Acute Diarrhea

© World Gastroenterology Organisation, 2012
World Gastroenterology Organisation Global Guidelines
Acute diarrhea
in adults and children:
a global perspective
February 2012

Review Team
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)
© World Gastroenterology Organisation, 2012
Contents
1 Introduction and epidemiologic features 3
2 Causative agents and pathogenic mechanisms 4
3 Clinical manifestations and diagnosis 7
4 Treatment options and prevention 12
5 Clinical practice 19
List of tables
Table 1 Overview of causative agents in diarrhea 7
Table 2 Episodes of diarrhea can be classified into three categories 7
Table 3 Linking the main symptoms to the causes of acute diarrhea—
enterohemorrhagic E. coli (EHEC) 7
Table 4 Clinical features of infection with selected diarrheal pathogens 8
Table 5 Medical assessment in diarrhea 8
Table 6 Assessment of dehydration using the “Dhaka method” 9
Table 7 Patient history details and causes of acute diarrhea 10
Table 8 Incubation period and likely causes of diarrhea 10
Table 9 Patient details and bacterial testing to consider 10
Table 10 Prognostic factors in children 11
Table 11 Constituents of oral rehydration salts (ORS) 13
Table 12 Recommended daily allowance (RDA) guide for a 1-year-old child 13
Table 13 Dietary recommendations 14
Table 14 Nonspecific antidiarrheal agents 16
Table 15 Antimicrobial agents for the treatment of specific causes of diarrhea 16
Table 16 Treatment for children based on the degree of dehydration 20
List of figures
Fig. 1 Therapeutic approach to acute bloody diarrhea in children 21
Fig. 2 Cascade for acute, severe, watery diarrhea—cholera-like, with severe
dehydration 23
Fig. 3 Cascade for acute, mild/moderate, watery diarrhea—with mild/moderate
dehydration 24
Fig. 4 Cascade for acute bloody diarrhea—with mild/moderate dehydration 24
© World Gastroenterology Organisation, 2012
1 Introduction and epidemiologic features
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.
© World Gastroenterology Organisation, 2012
2 Causative agents and pathogenic mechanisms
Bacterial agents
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.
• Enterotoxigenic E. coli (ETEC) causes traveler’s diarrhea.
• Enteropathogenic E. coli (EPEC) rarely causes disease in adults.
• Enteroinvasive E. coli (EIEC)* causes bloody mucoid (dysentery) diarrhea; fever
is common.
• Enterohemorrhagic E. coli (EHEC)* causes bloody diarrhea, severe hemorrhagic
colitis, and the hemolytic uremic syndrome in 6–8% of cases; cattle are the
predominant reservoir of infection.
Pediatric details. Nearly all types cause disease in children in the developing world:
• Enteroaggregative E. coli (EAggEC) causes watery diarrhea in young children
and persistent diarrhea in children with human immunodeficiency virus (HIV).
• Enterotoxigenic E. coli (ETEC) causes diarrhea in infants and children in
developing countries.
• Enteropathogenic E. coli (EPEC) causes disease more commonly in children
< 2 years, and persistent diarrhea in children.
* EIEC and EHEC are not found (or have a very low prevalence) in some developing
countries.
Campylobacter:
• Asymptomatic infection is very common in developing countries and is
associated with the presence of cattle close to dwellings.
• Infection is associated with watery diarrhea; sometimes dysentery.
• Guillain–Barré syndrome develops in about one in 1000 of people with
Campylobacter colitis; it is thought to trigger about 20–40% of all cases of
Guillain–Barré syndrome. Most people recover, but muscle weakness does not
always completely resolve.
• Poultry is an important source of Campylobacter infections in developed
countries, and increasingly in developing countries, where poultry is proliferating
rapidly.
• The presence of an animal in the cooking area is a risk factor in 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.
© World Gastroenterology Organisation, 2012
Shigella species:
• Hypoglycemia, associated with very high case fatality rates (CFRs) (43% in one
study) occurs more frequently than in other types of diarrheal diseases
• S. sonnei is common in developed countries, causes mild illness, and may cause
institutional outbreaks.
• S. flexneri is endemic in many developing countries and causes dysenteric
symptoms and persistent illness; uncommon in developed countries.
