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Herbert L DuPont

Publications and source records attributed to Herbert L DuPont.

At least 19 recordsLinked to original sources
PubMed2026

First-line fecal microbiota transplantation for the management of immune checkpoint inhibitor-mediated diarrhea and colitis.

Immune checkpoint inhibitor (ICI) therapy commonly leads to adverse events such as ICI-mediated diarrhea and colitis (IMDC). Fecal microbiota transplantation (FMT) remains an option for patients with refractory colitis. We report a multi-omics profiling of patients receiving first-line FMT for IMDC. In our preliminary analysis, 10 (76.9%) patients achieve clinical response, with a median time to clinical improvement of 1.5 (1-10.5) days. Among responder patients with baseline and follow-up samples, 6 (75%) show an increase in alpha-diversity post-FMT. Pre-FMT samples show an increase in the abundance scores of plasma cells, neutrophils, macrophages (M1 and M2), memory activated and resting memory CD4+ T cells, CD8+ T cells, T follicular helper (Tfh) cells, and regulatory T cells (Tregs), all of which decrease post-FMT. In a small cohort of patients, we identify potential mechanisms for FMT response and demonstrate that first-line FMT in patients with IMDC (NCT04038619) can be effective.

FMT↗
PubMed2006

Association of putative enteroaggregative Escherichia coli virulence genes and biofilm production in isolates from travelers to developing countries.

Enteroaggregative Escherichia coli (EAEC) is an emerging enteric pathogen that causes acute and chronic diarrhea among children, human immunodeficiency virus-infected patients, and travelers to developing regions of the world. The pathogenesis of EAEC strains involves the production of biofilm. In this study, we determined the association between presence of putative EAEC virulence genes and biofilm formation in 57 EAEC isolates (as defined by HEp-2 adherence) from travelers with diarrhea and in 18 EAEC isolates from travelers without diarrhea. Twelve nondiarrheagenic E. coli isolates from healthy travelers were used as controls. Biofilm formation was measured by using a microtiter plate assay with the crystal violet staining method, and the presence of the putative EAEC virulence genes aap, aatA, aggR, astA, irp2, pet, set1A, and shf was determined by PCR. EAEC isolates were more likely to produce biofilm than nondiarrheagenic E. coli isolates (P = 0.027), and the production of biofilm was associated with the virulence genes aggR, set1A, aatA, and irp2, which were found in 16 (40%), 17 (43%), 10 (25%), and 27 (68%) of the biofilm producers versus only 4 (11%), 6 (6%), 2 (6%), and 15 (43%) in non-biofilm producers (P = 0.008 for aggR, P = 0.0004 for set1A, P = 0.029 for aatA, and P = 0.04 for irp2). Although the proportion of EAEC isolates producing biofilm in patients with diarrhea (51%) was similar to that in patients without diarrhea (61%), biofilm production was related to the carriage of aggR (P = 0.015), set1A (P = 0.001), and aatA (P = 0.025). Since aggR is a master regulator of EAEC, the presence of aap (P = 0.004), astA (P = 0.001), irp2 (P = 0.0006), pet (P = 0.002), and set1A (P = 0.014) in an aggR versus an aggR-lacking background was investigated and was also found to be associated with biofilm production. This study suggests that biofilm formation is a common phenomenon among EAEC isolates derived from travelers with or without diarrhea and that multiple genes associated with biofilm formation are regulated by aggR.

Biofilms↗
PubMed2006

Impact of vitamin A on selected gastrointestinal pathogen infections and associated diarrheal episodes among children in Mexico City, Mexico.

