Enteroaggregative Escherichia coli Subclinical Infection and Coinfections and Impaired Child Growth in the MAL-ED Cohort Study.

OBJECTIVE: We evaluated the impact of subclinical enteroaggregative Escherichia coli (EAEC) infection alone and in combination with other pathogens in the first 6 months of life on child growth. METHODS: Nondiarrheal samples from 1684 children across 8 Multisite Birth Cohort Study, Malnutrition and Enteric Diseases (MAL-ED) sites in Asia, Africa, and Latin America were tested monthly; more than 90% of children were followed-up twice weekly for the first 6 months of life. RESULTS: Children with subclinical EAEC infection did not show altered growth between enrollment and 6 months. Conversely, EAEC coinfection with any other pathogen was negatively associated with delta weight-for-length (P < 0.05) and weight-for-age (P > 0.05) z scores between 0 and 6 months. The presence of 2 or more pathogens without EAEC was not significantly associated with delta weight-for-length and weight-for-age. The most frequent EAEC coinfections included Campylobacter spp, heat-labile toxin-producing enterotoxigenic E coli, Cryptosporidium spp, and atypical enteropathogenic E coli. Myeloperoxidase levels were increased with EAEC coinfection (P < 0.05). EAEC pathogen codetection was associated with lower neopterin levels compared to those of no-pathogen control children (P < 0.05). Mothers of children with EAEC coinfections had lower levels of education, poorer hygiene and sanitation, lower socioeconomic status, and lower breast-feeding rates compared to mothers of children in whom no pathogen was detected (P < 0.05). CONCLUSIONS: These data emphasize the public health importance of subclinical EAEC infection in early infancy in association with other pathogens and the need for improved maternal and child care, hygiene, sanitation, and socioeconomic factors.

Genotyping of Mycobacterium leprae for better understanding of leprosy transmission in Fortaleza, Northeastern Brazil.

Leprosy is endemic in large part of Brazil with 28,761 new patients in 2015, the second largest number worldwide and reaches 9/10.000 in highly endemic regions and 2.7/10.000 in the city of Fortaleza, Ceará, Northeast Brazil. For better understanding of risk factors for leprosy transmission, we conducted an epidemiologic study supplemented by 17 locus VNTR and SNP 1-4 typing of Mycobacterium leprae in skin biopsy samples from new multibacillary (MB) patients diagnosed at a reference center in 2009 and 2010. Among the 1,519 new patients detected during the study period, 998 (65.7%) were MB and we performed DNA extraction and genotyping on 160 skin biopsy samples, resulting in 159 (16%) good multilocus VNTR types. Thirty-eight of these patients also provided VNTR types from M. leprae in nasal swabs. The SNP-Type was obtained for 157 patients and 87% were of type 4. Upon consideration all VNTR markers, 156 different genotypes and three pairs with identical genotypes were observed; no epidemiologic relation could be observed between individuals in these pairs. Considerable variability in differentiating index (DI) was observed between the different markers and the four with highest DI [(AT)15, (TA)18, (AT)17 and (GAA)21] frequently demonstrated differences in copy number when comparing genotypes from both type of samples. Excluding these markers from analysis resulted in 83 genotypes, 20 of which included 96 of the patients (60.3%). These clusters were composed of two (n = 8), three (n = 6), four (n = 1), five (n = 2), six (n = 1), 19 (n = 1) and 23 (n = 23) individuals and suggests that recent transmission is contributing to the maintenance of leprosy in Fortaleza. When comparing epidemiological and clinical variables among patients within clustered or with unique M. leprae genotypes, a positive bacterial index in skin biopsies and knowledge of working with someone with the disease were significantly associated with clustering. A tendency to belong to a cluster was observed with later notification of disease (mean value of 3.4 months) and having disability grade 2. A tendency for lack of clustering was observed for patients who reported to have lived with another leprosy case but this might be due to lack of inclusion of household contacts in the study. Although clusters were spread over the city, kernel analysis revealed that some of the patients belonging to the two major clusters were spatially related to some neighborhoods that report poverty and high disease incidence in children. Finally, inclusion of genotypes from nasal swabs might be warranted. A major limitation of the study is that sample size of 160 patients from a two year period represents only 15% of the new patients and this could have weakened statistical outcomes. This is the first molecular epidemiology study of leprosy in Brazil and although the high clustering level suggests that recent transmission is the major cause of disease in Fortaleza; the existence of two large clusters needs further investigation.