• S. dysenteriae type 1 (Sd1) — the only serotype that produces Shiga toxin, as
does EHEC. It also is the epidemic serotype that has been associated with many
outbreaks during which CFRs can be as high as 10% in Asia, Africa, and Central
America. For unexplained reasons, this serotype has not been isolated since the
year 2000 in Bangladesh and India.
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.
Vibrio cholerae:
• Many species of Vibrio cause diarrhea in developing countries.
• All serotypes (>2000) are pathogenic for humans.
• V. cholerae serogroups O1 and O139 are the only two serotypes that cause severe
cholera, and large outbreaks and epidemics.
• In the absence of prompt and adequate rehydration, severe dehydration leading to
hypovolemic shock and death can occur within 12–18 h after the onset of the first
symptom.
• Stools are watery, colorless, and flecked with mucus; often referred to as “rice-
watery” stools.
• Vomiting is common; fever is typically absent.
• There is a potential for epidemic spread; any infection should be reported
promptly to the public health authorities.
Pediatric details. In children, hypoglycemia can lead to convulsions and death.
Salmonella:
• Enteric fever — Salmonella enterica serovar Typhi and Paratyphi A, B, or C
(typhoid fever); fever lasts for 3 weeks or longer; patients may have normal
bowel habits, constipation or diarrhea.
• Animals are the major reservoir for salmonellae. Humans are the only carriers of
typhoidal Salmonella.
• In nontyphoidal salmonellosis (Salmonella gastroenteritis), there is an acute
onset of nausea, vomiting, and diarrhea that may be watery or dysenteric in a
small fraction of cases.
• The elderly and people with immune-compromised status for any reason (e.g.,
hepatic and lymphoproliferative disorders, hemolytic anemia), appear to be at the
greatest risk.
Pediatric details:
• Infants and children with immune-compromised status for any reason (e.g.,
severe malnourishment) appear to be at the greatest risk.
© World Gastroenterology Organisation, 2012
• Fever develops in 70% of affected children.
• Bacteremia occurs in 1–5%, mostly in infants.
Viral agents
In both industrialized and developing countries, viruses are the predominant cause of
acute diarrhea, particularly in the winter season.
Rotavirus:
• Accounts for one-third of diarrhea hospitalizations and 500,000 deaths worldwide
each year.
• Associated with gastroenteritis of above-average severity.
Pediatric details:
• Leading cause of severe, dehydrating gastroenteritis among children.
• Nearly all children in both industrialized and developing countries get infected by
the time they are 3–5 years of age.
• Neonatal infections are common, but often asymptomatic.
• The incidence of clinical illness peaks in children between 4 and 23 months of
age.
Human caliciviruses (HuCVs):
• Belong to the family Caliciviridae—the noroviruses and sapoviruses (previously
called “Norwalk-like viruses” and “Sapporo-like viruses.”
• Noroviruses are the most common cause of outbreaks of gastroenteritis, affecting
all age groups.
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.
Parasitic agents
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.
• These agents account for a relatively small proportion of cases of infectious
diarrheal illnesses among children in developing countries.
• G. intestinalis has a low prevalence (approximately 2–5%) among children in
developed countries, but as high as 20–30% in developing regions.
• Cryptosporidium and Cyclospora are common among children in developing
countries; frequently asymptomatic.
© World Gastroenterology Organisation, 2012
Table 1 Overview of causative agents in diarrhea
Bacteria Viruses Parasites
Protozoan
z Cryptosporidium parvum
z Giardia intestinalis
z Microsporida*
z Entamoeba histolytica
z Isospora belli*
z Cyclospora cayetanensis
z Dientamoeba fragilis
z Blastocystis hominis
z Diarrheagenic Escherichia
coli
z Campylobacter jejuni
z Vibrio cholerae O1
z V. cholerae O139*
z Shigella species
z V. parahaemolyticus
z Bacteroides fragilis
z C. coli
z C. upsaliensis
z Nontyphoidal Salmonellae
z Clostridium difficile
z Yersinia enterocolitica
z Y. pseudotuberculosis
z Rotavirus
z Norovirus (calicivirus)
z Adenovirus (serotype
40/41)
z Astrovirus
z Cytomegalovirus*
Helminths
z Strongyloides stercoralis
z Angiostrongylus costaricensis
z Schistosoma mansoni,
S. japonicum
* These agents are no longer reported in the Indian subcontinent.
