Acute diarrheal disease in children: epidemiology, prevention, and treatment

Diarrhea is one of the most common causes of morbidity and mortality in children worldwide. The causes of acute diarrhea in children vary with the location, time of year, and population studied. There is increasing recognition of a widening array of enteric pathogens associated with diarrheal diseases. Adequate fluid and electrolyte replacement and maintenance are key to managing diarrheal illnesses. Thorough clinical and epidemiologic evaluation is needed to define the severity and type of illness, exposures, and whether the patient in is immunocompromised to direct the performance of selective diagnosis cultures, toxin testing, parasite studies, and the administration of antimicrobial therapy.     

The treatment of acute diarrhea in the third millennium: a pediatrician's perspective

Diarrheal diseases continue to be a major cause of morbidity and mortality worldwide. Although new, potentially useful drugs such as acetorphan are appearing at the horizon, the cornerstone of treatment remains a proper oral rehydration (ORT). Yet, the rates at which ORT is used are still disappointingly low. Despite dramatic progresses in the understanding of the pathophysiology of diarrhea, the list of available drugs is indeed short. Recently however, several new options have appeared that may bear a great potential in the near future. The first is a potential improvement of ORS. It was recently shown that the addition of a resistant starch to oral rehydration solution reduces fecal fluid loss and shortens the duration of diarrhea in patients with cholera. Starches that are resistant to hydrolysis by amylase in fact generate in the colon short-chain fatty acids, which are known to enhance sodium absorption. The second development in treating diarrheal disease is acetorphan (racecadotril). This enkephalinase inhibitor has in fact been shown to be effective in reducing by almost half the stool output of 135 young children with acute diarrhea. Finally, probiotics. In the last few years, they have attracted a great deal of renewed interest, particularly focusing on their effects in treating and preventing diarrheal diseases. Lactobacillus GG proved effective in several clinical trials, mostly randomized and placebo-controlled, in the prevention and/or treatment of acute diarrheal disease in children. We have recently shown (6) the safety and efficacy in its administration in the ORS, especially in Rotavirus-induced diarrheas, in a large multicenter, randomized, double blind and placebo-controlled study conducted on behalf of the ESPGHAN Working Group on Acute Diarrhea.     

Antimicrobial use in children under five years with diarrhea in a central region province, Thailand

This cross-sectional study aimed to estimate the prevalence of appropriate antimicrobial prescribing for treating childhood diarrhea within the public hospital system in a central region province, Thailand. Reported are findings of a prospective clinical audit of 424 cases treated by 38 physicians. Appropriate use of antimicrobials was defined as prescribing antimicrobials for managing an invasive bacterial-type, bloody diarrhea or not prescribing antimicrobials for managing a watery-type or non-bloody diarrhea. Among 424 cases with diarrhea, 12.5% were invasive bacterial-type. Of the 66 diarrheal episodes in which stool samples were cultured, 7 stool specimens were positive, two with Shigella sonnei, two with Vibrio cholerae Ogawa and three with E. coli. Based on the presence of mucus and blood in stools, 27.4% of 424 cases received appropriate antimicrobial drugs. Cotrimoxazole was the most commonly prescribed drug (51%), followed by colistin sulfate (15.3%), norfloxacin (11%), and nalidixic acid (0.5%). The average number of antimicrobials per case of inpatients was higher than outpatients (1.15 vs 0.84, p < 0.001). There was a trend toward prescribing norfloxacin in childhood diarrhea. The Ministry of Public Health should continue providing effective interventions aimed at improving physicians' knowledge of diarrhea treatment. Similar efforts should be directed toward improving caretakers' knowledge about home care for childhood diarrhea and encouraging widespread correct use of oral rehydration therapy (ORT) in the community. Hopefully, such activities will help reduce the inappropriate use of antimicrobial agents in treating diarrheal disease.     

