An Adjuvanted A(H5N1) Subvirion Vaccine Elicits Virus-Specific Antibody Response and Improves Protection Against Lethal Influenza Viral Challenge in Mouse Model of Protein Energy Malnutrition.

Background: Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including influenza infection, but no studies have addressed the potential influences of PEM on the immunogenicity and protective efficacy of avian influenza A(H5N1) vaccine. Methods: We investigated the role of PEM on vaccine-mediated protection after a lethal challenge with recombinant A(H5N1) virus using isocaloric diets providing either adequate protein (AP; 18% protein) or very low protein (VLP; 2% protein) in an established murine model of influenza vaccination. Results: We demonstrated that mice maintained on a VLP diet succumb to lethal challenge at greater rates than mice maintained on an AP diet, despite comparable immunization regimens. Importantly, there was no virus-induced mortality in both VLP and AP groups of mice when either group was immunized with adjuvanted low-dose A(H5N1) subvirion vaccine. Conclusions: Our results suggest that adjuvanted vaccination in populations where PEM is endemic may be one strategy to boost vaccination-promoted immunity and improve outcomes associated with highly pathogenic A(H5N1).

Acute effects of rotavirus and malnutrition on intestinal barrier function in neonatal piglets.

AIM: To investigate the effect of protein-energy malnutrition on intestinal barrier function during rotavirus enteritis in a piglet model. METHODS: Newborn piglets were allotted at day 4 of age to the following treatments: (1) full-strength formula (FSF)/noninfected; (2) FSF/rotavirus infected; (3) half-strength formula (HSF)/noninfected; or (4) HSF/rotavirus infected. After one day of adjustment to the feeding rates, pigs were infected with rotavirus and acute effects on growth and diarrhea were monitored for 3 d and jejunal samples were collected for Ussing-chamber analyses. RESULTS: Piglets that were malnourished or infected had lower body weights on days 2 and 3 post-infection (P < 0.05). Three days post-infection, marked diarrhea and weight loss were accompanied by sharp reductions in villus height (59%) and lactase activity (91%) and increased crypt depth (21%) in infected compared with non-infected pigs (P < 0.05). Malnutrition also increased crypt depth (21%) compared to full-fed piglets. Villus:crypt ratio was reduced (67%) with viral infection. There was a trend for reduction in transepithelial electrical resistance with rotavirus infection and malnutrition (P = 0.1). (3)H-mannitol flux was significantly increased (50%; P < 0.001) in rotavirus-infected piglets compared to non-infected piglets, but there was no effect of nutritional status. Furthermore, rotavirus infection reduced localization of the tight junction protein, occludin, in the cell membrane and increased localization in the cytosol. CONCLUSION: Overall, malnutrition had no additive effects to rotavirus infection on intestinal barrier function at day 3 post-infection in a neonatal piglet model.

Testosterone supplementation of megestrol therapy does not enhance lean tissue accrual in men with human immunodeficiency virus-associated weight loss: a randomized, double-blind, placebo-controlled, multicenter trial.

CONTEXT: Reduced energy intake is a primary factor in HIV-associated wasting. Megestrol acetate (MA) stimulates appetite and weight gain. However, much of the weight gained is fat, possibly as a result of MA-induced hypogonadism. OBJECTIVE: The objective of the study was to determine whether coadministration of testosterone with MA could enhance lean body mass (LBM) accrual and evaluate the effects of MA, alone or combined with testosterone, on sexual functioning and the hypothalamic-pituitary-adrenal axis. DESIGN: This was a randomized, double-blind, placebo-controlled, multicenter trial. SETTING: Fourteen AIDS Clinical Trials Units in the United States participated in the study. SUBJECTS: Seventy-nine HIV-positive men with 5% or more weight loss or body mass index less than 20 kg/m2 took part in the study. INTERVENTION: Subjects were randomized to receive MA (800 mg daily) plus testosterone enanthate (200 mg; MA/TE; n = 41) or placebo (MA/PL; n = 38) biweekly for 12 wk. MAIN OUTCOME MEASURES: Weight, body composition (bioelectric impedance analysis), adrenal and gonadal hormones, and sexual functioning (questionnaire) were measured. RESULTS: Both groups experienced robust increases in weight (median 5.3 and 7.3 kg in MA/TE and MA/PL, respectively), LBM (3.3 and 3.3 kg), and fat (3.0 and 3.8 kg). There were no significant differences between groups in the magnitude or composition of weight gain (P = 0.44, 0.90, and 0.11 for weight, LBM, and fat, respectively). Trough testosterone concentrations decreased to a greater extent in MA/PL (-12.3 vs. -6.1 nmol/liter in MA/TE; P = 0.04). Cortisol levels became nearly undetectable in subjects with plasma MA levels greater than 150 ng/ml. Sexual functioning was preserved with MA/TE but worsened in MA/PL. CONCLUSIONS: MA produced robust weight gain. Coadministration of testosterone preserved sexual functioning but did not enhance LBM accrual.

