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Biomedical subjects

R L Guerrant

Publications and source records attributed to R L Guerrant.

At least 19 recordsLinked to original sources
PubMed2006

Prevalence of Campylobacter species, Helicobacter pylori and Arcobacter species in stool samples from the Venda region, Limpopo, South Africa: studies using molecular diagnostic methods.

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%) (chi2=21.025, P<0.001) and elevated levels of lactoferrin (78.8%) (chi2=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.

Adolescent↗
PubMed2006

Cryptosporidium species: preliminary descriptions of the prevalence and genotype distribution among school children and hospital patients in the Venda region, Limpopo Province, South Africa.

In the present study, the prevalence and species distribution of Cryptosporidium among school children and hospital patients in the Venda region of South Africa was determined. Real time PCR (qPCR) was used for initial screening to detect positive samples while a nested PCR followed by restriction fragment length polymorphism was used to determine the species genotype. From a total of 244 stool samples tested, 44 (18%) had Cryptosporidium with no significant difference (chi(2)=0.04; P=0.841) between samples collected from patients attending hospitals 36/197 (18%) and the samples from primary schools 8/47 (17%). The age groups most affected were those from 2 to 5 years old (28.6%) and 50 to 59 years old (50.0%). Cryptosporidium was detected in 4 (12.5%) of the 31 HIV positive individuals. Fifty-seven percent of the Cryptosporidium positive samples were diarrheic and 26 (59.1%) had elevated lactoferrin content. C. hominis (82%) was more common than C. parvum (18%). This study has demonstrated the high prevalence of Cryptosporidium infections in the Venda region and its implications in causing diarrhea and inflammation.

Adolescent↗
PubMed2006

Effect of novel A2A adenosine receptor agonist ATL 313 on Clostridium difficile toxin A-induced murine ileal enteritis.

Clostridium difficile is a spore-forming, anaerobic, gram-positive bacillus that releases two main virulence factors: toxins A and B. Toxin A plays an important pathogenic role in antibiotic-induced diarrhea and pseudomembranous colitis, a condition characterized by intense mucosal inflammation and secretion. Agonist activity at A2A adenosine receptors attenuates inflammation and damage in many tissues. This study evaluated the effects of a new selective A2A adenosine receptor agonist (ATL 313) on toxin A-induced injury in murine ileal loops. ATL 313 (0.5 to 5 nM) and/or the A2A adenosine receptor antagonist (ZM241385; 5 nM) or phosphate-buffered saline (PBS) were injected into ileal loops immediately prior to challenge with toxin A (1 to 10 microg/loop) or PBS. Intestinal fluid volume/length and weight/length ratios were calculated 3 h later. Ileal tissues were collected for the measurement of myeloperoxidase, adenosine deaminase activity, tumor necrosis factor alpha (TNF-alpha) production, histopathology, and detection of cell death by the TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) method. Toxin A significantly increased volume/length and weight/length ratios in a dose-dependent fashion. ATL 313 treatment significantly (P < 0.05) reduced toxin A-induced secretion and edema, prevented mucosal disruption, and neutrophil infiltration as measured by myeloperoxidase activity. ATL 313 also reduced the toxin A-induced TNF-alpha production and adenosine deaminase activity and prevented toxin A-induced cell death. These protective effects of ATL 313 were reversed by ZM241385. In conclusion, the A2A adenosine receptor agonist, ATL 313, reduces tissue injury and inflammation in mice with toxin A-induced enteritis. The finding of increased ileal adenosine deaminase activity following the administration of toxin A is new and might contribute to the pathogenesis of the toxin A-induced enteritis by deaminating endogenous adenosine.

Adenosine A2 Receptor Agonists↗
PubMed2003

Anti-ganglioside antibodies and clinical outcome of patients with Guillain-Barré Syndrome in northeast Brazil.

OBJECTIVES: The goal of this study was to investigate the frequency of GM1 antibodies and to assess whether exposure to Campylobacter jejuni was associated with a distinct clinical variant of Guillain-Barré Syndrome (GBS) or disease outcome in Rio Grande do Norte, Brazil. MATERIAL AND METHODS: Forty-one patients with a presumed diagnosis of GBS were enrolled and prospectively studied between June 1994 and November 1999. RESULTS: Anti-GM1 was present in 51.2% (n = 21) of patients. The presence of anti-GM1 was significantly associated with acute axonal motor neuropathy when compared to acute inflammatory demyelinating polyneuropathy (P = 0.01). Patients with anti-GM1 antibodies presented distal muscle involvement and fewer sensory deficits. Age, time to nadir and ventilatory assistance were not associated with anti-GM1 antibodies. Eight out of 21 patients (32%) presented with anti-C. jejuni antibodies. Clinical features were similar for patients with GBS with positive and negative C. jejuni antibodies. Anti-GM1 antibodies were associated with C. jejuni infection (P = 0.0005). Presence of anti-GM1 and C. jejuni antibodies did not indicate a worse prognosis. CONCLUSION: Patients with GBS and anti-GM1 antibodies had more distal muscle weakness, fewer sensory deficits, more axonal degeneration and C. jejuni infection, but these findings were not associated with a worse prognosis.

