World Gastroenterology Organisation Global Guidelines
Prof. M. Farthing (Chair, United Kingdom)
Prof. M. Salam (Special Advisor, Bangladesh)
Prof. G. Lindberg (Sweden)
Prof. P. Dite (Czech Republic)
Prof. I. Khalif (Russia)
Prof. E. Salazar-Lindo (Peru)
Prof. B.S. Ramakrishna (India)
Prof. K. Goh (Malaysia)
Prof. A. Thomson (Canada)
Prof. A.G. Khan (Pakistan)
Drs. J. Krabshuis (France)
Dr. A. LeMair (Netherlands)
(Click to expand section)
According to the World Health Organization (WHO) and UNICEF, there are about two billion cases of diarrheal disease worldwide every year, and 1.9 million children younger than 5 years of age perish from diarrhea each year, mostly in developing countries. This amounts to 18% of all the deaths of children under the age of five and means that more than 5000 children are dying every day as a result of diarrheal diseases. Of all child deaths from diarrhea, 78% occur in the African and South-East Asian regions.
Each child under 5 years of age experiences an average of three annual episodes of acute diarrhea. Globally in this age group, acute diarrhea is the second leading cause of death (after pneumonia), and both the incidence and the risk of mortality from diarrheal diseases are greatest among children in this age group, particularly during infancy – thereafter, rates decline incrementally. Other direct consequences of diarrhea in children include growth faltering, malnutrition, and impaired cognitive development in resource-limited countries.
During the past three decades, factors such as the widespread availability and use of oral rehydration salts (ORS), improved rates of breastfeeding, improved nutrition, better sanitation and hygiene, and increased coverage of measles immunization are believed to have contributed to a decline in the mortality rate in developing countries. In some countries, such as Bangladesh, a reduction in the case fatality rate (CFR) has occurred without appreciable changes in the water supply, sanitation, or personal hygiene, and this can be attributed largely to improved case management.
ORS and nutritional improvements probably have a greater impact on mortality rates than the incidence of diarrhea. Prevailing poor living conditions and insignificant improvements in water, sanitation, and personal hygiene, despite some improvement in nutrition, is perhaps important in explaining the lack of impact on the incidence. Interventions such as exclusive breastfeeding (which prevents diarrhea), continuation of breastfeeding until 24 months of age, and improved complementary feeding (by way of improved nutrition), along with improved sanitation, are expected to affect mortality and morbidity simultaneously. The recommended routine use of zinc in the management of childhood diarrhea, not currently practiced in many countries, is expected to reduce disease incidence.
In industrialized countries, relatively few patients die from diarrhea, but it continues to be an important cause of morbidity that is associated with substantial health-care costs. However, the morbidity from diarrheal diseases has remained relatively constant during the past two decades.
In this guideline, specific pediatric details are provided in each section as appropriate.
In developing countries, enteric bacteria and parasites are more prevalent than viruses and typically peak during the summer months.
Diarrheagenic Escherichia coli. The distribution varies in different countries, but enterohemorrhagic E. coli (EHEC, including E. coli O157:H7) causes disease more commonly in the developed countries.
Pediatric details. Nearly all types cause disease in children in the developing world:
* EIEC and EHEC are not found (or have a very low prevalence) in some developing countries.
Pediatric details. Campylobacter is one of the most frequently isolated bacteria from the feces of infants and children in developing countries, with peak isolation rates in children 2 years of age and younger.
Pediatric details. An estimated 160 million episodes occur in developing countries, primarily in children. It is more common in toddlers and older children than in infants.
Pediatric details. In children, hypoglycemia can lead to convulsions and death.
In both industrialized and developing countries, viruses are the predominant cause of acute diarrhea, particularly in the winter season.
Human caliciviruses (HuCVs):
Pediatric details. Sapoviruses primarily affect children. This may be the second most common viral agent after rotavirus, accounting for 4–19% of episodes of severe gastroenteritis in young children.
Adenovirus infections most commonly cause illnesses of the respiratory system.
Pediatric details: depending on the infecting serotype, this virus may cause gastroenteritis especially in children.
Cryptosporidium parvum, Giardia intestinalis, Entamoeba histolytica, and Cyclospora cayetanensis: these are uncommon in the developed world and are usually restricted to travelers.