Treatment of diarrhea

Diarrheal diseases remain a leading cause of morbidity and mortality in the developing countries and represent at least a nuisance in the industrialized world. Fluid and electrolyte replacement, particularly via oral rehydration, is the mainstay of therapy for the prevention and treatment of dehydration associated with these illnesses. Antibiotics are not indicated for the majority of enteric infections, and their promiscuous use can contribute to the escalating prevalence of bacterial resistance worldwide. Used judiciously, however, antimicrobial agents can ameliorate illness or curtail pathogen excretion and spread of disease, or both, in some diarrheal infections. Antimicrobial agents are indicated for shigellosis, cholera, traveler's diarrhea, amebiasis, and giardiasis. They are indicated in some specific circumstances to treat infections caused by Campylobacter, some categories of diarrheagenic E. coli, C. difficile, nontyphoidal Salmonella, and certain Vibrionaceae. Few adjunctive treatments provide proven benefit without risk of adverse reactions; most offer no advantage over placebo, and their general use is not encouraged.     

Norovirus gastroenteritis successfully treated with nitazoxanide

Infectious diarrhea is a common occurrence in the immunosuppressed population. We present a 43-year-old individual with large-volume stool output Norovirus acute gastroenteritis in the setting of relapsed refractory acute myelogenous leukemia, hematopoietic stem cell transplantation, and biopsy-proven cutaneous and pulmonary graft-versus-host disease. Therapeutic options such as intravenous immunoglobulin or reduction of immunosuppressants were not a feasible choice. A prompt clinical cure was achieved with nitazoxanide, a broad-spectrum antimicrobial agent. Nitazoxanide may be a safe therapeutic alternative, in which a reduction in immunosuppression may not be a viable option.     

Diarrheogenic Escherechia coli in potable water sources of West Bengal,India

Diarrheal diseases are a major cause of morbidity and mortality in developing countries. Among the bacterial pathogens, diarrheagenic Escherichia coli are most frequently connected in cases with epidemic and endemic diarrhea worldwide. Environmental surveillance for monitoring of E.coli is very rare. In the present study, we have applied a modified technique to quantify coliform and E. coli in different potable water sources and their subsequent characterization (in relation to diarrheal pathogenicity) in the diarrhea endemic foci of West Bengal. More than one-fifth of the targeted sources (21.4%) have been identified harboring E. coli. Serotyping and molecular analysis reveals multidrug resistant EPEC, EIEC and ETEC among 9% of positive sources. Rainy season seems to be the most conducive period for E. coli induced diarrhea. While non-diarrheogenic E.coli were sensitive to most of the drugs, diarrheogenic E. coli, possessing toxicity, showed resistance against tetracycline, kanamycin, furazolidone, amoxicillin, ampicillin, norfloxacin, ciprofloxacin. Presence of multidrug resistant diarrheogenic E.coli justifies the potentiality of potable water sources as its vehicle and as a potent diarrheal inducer in diarrhea prone area along with increasing concern of drug resistance. Presence of diarrheogenic E. coli stresses the urgent need of its environmental surveillance like diarrheogenic Vibrios.     

Ciprofloxacin or trimethoprim-sulfamethoxazole as initial therapy for travelers' diarrhea. A placebo-controlled, randomized trial

The efficacy of ciprofloxacin was compared with that of trimethoprim-sulfamethoxazole in a placebo-controlled trial of the 5-day treatment of acute diarrhea among 181 adults recently arrived in Guadalajara, Mexico. Both antimicrobial agents were significantly (p less than 0.0001) more efficacious than placebo in the treatment of diarrhea, with the average duration of diarrhea being 29, 20, and 81 hours, respectively, in the ciprofloxacin, trimethoprim-sulfamethoxazole, and placebo treatment groups. The antimicrobial agents were also more efficacious than placebo in treating diarrhea caused by enterotoxigenic Escherichia coli, invasive enteropathogens, and unknown pathogens. Both antimicrobials were effective in treating mild-to-moderate and moderate-to-severe disease, and both were well tolerated. Ciprofloxacin appears to be a logical alternative to trimethoprim-sulfamethoxazole in the initial treatment of acute travelers' diarrhea.     

