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Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. In this prospective cohort study, we measure maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India ( n  = 307), Malawi ( n  = 119), and the UK ( n  = 60), using standardised methods across cohorts. We observe ORV shedding and seroconversion rates to be significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk are negatively correlated with ORV response in India and Malawi, mediated partly by a reduction in ORV shedding. In the UK, ORV shedding is not inhibited despite comparable maternal antibody levels to the other cohorts. In both India and Malawi, increased microbiota diversity is negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy. Oral rotavirus vaccine (ORV) efficacy varies between countries, but underlying reasons aren’t fully understood. In this prospective cohort study, authors show that maternal rotavirus-specific antibodies in serum and breastmilk and pre-vaccination microbiota diversity are negatively correlated with ORV response in India and Malawi but not in the UK.

The efficacy of a Vi polysaccharide typhoid conjugate vaccine (Vi-TCV) was assessed in 28,130 Malawian children who were 9 months to 12 years of age. The incidence of blood culture–confirmed typhoid fever was significantly lower among children who received Vi-TCV than among those who received a control vaccine.

Randomised controlled trials of typhoid conjugate vaccines among children in Africa and Asia have shown high short-term efficacy. Data on the durability of protection beyond 2 years are sparse. We present the final analysis of a randomised controlled trial in Malawi, encompassing more than 4 years of follow-up, with the aim of investigating vaccine efficacy over time and by age group. In this phase 3, double-blind, randomised controlled efficacy trial in Blantyre, Malawi, healthy children aged 9 months to 12 years were randomly assigned (1:1) by an unmasked statistician to receive a single dose of Vi polysaccharide conjugated to tetanus toxoid vaccine (Vi-TT) or meningococcal capsular group A conjugate (MenA) vaccine. Children had to have no previous history of typhoid vaccination and reside in the study areas for inclusion and were recruited from government schools and health centres. Participants, their parents or guardians, and the study team were masked to vaccine allocation. Nurses administering vaccines were unmasked. We did surveillance for febrile illness from vaccination until follow-up completion. The primary outcome was first occurrence of blood culture-confirmed typhoid fever. Eligible children who were randomly assigned and vaccinated were included in the intention-to-treat analyses. This trial is registered at ClinicalTrials.gov, NCT03299426. Between Feb 21, 2018, and Sept 27, 2018, 28 130 children were vaccinated; 14 069 were assigned to receive Vi-TT and 14 061 to receive MenA. After a median follow-up of 4·3 years (IQR 4·2–4·5), 24 (39·7 cases per 100 000 person-years) children in the Vi-TT group and 110 (182·7 cases per 100 000 person-years) children in the MenA group were diagnosed with a first episode of blood culture-confirmed typhoid fever. In the intention-to-treat population, efficacy of Vi-TT was 78·3% (95% CI 66·3–86·1), and 163 (129–222) children needed to be vaccinated to prevent one case. Efficacies by age group were 70·6% (6·4–93·0) for children aged 9 months to 2 years; 79·6% (45·8–93·9) for children aged 2–4 years; and 79·3% (63·5–89·0) for children aged 5–12 years. A single dose of Vi-TT is durably efficacious for at least 4 years among children aged 9 months to 12 years and shows efficacy in all age groups, including children younger than 2 years. These results support current WHO recommendations in typhoid-endemic areas for mass campaigns among children aged 9 months to 15 years, followed by routine introduction in the first 2 years of life. Bill & Melinda Gates Foundation.

Background Low blood glucose concentration is a well-recognized risk factor for mortality in children admitted to hospitals in low-income settings. Current WHO guidelines define hypoglycaemia as a blood glucose level below 2.5 mmol/L; however, this threshold has been questioned. In a trial conducted in Malawian hospitals, increasing the treatment threshold to 5.0 mmol/L did not reduce in-hospital mortality among children aged 1 month to 5 years. The physiological response to low glucose and dextrose treatment in older children may differ yet remains understudied. This exploratory analysis was conducted to assess potential effects of dextrose treatment in severely ill children aged 5–12 years with blood glucose concentrations between 2.5 and 5.0 mmol/L. Methods The study is an exploratory extension of a pragmatic randomised controlled trial where all eligible children were randomised to receive either a 5 ml/kg intravenous bolus followed by maintenance infusion of 10% dextrose (intervention group) or observation and standard care (control group). The primary outcome was in-hospital mortality; the secondary outcome was 24-hour mortality. Results Seventy-two children were enrolled with 36 allocated to each group. In-hospital mortality was 8% (3/36) in the intervention group and 19% (7/36) in the control group with an odds ratio (OR) for mortality of 0.8 (95% CI 0.46–2.25). The mortality after 24 h was 3% (1/36) in the intervention group and 8% (3/36) in the control group, with an OR of 0.4 (95% CI. 0.06–2.90). Adverse events occurred in 19% (7/36) in the intervention group and 39% (14/36) in the control group. Conclusion This exploratory analysis suggests a potential reduction in mortality when intravenous dextrose treatment is administered to severely ill children aged 5–12 years who present to hospital with a low blood glucose. However, as the parent trial was powered for children less than 5 years the sample size for this older age group was insufficient to draw definitive conclusions. Larger, age-specific studies are warranted to determine the potential benefit of dextrose treatment in this population. Trial Registration The study is registered with ClinicalTrials.gov, NCT02989675 on 7th December 2016.

