagnostic work-up. CONCLUSION: Priority areas for action include infection prevention and improved diagnosis and management. There is also scope to reduce hypothermia with feasible interventions particularly targeting preterm infants. Improved patient records and audit data with linked action and accountability are interventions which could prevent such deaths of newborns in The Gambia and other developing countries