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Traveler's diarrhea [keywords]
- Arginine deiminase pathway is far more important than urease for acid resistance and intracellular survival in Laribacter hongkongensis: a possible result of arc gene cassette duplication. [Journal Article]
- BMC Microbiol 2014; 14(1):42.
Laribacter hongkongensis is a Gram-negative, urease-positive bacillus associated with invasive bacteremic infections in liver cirrhosis patients and fish-borne community-acquired gastroenteritis and traveler's diarrhea. Its mechanisms of adaptation to various environmental niches and host defense evasion are largely unknown. During the process of analyzing the L. hongkongensis genome, a complete urease cassette and two adjacent arc gene cassettes were found. We hypothesize that the urease cassette and/or the arc gene cassettes are important for L. hongkongensis to survive in acidic environment and macrophages. In this study, we tested this hypothesis by constructing single, double and triple non-polar deletion mutants of the urease and two arc gene cassettes of L. hongkongensis using the conjugation-mediated gene deletion system and examining their effects in acidic environment in vitro, in macrophages and in a mouse model.HLHK9∆ureA, HLHK9∆ureC, HLHK9∆ureD and HLHK9∆ureE all exhibited no urease activity. HLHK9∆arcA1 and HLHK9∆arcA2 both exhibited arginine deiminase (ADI) activities, but HLHK9∆arcA1/arcA2 double deletion mutant exhibited no ADI activity. At pH 2 and 3, survival of HLHK9∆arcA1/arcA2 and HLHK9∆ureA/arcA1/arcA2 were markedly decreased (p < 0.001) but that of HLHK9∆ureA was slightly decreased (p < 0.05), compared to wild type L. hongkongensis HLHK9. Survival of HLHK9∆ureA/arcA1/arcA2 and HLHK9∆arcA1/arcA2 in macrophages were also markedly decreased (p < 0.001 and p < 0.01 respectively) but that of HLHK9∆ureA was slightly decreased (p < 0.05), compared to HLHK9, although expression of arcA1, arcA2 and ureA genes were all upregulated. Using a mouse model, HLHK9∆ureA exhibited similar survival compared to HLHK9 after passing through the murine stomach, but survival of HLHK9∆arcA1/arcA2 and HLHK9∆ureA/arcA1/arcA2 were markedly reduced (p < 0.01).In contrast to other important gastrointestinal tract pathogens, ADI pathway is far more important than urease for acid resistance and intracellular survival in L. hongkongensis. The gene duplication of the arc gene cassettes could be a result of their functional importance in L. hongkongensis.
- Acute diarrhea. [Journal Article]
- Am Fam Physician 2014 Feb 1; 89(3):180-9.
Acute diarrhea in adults is a common problem encountered by family physicians. The most common etiology is viral gastroenteritis, a self-limited disease. Increases in travel, comorbidities, and foodborne illness lead to more bacteria-related cases of acute diarrhea. A history and physical examination evaluating for risk factors and signs of inflammatory diarrhea and/or severe dehydration can direct any needed testing and treatment. Most patients do not require laboratory workup, and routine stool cultures are not recommended. Treatment focuses on preventing and treating dehydration. Diagnostic investigation should be reserved for patients with severe dehydration or illness, persistent fever, bloody stool, or immunosuppression, and for cases of suspected nosocomial infection or outbreak. Oral rehydration therapy with early refeeding is the preferred treatment for dehydration. Antimotility agents should be avoided in patients with bloody diarrhea, but loperamide/simethicone may improve symptoms in patients with watery diarrhea. Probiotic use may shorten the duration of illness. When used appropriately, antibiotics are effective in the treatment of shigellosis, campylobacteriosis, Clostridium difficile, traveler's diarrhea, and protozoal infections. Prevention of acute diarrhea is promoted through adequate hand washing, safe food preparation, access to clean water, and vaccinations.
- Commercializing diarrhea vaccines for travelers. [REVIEW]
- Hum Vaccin Immunother 2014 Feb 4; 10(6)
Continued growth in international travel and forecasts for a great increase in the number of people who travel from industrialized to emerging and developing countries make it necessary to develop and improve the capacity to provide health protection to travelers. Measures available to prevent some diseases include a currently limited number of marketed vaccines which represent extremely useful tools to protect travelers. Travelers very often experience diarrheal and gastrointestinal diseases for which some vaccines are available. Use of these vaccines should be evaluated based on traveler and travel destination and characteristics. Vaccines available include those against cholera, typhoid fever, hepatitis A, hepatitis E (only available in China), and rotavirus. The aim of this review is to provide an updated summary about each of the abovementioned vaccines that may be useful for making decisions regarding their use and assessing their indications in recommendations for travelers.
- Effects of pre-deployment loperamide provision on use and travelers' diarrhea outcomes among U.S. military personnel deployed to Turkey. [JOURNAL ARTICLE]
- Travel Med Infect Dis 2014 Jan 21.
