Malnutrition and cryptosporidiosis form a vicious cycle and lead to acute and long-term growth impairment in children from developing countries. Insights into mechanisms underlying the vicious cycle ...will help to design rational therapies to mitigate this infection. We tested the effect of short-term protein malnutrition on Cryptosporidium parvum infection in a murine model by examining stool shedding, tissue burden, and histologic change and explored the mechanism underlying the interaction between malnutrition and cryptosporidiosis through immunostaining and immunoblotting. Protein malnutrition increased stool shedding and the number of intestine-associated C. parvum organisms, accompanied by significant suppression of C. parvum-induced caspase 3 activity and expression of PCNA and Ki67, but activation of the Akt survival pathway in intestinal epithelial cells. We find that even very brief periods of protein malnutrition may enhance (or intensify) cryptosporidiosis by suppressing C. parvum-induced cell turnover and caspase-dependent apoptosis of intestinal epithelial cells. This implicates a potential strategy to attenuate C. parvum's effects by modulating apoptosis and promoting regeneration in the intestinal epithelium.
The increased incidence and severity of Clostridium difficile infection (CDI) in older adults (age, ⩾65 years) corresponds with the emergence of the BI/NAP1 strain, making elucidation of the host ...immune response extremely important. We therefore infected germ-free C57BL/6 mice aged 7–14 months with a BI/NAP1 strain and monitored the mice for response. Infected mice were moribund 48–72 h after infection and developed gross and histological cecitis and colitis and elevated concentrations of keratinocyte chemoattractant, interleukin 1β, monocyte chemotactic protein 1, and granulocyte colony-stimulating factor and decreased levels of interferon γ, interleukin 12 p40, interleukin 12 p70, and interleukin 10 compared with controls. We conclude that aged, germ-free C57BL/6 mice are susceptible to fulminant CDI from a BI/NAP1 strain and represent a novel model to further elucidate the host immune response to acute CDI.
Enterotoxigenic
(ETEC) is a major cause of traveler's diarrhea as well as of endemic diarrhea and stunting in children in developing areas. However, a small-mammal model has been badly needed to ...better understand and assess mechanisms, vaccines, and interventions. We report a murine model of ETEC diarrhea, weight loss, and enteropathy and investigate the role of zinc in the outcomes. ETEC strains producing heat-labile toxins (LT) and heat-stable toxins (ST) that were given to weaned C57BL/6 mice after antibiotic disruption of normal microbiota caused growth impairment, watery diarrhea, heavy stool shedding, and mild to moderate intestinal inflammation, the latter being worse with zinc deficiency. Zinc treatment promoted growth in zinc-deficient infected mice, and subinhibitory levels of zinc reduced expression of ETEC virulence genes
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Zinc supplementation increased shedding and the ileal burden of wild-type (WT) ETEC but decreased shedding and the tissue burden of LT knockout (LTKO) ETEC. LTKO ETEC-infected mice had delayed disease onset and also had less inflammation by fecal myeloperoxidase (MPO) assessment. These findings provide a new murine model of ETEC infection that can help elucidate mechanisms of growth, diarrhea, and inflammatory responses as well as potential vaccines and interventions.
Summary Objectives This study determined the prevalence of Campylobacter spp., Helicobacter pylori and Arcobacter spp. in stool samples from Venda in relation to diarrhea, intestinal inflammation and ...HIV status using specific molecular methods. Methods Stool samples were collected from hospital patients (255) and primary school children (67). Genomic DNA was extracted from the stools and molecular methods including PCR, PCR followed by restriction analysis and multiplex PCR were used to test for the different organisms. The lactoferrin content of the stools was determined using commercial kits from TechLab (Blacksburg, VA, USA). Results The prevalence of the different organisms was 50.6% for H. pylori , 10.2% for C. jejuni , 6.2% for A. butzleri , 6.5% for C. coli , 3.1% for C. concisus , 2.8% for A. cryaerophilus and 1.9% for A. skirrowii . Of all the organisms, only C. jejuni was significantly associated with diarrhea (84.8%) ( χ2 = 21.025, P < 0.001) and elevated levels of lactoferrin (78.8%) ( χ2 = 16.919, P < 0.005) and was an important pathogen associated with diarrhea among HIV positive individuals (22.8%). Conclusions Campylobacter infections are common causes of gastroenteritis in Venda. Non- C. jejuni / coli Campylobacters such as C. concisus as well as A. butzleri and H. pylori may be involved in gastrointestinal diseases in the region but further studies are needed to confirm this hypothesis.
