Nonsterile immunity to cryptosporidiosis in infants is associated with mucosal IgA against the sporozoite and protection from malnutrition.

We conducted a longitudinal study of cryptosporidiosis from birth to three years of age in an urban slum of Dhaka Bangladesh. Fecal DNA was extracted from monthly surveillance samples and diarrheal stool samples collected from 392 infants from birth to three years. A pan-Cryptosporidium qPCR assay was used to identify sub-clinical and symptomatic cryptosporidiosis. Anthropometric measurements were collected quarterly to assess child nutritional status. 31% (121/392) of children experienced a single and 57% (222/392) multiple infections with Cryptosporidium. Repeat infections had a lower burden of parasites in the stool (Cq slope = -1.85; p<0.0001) and were more likely to be sub-clinical (Chi square test for trend; p = 0.01). Repeat infections were associated with the development of growth faltering (Pearson correlation = -0.18; p = 0.0004). High levels of fecal IgA antibodies against the Cryptosporidium Cp23 sporozoite protein at one year of life were associated with a delay in reinfection and amelioration of growth faltering through three years of life (HAZ IgA high responders -1.323 ± 0.932 versus HAZ -1.731 ± 0.984 p = 0.0001). We concluded that nonsterile immunity to cryptosporidiosis in young children was associated with high levels of mucosal IgA anti-Cp23 and protection from diarrhea and growth faltering. Trial Registration: NCT02764918.

Current Understanding of Innate Immune Cell Dysfunction in Childhood Undernutrition.

Undernutrition affects millions of children in low- and middle-income countries (LMIC) and underlies almost half of all deaths among children under 5 years old. The growth deficits that characterize childhood undernutrition (stunting and wasting) result from simultaneous underlying defects in multiple physiological processes, and current treatment regimens do not completely normalize these pathways. Most deaths among undernourished children are due to infections, indicating that their anti-pathogen immune responses are impaired. Defects in the body's first-line-of-defense against pathogens, the innate immune system, is a plausible yet understudied pathway that could contribute to this increased infection risk. In this review, we discuss the evidence for innate immune cell dysfunction from cohort studies of childhood undernutrition in LMIC, highlighting knowledge gaps in almost all innate immune cell types. We supplement these gaps with insights from relevant experimental models and make recommendations for how human and animal studies could be improved. A better understanding of innate immune function could inform future tractable immune-targeted interventions for childhood undernutrition to reduce mortality and improve long-term health, growth and development.

Modulation of Intestinal Immune and Barrier Functions by Vitamin A: Implications for Current Understanding of Malnutrition and Enteric Infections in Children.

The micronutrient vitamin A refers to a group of compounds with pleiotropic effects on human health. These molecules can modulate biological functions, including development, vision, and regulation of the intestinal barrier. The consequences of vitamin A deficiency and supplementation in children from developing countries have been explored for several years. These children live in an environment that is highly contaminated by enteropathogens, which can, in turn, influence vitamin A status. Vitamin A has been described to modulate gene expression, differentiation and function of diverse immune cells; however, the underlying mechanisms are not fully elucidated. This review aims to summarize the most updated advances on elucidating the vitamin A effects targeting intestinal immune and barrier functions, which may help in further understanding the burdens of malnutrition and enteric infections in children. Specifically, by covering both clinical and in vivo/in vitro data, we describe the effects of vitamin A related to gut immune tolerance/homeostasis, intestinal barrier integrity, and responses to enteropathogens in the context of the environmental enteric dysfunction. Some of the gaps in the literature that require further research are also highlighted.

Use of tuberculin skin test for assessment of immune recovery among previously malnourished children in Ethiopia.