This study assessed the efficacy of education and self-treatment with loperamide on diarrhea morbidity and healthcare utilization in a deployed military setting.In this prospective, controlled study, volunteers from military personnel deployed to Incirlik Air Base received either travelers' diarrhea education (non-loperamide group) or education plus a supply of loperamide (loperamide group). Volunteers were surveyed to determine frequency and outcomes of diarrheal illness.109 deployed personnel were enrolled with 48 assigned to the loperamide group, and 61 to the non-loperamide group. Overall, 41 (38%) service members had at least one diarrheal episode. Only 10 (9%) service members sought treatment from a healthcare provider and the distribution was similar in both groups. Loperamide use for self-treatment was more common in the loperamide group (85%) vs. (57%), [p = 0.02]) but use of antibiotics was similar in both groups (loperamide (30%) vs. non-loperamide (20%).Provision of loperamide and education did not significantly affect healthcare utilization or antibiotic use to manage diarrheal episodes, when compared to education alone. Further prospective studies will either need a very large patient population to power them or should use other primary end points such a functional assessment in addition to seeking care.
- Recovery of Cyclospora cayetanensis among asymptomatic rural Thai schoolchildren. [Journal Article]
- Asian Pac J Trop Med 2014 Feb; 7(2):119-23.
To obtain the prevalence with clinical symptoms of Cyclospora cayetanensis (C. cayetanensis), a coccidian protozoan parasite, in Thailand which is the cause of an intestinal infection characterized by sporadic-to-frequent explosive diarrhea.In a field survey conducted by the Faculty of Tropical Medicine, Mahidol University, as part of the existing parasite-control program, a total of 2 540 faecal samples from villagers in Nan Province, Thailand, were collected and examined to determine the prevalence and clinical characteristics of parasitic infections.Twelve cases of C. cayetanensis infection were found during faecal examination of schoolchildren aged 5-12 years. None exhibited obvious clinical symptoms, especially evidence of diarrhea; 5 of 12 had loose faeces, one reported frequent symptoms of abdominal discomfort, and another had pale conjunctiva with low hematocrit. The children were generally asymptomatic.This finding confirms a public-health issue with potentially serious consequences whereby children can be exposed to an environment contaminated with food-and water-borne transmitted oocysts, and can hence become infected with C. cayetanensis.
- A CssA, CssB and LTB chimeric protein induces protection against Enterotoxigenic Escherichia coli. [JOURNAL ARTICLE]
- Braz J Infect Dis 2014 Jan 3.
Enterotoxigenic Escherichia coli (ETEC), a major cause of diarrhea in children under 5, is an important agent for traveler's diarrhea. Heat-labile enterotoxin (LT) and colonization factors (CFs) are two main virulence mechanisms in ETEC. CS6 is one of the most prevalent CFs consisting of two structural subunits viz., CssA, CssB, necessary for attachment to the intestinal cells.In the present research, a chimeric trivalent protein composed of CssB, CssA and LTB was constructed. The chimeric gene was synthesized with codon bias of E. coli for enhanced expression of the protein. Recombinant proteins were expressed and purified. Mice were immunized with the recombinant protein. The antibody titer and specificity of the immune sera were analyzed by ELISA and Western blotting. Efficiency of the immune sera against ETEC was evaluated.Antibody induction was followed by immunization of mice with the chimeric protein. Pretreatment of the ETEC cells with immunized animal antisera remarkably decreased their adhesion to Caco-2 cells.The results indicate efficacy of the recombinant chimeric protein as an effective immunogen, which induces strong humoral response as well as protection against ETEC adherence and toxicity.
- Cytokeratin 8 is an epithelial cell receptor for Pet, a cytotoxic serine protease autotransporter of Enterobacteriaceae. [Journal Article, Research Support, Non-U.S. Gov't]
- MBio 2013; 4(6):e00838-13.
The group of proteins known as serine protease autotransporters of Enterobacteriaceae (SPATE) is a growing family of serine proteases secreted to the external milieu by the type V secretion system. Pet toxin and some other SPATE belong to the class 1 cytotoxic SPATE, which have comparable protease strength on fodrin. Pet is internalized and is directed to its intracellular substrate by retrograde transport. However, the epithelial cell receptor for Pet has yet to be identified. We show that Pet has affinity for the epithelial cell surface until the saturation of the binding sites at 100 nM Pet. Affinity column assays and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis identified a cytokeratin (CK8) which directly binds to Pet, and both proteins colocalized on the cell surface. Interestingly, CK8 is not present in kidney cell lines, which are not susceptible to Pet. Inhibition experiments by using anti-CK8 and ck8 small interfering RNA (siRNA) blocked the cytotoxic effect induced by Pet, while exogenous CK8 expression in kidney cells made them susceptible to Pet intoxication. Recombinant CK8 showed a Pet-binding pattern similar to that seen by using fixed cells. Remarkably, Pet colocalized with CK8 and clathrin at early times (receptor-mediated endocytosis), and subsequently, Pet colocalized with CK8 and Rab5b in the early endosomes. These data support the idea that CK8 is an important receptor for Pet on epithelial cells for starting its cytotoxic effects. These data suggest that therapeutics that block Pet-CK8 interaction may improve outcome of diseases caused by Pet-secreting Enterobacteriaceae such as enteroaggregative Escherichia coli.Receptor-ligand binding is one mechanism by which cells sense and respond to external cues. Receptors may also be utilized by toxins to mediate their own internalization. Pet toxin is secreted by enteroaggregative Escherichia coli, an organism that causes persistent diarrhea in children, traveler's diarrhea, and acute and persistent diarrhea in patients with HIV. Pet is a member of the family of serine protease autotransporters of Enterobacteriaceae (SPATE). SPATE in different pathogens are virulence factors, and Pet belongs to the class 1 cytotoxic SPATE, which have comparable protease strength on their biological substrate, fodrin (a cytoskeletal protein important for maintaining cell viability). To cleave fodrin, Pet enters the cells by clathrin-mediated endocytosis. This mechanism includes receptor-mediated endocytosis (a receptor-ligand complex triggers the endocytosis). We show that CK8 is an important receptor for Pet on epithelial cells and that it may be useful for identifying molecules that block the interaction of CK8 with Pet.
