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Severe acute malnutrition (SAM) constitutes a substantial burden in African hospitals. Despite adhering to international guidelines, high inpatient mortality rates persist and the underlying contributing factors remain poorly understood. We evaluated the 10-year trend (2011-2021) in clinical factors and outcomes among children with severe wasting and/or nutritional edema at Malawi's largest nutritional rehabilitation unit (NRU). This retrospective study analyzed trends in presentation and outcomes using generalized additive models. The association between clinical characteristics and mortality or readmission was examined and key features were also related to time to either mortality or discharge. 1497 children (53%, females) were included. Median age at admission (23 months, IQR 14, 34) or anthropometry (i.e., weight-for-age, height-for-age and weight-for-height) did not change over the 10-years. But the prevalence of edema decreased by 40% whereas dehydration, difficulty breathing, and pallor became more common. Yearly HIV testing increased but positive-detection remained around 11%. Reporting of complete vaccination dropped by 49%, and no reduction in 'watch' antibiotic usage was detected. Overall admissions declined but mortality remained around 23% [95%CI; 21, 25], and deaths occurred earlier (5.6 days [95%CI; 4.6, 6.9] in 2011 vs. 3.5 days [95%CI; 2.5, 4.7] in 2021; p<0.001). Duration of hospitalization was shortened and readmissions surged from 4.9% [95%CI; 3.3, 7.4] in 2011 to 25% [95%CI; 18, 33] in 2021 (p<0.001). Age, wasting, having both dehydration and diarrhea, or having vomiting, cough, or difficulty breathing were associated with mortality but these associations did not show any interaction over time. Over 10 years, mortality risk remained high among hospitalized children with SAM and coincided with worsened clinical presentation at admission and increased readmission. Longitudinal data from major NRUs can identify shifts in clinical profiles or outcomes, and this information can be leveraged to promote earlier care-seeking, improved risk stratification, and implementation of more patient-centered treatments.

In low- and middle-income countries (LMICs), child mortality rates remain substantially higher compared to high-income countries, with many deaths preventable through early recognition of deterioration. This systematic review and meta-analysis investigated predictive values of vital signs and anthropometric measurements for paediatric in-hospital mortality in LMICs. A search of publicly available data in PubMed and OVID Embase was conducted in November 2021 and last updated in March 2025. Studies that reported on oxygen saturation; respiratory rate; heart rate; blood pressure; temperature; mid-upper arm circumference (MUAC); and/or weight-for-height z-score (WHZ), and paediatric in-hospital mortality were included. Neonatal and paediatric intensive care unit (PICU) studies were excluded. Data was extracted by two independent authors. Forest plots presented odds ratios (OR) using random effect models. Newcastle Ottawa Scale assessed risk of bias. 104 out of 21,494 yielded studies were included in descriptive analysis and 75 in meta-analysis, encompassing 255,546 children. Associations with in-hospital mortality were observed in hypoxaemia (OR 5.53, 95% CI 4.18-7.30), tachypnoea (OR 1.65, 95% CI 1.16-2.34), tachycardia (OR 1.80, 95% CI 1.22-2.66), bradycardia (OR 3.29, 95% CI 1.38-7.83), hypotension (OR 4.42, 95% CI 2.54-7.70), hyperthermia (OR 1.31, 95% CI 1.04-1.66), hypothermia (OR 3.92, 95% CI 2.76-5.58), low MUAC (OR 3.22, 95% CI 2.12-4.91), and low WHZ (OR 3.19, 95% CI 2.47-4.11). Several vital signs and anthropometric measurements are strongly associated with in-hospital mortality in children. Hypoxaemia demonstrated the highest odds of mortality, followed by hypotension, hypothermia, bradycardia and severe malnutrition. These findings highlight the need for early recognition and targeted interventions for children presenting with these high-risk signs, to improve outcomes in resource-limited settings and stress the need to monitor vital signs. None.