OBJECTIVE: To compare levels of immunity in children recovering from severe acute malnutrition (cases) against those of community controls (controls). RESULTS: At baseline children recovering from severe acute malnutrition had lower, mid upper arm circumference (122 mm for cases and 135 mm for controls; p < 0.001), weight-for-height Z-score (- 1.0 for cases and - 0.5 for controls; p < 0.001), weight-for-age Z-score (- 2.8 for cases and - 1.1 for controls; p < 0.001) and height/length-for-age Z-score (- 3.6 for cases and - 1.4 for controls; p < 0.001), than controls. Age and gender matched community controls. At baseline, prevalence of a positive tuberculin skin test, assessed by cutaneous delayed-type hypersensitivity reaction skin test, was very low in both cases (3/93 = 3.2%) and controls (2/94 = 2.1%) and did not significantly increase at 6 months follow up (6/86 = 7.0% in cases and 3/84 = 3.4% in controls). The incidences of common childhood morbidities, namely fever, diarrhoea and cough, were 1.7-1.8 times higher among cases than controls. In conclusion, these results show that tuberculin skin test does not enable any conclusive statements regarding the immune status of patients following treatment for severe acute malnutrition. The increased incidence of infection in cases compared to controls suggests persistence of lower resistance to infection even after anthropometric recovery is achieved.

Infected malnourished children displayed changes in early activation and lymphocyte subpopulations.

AIM: Malnutrition and infections cause immunological changes in lymphocyte subpopulations and their functionality. We evaluated the activation capacity of lymphocytes and memory cells in 10 well nourished, seven well-nourished infected and eight malnourished infected children before and after treatment. METHODS: All the children were patients in Mexico City and were less than three years of age. The expression of various cluster of differentiation (CD) cells was assessed by flow cytometry: CD45RA (naïve) and CD45RO (memory) antigens on CD4 lymphocytes and CD69 in all lymphocytes. RESULTS: Well-nourished infected children showed a higher percentage of activated T lymphocyte (T cells), CD8+ and CD4+ memory cells during the infectious phase, suggesting that the activation mechanisms were triggered by infection. T cells from malnourished infected children showed a lower percentage of activated and memory cells. The T cell population size returned to baseline during the resolution phase of the infection in well-nourished infected children, but their T, B lymphocyte and natural killer (NK) cell counts remained high. In malnourished infected children, activated NK cells counts were low before and after therapy. CONCLUSION: After therapy, malnourished infected children showed poor NK cell responses during the infection's resolution phase, suggesting a persistent malnutrition-mediated immunological deficiency.

XV Congreso SEINAP. Inmunonutrición / XV Congreso SEINAP. Immunonutrition

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IMMUNE RESPONSE OF SEVERE MALNUTRITION CHILDREN TREATED ACCORDING TO THE PROTOCOL OF THE WORLD HEALTH ORGANIZATION.

The aim of the study was to compare the innate immune system of severely malnourished children admitted to the Instituto de Medicina Integral Professor Fernando Figueira and treated according to the protocol of the World Health Organization (WHO) at admission and discharge. An experimental study was conducted with 20 children under two years of age. Ten of them had severe malnutrition and ten were a control group. The malnourished group consisted of hospitalized infants and it was submitted to WHO's protocol. Children with HIV and re-admitted during the study period were excluded. A blood sample was taken at admission and at discharge. Later, an analysis of blood leukocytes, adherence index, phagocytic capacity, production of free radicals superoxide and nitric oxide was performed. Patients with severe malnutrition at hospital discharge showed improved phagocytic function, release of oxygen radicals and reduction of the number of lymphocytes when compared to the time of admission. When compared to the control group, patients at hospital discharge had lower lymphocyte values and lower production of free radicals. Thus, it can be concluded that the duration of hospitalization was insufficient to restore cell-mediated immunity and microbicide activity.

El objetivo del estudio fue comparar el sistema inmune innato de niños con malnutrición grave ingresados en el Instituto de Medicina Integral Professor Fernando Figueira, tratados de acuerdo con el protocolo de la Organización Mundial de la Salud (OMS), al ingreso y al alta hospitalaria. Se llevó a cabo un estudio experimental con 20 niños menores de dos años de edad, 10 con malnutrición grave y 10 niños del grupo de control. El grupo de malnutridos se compuso de lactantes hospitalizados y sometidos al protocolo de la OMS. Se excluyeron los niños afectados por el HIV y los readmitidos durante el período del estudio. Se recogió una muestra de sangre al ingreso y otra al alta, y posterioriormente se realizó el análisis del perfil leucocitario, y el índice de adherencia, la capacidad fagocítica y la producción de los radicales libres superóxido y óxido nítrico. Los pacientes con malnutrición grave en el alta hospitalaria mostraron mejoría de la función fagocítica, la liberación de radicales oxidantes y la reducción del número de linfocitos en comparación con el ingreso hospitalario. En comparación con el grupo de control, los pacientes en el alta hospitalario presentaron valores más bajos de linfocitos y de producción de radicales libres. Por lo tanto, se puede concluir que el tiempo de hospitalización fue insuficiente para restablecer la inmunidad mediada por células, así como para restaurar la actividad microbicida.

