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.

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.

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.

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.

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.

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.

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.

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.

Increased production of tumor necrosis factor-alpha in whole blood cultures from children with primary malnutrition.

Because low tumor necrosis factor-alpha (TNF-alpha) production has been reported in malnourished children, in contrast with high production of TNF-alpha in experimental protein-energy malnutrition, we reevaluated the production of TNF-alpha in whole blood cultures from children with primary malnutrition free from infection, and in healthy sex- and age-matched controls. Mononuclear cells in blood diluted 1:5 in endotoxin-free medium released TNF-alpha for 24 h. Spontaneously released TNF-alpha levels (mean +/- SEM), as measured by enzyme immunoassay in the supernatants of unstimulated 24-h cultures, were 10,941 +/- 2,591 pg/ml in children with malnutrition (N = 11) and 533 +/- 267 pg/ml in controls (N = 18) (P < 0.0001). TNF-alpha production was increased by stimulation with lipopolysaccharide (LPS), with maximal production of 67,341 +/- 16,580 pg/ml TNF-alpha in malnourished children and 25,198 +/- 2,493 pg/ml in controls (P = 0.002). In control subjects, LPS dose-dependently induced TNF-alpha production, with maximal responses obtained at 2000 ng/ml. In contrast, malnourished patients produced significantly more TNF-alpha with 0.02-200 ng/ml LPS, responded maximally at a 10-fold lower LPS concentration (200 ng/ml), and presented high-dose inhibition at 2000 ng/ml. TNF-alpha production a) was significantly influenced by LPS concentration in control subjects, but not in malnourished children, who responded strongly to very low LPS concentrations, and b) presented a significant, negative correlation (r = -0.703, P = 0.023) between spontaneous release and the LPS concentration that elicited maximal responses in malnourished patients. These findings indicate that malnourished children are not deficient in TNF-alpha production, and suggest that their cells are primed for increased TNF-alpha production.

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.

Titers of antibody to common pathogens: relation to food-based interventions in rural Kenyan schoolchildren.

BACKGROUND: Undernutrition is widely perceived to affect the development of an effective immune system. OBJECTIVE: We used a mini-analysis system to quantitate antibody titers and evaluate the sera of 200 Kenyan schoolchildren for antibodies to Helicobacter pylori [isotypes of immunoglobulins A (IgA), G (IgG), and M (IgM)], hepatitis A virus, rotavirus, tetanus toxoid (IgG), and a panel of recombinant malarial antigens (MSP1(19), MSP2, Ag512, MSP4, and MSP5). DESIGN: Children participated in a school-based feeding intervention with meat, milk, or nonanimal-source foods or in a nonintervention control group. Microvolumes (200 mL) of sera were analyzed at baseline and after 1 y. RESULTS: Nearly all children had elevated titers of antibody to H. pylori, hepatitis A virus, rotavirus, and malaria at the outset, despite a high prevalence of apparent biochemical micronutrient deficiencies and stunting, but many had titers of tetanus toxoid IgG antibodies below the protective concentration. Children with low hemoglobin had a greater proportion of elevated H. pylori IgM antibody titers at baseline, which suggests that current infection with H. pylori may be associated with anemia. Compared with the control subjects, only the group eating meat had a significant increase in H. pylori IgM antibodies during the intervention (P = 0.019). No other group comparisons with the control subjects were statistically significant. The additional finding that the sera of some children showed inadequate tetanus-protective antibodies, despite immunization, suggests that the vaccination program was suboptimal. CONCLUSIONS: A large battery of immune assays can be performed on microvolumes of sera. Furthermore, despite evidence of malnutrition, children do develop significant antibody-mediated responses to common pathogens.

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.

Visceral leishmaniasis: a model for infection-induced cachexia.

Parasitic infections and malnutrition coexist in many tropical and subtropical areas. Studies of Leishmania donovani and of experimentally infected Syrian hamsters have provided important insights into the complex interrelationships between malnutrition and this parasitic disease. Malnutrition, which adversely affects cell-mediated immunity, is associated with the development of visceral leishmaniasis (kala-azar) in children living in endemic areas. In turn, L. donovani can cause wasting as well as hepatosplenomegaly, fever, and anemia. Syrian hamsters infected with L. donovani develop a disease that is comparable to that of humans with kala-azar. Weight loss in infected hamsters is associated with splenic macrophage secretion of potentially catabolic cytokines as measured by the D10.G4.1 assay for interleukin-1 and the L929 cytotoxicity assay for tumor necrosis factor/cachectin. Although decreased food intake contributes to wasting in infected hamsters, studies of skeletal muscle function indicate that it is not the sole factor. Leishmania donovani-infected hamsters have also been used to study drugs with the potential to prevent or reverse cachexia.

[Malnutrition and immunodeficiency in children]. / Malnutrition et déficit immunitaire chez l'enfant.

Our knowledge on relationships between nutrition, immunity and infection has much progressed. Malnutrition affects all three defence mechanisms: unspecific immunity, cellular immunity and humoral immunity. Any kind of nutriment is concerned: nitrogen-caloric nutriments, trace elements, vitamins. Restoration and maintenance of a good nutritional status have become imperative in order to stop the vicious cercle of malnutrition-infection in infants and children.

The transformation in vitro of peripheral lymphocytes of malnourished children.

Children with protein energy malnutrition showed high deranged cellular immunity as evidenced by impairment of lymphocyte transformation after stimulation by phytohaemagglutination (PHA). The proliferative response (PR) to PHA measured by estimating incorporation of tritiated thymidine into newly synthesized DNA. In-vitro proliferative response to PHA was used as a marker for studying the functional characteristics of T lymphocytes of children with different categories of malnutrition. PHA response of peripheral blood lymphocytes obtained from different categories of severely malnourished children were significantly low compared to healthy control children (P < 0.01). The results indicate that cell mediated immunity was grossly depressed in severe malnutrition.

Leucocyte migration inhibition factor (L-MIF) in malnourished Nigerian children.

Leucocyte Migration Inhibition Factor (L-MIF) was measured in 41 children with marasmus, 19 with kwashiorkor, 5 with marasmic-kwashiorkor and 35 well-fed healthy children serving as controls. For L-MIF assay, two different antigens (live attenuated measles virus vaccine and diptheria pertussis tetanus (DPT) vaccine were used. Percentage migration indices obtained with the two antigens were significantly higher in the malnourished than in the well-fed healthy sex and age-matched controls (P < 0.01). The total serum protein and albumin concentrations were significantly reduced in the malnourished children compared with the controls (P < 0.01). Mean total leucocyte numbers were not significantly different in marasmic and marasmic-kwashiorkor children compared with the controls (P > 0.21).