Determinant Variables, Enteric Pathogen Burden, Gut Function and Immune-related Inflammatory Biomarkers Associated With Childhood Malnutrition: A Prospective Case-Control Study in Northeastern Brazil.

Malnutrition results in serious consequences for growth and cognitive development in children. We studied select child and maternal biologic factors, socioeconomic factors, enteric pathogenic burden and gut function biomarkers in 402 children 6-24 months of age in Northeastern Brazil. In this prospective case-control study, not being fed colostrum [odds ratio (OR): 3.29, 95% confidence interval (CI): 1.73-6.26], maternal age ≥18 years (OR: 1.88, 95% CI: 1.10-3.22) and no electric fan (OR: 2.46, 95% CI: 1.22-4.96) or bicycle (OR: 1.80, 95% CI: 1.10-2.95) in the household were positively associated, and higher birth weight (OR: 0.27, 95% CI: 0.19-0.38), larger head circumference (OR: 0.74, 95% CI: 0.66-0.82) and shortness of breath in the last 2 weeks (OR: 0.49, 95% CI: 0.27-0.90) were negatively associated with malnutrition. Subclinical enteric pathogen infections were common, and enteroaggregative Escherichia coli infections were more prevalent in malnourished children (P = 0.045). Biomarkers such as the lactulose-mannitol test, myeloperoxidase, neopterin and calprotectin were highly elevated in both malnourished and nourished children. Nourished children had a better systemic immune response than the malnourished children, as detected by elevated serum amyloid A-1 and soluble cluster of differentiation protein 14 biomarkers (P < 0.001). Serum amyloid A-1 and soluble cluster of differentiation protein 14 were also associated with better nutritional Z scores. Neonatal, maternal and socioeconomic factors were associated with malnutrition in children. There was a substantial subclinical enteric pathogen burden, particularly with enteroaggregative E. coli, in malnourished children.

Prevalence, Risk Behaviors, and Virological Characteristics of Hepatitis B Virus Infection in a Group of Men Who Have Sex with Men in Brazil: Results from a Respondent-Driven Sampling Survey.

BACKGROUND: Men who have sex with men (MSM) are at increased risk of exposure to hepatitis B virus (HBV) compared with the general population. This study aims to assess the epidemiological and virological characteristics of HBV infection in a sample of MSM in Brazil, where data are scarce. METHODS: A cross-sectional study was conducted among MSM in the City of Goiânia, Central Brazil, from March to November 2014, using Respondent-Driven Sampling (RDS). After signing the consent form, participants were interviewed and a blood sample collected. All samples were tested for HBV serological markers and HBV DNA. HBV nucleotide sequence analysis was also performed. RESULTS: A total of 522 MSM were recruited in the study. The prevalence of HBV infection (current or past [presence of anti-HBc marker]) was 15.4% (95% CI: 8.7-25.8) and the rate of HBsAg carriers was 0.6% (95% CI: 0.2-1.6). About 40% (95% CI: 32.3-48.8) of the participants had serological evidence of previous HBV vaccination (reactive for isolated anti-HBs). In addition, 44.3% (95% CI: 36.1-52.9) were seronegative for all HBV markers. Age over 25 years old, receptive anal intercourse, previous sex with women, and history of sexually transmitted infections (STIs) were factors associated with HBV infection. HBV DNA was detected only in HBsAg-positive individuals. HBV isolates were classified into genotype A (subgenotypes A1 and A2), and some mutations were identified throughout the genome. Therefore, occult HBV infection was not observed in the study population. CONCLUSIONS: Public health strategies should be improved for the MSM population in order to prevent HBV and other STIs, as well as to provide appropriate management of patients with active infections.

