Determinants and impact of giardia infection in the first 2 years of life in the MAL-ED birth cohort

Background: Giardia are among the most common enteropathogens detected in children in low-resource settings. We describe here the epidemiology of infection with Giardia in the first 2 years of life in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED), a multisite birth-cohort study.Methods: From 2089 children, 34916 stool samples collected during monthly surveillance and episodes of diarrhea were tested for Giardia using an enzyme immunoassay. We quantified the risk of Giardia detection, identified risk factors, and assessed the associations with micronutrients, markers of gut inflammation and permeability, diarrhea, and growth using multivariable linear regression.Results: The incidence of at least 1 Giardia detection varied according to site (range, 37.7%-96.4%) and was higher in the second year of life. Exclusive breastfeeding (HR for first Giardia detection in a monthly surveillance stool sample, 0.46 [95% confidence interval (CI), 0.28-0.75]), higher socioeconomic status (HR, 0.74 [95% CI, 0.56-0.97]), and recent metronidazole treatment (risk ratio for any surveillance stool detection, 0.69 [95% CI, 0.56-0.84]) were protective. Persistence of Giardia (consecutive detections) in the first 6 months of life was associated with reduced subsequent diarrheal rates in Naushahro Feroze, Pakistan but not at any other site. Giardia detection was also associated with an increased lactulose/mannitol ratio. Persistence of Giardia before 6 months of age was associated with a -0.29 (95% CI, -0.53 to -0.05) deficit in weight-for-age z score and -0.29 (95% CI, -0.64 to 0.07) deficit in length-for-age z score at 2 years.Conclusion: Infection with Giardia occurred across epidemiological contexts, and repeated detections in 40% of the children suggest that persistent infections were common. Early persistent infection with Giardia, independent of diarrhea, might contribute to intestina

Pathogen-specifi c burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED)

Background Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specifi c diarrhoea burdens in the community. Methods We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defi ned as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identifi ed through twice-weekly home visits by fi eldworkers over a follow-up period of 24 months. Non-diarrhoeal stool specimens were also collected for surveillance for months 1–12, 15, 18, 21, and 24. Stools were analysed for a broad range of enteropathogens using culture, enzyme immunoassay, and PCR. We used the adjusted attributable fraction (AF) to estimate pathogen-specifi c burdens of diarrhoea. Findings Between Nov 26, 2009, and Feb 25, 2014, we tested 7318 diarrhoeal and 24 310 non-diarrhoeal stools collected from 2145 children aged 0–24 months. Pathogen detection was common in non-diarrhoeal stools but was higher with diarrhoea. Norovirus GII (AF 5·2%, 95% CI 3·0–7·1), rotavirus (4·8%, 4·5–5·0), Campylobacter spp (3·5%, 0·4–6·3), astrovirus (2·7%, 2·2–3·1), and Cryptosporidium spp (2·0%, 1·3–2·6) exhibited the highest attributable burdens of diarrhoea in the fi rst year of life. The major pathogens associated with diarrhoea in the second year of life were Campylobacter spp (7·9%, 3·1–12·1), norovirus GII (5·4%, 2·1–7·8), rotavirus (4·9%, 4·4–5·2), astrovirus (4·2%, 3·5–4·7), and Shigella spp (4·0%, 3·6–4·3). Rotavirus had the highest AF for sites without rotavirus vaccination and the fi fth highest AF for sites with the vaccination. There was substantial variation in pathogens according to geography, diarrhoea severity, and season. Bloody diarrhoea was primarily associated with Campylobacter spp and Shigella spp, fever and vomiting with rotavirus, and vomiting with norovirus GII. Interpretation There was substantial heterogeneity in pathogen-specifi c burdens of diarrhoea, with important determinants including age, geography, season, rotavirus vaccine usage, and symptoms. These fi ndings suggest that although single-pathogen strategies have an important role in the reduction of the burden of severe diarrhoeal disease, the eff ect of such interventions on total diarrhoeal incidence at the community level might be limited