3 Clinical manifestations and diagnosis
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
Category Clinical manifestation
Acute diarrhea Presence of three or more abnormally loose or watery stools in the
preceding 24 h
Dysentery Presence of visible blood in stools
Persistent diarrhea Acutely starting episode of diarrhea lasting more than 14 days
Table 3 Linking the main symptoms to the causes of acute diarrhea—enterohemorrhagic
E. coli (EHEC)
Symptoms Causes of acute diarrhea
Fever z Common and associated with invasive pathogens
z zz z Pediatric details: initially present in the majority of children with
rotavirus diarrhea
Bloody stools z Invasive and cytotoxin-producing pathogens
z Suspect EHEC infection in the absence of fecal leukocytes
z Not with viral agents and enterotoxins producing bacteria
Vomiting z Frequently in viral diarrhea and illness caused by ingestion of
bacterial toxins (e.g., Staphylococcus aureus)
z Common in cholera
© World Gastroenterology Organisation, 2012
Table 4 Clinical features of infection with selected diarrheal pathogens
Clinical features
Pathogens
Abdominal
pain Fever
Fecal evidence
of inflammation
Vomiting,
nausea
Heme-positive
stool
Bloody
stool
Shigella ++ ++ ++ ++ +/– +
Salmonella ++ ++ ++ + +/– +
Campylobacter ++ ++ ++ + +/– +
Yersinia ++ ++ + + + +
Norovirus ++ +/– – ++ – –
Vibrio +/– +/– +/– +/– +/– +/–
Cyclospora +/– +/– – + – –
Cryptosporidium +/– +/– + + – –
Giardia ++ – – + – –
Entamoeba histolytica + + +/– +/– ++ +/–
Clostridium difficile + + ++ – + +
Shiga toxin-producing
Escherichia coli
(including O157:H7)
++ 0 0 + ++ ++
Key: ++, common: +, occurs, +/–, variable; –, not common: 0, atypical/often not present.
Clinical evaluation
The initial clinical evaluation of the patient (Table 5) should focus on:
• Assessing the severity of the illness and the magnitude (degree) of dehydration
(Table 6)
• Determining likely causes on the basis of the history and clinical findings,
including stool characteristics
Table 5 Medical assessment in diarrhea
Patient history Physical examination
z Onset, stool frequency, type and
volume
z Presence of blood
z Vomiting
z Medicines received
z Past medical history
z Underlying conditions
z Epidemiological clues
z Body weight
z Temperature
z Pulse/heart and respiratory rate
z Blood pressure
Pediatric details: Evidence of associated problems
in children
© World Gastroenterology Organisation, 2012
Table 6 Assessment of dehydration using the “Dhaka method”
Assessment Plan A Plan B Plan C
1 General condition Normal Irritable/less active* Lethargic/comatose*
2 Eyes Normal Sunken –
3 Mucosa Normal Dry –
4 Thirst Normal Thirsty Unable to drink*
5 Radial pulse Normal Low volume* Absent/ uncountable*
6 Skin turgor Normal Reduced* –
Diagnosis No dehydration Some dehydration
At least two signs,
including at least
one key sign (*) are
present
Severe dehydration
Signs of “some
dehydration” plus at least
one key sign (*) are
present
Treatment Prevent
dehydration
Rehydrate with
ORS solution
unless unable to
drink
Rehydrate with i.v. fluids
and ORS
Reassess
periodically
Frequent
reassessment
More frequent
reassessment
* Key signs.
Laboratory evaluation
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).
© World Gastroenterology Organisation, 2012
Table 7 Patient history details and causes of acute diarrhea
Patient history details Causes of acute diarrhea
Food-borne outbreak Salmonella Shiga-toxigenic
E. coli
Yersinia Cyclospora
Water-borne transmission Vibrios Giardia intestinalis Cryptosporidium
Seafood, shellfish Vibrio Norovirus Salmonella
Poultry Campylobacter Salmonella
Beef, raw seed sprouts Shiga toxin–
producing E. coli
(STEC)
Enterohemorrhagic
E. coli
Eggs Salmonella
Mayonnaise and cream Staphylococcus Clostridium
perfringens?
