INFECTIOUS ENTERITIS
 |
| VIRAL ENTERITIS |
Infectious enteritis is a common worldwide illness with a multitude of underlying pathogens at play. The majority of infectious diarrheal diseases are acute in onset duration (< 2 weeks). Globally, acute enteritis is the fifth leading cause of death across all ages. Innumerable studies demonstrate that approximately 70% to 75% of acute diarrhea cases are viral in cause. Previously, culture techniques could not isolate most bacteria. With the advent of deep 16S ribosomal polymerase chain reaction sequencing techniques, genetic signatures can now identify bacteria, so it is not necessary to rely on tedious culture techniques. These technologies have isolated a bacterial source in approximately 15% of acute enteritis cases. Protozoal organisms are responsible for a lesser fraction of these cases.
In
underprivileged nations, overcrowding, poor sanitation, and a growing
prevalence of human immunodeficiency virus (HIV) infections help propagate
infectious causes and fuel worldwide mortality rates. In contrast, developed
nations exhibit low mortality rates because medical resources are more readily
available. In these developed nations, infectious diarrhea still accounts for a
significant amount of morbidity and health care expenditure; accurate diagnosis
and prompt management are therefore of utmost importance.
Several
viral culprits have been elucidated, including norovirus, rotavirus,
adenovirus, and astrovirus. Viral gastroenteritides classically exhibit short
prodromes of fever, vomiting, and self-limited watery, nonbloody diarrhea.
These viruses are generally spread via fecal-oral contamination. Notably, norovirus
and enteric adenovirus can also be aerosolized.
Of
the five genera of caliciviruses (named for their physical cuplike
depressions), two are known causes of human gastroenteritis: norovirus and
sapovirus. Noro-virus is notoriously known as a cause of epidemic diarrhea on
cruise ships but is a factor in outbreaks in any facility in which people exist
in close quarters, such as schools and dormitories. Though the disease may
occur throughout the year, a peak has been noted in the winter months. It
demonstrates a short incubation period of 1 to 2 days, followed by acute onset
of nausea, vomiting, and a high-volume, noninflammatory, non-bloody diarrhea.
No enterotoxin unique to norovirus has been isolated, but marked jejunal
villous blunting and impairment of brush-border enzymes has been observed that
reverts after approximately 2 to 3 weeks following the onset of symptoms.
Symptoms can last anywhere from 2 to 4 days. Upon resolution of symptoms,
marked reflux, dyspepsia, and, paradoxically, constipation have occurred.
Sapovirus
has a clinical presentation similar to that of norovirus. Whereas norovirus is
not thought to discriminate based on age, sapovirus may have a predilection for
children. Diagnostically, polymerase chain reaction testing is superior to immunoassays
in regard to severity, but caution must be used in interpreting positive tests
because asymptomatic carrier states are commonly observed. As always, positive
tests should be interpreted in the context of clinical symptoms.
Rotavirus
has a minimum 2-day incubation period and infamously affects infants and
toddlers, leading to severe dehydration with shedding known to last up to 2
weeks. Rotavirus can cause villous blunting with sub- sequent loss of
brush-border enzymes (lactase, maltase, sucrase), resulting in severe osmotic
diarrhea. Distinct rotavirus proteins have been isolated that cause the patchy
mucosal inflammation observed on endoscopy that stimulates an increase of
intraluminal fluid secretion via the enteric
nervous system and leads to electrolyte abnormalities. Transaminitis is an
uncommon “red herring” effect, similar to celiac disease, caused by increased
reabsorption via the damaged villi in the enterohepatic circulation. Diagnosis
is generally a clinical decision, although assays based on polymerase chain
reaction testing exist to identify the virus. Rare manifestations of rotavirus
causing seizures and neonatal necrotizing enterocolitis have been reported.
Infant rotavirus vaccination should be strictly maintained.
Over
50 subgroups of adenoviruses have been identified so far, with disease
manifested most famously in the respiratory tree but extending to numerous
organ systems. Specifically, subgroup F viruses make up the enteric-specific
adenoviruses. These rarely affect adults but commonly
affect children younger than 2 years of age. The viruses may be transmitted via
droplet aero-solization or fecal-oral contamination or may exist on fomites
resistant to typical disinfectants. A minimum incubation period of 7 to 10 days
is typical before the onset of diarrhea, which can last for 1 to 2 weeks.
Anti-viral agents are rarely required. In contrast to norovirus disease,
enteric adenovirus diarrhea generally does not present with significant
vomiting. Enteric adenoviruses are the second most common agents, after
rotaviruses, in causing acute diarrhea in children. They may be distinguished
with a dedicated enzyme-linked immunosorbent assay kit.
