OBJECTIVE: To identify the impact of supplemental zinc, vitamin A, and glutamine, alone or in combination, on long-term cognitive outcomes among Brazilian shantytown children with low median height-for-age z-scores. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in children aged three months to nine years old from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for cognitive testing (total of 167 children) were: (1) placebo, n = 25; (2) glutamine, n = 23; (3) zinc, n = 18; (4) vitamin A, n = 19; (5) glutamine+zinc, n = 20; (6) glutamine+vitamin A, n = 21; (7) zinc+vitamin A, n = 23; and (8) glutamine+zinc+vitamin A, n = 18. Neuropsychological tests were administered for the cognitive domains of non-verbal intelligence and abstraction, psychomotor speed, verbal memory and recall ability, and semantic and phonetic verbal fluency. Statistical analyses were performed using SPSS, version 16.0. ClinicalTrials.gov: NCT00133406. RESULTS: Girls receiving a combination of glutamine, zinc, and vitamin A had higher mean age-adjusted verbal learning scores than girls receiving only placebo (9.5 versus 6.4, p = 0.007) and girls receiving zinc+vitamin A (9.5 versus 6.5, p = 0.006). Similar group differences were not found between male study children. CONCLUSIONS: The findings suggest that combination therapy offers a sex-specific advantage on tests of verbal learning, similar to that seen among female patients following traumatic brain injury.

OBJECTIVE: Apolipoprotein E4 may benefit children during early periods of life when the body is challenged by infection and nutritional decline. We examined whether apolipoprotein E4 affects intestinal barrier function, improving short-term growth and long-term cognitive outcomes in Brazilian shantytown children. METHODS: A total of 213 Brazilian shantytown children with below-median height-for-age z-scores (HAZ) received 200,000 IU of retinol (every four months), zinc (40 mg twice weekly), or both for one year, with half of each group receiving glutamine supplementation for 10 days. Height-for-age z-scores, weight-for-age z-scores, weight-forheight z-scores, and lactulose:mannitol ratios were assessed during the initial four months of treatment. An average of four years (range 1.4-6.6) later, the children underwent cognitive testing to evaluate non-verbal intelligence, coding, verbal fluency, verbal learning, and delayed verbal learning. Apolipoprotein E4 carriage was determined by PCR analysis for 144 children. RESULTS: Thirty-seven children were apolipoprotein E4(+), with an allele frequency of 13.9%. Significant associations were found for vitamin A and glutamine with intestinal barrier function. Apolipoprotein E4(+) children receiving glutamine presented significant positive Pearson correlations between the change in height-for-age z-scores over four months and delayed verbal learning, along with correlated changes over the same period in weight-for-age z-scores and weight-for-height z-scores associated with non-verbal intelligence quotients. There was a significant correlation between vitamin A supplementation of apolipoprotein E4(+) children and improved delta lactulose/mannitol. Apolipoprotein E4(-) children, regardless of intervention, exhibited negative Pearson correlations between the change in lactulose-to-mannitol ratio over four months and verbal learning and non-verbal intelligence. CONCLUSIONS: During development, apolipoprotein E4 may function concomitantly with gut-tropic nutrients to benefit immediate nutritional status, which can translate into better long-term cognitive outcomes.

Low antimycobacterial drug concentrations have been observed in tuberculosis (TB) patients under treatment. The lactulose/mannitol urinary excretion test (L/M), normally used to measure intestinal permeability, may be useful to assess drug absorption. The objective of this research was to study intestinal absorptive function and bioavailability of rifampin and isoniazid in TB patients. A cross sectional study was done with 41 patients and 28 healthy controls, using the L/M test. The bioavailabilities of rifampin (R) and isoniazid (H) were evaluated in 18 patients receiving full doses. Urinary excretion of mannitol and lactulose, measured by HPLC, was significantly lower in TB patients. The serum concentrations of the drugs were below the expected range for R (8-24 mcg/mL) or H (3-6 mcg/mL) in 16/18 patients. Analyzing the drugs individually, 12/18 patients had low serum concentrations of R, 13/18 for H and 8/18 for both drugs. We suggest that there is a decrease in the functional absorptive area of the intestine in TB patients, which would explain the reduced serum concentrations of antituberculosis drugs. There is a need for new approaches to improve drug bioavailability in TB patients.