Salmonella
Pies Salmonella Campylobacter
jejuni
Cryptosporidium Giardia
intestinalis
Antibiotics, chemotherapy Clostridium difficile
Person to person Shigella Rotavirus
Table 8 Incubation period and likely causes of diarrhea
Incubation
period
Likely causes
< 6 h Preformed toxin of
S. aureus and
Bacillus cereus
6–24 h Preformed toxin of
C. perfringens and
B. cereus
16–72 h Noroviruses, ETEC,
Vibrio, Salmonella
Shigella,
Campylobacter,
Yersinia
Shiga toxin–
producing
E. coli, Giardia
Cyclospora,
Cryptosporidium
Table 9 Patient details and bacterial testing to consider
Patient details Test or consider
Community-acquired or
traveler’s diarrhea
Culture or test for ETEC, Salmonella, Shigella, Campylobacter
Nosocomial diarrhea (onset
> 2 days after
hospitalization)
Test for Clostridium difficile toxins A and B
Salmonella, Shigella, Campylobacter (when associated with
outbreak, and when patient is > 65 yr of age with coexisting
conditions, or in immunocompromised or neutropenic
individuals, or when systemic infection is suspected
Shiga toxin–producing E. coli (when dysenteric presentation)
Persistent diarrhea
(> 14 days)
EPEC, EAggEC
Consider protozoa: Cryptosporidium, Giardia, Cyclospora,
Isospora belli
Screening for inflammation
HIV/AIDS
© World Gastroenterology Organisation, 2012
Patient details Test or consider
If patient is
immunocompromised
(especially if HIV+) add:
Test for Microsporidia, Mycobacterium avium complex,
Cytomegalovirus, Strongyloides
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.
Prognostic factors and differential diagnosis in children
Table 10 Prognostic factors in children
Factor Remarks
Malnutrition z Approximately 10% of children in developing countries are severely
underweight
z Macronutrient or micronutrient deficiencies in children are related to
more severe and prolonged diarrhea, and hypokalemia and rectal
prolapse are likely to develop in association with dysentery
z Poor nutritional status leads to a higher risk of death
Zinc deficiency z Suppresses immune function and is associated with an increased
prevalence of persistent diarrhea and a higher frequency of diarrhea
Persistent diarrhea z Often results in malabsorption and significant weight loss, further
promoting the cycle
Immunosuppression z Secondary to infection with HIV or other chronic conditions, may be
associated with an increased risk for developing clinical illness,
prolonged resolution of symptoms, or frequent recurrence of
diarrheal episodes
Differential diagnosis of acute diarrhea in children:
• Pneumonia—may occur together with diarrhea in developing countries
• Otitis media
• Urinary tract infection
• Bacterial sepsis
• Meningitis
© World Gastroenterology Organisation, 2012
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).
4 Treatment options and prevention
Rehydration in adults and children
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:
• Rehydration—water and electrolytes are administered to replace losses.
• Maintenance fluid therapy to take care of ongoing losses once rehydration is
achieved (along with appropriate nutrition).
© World Gastroenterology Organisation, 2012
Table 11 Constituents of oral rehydration salts (ORS)
Sodium 75 mmol/L
Chloride 65 mmol/L
Anhydrous glucose 75 mmol/L
Potassium 20 mmol/L
Trisodium citrate 10 mmol/L
Total osmolarity 245 mmol/L
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.
Supplemental zinc therapy, multivitamins, and minerals in children
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
Folate 50 µg
Zinc 20 mg
Vitamin A 400 µg
Copper 1 mg
Magnesium 80 mg
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
© World Gastroenterology Organisation, 2012
as possible, including at least two recommended daily allowances (RDAs) of folate,
vitamin A, zinc, magnesium, and copper (WHO 2005).
Diet
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
Provide:
z An age-appropriate diet—regardless of the fluid used for ORT/maintenance
z Frequent, small meals throughout the day (six meals/day), particularly for infants and
young children
z Energy and micronutrient-rich, mixed foods (grains, eggs, meats, fruits, and vegetables)
z Increasing energy intake as tolerated following the diarrheal episode
z Pediatric details. Infants require more frequent breastfeeding or bottle feedings—special
formulas or dilutions are unnecessary. Older children and adults should receive their
normal food and drinks. Children, particularly young children, should be given one
additional meal following resolution of their diarrhea for catch-up growth.
Avoid:
z Canned fruit juices — these are hyperosmolar and can aggravate diarrhea
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.
Probiotics for the treatment of acute diarrhea
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
© World Gastroenterology Organisation, 2012
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.
Prevention of acute diarrhea
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).
Antibiotic-associated diarrhea
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.
