key: cord-021554-uxxrpfl0 authors: Resta-Lenert, Silvia title: Diarrhea, Infectious date: 2004-06-17 journal: Encyclopedia of Gastroenterology DOI: 10.1016/b0-12-386860-2/00180-5 sha: doc_id: 21554 cord_uid: uxxrpfl0 nan Diarrheal diseases are a major cause of morbidity and mortality around the world, especially in developing countries where children suffer the greatest brunt of infectious diarrhea, malnutrition, and death. Annually, approximately 5 million children and infants die worldwide due to diarrheal diseases. In North America, the rate per year is still 0.9 diarrheal episodes per child, and in special circumstances (daycare centers, institutions), the incidence is as high as 5 episodes per year. Fourteen hospital admissions per 1000 children younger than 12 months, per year, result from acute diarrhea. Among the adult population, most patients developing acute diarrhea are managed as outpatients or will not seek medical attention. However, 0.5 million hospital admissions per year, or 1.5% of all adult hospital admissions annually, are due to diarrhea. In developing countries, inadequate water supply, inef®cient or nonexistent sewage removal systems, chronic malnutrition, and lack of access to oral rehydration are responsible for the high incidence of infectious diarrheal diseases. In the industrialized world, acute diarrhea is still one of the most frequent diagnoses in general practice and children, elderly, and immunocompromised patients are the most vulnerable individuals and account for the majority of these cases. Regardless of the etiology, diarrhea is de®ned clinically as the occurrence of three or more episodes of loose stool or any loose stool with blood during a 24 h time period. Symptoms lasting less than 14 days represent acute diarrhea, whereas persistent diarrhea lasts more than 14 days but less than 4 weeks, and chronic diarrhea is de®ned by a duration of symptoms greater than 4 weeks. Infectious diarrheas are miserable illnesses of overwhelming impact on the general survival of entire populations. Throughout history, thousands-strong armies have been defeated by raging diarrheal diseases: from the Greeks and Macedons under Alexander (Tucidides), to the Romans in the campaigns against the Gauls ( Julius Caesar), to the Hundred Years War in 13th century Europe, to Napoleon, the Civil War in America, World War II, and the Vietnam War. Scores of previously healthy men suffered and died from the scourge of diarrhea and dysentery in all of these con¯icts. Twenty years ago, 800 million to 1 billion episodes of infectious diarrhea and nearly 5 million deaths occurred per year worldwide, primarily in developing countries. Ten years later, survival had improved, but the incidence was virtually unchanged despite greater knowledge of the pathophysiology of diarrhea and greater intervention by the World Health Organization (WHO). Approximately 100 million episodes of acute diarrhea occur in the United States yearly, with an incidence of 1.2 to 1.5 diarrheal episodes per person-year. Medical costs/analyses show that 8.0 million Americans sought physician care for diarrhea yearly and 250,000 required hospitalization. Hospitalization and medical costs approached $560 million, whereas lost productivity totaled $200 million. Approximately another 8 million people sought physician care but were not hospitalized. These patients incurred $690 million in medical costs and $2 billion in loss of work hours. An estimated 90 million cases occurred in people who did not seek physician care, costing nearly $20 billion in lost productivity. Approximately 90% of all these cases were presumably of infectious origin. Thus, the total cost estimate for diarrheal diseases exceeds $23 billion annually in the United States alone. Although the elderly have an increased risk for death from diarrhea, death from diarrhea is rare among young children in industrialized countries. In fact, of all pediatric admissions for diarrhea, 0.05% resulted in death, compared with 3% in patients older than age 80. Increased age was the most important risk factor for death with an odds ratio of 52.6 (95% con®dence interval, 37.0 to 76.9) for age 70 or older versus children b5 years. The national mortality ®gures for the 9-year period 1979À1988 in the United States show 51% of diarrheal deaths occurring in individuals older than age 74. Acute infectious diarrhea is transmitted mostly through the fecalÀoral route and by ingestion of contaminated water and food. Infection via the fecalÀoral route occurs by direct contact with index cases, especially under conditions of crowding, such as daycare centers or nursing homes. Waterborne and foodborne outbreaks are another important source of disease transmission and result from general and/or individual failures in proper standards for the safe handling of foods. In most developing nations, acute diarrhea is endemic due to poor sanitation. Furthermore, epidemics of signi®cant proportions often result from natural disasters in areas where water and food supplies are already chronically jeopardized. In some areas of the world, such as Asia, Africa, and Latin America, certain infectious diarrheas (e.g., cholera) have become ongoing pandemics lasting several decades, notwithstanding WHO efforts at eradication. In most parts of the world, a de®nite seasonality is recognized in the incidence of acute diarrhea. In industrialized nations, the highest incidence of hospital admissions for diarrhea occurs in August and September and in the winter months. In developing nations with warmer climates