Mechanisms of infectious diarrhea

Infectious diarrhea is an important public health problem worldwide. Research has provided new insights into the mechanisms of diarrhea caused by various pathogens that are classified as noninflammatory, inflammatory or invasive. These three groups of organisms cause two diarrheal syndromes--noninflammatory diarrhea and inflammatory diarrhea. The noninflammatory diarrheas are caused by enterotoxin-producing organisms such as Vibrio cholerae and enterotoxigenic Escherichia coli, or by viruses that adhere to the mucosa and disrupt the absorptive and/or secretory processes of the enterocyte without causing acute inflammation or mucosal destruction. Inflammatory diarrhea is caused by two groups of organisms--cytotoxin-producing, noninvasive bacteria (e.g. enteroaggregative Escherichia coli, enterohemorrhagic Escherichia coli and Clostridium difficile), or by invasive organisms (e.g. Salmonella spp., Shigella spp., Campylobacter spp., Entamoeba histolytica). The cytotoxin-producing organisms adhere to the mucosa, activate cytokines and stimulate the intestinal mucosa to release inflammatory mediators. Invasive organisms, which can also produce cytotoxins, invade the intestinal mucosa to induce an acute inflammatory reaction, involving the activation of cytokines and inflammatory mediators. Regardless of the underlying mechanism they use, these various types of pathogen have all successfully evolved to evade and modulate the host defense systems. The mechanisms by which the different pathogens invade the host and cause infectious diarrhea are the topic of this Review.     

Traveler's Diarrhea

Travelers' diarrhea (TD) is the most important health issue among international travelers. In high risk areas, 50-90% of travelers may experience an episode of TD. The risk of acquiring TD is influenced by factors such as the destination, duration of stay, standard of accommodation, type of travel, age of the traveler, and also by individual risk factors. Most cases of TD are caused by bacteria; treatment for TD are loperamide and antibiotics. Preventive strategies such as hygiene measures have limited impact. Prophylactic intake of antibiotics or vaccines to prevent from TD can be considered in special situations.     

Probiotics for children with diarrhea: an update

This review focuses on the efficacy of probiotics for diarrhea in children in different settings: day-care centers, diarrhea acquired in the hospital, antibiotic-associated diarrhea, and treatment of acute infectious diarrhea. For prevention of diarrhea acquired in day-care centers, 5 randomized and placebo-controlled trials have been published. Probiotics tested were Lactobacillus GG, Bifidobacterium lactis (alone or in combination with Streptococcus thermophilus), and Lactobacillus reuteri. The evidence of their efficacy in these settings is only modest: statistically significant for some strains only and in any case of minimal to mild clinical importance. Few trials have examined the potential role of probiotics in preventing the spread of diarrhea in hospitalized children, an event most commonly due to either rotavirus or Clostridium difficile, and they have yielded conflicting results. Overall, these studies provide only weak evidence on the efficacy of probiotics. On the other hand, a large number of trials on the role of probiotics in preventing the onset of antibiotic-associated diarrhea have been published. Most commonly employed probiotics were Lactobacillus GG, Bifidobacterium spp., Streptococcus spp., and the yeast Saccharomyces boulardii. In general, these trials do show clear evidence of efficacy, with the 2 most effective strains being Lactobacillus GG and S. boulardii. Today, we have a large number of published clinical trials on the role of probiotics in treating sporadic infectious diarrhea in children, and many of them are randomized, blinded, and controlled. They consistently show a statistically significant benefit and moderate clinical benefit of a few, well-identified probiotic strains-mostly Lactobacillus GG and S. boulardii, but also L. reuteri-in the treatment of acute watery diarrhea, primarily rotaviral, in infants and young children of developed countries. Such a beneficial effect seems to result in a reduction of diarrhea duration of little more than 1 day, and to be exerted mostly on diarrhea due to rotavirus. The effect is not only strain-dependent, but also dose-dependent, with doses of at least 10 billion/d being necessary.     