Radiation-induced 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.
Nonspecific antidiarrheal treatment
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.
© World Gastroenterology Organisation, 2012
Table 14 Nonspecific antidiarrheal agents
z Should be used mostly for mild to moderate traveler’s
diarrhea (without clinical signs of invasive diarrhea)
z Inhibits intestinal peristalsis and has mild antisecretory
properties
z Should be avoided in bloody or suspected inflammatory
diarrhea (febrile patients)
z Significant abdominal pain also suggests inflammatory
diarrhea (this is a contraindication for loperamide use)
Antimotility agents
Loperamide (4–6 mg/day) is the
agent of choice for adults
z Pediatric details. Not recommended for use in
children—has been demonstrated to increase disease
severity and complications, particularly in children with
invasive diarrhea
z Not useful in adults with cholera Antisecretory agents
Racecadotril is an
enkephalinase inhibitor
(nonopiate) with antisecretory
activity
z Pediatric details. It has been found useful in children
with diarrhea, and is now licensed in many countries in
the world for use in children
Adsorbents
Kaolin-pectin, activated
charcoal, attapulgite
z Inadequate proof of efficacy in acute adult diarrhea,
adds to the costs, and thus should not be used
Antimicrobials in adults and children
Table 15 Antimicrobial agents for the treatment of specific causes of diarrhea
Cause First choice
Alternative(s)
Doxycycline
Adults: 300 mg once
Children: 2 mg/kg (not recommended)
Azithromycin
Adults: 1.0 g as a single dose, only once
Children: 20 mg/kg as one single dose
Cholera
Ciprofloxacin*
Adults: 500 mg 12-hourly for 3 days, or 2.0 grams as a single dose
only once
Children: 15 mg/kg every 12 hours for 3 days
* The minimum inhibitory concentration (MIC) has increased in
many countries—multiple-dose therapy over 3 days
Shigellosis Ciprofloxacin
Adults: 500 mg 2×/day for 3 days, or 2.0 g as a single dose only
once
Pivmecillinam
Adults: 400 mg 3–4 times/day for 5 days
Children: 20 mg/kg 4×/day for 5 days
Ceftriaxone
Adults: 2–4 g as a single daily dose
Children: 50–100 mg/kg 1×/day i.m. for 2–5 days
© World Gastroenterology Organisation, 2012
Cause First choice
Alternative(s)
Amebiasis—invasive
intestinal
Metronidazole
Adults: 750 mg 3×/day for 5 days*
Children: 10 mg/kg 3×/day for 5 days*
*10 days for severe disease
Giardiasis Metronidazole
Adults: 250 mg 3×/day for 5 days
Children: 5 mg/kg 3×/day for 5 days
Tinidazole
Can also be given in a single dose—50 mg/kg orally; maximum
dose 2 g
Ornidazole
Can be used in accordance with the manufacturer’s
recommendations—single, 2-g dose
Secnidazole
For adults (not available in USA)
Campylobacter Azithromycin
Adults: 500 mg 1×/day for 3 days
Children: single dose of 30 mg/kg early after disease onset
Fluoroquinolones such as ciprofloxacin
Adults: 500 mg 1×/day for 3 days
Important notes
• All doses shown are for oral administration.
• Selection of an antimicrobial should be based on the susceptibility patterns of
strains of the pathogens in the locality/region.
• Antimicrobials are reliably helpful and their routine use is recommended in the
treatment of severe (clinically recognizable):
— Cholera, shigellosis, typhoid and paratyphoid fevers .
— Dysenteric presentation of campylobacteriosis and nontyphoidal salmonellosis
when they cause persistent diarrhea, and when host immune status is
compromised for any reason such as severe malnutrition, chronic liver disease, or
lymphoproliferative disorders.
— Invasive intestinal amebiasis.
— Symptomatic giardiasis (anorexia and weight loss, persistent diarrhea, failure
to thrive).
• Consider antimicrobial treatment for:
— Shigella, Salmonella, Campylobacter (dysenteric form) or parasitic infections.
— Nontyphoidal salmonellosis among at-risk populations (malnutrition, infants
and elderly, immunocompromised patients, and those with liver diseases and
lymphoproliferative disorders), and in dysenteric presentation.
— Moderate/severe traveler’s diarrhea or diarrhea with fever and/or with bloody
stools.
