++
Acute watery diarrhea is a ubiquitous symptom in childhood. Good
global data on the etiology of diarrhea is lacking, but worldwide, rotavirus
is the most common etiologic agent of acute gastroenteritis in children.3 Rotavirus is
seasonal in temperate climates, with peak incidence occurring in
late winter, but shows no seasonal pattern in the tropics. The highest incidence
of rotavirus infection occurs in children ages 6 months to 2 years.
Rotavirus is spread via the fecal-oral route and can be acquired
nosocomially. The incubation period for rotavirus is 1 to 3 days.
++
Other important viral causes of acute watery diarrhea in the
United States include adenovirus and norovirus. Adenovirus gastroenteritis
is predominantly caused by types 40 and 41 in children younger than
2. Adenovirus gastroenteritis is seen year-round. The incubation
period is 3 to 10 days. Norovirus, a type of calicivirus, causes acute
watery diarrhea that is generally associated with outbreaks in which
the virus is spread via the fecal-oral route, with an incubation
period of 1 to 2 days. Other causes of acute watery diarrhea include
astrovirus and other caliciviruses. In developing countries, bacterial
infections account for many cases of watery diarrhea. Important bacterial
causes of watery diarrhea include Vibrio cholerae,
enterotoxigenic Escherichia coli (ETEC), enteropathogenic E
coli (EPEC), and enteroaggregative E coli (EAEC).
++
Rotavirus is excreted in high concentration in stool (perhaps
more than 109 virions per gram). Viral replication
is generally confined to the intestinal epithelium. However, in
the immunodeficient host, rotavirus has been detected in the liver
and kidneys.4 The virus infects mature enterocytes
of the small intestinal villi to induce watery diarrhea by inhibiting
the sodium/glucose cotransport system and causing a net
chloride secretion.5 The virus also decreases the disaccharidase
enzyme activity of the small intestinal brush border to cause malabsorption
of carbohydrates and nutrients. The end result is a combined osmotic
and secretory diarrhea that does not contain blood.
++
Gastrointestinal adenoviruses, unlike strains found in the respiratory
tract, have enhanced the ability to attach to gastric and intestinal
epithelium in an acidic environment because of their basic charge
and stability in the face of intestinal enzymatic activity.6 Patients
may continue to shed the virus in stool months after the acute infection
has resolved. Caliciviruses do not grow in culture, which has made
characterization of their properties and pathogenesis difficult.
Acute calicivirus infection is associated with villous changes in
the jejunum and infiltration of monocytes in the mucosal layer.
Like rotavirus, caliciviruses have been associated with decreased
intestinal enzymatic activity.
++
Bacteria that produce enterotoxins without cellular invasion
cause increased intestinal secretion, but may also cause histological
damage. V cholerae serogroups O1 and O139 cause
severe watery diarrhea by producing an enterotoxin (cholera toxin)
that indirectly activates adenylyl cyclase. Elevated levels of cyclic
adenosine monophosphate (AMP) induce chloride secretion in crypt
cells through the cystic fibrosis transmembrane conductance regulator,
and sodium and water follow passively. In villous cells, sodium
and chloride transport from the lumen into the intestinal cells
is inhibited. ETEC strains colonize the epithelium via surface adhesins known
as colonization factor antigens and produce either a heat-labile
toxin (LT), a heat-stable toxin (ST), or both toxins. Heat-labile
toxin has a structure very similar to that of cholera toxin and
an identical mechanism of action, whereas heat-stable toxin directly
stimulates apical guanylyl cyclase. Enteropathogenic E coli strains cause
severe diarrhea and vomiting in infants in developing countries.
Typical enteropathogenic E coli strains produce
bundle-forming pili that enable the bacteria to adhere in clusters
to epithelial cells, whereas all enteropathogenic E coli strains
inject a receptor known as Tir into the host cell membrane using
a type III secretion system (T3SS). A surface protein called intimin binds
to Tir and the host cell forms a cuplike pedestal composed of cytoskeletal
proteins upon which the bacteria rest. The loss of intestinal microvilli
and intimate adherence induced by enteropathogenic E coli is
known as the attaching and effacing effect. Enteroaggregative E
coli produces pili that cause a distinctive aggregative pattern
of adherence and enterotoxins including Pet and EAST 1, which resembles
heat-stable toxin.
+++
Clinical Manifestations
++
The etiology of watery diarrhea cannot be determined on the basis
of clinical features because there is much overlap in symptoms and signs.
Moreover, agents that cause inflammatory diarrhea can also induce
watery diarrhea without fever or mucus or blood in the stool. In addition
to acute, watery diarrhea, symptoms may include vomiting and fever.