Intrapatient comparison of Mycobacterium leprae by VNTR analysis in nasal secretions and skin biopsy in a Brazilian leprosy endemic region.

Background: This study compares the strains of genotypes of M. leprae from nasal secretions (NS) and skin biopsy (SB) in the same patient, supplementing conventional epidemiology to gain insight into the infection of leprosy in Fortaleza, Brazil. Methods: The sample consisted of 38 newly diagnosed leprosy patients attending the National Reference Center of Dermatology Dona Libania (CDERM), in Fortaleza, who tested positive for M. leprae by PCR in DNA extracts of nasal secretions. DNA was also extracted from skin biopsy (SB) scrapings of each patient and used for multiplex PCR amplification of M. leprae VNTR loci. The number of repeats at 15 loci were determined by the fragment length analysis method. Results: Locus VNTR genotypes were achieved in 38 NS, and in 38 SB specimens. M. leprae strains differed in their genotypes in paired specimens in all but two of 38 patients. The genotype similarity in the remainder ranged from 53% to 87%. Conclusion: M. leprae 15 VNTR loci genotypes of paired nasal and biopsy skin samples from five patients were identical, while as many as seven loci differed in the 33 other patients. When the NS and biopsy genotypes were pooled and compared, it was found that there was a great variability among different VNTR markers. It is important to investigate other molecular markers suitable for typing genetic variations of the bacilli.

Acute kidney injury after snakebite accident treated in a Brazilian tertiary care centre.

AIM: Acute kidney injury (AKI) is one of the main causes of morbidity and mortality in cases of envenomation by venomous snakes. The present study was carried out to investigate the clinical and laboratory manifestations in accidents with venomous snakes and the risk factors associated with AKI in these accidents. METHODS: A retrospective study was carried out with patients victims of snakebite admitted to a reference centre. AKI was defined according to the RIFLE and AKIN criteria. RESULTS: A total of 276 patients were included, of which 230 (83.7%) were males. AKI was observed in 42 cases (15.2%). The mean genus involved in the accidents was Bothrops (82.2%). Mean age of patients with AKI was higher than in patients without AKI (43 ± 20 vs. 34 ± 21 years, P = 0.015). The time elapsed between the accident and medical care was higher in the AKI group (25 ± 28 vs. 14 ± 16h, P = 0.034), as well as the time elapsed between the accident and the administration of antivenom (30.7 ± 27 vs. 15 ± 16 h, P = 0.01). Haemodialysis was required in 30% of cases and complete renal function recovery was observed in 54.8% of cases at hospital discharge. There were four deaths, none of which had AKI. Factors associated with AKI were haemorrhagic abnormalities (P = 0.036, OR = 6.718, 95% CI: 1.067-25.661) and longer length of hospital stay (P = 0.004, OR = 1.69, 95% CI 1.165-2.088). CONCLUSION: Acute kidney injury is an important complication of snakebite accidents, showing low mortality, but high morbidity, which can lead to partial renal function recovery.

Effects of glutamine alone or in combination with zinc and vitamin A on growth, intestinal barrier function, stress and satiety-related hormones in Brazilian shantytown children.