OBJETIVOS: Estudar os aspectos epidemiológicos e clínicos da leishmaniose visceral americana em crianças hospitalizadas do Ceará. MÉTODOS: Estudo retrospectivo e observacional de crianças com leishmaniose visceral americana admitidas no Hospital Infantil Albert Sabin, em Fortaleza. Os prontuários foram revistos sistematicamente. Os critérios de inclusão foram crianças com esfregaços positivos para Leishmania em aspirado de medula óssea ou de baço, ou teste de imunoensaio positivo para Leishmania sp. RESULTADOS: Entre janeiro de 1995 e dezembro de 2002, foram identificados 450 pacientes, perfazendo 9 a 27% dos casos de leishmaniose visceral americana notificados no Ceará no período, com picos de admissão em 1995 e 2000. A idade média foi de 4,4 anos (12% < 1 ano e 65% < 5 anos de idade). A relação masculino:feminino foi de 1,1 em geral e de 1,48 em < 5 anos (p = 0,04). Os pacientes urbanos aumentaram regularmente no período de 8 anos (<FONT FACE=Symbol>X²</FONT>, p = 0,01). As principais queixas foram febre (90%), palidez (90%) e aumento abdominal (75%). A cura clínica foi constatada por ausência de febre, regressão da hepato-esplenomegalia e da pancitopenia. A letalidade geral foi de 9,2%, e 21,2% em lactentes < 1 ano. Desnutrição, edema, sangramento, icterícia e infecção intercorrentes foram fatores relacionados com maior letalidade. CONCLUSÕES: Casos hospitalizados de leishmaniose visceral americana apresentaram picos a cada 5 anos e afetaram crianças urbanas < 5 anos. A mortalidade esteve associada à baixa idade, sinais de gravidade e infecção concomitante.

OBJECTIVE: To study epidemiological and clinical aspects of American visceral leishmaniasis in hospitalized children in Ceará, Brazil. METHODS: A retrospective and observational study was carried out with children suffering from American visceral leishmaniasis admitted to Hospital Infantil Albert Sabin in Fortaleza. Medical records were reviewed consistently. Inclusion criteria were children with amastigote-positive smears in bone marrow or in splenic aspirates, or a positive Leishmania sp immunofluorescence assay. RESULTS: From January 1995 to December 2002, 450 children with American visceral leishmaniasis were identified, accounting for 9 to 27% of all reported cases in Ceará in that period, with peak hospitalization rates in 1995 and 2000. The mean age was 4.4 years (12% < 1 year and 65% < 5 years of age). The overall male: female ratio was 1.1 and 1.48 in children > 5 year (p = 0.04). Urban patients infected by American visceral leishmaniasis increased steadily over an 8-year period (chi2 p = 0.01). The main clinical complaints on admission were fever (96%), pallor (90%) and abdominal swelling (75%). Clinical cure was defined as the absence of fever, regression of splenic and hepatic enlargement and of pancytopenia. Overall mortality was 9.2% and 21.2% in patients younger than one year. Malnutrition, edema, bleeding, jaundice, and concomitant infections were related to higher mortality. CONCLUSIONS: Cases of American visceral leishmaniasis spiked with a 5-year interval, and affected most under-five urban children. Mortality was related to low age, signs of severe disease and concomitant infection.