Aeromonas hydrophila diarrhea in a long-term care setting

Infectious diarrheal diseases can be a serious problem in long-term care institutions. Aeromonas hydrophila, a facultative, anaerobic gram-negative rod, has not been implicated previously in an acute diarrheal outbreak in this setting. We report 17 patients with this disorder all characterized by the acute onset of painless, nonbloody diarrhea. Thirteen of 17 (76%) patients had two to four loose bowel movements and a duration of illness of less than 48 hours. Eleven of 17 (65%) patients were afebrile. Stool cultures were obtained in 11 patients; 4 (36%) were positive for A. hydrophila. The disease was fatal in one patient who experienced profuse diarrhea and developed fever, tachycardia, and hypotension. The original source of the A. hydrophila was not identified but transmission is known to be water- or food-borne. Although usually mild and self-limited, A. hydrophila infection as noted in one patient can be fulminant and severe. A. hydrophila diarrhea responds to antibiotic therapy; it is important to consider in the differential diagnosis of acute diarrheal illness among older persons in an institutional setting.     

Acute diarrhea: a practical review.

This review provides a practical, simple, and logical approach to the diagnosis and management of patients with acute infectious diarrhea, one of the most common diagnoses in clinical practice. Diarrhea in the immunocompromised host, traveler's diarrhea, and diarrhea in the hospitalized patient are also discussed. Most episodes of acute diarrhea are self-limited, and investigations should be performed only if the results will influence management and outcome. After an adequate history and physical examination, the clinician should be able to classify the acute diarrheal illness, assess the severity, and determine whether investigations are needed. Most patients do not require specific therapy. Therapy should mainly be directed at preventing dehydration. Various home remedies frequently suffice in mild, self-limited diarrhea. However, in large-volume, dehydrating diarrhea, oral rehydration solutions should be used, as they are formulated to stimulate sodium and water absorption. Antidiarrheal agents can be useful in reducing the number of bowel movements and diminishing the magnitude of fluid loss. The most useful agents are opiate derivatives and bismuth subsalicylate. Antibiotic therapy is not required in most patients with acute diarrheal disorders. Guidelines for their use are presented.     

Crofelemer for the treatment of secretory diarrhea

Secretory diarrhea is a leading cause of morbidity and mortality worldwide. Crofelemer is a first-in-class antidiarrheal agent that simultaneously targets two distinct channels, the cystic fibrosis conductance regulator and calcium-activated chloride channel, responsible for chloride and fluid secretion in the GI tract. Crofelemer is a novel compound extracted from the stem bark latex of the Croton lechleri tree found in the western Amazonian region of South America. There is little to no systemic absorption of crofelemer when given orally and studies have shown minimal toxicity beyond mild gastrointestinal effects. In studies in diarrheal illness associated with primarily a secretory component, such as cholera, travelers’ diarrhea and acute infectious diarrhea, crofelemer has shown improvements in stool consistency and duration of symptoms. Less clear, but interesting, results have been observed in other diarrheal diseases associated with a mixed pathology, including diarrhea in patients with HIV and diarrhea-predominant irritable bowel syndrome.     

Medikamentöse Therapie der infektiösen Diarrhö

Diarrheal diseases are among the most common diseases worldwide. In this review the current treatment recommendations for acute (Part 1) and chronic (Part 2) infectious diarrhea are summarized and typical enteropathogens are discussed. The second part of the article describes chronic diarrhea, its related pathogens and treatment. In contrast to acute diarrhea which is mainly caused by viral and typical bacterial pathogens, chronic diarrhea has mainly non-infectious origins. Protozoal pathogens, such as Giardia lamblia and Entamoeba histolytica in particular are found and more rarely bacterial pathogens, such as Tropheryma whipplei. Opportunistic pathogens cause diarrhea in immunocompromised patients, such as in HIV patients. In these patients cytomegalovirus (CMV) colitis or infections with Cryptosporidium spp., Cyclospora cayetanensis, Isospora belli or microsporidia have to be considered. Besides targeted specific antimicrobial therapy, anti-retroviral drugs improving the underlying immunosuppression and thus the reconstitution of the adaptive immune response remain a cornerstone of the treatment in HIV-positive patients.     