Validity of antibodies in lymphocyte supernatant in diagnosing tuberculosis in severely malnourished children presenting with pneumonia.

BACKGROUND: The diagnosis of tuberculosis (TB) in young children can be challenging, especially in severely malnourished children. There is a critical need for improved diagnostics for children. Thus, we sought to evaluate the performance of a technique that measures antibodies in lymphocyte supernatant (ALS) for the diagnosis of TB in severely malnourished children presenting with suspected pneumonia. METHODS: Children less than 5 years with severe acute malnutrition and radiological features of pneumonia admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh, were enrolled consecutively following informed written consent. In addition to clinical and radiological assessment, samples taken for TB diagnosis included gastric lavage fluid and induced sputum for microbiological confirmation. ALS was measured from venous blood, and results were evaluated in children classified as "confirmed", "non-confirmed TB" or "not TB". RESULTS: Among 224 children who had ALS analysis, 12 (5.4%) children had microbiologically "confirmed TB", a further 41 (18%) had clinically diagnosed "non-confirmed TB" and the remaining 168 (75%) were considered not to have TB. ALS was positive in 89 (40%) and negative in 85 (39%) of children, with a large number (47 or 21%) reported as "borderline". These proportions were similar between the three diagnostic groups. The sensitivity and specificity of ALS when comparing "Confirmed TB" to "Not TB" was only 67% (95% CI: 31-91%) and 51% (95% CI: 42-60%), respectively. CONCLUSIONS AND SIGNIFICANCE: Our data suggest that ALS is not sufficiently accurate to improve the diagnosis of TB in children with severe malnutrition.

Challenges of malnutrition care among HIV-infected children on antiretroviral treatment in Africa.

More than 90% of the estimated 3.2 million children with HIV worldwide, at the end of 2013, were living in sub-Saharan Africa. The management of these children was still difficult in 2014 despite the progress in access to antiretroviral drugs. A great number of HIV-infected children are not diagnosed at 6 weeks and start antiretroviral treatment late, at an advanced stage of HIV disease complicated by other comorbidities such as malnutrition. Malnutrition is a major problem in the sub-Saharan Africa global population; it is an additional burden for HIV-infected children because they do not respond as well as non-infected children to the usual nutritional care. HIV infection and malnutrition interact, creating a vicious circle. It is important to understand the relationship between these 2 conditions and the effect of antiretroviral treatment on this circle to taking them into account for an optimal management of pediatric HIV. An improved monitoring of growth during follow-up and the introduction of a nutritional support among HIV-infected children, especially at antiretroviral treatment initiation, are important factors that could improve response to antiretroviral treatment and optimize the management of pediatric HIV in resource-limited countries.

Immunonutrition: methodology and applications / Inmunonutrición: metodología y aplicaciones

