Laboratory approaches to infectious diarrhea

Future applications of advanced molecular diagnostics in clinical laboratories will enhance significantly capabilities to diagnose bacterial, parasitic, and viral agents in the early course of disease through enhanced assay sensitivities and specificities and improved turnaround times, theoretically leading to more timely and directed therapeutic intervention. Until such time, clinicians must continue to rely on clinical judgment and the diverse battery of traditional culture techniques, direct examination (including light microscopy and electron microscopy), and immunoassays that are available. Cost considerations and the ever-increasing array of infectious agents responsible for infectious gastroenteritis will continue to drive the development of practice guidelines to assist practitioners with reasoned and reasonable approaches to management of diarrheal illnesses.     

The microbiota and infectious diarrhea

Understanding the importance of the fecal microbiota has been key in understanding the pathophysiology of some infectious diarrheas. In addition to normal protective measures of bile, gastric acid, and immune response, among others, we now know that the healthy gut flora protects us from some infectious diarrheas. Antibiotic associated diarrhea (AAD) is an excellent example, as antibiotics perturb the normal flora; the resulting diarrhea may be due to changes in short chain fatty acid metabolism. A severe form of AAD is due to Clostridium difficile, a pathogen that can cause severe diarrhea, colitis and even death. Recurrent Clostridium difficile diarrhea is a difficult clinical problem to treat successfully because one recurrence makes further recurrences more likely, probably because antibiotics are still needed to treat and thus the fecal flora remains abnormal. There is no single effective treatment but therapies include pulsed and tapered antibiotics, the probiotic Saccharomyces boulardii as an adjunct to antibiotics, and even fecal flora reconstitution. It is likely that we will learn even more in the future about the beneficial effect of our microbiota.     

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.     

Pathogenesis of infectious diarrhea.

A brief overview of some of the main features involved in normal physiological bi-directional absorption and secretion of fluid in the gut is given, including the nature and cellular location of key enzymes, ion pumps, symports, antiports and diffusion channels; the microanatomy of intestinal villous vasculature and the dynamics of villus blood flow, which together generate hypertonic zones in villus tip regions; and the production, differentiation, escalator movement (from crypt to villus tip) and subsequent shedding of intestinal epithelial cells. (Neural and hormonal mechanisms that regulate normal mucosal ion transport are not discussed.) The manner in which Vibrio cholerae, several pathotypes of Escherichia coli, several Salmonella serotypes, rotavirus, Campylobacter species, Shigella dysenteriae, Yersinia species and Clostridium difficile perturb these mechanisms and cause diarrhea, is discussed. Throughout the article, the main emphasis is on experimental studies designed to elucidate biological mechanisms and (where relevant) the microbial determinants responsible for diarrheal disease. Allusions are also made to the involvement of host responses such as the inflammatory response, the production and release of potent cytokines and accelerated homeostatic responses (such as increased rates of crypt cell division seen in some infections), and the role that they play in pathophysiological fluid secretion.     

New issues in infectious diarrhea

Infectious diarrhea remains a leading cause of both mortality and morbidity worldwide. Novel organisms recently have been described as causes of previously undiagnosed diarrhea. In addition, changes in epidemiologic trends of known pathogens, such as Clostridium difficile, are occurring, including multiple outbreaks of a newly recognized epidemic strain associated with increased severity of cases and poor response to current antibiotics. Given rising resistance rates, new antimicrobial agents are being studied. Rifaximin is a nonabsorbable, gut-selective antibiotic recently approved by the US Food and Drug Administration for the treatment of travelers' diarrhea caused by noninvasive Escherichia coli. This novel antibiotic has also shown promise in the prevention of travelers' diarrhea, as well as a host of other gastrointestinal disorders. Development of a vaccine against diarrheagenic organisms is of high global importance but has been a challenge, owing to the multiple causative serotypes of E. coli and other organisms.     

感染性腹泻的治疗选择

感染性腹泻在全球范围内都是严重的公共卫生问题,其治疗原则依然存在争议和误区.本文总结近期国内外研究进展,结合作者自身诊治经验,讨论感染性腹泻的治疗时机和治疗策略问题.     

