Malnutrition and infection: complex mechanisms and global impacts.
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ABSTRACT:
SUBMITTER: Schaible UE
PROVIDER: S-EPMC1858706 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice.
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Project description:Gene regulatory networks exhibit complex, hierarchical features such as global regulation and network motifs. There is much debate about whether the evolutionary origins of such features are the results of adaptation, or the by-products of non-adaptive processes of DNA replication. The lack of availability of gene regulatory networks of ancestor species on evolutionary timescales makes this a particularly difficult problem to resolve. Digital organisms, however, can be used to provide a complete evolutionary record of lineages. We use a biologically realistic evolutionary model that includes gene expression, regulation, metabolism and biosynthesis, to investigate the evolution of complex function in gene regulatory networks. We discover that: (i) network architecture and complexity evolve in response to environmental complexity, (ii) global gene regulation is selected for in complex environments, (iii) complex, inter-connected, hierarchical structures evolve in stages, with energy regulation preceding stress responses, and stress responses preceding growth rate adaptations and (iv) robustness of evolved models to mutations depends on hierarchical level: energy regulation and stress responses tend not to be robust to mutations, whereas growth rate adaptations are more robust and non-lethal when mutated. These results highlight the adaptive and incremental evolution of complex biological networks, and the value and potential of studying realistic in silico evolutionary systems as a way of understanding living systems.
| S-EPMC2924499 | biostudies-literature
Project description:Pollinators contribute around 10% of the economic value of crop production globally, but the contribution of these pollinators to human nutrition is potentially much higher. Crops vary in the degree to which they benefit from pollinators, and many of the most pollinator-dependent crops are also among the richest in micronutrients essential to human health. This study examines regional differences in the pollinator dependence of crop micronutrient content and reveals overlaps between this dependency and the severity of micronutrient deficiency in people around the world. As much as 50% of the production of plant-derived sources of vitamin A requires pollination throughout much of Southeast Asia, whereas other essential micronutrients such as iron and folate have lower dependencies, scattered throughout Africa, Asia and Central America. Micronutrient deficiencies are three times as likely to occur in areas of highest pollination dependence for vitamin A and iron, suggesting that disruptions in pollination could have serious implications for the accessibility of micronutrients for public health. These regions of high nutritional vulnerability are understudied in the pollination literature, and should be priority areas for research related to ecosystem services and human well-being.
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| S-EPMC7384798 | biostudies-literature
Project description:BackgroundLow- to middle-income countries (LMICs) are believed to be characterized by the coexistence of underweight and overweight. It has also been posited that such coexistence is appearing among the low socioeconomic status (SES) groups.MethodsWe conducted a cross-sectional analysis of nationally representative samples of 451,321 women aged 20-49 years drawn from 57 Demographic and Health Surveys conducted between 1994 and 2008. Body Mass Index (BMI in kg/m²), was used to define underweight and overweight following conventional cut-points. Covariates included age, household wealth, education, and residence. We estimated multinomial multilevel models to assess the extent to which underweight (BMI<18.5 kg/m²) and overweight (BM I≥ 25.0 kg/m²) correlate at the country-level, and at the neighborhood-level within each country.ResultsIn age-adjusted models, there was a strong negative correlation between likelihood of being underweight and overweight at country- (r = -0.79, p<0.001), and at the neighborhood-level within countries (r = -0.51, P<0.001). Negative correlations ranging from -0.11 to -0.90 were observed in 46 of the 57 countries at the neighborhood-level and 29/57 were statistically significant (p ≤ 0.05). Similar negative correlations were observed in analyses restricted to low SES groups. Finally, the negative correlations across countries, and within-countries, appeared to be stable over time in a sub-set of 36 countries.ConclusionThe explicitly negative correlations between prevalence of underweight and overweight at the country-level and at neighborhood-level suggest that the hypothesized coexistence of underweight and overweight has not yet occurred in a substantial manner in a majority of LMICs.
| S-EPMC3182195 | biostudies-literature
Project description:Dietary protein deficiency results in diminished capacity of the pancreas to secrete enzymes needed for macronutrient digestion. Previous work has suggested that modulation of the mammalian target of rapamycin (mTOR) pathway by the hormone cholecystokinin (CCK) plays an important role in normal digestive enzyme synthesis after feeding. The purpose of this study was to elucidate the role of mTOR in protein deficiency-induced pancreatic dysfunction.Wild-type and CCK-null mice were fed protein-deficient chow for 4 days and then allowed to recover on control chow in the presence or absence of the mTOR inhibitor rapamycin.The size and secretory capacity of the pancreas rapidly decreased after feeding protein-deficient chow. Refeeding protein-replete chow reversed these changes in both wild-type and CCK-null mice. Changes in the size of the pancreas were paralleled by changes in the content and secretion of digestive enzymes, as well as the phosphorylation of downstream targets of mTOR. Administration of the mTOR inhibitor rapamycin decreased regrowth of the pancreas but did not affect digestive enzyme content or secretory capacity.These studies demonstrate that dietary protein modulates pancreatic growth, but not digestive enzyme synthesis, via CCK-independent activation of the mTOR pathway.