Immunonutrition is an emergent and interdisciplinary subject, since it comprises several aspects related to Nutrition, Immunity, Infection, Inflammation, and Injury or tissue damage, what is known as Nutrition and 4 'Is'. Within these interactions the endocrine, nervous and immune systems are involved, microbiota being a part of the last one. Nowadays, gut microbiota has been shown to play an essential role, not only in the gastrointestinal tract but also into the nervous system, because of its bilateral connection. There are several methods to study Immunonutrition, which allow measuring different immunological biomarkers to provide information about the nutritional status. However, it should be taken into account that there is not a single gold standard parameter to evaluate the cause-effect relationship between nutrition and the immune system. On the contrary, a combination of biomarkers have to be assessed depending on the different nutritional situations. Since Immunonutrition is a multidisciplinary matter as mentioned above, the study on the interactions between nutrition and the immune system has not been exclusively focused as such, but bearing in mind other systems of the organisms as well as a wide range of confounding factors and determinants coming from idiosyncratic features, genes and lifestyle of each individual. Therefore, Immunonutrition allows to study the following research fields: 1) Evaluation of nutritional status in presumably healthy people with risk of malnutrition (children, adolescents, adults, pregnant women, elderly, and sportspeople); 2) Assessment of the evolution and progress of patients with nutrition and immune-related diseases, such as food allergies, eating and metabolic disorders; 3) Evaluation of the effects of nutrients, bioactive compounds and both conventional and functional foods on the immune system; 4) Evaluation of impact of lifestyle determinants on the immune system, such as diet, food behaviour, physical activity, sedentariness, sleep quality and quantity, and as a key factor, stress (AU)

La Inmunonutrición es una materia emergente e interdisciplinar, ya que abarca distintos aspectos relacionados con la Nutrición, la Inmunidad, la Infección, la Inflamación y la Injuria o daño tisular, lo que se ha denominado como la Nutrición y las 4 'Ies'. En estas interacciones se encuentran implicados los sistemas endocrino, nervioso e inmune, formando parte la microbiota de este último. Actualmente la microbiota intestinal tiene un papel fundamental no solo a nivel del tracto gastrointestinal sino que presenta además un eje de conexión bilateral con el sistema nervioso Para el estudio de la Inmunonutrición existen diferentes biomarcadores del sistema inmune que proporcionan información acerca del estado nutricional del individuo. Sin embargo, se debe tener en cuenta que no existe un solo parámetro para evaluar la relación causa-efecto de la nutrición sobre el sistema inmunitario, sino que es un conjunto de biomarcadores a tener en cuenta dependiendo de los distintas situaciones nutricionales. Si bien está claro que se trata de una materia multidisciplinar, no solo se deben focalizar los estudios sobre las interacciones entre la nutrición y el sistema inmune de manera aislada, sino sobre otros sistemas del organismo teniendo en cuenta un gran abanico de factores de confusión y determinantes derivados de las condiciones idiosincrásicas de cada individuo, su genética y su estilo de vida. Por todo ello, la Inmunonutrición permite llevar a cabo una serie de estudios basados fundamentalmente en cuatro líneas de investigación: 1) Evaluación de poblaciones supuestamente sanas pero con riesgo de malnutrición (niños, adolescentes, adultos, gestantes, lactantes, personas mayores y deportistas), 2) Estudio de la evolución de pacientes con enfermedades relacionadas con la nutrición y el sistema inmunitario, 3) Estudio de los efectos de nutrientes, compuestos bioactivos y alimentos convencionales y funcionales sobre el sistema inmunitario; 4) Estudio del impacto del estilo de vida sobre el comportamiento del sistema inmunitario, teniendo como determinantes principales la dieta, el comportamiento alimentario, la actividad física, el sedentarismo, la calidad y cantidad de sueño, y como factor clave, el estrés (AU)

The MAL-ED study: a multinational and multidisciplinary approach to understand the relationship between enteric pathogens, malnutrition, gut physiology, physical growth, cognitive development, and immune responses in infants and children up to 2 years of age in resource-poor environments.

