Publications by authors named "James A Berkley"

Background: Improved causes of death (CoD) understanding in low- and middle-income countries is needed to reduce child mortality. Compared to full autopsy, minimally invasive tissue sampling (MITS), using transcutaneous needle sampling, is a feasible, socially acceptable, and validated method. We aimed to quantify the additional contribution of MITS to CoD attribution based on clinical records and inpatient research data with intensive patient characterisation.

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Background: Newborns infected with Hepatitis B Virus (HBV) are at risk of chronic liver disease and hepatocellular carcinoma.

Objectives: This study investigated the prevalence of HBV infection among pregnant women and cord blood Hepatitis B surface antigen (HBsAg) positivity of their newborns in Bangladesh, Bhutan, India, Ethiopia, Mozambique, Kenya, Nigeria, Mali, and South Africa.

Study Design: Randomly selected paired maternal and cord blood samples (n = 101 each site) taken at delivery were tested for HBsAg and Hepatitis B extractable antigen (HBeAg) in the women using a chemiluminescent microparticle immunoassay.

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Interfaces between humans, livestock, and wildlife, mediated by the environment, are critical points for the transmission and emergence of infectious pathogens and call for leveraging the One Health approach to understanding disease transmission. Current research on pathogen transmission often focuses on single-pathogen systems, providing a limited understanding of the broader microbial interactions occurring at these interfaces. In this review, we make a case for the study of host-associated microbiota for understanding connectivity between host populations at human-animal interfaces.

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Background: Small for gestational age is a complex perinatal syndrome associated with increased neonatal morbidity, mortality, and impaired childhood growth and neurodevelopment. Current classifications rely primarily on birthweight, which does not capture the heterogeneity of the condition nor predict long-term health outcomes. Here we aim to identify and characterize distinct small for gestational age subgroups and assess their neonatal and early childhood health trajectories.

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The first WHO Global Clinical Trials Forum was convened in November, 2023 to develop a shared vision of an effective global clinical trial infrastructure. The Paediatric Clinical Trials Working Group was formed to provide perspectives, identify challenges, and propose solutions to strengthen the paediatric clinical trials ecosystem. Participants represented paediatric disciplines, including infectious diseases, nutrition, neonatology, pharmacology, oncology, neurodevelopment, public health, and policy.

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Objectives: To investigate the transplacental acquisition of measles immunoglobulin (Ig)G in newborns at delivery in Bangladesh, Bhutan, India, Ethiopia, Mozambique, Kenya, Nigeria, Mali, and South Africa.

Methods: Archived cord serum, from a multicenter study on Group B Streptococcus, were tested for measles IgG using a commercial enzyme link immunosorbent assay (ELISA). We tested 323 randomly selected samples from each of the sites.

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Background: Successful introduction, high uptake and program effectiveness of new maternal vaccines aimed to prevent disease among infants require prior knowledge of their safety during pregnancy. We aimed to identify background adverse birth outcomes and their predictors in Kenya by which to aid future interpretation of outcomes for new maternal vaccination programs.

Methods: A cross-sectional survey was conducted to assess birth outcomes from women residents within the health and demographic surveillance systems of Kilifi, Siaya and Nairobi, Kenya.

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Background: Risk prediction tools for acutely ill children have been developed in high- and low-income settings, but few are validated or incorporated into clinical guidelines. We aimed to assess the performance of existing paediatric early warning scores for use in low- and middle-income countries using clinical data from a recent large multi-country study in Africa and South-Asia.

Methods: We used data (children across three nutritional strata) from the Childhood Acute Illness and Nutrition (CHAIN) Network cohort study (n = 3101).

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Introduction: Medicine quality can be influenced by environmental factors. In low- and middle-income countries (LMICs) with tropical climates, storage facilities of medicines in healthcare settings and homes may be suboptimal. However, knowledge of the effects of temperature and other climatic and environmental factors on the quality of medicines is limited.

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Article Synopsis
  • HEU (HIV-exposed uninfected) children face a higher risk of hospitalization and mortality compared to HUU (HIV-unexposed uninfected) children, prompting a closer look at their health outcomes.
  • A study of 1486 children revealed that HEU children had significantly higher rates of hospitalization mortality and were more prone to wasting and stunting.
  • Despite similar illness severity and resource use in hospitals, HEU children had longer stays and a two-fold increased risk of dying within 30 days of hospitalization compared to HUU peers.
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Purpose: To provide details of a pooled data set that will be used to estimate absolute and relative mortality risks and other outcomes among children less than 59 months of age and the predictive performance of common risk exposures, both individually and in combination.