OBJECTIVE: To determine the impact of supplemental zinc, vitamin A, and glutamine alone or in combination on growth, intestinal barrier function, stress and satiety-related hormones 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 two months to nine years from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for testing (a total of 120 children) were as follows: (1) glutamine alone, n = 38; (2) glutamine plus vitamin A plus zinc, n = 37; and a placebo (zinc plus vitamin A vehicle) plus glycine (isonitrogenous to glutamine) control treatment, n = 38. Leptin, adiponectin, insulin-like growth factor (IGF-1), and plasma levels of cortisol were measured with immune-enzymatic assays; urinary lactulose/mannitol and serum amino acids were measured with high-performance liquid chromatography. ClinicalTrials.gov: NCT00133406. RESULTS: Glutamine treatment significantly improved weight-for-height z-scores compared to the placebo-glycine control treatment. Either glutamine alone or all nutrients combined prevented disruption of the intestinal barrier function, as measured by the percentage of lactulose urinary excretion and the lactulose:mannitol absorption ratio. Plasma leptin was negatively correlated with plasma glutamine (p = 0.002) and arginine (p = 0.001) levels at baseline. After glutamine treatment, leptin was correlated with weight-for-age (WAZ) and weight-for-height z-scores (WHZ) (p≤0.002) at a 4-month follow-up. In addition, glutamine and all combined nutrients (glutamine, vitamin A, and zinc) improved the intestinal barrier function in these children. CONCLUSION: Taken together, these findings reveal the benefits of glutamine alone or in combination with other gut-trophic nutrients in growing children via interactions with leptin.

Effects of glutamine alone or in combination with zinc and vitamin A on growth, intestinal barrier function, stress and satiety-related hormones in Brazilian shantytown children

OBJECTIVE: To determine the impact of supplemental zinc, vitamin A, and glutamine alone or in combination on growth, intestinal barrier function, stress and satiety-related hormones 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 two months to nine years from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for testing (a total of 120 children) were as follows: (1) glutamine alone, n = 38; (2) glutamine plus vitamin A plus zinc, n = 37; and a placebo (zinc plus vitamin A vehicle) plus glycine (isonitrogenous to glutamine) control treatment, n = 38. Leptin, adiponectin, insulin-like growth factor (IGF-1), and plasma levels of cortisol were measured with immune-enzymatic assays; urinary lactulose/mannitol and serum amino acids were measured with high-performance liquid chromatography. ClinicalTrials.gov: NCT00133406. RESULTS: Glutamine treatment significantly improved weight-for-height z-scores compared to the placebo-glycine control treatment. Either glutamine alone or all nutrients combined prevented disruption of the intestinal barrier function, as measured by the percentage of lactulose urinary excretion and the lactulose:mannitol absorption ratio. Plasma leptin was negatively correlated with plasma glutamine (p = 0.002) and arginine (p = 0.001) levels at baseline. After glutamine treatment, leptin was correlated with weight-for-age (WAZ) and weight-for-height z-scores (WHZ) (p≤0.002) at a 4-month follow-up. In addition, glutamine and all combined nutrients (glutamine, vitamin A, and zinc) improved the intestinal barrier function in these children. CONCLUSION: Taken together, these findings reveal the benefits of glutamine alone or in combination ...

Factors associated with thrombocytopenia in severe leptospirosis (Weil's disease).

OBJECTIVE: This study was conducted to investigate factors associated with thrombocytopenia in a large cohort of patients with leptospirosis in an endemic area. METHODS: This retrospective study included 374 consecutive patients with leptospirosis who were admitted to tertiary hospitals in Fortaleza, Brazil. All patients had a diagnosis of severe leptospirosis (Weil's disease). Acute kidney injury was defined according to the RIFLE criteria. Thrombocytopenia was defined as a platelet count <100,000/mm3. RESULTS: A total of 374 patients were included, with a mean age of 36.1 ± 15.5 years, and 83.4% were male. Thrombocytopenia was present at the time of hospital admission in 200 cases (53.5%), and it developed during the hospital stay in 150 cases (40.3%). The patients with thrombocytopenia had higher frequencies of dehydration (53% vs. 35.3%, p=0.001), epistaxis (5.7% vs. 0.8%, p=0.033), hematemesis (13% vs. 4.6%, p=0.006), myalgia (91.5% vs. 84.5%, p=0.038), hematuria (54.8% vs. 37.6%, p=0.011), metabolic acidosis (18% vs. 9.2%, p=0.016) and hypoalbuminemia (17.8% vs. 7.5%, p=0.005). The independent risk factors associated with thrombocytopenia during the hospital stay were lengthy disease (OR: 1.2, p=0.001) and acute kidney injury (OR: 6.6, p=0.004). Mortality was not associated with thrombocytopenia at admission (12.5% vs. 12.6%, p=1.000) or during the hospital stay (12.6% vs. 11.3%, p=0.748). CONCLUSIONS: Thrombocytopenia is a frequent complication in leptospirosis, and this condition was present in more than half of patients at the time of hospital admission. Lengthy disease and acute kidney injury are risk factors for thrombocytopenia. There was no significant association between thrombocytopenia and mortality.