Background An acute (i.e. unplanned) admission implies uncertainty about the length of stay (LOS) for children, their parents and hospital staff. An improved understanding of the prognostic factors associated with LOS in children is essential for adequate discharge planning, optimal use of bed capacity, and patient counseling. We aimed to explore which prognostic factors were associated with LOS in children between 0 and 18 years old, who were acutely admitted to a pediatric academic hospital ward. Methods We conducted a historical cohort study using electronic data from all children who were acutely admitted to the Emma Children’s Hospital, the Netherlands, between 2017 and 2022. Selection of potential prognostic factors was based on literature and expert opinion. Univariable linear regression analysis was used to select prognostic factors associated with LOS, followed by multivariable regression analysis to obtain the final model. Results We included 9209 children with a median LOS of 2.7 days (IQR 1.1 to 5.8). Out of 16 potential prognostic factors, 10 were associated with an increased LOS, while 4 decreased the LOS. The strongest associations were (1) the involvement of ≥ 3 sub-specialties during the first 24 h of admission, (2) the severity of illness and (3) medical home care after discharge, and were all prognostic for an increased LOS. The final model explained 29% of the variance in LOS. Conclusions The results of this study support patient and hospital expectations and bed capacity management. The explained variance is limited despite the inclusion of multiple factors, suggesting predicting LOS for this population is challenging.

Severe acute malnutrition (SAM) constitutes a substantial burden in African hospitals. Despite adhering to international guidelines, high inpatient mortality rates persist and the underlying contributing factors remain poorly understood. We evaluated the 10-year trend (2011-2021) in clinical factors and outcomes among children with severe wasting and/or nutritional edema at Malawi's largest nutritional rehabilitation unit (NRU). This retrospective study analyzed trends in presentation and outcomes using generalized additive models. The association between clinical characteristics and mortality or readmission was examined and key features were also related to time to either mortality or discharge. 1497 children (53%, females) were included. Median age at admission (23 months, IQR 14, 34) or anthropometry (i.e., weight-for-age, height-for-age and weight-for-height) did not change over the 10-years. But the prevalence of edema decreased by 40% whereas dehydration, difficulty breathing, and pallor became more common. Yearly HIV testing increased but positive-detection remained around 11%. Reporting of complete vaccination dropped by 49%, and no reduction in 'watch' antibiotic usage was detected. Overall admissions declined but mortality remained around 23% [95%CI; 21, 25], and deaths occurred earlier (5.6 days [95%CI; 4.6, 6.9] in 2011 vs. 3.5 days [95%CI; 2.5, 4.7] in 2021; p<0.001). Duration of hospitalization was shortened and readmissions surged from 4.9% [95%CI; 3.3, 7.4] in 2011 to 25% [95%CI; 18, 33] in 2021 (p<0.001). Age, wasting, having both dehydration and diarrhea, or having vomiting, cough, or difficulty breathing were associated with mortality but these associations did not show any interaction over time. Over 10 years, mortality risk remained high among hospitalized children with SAM and coincided with worsened clinical presentation at admission and increased readmission. Longitudinal data from major NRUs can identify shifts in clinical profiles or outcomes, and this information can be leveraged to promote earlier care-seeking, improved risk stratification, and implementation of more patient-centered treatments.

Undernutrition and malnutrition in children in low- and middle-income countries contribute to high mortality rates. Stunting, a prevalent form of malnutrition, is associated with educational and productivity losses. Environmental enteric dysfunction (EED) and human immunodeficiency virus (HIV) infection worsen these conditions. This study seeks to investigate the presence of enteropathy using EED fecal biomarkers in HIV-infected children who are stable on antiretroviral therapy (ART) across various nutritional statuses. By understanding the interplay between EED, HIV, and nutritional status, this study aims to provide insights that can inform targeted interventions to optimize nutritional outcomes in HIV infected children. This study evaluated the levels of alpha-1-antitrypsin, calprotectin and myeloperoxidase in frozen fecal samples from 61 HIV infected (mean age 9.16 ±3.08 years) and 31 HIV uninfected (6.65 ±3.41 years) children in Malawi. Anthropometric measurements and clinical data were collected. The height-for-age z-score (-1.66 vs -1.27, p = 0.040) and BMI-for-age z-score (-0.36 vs 0.01, p = 0.037) were lower in HIV infected children. Enzyme-linked immunosorbent assays were used to measure biomarker concentrations. Statistical tests were applied to compare biomarker levels based on HIV status and anthropometric parameters. Myeloperoxidase, alpha-1-antitrypsin, and calprotectin concentrations did not differ between HIV infected and HIV uninfected children of different age groups. In HIV infected children from 5-15 years, there is no difference in biomarker concentration between the stunted and non-stunted groups. Our study found a higher prevalence of stunting in HIV infected children compared to uninfected children, but no significant differences in biomarker concentrations. This suggests no causal relationship between enteropathy and stunting in HIV infected children. These results contribute to the understanding of growth impairment in HIV infected children and emphasize the need for further research, particularly a longitudinal, biopsy-controlled study.