Highly prevalent conditions with multiple and complex underlying etiologies are a challenge to public health. Undernutrition, for example, affects 20% of children in the developing world. The cause and consequence of poor nutrition are multifaceted. Undernutrition has been associated with half of all deaths worldwide in children aged <5 years; in addition, its pernicious long-term effects in early childhood have been associated with cognitive and physical growth deficits across multiple generations and have been thought to suppress immunity to further infections and to reduce the efficacy of childhood vaccines. The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health (MAL-ED) Study, led by the Fogarty International Center of the National Institutes of Health and the Foundation for the National Institutes of Health, has been established at sites in 8 countries with historically high incidence of diarrheal disease and undernutrition. Central to the study is the hypothesis that enteropathogen infection contributes to undernutrition by causing intestinal inflammation and/or by altering intestinal barrier and absorptive function. It is further postulated that this leads to growth faltering and deficits in cognitive development. The effects of repeated enteric infection and undernutrition on the immune response to childhood vaccines is also being examined in the study. MAL-ED uses a prospective longitudinal design that offers a unique opportunity to directly address a complex system of exposures and health outcomes in the community-rather than the relatively rarer circumstances that lead to hospitalization-during the critical period of development of the first 2 years of life. Among the factors being evaluated are enteric infections (with or without diarrhea) and other illness indicators, micronutrient levels, diet, socioeconomic status, gut function, and the environment. MAL-ED aims to describe these factors, their interrelationships, and their overall impact on health outcomes in unprecedented detail, and to make individual, site-specific, and generalized recommendations regarding the nature and timing of possible interventions aimed at improving child health and development in these resource-poor settings.

Global burden of childhood diarrhea and interventions.

PURPOSE OF REVIEW: Diarrhea is a leading cause of morbidity and mortality among children under 5 years in low-income and middle-income countries. Over the past 2 decades under-five mortality has decreased substantially, but reductions have been uneven and unsatisfactory in resource-poor regions. RECENT FINDINGS: There are known interventions which can prevent diarrhea or manage children who suffer from it. Interventions with proven effectiveness at the prevention level include water, sanitation, and hygiene interventions, breastfeeding, complementary feeding, vitamin A and zinc supplementation, and vaccines for diarrhea (rotavirus and cholera). Oral rehydration solution, zinc treatment, continued feeding, and antibiotic treatment for certain strains of diarrhea (cholera, Shigella, and cryptosporidiosis) are effective strategies for treatment of diarrhea. The recent Lancet series using the 'Lives Saved' tool suggested that if these identified interventions were scaled up to a global coverage to at least 80%, and immunizations to at least 90%; almost all deaths due to diarrhea could be averted. SUMMARY: The current childhood mortality burden highlights the need of a focused global diarrhea action plan. The findings suggest that with proper packaging of interventions and delivery platforms, the burden of childhood diarrhea can be reduced to a greater extent. All that is required is greater attention and steps toward right direction.

Effects of malnutrition on children's immunity to bacterial antigens in Northern Senegal.

To evaluate immunity to vaccine-preventable diseases according to nutritional status, a longitudinal study was conducted in Senegalese children ages 1-9 years old. A linear regression analysis predicted that weight for age was positively associated with immunoglobulin G (IgG) response to tetanus toxoid in children born during the rainy season or at the beginning of the dry season. A relationship between village, time of visits, and levels of antibodies to tetanus showed that environmental factors played a role in modulating humoral immunity to tetanus vaccine over time. Moreover, a whole-blood stimulation assay highlighted that the production of interferon-γ (IFN-γ) in response to tetanus toxoid was compromised in stunted children. However, the absence of cytokine modulation in response to Mycobacterium tuberculosis-purified protein derivatives and phytohemagglutinin suggests that the overall ability to produce IFN-γ was preserved in stunted children. Therefore, these results show that nutritional status can specifically alter the efficacy of long-lasting immunity to tetanus.

Role of combined zinc, vitamin A, and fish oil supplementation in childhood tuberculosis.

This objective of this study was to determine benefit of one month combined supplementation (zinc, vitamin A, fish oil) along with anti-tuberculosis drugs (ATD) on increasing serum leptin levels and decreasing tumor necrosis factor-alpha (TNF-alpha) in children with tuberculosis (TB). A quasi experimental study was conducted on 22 children (aged 5-14 years) with a positive acid-fast bacilli (AFB) smear. The children were divided into 2 groups. A history, physical examination, anthropometric measurements, serum leptin levels, TNF-alpha levels, retinol and zinc levels were examined in all subjects before and after treatment. Nutritional supplementation and ATD were given to group I while ATD only were given to group II. The change in leptin, TNF-alpha, retinol and zinc levels were analyzed with the Mann-Whitney test, while a t-test was used to determine changes in body mass index (BMI). Group I had a higher significant increase in serum leptin levels than group II (p=0.034). Group I had a significantly greater decrease in TNF-a levels than group II (p=0.032). No significant differences in retinol or zinc levels were seen between the two, but both groups had an increase after treatment. Both groups had a significant increase in BMI (p=<0.001) post-treatment compared to pre-treatment. Supplementation with zinc, vitamin A and fish oil is associated with a significant increase in leptin levels and a significant decrease in TNF-alpha levels among children treated for TB. No significant benefit was seen in BMI among children receiving supplementation compared to those without it, although ATD resulted in a significant increase in BMI in both groups.