Acute diarrhea due to enteropathogenic bacteria in patients at hospitals in Tehran

During a study examining causes of diarrhea from May 2004 to May 2005, 808 stool specimens were collected from patients with acute diarrhea in Tehran. Fecal samples were cultured and identified according to the standard biochemical methods. Molecular identification of enteropathogens was carried out by amplification of their virulence genes by polymerase chain reaction. A total of 369 (45.6%) bacterial pathogens were recovered from 808 patients as follows: Shigella spp., 155 (45.6%); diarrheagenic Escherichia coli 143 (38.8%); Salmonella spp., 51 (13.8%); and Campylobacter spp., 20 (5.4%). Most of the diarrheagenic E. coli were Shiga toxin-producing E. coli, with 64 (44.7%) isolates, followed by 47 (32.9%) enterotoxigenic E. coli isolates; among Shigella spp. isolates, 69 (44.5%) Shigella flexneri were predominant. The molecular diagnosis of enteropathogens yielded a more accurate characterization of the prevalence of diarrhea-causing bacterial strains in Iran. The present study revealed a high prevalence of Shigella and diarrheagenic E. coli as the predominant causes of bacterial diarrhea in this region of the world. These two types of bacteria should therefore be considered when designing preventive strategies for people living in Iran.     

Characterization of the human gut microbiome during travelers' diarrhea

Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers'' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the β-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different β-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel.     

Characterization of the human gut microbiome during travelers' diarrhea

Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the β-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different β-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel.     

北京地区1994-2005年腹泻病原菌的分布及其耐药趋势

目的 监测我院1994-2005年与腹泻有关的肠道致病菌的分布及耐药趋势,为本地区流行病学研究、疫苗制备及临床合理用药提供依据.方法 通过常规大便培养,筛出致病菌后经生化及血清学进一步鉴定到种、群或血清型,并以纸片扩散法测定抗菌药物的敏感性.结果 12年分离到肠道病原菌8426株,患者以男性为主,儿童和青年发病为多,每年7～9月为腹泻发病高峰.病原以志贺菌属居首位(占75.11%),其次是弧菌(占12.70%),再依次为沙门菌属、气单胞菌、致病及侵袭大肠埃希菌分别占6.28%、4.43%及1.25%.6329株志贺菌中,福氏志贺菌占75.62%,其次是宋内菌群(23.98%),痢疾志贺菌及鲍氏志贺菌分别占0.22%及0.01%.12年的变化趋势是,每年肠道病原菌总数在逐渐减少,特别是志贺菌、沙门菌减少明显,而弧菌及气单胞菌相对逐渐增多.各菌属及不同的血清型对抗菌药物的敏感率有差异,福氏志贺菌和气单胞菌属多重耐药较多,而宋内志贺菌和弧菌属对多数抗菌药物敏感.结论 北京地区感染性腹泻的病原种类多,随时间的变迁病原变化明显,耐药性不同,应重视监测.     

Reisediarrhö

Traveler’s diarrhea is the common disease contracted when visiting tropical countries, and these countries have a continuously increasing number of visitors. Traveler’s diarrhea may incapacitate but is rarely fatal. In most cases, a spontaneous cure occurs after about 4 days, however a few patients have symptoms lasting several weeks and irritable bowel syndrome can develop. Risk factors involve both the patient (e.g. age, behavior, nationality, genetic factors) and the environment (destination, hotel). The etiology is mostly bacterial, involving pathogens such as enterotoxigenic Escherichia coli (ETEC), Salmonella spp., Shigella spp., and Campylobacter spp., although viruses and parasites may also cause the disease. If complications occur or the diarrhea becomes persistent, diagnostic approaches aim at examining the stool and possibly blood. Treatment for mild diarrhea may include rehydration and antimotility agents; antibiotic treatment may shorten the duration of the acute state and prevent long lasting bowel disorders.     

Isolation of enteropathogenic microorganism from patients with infection of the digestive tract during 1976 to 1988 in Tenri Hospital]

