Genetic Diversity of Norovirus Infections, Coinfections, and Undernutrition in Children From Brazilian Semiarid Region.

BACKGROUND AND OBJECTIVE: Norovirus (NoV) infections are known to have high-morbidity and mortality rates and are a major health problem globally. The impact of NoV on child development is, however, poorly understood. We evaluated the distribution of NoV genotypes in children from a low-income Brazilian semiarid region, in relation with their clinical symptoms, nutritional status, and co-pathogens. METHODS: The test population included children aged 2 to 36 months from 6 cities of the Brazilian semiarid region. Fecal samples were collected from each child, along with the information regarding their socioeconomic/clinical conditions using a standardized questionnaire. Detection and quantification of NoV were performed by reverse-transcription quantitative polymerase chain reaction, followed by molecular and phylogenetic analyses. RESULTS: The NoV detection rate was 45.2%. Presence of NoV was associated with lower z scores for weight-for-age (P = 0.03), weight-for-height (P = 0.03), and body mass index-for-age (P = 0.03). NoV infection was associated with more frequent respiratory illnesses (P < 0.01). GII.P7 (polymerase) and GII.3 (capsid) were the most frequent NoV genotypes. Analysis of the open reading frame (ORF)1-2 junction identified recombinant NoV strains in 80% of the sequenced samples. Enteroaggregative Escherichia coli coinfection was the major predictor for diarrhea in NoV-positive samples (P < 0.02). Moreover, Shigella spp was also associated with NoV-positive diagnosis (P = 0.02). CONCLUSIONS: This study highlights the genetic variability of NoV and, associated co-infections and undernutrition in infants from low-income Brazilian semiarid region.

Association between enteropathogens and malnutrition in children aged 6-23 mo in Bangladesh: a case-control study.

Background: Early exposure to enteropathogens has been associated with malnutrition in children in low-resource settings. However, the contribution of individual enteropathogens remains poorly defined. Molecular diagnostics offer an increase in sensitivity for detecting enteropathogens but have not been comprehensively applied to studies of malnutrition.Objective: We sought to identify enteropathogens associated with malnutrition in Bangladesh.Design: Malnourished children [weight-for-age z score (WAZ) <-2] aged 6-23 mo in Dhaka, Bangladesh, and identified by active community surveillance were enrolled as cases, and normal-weight children (WAZ >-1) of the same age and from the same community were enrolled as controls. Stools were collected at enrollment and, for cases, after a 5-mo nutritional intervention. Enrollment and follow-up stools were tested by quantitative polymerase chain reaction for 32 enteropathogens with the use of a custom-developed TaqMan Array Card.Results: Enteropathogen testing was performed on 486 cases and 442 controls upon enrollment and 365 cases at follow-up. At enrollment, the detection of enteroaggregative Escherichia coli (OR: 1.39; 95% CI: 1.05, 1.83), Campylobacter spp. (OR: 1.46; 95% CI: 1.11, 1.91), heat-labile enterotoxin-producing E. coli (OR: 1.55; 95% CI: 1.04, 2.33), Shigella/enteroinvasive E. coli (OR: 1.65; 95% CI: 1.10, 2.46), norovirus genogroup I (OR: 1.66; 95% CI: 1.23, 2.25), and Giardia (OR: 1.73; 95% CI: 1.20, 2.49) were associated with malnourished cases, and the total burden of these pathogens remained associated with malnutrition after adjusting for sociodemographic factors. The number of these pathogens at follow-up was negatively associated with the change in WAZ during the intervention (-0.10 change in WAZ per pathogen detected; 95% CI: -0.14, -0.06), whereas the number at enrollment was positively associated with the change in WAZ (0.05 change in WAZ per pathogen detected; 95% CI: 0.00, 0.10).Conclusions: A subset of enteropathogens was associated with malnutrition in this setting. Broad interventions designed to reduce the burden of infection with these pathogens are needed. This trial was registered at clinicaltrials.gov as NCT02441426.

Effects of HIV infection on the metabolic and hormonal status of children with severe acute malnutrition.