Age Factors↗
PubMed2001

Role of inducible cyclooxygenase and prostaglandins in Clostridium difficile toxin A-induced secretion and inflammation in an animal model.

Cyclooxygenase (Cox)-2 expression and inhibition were investigated in a rabbit ileal loop model of Clostridium difficile colitis and diarrhea. Intestinal tissue stimulated with C. difficile toxin A showed up-regulation of Cox-2 expression in lamina propria macrophages and elevated prostaglandin levels. Toxin A-stimulated loops exhibited severe inflammation and increased secretory volume. Celecoxib, a specific Cox-2 inhibitor, significantly reduced toxin A-induced prostaglandin production. Furthermore, celecoxib (> or =0.02 mg/mL) blocked both histologic damage (mean histologic grade, 1.25 vs. 3.44 in rabbits receiving toxin A alone; P<.0005) and secretion (volume:length ratio, 0.18 vs. 0.72 in those receiving toxin A alone; P=.002) in toxin A-stimulated loops in a dose-related manner. Thus, toxin A induced expression of Cox-2 in the host, and prostaglandins produced through Cox-2 were involved in the mediation of the increased secretion of electrolytes and water and the inflammatory response induced by toxin A.

Animals↗
PubMed2001

Cryptosporidiosis: an update.

Cryptosporidiosis was recognised in human beings in 1976, and was prominent in the 1980s and 1990s as a cause of severe diarrhoeal illness in patients with AIDS. It is now additionally recognised as a major cause of waterborne diarrhoeal illness in developed regions, and as a pathogen with long-term effect on childhood growth and development in impoverished areas. This update focuses on recent changes in our understanding of the taxonomy of cryptosporidium, its epidemiology, effects, pathogenesis, diagnosis, and treatment.

Animals↗
PubMed2001

A longitudinal study of Giardia lamblia infection in north-east Brazilian children.

OBJECTIVE: To evaluate the epidemiology of Giardia lamblia infection, investigate factors which might be associated with clinical manifestations and recurrence, and examine the role of copathogens in disease course. METHODS: Prospective 4-year cohort study of children born in an urban slum in north-eastern Brazil. RESULTS: Of 157 children followed for > or = 3 months, 43 (27.4%) were infected with Giardia. The organism was identified in 8.8% of all stool specimens, and although found with similar frequency in non-diarrhoeal (7.4%) and diarrhoeal stools (9.7%), was more common in children with persistent (20.6%) than acute diarrhoea (7.6%, P=0.002). Recurrent or relapsing infections were common (46%). Children with symptomatic infections had significantly lower weight-for-age and height-for-age than asymptomatic children. Copathogens were not associated with disease course. CONCLUSION With its protean clinical manifestations, Giardia may be associated with substantial morbidity amongst children in Brazil.

Animals↗
PubMed2001

Early childhood diarrhoea and helminthiases associate with long-term linear growth faltering.

BACKGROUND: Although the acute mortality from diarrhoeal diseases is well recognized, the potentially prolonged impact of early childhood diarrhoea on background growth and development is often overlooked. To examine the magnitude and duration of the association of early childhood enteric infections with growth faltering in later childhood, we investigated associations of early childhood diarrhoea (0-2 years) and intestinal helminthiases with nutritional status from age 2 to 7 years. METHODS: Twice-weekly diarrhoea surveillance and quarterly anthropometrics were followed from 1989 to 1998 in 119 children born into a Northeast Brazilian shantytown. RESULTS: Diarrhoea burdens at 0-2 years old were significantly associated with growth faltering at ages 2-7 years, even after controlling for nutritional status in infancy, helminthiases at 0-2 years old, family income, and maternal education by Pearson correlation, multivariate linear regression, and repeat measures analysis. The average 9.1 diarrhoeal episodes before age 2 years was associated with a 3.6 cm (95% CI : 0.6-6.6 cm) growth shortfall at age 7 years. Early childhood helminthiasis was also associated with linear growth faltering and a further 4.6 cm shortfall (95% CI : 0.8-7.9 cm) at age 7 years. CONCLUSIONS: Early childhood diarrhoea and helminthiases independently associate with substantial linear growth shortfalls that continue beyond age 6 years. Targeted interventions for their control may have profound and lasting growth benefits for children in similar settings.