Summary Intestinal inflammation was evaluated using faecal lactoferrin and ribotype in 196 hospitalized adults with Clostridium difficile infection to determine the impact of ribotype 027 in ...long-term care facilities (LTCFs). LTCF residents ( n = 28) had greater antibiotic use ( P = 0.049) and more ribotype 027 infection odds ratio (OR): 4.87; 95% confidence interval (CI): 2.02–11.74; P < 0.01, compared to those admitted from home. Patients infected with ribotype 027 strains had worse six-month mortality (OR: 1.90; 95% CI: 1.08–3.34; P = 0.03) and more inflammation (95.26 vs 36.08 μg/mL; P = 0.006), compared to those infected with non-027 strains. This study was not designed to determine acquisition site, but, in this population, suggests that the location from which the patient has been admitted is strongly associated with ribotype 027 and more severe C. difficile disease.
The present study aimed to describe breast-feeding, complementary feeding and determining factors for early complementary feeding from birth to 8 months of age in a typical Brazilian low-income urban ...community.
A birth cohort was conducted (n 233), with data collection twice weekly, allowing close observation of breast-feeding, complementary feeding introduction and description of the WHO core indicators on infant and young child feeding. Infant feeding practices were related to socio-economic status (SES), assessed by Water/sanitation, wealth measured by a set of eight Assets, Maternal education and monthly household Income (WAMI index). Two logistic regression models were constructed to evaluate risk factors associated with early complementary feeding.
Based on twice weekly follow-up, 65 % of the children received exclusive breast-feeding in the first month of life and 5 % in the sixth month. Complementary feeding was offered in the first month: 29 % of the children received water, 15 % infant formulas, 13 % other milks and 9·4 % grain-derived foods. At 6 months, dietary diversity and minimum acceptable diet were both 47 % and these increased to 69 % at 8 months. No breast-feeding within the first hour of birth was a risk factor for the early introduction of water (adjusted OR=4·68; 95 % CI 1·33, 16·47) and low WAMI index a risk factor for the early introduction of other milks (adjusted OR=0·00; 95 % CI 0·00, 0·02).
Data suggest local policies should promote: (i) early breast-feeding initiation; (ii) SES, considering maternal education, income and household conditions; (iii) timely introduction of complementary feeding; and (iv) dietary diversity.
To determine potential, long-term deficits associated with early childhood diarrhea and parasitic infections, we studied the physical fitness (by the Harvard Step Test) and cognitive function (by ...standardized tests noted below) of 26 children who had complete surveillance for diarrhea in their first 2 years of life and who had continued surveillance until 6-9 years of age in a poor urban community (favela) in Fortaleza in northeast Brazil. Early childhood diarrhea at 0-2 years of age correlated with reduced fitness by the Harvard Step Test at 6-9 years of age (P = 0.03) even after controlling for anthropometric and muscle area effects, anemia, intestinal helminths, Giardia infections, respiratory illnesses, and socioeconomic variables. Early childhood cryptosporidial infections (6 with diarrhea and 3 without diarrhea) were also associated with reduced fitness at 6-9 year of age, even when controlling for current nutritional status. Early diarrhea did not correlate with activity scores (P = 0.697), and early diarrhea remained significantly correlated with fitness scores (P = 0.035) after controlling for activity scores. Early diarrhea burdens also correlated in pilot studies with impaired cognitive function using a McCarthy Draw-A-Design (P = 0.01; P = 0.017 when controlling for early helminth infections), Wechsler Intelligence Scale for Children coding tasks (P = 0.031), and backward digit span tests (P = 0.045). These findings document for the first time a potentially substantial impact of early childhood diarrhea and cryptosporidial infections on subsequent functional status. If confirmed, these findings have major implications for calculations of global disability adjusted life years and for the importance and potential cost effectiveness of targeted interventions for early childhood diarrhea.
A child's diet contains nutrients and other substances that influence intestinal health. The present study aimed to evaluate the relations between complementary feeding, intestinal barrier function ...and environmental enteropathy (EE) in infants. Data from 233 children were obtained from the Brazilian site of the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project cohort study. Habitual dietary intake from complementary feeding was estimated using seven 24-h dietary recalls, from 9 to 15 months of age. Intestinal barrier function was assessed using the lactulose-mannitol test (L-M), and EE was determined as a composite measure using faecal biomarkers concentrations - α-1-antitrypsin, myeloperoxidase (MPO) and neopterin (NEO) at 15 months of age. The nutrient adequacies explored the associations between dietary intake and the intestinal biomarkers. Children showed adequate nutrient intakes (with the exception of fibre), impaired intestinal barrier function and intestinal inflammation. There was a negative correlation between energy adequacy and L-M (ρ = -0·19, P < 0·05) and between folate adequacy and NEO concentrations (ρ = -0·21, P < 0·01). In addition, there was a positive correlation between thiamine adequacy and MPO concentration (ρ = 0·22, P < 0·01) and between Ca adequacy and NEO concentration (ρ = 0·23; P < 0·01). Multiple linear regression models showed that energy intakes were inversely associated with intestinal barrier function (β = -0·19, P = 0·02), and fibre intake was inversely associated with the EE scores (β = -0·20, P = 0·04). Findings suggest that dietary intake from complementary feeding is associated with decreased intestinal barrier function and EE in children.
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