Malawi experienced its deadliest Vibrio cholerae ( Vc ) outbreak following devastating cyclones, with >58,000 cases and >1700 deaths reported between March 2022 and May 2023. Here, we use population genomics to investigate the attributes and origin of the Malawi 2022–2023 Vc outbreak isolates. Our results demonstrate the predominance of ST69 clone, also known as the seventh cholera pandemic El Tor (7PET) lineage, expressing O1 Ogawa (~ 80%) serotype followed by Inaba (~ 16%) and sporadic non-O1/non-7PET serogroups (~ 4%). Phylogenetic reconstruction revealed that the Malawi outbreak strains correspond to a recent importation from Asia into Africa (sublineage AFR15). These isolates harboured known antimicrobial resistance and virulence elements, notably the ICE GEN /ICEVchHai1/ICEVchind5 SXT/R391-like integrative conjugative elements and a CTXφ prophage with the ctxB7 genotype compared to historical Malawian Vc isolates. These data suggest that the devastating cyclones coupled with the recent importation of 7PET serogroup O1 strains, may explain the magnitude of the 2022–2023 cholera outbreak in Malawi. Malawi experienced a large cholera outbreak in 2022-2023 that was associated with high morbidity and mortality and distributed across all 29 districts of the country. This study describes the epidemiological and genomic features of the outbreak and attempts to understand the reasons for its severity.

Background Hospital-based kangaroo mother care can help reduce preventable newborn deaths and has been recommended by the World Health Organization in the care of low birthweight babies weighing 2000 g or less. However, implementation has been limited. The objective of this review is to understand the barriers and facilitators of kangaroo mother care implementation in health facilities in sub-Saharan Africa, where there are the highest rates of neonatal mortality in the world. Methods A systematic search was performed on MEDLINE, Web of Science, Cumulative Index to Nursing and Allied Health, African Journals Online, African Index Medicus as well as the references of relevant articles. Inclusion criteria included primary research, facility-based kangaroo mother care in sub-Saharan Africa. Studies were assessed by the Critical Appraisal Skills Programme Qualitative Checklist and the National Institutes of Health quality assessment tools and underwent narrative synthesis. Results Thirty studies were included in the review. This review examined barriers and facilitators to kangaroo mother care practice at health systems level, health worker experiences and perspectives of mothers and their families. Strong local leadership was essential to overcome barriers of inadequate space, limited budget for supplies, inadequate staffing, lack of guidelines and policies and insufficient supportive supervision. Workload burdens, knowledge gaps and staff attitudes were highlighted as challenges at health workers’ level, which could be supported by sharing of best practices and success stories. Support for mothers and their families was also identified as a gap. Conclusion Building momentum for kangaroo mother care in health facilities in sub-Saharan Africa continues to be a challenge. Strengthening health systems and communication, prioritizing preterm infant care in public health strategies and supporting health workers and mothers and their families as partners in care are important to scale up. This will support sustainable kangaroo mother care implementation as well as strengthen quality of newborn care overall. PROSPERO registration: CRD42020166742.

GBS is a leading cause of mortality in newborn babies in high- and low-income countries worldwide. Different strains of GBS are characterized by different degrees of virulence, where some are harmlessly carried by humans or animals and others are much more likely to cause disease. The genome sequences of almost 2,000 GBS samples isolated from both animals and humans in high- and low- income countries were analyzed using a pan-genome-wide association study approach. This allowed us to identify 279 genes which are associated with different lineages of GBS, characterized by a different virulence and preferred host. Additionally, we propose that the GBS now carried in humans may have first evolved in animals before expanding clonally once adapted to the human host. These findings are essential to help understand what is causing GBS disease and how the bacteria have evolved and are transmitted. Streptococcus agalactiae (group B streptococcus; GBS) is a colonizer of the gastrointestinal and urogenital tracts, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterized by clonal complexes (CCs) with different invasive potentials. CC17, for example, is a hypervirulent lineage commonly associated with neonatal sepsis and meningitis, while CC1 is less invasive in neonates and more commonly causes invasive disease in adults with comorbidities. The genetic basis of GBS virulence and the extent to which different CCs have adapted to different host environments remain uncertain. We have therefore applied a pan-genome-wide association study (GWAS) approach to 1,988 GBS strains isolated from different hosts and countries. Our analysis identified 279 CC-specific genes associated with virulence, disease, metabolism, and regulation of cellular mechanisms that may explain the differential virulence potential of particular CCs. In CC17 and CC23, for example, we have identified genes encoding pilus, quorum-sensing proteins, and proteins for the uptake of ions and micronutrients which are absent in less invasive lineages. Moreover, in CC17, carriage and disease strains were distinguished by the allelic variants of 21 of these CC-specific genes. Together our data highlight the lineage-specific basis of GBS niche adaptation and virulence. IMPORTANCE GBS is a leading cause of mortality in newborn babies in high- and low-income countries worldwide. Different strains of GBS are characterized by different degrees of virulence, where some are harmlessly carried by humans or animals and others are much more likely to cause disease. The genome sequences of almost 2,000 GBS samples isolated from both animals and humans in high- and low- income countries were analyzed using a pan-genome-wide association study approach. This allowed us to identify 279 genes which are associated with different lineages of GBS, characterized by a different virulence and preferred host. Additionally, we propose that the GBS now carried in humans may have first evolved in animals before expanding clonally once adapted to the human host. These findings are essential to help understand what is causing GBS disease and how the bacteria have evolved and are transmitted.