BACKGROUND: The overall effect of vitamin A supplementation on diarrheal disease in community trials may result from its effect on specific diarrheal pathogens. METHODS: We conducted a placebo-controlled, double-blind trial of the prophylactic effect of vitamin A on gastrointestinal pathogen infections and clinical symptoms among 188 children in Mexico City, Mexico, from January 1998 to May 1999. Children 6-15 months of age were randomly assigned to receive either a vitamin A supplement (for children <12 months of age, 20,000 international units [IU] of retinol; for children > or =12 months of age, 45,000 IU of retinol) every 2 months or a placebo and were followed for up to 15 months. Stool samples, collected semimonthly, were screened for enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC), Shiga toxin-producing E. coli (STEC), enteroinvasive E. coli (EIEC), and Giardia lamblia. RESULTS: Vitamin A supplementation reduced the prevalence of EPEC infections (rate ratio [RR], 0.52 [95% confidence interval {CI}, 0.23-0.86]) and led to shorter durations of both EPEC and ETEC infections. Supplementation also reduced the prevalence of EPEC-associated diarrhea (RR, 0.41 [95% CI, 0.16-1.00]), EPEC-associated fever (RR, 0.15 [95% CI, 0.02-0.98]), and G. lamblia-associated fever (RR, 0.27 [95% CI, 0.13-0.80]). Finally, children who received vitamin A supplementation had shorter durations of EPEC-associated diarrhea than did children who did not receive supplementation but had longer durations of G. lamblia-associated diarrhea. CONCLUSIONS: These results suggest that the effect of vitamin A supplementation on clinical outcomes may be pathogen dependent.

Diarrhea↗
PubMed2006

Enteroaggregative Escherichia coli is a cause of acute diarrheal illness: a meta-analysis.

BACKGROUND: Conflicting studies exist regarding the role of enteroaggregative Escherichia coli (EAEC) as a cause of acute diarrheal illness. The objective of this meta-analysis was to determine whether identification of EAEC in stool samples is associated with acute diarrheal illness among different subpopulations, by geographic area. METHODS: A comprehensive search of electronic bibliographic databases (Medline and PubMed) from August 1985 to January 2006, as well as a search of conference proceedings, references of articles, and contacts with investigators of EAEC, yielded 354 studies. RESULTS: Forty-one studies (12%) that met the selection criteria (i.e., that examined the association between acute diarrheal illness and the excretion of EAEC among different subpopulations) were included. In this meta-analysis, presence of EAEC identified with the HEp-2 cell adherence assay was found to be significantly associated with acute diarrheal illness among children residing in developing regions (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.36-1.83) and industrialized regions (OR, 1.23; 95% CI, 1.03-1.48), adults with human immunodeficiency virus infection residing in developing regions (OR, 6.43; 95% CI, 2.91-14.16), adults residing in developing regions (OR, 7.15; 95% CI, 1.96-26.04), and international travelers to developing regions (OR, 6.72; 95% CI, 2.62-17.20). A limited number of studies were available that examined the role of EAEC identified by its virulence genes by a DNA probe. CONCLUSIONS: On the basis of this meta-analysis, we conclude that EAEC is a cause of acute diarrheal illness among many different subpopulations in both developing and industrialized regions, that EAEC strains are very heterogeneous and that additional studies that examine the role of EAEC in acute diarrheal illness are needed.

Escherichia coli Infections↗
PubMed2006

Enteroinvasive Escherichia coli severe dysentery complicated by rotavirus gastroenteritis.

Enteroinvasive Escherichia coli (EIEC) is an important agent of pediatric diarrhea and dysentery in developing countries. We report a life-threatening severe dysentery case due to EIEC in a malnourished 4-month-old male, native Indian infant co-infected with rotavirus. The severe gastrointestinal bleeding anemia and hypovolemic shock was successfully treated with IV blood transfusions, rehydration and antibiotic therapy.

Acidosis↗
PubMed2006

Rifaximin: a novel nonabsorbed rifamycin for gastrointestinal disorders.

Rifaximin, a virtually nonabsorbed (<0.4%) rifamycin drug, has in vitro activity against aerobic and anaerobic gram-positive and gram-negative microorganisms. Because rifaximin is nonabsorbed, systemic adverse effects are unusual, and after 3 days of therapy, the fecal level of the drug reaches 8000 microg/g. Moreover, the important selection of resistant mutants by the related drug, rifampin, has not yet been observed for rifaximin. Rifaximin has been demonstrated to reduce the duration of traveler's diarrhea secondary to noninvasive bacterial pathogens and recently has been shown to reduce the occurrence of the disease when used for chemoprophylaxis. Preliminary studies have demonstrated its potential for the treatment of other gastrointestinal disorders, such as hepatic encephalopathy. Additional studies should be performed to further define the role of rifaximin in the treatment of gastrointestinal diseases in adults and children.