Enteropathogenic microorganisms isolated from feces of 9,393 patients with diarrhea or enteritis in our hospital between 1976 and 1988 were analyzed. As the result of the examination of 5,443 outpatients, 1,811 strains of pathogens were isolated from 1,686 cases (31.0%). Several species including Salmonella spp., Escherichia coli serotype, Vibrio parahaemolyticus, were isolated before 1978, and the incidence of pathogens was low (14.8%). For the 10-year period since 1979, the incidence markedly increased to 34.4%, and the number of pathogens isolated also increased to about twice that before 1978. The main cause of the increase was Campylobacter species. The major pathogens detected since 1979 were Campylobacter spp., E. coli serotype, Salmonella spp., V. parahaemolyticus, etc., but Rota virus, Clostridium difficile, Aeromonas spp., Vibrio fluvialis, etc. have also been detected, showing an increase in the number and diversity of the detected pathogens. As the result of the examination of 3,950 inpatients, 835 strains of pathogens were isolated from 800 cases (20.3%). The incidence of C. difficile was the highest, 423 of 800, followed by E. coli serotype, Salmonella spp., Campylobacter spp., V. parahaemolyticus and Aeromonas spp., in that order. All the inpatients from whom C. difficile was isolated manifested diarrhea or enteritis after administration of antimicrobial agents. The pathogens causing communicable disease were Salmonella spp. serovar Typhi, Salmonella spp. serovar Paratyphi A, Shigella flexneri, Shigella sonnei and Entamoeba histolytica, which were isolated from 5, 1, 3, 2 and inpatients, respectively.     

Advances in the Treatment of Travelers’ Diarrhea

Diarrhea is the most common complaint reported by travelers from industrialized countries visiting developing nations. High-risk areas for travelers’ diarrhea (TD) include South Asia, Sub-Saharan Africa, and Latin America, while moderate-risk areas include Southeast Asia, Middle East, Oceania and the Caribbean. Bacterial pathogens are the major cause of TD. Recent advances in the therapy for diarrhea include a better understanding of the potential benefit of symptomatic and antimicrobial therapy. The mainstay of treatment includes antibacterial therapy with one of three drugs, a fluoroquinolone, rifaximin, or azithromycin. Probiotics have been used in preliminary studies for both treatment and prevention of TD, but more studies are needed with these biologic agents. The aim of this review is to identify the recent advances in the therapy of TD and to provide recommendations for treatment during international travel.     

Antibacterial activity of GUAVA, Psidium guajava Linnaeus, leaf extracts on diarrhea-causing enteric bacteria isolated from Seabob shrimp, Xiphopenaeus kroyeri (Heller)

Guava leaf tea of Psidium guajava Linnaeus is commonly used as a medicine against gastroenteritis and child diarrhea by those who cannot afford or do not have access to antibiotics. This study screened the antimicrobial effect of essential oils and methanol, hexane, ethyl acetate extracts from guava leaves. The extracts were tested against diarrhea-causing bacteria: Staphylococcus aureus, Salmonella spp. and Escherichia coli. Strains that were screened included isolates from seabob shrimp, Xiphopenaeus kroyeri (Heller) and laboratory-type strains. Of the bacteria tested, Staphylococcus aureus strains were most inhibited by the extracts. The methanol extract showed greatest bacterial inhibition. No statistically significant differences were observed between the tested extract concentrations and their effect. The essential oil extract showed inhibitory activity against S. aureus and Salmonella spp. The strains isolated from the shrimp showed some resistance to commercially available antibiotics. These data support the use of guava leaf-made medicines in diarrhea cases where access to commercial antibiotics is restricted. In conclusion, guava leaf extracts and essential oil are very active against S. aureus, thus making up important potential sources of new antimicrobial compounds.     

The Traveling Microbiome

Given the recent interest in the human gut microbiome in health and disease, we have undertaken a review of the role of the gut microbiome as it relates to travel. Considering the microbiome as the interface with the external world of the traveler, not only from the perspective of protection from enteric infection by colonization resistance but also the possibility that a traveler’s unique microbiome may place him or her at lesser or greater risk for enteric infection. We review available data on travel, travelers’ diarrhea, and the use of antibiotics as it relates to changes in the microbiome and the acquisition of multi-drug-resistant bacteria and explore the interplay of these factors in the development of dysbiosis and the post-infectious sequelae of TD, specifically PI-IBS. In addition, we explore whether dietary changes in travel affect the gut microbiome in a way which modulates gastrointestinal function and susceptibility to infection and discuss whether pre- or probiotics have any meaningful role in prevention or treatment of TD. Finally, a discussion of important research gaps and opportunities in this area is identified.     