Factors associated with thrombocytopenia in severe leptospirosis (Weil's disease)

OBJECTIVE: This study was conducted to investigate factors associated with thrombocytopenia in a large cohort of patients with leptospirosis in an endemic area. METHODS: This retrospective study included 374 consecutive patients with leptospirosis who were admitted to tertiary hospitals in Fortaleza, Brazil. All patients had a diagnosis of severe leptospirosis (Weil's disease). Acute kidney injury was defined according to the RIFLE criteria. Thrombocytopenia was defined as a platelet count <100,000/mm3. RESULTS: A total of 374 patients were included, with a mean age of 36.1±15.5 years, and 83.4% were male. Thrombocytopenia was present at the time of hospital admission in 200 cases (53.5%), and it developed during the hospital stay in 150 cases (40.3%). The patients with thrombocytopenia had higher frequencies of dehydration (53% vs. 35.3%, p = 0.001), epistaxis (5.7% vs. 0.8%, p = 0.033), hematemesis (13% vs. 4.6%, p = 0.006), myalgia (91.5% vs. 84.5%, p = 0.038), hematuria (54.8% vs. 37.6%, p = 0.011), metabolic acidosis (18% vs. 9.2%, p = 0.016) and hypoalbuminemia (17.8% vs. 7.5%, p = 0.005). The independent risk factors associated with thrombocytopenia during the hospital stay were lengthy disease (OR: 1.2, p = 0.001) and acute kidney injury (OR: 6.6, p = 0.004). Mortality was not associated with thrombocytopenia at admission (12.5% vs. 12.6%, p = 1.000) or during the hospital stay (12.6% vs. 11.3%, p = 0.748). CONCLUSIONS: Thrombocytopenia is a frequent complication in leptospirosis, and this condition was present in more than half of patients at the time of hospital admission. Lengthy disease and acute kidney injury are risk factors for thrombocytopenia. There was no significant association between thrombocytopenia and mortality. .

Endothelial dysfunction after pregnancy-induced hypertension.

OBJECTIVE: To carry out long-term analysis of the presence of endothelial dysfunction after the development of pregnancy-induced hypertension (PIH). METHODS: In a retrospective cohort study, data were analyzed from 60 women who delivered at a tertiary maternity hospital in Fortaleza, Ceara, Brazil, between 1992 and 2002. Thirty women had a history of PIH and 30 had no history of complications. Anthropometric and laboratory data were collected, and endothelial function was evaluated by flow-mediated dilatation of the brachial artery. Continuous variables were analyzed via Student t test, and Mann-Whitney test was used to compare means. Clinical and metabolic measures were categorized according to cardiovascular risk by cutoff points determined by national consensus; χ2 and Fisher exact tests were used to compare the groups. Relative risk was calculated for variables that were statistically significant (P<0.05). RESULTS: Women with a history of PIH had higher body mass index (P=0.03), systolic blood pressure (P=0.03), low-density lipoprotein cholesterol (P=0.02), and fasting glucose (P=0.02) compared with women with no pregnancy complications. The frequency of endothelial dysfunction was 60% among all women, with a significant difference between the 2 groups (P=0.01). CONCLUSION: Women with a history of PIH were found to have a higher frequency of long-term endothelial dysfunction.

Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning.

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.

Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning

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.

Differences in community, hospital and intensive care unit-acquired acute kidney injury: observational study in a nephrology service of a developing country.