Aspectos funcionais, microbiológicos e morfológicos intestinais em crianças infectadas pelo vírus da imunodeficiência humana / Functional, microbiological and morphological intestinal findings among human immunodeficiency virus infected children

RACIONAL: O trato gastrointestinal é freqüentemente acometido nas crianças infectadas pelo vírus da imunodeficiência humana, com importantes repercussões no seu estado nutricional e sobrevida. A maioria dos estudos relacionados a esse tema foi desenvolvida com adultos, sendo menos investigado o problema nas crianças OBJETIVOS: Estudar aspectos digestivo-absortivos, microbiológicos e morfológicos intestinais em crianças infectadas pelo vírus da imunodeficiência humana MATERIAL E MÉTODOS: Onze crianças infectadas pelo vírus da imunodeficiência humana, menores de 13 anos, pertencentes às categorias clínicas A, B ou C, divididas em dois grupos: cinco pacientes com relato atual ou recente de diarréia e seis pacientes sem diarréia nos 30 dias que antecederam à inclusão no estudo. Investigação proposta: biopsia de intestino delgado e reto para análise morfológica e microbiológica, coprocultura, protoparasitológico de fezes, pesquisa de rotavírus, micobactérias e Cryptosporidium; teste da D-xilose RESULTADOS: Todos os pacientes testados (9/11) apresentavam má absorção da D-xilose (8,4-24,4 mg/dL). Os achados histopatológicos de intestino delgado foram inespecíficos, representados em sua maioria, por enteropatia grau I a II (6/10). Em todos os casos foi constatado aumento do infiltrado celular do córion. As alterações histopatológicas do reto também foram inespecíficas, com presença de aumento do infiltrado celular do córion. A pesquisa de microorganismos enteropatogênicos só foi positiva em dois casos, sendo identificado Mycobacterium avium intracellulare e Cryptosporidium nas fezes CONCLUSÕES: Demonstrou-se alta prevalência (100 por cento) de má absorção intestinal em crianças infectadas pelo vírus da imunodeficiência humana, com ou sem diarréia. Não foi possível estabelecer correlações quanto à presença de agentes enteropatogênicos, má absorção intestinal, alterações morfológicas intestinais e ocorrência ou não de diarréia. Não houve correlação...

BACKGROUD: Gastrointestinal tract disorders are frequent among human immunodeficiency virus infected children, with important repercussions on nutrition and survival. Most studies related to this subject were restricted to adults, being less investigated the problem in the children. AIMS: To study intestinal digestion, absorption, microbiological and morphological findings among human immunodeficiency virus infected children. MATERIAL AND METHODS: Eleven human immunodeficiency virus infected children under 13 years old, belonging to clinical categories A, B or C, separated in two groups: five patients with current or recent episode of diarrhea and six patients without diarrhea in the last 30 days preceding entering in study. Investigation proposed: microbiological and morphological analysis of small intestine and rectum biopsy; stool exams for bacterium, parasite, rotavirus, Mycobacterium species and Cryptosporidium; D-xylose test RESULTS: All tested subjects (9/11) had low D-xylose absorption (8,4 _ 24,4 mg d/L). Small intestinal mucosa histology findings were nonspecific, represented, in majority, of grade I/II enteropathy (6/10). Increased cellular infiltration of the chorion was observed in all specimens. Rectum histology alterations were also nonspecific, with chorion increased cellular infiltration. Mycobacterim avium intracellulare and Cryptosporidium were the solely microorganisms founded, both in stool CONCLUSIONS: Our study demonstrated high prevalence (100 percent) of intestinal malabsorption among human immunodeficiency virus infected children, despite the occurrence or not of diarrhea. It was not possible to establish relationships between the presence of microorganisms, intestinal malabsorption, intestinal morphologic findings and the occurrence or not of diarrhea. There was no correlation between D-xylose and intensity of villous atrophy.