Pediatric details. Most commonly cause acute diarrheal illness in children.
Table 1 Overview of causative agents in diarrhea
* These agents are no longer reported in the Indian subcontinent.
Although there may be clinical clues, a definitive etiological diagnosis is not possible clinically (Tables 2–4).
Table 2 Episodes of diarrhea can be classified into three categories
Table 3 Linking the main symptoms to the causes of acute diarrhea—enterohemorrhagic E. coli (EHEC)
Table 4 Clinical features of infection with selected diarrheal pathogens
Key: ++, common: +, occurs, +/–, variable; –, not common: 0, atypical/often not present.
The initial clinical evaluation of the patient (Table 5) should focus on:
Table 5 Medical assessment in diarrhea
Table 6 Assessment of dehydration using the “Dhaka method”
* Key signs.
For acute enteritis and colitis, maintaining adequate intravascular volume and correcting fluid and electrolyte disturbances take priority over identifying the causative agent. Presence of visible blood in febrile patients generally indicates infection due to invasive pathogens, such as Shigella, Campylobacter jejuni, Salmonella, or Entamoeba histolytica. Stool cultures are usually unnecessary for immune-competent patients who present with watery diarrhea, but may be necessary to identify Vibrio cholerae when there is clinical and/or epidemiological suspicion of cholera, particularly during the early days of outbreaks/epidemics (also to determine antimicrobial susceptibility) and to identify the pathogen causing dysentery.
Epidemiologic clues to infectious diarrhea can be found by evaluating the incubation period, history of recent travel in relation to regional prevalence of different pathogens, unusual food or eating circumstances, professional risks, recent use of antimicrobials, institutionalization, and HIV infection risks.
Stool analysis and culture costs can be reduced by improving the selection and testing of the specimens submitted on the basis of interpreting the case information—such as patient history, clinical aspects, visual stool inspection, and estimated incubation period (Tables 7–9).
Table 7 Patient history details and causes of acute diarrhea
Table 8 Incubation period and likely causes of diarrhea
Table 9 Patient details and bacterial testing to consider
Wherever possible: fecal analysis in cases of severe bloody inflammatory or persistent diarrhea. This is extremely important for developing management protocols during early outbreaks or epidemics.
Screening usually refers to noninvasive fecal tests. Certain laboratory studies may be important when the underlying diagnosis is unclear or diagnoses other than acute gastroenteritis are possible. Where applicable, rapid diagnostic tests (RDTs) may be considered for cholera quick testing at the patient’s bedside.
Pediatric details. Identification of a pathogenic bacterium, virus, or parasite in a stool specimen from a child with diarrhea does not indicate in all cases that it is the cause of illness.
Measurement of serum electrolytes may be required in some children with a longer duration of diarrhea with moderate or severe dehydration, particularly with an atypical clinical history or findings. Hypernatremic dehydration is more common in well-nourished children and those infected with rotavirus, and features irritability, increased thirst disproportionate to clinical dehydration, and a doughy feel to the skin. This requires specific rehydration methods.
Table 10 Prognostic factors in children
Differential diagnosis of acute diarrhea in children:
Integrated management of childhood illness (IMCI). In developing countries, a large proportion of childhood morbidity and mortality is caused by five conditions: acute respiratory infections, diarrhea, measles, malaria, and malnutrition. The IMCI strategy has been developed to address the overall health of children presenting with signs and symptoms of more than one condition. In such cases, more than one diagnosis may be necessary and treatments for the conditions may have to be combined. Care needs to be focused on the child as a whole and not just the individual diseases or conditions affecting the child, while other factors that affect the quality of care delivered to children—such as drug availability, organization of the health-care system, referral pathways and services, and community behaviors—are best addressed through an integrated strategy.
The IMCI strategy encompasses a range of interventions to prevent and manage major childhood illness, both in health facilities and in the home. It incorporates many elements of the diarrheal and acute respiratory infection control program, as well as child-related aspects of malaria control, nutrition, immunization, and essential drugs program (WHO, Bangladesh; see www.whoban.org).
Oral rehydration therapy (ORT) is the administration of appropriate solutions by mouth to prevent or correct diarrheal dehydration. ORT is a cost-effective method of managing acute gastroenteritis and it reduces hospitalization requirements in both developed and developing countries.