A Bayesian approach to acute infectious diarrhea in adults

Acute infectious diarrhea is a yearly occurrence for most Americans, and is associated with 1 million hospitalizations and about 6000 deaths in the United States annually. Up to 80% of acute infectious diarrhea is caused by noroviruses, which produce a clinically mild illness with a predictable short course and good outcome that make laboratory testing and antimicrobial treatment unnecessary. Most diarrhea-causing bacteria and protozoa can cause a clinical illness "like norovirus"; when they do so in healthy adults neither specialized testing nor antimicrobials is required. The presence or absence of epidemiologic evidence (such as travel, hospitalization, antibiotic use, other exposures)and clinical evidence (such as diarrhea frequency and duration, severity of abdominal pain and fever, character of stool, presence of chronic illness or immune deficiency) can change the probability of "not norovirus" from as low as 8% to as high as 100%. Such probabilities guide the use of laboratory testing and antimicrobial therapy in patients who have acute infectious diarrhea.     

感染性腹泻的临床诊治

本文从病原学、流行病学、诊断和治疗等方面对国内外感染性腹泻的临床诊治作一回顾性总结与评述,并指出感染性腹泻绝不是一个单纯的医学问题,而是错综复杂的社会问题;感染性腹泻是无国界的,是全人类的公害;我国应从现实情况出发,强调预防和控制措施的落实。     

感染性腹泻病的诊断和治疗

编者按感染性腹泻病(infectious diarrhea diseases)是一组多病原体、多因素引起的肠道传染病,长期危害着人类的健康.近年来,我国对感染性腹泻病的研究与控制已取得了重大进展,尤其是1992年在国家卫生部领导下制定了我国统一的《中国腹泻病诊断治疗方案》,对加强我国感染性腹泻病管理,不断改进腹泻病的诊断治疗水症,以及合理使用抗生素等方面起到重要作用.但由于经济文化、卫生条件及地区特殊性等方面存在的差异,加之旅游业迅速发展,外事、商务活动频度的增加,给感染性腹泻病的防治带来许多问题和困难,使其发病率仍列各类传染病之首位.然而,与现代医学突飞猛进的发展相比,感染性腹泻的研究进展显得较为缓慢,为了加强这个领域的研究,使其临床应用和基础理论研究不断深入,本刊特邀有关专家就感染性腹泻病的诊断和治疗问题,结合自已的研究和应用经验,进行系统介绍和讨论,以期对读者有所裨益.1感染性腹泻病原及诊断程序………………………………………………………9252感染性腹泻病原微生物的实验诊断………………………………………………………9273液体疗法在感染性腹泻中的合理应用………………………………………………………9294感染性腹泻的抗生素疗法…………………………………………………………………9305感染性腹泻的微生态疗法…………………………………………………………………9326感染性腹泻中基因疫苗、植物疫苗的应用………………………………………………9347旅游者腹泻………………………………………………………………………………9368艾滋病相关性腹泻………………………………………………………………………………9379病毒性腹泻诊断与治疗………………………………………………………………………93810细菌性痢疾的诊断与治疗………………………………………………………94011 O139群霍乱弧菌感染…………………………………………………………………………94112出血性大肠杆菌O157:H7感染……………………………………………………………………94413隐孢子虫病的诊断与治疗…………………………………………………………945     

慢性感染性腹泻的诊断与治疗

在感染性腹泻中以急性腹泻最为常见 ,但慢性腹泻也时有发生。尤其是现代社会人员流动的频繁及肿瘤、艾滋病等免疫低下人群的增加 ,使其发生率和病死率均显著上升。1　病因与发病因素引起慢性感染性腹泻的病原主要有 :(1)寄生虫如溶组织内阿米巴、贾第鞭毛虫、粪类圆线虫、血吸虫、结肠小袋纤毛虫、隐孢子虫、人芽囊原虫等 ;(2 )细菌如福氏志贺菌、结核杆菌等 ;在一些免疫低下人群中 ,也可由常见细菌 (亲水气单胞菌、耶尔森菌、空肠弯曲菌、艰难梭菌、沙门菌等 )感染所致 ;(3)其它如病毒 (巨细胞病毒等 )、真菌 (白念珠菌等 )亦可发生。造成…     