Astroviruses
generally affect children, though there have been cases in adults, in whom a
much milder diarrheal presentation has been
reported. The astro-virus incubates for 3 to 4 days, with diarrhea usually
lasting up to 3 days. Again, polymerase chain reaction testing is more
sensitive than immunoassays in identifying specific isolates.
In
acute viral gastroenteritis, antibiotics are not advocated. Management should
focus on aggressive intravenous fluid hydration and/or oral rehydration
solutions (e.g., Pedialyte, coconut water, WHO oral rehydration solution).
Symptomatically, antimotility agents (e.g., loperamide) and antiemetics may be
used. Bacterial pathogens are abundant and should certainly be considered when
the diarrhea is particularly severe in regard to abdominal pain, volume
depletion, or presence of blood. Standard cultures will test for the most
common bacterial causes of enteritis, such as Campylobacter, Salmonella,
and Shigella. Dairy and meat products contaminated with Campylobacter,
Salmonella, or Shigella dysenteriae are associated with high
incidence rates during the summer months.
Campylobacter
jejuni and Campylobacter coli cause identical infectious
presentations and are detected in contaminated water, poultry, and dairy
products. Abdominal pain may be diffuse or localized to the right lower
quadrant, simulating appendicitis. Most patients will experience diarrhea
lasting up to 1 week, though some may not have diarrhea. Bloody diarrhea may
ensue several days into the infectious cycle but will promptly clear. The
bacteria may continue to be shed for up to 1 to 2 months
following resolution of symptoms. Immunocompromised individuals may have
atypical complications of Campylobacter enteritis, including extension
into colitis, cholecystitis, pericarditis, and peritonitis. Other
extraintestinal complications may occur, as detailed below.
Salmonellae
are
divided into organisms that cause typhoid fever (discussed separately) and
those that do not. Diseases caused by the group of nontyphoidal Salmonellae manifest
with gastroenteritis. There are numerous genera adapted to infection primarily
in animals that may cause rare human disease (Salmonella dublin in
cattle, Salmonella choleraesuis in pigs). Salmonella enteritidis and
Salmonella typhimurium, found in mice and poultry, may colonize and/or
cause gastroenteritis in humans. Salmonellosis generally results from
contaminated foodstuffs, such as egg yolks, vegetables, or peanut butter, and
even contact with reptilian animals, such as turtles, lizards, and snakes. When
present in an encouraging medium such as meat or dairy products, Salmonella may
persist for months and still cause infection. Mass recalls of contaminated food
products are not uncommon.
 |
| FOOD POISONING: INFECTION TYPE |
Salmonellae
have a unique ability to bypass the acidic environment of the stomach prior to
colonizing the small intestinal tract, where the normal enteric microbiome
serves a protective role by competing for villous binding sites, producing
locally toxic fatty acids, secreting antibacterial peptides, and jockeying for
nutrition. Hence, antibiotics may have a deleterious role in ablating these protective microflora,
resulting in disease that is more symptomatic. Interestingly, Salmonellae can
influence enterocytes to endocytose them, promoting invasion. Though an
endotoxin has been identified, only a small fraction of Salmonella agents
produce and secrete the toxin. The inflammatory response is
incompletely understood, but it is clear that Salmonella is able to
direct neutrophil traffic to the intestine to ultimately cause diarrhea. The
symptoms, however, are similar to those of other causes of acute diarrhea,
namely, nausea, vomiting, diarrhea, fever, and
abdominal cramping. Bacteremia has been reported in less than 5% of cases,
manifesting as osteomyelitis, myocarditis, endovascular infection (e.g.,
mycotic aneurysms), and hepatobiliary and respiratory infections. Fortunately,
the diarrhea is self-limited, lasting between 5 and 10 days. Antibiotics are
not indicated unless infection is severe or complex. In fact, they may prolong
the carrier state and result in relapse.
During
the World Wars, an aseptic reactive arthritis was recognized secondary to
immune cross-reactivity from bacteremia with Campylobacter, Salmonella, and
Shigella. Also recognized were manifestations of conjunctivitis,
mucocutaneous disease, and urethritis/ cervicitis. Interestingly, up to 30% of
Guillain-Barré patients have a history of Campylobacter jejuni infection due to antibody cross-reactivity to human
neurogangliosides.
Vibrio
cholerae and Shigella are common causes of diarrheal epidemics,
though the latter primarily causes colitis. V. cholerae is found in
fecally contaminated bodies of water or transmitted directly via the fecal-oral route. Consumption of fish and shellfish from
contaminated aquatic reservoirs is not uncommon. V. cholerae possesses
virulence factors allowing successful colonization of the small intestine; this
stimulates secretion of a potent cholera toxin and leads to uninhibited adenylate cyclase stimulation and luminal chloride secretion, resulting in massive
volume loss. The incubation period varies in regard to the quantity of ingested
inoculum but can last anywhere from 1 to 5 days. The subsequent voluminous
diarrhea may take on the appearance of “rice water”
and have a malodorous fishy odor. Aggressive volume repletion is critical. V.
cholerae responds well to fluoroquinolones, macrolides, and tetracycline
antibiotics.