Childhood mortality remains high in low-resource settings, where environmental enteric dysfunction (EED) is prevalent. Peripheral blood bacterial lipopolysaccharides (LPS) are potential biomarkers of intestinal microbial translocation and inflammation; however, the effects of LPS translocation on mortality in this context remains unexplored. We investigate the association between plasma LPS and mortality among 638 acutely ill hospitalised children and compare them to 251 well community peers in a nested case-cohort (NCC) conducted between November 2016 and January 2019 across 9 sites in 6 countries in sub-Saharan Africa and South Asia. Higher levels of plasma LPS and inflammatory biomarkers (fecal calprotectin, plasma myeloperoxidase, and CD14) are associated with elevated 90-day mortality, and those associations are independent of wasting status. Non-survivors with high plasma LPS exhibit elevated gram-negative enteric microbiota, increased fecal biomarkers of EED, systemic inflammatory proteins, and differentially expressed proteins linked to the Insulin-like growth factor (IGF) nutritional axis, Interleukin-1 and collagen regeneration. Cellular interaction network models deconvoluted from a single-cell transcriptomic dataset enable an exploratory investigation of systemic immune responses and epithelial-immune cells crosstalk active in pathways leading to mortality. This knowledge can guide the identification of potential therapeutic signaling pathways in settings with high EED and malnutrition. Childhood mortality is a global health problem. Plasma lipopolysaccharide levels, inflammatory stool biomarkers and proteomics were used in a nested case-cohort in sub-Saharan Africa and South Asia to predict mortality and decode immune mechanisms.

Background Diarrhoeal diseases are common among children in low- and middle-income countries and are major causes of morbidity and mortality. Cryptosporidium and Giardia are considered to be the main parasitic causes of diarrhoea in children. The aim of the present study was to determine the prevalence and associated factors of Cryptosporidium and Giardia infection in children under five years of age presenting at two health centres (Ndirande and Limbe) in Blantyre, Malawi. Methods This cross-sectional study was performed from February to July 2019 and included 972 children under 5 years of age with diarrhoea. Stool samples were immediately tested after collection at enrolment with a rapid diagnostic test for Cryptosporidium and Giardia infection. Descriptive statistics were used to assess the prevalence of these protozoan parasitic infections, and differences in the basic demographic and anthroponotic variables (between children with diarrhoea and parasite infection, being either Cryptosporidium and Giardia or both versus children with diarrhoea but no RDT confirmed parasite infection) were assessed. Their association with Cryptosporidium and Giardia infection was analysed using simple logistic regressions. Results Of the children recruited, 88 (9.1%) tested positive for Cryptosporidium and 184 (18.9%) for Giardia . Children with only a Giardia infection or a coinfection (of both parasites) were significantly older (mean age 24–26 months) compared to children with only a Cryptosporidium infection (mean age 13 months) or no parasitic infection (mean age 14 months). No significant differences were found with respect to gender, body temperature, stunting or wasting between the different groups of children with moderate to severe diarrhoea. Children attending the Ndirande health centre had almost two times higher odds of testing positive for both infections than those attending Limbe health centre. Conclusion Cryptosporidium and Giardia infections are highly prevalent in children < 5 years with moderate to severe diarrhoea attending the Limbe and Ndirande health centres in Blantyre, Malawi.