— Antimicrobials are also indicated for associated health problems such as
pneumonia.
• Amebae. Nonpathogenic amebae are more often detected in stool microscopy and
get wrongly treated. The presence of ingested erythrocyte in an ameba
(hematophagus) stool microscopy indicates invasiveness and a need for
© World Gastroenterology Organisation, 2012
treatment; also when the presentation is dysenteric and no other invasive
pathogen has been detected. Treatment for amebiasis should ideally include
diloxanide furoate following the metronidazole, to get rid of the cysts that may
remain after the metronidazole treatment; nitazoxanide is an alternative.
• Azithromycin is widely available and has the convenience of single dosing. For
treating most types of common bacterial infection, the recommended
azithromycin dosage is 250 mg or 500 mg once daily for 3–5 days. Pediatric
dosage: the azithromycin dosage for children can range (depending on body
weight) from 10 mg to 20 mg per kilogram of body weight per day, once daily for
3 days.
• Campylobacter. Quinolone-resistant Campylobacter is present in several areas of
South-East Asia (e.g., Thailand) and azithromycin is the appropriate option in
such situations.
• Cholera. Routine antimicrobial therapy is recommended for treatment of severe
(clinically recognizable) cholera. The actual selection of an antimicrobial will
depend on recent susceptibility of the pathogen in specific countries; in the
absence of such information, susceptibility reports from neighboring countries is
the only other choice.
• Erythromycin is hardly used for diarrhea today.
• Nitazoxanide is an effective antiprotozoal in the treatment of diarrhea caused by
parasites such as Giardia intestinalis, Entamoeba histolytica, and
Cryptosporidium parvum.
• Traveler’s diarrhea. For adults with acute diarrhea, there is good evidence that a
single-dose therapy with some newer quinolones, such as ciprofloxacin, shortens
the duration of acute traveler’s diarrhea. However, this is still controversial; use
should be limited to high-risk individuals or those needing to remain well for
short visits to a high-risk area. Antimicrobials should be considered the drugs of
choice for empirical treatment of traveler’s diarrhea and of community-acquired
secretory diarrhea when the pathogen is known (Table 15).
Pediatric details:
• If drugs are not available in liquid form for use in young children, it may be
necessary to use tablets and estimate the doses given in Table 15.
• Consider antimicrobial treatment for:
— When Shigella, Salmonella, Campylobacter (dysenteric form) are the only
pathogen isolated from children with persistent diarrhea.
— Nontyphoidal salmonellosis in infants.
• Alternative antimicrobials for treating cholera in children are
trimethoprim/sulfamethoxazole (TMP/SMX; 5 mg/kg TMP + 25 mg/kg SMX,
12-hourly for 3 days), and norfloxacin.
Prevention of diarrhea with vaccines
• Salmonella typhi: two typhoid vaccines (with limited cost-efficiency) currently
are approved for clinical use.
• Shigella organisms: three vaccines have been shown to be immunogenic and
protective in field trials. Parenteral vaccines may be useful for travelers and
military personnel, but are impractical for use in developing countries. More
promising is a single-dose live-attenuated vaccine currently under development in
several laboratories.
© World Gastroenterology Organisation, 2012
• V. cholerae: the current price and need for multiple doses (at least two) and
shorter protective efficacy are limitations. A new, cheaper killed-cell vaccine is
likely to be available soon; oral cholera vaccines are still being investigated, and
their use is recommended only in complex emergencies such as epidemics. Their
use in endemic areas remains controversial. In traveler’s diarrhea, oral cholera
vaccine is only recommended for those working in refugee or relief camps, since
the risk of cholera for the usual traveler is very low.
• Enterotoxigenic E. coli (ETEC) vaccines: the most advanced ETEC vaccine
candidate consists of a killed whole-cell formulation plus recombinant cholera
toxin B subunit. No vaccines are currently available for protection against Shiga
toxin–producing E. coli infection.
Pediatric details:
• Salmonella typhi: no available vaccine is currently suitable for routine use for
children in developing countries.
• Rotavirus: in 1998, a rotavirus vaccine, RotaShield (Wyeth), was licensed in the
USA for routine immunization of infants. In 1999, production was stopped after
the vaccine was causally linked to intussusception in infants. Other rotavirus
vaccines are being developed, and preliminary trials are promising. Currently,
two vaccines have been approved: a live oral vaccine, RotaTeq, made by Merck
for use in children, and GSK’s Rotarix.