- The therapeutic effect of probiotic bacteria on gastrointestinal diseases. [Journal Article]
- Adv Clin Exp Med 2013 Sep-Oct; 22(5):759-66.
The cause of many gastrointestinal diseases, such as irritable bowel syndrome, chronic inflammatory bowel disease: inflammatory and necrotizing enterocolitis or diarrhea: infectious, traveler's diarrhea, and diarrhea caused by antibiotic treatment is an imbalance of intestinal microflora. Probiotics are live microorganisms, which administered in sufficient quantities, have beneficial health effects. The phenomenon of eating probiotic products started 100 years ago, when the first reports showed beneficial effects of probiotic bacteria on human health. Since then, probiotic preparations have become an essential element in the prevention and treatment of certain diseases. Currently, probiotics are of the utmost importance in supporting the treatment of gastrointestinal diseases and autoimmune disorders. Probiotic microorganisms are primarily lactic acid-producing bacteria of the general Lactobacillus, Bifidobacterium. Many studies have confirmed the beneficial effects of probiotics, particularly in the treatment of acute diarrhea. This applies in particular to diarrhea of viral etiology, especially in infants and young children.
- Vaccination for safe travel to India. [JOURNAL ARTICLE]
- Hum Vaccin Immunother 2013 Nov 27; 10(4)
Worldwide more than 900 million international journeys are undertaken every year. India is one of the favorite tourist destinations around the world. International travel exposes travelers to a range of health risks. Traveling to India possess a threat to travelers with waterborne diseases like bacterial diarrhea, hepatitis A and E, and typhoid fever; vector borne diseases like dengue fever, Japanese encephalitis, and malaria; animal contact disease like rabies. Furthermore diseases spreading through behavior aspects cannot be ruled out hence posing a risk for hepatitis B, HIV/AIDS, hepatitis C as well. Hence, before travel the travelers are advised about the risk of disease in the country or countries they plan to visit and the steps to be taken to prevent illness. Vaccination offers the possibility of avoiding a number of infectious diseases that may be countered abroad. There is no single vaccination schedule that fits all travelers. Each schedule must be individualized according to the traveler's previous immunizations, countries to be visited, type and duration of travel, and the amount of time available before departure.
- Safety and immunogenicity of a single oral dose of recombinant double mutant heat-labile toxin derived from enterotoxigenic Escherichia coli. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- Clin Vaccine Immunol 2013 Nov; 20(11):1764-70.
Enterotoxigenic Escherichia coli (ETEC) is a primary cause of traveler's diarrhea for which there is no licensed vaccine. This phase 1 trial determined the safety and immunogenicity of a recombinantly produced double mutant heat-labile enterotoxin (dmLT) of ETEC. It was administered as a single oral dose of dmLT in escalating doses of 5 μg, 25 μg, 50 μg, and 100 μg, followed by a 72-h inpatient observation, outpatient visits at 8, 14, and 28 days, and telephone calls at 2 and 6 months postvaccination. Safety was assessed by frequency of adverse events, and immune responses determined after immunization included dmLT-specific serum IgA and IgG, fecal IgA, antibody-secreting cells (ASC), and antibodies in lymphocyte supernatant (ALS) responses. All doses were well tolerated by the 36 healthy adults enrolled. Immune responses were limited in the 5- and 25-μg dose recipients. The 50-μg dose recipients trended toward stronger responses than the 100-μg dose recipients by serum IgA (67% versus 33%, P = 0.22), serum IgG (58% versus 33%, P = 0.41), and fecal IgA (58% versus 33%, P = 0.41). By day 14 postvaccination, there were significantly more positive responders (≥4-fold increase from baseline) among the 50- versus 100-μg dose recipients for serum IgA (P = 0.036) but not serum IgG (P = 0.21). In conclusion, a single oral dose of dmLT was well tolerated and immunogenic, with immune responses plateauing at the 50-μg dose. (This clinical trial is registered at www.clinicaltrials.gov, registration number NCT01147445.).