IntroductionChildhood cancer presents significant challenges in low- and middle-income countries (LMICs), as survival rates remain substantially low. Supportive care, including nutritional support and infection prevention plus management, is crucial in improving outcomes of childhood cancer patients. To develop evidence-based interventions improving supportive care and survival, insight is needed into local prevalences of malnutrition, colonisation and infections, their association with clinical outcomes and the attitude of parents or legal guardians towards nutritional care and infection prevention. The overall aim of this prospective cohort study is to identify modifiable nutritional and infection-related determinants of clinical outcomes at 6 months in children with cancer (1–15 years of age) treated with curative intent at the Paediatric Oncology ward of the Shoe4Africa Children’s Hospital at the Moi Teaching and Referral Hospital in Eldoret, Kenya.Methods and analysisWe will conduct a prospective cohort study on 150 children aged 1–15 years who are newly diagnosed with cancer and treated with curative intent. During 6 months of follow-up, we will collect clinical data, perform nutritional assessments and monitor pathogen exposure, colonisation and infections. Parents or legal guardians will receive one questionnaire to assess attitudes towards supportive care. Six-month mortality is the primary outcome. Other outcomes include the prevalence and characteristics of malnutrition, rectal colonisation with bacterial and fungal pathogens, infections and neutropenic fever episodes. Statistical analyses will include descriptive statistics, chi-square tests, logistic regression and thematic analysis.Ethics and disseminationThe Institutional Research and Ethics Committee has approved the study protocol (FAN: 0004674, protocol version 1.0). Informed consent from parents or legal guardians and assent from children ≥12 years will be obtained. Findings will be disseminated through peer-reviewed publications, presentations at academic conferences and engagement with local and national policymakers and stakeholders. Data from this study could guide the development of locally informed, evidence-based supportive care interventions, with the ultimate goal to improve overall survival for children with cancer in LMICs.

HIV infection affects up to 30% of children presenting with severe acute malnutrition (SAM) in Africa and is associated with increased mortality. Children with SAM are treated similarly regardless of HIV status, although mechanisms of nutritional recovery in HIV and/or SAM are not well understood. We performed a secondary analysis of a clinical trial and plasma proteomics data among children with complicated SAM in Kenya and Malawi. Compared to children with SAM without HIV (n = 113), HIV-infected children (n = 54) had evidence (false discovery rate (FDR) corrected p < 0.05) of metabolic stress, including enriched pathways related to inflammation and lipid metabolism. Moreover, we observed reduced plasma levels of zinc-α-2-glycoprotein, butyrylcholinesterase, and increased levels of complement C2 resembling findings in metabolic syndrome, diabetes and other non-communicable diseases. HIV was also associated (FDR corrected p < 0.05) with higher plasma levels of inflammatory chemokines. Considering evidence of biomarkers of metabolic stress, it is of potential concern that our current treatment strategy for SAM regardless of HIV status involves a high-fat therapeutic diet. The results of this study suggest a need for clinical trials of therapeutic foods that meet the specific metabolic needs of children with HIV and SAM.

Child mortality rates remain unacceptably high in low-resource settings. Cause of death (CoD) is often unknown. Minimally invasive tissue sampling (MITS)-using biopsy needles to obtain post-mortem samples-for histopathological and microbiologic investigation is increasingly being promoted to improve child and adult CoD attribution. \"MITS in Malawi\" is a sub-study of the Childhood Acute Illness & Nutrition (CHAIN) Network, which aims to identify biological and socioeconomic mortality risk factors among young children hospitalized for acute illness or undernutrition. MITS in Malawi employs standard MITS and a novel post-mortem endoscopic intestinal sampling approach to better understand CoD among children with acute illness and/or malnutrition who die during hospitalization. To understand factors that may impact MITS acceptability and inform introduction of the procedure to ascertain CoD among children with acute illness or malnutrition who die during hospitalization in Malawi. We conducted eight focus group discussions with key hospital staff and community members (religious leaders and parents of children under 5) to explore attitudes towards MITS and inform consent processes prior to commencing the MITS in Malawi study. We used thematic content analysis drawing on a conceptual framework developed from emergent themes and MITS acceptability literature. Feelings of power over decision-making within the hospital and household, trust in health systems, and open and respectful health worker communication with parents were important dimensions of MITS acceptability. Other facilitating factors included the potential for MITS to add CoD information to aid sense-making of death and contribute to medical knowledge and new interventions. Potential barriers to acceptability included fears of organ and blood harvesting, disfigurement to the body, and disruption to transportation and burial plans. Social relationships and power dynamics within healthcare systems and households are a critical component of MITS acceptability, especially given the sensitivity of death and autopsy.