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.

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.

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.

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.

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.

A possible central mechanism in autism spectrum disorders, part 1.

The autism spectrum disorders (ASD) are a group of related neurodevelopmental disorders that have been increasing in incidence since the 1980s. Despite a considerable amount of data being collected from cases, a central mechanism has not been offered. A careful review of ASD cases discloses a number of events that adhere to an immunoexcitotoxic mechanism. This mechanism explains the link between excessive vaccination, use of aluminum and ethylmercury as vaccine adjuvants, food allergies, gut dysbiosis, and abnormal formation of the developing brain. It has now been shown that chronic microglial activation is present in autistic brains from age 5 years to age 44 years. A considerable amount of evidence, both experimental and clinical, indicates that repeated microglial activation can initiate priming of the microglia and that subsequent stimulation can produce an exaggerated microglial response that can be prolonged. It is also known that one phenotypic form of microglia activation can result in an outpouring of neurotoxic levels of the excitotoxins, glutamate and quinolinic acid. Studies have shown that careful control of brain glutamate levels is essential to brain pathway development and that excesses can result in arrest of neural migration, as well as dendritic and synaptic loss. It has also been shown that certain cytokines, such as TNF-alpha, can, via its receptor, interact with glutamate receptors to enhance the neurotoxic reaction. To describe this interaction I have coined the term immunoexcitotoxicity, which is described in this article.

Effects of zinc supplementation as adjunct therapy on the systemic immune responses in shigellosis.

BACKGROUND: Zinc is lost during diarrheal diseases, and zinc deficiency induces intestinal morphology-altering inflammatory responses that zinc supplementation can correct. OBJECTIVE: We assessed the in vivo effect of zinc supplementation on systemic and mucosal responses in mildly to moderately malnourished (defined as <-1 but >-2 and <-2 but >-3 weight-for-height z scores, respectively, based on the National Center for Health Statistics growth reference) children with shigellosis. DESIGN: A double-blind placebo-controlled trial was conducted in Shigella flexneri-infected children aged 12-59 mo. Daily for 14 d, elemental zinc (20 mg) and multivitamins (vitamins A and D, thiamine, riboflavin, and nicotinamide) plus calcium were given at twice the US recommended dietary allowance to the zinc group (n=28), and multivitamins plus calcium were given to the control group (n=28). All subjects received standard antibiotic therapy. RESULTS: There was no significant interaction between zinc supplementation and time, but zinc supplementation showed a significant effect on serum zinc concentrations. With a >or=4-fold increase in serum shigellacidal antibody titers from baseline used as the cutoff, the proportion of children with shigellacidal antibody response was greater in the zinc group than in the control group (P<0.03). There was a significant (P=0.02) treatment x time interaction for the proportions of circulating CD20+ and CD20+CD38+ cells, which were higher on day 7 in the zinc group than in the control group (P<0.007). No effect was seen on histopathologic features or the expression of innate and inflammatory mediators in the rectum. CONCLUSION: Adjunct therapy with zinc during acute shigellosis significantly improved seroconversion to shigellacidal antibody response and increased the proportions of circulating B lymphocytes and plasma cells.

Effect of zinc supplementation on immune and inflammatory responses in pediatric patients with shigellosis.

BACKGROUND: Several studies showed benefits of long-term zinc supplementation on the incidence, severity, and duration of diarrhea and on the incidence of respiratory infections. Prolonged zinc supplementation also improves cell-mediated immunity in severely malnourished children. OBJECTIVE: We studied the effect of short-term zinc supplementation on intrinsic and specific immune and inflammatory responses in moderately malnourished children with acute shigellosis. DESIGN: A randomized, double-blind, placebo-controlled trial was conducted in Shigella-infected children aged 12-59 mo. Elemental zinc (20 mg) and a multivitamin containing vitamins A and D, thiamine, riboflavin, nicotinamide, and calcium at twice the recommended dietary allowance were given daily for 2 wk to the zinc group (n = 28), whereas the multivitamin alone was given to the control group (n = 28). Standard antibiotic therapy was given to all patients. RESULTS: Serum zinc concentrations increased in both groups during convalescence; however, zinc supplementation showed a significant effect. The lymphocyte proliferation response in the zinc group increased relative to that in the control group (P = 0.002), but no significant effects were seen on concentrations of cytokines (interleukin 2 and interferon gamma) released from mitogen-stimulated mononuclear cells or on concentrations of cytokines (interleukin 2, interferon gamma, and interleukin 1beta) in feces. Among the antigen [lipopolysaccharide and invasion plasmid-encoded antigen (Ipa)]-specific antibodies, plasma Ipa-specific immunoglobulin G responses at day 30 were significantly higher in the zinc group than in the control group. However, the 2 groups did not differ significantly in the other antigen-specific responses in plasma and stool. CONCLUSION: A 14-d course of zinc supplementation during acute shigellosis increases the lymphocyte proliferation response and the Ipa-specific immunoglobulin G response.