Malnutrition in childhood cancer patients: a review on its prevalence and possible causes.

PURPOSE: To perform a systematic literature review for critical evaluation of prevalence and factors contributing to malnutrition in childhood cancer. METHODS: A systematic search resulting in 46 suitable articles. RESULTS: Due to lack of uniform criteria and adequate studies, the prevalence rates of malnutrition can only be estimated. Based on strengths and weaknesses of included references, prevalence rates are estimated to be 0-10% for leukemia, 20-50% for neuroblastoma, and 0-30% for other malignancies. Whether energy deficiency or inflammation contributed to malnutrition could not be confirmed because the occurrence of energy deficit (low energy intake, increased metabolic rate) or inflammation (related to cachexia) was not convincing. Also, a relationship between these factors and malnutrition was not studied. CONCLUSION: Longitudinal studies are needed to determine which children are at risk of malnutrition, and to investigate the impact of energy deficiency and inflammation on the nutritional status and body composition of childhood cancer patients.

Malnutrition and gastrointestinal and respiratory infections in children: a public health problem.

Infectious disease is the major cause of morbidity and mortality in developing countries, particularly in children. Increasing evidence suggests that protein-calorie malnutrition is the underlying reason for the increased susceptibility to infections observed in these areas. Moreover, certain infectious diseases also cause malnutrition, which can result in a vicious cycle. Malnutrition and bacterial gastrointestinal and respiratory infections represent a serious public health problem. The increased incidence and severity of infections in malnourished children is largely due to the deterioration of immune function; limited production and/or diminished functional capacity of all cellular components of the immune system have been reported in malnutrition. In this review, we analyze the cyclical relationship between malnutrition, immune response dysfunction, increased susceptibility to infectious disease, and metabolic responses that further alter nutritional status. The consequences of malnutrition are diverse and included: increased susceptibility to infection, impaired child development, increased mortality rate and individuals who come to function in suboptimal ways.

Scrofuloderma--a case series from rural India.

Cutaneous tuberculosis is the rarest presentation of all the forms of tuberculosis. Scrofuloderma is a frequent manifestation of cutaneous tuberculosis in Indian scenario. Males are affected one and half times more than females. The most common affected age group showing clinical infection is within the first three decades of life. A series of cases mostly malnourished children attending a tertiary care centre in a rural area of central India is being reported. They have presented with a wide spectrum of clinical features, forcing us to establish the final diagnosis by Mantoux test, fine needle aspiration cytology and histopathological examination. The mainstay of treatment remains medical therapy but the underlying cause for severe immunosuppression needs to be ruled out and treated.

Efeitos da deficiência de cobre, zinco e magnésio sobre o sistema imune de crianças com desnutrição grave: [revisão] / Effects of copper, zinc and magnesium deficiency on the immune system of severely malnourished children: [review]

OBJETIVO: Esclarecer as repercussões da deficiência de cobre, zinco e magnésio sobre o sistema imune de crianças desnutridas graves. FONTES DE DADOS: Foi realizada revisão bibliográfica mediante consulta às bases de dados Pubmed Medline, Lilacs e SciELO, selecionando-se publicações científicas recentes, da última década, e representativas do tema por meio dos descritores: desnutrição infantil, cobre, zinco, magnésio e sistema imune. SÍNTESE DE DADOS: Os micronutrientes são compostos orgânicos essenciais. Além de sua função regulatória, atuam de maneira decisiva na modulação da resposta imune. Sua deficiência pode ocorrer devido à ingestão inadequada ou associada a doenças específicas. Quando associada à desnutrição, a multideficiência de minerais pode acarretar disfunções imunológicas e aumento na suscetibilidade a infecções, afetando gravemente a eficácia de intervenções terapêuticas. Cobre, zinco e magnésio atuam como cofatores de enzimas responsáveis tanto por diversas atividades metabólicas como na resposta imune inata e adquirida, além do papel importante na maturação dos tecidos e células linfoides. Sua deficiência acarreta neutropenia e linfopenia, comprometendo a imunocompetência. CONCLUSÕES: As alterações ocasionadas pelos déficits séricos dos minerais cobre, zinco e magnésio comprometem o funcionamento do sistema imune, levando à imunossupressão. A reposição desses elementos no manejo da desnutrição grave, como preconizada pela Organização Mundial da Saúde, é essencial, uma vez que tais alterações podem ser reversíveis.