BACKGROUND: Acute kidney injury (AKI) complicates more than 7% of all in-hospital patients. The aim of this study is to investigate the differences in community, hospital and intensive care unit-acquired AKI in patients undergoing nephrology consultation in a tertiary hospital in a developing country. METHODS: An observational cohort study of all patients with AKI admitted to the General Hospital of Fortaleza, Brazil was conducted. RIFLE criteria were used to classify the patients and to assess their association with death. Univariate and multivariate analyses were performed to investigate the factors associated with death. RESULTS: Of 491 AKI patients undergoing nephrology consultation, the mean age was 55.2 ± 22.9 years. Community-acquired AKI was observed in 55% of cases, general ward-acquired in 29% and ICU-acquired in 15.3%. Late Nephrology consultation was observed, and the great majority of patients had "Failure" classification (90%) according to RIFLE criteria. Intermittent hemodialysis was required in 68% of cases. The overall in-hospital mortality was 23%. The in-hospital mortality was higher in ICU-acquired AKI (33.6%). Community acquired AKI had a higher mortality than general ward-acquired AKI (23% vs. 11.6%, p = 0.001). Risk factors for death were infection (OR = 2.0, p = 0.003), neoplasms (OR = 1.89, p = 0.042), community acquired-AKI (OR = 1.27, p = 0.003), ICU acquired-AKI (OR = 2.76, p < 0.0001) and need for renal replacement therapy (OR = 2.64, p < 0.001). CONCLUSIONS: AKI is a frequent and frequently fatal condition. Mortality was higher in community and ICU-acquired than hospital ward-acquired AKI.

Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil.

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-for-height 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.

Campylobacter jejuni infection and virulence-associated genes in children with moderate to severe diarrhoea admitted to emergency rooms in northeastern Brazil.

Campylobacter is an important cause of foodborne gastroenteritis. We determined the occurrence of Campylobacter jejuni and Campylobacter coli, using culture-based methods and PCRs targeting virulence-associated genes (VAGs) among children aged ≤14 years who were treated for diarrhoea at emergency rooms in northeastern Brazil. Genomic DNA was extracted directly from stool samples collected from 366 children. A questionnaire was also applied to qualify the clinical conditions presented by each child at the time of admission. C. jejuni and C. coli were detected in 16.4 % (60/366) and 1.4 % (5/366) of the diarrhoeal samples, respectively, by PCR, a much higher proportion than that detected by conventional methods. C. jejuni VAGs were detected in the following proportions of hipO-positive samples: ciaB, 95 % (57/60); dnaJ, 86.7 % (52/60); racR, 98.3 % (59/60); flaA, 80 % (48/60); pldA, 45 % (27/60); cdtABC, 95 % (57/60); and pVir 0 % (0/60). Particular symptoms, such as blood in faeces, vomiting, fever, and/or abdominal pain, were not associated with detection of C. jejuni nor were they associated with any particular VAG or combination of VAGs (P>0.05). C. jejuni and its VAGs were detected in a substantial proportion of the children admitted. Further efforts shall be directed towards elucidating whether these genetic factors or their expressed proteins play a role in Campylobacter pathogenesis.

Different patterns in a cohort of patients with severe leptospirosis (Weil syndrome): effects of an educational program in an endemic area.

The aim of this study is to investigate the changes in clinical pattern and therapeutic measures in leptospirosis-associated acute kidney injury; a retrospective study with 318 patients in Brazil. Patients were divided according to the time of admission: 1985-1996 (group I) and 1997-2010 (group II). Patients were younger in group I (36 ± 13 versus 41 ± 16 years, P = 0.005) and the numbers of oliguria increased (21% versus 41% in group II, P = 0.014). Higher frequency of lung manifestations was observed in group II (P < 0.0001). Although increased severity, there was a significant reduction in mortality (20% in group I versus 12% in group II, P = 0.03). Mortality was associated with advanced age, low diastolic blood pressure, oliguria, arrhythmia, and peritoneal dialysis, besides a trend to better mortality with penicillin administration. Leptospirosis is occurring in an older population, with a higher number of oliguria and lung manifestations. However, mortality is decreasing and can be the result of changes in treatment.