乌鲁木齐地区2010年腹泻病原菌耐药性监测与分析

目的 调查2010年乌鲁木齐地区腹泻病原菌耐药性特征,为指导本地区临床合理用药提供参考.方法 对腹泻标本进行细菌学培养,利用生化、血清学方法 对分离菌株进行特异性鉴定.在此基础上,利用K-B纸片扩散法检测病原菌的耐药性.结果 从392份腹泻标本中,分离获得病原菌103株,主要包括47株志贺菌、33株致泻性大肠埃希菌及1...     

Virulence blockers as alternatives to antibiotics: type III secretion inhibitors against Gram-negative bacteria

In recent years mounting problems related to antibiotic-resistant bacteria have resulted in the prediction that we are entering the preantibiotic era. A way of preventing such a development would be to introduce novel antibacterial medicines with modes of action distinct from conventional antibiotics. Recent studies of bacterial virulence factors and toxins have resulted in increased understanding of the way in which pathogenic bacteria manipulate host cellular processes. This knowledge may now be used to develop novel antibacterial medicines that disarm pathogenic bacteria. The type III secretion system (T3SS) is known to be a potent virulence mechanism shared by a broad spectrum of pathogenic Gram-negative bacteria that interact with human, animal and plant hosts by injecting effector proteins into the cytosol of host cells. Diseases, such as bubonic plague, shigellosis, salmonellosis, typhoid fever, pulmonary infections, sexually transmitted chlamydia and diarrhoea largely depend on the bacterial proteins injected by the T3SS machinery. Recently a number of T3SS inhibitors have been identified using screening-based approaches. One class of inhibitors, the salicylidene acylhydrazides, has been subjected to chemical optimization and evaluation in several in vitro and ex vivo assays in multiple bacterial species including Yersinia spp., Chlamydia spp., Salmonella spp. and Pseudotuberculosis aeruginosa. Reports published up to date indicate that T3SS inhibitors have the potential to be developed into novel antibacterial therapeutics.     

Pericarditis due to anaerobic bacteria

This review describes the microbiology, diagnosis and management of pericarditis due to anaerobic bacteria. The predominant anaerobes recovered from patients with pericarditis were: gram-negative bacilli (mostly of the Bacteroides fragilis group), anaerobic streptococci, Clostridium spp., Fusobacterium spp., and Bifidobacterium spp. Anaerobic bacteria can be isolated in pericarditis resulting from the following mechanisms: (1) spread from a contiguous focus of infection, either de novo or after surgery or trauma (pleuropulmonary, esophageal fistula or perforation, and odontogenic); (2) spread from a focus of infection within the heart, most commonly from endocarditis; (3) hematogenous infection, and (4) direct inoculation as a result of a penetrating injury or cardiothoracic surgery. No differences were found in the clinical diagnostic features between cases of pericarditis due to anaerobic bacteria and those due to aerobic and facultative bacteria. Anaerobic gram-negative bacilli have increased their resistance to penicillins and other antimicrobials in the last decade. Complete identification and testing for antimicrobial susceptibility and lactamase production are therefore essential for the management of infections caused by these bacteria. Treatment of pericarditis involving anaerobic bacteria includes the use of antibiotic therapy effective against these organisms.     

Infection‐associated vasculitides

Vasculitides are disorders characterized by inflammation of the vessel walls, often caused by autoimmunity, but sometimes as a result of microbial invasion. Almost all types of microbes including bacteria, viruses, protozoa and fungi have been incriminated in the pathogenesis of vasculitis. Accurate etiological diagnosis is important since immunosuppressive treatment may lead to further deterioration if infection is the cause of vasculitis. Clinical features sometimes provide clues to the etiology. Further evaluation requires a focused and cost‐effective plan of laboratory investigation. The investigations aim at establishing the diagnosis of vasculitis and identify the causative organism. An accurate diagnosis of vasculitis optimally requires histological examination and imaging. For infection‐associated vasculitis, the identification of the organism requires studies of stained specimens, cultures, and/or detection of antigens and antibodies. Ideally, the treatment involves administration of an appropriate antimicrobial. In non‐self‐limiting types of vasculitides, glucocorticoids are needed when the symptoms are progressive, with vital organs involvement, and sometimes, when there is no antimicrobial agent of proven efficacy against the incriminated agent. Additional immunosuppressive agents or interventions must be considered when the disease is severe and/or post‐infective immune mechanisms are involved in the pathogenesis, e.g., severe HBV‐ or HCV‐associated vasculitides. Available preventative vaccinations are also crucial. The incidence of HBV‐associated vasculitides dramatically decreased following HBV vaccination campaigns, and other infection‐associated vasculitides may as well in the future.     