[Functional, microbiological and morphological intestinal findings among human immunodeficiency virus infected children]. / Aspectos funcionais, microbiológicos e morfológicos intestinais em crianças infectadas pelo vírus da imunodeficiência humana.

BACKGROUND: [corrected] Gastrointestinal tract disorders are frequent among human immunodeficiency virus infected children, with important repercussions on nutrition and survival. Most studies related to this subject were restricted to adults, being less investigated the problem in the children. AIMS: To study intestinal digestion, absorption, microbiological and morphological findings among human immunodeficiency virus infected children. MATERIAL AND METHODS: Eleven human immunodeficiency virus infected children under 13 years old, belonging to clinical categories A, B or C, separated in two groups: five patients with current or recent episode of diarrhea and six patients without diarrhea in the last 30 days preceding entering in study. Investigation proposed: microbiological and morphological analysis of small intestine and rectum biopsy; stool exams for bacterium, parasite, rotavirus, Mycobacterium species and Cryptosporidium; D-xylose test RESULTS: All tested subjects (9/11) had low D-xylose absorption (8,4 _ 24,4 mg d/L). Small intestinal mucosa histology findings were nonspecific, represented, in majority, of grade I/II enteropathy (6/10). Increased cellular infiltration of the chorion was observed in all specimens. Rectum histology alterations were also nonspecific, with chorion increased cellular infiltration. Mycobacterim avium intracellulare and Cryptosporidium were the solely microorganisms founded, both in stool CONCLUSIONS: Our study demonstrated high prevalence (100%) of intestinal malabsorption among human immunodeficiency virus infected children, despite the occurrence or not of diarrhea. It was not possible to establish relationships between the presence of microorganisms, intestinal malabsorption, intestinal morphologic findings and the occurrence or not of diarrhea. There was no correlation between D-xylose and intensity of villous atrophy.

Evaluation of the WHO clinical case definition for pediatric HIV infection in Bloemfontein, South Africa.

The WHO clinical case definition for pediatric HIV infection has been designed to be used in countries where diagnostic laboratory resources are limited. We evaluated the WHO case definition to determine whether it is a useful instrument to discriminate between HIV-positive and HIV-negative children. In addition, clinical features not included in this case definition were recorded. We recorded clinical data from 300 consecutively admitted children in a state hospital in Bloemfontein, South Africa, and tested these children for HIV infection. A total of 222 children were included in the study; 69 children (31.1 per cent) were HIV positive. The sensitivity of the WHO case definition in this study was 14.5 per cent, the specificity was 98.6 per cent. Apart from weight loss and generalized dermatitis, the signs of the WHO case definition were significantly more often seen in HIV-positive than in HIV-negative children. Of the clinical signs not included in the WHO case definition, marasmus and hepatosplenomegaly especially occurred more frequently in HIV-positive children. Based on these findings we composed a new case definition consisting of four signs: marasmus, hepatosplenomegaly, oropharyngeal candidiasis, and generalized lymphadenopathy. HIV infection is suspected in a child presenting with at least two of these four signs. The sensitivity of this case definition was 63.2 per cent, the specificity was 96.0 per cent. We conclude that in this study the WHO case definition was not a useful instrument to discriminate between HIV-positive and HIV-negative children, mainly because its sensitivity was strikingly low. The simplified case definition we propose, proved to be more sensitive than the WHO case definition (63.2 vs. 14.5 per cent), whilst its specificity remained high.