Participants: Children from birth to 5 years of age recruited at health facilities or community settings into 33 longitudinal observational or intervention studies in 17 low- and middle-income countries.

Findings To Date: The data set includes 75 287 children with a median age of 3 months (IQR 1-12) at first measurement.

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In sub-Saharan Africa, children with severe malnutrition (SM) and HIV have substantially worse outcomes than children with SM alone, facing higher mortality risk and impaired nutritional recovery post-hospitalisation. Biological mechanisms underpinning this risk remain incompletely understood. This case-control study nested within the CHAIN cohort in Kenya, Uganda, Malawi, and Burkina Faso examined effect of HIV on six months post-discharge growth among children with SM and those at risk of malnutrition, assessed proteomic signatures associated with HIV in these children, and investigated how these systemic processes impact post-discharge growth in children with SM.

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Background: There are limited data from sub-Saharan Africa describing the demographic characteristics, clinical features and outcome of patients admitted to public hospitals with severe acute respiratory infections during the COVID-19 pandemic.

Methods: We conducted a prospective longitudinal hospital-based sentinel surveillance between May 2020 and December 2022 at 16 public hospitals in Kenya. All patients aged above 18 years admitted to adult medical wards in the participating hospitals were included.

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Background: Pneumococcal conjugate vaccines are an expensive component of the routine immunization schedule. Fractional-dose regimens may be one option to increase the sustainability of the vaccine program.

Methods: We assessed whether the immunogenicity of fractional doses of the 10-valent and 13-valent pneumococcal conjugate vaccines (PCV10 [GSK] and PCV13 [Pfizer], respectively) would be noninferior to that of the full doses and analyzed the prevalence of vaccine-serotype carriage.

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Article Synopsis
  • The study aimed to investigate liver histopathology in children who died of acute illness in Malawi, specifically looking at nutritional status and its effects on liver mitochondria and peroxisomes.
  • Researchers collected liver tissue from eleven children under five, categorizing them into non-wasted, severely wasted, and edematous malnutrition groups to analyze histological differences using advanced microscopy techniques.
  • Results showed that children with edematous malnutrition had significantly fewer and more abnormal mitochondria compared to the other groups, indicating that targeting liver metabolic functions could help improve outcomes for children suffering from severe malnutrition.
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Article Synopsis
  • The study investigates the prevalence of rectovaginal group B Streptococcus (GBS) colonization in pregnant women during labor and its transmission to newborns in selected low-income and middle-income African and South Asian countries.
  • Conducted across 11 maternity and obstetric facilities, the research involved collecting samples from 6,514 HIV-negative pregnant women at least 37 weeks gestation to analyze GBS culture and serotyping.
  • The findings revealed a 24.1% rate of maternal GBS colonization, with the highest prevalence in Mali (41.1%) and the lowest in Ethiopia (11.6%), highlighting significant regional variations in GBS rates among pregnant women.
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Children are not born equal in their likelihood of survival. The risk of mortality is highest during and shortly after birth. In the immediate postnatal period and beyond, perinatal events, nutrition, infections, family and environmental exposures, and health services largely determine the risk of death.

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Although most children with cerebral malaria fully recover, more than a fifth of the survivors develop post-discharge neurodevelopmental sequelae suggestive of advanced neuronal injury. However, the cerebral molecular processes initiating neurological dysfunction in cerebral malaria are still debatable. In this article, we explore available data and hypothesise that cerebral malaria might be linked to APOE-mediated amyloidosis, one of the pathological processes associated with Alzheimer's disease.

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One-third of people with HIV in sub-Saharan Africa start antiretroviral therapy (ART) with advanced disease. We investigated associations between immune biomarkers and mortality in participants with advanced HIV randomised to cotrimoxazole or enhanced antimicrobial prophylaxis in the Reduction of Early Mortality in HIV-Infected Adults and Children Starting Antiretroviral Therapy (REALITY) trial (ISRCTN43622374). Biomarkers were assayed using ELISA and Luminex.

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Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs.

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