Renal tubular dysfunction in patients with American cutaneous leishmaniasis.

Renal dysfunction seen in patients with American cutaneous leishmaniasis (ACL) has been attributed to the use of antimonials for treatment. To determine whether ACL itself causes tubular dysfunction, we measured renal function in 37 patients with ACL prior to their treatment and compared results to that in 10 healthy volunteers of similar mean age. None of the patients presented with glomerular dysfunction; however, 27 had a urinary concentrating defect. There was no statistical difference between groups in the pre- and post-desmopressin test of urine osmolality, but the post-test urine osmolality of the controls was significantly higher. Urinary AQP2 levels, determined by western blot of isolated exosomes, were found to be significantly lower in patients than in controls, whereas that of the cotransporter (NKCC2) was significantly higher. A urinary acidification defect (post-test pH greater than 5.50 following calcium chloride) was found in 15 patients. Pretest plasma bicarbonate was below normal in 12 patients as was the pretest plasma pH in 14. Expression of the Na/H exchanger (NHE3), H(+)-ATPase, and pendrin were all significantly higher in patients with ACL than in controls. A combined urinary concentration and acidification defect was found in 12 patients. Thus, the urinary concentrating defect of ACL may be caused by decreased AQP2, with increased NKCC2 compensatory. Pendrin upregulation may be related to the urinary acidification defect with increased NHE3 and H(+)-ATPase also compensatory. Hence, ACL can cause asymptomatic renal tubular dysfunction.

Renal dysfunction in leprosy: a historical cohort of 923 patients in Brazil.

We investigated the factors associated with renal dysfunction in leprosy patients from Brazil. We report on a historical cohort of leprosy patients followed in two hospitals in Fortaleza City in northeastern Brazil. The factors associated with renal dysfunction were investigated. A total of 923 patients were included, with a mean age of 41.5 ± 19.1 years, and 53.3% were male. Renal dysfunction was found in 35 cases (3.8%). Proteinuria was found in 4.8% of cases, haematuria in 6.8% and leukocyturia in 10.4%. Factors associated with renal dysfunction by multivariate analysis were: reaction episode (odds ratio [OR] = 3.9, P = 0.03), multibacillary classification (OR = 3.5, P = 0.02) and advanced age (OR = 1.04, P = 0.01). Four patients (0.4%) died. Leprosy is associated with renal dysfunction, especially in older patients and those presenting with reaction episode and multibacillary classification.

RIFLE and Acute Kidney Injury Network classifications predict mortality in leptospirosis-associated acute kidney injury.

AIM: Acute kidney injury (AKI) is a common complication in leptospirosis. The aim of this study is to investigate the association between RIFLE and AKIN classifications with mortality in leptospirosis-associated AKI. METHODS: A retrospective study was conducted in patients with leptospirosis admitted to tertiary hospitals in Brazil. The association between RIFLE and AKIN classifications with mortality was investigated. Univariate and multivariate analysis was performed to investigate risk factors for death. RESULTS: A total of 287 patients were included, with an average age of 37 ± 16 years, and 80.8% were male. Overall mortality was 13%. There was a significant association between these classifications and death. Among non-survivors, 86% were in the class 'failure' and AKIN 3. Increased mortality was observed according to the worse classifications: 'risk' (R; 2%), 'injury' (I; 8%) and 'failure' (F; 23%), as well as in AKIN 1 (2%), AKIN 2 (8%) and AKIN 3 (23%) (P < 0.0001). The worst classifications were significantly associated with death: RIFLE F (odds ratio = 11.6, P = 0.018) and AKIN 3 (odds ratio = 12.8, P = 0.013). Receiver-operator curve for patients with AKI showed high areas under the curve (0.71, 95% confidence interval = 0.67-0.74) for both RIFLE and AKIN classifications in determining the sensitivity for mortality. CONCLUSION: There is a significant association between RIFLE and AKIN classifications with mortality in patients with leptospirosis. Initiation of dialysis in patients with RIFLE F and AKIN 3 should always be considered.