and endemic conditions, variations in incidence occur from year to year in relation to precipitation indices and crop failures. Infectious diarrheas may be classi®ed according to various criteria: duration, underlying mechanism, clinical presentation, etiology, and history. Table I summarizes the various criteria for classifying diarrheas in general and infectious diarrheas in particular. In this section, infectious diarrheas are described according to the duration of the main gastrointestinal symptom. Acute diarrheas last, by de®nition, less than 4 days and the majority are due to infectious agents. Most of these infections are self-limited and generally do not require medical intervention, unless severe dehydration and toxicity develop. However, immunocompromised patients, the elderly, and the very young may develop complications from enteric pathogens that warrant prompt and decisive medical intervention. A list of the major organisms involved in the etiology of acute infectious diarrheas is presented in Table II . Not listed is a type of acute enteritis, waterborne and of presumed infectious origin, that has been responsible for several outbreaks of traveler's diarrhea, known as Brainerd diarrhea. The etiologic agent of this disease still escapes de®nition. Many of the acute infectious diarrheas observed worldwide are diagnosed in the course of local or epidemic outbreaks. Three major situations may be encountered: (1) waterborne infections; (2) Food-borne diarrhea; and (3) traveler's diarrhea. Whereas foodborne diarrhea is often associated with residual microbial toxins, waterborne and traveler's diarrheas are more often caused by active infection via the fecalÀoral route. Table III summarizes the most common causes in these epidemiological situations. A successful enteric pathogen possesses well-developed abilities to colonize, grow, and compete for nutrients in a crowded environment and to interact effectively with the host's enterocytes, inducing changes in the balance between absorption and secretion of water and electrolytes. In most gut infections, a pathogen enters via the oral route and colonizes an area of the ]. In addition to direct effects by microorganisms and their products, enteropathogens induce intestinal damage indirectly via the mucosal in¯ammatory response, which involves secretion of various powerful mediators of secretion and apoptosis. A summary of the current knowledge about the pathogenesis of the most common acute infectious diarrheal syndromes is shown in Fig. 1 . On the basis of these three mechanisms, acute infections present as watery, nonin¯ammatory diarrheal syndromes or in¯ammatory diarrheal syndromes. The majority of watery, nonin¯ammatory diarrhea cases are self-limited diseases characterized by low-grade fever, nausea, vomiting, large-volume diarrhea, and the absence of blood and leukocytes in the stools. This presentation is typically reported in patients infected with enterotoxigenic Escherichia coli, V. cholerae, clostridial and staphylococcal food poisoning, rotavirus, Norwalk virus agent, Giardia lamblia, and Cryptosporidium. On the other hand, the in¯ammatory diarrheal syndrome is characterized by frequent, small-volume stools that may contain blood and leukocytes, tenesmus, fever, and severe abdominal pain. The most common microorganisms causing this syndrome include Salmonella, Shigella, Campylobacter, enterohemorrhagic E. coli, EIEC, Clostridium dif®cile, Entamoeba histolytica, and Yersinia. Table IV describes the basic biologic, pathophysiologic, and clinical characteristics pertinent to the most common enteric pathogens. Persistent diarrhea is emerging as a major world health problem. Children are more likely to develop persistent diarrhea and suffer malnutrition, wasting, and immunocompromise as a consequence. Persistent diarrhea is de®ned by looseÀsoft stools occurring at increased frequency and lasting for more than Postinfectious persistent diarrhea is a poorly de®ned syndrome that occurs as a sequela of an acute episode with de®nite infectious etiology. Patients may develop mild to severe degrees of malabsorption, from lactose intolerance to inability to absorb proteins, fat, and sugars, as well as permanent blunting of villi as assessed by histopathology. The condition is characterized by watery, malodorous stools and progressive wasting. Chronic infectious diarrhea occurs mostly in immunocompromised patients. After an acute infectious episode, patients sometimes develop chronic symptoms that are independent of the etiologic agents of acute diarrhea (irritable bowel syndrome with diarrhea, or, occasionally, ulcerative colitis). Table VI lists the most common agents isolated from cases of chronic infectious diarrhea. By de®nition, chronic diarrhea lasts more than 4 weeks and patients developing this syndrome quite often are hospitalized and have undergone antibiotic therapy for other reasons. Elderly, human immunode-®ciency virus (HIV)/acquired immunode®ciency syndrome (AIDS), transplant, and cancer patients are easy targets for reinfections or reactivation of only partially subdued infectious organisms. In addition to the causes listed above, bacterial overgrowth can occur in areas of bowel stasis or impaired bowel motility. Postsurgery patients, diabetics, posttrauma patients, and intensive care patients are more likely targets of chronic infectious diarrheas from bacterial overgrowth. Infectious diarrhea causes high morbidity and mortality among the aging population worldwide. Multiorgan complications from an acute episode of