BACKGROUND: HIV infection occurs in 30% of children with severe acute malnutrition in sub-Saharan Africa. Effects of HIV on the pathophysiology and recovery from malnutrition are poorly understood. METHODS: We conducted a prospective cohort study of 75 severely malnourished Ugandan children. HIV status/CD4 counts were assessed at baseline; auxologic data and blood samples were obtained at admission and after 14 days of inpatient treatment. We utilized metabolomic profiling to characterize effects of HIV infection on metabolic status and subsequent responses to nutritional therapy. FINDINGS: At admission, patients (mean age 16.3 mo) had growth failure (mean W/H z-score -4.27 in non-edematous patients) that improved with formula feeding (mean increase 1.00). 24% (18/75) were HIV-infected. Nine children died within the first 14 days of hospitalization; mortality was higher for HIV-infected patients (33% v. 5%, OR = 8.83). HIV-infected and HIV-negative children presented with elevated NEFA, ketones, and even-numbered acylcarnitines and reductions in albumin and amino acids. Leptin, adiponectin, insulin, and IGF-1 levels were low while growth hormone, cortisol, and ghrelin levels were high. At baseline, HIV-infected patients had higher triglycerides, ketones, and even-chain acylcarnitines and lower leptin and adiponectin levels than HIV-negative patients. Leptin levels rose in all patients following nutritional intervention, but adiponectin levels remained depressed in HIV-infected children. Baseline hypoleptinemia and hypoadiponectinemia were associated with increased mortality. CONCLUSIONS: Our findings suggest a critical interplay between HIV infection and adipose tissue storage and function in the adaptation to malnutrition. Hypoleptinemia and hypoadiponectinemia may contribute to high mortality rates among malnourished, HIV-infected children.

Abnormalities in body composition and nutritional status in HIV-infected children and adolescents on antiretroviral therapy.

This cross-sectional study aimed to compare growth, nutritional status and body composition outcomes between a group of 94 HIV-infected children and adolescents on antiretroviral therapy (ART) and 364 healthy controls, and to evaluate their association with clinical and lifestyle variables within the HIV-infected group. When compared with the control group, HIV patients had higher risk of stunting (odds ratio [OR] 5.33, 95% confidence interval [CI]: 2.83-10.04) and thinness (OR 4.7, 95% CI: 2.44-9.06), higher waist-to-hip ratios (medians 0.89 versus 0.82 for boys and 0.90 versus 0.77 for girls, P < 0.001), and lower prevalence of overweight or obesity (OR 0.33, 95% CI: 0.14-0.78). Protease inhibitor usage was associated with thinness (OR 3.51, 95% CI 1.07-11.44) and lipoatrophy (OR 3.5, 95% CI 1.37-8.95). HIV-infected children on ART showed significant nutritional status and body composition abnormalities, consistent with the severity of vertical HIV infection and the consequences of prolonged ART.

The influence of nutritional status on the response to HAART in HIV-infected children in South Africa.

BACKGROUND: While the impact of HAART on growth in children is well established, the influence of prior nutritional status on the response to HAART is not well known. METHODS: A retrospective study was conducted on 120 children in South Africa. Patients were divided into 3 groups (normal, moderately underweight, and severely underweight) based on weight-for-age z-scores (WAZ). Age, weight, height, CD4 cell percentage, and viral load were recorded at initiation of HAART and after 24 months of therapy. Data were analyzed using t-tests, chi tests, and one-way ANOVA. RESULTS: At baseline, 58% of children were normal weight, 18% moderately underweight, and 23% severely underweight. After 24 months of HAART, WAZ improved significantly in moderately and severely underweight patient groups compared with the normal group. Height-for-age z-scores (HAZ) increased in all 3 groups with severely underweight children gaining more height than normal weight counterparts. Weight-for-height z-scores (WHZ) normalized in the severely underweight group. Mean CD4 cell percentages increased significantly in all 3 groups while viral loads decreased significantly in all groups with no differences among the groups at the end of 24 months of therapy. Of the entire cohort, 75% achieved undetectable HIV RNA viral loads. CONCLUSIONS: Underlying malnutrition does not adversely affect growth, immunologic or virologic response to HAART in HIV-infected children. Underweight children exhibit an equally robust response to treatment as their well-nourished peers.