Anti-Infective Agents↗
PubMed2006

Fecal cytokines and markers of intestinal inflammation in international travelers with diarrhea due to Noroviruses.

The intestinal immune and inflammatory responses of Norovirus (NoV) are poorly defined. The objective of this study was to investigate fecal cytokine and lactoferrin profiles in response to NoV gastroenteritis in travelers. Both fecal cytokines and fecal lactoferrin were measured for NoV-associated diarrhea (N = 7), mixed infection of NoV and enterotoxigenic E. coli (ETEC)-associated diarrhea (N = 10) and in pathogen-negative diarrhea cases (N = 19). Both IL-2 and IFN-gamma were significantly increased in NoV-associated diarrhea specimens, suggesting a predominant Th1 immune response to NoV infection in the gut. When a mixed infection of NoV and ETEC occurred, a combined Th1/Th2 response was observed suggesting a dual immune response secondary to infection by both pathogens. Intestinal inflammation associated with increased fecal lactoferrin, important in bacterial enteric infection, was not found in NoV-associated gastroenteritis.

Adult↗
PubMed2006

Travelers' diarrhea: modern concepts and new developments.

Travelers' diarrhea occurs when persons move from industrialized regions to developing countries with reduced hygiene. Bacterial enteropathogens from ingested food are the primary causes. Although it is possible to reduce the occurrence of illness by careful selection of food and beverages, travelers do not seem willing to restrict their diets. Diarrhea is associated with a disability of 24 hours per episode, interfering with travel plans and, of even greater concern, post-diarrhea irritable bowel syndrome (IBS) occurs in up to 10% of patients. The use of rifaximin, a poorly absorbed drug, is likely to become common as an attempt to prevent diarrhea and post-infectious IBS. All travelers to high-risk areas should take with them an effective antibacterial drug (rifaximin, fluoroquinolones, or azithromycin) for self-treatment of diarrhea occurring during travel. Additional work is needed to improve the hygienic conditions found in the developing world into which susceptible persons travel.

Journal Article↗
PubMed2006

Gender risk differences for surgical site infections among a primary coronary artery bypass graft surgery cohort: 1995-1998.

BACKGROUND: Knowledge about gender risk factors associated with acquiring postoperative coronary artery bypass graft (CABG) surgical site infections (SSIs) is limited. OBJECTIVE: Our objective was to determine whether the incidence of SSIs during 30 days postsurgery was greater among females compared with males who undergo primary (first time) CABG. METHODS: A retrospective cohort study of 3878 patients who had primary CABG surgery between January 1, 1995, and December 31, 1998, at a cardiovascular center in the American Southwest. Multivariate techniques were used to analyze outcome risk differences by gender. RESULTS: The nosocomial SSI incidence rate among 957 females was 10.56%; among 2921 males, it was 7.57%; relative risk (RR) was 1.39 (95% confidence interval: 1.12-1.75), and Mantel-Haenszel chi2 test was 8.47 (P = .004). Four preoperative variables were independent predictors of acquiring SSI: female gender, diabetes, body mass index, and urgency of surgery. CONCLUSION: Females were at greater risk for acquiring SSIs postprimary CABG surgery in this cohort. Also, preoperative, perioperative, and postoperative control of glucose levels in diabetics and preoperative reduction of weight in obese patients may help to reduce SSIs post-CABG surgery. More studies are needed to understand gender-associated risk of SSI after CABG surgery.

Aged↗
PubMed2006

New insights and directions in travelers' diarrhea.

Since first studied more than 5 decades ago the risk of travelers'diarrhea for persons going from industrialized regions to developing countries has remained high. Most cases of illness are caused by bacterial agents. Travelers' diarrhea is associated with temporary disability and it may progress to chronic intestinal illness and postinfectious irritable bowel syndrome. Exercising care about food and beverage intake, the use of rifaximin prophylaxis for selective patients, and self-treatment of all resultant illness will continue to be the way in which the disease is prevented or managed best by travelers. Future approaches will be aimed at making host regions safer and providing more effective methods of treatment and prevention of enteric disease during short-term international travel.