Isolated left oculomotor nerve palsy following measles.

A 10-month-old boy was admitted with ptosis on the left eyelid, which rapidly occurred following a disease with rash about 20 days before admission to our hospital. By history, none of the vaccinations had been performed. On physical examination, his vital signs were stable, and he had marasmus. Isolated left oculomotor nerve palsy was diagnosed. Cranial magnetic resonance imaging was normal. Serum IgM antibody to measles virus was positive. Oculomotor nerve palsy markedly improved on the 15th day of follow-up, and complete improvement was noted on the second month of follow-up. To our knowledge, this is the first case of oculomotor nerve palsy following measles.

The impact of the human immunodeficiency virus type 1 on the management of severe malnutrition in Malawi.

A study was undertaken in a central nutritional rehabilitation unit in southern Malawi to assess the impact of HIV infection on clinical presentation and case fatality rate. HIV seroprevalence in 250 severely malnourished children over 1 year of age was 34.4% and overall mortality was 28%. HIV infection was associated significantly more frequently with marasmus (62.2%) than with kwashiorkor (21.7%) (p < 0.0001). Breastfed children presenting with severe malnutrition were significantly more likely to be HIV-seropositive (p < 0.001). Clinical and radiological features were generally not helpful in distinguishing HIV-seropositive from HIV-seronegative children. The case fatality rate was significantly higher for HIV-seropositive children (RR 1.6 [95% CI 1.14-2.24]). The increasing difficulties of managing the growing impact of HIV infection on severely malnourished children in Malawi are discussed in the context of reduced support for nutritional rehabilitation units.

Seroprevalence and coprevalence of HIV and HBsAg in Nigerian children with/without protein energy malnutrition.

In order to assess the seroprevalence and coprevalence of hepatitis-B surface antigen (HBsAg), human immunodeficiency virus-1 and -2 (HIV-1 and -2) antibodies in Nigerian children with/without protein energy malnutrition (PEM), we studied plasma specimens of 206 children with PEM and 200 apparently healthy reference children aged between 1 and 3 years by enzyme-linked immunosorbent assays (ELISA). HIV-seropositive cases were confirmed by immunoblotting (IB). Of the children studied, eight (4%) of the healthy and four (1.9%) of the malnourished (P = 0.22, Fisher's exact test) were positive for HIV-1 antibodies, 40 (20%) of the healthy and 54 (26%) of the malnourished (P = 0.14) were positive for HBsAg, and five (2.5%) of the healthy and four (1.9%) of the malnourished (P = 0.70) were positive for both HIV-1/HBsAg. No case of HIV-2 antibodies was found. While the seroprevalence of HBsAg was higher in the malnourished subjects, the reverse was the case with HIV antibodies. However, all the four HIV-1-positive malnourished children and five of eight of the HIV-1-positive reference children were simultaneously positive for HBsAg. This is the first epidemiological report on the seroprevalence and coprevalence of HIV and HBsAg in apparently healthy and malnourished Nigerian children.

[AIDS and malnutrition in a pediatric semi-rural milieu of Ivory Coast]. / SIDA et malnutrition en milieu pédiatrique semi-rural ivoirien.

To assess the role of human immunodeficiency virus (HIV) infection in malnutrition in African children, clinical examination and serologic tests were performed in 183 undernourished children at the Protestant Hospital of Dabou which is located in a semi-urban area of Cote d'Ivoire. Malnutrition was noted in 18% of children admitted to the Pediatric Department including 70.5% with marasmus. Serologic tests were positive for HIV in 46 of the 183 children, i.e. 25.1%. The type of malnutrition was not significantly different in seropositive children. Breast feeding was more common in the seropositive than seronegative group (59% vs 39%) (p<0.05). Follow-up at the nutrition center was poorer quality and less effective in seropositive than seronegative children. The results of this study demonstrate the important role of HIV infection first as a cause and second as an impediment for management of malnutrition in Black Africa.