Hospitalization and mortality among primarily nonbreastfed children during a large outbreak of diarrhea and malnutrition in Botswana, 2006.

BACKGROUND: In 2006, a pediatric diarrhea outbreak occurred in Botswana, coinciding with heavy rains. Surveillance recorded a 3 times increase in cases and a 25 fold increase in deaths between January and March. Botswana has high HIV prevalence among pregnant women (33.4% in 2005), and an estimated 35% of all infants under the age of 6 months are not breastfed. METHODS: We followed all children <5 years old with diarrhea in the country's second largest referral hospital at the peak of the outbreak by chart review, interviewed mothers, and conducted laboratory testing for HIV and enteric pathogens. RESULTS: Of 153 hospitalized children with diarrhea, 97% were <2 years old; 88% of these were not breastfeeding. HIV was diagnosed in 18% of children and 64% of mothers. Cryptosporidium and enteropathogenic Escherichia coli were common; many children had multiple pathogens. Severe acute malnutrition (kwashiorkor or marasmus) developed in 38 (25%) patients, and 33 (22%) died. Kwashiorkor increased risk for death (relative risk 2.0; P = 0.05); only one breastfeeding child died. Many children who died had been undersupplied with formula. CONCLUSIONS: Most of the severe morbidity and mortality in this outbreak occurred in children who were HIV negative and not breastfed. Feeding and nutritional factors were the most important determinants of severe illness and death. Breastfeeding is critical to infant survival in the developing world, and support for breastfeeding among HIV-negative women, and HIV-positive women who cannot formula feed safely, may prevent further high-mortality outbreaks.

Nutritional status of children with chronic hepatitis B in a population with low socioeconomic status.

OBJECTIVE: Chronic infections and liver diseases may lead to malnutrition. However, growth failure is rarely reported in chronic hepatitis B. We aimed to establish the nutritional status of children with chronic hepatitis B and the relation between anthropometric data and laboratory findings in a population with low socioeconomic status. METHODS: Anthropometrical and laboratory findings were noted from the hospital records. Cases with and without malnutrition were compared with regard to sex, age, histological activity (HAI) scores, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, protein, albumin, and hepatitis B virus (HBV) DNA levels. RESULTS: Eighty children, of which 36 (45%) were girls, with a mean age of 11.5+/-3.2 years were enrolled in the study. Malnutrition was found in 39 (49%). Acute malnutrition (24 out of 39, 61.5%) was the most common form. There was no difference of age or sex between children with and without malnutrition. Age of diagnosis was higher and duration of follow-up was shorter in cases with malnutrition (P = 0.051 and P = 0.016, respectively). In children with malnutrition, aspartate aminotransferase levels were significantly higher but other laboratory results were not different. Malnutrition rate was not different between groups that did and did not receive treatment or that did and did not respond to treatment. Anthropometrical data and malnutrition rate was similar in children with high and low HAI scores. CONCLUSION: As features suggesting severe liver disease like high alanine aminotransferase values, HAI scores, or HBV DNA levels were not different in children with and without malnutrition, it may be proposed that chronic HBV infection does not have an effect on nutritional status.

Mortality and associated factors after initiation of pediatric antiretroviral treatment in the Democratic Republic of the Congo.

OBJECTIVE: We aimed to describe factors associated with mortality among children receiving antiretroviral treatment (ART) at a pediatric hospital in Kinshasa, Democratic Republic of the Congo. RESULTS: Two hundred ninety-nine children, <18 years old, were followed for a median of 77 weeks (interquartile range: 61-103) post-ART initiation. Survival probability was 89.6% [95% confidence interval (CI): 85.5-92.6%] at 12 months; 24 of 31 deaths (77.4%) occurred within 2 months of ART initiation. Predictors of mortality in bivariate analysis were >/=2 opportunistic infections before ART initiation, severe immunosuppression as defined by age-specific CD4 count or percentage criteria, hemoglobin <9 g/dL, oral candidiasis, and severe malnutrition. In multivariate analysis, weight for age z-score [hazard ratio (HR): 0.39; 95% CI: 0.27-0.61; P < 0.001] and oral candidiasis (HR: 5.86; 95% CI: 2.34-14.65; P = 0.0002) were independent predictors of mortality. Suspected septic shock was the most common cause of death (n = 12/31, 38.7%). CONCLUSIONS: Children receiving ART in this resource-poor setting were at the highest risk of dying in the first 2 months of ART, particularly when they presented with malnutrition or oral candidiasis. Optimal timing of ART initiation during nutritional rehabilitation should be determined. Promotion of early care seeking, strengthened health care, and prevention services are important to further improve outcome of pediatric ART in resource-poor settings.