Global ORS coverage rates are still less than 50% and efforts must be made to improve coverage.
Oral rehydration salts (ORS), used in ORT, contain specific amounts of important salts that are lost in diarrhea stool. The new lower-osmolarity ORS (recommended by WHO and UNICEF) has reduced concentrations of sodium and glucose and is associated with less vomiting, less stool output, lesser chance of hypernatremia, and a reduced need for intravenous infusions in comparison with standard ORS (Table 11). This formulation is recommended irrespective of age and the type of diarrhea including cholera.
ORT consists of:
Table 11 Constituents of oral rehydration salts (ORS)
ORT is contraindicated in the initial management of severe dehydration and also in children with paralytic ileus, frequent and persistent vomiting (more than four episodes per hour), and painful oral conditions such as moderate to severe thrush (oral candidiasis). However, nasogastric administration of ORS solution is potentially life-saving when intravenous rehydration is not possible and the patient is being transported to a facility where such therapy can be administered.
Rice-based ORS is superior to standard ORS for adults and children with cholera, and can be used to treat such patients wherever its preparation is convenient. It is not superior to standard ORS in the treatment of children with acute noncholera diarrhea, especially when food is given shortly after rehydration, as is recommended to prevent malnutrition.
Zinc deficiency is widespread among children in developing countries. Routine zinc therapy, as an adjunct to ORT is useful in modest reduction of the severity but more importantly reduce diarrhea episodes in children in developing countries. The recommendation for all children with diarrhea is 20 mg of zinc per day for 10 days. Infants aged 2 months or younger should receive 10 mg per day for 10 days.
Supplementation with zinc sulfate in recommended doses reduces the incidence of diarrhea during the following 3 months, and reduces nonaccidental deaths by as many as 50%. It is more important in the management of diarrhea in malnourished children and persistent diarrhea. The WHO and UNICEF recommend routine zinc therapy for children with diarrhea, irrespective of the types.
Table 12 Recommended daily allowance (RDA) guide for a 1-year-old child
All children with persistent diarrhea should receive supplementary multivitamins and minerals, including magnesium, each day for 2 weeks. Locally available commercial preparations are often suitable; tablets that can be crushed and given with food are least costly. These should provide as broad a range of vitamins and minerals as possible, including at least two recommended daily allowances (RDAs) of folate, vitamin A, zinc, magnesium, and copper (WHO 2005).
The practice of withholding food for > 4 hours is inappropriate—normal feeding should be continued for those with no signs of dehydration, and food should be started immediately after correction of some (moderate) and severe dehydration, which usually takes 2–4 hours, using ORT or intravenous rehydration.
Pediatric details. Breastfed infants and children should continue receiving food, even during the rehydration phase. However, for non-breastfed, dehydrated children and adults, rehydration is the first priority and that can be accomplished in 2–4 hours.
The notes below apply to both adults and children unless age is specified.
Table 13 Dietary recommendations
Probiotics are live microorganisms, such as Lactobacillus GG (ATCC 53103), with demonstrated beneficial health effects in humans. However, the effects are strain-specific and need to be verified for each strain in human studies. Extrapolation from the results of even closely related strains is not possible, and significantly different effects have been reported. Use of probiotics may not be appropriate in resource-constrained settings, mostly in developing countries.
Pediatric details. Controlled clinical intervention studies and meta-analyses support the use of specific probiotic strains and products in the treatment and prevention of rotavirus diarrhea in infants.
It has been confirmed that different probiotic strains (see Tables 8 and 9 in WGO's Guideline on probiotics at http://www.worldgastroenterology.org/probiotics-prebiotics.html) including L. reuteri ATCC 55730, L. rhamnosus GG, L. casei DN-114 001, and Saccharomyces cerevisiae (boulardii) are useful in reducing the severity and duration of acute infectious diarrhea in children. The oral administration of probiotics shortens the duration of acute diarrheal illness in children by approximately 1 day.