| S-EPMC2739082 | biostudies-literature
Project description:Human noroviruses are the primary cause of severe childhood diarrhea in the United States, and they are of particular clinical importance in pediatric populations in the developing world. A major contributing factor to the general increased severity of infectious diseases in these regions is malnutrition-nutritional status shapes host immune responses and the composition of the host intestinal microbiota, both of which can influence the outcome of pathogenic infections. In terms of enteric norovirus infections, mucosal immunity and intestinal microbes are likely to contribute to the infection outcome in substantial ways. We probed these interactions using a murine model of malnutrition and murine norovirus infection. Our results reveal that malnutrition is associated with more severe norovirus infections as defined by weight loss, impaired control of norovirus infections, reduced antiviral antibody responses, loss of protective immunity, and enhanced viral evolution. Moreover, the microbiota is dramatically altered by malnutrition. Interestingly, murine norovirus infection also causes changes in the host microbial composition within the intestine but only in healthy mice. In fact, the infection-associated microbiota resembles the malnutrition-associated microbiota. Collectively, these findings represent an extensive characterization of a new malnutrition model of norovirus infection that will ultimately facilitate elucidation of the nutritionally regulated host parameters that predispose to more severe infections and impaired memory immune responses. In a broad sense, this model may provide insight into the reduced efficacy of oral vaccines in malnourished hosts and the potential for malnourished individuals to act as reservoirs of emergent virus strains. IMPORTANCE Malnourished children in developing countries are susceptible to more severe infections than their healthy counterparts, in particular enteric infections that cause diarrhea. In order to probe the effects of malnutrition on an enteric infection in a well-controlled system devoid of other environmental and genetic variability, we studied norovirus infection in a mouse model. We have revealed that malnourished mice develop more severe norovirus infections and they fail to mount effective memory immunity to a secondary challenge. This is of particular importance because malnourished children generally mount less effective immune responses to oral vaccines, and we can now use our new model system to probe the immunological basis of this impairment. We have also determined that noroviruses evolve more readily in the face of malnutrition. Finally, both norovirus infection and malnutrition independently alter the composition of the intestinal microbiota in substantial and overlapping ways.
| S-EPMC3958801 | biostudies-literature
Project description:BACKGROUND:Scaling up improved management of severe acute malnutrition has been identified as the nutrition intervention with the largest potential to reduce child mortality, but lack of operational capacity at all levels of the health system constrains scale-up. We therefore developed an interactive malnutrition eLearning course that is accessible at scale to build capacity of the health sector workforce to manage severely malnourished children according to the guidelines of the World Health Organization. OBJECTIVE:The aim of this study was to test whether the malnutrition eLearning course improves knowledge and skills of in-service and preservice health professionals in managing children with severe acute malnutrition and enables them to apply the gained knowledge and skills in patient care. METHODS:This 2-year prospective, longitudinal, cross-country, interrupted time-series study took place in Ghana, Guatemala, El Salvador, and Colombia between January 2015 and February 2017. A subset of 354 in-service health personnel from 12 hospitals and 2 Ministries of Health, 703 preservice trainees from 9 academic institutions, and 204 online users participated. Knowledge gained after training and retention over time was measured through pre- and postassessments comprising questions pertaining to screening, diagnosis, pathophysiology and treatment, and prevention of malnutrition. Comprehension, application, and integration of knowledge were tested. Changes in perception, confidence, and clinical practice were assessed through questionnaires and interviews. RESULTS:Before the course, awareness of the World Health Organization guidelines was 36.73% (389/1059) overall, and 26.3% (94/358) among in-service professionals. The mean score gain in knowledge after access to the course in 606 participants who had pre- and postassessment data was 11.8 (95% CI 10.8-12.9; P<.001)-a relative increase of 41.5%. The proportion of participants who achieved a score above the pass mark posttraining was 58.7% (356/606), compared with 18.2% (110/606) in pretraining. Of the in-service professionals, 85.9% (128/149) reported applying their knowledge by changing their clinical practice in screening, assessment, diagnosis, and management. This group demonstrated significantly increased retained knowledge 6 months after training (mean difference [SD] from preassessment of 12.1 [11.8]), retaining 65.8% (12.1/18.4) of gained knowledge from the training. Changes in the management of malnutrition were reported by trained participants, and institutional, operational, and policy changes were also found. CONCLUSIONS:The malnutrition eLearning course improved knowledge, understanding, and skills of health professionals in the diagnosis and management of children with severe acute malnutrition, and changes in clinical practice and confidence were reported following the completion of the course.
| S-EPMC6231886 | biostudies-other
Project description:BackgroundMalnourished children are at increased risk for death due to diarrhea. Our goal was to determine the contribution of specific enteric infections to malnutrition-associated diarrhea and to determine the role of enteric infections in the development of malnutrition.MethodsChildren from an urban slum in Bangladesh were followed for the first year of life by every-other-day home visits. Enteropathogens were identified in diarrheal and monthly surveillance stools; intestinal barrier function was measured by serum endocab antibodies; and nutritional status was measured by anthropometry.ResultsDiarrhea occurred 4.69 ± 0.19 times per child per year, with the most common infections caused by enteric protozoa (amebiasis, cryptosporidiosis, and giardiasis), rotavirus, astrovirus, and enterotoxigenic Escherichia coli (ETEC). Malnutrition was present in 16.3% of children at birth and 42.4% at 12 months of age. Children malnourished at birth had increased Entamoeba histolytica, Cryptosporidium, and ETEC infections and more severe diarrhea. Children who became malnourished by 12 months of age were more likely to have prolonged diarrhea, intestinal barrier dysfunction, a mother without education, and low family expenditure.ConclusionsProspective observation of infants in an urban slum demonstrated that diarrheal diseases were associated with the development of malnutrition that was in turn linked to intestinal barrier disruption and that diarrhea was more severe in already malnourished children. The enteric protozoa were unexpectedly important causes of diarrhea in this setting. This study demonstrates the complex interrelationship of malnutrition and diarrhea in infants in low-income settings and points to the potential for infectious disease interventions in the prevention and treatment of malnutrition.
| S-EPMC3245731 | biostudies-literature