Preterm birth complications are the leading cause of neonatal deaths. Malawi has high rates of preterm birth, with 18.1 preterm births per 100 live births. More than 50% of preterm neonates develop respiratory distress which if left untreated, can lead to respiratory failure and death. Term and preterm neonates with respiratory distress can often be effectively managed with Continuous Positive Airway Pressure (CPAP) and this is considered an essential intervention for the management of preterm neonates by the World Health Organization. Bubble CPAP may represent a safe and cost-effective method for delivering CPAP in low-income settings. The study explored the factors that influence the implementation of bubble CPAP among health care professionals in secondary and tertiary hospitals in Malawi. This was a qualitative study conducted in three district hospitals and a tertiary hospital in southern Malawi. We conducted 46 in-depth interviews with nurses, clinicians and clinical supervisors, from June to August 2018. All data were digitally recorded, transcribed verbatim and thematically analyzed. Factors that influenced implementation of bubble CPAP occurred in an interconnected manner and included: inadequate healthcare provider training in preparation for use, rigid division of roles and responsibilities among providers, lack of effective communication among providers and between providers and newborn's caregivers, human resource constraints, and inadequate equipment and infrastructure. There are provider, caregiver and health system level factors that influence the implementation of bubble CPAP among neonates in Malawian health facilities. Ensuring adequate staffing in the nurseries, combined with ongoing training for providers, team cohesion, improved communication with caregivers, and improved hospital infrastructure would ensure optimal utilization of bubble CPAP and avoid inadvertent harm from inappropriate use.

White blood cell (WBC) and neutrophil counts are important laboratory tests used by clinicians to assess a variety of conditions. However, current methods to measure WBC and neutrophil counts are difficult to perform at the point of care, being either cost or labor prohibitive. To meet this need, we developed the LeukoScope: a portable, imaging-based system to measure WBC and neutrophil counts from a drop of blood. Here, we present the performance of the LeukoScope in 136 pediatric and 164 neonatal subjects at a central hospital in Malawi. For pediatric patients, 95.4, 66.7, and 80.0% of samples with normal, low, and high WBC counts, respectively, were correctly identified, and 88.6, 100.0, and 89.3% of samples with normal, low, and high neutrophil counts, respectively, were correctly identified. Accuracy was lower overall for neonatal samples; 92.1, 64.3, and 26.7% of samples with normal, low, and high WBC counts, respectively, were correctly identified, and 73.2 and 78.6% of samples with normal and high neutrophil counts, respectively, were correctly identified. Results of this study show that the LeukoScope can help meet need for point-of-care measurement of WBC counts in pediatric patients and highlight the challenges of point-of-care assessment of WBC counts in neonatal patients.

We use machine learning to identify innovative strategies to target azithromycin to the children with watery diarrhea who are most likely to benefit. Using data from a randomized trial of azithromycin for watery diarrhea (NCT03130114), we develop personalized treatment rules given sets of diagnostic, child, and clinical characteristics, employing a robust ensemble machine learning-based procedure. This procedure estimates the child-level expected benefit for a given set of covariates by combining predictions from a library of statistical models. For each rule, we estimate the proportion treated under the rule and the average benefits of treatment. Among 6692 children, treatment under the most comprehensive rule is recommended on average for one third of children. The risk of diarrhea on day 3 is 10.1% lower (95% CI: 5.4, 14.9) with azithromycin compared to placebo among children recommended for treatment (NNT: 10). For day 90 re-hospitalization and death, risk is 2.4% lower (95% CI: 0.6, 4.1; NNT: 42). While pathogen diagnostics are strong determinants of azithromycin effects on diarrhea duration, host characteristics may better predict benefits for re-hospitalization or death. This suggests that targeting antibiotic treatment for severe outcomes among children with watery diarrhea may be possible without access to pathogen diagnostics. Pathogen diagnostics are strong determinants of azithromycin effects on diarrhea duration, but host factors may better predict benefits for severe outcomes. In this work, authors utilise a machine learning-based approach to evaluate personalized rules for the decision to treat watery diarrhea with azithromycin.