Several meta-analyses of controlled clinical trials have been published that show consistent results in systematic reviews, suggesting that probiotics are safe and effective. The evidence from studies on viral gastroenteritis is more convincing than the evidence on bacterial or parasitic infections. Mechanisms of action are strain-specific: there is evidence for efficacy of some strains of lactobacilli (e.g., Lactobacillus casei GG and Lactobacillus reuteri ATCC 55730) and for Saccharomyces boulardii. The timing of administration is also of importance.
In the prevention of adult and childhood diarrhea, there is only suggestive evidence that Lactobacillus GG, L. casei DN-114 001, and S. boulardii are effective in some specific settings (see Tables 8 and 9 in WGO's Guideline on probiotics at http://www.worldgastroenterology.org/probiotics-prebiotics.html).
In antibiotic-associated diarrhea, there is strong evidence of efficacy for S. boulardii or L. rhamnosus GG in adults or children who are receiving antibiotic therapy. One study indicated that L. casei DN-114 001 is effective in hospitalized adult patients for preventing antibiotic-associated diarrhea and C. difficile diarrhea.
There is inadequate research evidence to be certain that VSL#3 (Lactobacillus casei, L. plantarum, L. acidophilus, L. delbrueckii, Bifidobacterium longum, B. breve, B. infantis, and Streptococcus thermophilus) is effective in the treatment of radiation-induced diarrhea.
None of these drugs addresses the underlying causes or effects of diarrhea (loss of water, electrolytes, and nutrients). Antiemetics are usually unnecessary in acute diarrhea management, and some that have sedative effects may make ORT difficult.
Pediatric details. In general, antidiarrheals have no practical benefits for children with acute or persistent diarrhea.
Table 14 Nonspecific antidiarrheal agents
Table 15 Antimicrobial agents for the treatment of specific causes of diarrhea
In 2002, WHO and UNICEF revised their recommendations for routine use of hypo-osmolar ORS, and in 2004 recommended routine use of zinc as an adjunct to ORT for treatment of childhood diarrhea, irrespective of etiology. Since then, more than 40 countries throughout the world have adopted the recommendations. In countries where both the new ORS and zinc have been introduced, the rate of ORS usage has dramatically increased. Principles of appropriate treatment for children with diarrhea and dehydration:
Table 16 Treatment for children based on the degree of dehydration
Fig. 1 Therapeutic approach to acute bloody diarrhea in children.
Milder and uncomplicated cases of nondysenteric diarrhea in both adults and children can be treated at home, regardless of the etiologic agent, using home-based fluid or ORS as appropriate. Parents/caregivers of children should be educated to recognize signs of dehydration, and when to take children to health facility for treatment. Early intervention and administration of home-based fluids/ORS reduces dehydration, malnutrition, and other complications and leads to fewer clinic visits and potentially fewer hospitalizations and deaths.
Self-medication is safe in otherwise healthy adults. It relieves discomfort and social dysfunction. There is no evidence that it prolongs the illness. However, this may not be appropriate in developing countries where diarrhea requiring specific interventions is more prevalent and people may not be competent in assessing their conditions.
Principles of self-medication:
Where feasible, families in localities with a high prevalence of diarrheal diseases should be encouraged to store a few ORS packets and zinc tablets if there are children under the age of five in the family for initiating home therapy as soon as diarrhea starts.
Antidiarrheal agents. Among hundreds of over-the-counter products promoted as antidiarrheal agents, only loperamide and bismuth subsalicylate have sufficient evidence of efficacy and safety.
Family knowledge: family knowledge about diarrhea must be reinforced in areas such as prevention, nutrition, ORT/ORS use, zinc supplementation, and when and where to seek care.
Indications for medical consultation or in-patient care are:
A cascade is a hierarchical set of diagnostic or therapeutic techniques for the same disease, ranked by the resources available. Cascades for acute diarrhea are shown in Figs. 2–4.
Fig. 2 Cascade for acute, severe, watery diarrhea—cholera-like, with severe dehydration. See above for the recipe for home-made oral fluid. ORT, oral rehydration therapy.
FDA Warning/Regulatory Alert
Fig. 3 Cascade for acute, mild/moderate, watery diarrhea—with mild/moderate dehydration. See above for the recipe for home-made oral fluid. ORT, oral rehydration therapy.
Fig. 4 Cascade for acute bloody diarrhea—with mild/moderate dehydration. See above for the recipe for home-made oral fluid. ORT, oral rehydration therapy.