Escherichia coli has numerous strains of which the following are known to contribute to enterically mediated diarrheal illness. Enterotoxigenic Escherichia coli (ETEC) is the most common bacterial cause of acute enteritis in developing nations and the most predominant cause of travelers’ diarrhea. Poor sanitation with contaminated water supplies is to blame. After a brief incubation period, voluminous watery diarrhea may begin and last from 1 day to 1 week. ETEC produces heat-labile toxins similar to those of cholera; they stimulate adenylate cyclase and increase intracellular cyclic adenosine monophosphate, which increases intraluminal chloride secretion and inhibits sodium chloride absorption, resulting in a net movement of fluid into the lumen and creating the watery diarrhea. ETEC also synthesizes a heat-stabile toxin that works by stimulating cyclic guanosine monophosphate to effect this same electrolyte shift. Enteropathogenic E. coli (EPEC) agents are novel in that they do not secrete toxin but directly adhere to the enterocyte, by which means they can introduce their own proteins that change signal transduction within the cell. This intracellular cascade changes intercellular and tight junction permeability, increasing electrolyte and water secretion into the lumen and producing severe, dehydrating watery diarrhea. Polymerase chain reaction assays can assess for ETEC toxin genes and the EPEC adherence factor gene. Enteroaggregative E. coli (EAEC) is a cause of diarrheal outbreaks in both developing and developed nations. It is so named because it was observed that it had a proclivity for binding to HEp-2 cells in tissue culture adherence assays. EAEC synthesizes a unique cytotoxin that causes mucosal tissue disruption. The diagnosis is made via tissue culture adherence assay alone. Enterohemorrhagic E. coli (EHEC), which includes Escherichia coli species O157:H7 and O104:H4, is commonly associated with contaminated beef and other fecally contaminated products (e.g., raw milk, vegetables, and fruits). EHEC produces Shiga toxin, which damages the vascular endothelium. It may begin as non- bloody diarrhea but evolve into hemorrhagic enteritis and colitis. The ensuing inflammatory cascade precipitates a microangiopathic hemolytic anemia and acute kidney injury known as hemolytic-uremic syndrome. This may not occur until 7 to 10 days after the bacteria have been naturally cleared by the immune system; this fact explains the ineffectiveness of antibiotics in ameliorating this condition. Antibiotics may precipitate hemolytic-uremic syndrome and are generally avoided.
 |
| FOOD POISONING: TOXIN TYPE |
Aeromonas species survive in fresh-water bodies and
chlorinated or polluted water supplies, making them hardy organisms. Diarrhea
ranges from watery, secretory choleretic-like diarrhea to bloody, mucusy,
dysenteric-like diarrhea. Though Aeromonas will grow on routine
microbiologic media cultures, it is not routinely distinguished from other
normal flora. Alert the microbiology laboratory if clinical suspicion exists
for Aeromonas, so that specific appropriate identification protocols may
be implemented. Antibiotics are generally unnecessary, but fluoroquinolone and
trimethoprim-sulfamethoxazole may be reasonable if clinically necessary. If the
infection is acquired abroad, this may affect its resistance pattern, and these
antibiotics may not be efficacious.
Organisms
such as Staphylococcus aureus and Bacillus cereus possess a
preformed toxin that more commonly leads to
nausea and vomiting and rarely diarrhea. S. aureus may contaminate dairy
products, eggs, meat, and produce; when these foods are left at normal room
temperature, bacteria may rapidly proliferate and synthesize the toxin. Onset
of symptoms within 1 to 6 hours eventually produces severe upper intestinal
symptoms that resolve spontaneously. B. cereus also produces an
enterotoxin commonly found in leftover or “take-out” rice; the temporal onset
and symptom severity are the same as with S. aureus.
Protozoal
causes of acute enteritis include Cryptosporidium, Giardia, Cystoisospora,
Microspora, and Cyclospora. Cryptosporidium and Giardia
are the most common protozoal enteric parasites. Unlike Giardia, Cryptosporidium
hominis is an intracellular protozoal parasite that causes a
self-limited diarrhea in healthy hosts and sometimes a
chronic diarrheal scenario in immunocompromised patients. Fecally contaminated
drinking water or recreational pool water commonly acts as a reservoir for
transmission. Fecal-oral contamination amongst house-hold members or anal-oral
intercourse between partners are other modes of transmission. Excystation of
oocysts frees four banana-shaped sporozoites, which attach to the small bowel
epithelium. These sporozoites mature into meronts, which eventually invade and
reinvade host cells. New oocysts are formed, which are expelled luminally into
the stool to begin the cycle once again. Fatigue, lethargy, abdominal cramping,
nausea, and diarrhea of variable severity ensues 1 to 2 weeks later. Organisms
may luminally invade the hepatobiliary tree and cause symptoms of hepatitis,
pancreatitis, cholecystitis, or cholangitis owing to stricture, occurring
more commonly in immunocompromised individuals (e.g., patients with acquired
immunodeficiency syndrome [AIDS]). Because of the need for multiple samples,
immunoassay has supplanted microscopy as the test of choice for its ease of use
and convenience. Nitazoxanide is generally effective at clearing the infection.