Natural Coinfection of Pseudomonas aeruginosa and Enteroaggregative Escherichia coli in a feral pigeon (Columba livia)

Background: Rock pigeon (Columba livia) is an exotic and invasive species of the Columbidae family found in several cities around the world, including Brazilian cities, and close to humans. This species is found in large populations often in public locations, where people may have contact. Several studies have demonstrated the isolation of human pathogens from these birds. However, there are scarce studies describing infections by Gram-negative bacteria to which pigeons are susceptible. Therefore, this report aimed to describe a case of natural coinfection of Pseudomonas aeruginosa and Enteroaggregative Escherichia coli in a feral pigeon.Case: A sick feral pigeon was delivered at the Laboratory of Ornithological Studies, State University of Ceará, Fortaleza, Brazil. Due to poor prognosis, the individual was euthanized with ketamine via intravenous injection and submitted to necropsy, in which samples were collected for microbiological and histopathological procedure. The procedure was performed aseptically and samples were collected from intestine, liver, spleen, heart and lung. Bacterial isolation was performed with culture media selective for Gram negative bacteria and strains were identified biochemically. Histopathological examination was performed with conventional method and slides were stained with hematoxylin and eosin. DNA from E. coli isolates was extracted with simples boiling method and submitted to uniplex conventional polymerase chain reaction (PCR) to diagnose diarrheagenic pathotypes with specific primers for the following genes: aaiC, aatA, eaeA, stx1, stx2, eltB, estA and ipaH. Escherichia coli was isolated from the intestine, liver, spleen and lung, while Pseudomonas aeruginosa was present in liver, spleen and lung. E. coli strains from liver and spleen were positive for the aaiC gene, which is a diagnostic gene for Enteroaggregative Escherichia coli (EAEC) pathotype. Necropsy revealed the presence of several caseous lesions around the head of the bird, cellulitis in the abdominal region, hepatomegaly, splenomegaly, hemorrhagic intestine and pericarditis. Microscopical findings were most intense in liver and lung samples, presenting vascular and inflammatory alterations. Histopathological alterations indicated an acute presentation of the infections and several lesions in different organs, demonstrating the septicemic characteristic of the microorganisms involved in this case.Discussion: Both pathogens in this report were identified mostly in the same organs, which may indicate that there was an association in the pathogenesis. However, the entry routes of infection in this case may have been different, considering that Pseudomonas aeruginosa was not isolated from the intestine. The histopathological findings were not pathognomonic for either pathogen. However, some characteristic lesions were observed, such as cellulitis, which is commonly attributed to Escherichia coli. EAEC strains are human pathogens that cause acute and persistent diarrhea around the world. These microorganisms could be potentially transmitted to humans, as suggested by other studies with feral pigeons and enteric pathogens. However, the absence of reports of pigeon-transmitted diarrheagenic infections in humans may suggest that pigeons are only reservoirs of these pathogens. In addition, as this report demonstrates, these birds may also suffer from these infections. In conclusion, the free-living pigeon presented a natural occurring case of coinfection by Pseudomonas aeruginosa and Enteroaggregative Escherichia coli. Both are human opportunistic pathogens, and may have public health implication

Clinical evaluation, biochemistry and genetic polymorphism analysis for the diagnosis of lactose intolerance in a population from northeastern Brazil

OBJECTIVE: This work aimed to evaluate and correlate symptoms, biochemical blood test results and single nucleotide polymorphisms for lactose intolerance diagnosis. METHOD: A cross-sectional study was conducted in Fortaleza, Ceará, Brazil, with a total of 119 patients, 54 of whom were lactose intolerant. Clinical evaluation and biochemical blood tests were conducted after lactose ingestion and blood samples were collected for genotyping evaluation. In particular, the single nucleotide polymorphisms C>;T-13910 and G>;A-22018 were analyzed by restriction fragment length polymorphism/polymerase chain reaction and validated by DNA sequencing. RESULTS: Lactose-intolerant patients presented with more symptoms of flatulence (81.4%), bloating (68.5%), borborygmus (59.3%) and diarrhea (46.3%) compared with non-lactose-intolerant patients (