Pharmacological management of diarrhea

According to the World Health Organization, there are approximately 2 billion annual cases of diarrhea worldwide. Diarrhea is the leading cause of death in children younger than 5 years and kills 1.5 million children each year. It is especially prevalent in the developing world, where mortality is related to dehydration, electrolyte disturbance, and the resultant acidosis, and in 2001, it accounted for 1.78 million deaths (3.7% of total deaths) in low- and middle-income countries. However, diarrhea is also a common problem in the developed world, with 211 million to 375 million episodes of infectious diarrheal illnesses in the United States annually, resulting in 73 million physician consultations, 1.8 million hospitalizations, and 3100 deaths. Furthermore, 4% to 5% of the Western population suffers from chronic diarrhea. Given the high prevalence of diarrhea, research has been directed at learning more about the cellular mechanisms underlying diarrheal illnesses in order to develop new medications directed at novel cellular targets. These cellular mechanisms and targets are discussed in this article.     

Bismuth therapy in gastrointestinal diseases

Bismuth therapy has shown efficacy against two major gastrointestinal disorders: peptic ulcer disease and diarrhea. In peptic ulcer disease it is as effective as the H2-receptor antagonists, costs considerably less, and offers a lower rate of relapse. When Helicobacter pylori is implicated, bismuth acts as an antimicrobial agent, suppressing the organism but not eliminating it. In recent studies, bismuth compounds have been used with conventional antibiotics, producing elimination of the organism, histological improvement, and amelioration of symptoms for periods longer than one year. Bismuth subsalicylate has shown modest efficacy in treating traveler's diarrhea and acute and chronic diarrhea in children, and it is effective prophylactically for traveler's diarrhea. An epidemic of neurological toxicity was reported in France in the 1970's with prolonged bismuth treatment, usually bismuth subgallate and subnitrate. Such toxicity has been rare with bismuth subsalicylate and colloidal bismuth subcitrate. However, recent studies have demonstrated intestinal absorption of bismuth (about 0.2% of the ingested dose) and sequestration of this heavy metal in multiple tissue sites, even occurring with conventional dosing over a 6-week period. These findings have inspired recommendations that treatment periods with any bismuth-containing compound should last no longer than 6-8 weeks, followed by 8-week bismuth-free intervals.     

Rice-powder salt solution in the treatment of acute diarrhea in young children.

Dehydration is the most common cause of death in diarrheal patients. Early oral rehydration therapy (ORT) can prevent or reverse dehydration from diarrhea in almost almost all cases. Shortages of oral rehydration salt (ORS) packets in certain areas remain a major problem of the Diarrheal Diseases Control Program of Thailand. To find an effective solution that can be prepared locally, a randomized trial of oral rehydration solutions was conducted. A rice-powder salt solution containing rice-power 30 g/l and salt 3.5 g/l (RPSS) was evaluated in a group (n = 23) of infants and young children aged between 4 months and 5 years with mild or moderate dehydration from acute watery diarrhea, and the results were compared with those who received WHO recommended glucose electrolyte solution (WHO-ORS) (n = 21), and glycine supplemented WHO-ORS (G-ORS) (n = 20). The efficacies of WHO ORS and G-ORS were found to be similar. The RPSS was found to be more effective than WHO-ORS and G-ORS as shown by a significantly lower stool frequency, lower rate of stool output, a significantly shorter duration of diarrhea, and a smaller intake of rehydration fluid. Promotion of the effective rice-salt solution could increase early implementation of ORT in many rural communities.     

The role of newer antibiotics in gastroenterology.