AIDS patients should undergo immune reconstitution with antiviral therapy to
help clear the infection. Giardia infection is discussed separately.
Cystoisospora
belli (formerly, Isospora belli) is an opportunistic protozoan
that exists as a sporulated oocyst in fecally contaminated food and water
supplies. The microbes must exist outside the host to undergo successful
sporulation after 1 to 2 days. Upon ingestion, the sporulated oocysts invade
the small and large bowel epithelial cells to complete their life cycle and
once again be reexcreted into the host lumen. Intestinal biopsies reveal an
inflammatory infiltrate, blunted villi, and crypt hyperplasia. Stool microscopy
will demonstrate thin-walled ellipsoidal oocysts. The secretory diarrhea that
results can cause significant dehydration, with prerenal kidney injury and
electrolyte abnormalities. The disease course is typically self-limited.
Treatment is reserved for individuals with severe dehydration, unrelenting
disease, or immunocompromise. A regimen of 7 to 10 days of
trimethoprim-sulfamethoxazole is effective.
Microsporidium
is
a poorly understood intracellular spore-forming organism, with over 1300
species identified. Fourteen of these are known to consistently infect humans,
particularly those afflicted with AIDS. Entero- cytozoon bieneusi and Encephalitozoon
species are the most commonly identified pathogenic organisms. Spores have
been observed in respiratory, fecal, and urine specimens and may be inhaled or
ingested. The spores use their polar filament to inject their nucleus inside a
host cell, where replication occurs with development of multinucleated
plasmodial forms that eventually are violently expelled from the host cell,
only to infect adjacent cells. In this fashion, they may invade the small
intestinal and biliary mucosa. Small intestinal villous blunting, architectural
distortion, and crypt hyperplasia are observed, which potentiate malabsorption
and secretory mechanisms of diarrhea. Extraintestinal infection of the brain,
eyes, and muscles has been reported in healthy patients; AIDS patients have
more severe presentations. The patchy nature of the affected small bowel mucosa
makes endoscopic biopsy insensitive. However, light microscopy and trichrome
staining are successful at detection. Most infections will respond to a short
course of albendazole; E. bieneusi is resistant to this organism,
however, and may require a macrolide or tetracycline.
Cyclospora
cayetanensis is an obligate intracellular parasite that is passed in
a noninfective state in the stool and is only known to be pathogenic in humans.
C. cayetanensis awaits in hot, humid climates in order to undergo
sporulation. Hence, an increased incidence in tropical climates such as those
of Southeast Asia, India, and Latin America is observed. Once the organism has
sporulated, its ingestion in contaminated water or food-stuffs leads to
excystation within the intestinal tract and the release of sporozoites, which infiltrate
the epithelial cells, where they undergo replication. Acute watery diarrhea,
fatigue, anorexia, and weight loss are common. Stool microscopy will identify
the oocysts, although they may be confused with Cryptosporidium; they
must be distinguished based on size, because Cryptosporidium (5 microns) is much smaller than Cyclospora (10 microns). A
short course of trimethoprim-sulfamethoxazole or nitazoxanide results in prompt
diarrheal resolution.
It
is worthwhile to note that some bacterial (e.g., Salmonella, Campylobacter)
and protozoal organisms (Giardia, Cryptosporidium) may rarely enter a
chronic diarrheal phase. Though uncommon in healthy patients, this
consideration should be made in immunocompromised populations. A postinfectious
irritable bowel syndrome may sometimes result, though this is a diagnosis of
exclusion.
 |
| REACTIVE ARTHRITIS |
Routine
stool cultures will not detect all pathogens. Instead, careful history taking
and an understanding of the risk factors for these pathogens are required in
order to direct assessment for the appropriate organisms by
the microbiology department. Polymerase chain reaction testing and immunoassay
have made detection much easier. However, some organisms still require multiple
stool microscopy specimens to ensure detection. Assessment of ova and parasites
should not be ordered routinely but should be reserved for the clinical
settings where the patient may be immunocompromised, immunosuppressed, or
chronically ill.
Prevention is key in many of these illnesses. It begins with promoting adequate breast feeding to ensure maternal-infant transfer of immunoglobulins. Availability of modern sanitation methods and frequent hand-washing promote optimal hygiene to reduce fecal-oral transfer of many illnesses.