BACKGROUND: Acute respiratory infection (ARI), diarrheal disease (DD) and infective dermatitis (ID) are important causes of morbidity in children under five, in Northeast Brazil. Objectives: (a) to evaluate the morbidity of ARI, DD and ID; and (b) to determine their association with cellular immunity in poor urban children from Fortaleza, Brazil. MATERIALS AND METHODS: A prospective cohort study. At enrollment, multipuncture skin-tests (Multitest CMI) were performed and interpreted according to standard procedures. Children were followed for infectious diseases by weekly home visits. RESULTS: Seventy-one children aged 6 to 21 months were recruited in an ongoing cohort of newborns. A mean of 39 (6 to 63) home visits per child were made, which detected 184.5 symptomatic days per child-year of observation. ARI was present in 62% of the days of illness (6,378 out of 10,221), DD in 23% (2,296 days), ID in 6% (597) and other infections in 4% (373). Episodes per child-year were: 10 for ARI, 7 for DD and 1 for ID. Twelve (17%) out of 71 children were anergic. The incidences of ARI, DD and ID were similar in responsive versus anergic children. The mean duration of ID in anergy was 8.5 days, while it was 4.3 in the responsive group (P=0.007). Anergy was independent of age, sex and nutritional status. CONCLUSIONS: A high incidence of ARI and DD was found in these poor urban children. Skin-test responsiveness was not related to malnutrition, nor to morbidity due to ARI and DD, however anergic children had a longer duration of infective dermatitis.

Advanced HIV infection is frequently complicated by diarrhea, disruption of bowel structure and function, and malnutrition. Resulting malabsorption of or pharmacokinetic changes in antiretroviral agents might lead to subtherapeutic drug dosing and treatment failure in individual patients, and could require dose adjustment and/or dietary supplements during periods of diarrheal illness. We determined the plasma levels of antiretroviral medications in patients that had already been started on medication by their physicians in an urban infectious diseases hospital in northeast Brazil. We also obtained blood samples from patients hospitalized for diarrhea or AIDS-associated wasting, and we found reduced stavudine and didanosine levels in comparison with outpatients without diarrhea or wasting who had been treated at the same hospital clinic. There was a predominance of the protozoal pathogens Cryptosporidium and Isospora belli, typical opportunistic pathogens of AIDS-infected humans, in the stool samples of inpatients with diarrhea. We conclude that severe diarrhea and wasting in this population is associated with both protozoal pathogens and subtherapeutic levels of antiretroviral medications.

Os autores apresentam os resultados do estudo epidemiológico de um caso autóctone da fase aguda da doença de Chagas na ilha do Mosqueiro, Estado do Pará, aproximadamente 75km da capital, Belém. 0 caso já havia sido objeto de uma publicação anterior. Agora são apresentadas informações epidemiológicas. Nas proximidades da casa do paciente foram capturados em duas palmeiras de Inajá ('Maximilian regi ay e em uma de Mucajá (Acrocomia sclerocarpia) 114 triatomíneos: Rhodnius pictipes, R. robustus, Panstrongylus lignarius, P. geniculatus e Microtriatoma trinidadensis, com tripanossomas em 31 deles. Na casa do paciente foram encontrados exemplares de Rhodnius pictipes, infectados com formas metacíclicas do Trypanosoma cruzi. Em 14 marsupiais, capturados na localidade, haviam 3 infectados com organismos semelhantes ao T. cruzi. A eletroforese dos isoenzimas nos tripanossomas isolados do paciente, de R. pictipes e de Didelphis marsupialis os classificou como zimodema 1. Os autores concluem que a doença de Chagas do paciente teve origem silvestre.

The authors present the results of an epidemiological study relating to a case of acute Chagas' disease acquired in the island of Mosqueiro, State of Para, approximately 75 km from the capital Belem. The patient has been the object of a previous publication but now epidemiological information is reported. Near the house of the patient in two Inaja palm trees (Maximilian regia) and one Mucaja palm (Acrocomia sclerocarpia) 114 triatomine bugs were captured of the following species: Rhodnius pictipes, R. robustus, Panstrongylus lignarius, P. geniculatus and Microtriatoma trinidadensis. Trypanosomes were found in 31 bugs. In the house of the patient specimens of R. pictipes were captured infected with metacyclic forms óf Trypanosoma cruzi. In 14 marsupials captured in the locality three had infections with cruzi like trypanosomes. Enzyme electrophoresis of the trypanosomes isolated from the patient, R. pictipes and Didelphis marsupialis were classified as zymodeme 1. The authors conclude that the patients Chagas' disease was of sylvatic origin.