The effect of Cratylia floribunda lectin on renal hemodynamics and ion transport

As lectinas são descritas como (glico)proteínas que se ligam, especificamente e reversivelmente, a carboidratos. Lectinas de leguminosas isoladas da subtribo Diocleinae (Canavalia, Dioclea eCratylia) são estruturalmente homólogas em relação às suas estruturas primárias. Demonstrou-se que as lectinas de DiocleinaeCanavalia brasiliensis, Dioclea guianensis eCanavalia ensiformis alteram diferentemente parâmetros fisiológicos em rins isolados de ratos. Dessa maneira, o objetivo deste estudo foi investigar o papel da lectina de Cratylia floribunda (CFL) na hemodinâmica renal e no transporte de íons em ratos. Em rins isolados perfundidos, CFL (10 mg/mL, n=5) aumentou a pressão de perfusão renal, a resistência vascular renal e reduziu o percentual do transporte tubular de K+, mas não alterou o fluxo urinário, a taxa de filtração glomerular e o percentual de transporte tubular dos íons sódio e cloreto. No leito mesentérico isolado perfundido, CFL (3 e 10 mg/mL/min, n=4) não alterou o tônus basal ou a contração do tecido induzida por fenilefrina (1 mM/mL/min). Em conclusão, a lectina de sementes de Cratylia floribunda altera parâmetros hemodinâmicos renais, provavelmente de origem tubular, e não por alterações hemodinâmicas.Lectins have been described as glycoproteins that reversibly and specifically bind to carbohydrates. Legume lectins isolated from the subtribe Diocleinae (Canavalia, Dioclea andCratylia) are structurally homologous with respect to their primary structures. The Diocleinae lectins of Canavalia brasiliensis, Dioclea guianensis andCanavalia ensiformis have been shown to distinctly alter physiological parameters in isolated rat kidneys. Thus, the aim of this study was to investigate the effect of Cratylia floribunda lectin (CFL) on renal hemodynamics and ion transport in rats. In isolated perfused kidneys, CFL (10 mg/mL, n=5) increased RPP, RVR and decreased %TK+, but did not change urinary flow, glomerular filtration rate, sodium or chloride tubular transport. In isolated perfused mesenteric bed, CFL (3 and 10 mg/mL/min; n=4) did not alter tissue basal tonus or tissue contraction by phenylephrine (1 mM/mL/min). In conclusion, the seed lectin of Cratylia floribunda increased renal hemodynamic parameters showing a kaliuretic effect. This effect could be of tubular origin, rather than a result from haemodynamic alterations

Epidemiology and Risk Factors for Cryptosporidiosis in Children from 8 Low-income Sites : Results from the MAL-ED Study

Funding Information: The MAL-ED study is carried out as a collaborative project supported by the Bill & Melinda Gates Foundation, the Foundation for the National Institutes of Health (NIH), and the NIH Fogarty International Center. This work was also supported by the National Institute of Allergy and Infectious Diseases of the NIH (grant numbers K23 AI087910 to P. K. and K23 AI087910 to W. A. P.) and by the Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases Discovery Program (to P. D.).Peer reviewedPublisher PD

Determinants and Impact of Giardia Infection in the First 2 Years of Life in the MAL-ED Birth Cohort