Post-traveler's diarrhea irritable bowel syndrome: a prospective study

OBJECTIVE: Anecdotal evidence suggests that irritable bowel syndrome (IBS) can develop after an episode of traveler's diarrhea (TD). This observation supports a contemporary paradigm proposed for the etiology of IBS and may have important implications for public health strategies aimed at preventing TD. This study aimed to determine the incidence of IBS in people experiencing TD. METHODS: A total of 109 healthy adults traveling outside of Canada or the United States were identified and enrolled in a prospective, cohort field study. GI symptoms before and after travel were assessed using the Rome I criteria. Travel diaries and questionnaires were used to assess for TD. RESULTS: The incidence of TD in the study cohort was 44%. Among those experiencing TD, the incidence of IBS was 4.2%. In those not experiencing TD, the incidence of IBS post-travel was 1.6% (relative risk = 2.5, 95% CI = 0.2-27.2, p = 0.41, ns). There was no significant difference in the incidence of IBS between the exposed and nonexposed groups. CONCLUSIONS: This study does not support a large association between TD and an increased risk of developing IBS. A small increase in relative risk may have been undetected because of the size of the study.     

Risk of Functional Gastrointestinal Disorders in U.S. Military Following Self-Reported Diarrhea and Vomiting During Deployment

Introduction  

Military personnel are frequently deployed to regions of the world with high travelers’ diarrhea (TD) rates. Pathogens associated with TD have been linked to several post-infectious sequelae, including functional gastrointestinal disorders (FGD), such as irritable bowel syndrome (IBS) and functional dyspepsia. Furthermore, stress associated with deployment may potentiate the increased FGD risk.     

Bacterial infections other than spontaneous bacterial peritonitis in cirrhosis

Cirrhotic patients are immunocompromised with a high risk of infection.Proinflammatory cytokines and hemodynamic circulation derangement further facilitate the development of serious consequences of infections.Other than spontaneous bacterial peritonitis,bacteremia and bacterial infections of other organ systems are frequently observed.Gram-negative enteric bacteria are the most common causative organism.Other bacterial infections,such as enterococci,Vibrio spp.,Aeromonas spp.,Clostridium spp.,Listeria monocytogenes,Plesiomonas shigelloides and Mycobacterium tuberculosis are more prevalent and more virulent.Generally,intravenous third generation cephalosporins are recommended as empirical antibiotic therapy.Increased incidences of gram-positive and drug-resistant organisms have been reported,particularly in hospitalacquired infections and in patients receiving quinolones prophylaxis.This review focuses upon epidemiology,microbiology,clinical features and treatment of infections in cirrhosis other than spontaneous bacterial peritonitis,including pathogen-specific and liver diseasespecific issues.     

Infectious diarrhea: Cellular and molecular mechanisms

Diarrhea caused by enteric infections is a major factor in morbidity and mortality worldwide. An estimated 2-4 billion episodes of infectious diarrhea occur each year and are especially prevalent in infants. This review highlights the cellular and molecular mechanisms underlying diarrhea associated with the three classes of infectious agents, i.e., bacteria, viruses and parasites. Several bacterial pathogens have been chosen as model organisms, including Vibrio cholerae as a classical example of secretory diarrhea, Clostridium difficile and Shigella species as agents of inflammatory diarrhea and selected strains of pathogenic Escherichia coli (E. coli) to discuss the recent advances in alteration of epithelial ion absorption. Many of the recent studies addressing epithelial ion transport and barrier function have been carried out using viruses and parasites. Here, we focus on the rapidly developing field of viral diarrhea including rotavirus, norovirus and astrovirus infections. Finally we discuss Giardia lamblia and Entamoeba histolytica as examples of parasitic diarrhea. Parasites have a greater complexity than the other pathogens and are capable of creating molecules similar to those produced by the host, such as serotonin and PGE(2). The underlying mechanisms of infectious diarrhea discussed include alterations in ion transport and tight junctions as well as the virulence factors, which alter these processes either through direct effects or indirectly through inflammation and neurotransmitters.