• Measles immunization can substantially reduce the incidence and severity of
diarrheal diseases. Every infant should be immunized against measles at the
recommended age.
5 Clinical practice
Approach in adults with acute diarrhea
1. Perform initial assessment.
2. Manage dehydration.
3. Prevent dehydration in patients with no signs of dehydration, using home-based
fluids or ORS solution.
• Rehydration of patients with some dehydration using ORS, and correct
dehydration of a severely dehydrating patient with an appropriate intravenous
fluid.
• Maintain hydration using ORS solution.
• Treat symptoms (if necessary, consider bismuth subsalicylate or loperamide in
cases of nondysenteric traveler’s diarrhea).
4. Stratify subsequent management:
• Epidemiological clues: food, antibiotics, sexual activity, travel, day-care
attendance, other illness, outbreaks, season.
• Clinical clues: bloody diarrhea, abdominal pain, dysentery, wasting, fecal
inflammation.
5. Obtain a fecal specimen for analysis:
• If there is severe, bloody, inflammatory, or persistent diarrhea, and at the
beginning of an outbreak/ epidemic.
6. Consider antimicrobial therapy for specific pathogens.
© World Gastroenterology Organisation, 2012
7. Report to the public health authorities.
• In outbreaks, save culture plates and isolates; freeze fecal specimens and food
or water specimens at –70 °C
• Notifiable in the USA: cholera, cryptosporidiosis, giardiasis, salmonellosis,
shigellosis, and infection with Shiga toxin–producing E. coli (STEC).
Approach in children with acute 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:
• 1. No unnecessary laboratory tests or medications.
• 2. Use ORS for rehydration:
— Perform ORT rapidly, within 3–4 hours.
— Routine adjunct zinc therapy for children aged 5 years or younger.
• 3. When dehydration is corrected, rapid re-alimentation:
— Normal food or age-appropriate unrestricted diet.
— Continue breastfeeding.
• 4. Administer additional ORS for ongoing losses through diarrhea.
Table 16 Treatment for children based on the degree of dehydration
Cautionary notes
• It is dangerous to treat patients with severe diarrheal dehydration using 5%
dextrose with 1/4 normal saline, and the risk of death is very high. In diarrheal
dehydration, not only water but also a number of electrolytes are lost; the
important ones are sodium, potassium, and bicarbonate.
Degree of dehydration No or minimal
dehydration
Mild to moderate
dehydration
Severe dehydration
Rehydration therapy None ORS 50–100 mL/kg
body weight over 3–
4 hours
If vomiting is
persistent, the patient
(child or adult) will not
take ORS and is likely
to need intravenous
fluids
Rehydrate with
Ringer's lactate
solution (100 mg/kg)
intravenously within
4–6 hours
Then administer ORS
to maintain hydration
until patient recovers
Replacement of
losses
< 10 kg body weight: 50–100 mL ORS for each diarrheal stool or
vomiting episode
Nutrition Continue
breastfeeding or
age-appropriate
normal diet
Continue breastfeeding, or resume age-
appropriate normal diet after initial hydration
© World Gastroenterology Organisation, 2012
• The loss of sodium is greater in cholera than in ETEC diarrhea (60–110 mmol/L),
followed by rotavirus diarrhea (around 20–40 mmol/L)—three leading causes of
severe dehydrating diarrhea.
• Efforts to correct dehydration using solutions with lower amounts of sodium
(such as 38.5 mmol/L in 1/4 saline with 5% dextrose) would lead to sudden and
severe hyponatremia with a high risk of death.
• Ringer’s lactate is the appropriate solution for management of severe
dehydration, but normal saline may be life-saving, irrespective of age, when
Ringer’s lactate is not available. In such cases, ORS should be initiated as soon as
patients (adults and children) are able to drink, to replace bicarbonate and
potassium lost in diarrheal stools, particularly for children.
• For acute bloody diarrhea (dysentery) in children, the main principles of the
therapeutic approach are:
—Treatment of dehydration
—Stool microscopy to assess the need for antimicrobial therapy. Demonstration
of invasive forms of E. histolytica and vegetative Giardia intestinalis in a
symptomatic patient would provide a direct diagnosis, and the presence of
inflammatory cells would indicate invasive diarrhea and institution of an
appropriate antimicrobial agent after a fecal specimen has been sent for culture
where possible.
