Abstract
Introduction Childhood illness and hospitalisation result in both direct and indirect costs to families before, during and after admission. We aimed to estimate the catastrophic expenditure during hospitalisation for children with acute illness.
Methods This was a prespecified cross-sectional substudy nested within two prospective studies. Participants were recruited and interviewed from three rural and three urban hospitals in Kenya and Uganda. A costing questionnaire was administered to the caregivers of 731 children hospitalised for acute illness to evaluate direct and indirect costs incurred by caregivers and families. Costs incurred were compared for families with children both with and without complicated severe malnutrition (CSM). Catastrophic out-of-pocket expenditure exceeding 10% and 25% of monthly income was assessed.
Results The median (IQR) total cost during hospitalisation per child was US$47 (US$24–US$84), with higher costs for children with CSM, especially during hospitalisation (US$56 (US$26–US$99) vs US$36 (US$20–US$65); p<0.001). During hospitalisation, bed charges followed by food were the main cost drivers. Caregivers reported losing a median of 7 (4–11) days of productive time during a child’s hospitalisation with a mean loss of income of US$10 (SD US$25.6, median US$0 (US$0–US$10)). 92% and 74% of households experienced catastrophic expenditure at thresholds of 10% and 25% of monthly income, respectively. Caregivers reported borrowing, selling property and withdrawing other children from school to cope with costs.
Conclusions Despite intentions of free healthcare services for under 5, families of acutely ill children very commonly faced catastrophic expenditure, especially for children with CSM. Interventions aimed at supporting financial protection, reducing additional healthcare costs, and lowering health service charges may help prevent catastrophic expenditures.
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. We argue that current public health programmes
do not fully acknowledge this spectrum of risk or respond accordingly. As a result, opportunities to improve the care,
survival, and development of children in resource-poor settings are overlooked. Children at high risk of mortality are
underidentified and commonly treated using guidelines that do not differentiate care according to the magnitude or
drivers of those risks. Children at low risk of mortality are often provided with more intensive care than needed,
disproportionately using limited health-care resources with minimal or no benefits. Declines in newborn, infant, and
child mortality rates globally are slowing, and further reductions are likely to be incrementally more difficult to
achieve once simple, high impact interventions have been universally implemented. Currently, 63 countries have
rates of neonatal mortality that are off track to meet the Sustainable Development Goal 2030 target
of 12 deaths per 1000 livebirths or less, and 54 countries have rates of mortality in children younger than 5 years that
are off track to meet the target of 25 deaths per 1000 livebirths or less. If these targets are to be met, a change of
approach is needed to address infant and child mortality and for health-care systems to more efficiently address
residual mortality.
Abstract
Addressing the hurdles and opportunities associated with omics research in low- and middle-income countries may inform strategies for its effective execution, and thus increase our ability to tackle health challenges that transcend geographical boundaries.
Abstract
Background Children admitted to hospital with complicated severe malnutrition (CSM) have high mortality despite compliance with standard WHO management guidelines. Limited data suggests a relationship between intestinal dysfunction and poor prognosis in CSM, but this has not been explicitly studied. This study aimed to evaluate the role of intestinal disturbances in CSM mortality.
Abstract
Background
The intestine of children with severe malnutrition (SM) shows structural and functional changes that are linked to increased infection and mortality. SM dysregulates the tryptophan-kynurenine pathway, which may impact
processes such as SIRT1- and mTORC1-mediated autophagy and mitochondrial homeostasis. Using a mouse and
organoid model of SM, we studied the repercussions of these dysregulations on malnutrition enteropathy and the protective capacity of maintaining autophagy activity and mitochondrial health.
Abstract
Severe malnutrition accounts for half-a-million deaths annually in children under the age of five. Despite improved WHO guidelines, inpatient mortality remains high and is associated with metabolic dysfunction. Previous studies suggest a correlation between hepatic metabolic dysfunction and impaired autophagy. We aimed to determine the role of mTORC1 inhibition in a murine model of malnutrition-induced hepatic dysfunction. Wild type weanling C57/B6 mice were fed a 18 or 1% protein diet for two weeks. A third low-protein group received daily rapamycin injections, an mTORC1 inhibitor. Hepatic metabolic function was assessed by histology, immunofluorescence, gene expression, metabolomics and protein levels. Low protein-fed mice manifested characteristics of severe malnutrition, including weight loss, hypoalbuminemia, hypoglycemia, hepatic steatosis and cholestasis. Low protein-fed mice had fewer mitochondria and showed signs of impaired mitochondrial function. Rapamycin prevented hepatic steatosis, restored ATP levels and fasted plasma glucose levels compared to untreated mice. This correlated with increased content of LC3-II, and decreased content mitochondrial damage marker, PINK1. We demonstrate that hepatic steatosis and disturbed mitochondrial function in a murine model of severe malnutrition can be partially prevented through inhibition of mTORC1. These findings suggest that stimulation of autophagy could be a novel approach to improve metabolic function in severely malnourished children.
ABSTRACT
Hospitalized children with severe malnutrition face high mortality rates and often suffer from hepatic and intestinal dysfunction, with negative impacts on their survival. New treatments cannot be developed without
understanding the underlying pathophysiology. We have established and characterized translational organoid
models of severe malnutrition of the liver and the intestine. In these models, amino acid starvation recapitulates
the expected organ-specific functional changes (e.g., hepatic steatosis, barrier dysfunction) accompanied by
reduced mitochondrial and peroxisomal proteins, and altered intestinal tight junction proteins. Resupplementation of amino acids or pharmacological interventions with rapamycin or fenofibrate lead to partial recovery. Restoration of protein levels aligned with signs of improved peroxisomal function in both organoids, and increased mitochondrial proteins and tight junction protein claudin-3 in intestinal organoids. We
present two organoid models as novel tools to gain mechanistic insights and to act as a testing platform for
potential treatments for intestinal and hepatic dysfunction in severe malnutrition.
Abstract
Mortality in children with severe malnutrition is strongly related to signs of metabolic dysfunction, such as hypoglycemia. Lower circulating tryptophan levels in children with severe malnutrition suggest a possible disturbance in the tryptophan-nicotinamide adenine dinucleotide (TRP-NAD+) pathway and subsequently in NAD+ dependent metabolism regulator sirtuin1 (SIRT1). Here we show that severe malnutrition in weanling mice, induced by 2-weeks of low protein diet feeding from weaning, leads to an impaired TRP-NAD+ pathway with decreased NAD+ levels and affects hepatic mitochondrial turnover and function. We demonstrate that stimulating the TRP-NAD+ pathway with NAD+ precursors improves hepatic mitochondrial and overall metabolic function through SIRT1 modulation. Activating SIRT1 is sufficient to induce improvement in metabolic functions. Our findings indicate that modulating the TRP-NAD+ pathway can improve liver metabolic function in a mouse model of severe malnutrition. These results could lead to the development of new interventions for children with severe malnutrition.