Home-based therapy with ready-to-use therapeutic food is of benefit to malnourished, HIV-infected Malawian children.

AIM: To determine if home-based nutritional therapy will benefit a significant fraction of malnourished, HIV-infected Malawian children, and to determine if ready-to-use therapeutic food (RUTF) is more effective in home-based nutritional therapy than traditional foods. METHODS: 93 HIV-positive children >1 y old discharged from the nutrition unit in Blantyre, Malawi were systematically allocated to one of three dietary regimens: RUTF, RUTF supplement or blended maize/soy flour. RUTF and maize/soy flour provided 730 kJ x kg(-1) x d(-1), while the RUTF supplement provided a fixed amount of energy, 2100 kJ/d. These children did not receive antiretroviral chemotherapy. Children were followed fortnightly. Children completed the study when they reached 100% weight-for-height, relapsed or died. Outcomes were compared using regression modeling to account for differences in the severity of malnutrition between the dietary groups. RESULTS: 52/93 (56%) of all children reached 100% weight-for-height. Regression modeling found that the children receiving RUTF gained weight more rapidly and were more likely to reach 100% weight-for-height than the other two dietary groups (p < 0.05). CONCLUSION: More than half of malnourished, HIV-infected children not receiving antiretroviral chemotherapy benefit from home-based nutritional rehabilitation. Home-based therapy RUTF is associated with more rapid weight gain and a higher likelihood of reaching 100% weight-for-height.

The role of nutrition in pediatric HIV/AIDS: a review of micronutrient research.

It is becoming increasingly evident that nutrition is not only an important component of health but also that levels of specific nutrients can affect disease expression. This is particularly apparent in the realm of HIV disease. Despite this knowledge, research in this area, especially pertaining to the pediatric population, has been limited. This report presents a narrative review and critique of the work that has been conducted in the area of micronutrients including descriptive, correlational, and intervention studies. Gaps in knowledge, recommendations for future research, and nursing implications are highlighted. Current information suggests a role for micronutrients in the treatment of HIV disease, and further research will help develop these adjunct therapies that can affect the overall outcomes and quality of life of these patients.

Burden and cost of inpatient care for HIV-positive paediatric patients--status in the Cape Town metropole during the second week of March 1999. Paediatric HIV Census Group.

OBJECTIVE: To determine the burden of the HIV epidemic on paediatric inpatient facilities in the teaching hospitals of the Cape metropole and tributaries to these hospitals. SETTING: Second- and third-level hospitals. METHOD: During the second week of March 1999 a multicentre collaborative census was performed of all paediatric beds in the teaching hospitals of Cape Town and all facilities draining to and from them. RESULTS: One hundred and six HIV-infected patients were identified from a total of 1,264 beds. Thirty-nine children were in second-level beds or in a long-term residential facility. Fifty-six children were in second-level beds designated for acute care, and occupied 12% of all such beds. Ten children were in beds designated for the care of tuberculosis. Thirty-two (56%) of the acute admissions were for gastro-enteritis, and 13 (23%) were for pneumonia. In 10 children (18% of all admissions) recognised complications of HIV infection were direct causes of admission. For 29 children (35% of all admissions) the current admission was the first; the remainder had had a mean of 2.4 previous admissions. Fourteen children (25%) had received oxygen, and 26 (46%) had received intravenous therapy. Mean lifetime hospitalisation cost per infected child was calculated to be R19,712. The projected cost of a local initiative to reduce mother-to-child transmission is between R8,326 and R10,806 per vertical infection prevented. CONCLUSION: The inpatient burden of HIV-infected children in Cape Town reflects an early stage of the epidemic. Compared with projected lifetime hospitalisation cost for infected children, an intervention to reduce vertical transmission cost would be cost effective.

[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.