Diarrhea↗
PubMed2006

The effect of vitamin A supplementation on the intestinal immune response in Mexican children is modified by pathogen infections and diarrhea.

Vitamin A supplementation has consistently reduced infant mortality and the severity of pathogen-induced diarrhea. The mechanism by which vitamin A modulates the mucosal immune response to produce these effects remains poorly defined. To address this issue, stools collected during the summer months from 127 Mexican children 5-15 mo old enrolled in a larger, randomized, double-blind, placebo-controlled, vitamin A supplementation trial were screened for interleukin (IL)-4, IL-6, interferon-gamma (IFN-gamma), and gastrointestinal pathogens. Fecal cytokine values were categorized into 3 levels (undetectable, or =median). Multinomial regression models were used to determine the probability that vitamin A-supplemented children had higher categorical values of a cytokine than children in the placebo group. Differences in categorical values were also analyzed after stratification by gastrointestinal pathogen infections and diarrheal symptoms. Overall, fecal cytokine categorical levels did not differ between children randomized to the 2 arms. Vitamin A-supplemented children infected with enteropathogenic E. coli (EPEC) had reduced IL-4 and IFN-gamma levels [odds ratio (OR) = 0.3, 95% CI 0.13-0.67 and OR = 0.34, 95% CI 0.14-0.83, respectively] compared with children in the placebo group. Vitamin A-supplemented children had increased IL-4 levels when infected with A. lumbricoides (OR = 12.06, 95% CI 0.95-153.85). In contrast, IL-4 levels increased (OR = 2.14, 95% CI 0.94-4.87) and IFN-gamma levels decreased (OR = 0.51, 95% CI 0.26-0.99) among vitamin A-supplemented children with diarrhea compared with children in the placebo group. These findings suggest that the regulation of the mucosal immune response by vitamin A may depend on the type of enteric pathogen infecting the child and the presence of clinical symptoms.

Animals↗
PubMed2006

A review of an emerging enteric pathogen: enteroaggregative Escherichia coli.

Enteroaggregative Escherichia coli (EAEC) is an increasingly recognized enteric pathogen. It is a cause of both acute and persistent diarrhoea among children, adults and HIV-infected persons, in both developing and developed countries. In challenge studies, EAEC has caused diarrhoeal illness with the ingestion of 10(10) c.f.u. Outbreaks of diarrhoeal illness due to EAEC have been reported, and linked to the ingestion of contaminated food. Diarrhoeal illness due to EAEC is the result of a complex pathogen-host interaction. Some infections due to EAEC result in diarrhoeal illness and elicit an inflammatory response, whereas other infections do not result in a symptomatic infection. Many putative virulence genes and EAEC strains that produce biofilm have been identified; however, the clinical significance of these genes and of biofilm production has yet to be defined. A -251 AA single nucleotide polymorphism (SNP) in the interleukin (IL)-8 promoter region is reported to increase host susceptibility to EAEC diarrhoea. Ciprofloxacin and rifaximin continue to be an effective treatment in persons infected with EAEC. This review is intended to provide an updated review for healthcare workers on EAEC, an emerging enteric pathogen.

Adult↗
PubMed2006

A common polymorphism in the interleukin 8 gene promoter is associated with Clostridium difficile diarrhea.

OBJECTIVE: Mucosal interleukin 8 (IL-8) and neutrophil recruitment are central to the pathogenesis of Clostridium difficile (CD) toxin-induced diarrhea (CDD). We hypothesized that like other inflammatory mucosal infections, susceptibility to CDD would relate to genetically determined variations in the production of IL-8. METHODS: Fecal IL-8 production and single nucleotide polymorphism (SNP) frequency in the -251 region of the IL-8 gene were determined in hospitalized patients: 42 with CDD, 42 with CD-negative diarrhea, and 41 without diarrhea. Cases and controls were matched by age, length of hospital stay, comorbidity, and receipt of antibiotics. RESULTS: An association was found between the IL-8 -251 A/A allele and occurrence of CDD, 39%versus 16% (OR = 3.26, 95% CI 1.09-9.17) and 17% (OR = 5.50, 95% CI 1.22-24.8) for the two control groups. Comparing results by IL-8 genotype for the CDD cases, median and mean fecal IL-8 levels were significantly higher for the -251 A/A genotype (p = 0.03 for median and 0.001 for mean). CONCLUSIONS: These studies indicate a common SNP in the IL-8 gene is associated with increased susceptibility to CDD and with increased fecal IL-8 in diarrheal stools.