Anthropometry↗
PubMed2000

Persistent diarrhea signals a critical period of increased diarrhea burdens and nutritional shortfalls: a prospective cohort study among children in northeastern Brazil.

Persistent diarrhea (PD; duration >/=14 days) is a growing part of the global burden of diarrheal diseases. A 45-month prospective cohort study (with illness, nutritional, and microbiologic surveillance) was conducted in a shantytown in northeastern Brazil, to elucidate the epidemiology, nutritional impact, and causes of PD in early childhood (0-3 years of age). A nested case-control design was used to examine children's diarrhea burden and nutritional status before and after a first PD illness. PD illnesses accounted for 8% of episodes and 34% of days of diarrhea. First PD illnesses were preceded by a doubling of acute diarrhea burdens, were followed by further 2.6-3.5-fold increased diarrhea burdens for 18 months, and were associated with acute weight shortfalls. Exclusively breast-fed children had 8-fold lower diarrhea rates than did weaned children. PD-associated etiologic agents included Cryptosporidium, Giardia, enteric adenoviruses, and enterotoxigenic Escherichia coli. PD signals growth shortfalls and increased diarrhea burdens; children with PD merit extended support, and the illness warrants further study to elucidate its prevention, treatment, and impact.

Bacterial Infections↗
PubMed2000

Seroprevalence and seroincidence of Norwalk-like virus infection among Brazilian infants and children.

To determine the importance of Norwalk-like viruses (NLVs) as pediatric pathogens in a developing country, the seroprevalence and seroincidence of this group of viruses in a cohort of children less than 4 years of age in an urban shantytown in northeastern Brazil was examined. Serum samples were collected approximately every 6 months from 135 children who were surveyed three times each week for diarrhea and vomiting. NLV IgG was measured by an enzyme immunosorbent assay (EIA) with recombinant Norwalk virus capsid protein. Overall NLV seroprevalence was 71%, and the overall NLV seroconversion rate was 0.7 seroconversions per child-year. The highest age-specific NLV seroconversion rate (0.8 seroconversions per child-year) was observed in the 13-24-month age group. For all study children, the incidence of diarrhea and vomiting was significantly greater (P < 0.01) during time periods spanned by serum pairs that indicated NLV seroconversion compared with time periods without NLV seroconversion. However, NLV seroconversion was not associated with gastrointestinal symptoms during the first year of life.

Brazil↗
PubMed2000

Update on Clostridium difficile infection.

Clostridium difficile is a major cause of antibiotic-associated diarrhea in hospital and community settings, spreading endemic and epidemic disease in developed and developing areas throughout the world. Its toxins A and B cause epithelial disruption, inflammation, and secretion. Diagnosis of infection with C. difficile is based on appropriate clinical presentation and demonstration of the presence of either toxin A or B, or both. Established treatment is still predominantly metronidazole and vancomycin. The association of antibiotic therapy with recurrent disease and antimicrobial resistance, especially vancomycin-resistant enterococci, highlights the need for new approaches to managing C. difficile infection.

Anti-Bacterial Agents↗
PubMed2000

Changes over time in the epidemiology of diarrhea and malnutrition among children in an urban Brazilian shantytown, 1989 to 1996.

BACKGROUND: Endemic diarrhea and its associated malnutrition remain leading causes of childhood morbidity and mortality in developing countries. This study was undertaken to describe changes in the incidence of diarrhea and prevalence of malnutrition among children in an urban Brazilian shantytown from 1989 to 1996. A secondary purpose was to examine associations between malnutrition and increased incidence and duration of diarrhea. METHODS: From August 1989 through December 1996 a dynamic birth cohort of 315 children was followed for surveillance of diarrhea and nutrition. Study homes were visited twice or thrice weekly to assess the occurrence of diarrhea. Length and weight of the subjects were measured quarterly. Poisson regression was used to test for associations between prior nutritional status and subsequent diarrhea during a quarter. Multiple regression was used to test for an association between nutritional status and episode duration. RESULTS: Declines in both age-adjusted attack rates (6.0 episodes/child-year in study year 3 [1991] to 2.5 episodes per child-year in study year 8 [1996] and days of diarrhea per child-year (30.8 days/child-year in year 3 to 8.5 days/child-year in year 8) were correlated with yearly improvements in mean nutritional status (R2= 0.84, P < 0.05, for mean length-for-age with mean number of episodes/child-year [corrected]. Both length- and weight-for-age were significant predictors of diarrhea incidence, including persistent episodes (> or =14 d), but not duration. CONCLUSIONS: These results demonstrate marked changes over time in the diarrhea burden and nutritional status of children in this population and provide further evidence of a significant association between malnutrition and increased incidence of diarrhea.