The past decade has seen the introduction of a number of new potent antimicrobial agents, including broad-spectrum beta-lactam compounds such as the ureidopenicillins, third-generation cephalosporins, carbapenems, and monobactams; combinations of penicillins with inhibitors of beta-lactamase; and the quinolones. Most of these agents have excellent activity against enteric gram-negative rods and some are active against anaerobic organisms, the two bacterial groups most likely to be encountered in gastrointestinal infections. Despite the potency and wide spectrum of many of these new agents, there are currently relatively few clinical situations in which any of the newer antimicrobials are the first-line agents for therapy or prophylaxis of gastrointestinal diseases. Reluctance to use these agents as first-line therapy is based on concerns about the selection and spread of resistant organisms, superinfection syndromes, and the high cost of many of the newer agents. Specific clinical settings in which these agents may be given preference are as follows: 1. use of a third-generation cephalosporin (cefotaxime or ceftriaxone) in the treatment of spontaneous bacterial peritonitis. 2. use of broad-spectrum beta-lactam compounds to provide gram-negative coverage in patients who should not receive aminoglycosides 3. use of a third-generation cephalosporin (ceftriaxone) in the treatment of central nervous system relapses of Whipple's disease 4. use of quinolones for the empiric treatment of suspected bacterial diarrhea in patients sufficiently ill to require empiric initiation of antibiotics. 5. use of quinolones for the treatment of chronic carriers of Salmonella typhi 6. use of norfloxacin for prophylaxis against SBP. As further experience with these new antimicrobial agents is obtained and as more bacteria develop resistance to current first-line agents, there can be little doubt that these new antibiotics will play an increasing role in the prevention and treatment of gastrointestinal disease.     

Antimicrobial-resistant bacterial diarrhea in rural western Kenya

Bacterial diarrheal diseases cause substantial morbidity and mortality in sub-Saharan Africa, but data on the epidemiology and antimicrobial susceptibility patterns of enteric bacterial pathogens are limited. Between May 1997 and April 1998, a clinic-based surveillance for diarrheal disease was conducted in Asembo, a rural area in western Kenya. In total, 729 diarrheal specimens were collected, and 244 (33%) yielded >or=1 bacterial pathogen, as determined by standard culture techniques; 107 (44%) Shigella isolates, 73 (30%) Campylobacter isolates, 45 (18%) Vibrio cholerae O1 isolates, and 33 (14%) Salmonella isolates were identified. Shigella dysenteriae type 1 accounted for 22 (21%) of the Shigella isolates. Among 112 patients empirically treated with an antimicrobial agent and whose stool specimens yielded isolates on which resistance testing was done, 57 (51%) had isolates that were not susceptible to their antimicrobial treatment. Empiric treatment strategies for diarrheal disease in western Kenya need to be reevaluated, to improve clinical care.     

Diarrheal diseases in the elderly

Diarrhea in the elderly population is one disease that needs special attention in treatment and management, especially in acute- and long-term care residents, because of their multiple comorbidities, immunosenescence, frailty, and poor nutritional status. Close follow-up to ensure adequate hydration and electrolyte replacement and infection control measures to contain outbreaks should be emphasized to caregivers and nursing staff in acute- and long-term care facilities. Although C difficile colitis causes significant morbidity and mortality in this population, judicious use of antibiotics is important to decrease the incidence and recurrence of the disease. When the diarrhea is chronic and all stool testings and serologies have been performed, the patient may benefit from endoscopy and colonoscopy for biopsy. Attentive and vigilant nursing staff is crucial in the timely diagnosis and treatment of diarrheal diseases to improve quality of life and reduce mortality.     