OBJECTIVE: To report the effects of the deficiency of copper, zinc and magnesium on the immune system of severely malnourished children. DATA SOURCE: A literature review was performed by consulting the databases Pubmed Medline, Lilacs and SciELO, using the descriptors: child malnutrition, copper, zinc, magnesium and immune system. Representative studies published during the last decade were chosen. DATA SYNTHESIS: Micronutrients are essential organic compounds. Besides their regulatory function, the minerals act on the modulation of the immune response. Their deficiency may be due to inadequate intake or associated with specific diseases. When combined with malnutrition, a multimineral deficiency can cause immune dysfunction and increased susceptibility to infections, altering the effectiveness of therapeutic interventions. Copper, zinc and magnesium act as co-factors of both enzymes responsible for several metabolic activities and associated to the innate and acquired immune response. These minerals also play an important role in the maturation of lymphoid tissues and cells. Their deficiency causes neutropenia and lymphopenia, decreasing the immunocompetence. CONCLUSIONS: Deficits of serum copper, zinc and magnesium affect the function of the immune system, leading to immunosuppression. The replacement of these elements in the management of severe malnutrition, as recommended by the World Health Organization, is essential, since such changes may be reversible.

Progress of enteral feeding practice over time: moving from energy supply to patient- and disease-adapted formulations.

Enteral nutrition comprises the delivery of a liquid formula beyond the esophagus via a feeding tube in a patient with insufficient oral intake, as well as the provision of specialized nutritional formula irrespective of the route of delivery. Pediatric formulae have been designed for different age groups, and for children with certain diseases; examples are special formulations for regurgitating infants, metabolic diseases, cow's milk or multiple food allergies, intestinal, pancreatic, renal, and hepatic insufficiency. Exclusive enteral nutrition is a therapeutic concept to induce remission in children and adolescents with active Crohn's disease. A new area of nutritional research in pediatrics is potential immunonutrition in critically ill children. Formulae are enriched with single components or a combination of key substrates that might play a crucial role during intermediary metabolism in sepsis, inflammation, tissue healing, and growth. For pharmaconutrition, single components are investigated in a scientific stepwise procedure in order to identify effective disease-dedicated nutrition therapy. Any new formula needs to be evaluated, if possible in comparison to a normal diet or the reference formulation to demonstrate its safety and efficacy (equal or superior to standard formula).

Evaluation of dietetic product innovations: the relative role of preclinical and clinical studies.

A variety of systems are used to establish efficacy of food ingredients. Immortal human cell lines have the advantage of rapid throughput and often have the ability to point to mechanisms of action. Transgenic and natural variants of animals (usually rats and mice) have proven to be extremely useful in elucidating effects in vivo, although extrapolation of results to humans has risks. Animal models are also useful in establishing safety and toxic levels of ingredients. Human trials have the most relevance to society. Types of evidence for efficacy rise from improved status level in subjects as a result of eating food (long-chain polyunsaturated fatty acid, levels in erythrocytes), change in surrogate markers as a result of eating food (plasma cholesterol or glutathione peroxidase activity), change in a physiological outcome (such as visual evoked potential acuity or heart rate variability) through to the highest level of evidence, a change in a clinical outcome (improved global development, reduction in infections) established in randomized controlled trials. Ultimately, there is a need for tests of pragmatic interventions that can easily be incorporated into usual dietary practices of the culture in which it is tested.