—Frequent, smaller meals with higher protein intakes.
Fig. 1 Therapeutic approach to acute bloody diarrhea in children.
Home management of acute diarrhea in adults and 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
Severely malnourished?
Yes: refer to hospital No: give antimicrobial for Shigella
Better in 2 days?
Yes: complete 3 days’ treatment No: see next
Initially dehydrated, age < 1 y, or
measles in past 6 weeks?
Yes: refer to hospital No: change to second
antimicrobial for Shigella
Better in 2 days?
Yes: complete 3 days’ treatment No: refer to hospital or
treat for amebiasis
© World Gastroenterology Organisation, 2012
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:
• Maintain adequate fluid intake.
• Consumption of solid food should be guided by appetite in adults; small, but
more frequent meals for children.
• Antidiarrheal medication with loperamide (flexible dose according to loose bowel
movements) may diminish diarrhea and shorten the duration.
• Antimicrobial treatment is reserved for prescription only in residents’ diarrhea or
for inclusion in travel kits (add loperamide).
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.
Home-made oral fluid recipe
Preparing 1 L of oral fluid using salt, sugar and water at home. The ingredients to be
mixed are:
• One level teaspoon of salt.
• Eight level teaspoons of sugar.
• One liter (five cupfuls) of clean drinking water, or water that has been boiled and
then cooled.
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:
• Caregiver’s report of signs consistent with dehydration
• Changing mental status
• History of premature birth, chronic medical conditions, or concurrent illness
• Young age (< 6 months or < 8 kg weight)
• Fever • 38 °C for infants < 3 months old or • 39 °C for children aged 3–
36 months
• Visible blood in stool
• High-output diarrhea, including frequent and substantial volumes
• Persistent vomiting, severe dehydration, persistent fever
© World Gastroenterology Organisation, 2012
• Suboptimal response to ORT, or inability of caregiver to administer ORT
• No improvement within 48 hours—symptoms exacerbate and overall condition
gets worse
• No urine in the previous 12 hours
Cascades
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.
Level 1
Intravenous fluids + antibiotics + diagnostic tests:
stool microscopy/culture
Based on tests: tetracycline, fluoroquinolone
Level 2
Intravenous fluids + antibiotics
Empirical: tetracycline, fluoroquinolone, or other
Level 3
Intravenous fluids + ORT
Level 4
Nasogastric tube ORS—if persistent, vomiting
Level 5
ORT
Level 6
High
Ï ÏÏ Ï
Resources
Ð ÐÐ Ð
Low
Home-made oral fluid: salt, sugar, and clean water
Cautions
• If facilities for referral are available, patients with severe dehydration (at risk of
acute renal failure or death) should be referred to the nearest health-care facility
with access to intravenous fluids (levels 5 and 6 cannot replace the need for
referral in case of severe dehydration).
• Levels 5 and 6 must be seen as interim measures and are better than no treatment
if no intravenous facilities are available.
• When intravenous therapy is used, it must be ensured that disposable sterile
syringes, needles and drip sets are used, to avoid the risk of hepatitis B and C.
© World Gastroenterology Organisation, 2012
Notes
• Nasogastric therapy requires skilled staff.
• Often, intravenous fluid treatment is more easily available than nasogastric tube
feeding. (Caution: there is a risk of infection with contaminated intravenous
infusion equipment.)
Pediatric details
• Nasogastric feeding is not very feasible for healthy and active older children, but
it is suitable for malnourished, lethargic children.
• Nasogastric administration (ORS and diet) is especially helpful in long-term
severely malnourished children (anorexia).
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.
Level 1
Intravenous fluids (consider) + ORT
Level 2
Nasogastric tube ORS—if persistent, vomiting
Level 3
ORT
Level 4
High
Ï ÏÏ Ï
Resources
Ð ÐÐ Ð
Low
Home-made oral fluid: salt, sugar, and clean water
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.
Level 1
ORT + antibiotics + diagnostic tests: stool microscopy/culture
Consider causes: S. dysenteriae, E. histolytica,
severe bacterial colitis
Level 2
ORT + antibiotics
Empirical antibiotics for moderate/severe illness
Level 3
ORT
Level 4
High
Ï ÏÏ Ï
Resources
Ð ÐÐ Ð
Low
Home-made oral fluid: salt, sugar, and clean water