Clostridioides difficile↗
PubMed2006

Asymptomatic norovirus infection in Mexican children.

Sixty-three children in periurban Mexico City were examined for the occurrence of asymptomatic norovirus (NoV) infection from June to August 1998. NoV was detected in 48 of 161 stool specimens (29.8%), with 31 children (49.2%) having at least one positive stool. Asymptomatic NoV infection occurred commonly during summertime in a Mexican pediatric population.

Caliciviridae Infections↗
PubMed2006

Current and future developments in travelers' diarrhea therapy.

Diarrhea continues to be the leading health problem among international travelers to developing tropical and semi-tropical regions. Despite more than 50 years of research providing information about the etiology and pathogenesis of the disease, the rate of illness and consequences remain unchanged. An estimated 40% of travelers to developing nations will become ill with diarrhea. Although travelers' diarrhea is considered a self-limited disease, novel and effective approaches to disease prevention and treatment have been realized in recent years. Also, recent evidence has identified a potential for long-term complications of the illness, including postinfectious irritable bowel syndrome. With the advent of poorly absorbed (<0.4%) rifaximin, a treatment option for the common watery diarrhea syndrome equivalent to previously used absorbed antibacterial drugs has emerged. Rifaximin with an excellent safety profile and limited potential to induce coliform resistance, prevents most of the diarrhea that would otherwise occur. With further studies in different settings, new consideration should be given to the routine use of chemoprophylaxis for travelers to high-risk countries. Antibacterial drugs will continue to be the optimal treatment for travelers' diarrhea subjects for the most part caused by bacterial enteropathogens and shorten the duration of diarrhea by 1-2 days compared with no active drug treatment.

Bismuth↗
PubMed2006

Travellers' diarrhoea: contemporary approaches to therapy and prevention.

Travellers' diarrhoea remains a major public health problem, contributing to significant morbidity and disability. Because bacterial enteropathogens cause a majority of this form of diarrhoea, antibacterial drugs are effective when used in chemoprophylaxis or for empirical treatment.A review of the MEDLINE listings for travellers' diarrhoea for the past 4 years was conducted; a library of >1,000 scientific articles on the topic was also considered in developing this review. Persons who travel from industrialised countries to developing countries of the tropical and semi-tropical world are the individuals who experience travellers' diarrhoea. While diarrhoea occurs with reduced frequency among persons travelling to low-risk areas from other low- or other high-risk areas, and there remain areas of intermediate risk, this review looks primarily at the illness occurring in persons from industrialised regions visiting high-risk regions of Latin America, Africa and Southern Asia. The material reviewed deals with the high frequency of acquiring diarrhoea during international travel to high-risk areas, seen in approximately 40%, and the expected bacterial causes of illness, of which diarrhoeagenic Escherichia coli is the most important. The host risk factors associated with increased susceptibility to diarrhoea include young age, lack of previous travel to high-risk regions in the past 6 months, indiscriminate food and beverage selection patterns, and host genetics. It appears feasible to decrease the rate of illness among the travelling public by careful food and beverage selection or through chemoprophylaxis with nonabsorbed rifaximin. Chemoprophylaxis with rifaximin should help to reduce the occurrence of travellers' diarrhoea and hopefully prevent post-diarrhoea complications, including irritable bowel syndrome. Early empirical therapy with antibacterial drugs, including rifaximin, a fluoroquinolone or azithromycin, will decrease the duration of illness and return travellers more quickly to their planned activities.With collaboration between local governments and public health researchers, it may be possible to improve hygiene in areas to be visited, which may translate into reduced rates of illness. More liberal use of rifaximin prophylaxis is likely to reduce the occurrence of illness and complications of disease. Vaccines and immunoprophylactic products may be beneficial for prevention of a subset of individuals otherwise developing diarrhoea.

Anti-Bacterial Agents↗