Rotavirus infection is more likely to cause watery diarrhea in young
infants, and severe vomiting is the predominant symptom in those
> 2 years of age.7 Rotavirus is commonly associated
with fever, and cough and coryza may precede the onset of intestinal
symptoms. Rotavirus stool rarely contains blood, mucus, or white
blood cells. The dehydration that accompanies rotavirus diarrhea
is often associated with increased losses of sodium and chloride,
isotonic dehydration, and a compensated metabolic acidosis. The
most common complication is dehydration, and children with malnutrition
seem to be at highest risk. Vomiting often lasts 2 to 3 days and
diarrhea 5 to 8 days. Rarely, an encephalopathic picture may occur.
Because of acquired immunity, subsequent rotavirus infections are progressively
less likely to induce moderate to severe symptoms.
++
Enteric adenoviruses are generally characterized by fever and
diarrhea, occasionally with vomiting. Diarrhea tends to be more
prolonged when compared to rotavirus infections, lasting 9 days
on average. Respiratory symptoms may also accompany enteric adenovirus
symptoms.
++
Calicivirus infection is generally associated with an extremely
abrupt onset of vomiting, diarrhea, abdominal cramps, nausea, headache,
low-grade fever, myalgia, anorexia, and malaise. These last only
24 to 48 hours.
++
Enteric adenoviruses are generally characterized by fever and
diarrhea, occasionally with vomiting. Diarrhea tends to be more
prolonged when compared to rotavirus infections, lasting 9 days
on average. Respiratory symptoms may also accompany enteric adenovirus symptoms. Cholera
causes watery diarrhea with little fever. In cholera gravis, loss
of fluids can be so severe as to lead to shock within hours. Enterotoxigenic E
coli can be mild or severe, with variable vomiting and
fever. Enteropathogenic E coli usually causes acute
disease, often with vomiting and low-grade fever, but occasionally
causes protracted illness. Enteroaggregative E coli diarrhea
may contain mucus and may also be prolonged.
+++
Diagnosis and Treatment
++
Acute, watery diarrhea caused by rotavirus, enteric adenoviruses,
and caliciviruses can be detected directly in stools by electron
microscopy or polyacrylamide gel electrophoresis, but these methods
are generally not available in most hospitals. Rapid diagnosis of
rotavirus and adenovirus, however, can be accomplished by solid-phase
immunoassays of stool. These tests are relatively inexpensive and
are sensitive and specific compared to electron microscopy. Diagnosis
of caliciviruses can be accomplished using nucleic acid sequence-based
amplification or enzyme immunoassay detection.8 Diagnosis
of V cholerae infection in the appropriate geographical
and clinical context can be made by culture, while the diarrheagenic E
coli causing watery diarrhea can only be confirmed using
tissue culture assays, gene probing, or PCR in reference laboratories. When
watery diarrhea is persistent, agents of inflammatory diarrhea should be
investigated with appropriate testing (see below). Nonenteric infections
and conditions can occasionally present with diarrhea and should
be considered in the differential diagnosis. Such diseases include
urinary tract infection, otitis media, pneumonia, sepsis, meningitis,
acute abdomen, inflammatory bowel disease, and food allergy.
++
The cornerstone of acute watery diarrhea management is oral rehydration
therapy, which has saved millions of lives. Treatment guidelines
for the management of acute gastroenteritis in children were endorsed
and accepted by the American Association of Pediatrics in 2004 as
policy. These guidelines were published by the Centers for Disease
Control and Prevention and are available at http://www.cdc.gov/mmwr/PDF/RR/RR5216.pdf. The
evaluation and treatment of diarrhea is discussed in detail in Chapter 385.
++
Because most causes of acute, watery diarrhea are transmitted
via the fecal-oral route, the availability of safe drinking water
and routine hand-washing are the foundations of prevention. Also
important to the prevention of rotavirus is the recent approval
by the Food and Drug Administration (FDA) of a new live, orally
administered vaccine, RotaTeq, administered as a 3-dose series between
ages 6 and 32 weeks. RotaTeq is a pentavalent vaccine that contains
five reassortant viruses and was tested in more than 70,000 children
before licensure.9 Rotarix, a second vaccine used
to prevent rotavirus, is derived from an attenuated human strain
of rotavirus and is currently under evaluation for FDA licensure.
Both vaccines are currently used in the Americas and Europe and
have proven highly effective in preventing rotavirus disease. They
are also safe from the possible complication of intussusception,
which was associated with a rotavirus vaccine licensed by the FDA
from 1998 to 1999.