Assessing gut microbiota perturbations during the early phase of infectious diarrhea in Vietnamese children

Diarrheal diseases remain the second most common cause of mortality in young children in developing countries. Efforts have been made to explore the impact of diarrhea on bacterial communities in the human gut, but a thorough understanding has been impeded by inadequate resolution in bacterial identification and the examination of only few etiological agents. Here, by profiling an extended region of the 16S rRNA gene in the fecal microbiome, we aimed to elucidate the nature of gut microbiome perturbations during the early phase of infectious diarrhea caused by various etiological agents in Vietnamese children. Fecal samples from 145 diarrheal cases with a confirmed infectious etiology before antimicrobial therapy and 54 control subjects were analyzed. We found that the diarrheal fecal microbiota could be robustly categorized into 4 microbial configurations that either generally resembled or were highly divergent from a healthy state. Factors such as age, nutritional status, breastfeeding, and the etiology of the infection were significantly associated with these microbial community structures. We observed a consistent elevation of Fusobacterium mortiferum, Escherichia, and oral microorganisms in all diarrheal fecal microbiome configurations, proposing similar mechanistic interactions, even in the absence of global dysbiosis. We additionally found that Bifidobacterium pseudocatenulatum was significantly depleted during dysenteric diarrhea regardless of the etiological agent, suggesting that further investigations into the use of this species as a dysentery-orientated probiotic therapy are warranted. Our findings contribute to the understanding of the complex influence of infectious diarrhea on gut microbiome and identify new opportunities for therapeutic interventions.     

Risk factors of persistent diarrhea in children below five years of age.

BACKGROUND/OBJECTIVE: Persistent diarrhea is a known cause of childhood mortality, morbidity and malnutrition in developing countries. This study was conducted to find out the host and environmental risk factors associated with persistent diarrhea in Bangladeshi children below 5 years of age. DESIGN: Prospective analytic case-control study. SETTING: Tertiary hospital in Dhaka, Bangladesh. METHODS: Fifty children with persistent diarrhea and 50 controls with acute diarrhea (matched for age and sex) comprised the study subjects. RESULTS: Most of the children (82%) were aged below 2 years. Among the risk factors, Grade III malnutrition (p<0.008), irrational antibiotic use during acute diarrheal episode (p<0.0000005), use of unsafe drinking water (p<0.004) and lack of exclusive breast-feeding up to the first four months of life (p<0.004) were significantly associated with persistent diarrhea. Logistic analysis showed irrational antibiotic use (p<0.0001) during an episode of acute diarrhea and lack of exclusive breast-feeding (p<0.05) during the first four months of life as independent risk factors associated with persistent diarrhea. CONCLUSION: Improvement of nutritional status, encouraging exclusive breast-feeding during the first four months of life, discouraging the irrational use of antibiotic for the treatment of acute diarrhea, and provision of safe drinking water may be important for the prevention of persistent diarrhea as these have been identified as risk factors in Bangladeshi children below five years of age.     

Health seeking behavior among Malaysians with acute diarrheal disease

About 1.8 million people die annually from acute diarrheal disease globally. A nationwide cross-sectional survey was conducted via face-to-face interview with eligible subjects to determine the incidence and health seeking behavior of Malaysians with acute diarrheal disease (ADD). An acute diarrheal episode was defined as having three or more loose stools in any 24 hour period during the four weeks period prior to the interview. The exclusion criteria included pre-existing chronic diarrhea, such as with cancer of the bowel, ulcerative colitis or Chrohn's disease. Forty three point three percent of those with ADD (95% CI 41.3-45.4) sought treatment for the illness. Younger age groups (0-4 years, 67.7%; 95% CI 61.5-73.4; 5-9 years, 56.5%; 95% CI 48.6-64.1) were more likely to seek care for ADD. Seventy-one point eight percent of those seeking treatment, (95% CI 69.0-74.4) did so within 12 hours of the onset of symptoms. Most people with ADD sought treatment at private clinics. The main reasons given for not seeking treatment were the illness was mild and did not warrant treatment and the practice of self-medication (22.4%; 95% CI 20.0-24.9). These findings show self-medication is a major health seeking behavior among Malaysians with ADD. Self-medication of ADD deserves more in-depth study to ensure it is safe.