Travelers' diarrhea: antimicrobial therapy and chemoprevention

The use of preventive measures and self-treatment for travelers' diarrhea is routine in regions where the occurrence of diarrhea is predictably high. People traveling to these areas who do not exercise care in their selection of consumed foods and beverages will suffer high rates of illness. Such diarrhea normally affects the traveler for a day, although it can result in chronic postinfectious irritable bowel syndrome. Although systemic antibacterial drugs are effective in preventing diarrhea, their use is not routinely recommended because of side effects and their importance as a therapy for extra-intestinal infections. This review focuses on current and future uses of antibacterial drugs in the prevention and therapy of travelers' diarrhea. Minimally absorbed (< 0.4%) rifaximin can effectively reduce the occurrence of travelers' diarrhea without side effects. Bismuth subsalicylate is a useful alternative, although it is less effective than rifaximin for the prevention of travelers' diarrhea and the required doses are less convenient. All people who travel to high-risk areas should take curative antimicrobial agents with them for self-treatment of illness: rifaximin 200 mg three times a day for 3 days, or an absorbable agent such as a fluoroquinolone or azithromycin taken in a single dose initially, with the need for a second or third dose determined by clinical response. Loperamide (up to 8 mg per day for < or = 2 days) can be given with the antibiotic to offer rapid symptomatic improvement. In the future, the ability to evaluate the genetic risk of illness acquisition might allow person-specific recommendations to be made.     

感染性腹泻研究进展

感染性腹泻是一个古老而常见的疾患 ,是由病原微生物及其产物或寄生虫所引起的、以腹泻为主并广泛存在、流行于世界各地的肠道传染病 ,也是当今全球性重要的公共卫生问题之一 ,其发病率仅次于上呼吸道感染。在我国感染性腹泻的发病率居所有传染病之首位[1] 。感染性腹泻在世界大部分地区仍是重要的医学难题之一 ,细菌性痢疾、沙门菌感染的发病率居高不下 ,加之新病原体的出现、肠道致泻菌耐药问题等 ,给防治工作及实验室诊断带来了新的难题和挑战[2 ] 。1　霍乱新菌株Ｏ139的流行1993年 3月Ｌａｎｃｅｔ[3 ] 报道了在南亚的印度和孟加拉国多…     

Intestinal permeability to [51Cr]EDTA in infectious diarrhea

Orally administered [⁵¹Cr]EDTA was used to measure intestinal permeability in subjects with infectious diarrhea and in those without gastrointestinal complaints. [⁵¹Cr]EDTA was given to 87 subjects: 63 controls (32 normal controls, and 31 disease controls), and 24 patients with infectious diarrhea. Approximately 100 Ci of [⁵¹Cr]EDTA was given orally after an overnight fast. Urine was collected for the following 24 hr. Intestinal permeability to [⁵¹Cr]EDTA in both normal volunteers and in patients with a variety of diseases not associated with intestinal injury was low and results were in a relatively narrow range. Mean 24-hr urinary excretion of [⁵¹Cr]EDTA, calculated as a percent of the administered dose, in controls was 1.6% (0.2–3.5%). Patients with infectious diarrhea associated with invasive pathogens and/or intestinal inflammation had increased excretion of [⁵¹Cr]EDTA (mean 6.1%,P<0.0001), with elevated excretions in 75%. These results demonstrate that intestinal infections must be considered as possible causes for increased intestinal permeability as assessed by the [⁵¹Cr]EDTA test.     

感染性腹泻的研究现状

腹泻是患者消化道内水分和电解质的积聚和排出,临床表现为便次增多及粪便稀释度降低,排便超过每天3次或排便量>200～300g/d。当腹泻被怀疑或证实继发于病原微生物的感染时,称为感染性腹泻(infectious diarrhea)。感染性腹泻是一个古老而常见     

Empirical antimicrobial therapy for traveler's diarrhea.

Over 7 million cases of traveler's diarrhea, defined as the passage of > or = 3 unformed stools in a 24-h period, occur each year among visitors to developing countries. Bacterial enteric pathogens are the most common etiologic agents isolated. Preliminary clinical results for patients with diarrhea predominantly caused by Campylobacter species have shown that azithromycin may be an effective alternative to fluoroquinolones for the treatment of traveler's diarrhea.