infectious diarrhea are also more frequent among the elderly. Life expectancy in the United States has risen from an average of 45 years in the 20th century to 75 years at present. By the year 2025, 22% of the U.S. population will be older than age 65. Gastrointestinal physiology and gut colonization change constantly with aging and contribute in a signi®cant way to increasing the susceptibility of elderly people to enteric infections. Furthermore, the gastric acid barrier in the elderly is impaired. The most frequently isolated organisms and most deadly in elderly patients with diarrhea are C. dif®cile, Salmonella, and toxigenic E. coli. These three agents top the list of FIGURE 1 Infectious diarrhea: mechanisms of action of major enteric bacteria and viruses. Enteric pathogens can induce intestinal injury with consequent diarrhea in three ways: (1) by producing enterotoxins that interact with receptors located on the gut epithelial cells and evoke anion secretion, such as V. cholera, EPEC, EAEC, STEC, C. dif®cile, and S. aureus (A); (2) by invading the gut epithelium and M cells, thus altering the cell cytoskeleton and activating intracellular pathways through virulence factors. Organisms that lead to diarrhea through these mechanisms include EIEC, Shigella, EPEC, Salmonella, and rotaviruses (B); (3) by invading mucosal macrophages and inducing in¯ammatory responses leading to intestinal epithelial damage and anion secretion. Campylobacter and Yersinia use this mechanism (B). outbreaks in long-term and short-term care facilities and Salmonella by itself accounts for more than 50% of cases and more than 80% of deaths in food-borne outbreaks in nursing homes. More than 50% of HIV/AIDS patients in the United States experience infectious diarrhea and this estimate may approach 100% in developing countries where the HIV epidemic is currently raging unchecked. These patients are more likely to develop persistent or chronic diarrhea after an acute episode because of their impaired immunity, with a signi®cant increase in morbidity and mortality. Table VII lists the most common causes of infectious diarrhea in AIDS patients. The American Gastroenterological Association (AGA) has published a set of general guidelines for the management of chronic diarrhea in AIDS patients. At least three sets of stool samples should be secured for common enteric bacteria and parasites, including microsporidia, cryptosporidia, and C. dif®cile. Febrile patients with diarrhea should have blood cultures for common enteric bacteria. Patients with CD4 lymphocyte counts of 5100 cells/mm are at high risk for disseminated mycobacterial infection. The most important ®nding in patients presenting with acute diarrhea is the degree of volume depletion, i.e., dehydration. Postural changes in blood pressure are a reliable sign of dehydration. Fever, abdominal tenderness, increased bowel sounds, or blood on rectal examination should alert the physician to acute infectious diarrhea. Microscopic examination of a stool sample or rectal swab is a traditional and helpful tool in the rapid, bedside investigation of diarrheal illness. The specimen is placed on a glass slide and mixed thoroughly with two drops of methylene blue. The presence of ova, cysts, and/or leukocytes may point directly to a diagnosis. The AGA guidelines on managing acute diarrhea indicates empiric antimicrobial therapy in the case of positive fecal leukocytes in a febrile patients. Endoscopy has limited utility in the investigation of acute infectious diarrhea and is not cost-effective. It may have a place, however, in cases of persistent or chronic diarrhea. Preventative measures against infectious diarrhea must include improvements in sanitation (water supply, sewer systems, housing), education of the general population and, where applicable, vaccination campaigns. Unfortunately, no effective vaccines are available for the organisms that cause infectious diarrheas, with the exception of typhoid fever. TREATMENT Most acute diarrheal illnesses are self-limited and no speci®c therapy is required. Water and electrolyte loss can be prevented or treated with oral¯uidÀelectrolyte solutions. Intravenous salineÀglucose solutions are recommended in cases of moderate to severe dehydration. Glucose in the intestinal lumen facilitates the absorption of sodium and the cotransport mechanism for these solutes appears to be unhampered by infection with microorganisms or by their toxins. Antimotility therapy should be reserved for severe cases and chronic diarrheas and avoided in infants and children. Antibiotic or antiviral treatment should be considered in moderate to severe cases in which a microbiological diagnosis is obtained or strongly See Also the Following Articles AIDS, Gastrointestinal Manifestations of Anti-Diarrheal Drugs Campylobacter Cholera Cryptosporidium Cytomegalovirus Diarrhea Foodborne Diseases Food Poisoning Food Safety Giardiasis Rotavirus Salmonella Shigella Traveler's Diarrhea Further Reading Anonymous Epidemiology of Clostridium dif®cile-associated infections Ef®cacy and tolerability of racecadotril in acute diarrhea in children Practice guidelines for the management of infectious diarrhea Principles and Practice of Infectious Diseases Microbes and microbial toxins: Paradigms for microbialÀmucosal interactions. VIII. Pathological consequences of rotaviral infection and its enterotoxin Traveler's diarrhea due to intestinal protozoa The role of antibiotics in the treatment of infectious diarrhea Infectious diarrhea in children Pathogenesis of infectious diarrhea