Background. Giardia are among the most common enteropathogens detected in children in low-resource settings. We describe here the epidemiology of infection with Giardia in the first 2 years of life in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED), a multisite birth-cohort stu dy. Methods. From 2089 children, 34 916 stool samples collected during monthly surveillance and episodes of diarrhea were tested for Giardia using an enzyme immunoassay. We quantified the risk of Giardia detection, identified risk factors, and assessed the associations with micronutrients, markers of gut inflammation and permeability, diarrhea, and growth using multivariable linear regression. Results. The incidence of at least 1 Giardia detection varied according to site (range, 37.7%–96.4%) and was higher in the sec - ond year of life. Exclusive breastfeeding (HR for first Giardia detection in a monthly surveillance stool sample, 0.46 [95% confidence interval (CI), 0.28–0.75]), higher socioeconomic status (HR, 0.74 [95% CI, 0.56–0.97]), and recent metronidazole treatment (risk ratio for any surveillance stool detection, 0.69 [95% CI, 0.56–0.84]) were protective. Persistence of Giardia (consecutive detections) in the first 6 months of life was associated with reduced subsequent diarrheal rates in Naushahro Feroze, Pakistan but not at any other site. Giardia detection was also associated with an increased lactulose/mannitol ratio. Persistence of Giardia before 6 months of age was associated with a −0.29 (95% CI, −0.53 to −0.05) deficit in weight-for-age z score and −0.29 (95% CI, −0.64 to 0.07) deficit in length-for-age z score at 2 years. Conclusions. Infection with Giardia occurred across epidemiological contexts, and repeated detections in 40% of the children suggest that persistent infections were common. Early persistent infection with Giardia , independent of diarrhea, might contribute to intestinal permeability and stunted growth

Early Life Child Micronutrient Status, Maternal Reasoning, and a Nurturing Household Environment have Persistent Influences on Child Cognitive Development at Age 5 years : Results from MAL-ED

Funding Information: The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is carried out as a collaborative project supported by the Bill & Melinda Gates Foundation, the Foundation for the NIH, and the National Institutes of Health/Fogarty International Center. This work was also supported by the Fogarty International Center, National Institutes of Health (D43-TW009359 to ETR). Author disclosures: BJJM, SAR, LEC, LLP, JCS, BK, RR, RS, ES, LB, ZR, AM, RS, BN, SH, MR, RO, ETR, and LEM-K, no conflicts of interest. Supplemental Tables 1–5 and Supplemental Figures 1–3 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/jn/. Address correspondence to LEM-K (e-mail: [email protected]). Abbreviations used: HOME, Home Observation for Measurement of the Environment inventory; MAL-ED, The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project; TfR, transferrin receptor; WPPSI, Wechsler Preschool Primary Scales of Intelligence.Peer reviewe

Early life child micronutrient status, maternal reasoning, and a nurturing household environment have persistent influences on child cognitive development at age 5 years: Results from MAL-ED

Background: Child cognitive development is influenced by early-life insults and protective factors. To what extent these factors have a long-term legacy on child development and hence fulfillment of cognitive potential is unknown. Objective: The aim of this study was to examine the relation between early-life factors (birth to 2 y) and cognitive development at 5 y. Methods: Observational follow-up visits were made of children at 5 y, previously enrolled in the community-based MAL-ED longitudinal cohort. The burden of enteropathogens, prevalence of illness, complementary diet intake, micronutrient status, and household and maternal factors from birth to 2 y were extensively measured and their relation with the Wechsler Preschool Primary Scales of Intelligence at 5 y was examined through use of linear regression. Results: Cognitive T-scores from 813 of 1198 (68%) children were examined and 5 variables had significant associations in multivariable models: mean child plasma transferrin receptor concentration (β: −1.81, 95% CI: −2.75, −0.86), number of years of maternal education (β: 0.27, 95% CI: 0.08, 0.45), maternal cognitive reasoning score (β: 0.09, 95% CI: 0.03, 0.15), household assets score (β: 0.64, 95% CI: 0.24, 1.04), and HOME child cleanliness factor (β: 0.60, 95% CI: 0.05, 1.15). In multivariable models, the mean rate of enteropathogen detections, burden of illness, and complementary food intakes between birth and 2 y were not significantly related to 5-y cognition. Conclusions: A nurturing home context in terms of a healthy/clean environment and household wealth, provision of adequate micronutrients, maternal education, and cognitive reasoning have a strong and persistent influence on child cognitive development. Efforts addressing aspects of poverty around micronutrient status, nurturing caregiving, and enabling home environments are likely to have lasting positive impacts on child cognitive development.publishedVersio