Brazil↗
PubMed2000

The preterm prediction study: cervical lactoferrin concentration, other markers of lower genital tract infection, and preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: This study was undertaken to determine the relationship among cervical lactoferrin concentration, other cervical markers potentially related to infection, and spontaneous preterm birth. STUDY DESIGN: Cervical lactoferrin concentrations obtained at 22 to 24 weeks' gestation among 121 women who had a spontaneous preterm birth <35 weeks' gestation were compared with cervical lactoferrin concentrations among 121 women matched for race, parity, and center who were delivered at >/=37 weeks' gestation. Results were compared against levels of cervical interleukin 6, fetal fibronectin, and sialidase, against cervical length according to ultrasonography, and according to the bacterial vaginosis Gram stain score. RESULTS: Cervical lactoferrin concentrations ranged from not measurable (19% of the concentrations were below the threshold for this assay) to a titer of >/=1:64. There was no significant difference in the overall distributions of lactoferrin concentrations between the case patients and control subjects (P =.18). Only when the highest titers of lactoferrin were considered were there more women in the spontaneous preterm birth group (6/121 vs 0/121; P =.03). According to Spearman correlation analyses the cervical lactoferrin concentrations were strongly related to interleukin 6 concentration (r =.51; P =.0001), sialidase activity (r =.38; P =.0001), and bacterial vaginosis (r =.38; P =.0001), were weakly related to fetal fibronectin (r =. 16; P =.01), and were not related to cervical length. With the 90th percentile (a dilution of 1:32) used as a cutoff to establish a dichotomous variable, lactoferrin concentration had the following odds ratios and 95% confidence intervals for associations with other potential markers of infection: bacterial vaginosis odds ratio, 4.8 (95% confidence interval, 2.2-10.3); interleukin 6 concentration odds ratio, 2.8 (95% confidence interval, 1.2-6.5); sialidase activity odds ratio, 5. 5 (95% confidence interval, 2.2-13.7); fetal fibronectin concentration odds ratio, 0.6 (95% confidence interval, 0.2-2.0); chlamydiosis odds ratio, 2.3 (95% confidence interval, 0.8-6.9); and short cervix odds ratio, 0.5 (95% confidence interval, 0.2-1.4). CONCLUSIONS: Lactoferrin found in the cervix correlated well with other markers of lower genital tract infection. High lactoferrin levels were associated with spontaneous preterm birth but had a very low predictive sensitivity.

Bacterial Infections↗
PubMed2000

Retinol and retinol-binding protein: gut integrity and circulating immunoglobulins.

Vitamin A (retinol) is required to maintain immunity and epithelial turnover and is a key micronutrient needed for combating infection. Vitamin A actions on the immune system are diverse and cannot be accounted for by a single effect or mechanism. The actions of retinol in maintaining gut integrity in humans and immunoglobulin levels in mice was investigated. For 30 children, performance on the lactulose/mannitol test, a test commonly used to assess intestinal barrier function, was inversely correlated (P=.012) with serum retinol concentrations. Thus, children with lower serum retinol, and presumably poorer vitamin A nutritional status, are more likely to have impaired intestinal integrity. Knockout mice that have impairments in plasma retinol transport have circulating immunoglobulin levels that are half those observed in matched wild type mice. No differences were observed in B and T cell populations present in spleen, thymus, and bone marrow.

Animals↗
PubMed2000

Micronutrients and infection: interactions and implications with enteric and other infections and future priorities.

Symposium presentations have focused on the elegant molecular science and the biologic mechanisms by which micronutrients play critical roles in cellular and humoral immune responses, cellular signaling and function, and even in the evolution of microbial virulence. The concluding session examined the practical issues of how best to evaluate the nutritionally at-risk host, especially in the areas of greatest need-an analytical model of nutrient-immune interactions, implications of nutritional modulation of the immune response for disease, and the implications for international research and child health. This overview illustrated how malnutrition may be a major consequence of early childhood diarrhea and enteric infections, as enteric infections may critically impair intestinal absorptive function with potential long-term consequences for growth and development. The potentially huge, largely undefined DALY (disability-adjusted life years) impact of early childhood diarrheal illnesses demonstrates the importance of quantifying the long-term functional impact of largely preventable nutritional and infectious diseases, especially in children in developing areas.

Child↗