Seminars in Diagnostic Pathology 36 (2019) 187–192

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Seminars in Diagnostic Pathology

journal homepage: www.elsevier.com/locate/semdp

Review article

Emerging agents of gastroenteritis: Aeromonas, Plesiomonas, and the T

diarrheagenic pathotypes of Escherichia coli
Audrey N. Schuetz
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States

A R T I C LE I N FO A B S T R A C T

Keywords: Knowledge of the pathogenic roles of certain bacterial agents in gastroenteritis has been growing over the past
Gastroenteritis few decades. With the increasing use of multiplex molecular-based syndromic stool pathogen panels, the roles of
Aeromonas Plesiomonas shigelloides and some of the diarrheagenic pathotypes of Escherichia coli (enterotoxigenic E. coli
Plesiomonas shigelloides [ETEC], enteropathogenic E. coli [EPEC], enteroinvasive E. coli [EIEC], and enteroaggregative E. coli [EAEC])
E. coli
have been better understood. Although not currently targeted on Food and Drug Administration (FDA)-cleared
Enterotoxigenic
commercial multiplex stool panels, Aeromonas has also emerged as a possible cause of bacterial gastroenteritis.
Enteropathogenic
Shiga toxin The clinical presentation, pathophysiology, and diagnostic approaches to these pathogens in stool specimens are
Enteroaggregative reviewed. Variability in inclusion of these pathogens on multiplex molecular panels and difficulties in detection
Enteroinvasive by stool culture techniques utilized by clinical microbiology laboratories have contributed to an unclear un-
Multiplex molecular panel derstanding of the pathogenic role of several of these pathogens. Nonetheless, most evidence points towards a
STEC clear pathogenic role for P. shigelloides and ETEC, and possibly EPEC and EIEC. The contribution of Aeromonas
ETEC spp. and EAEC to bacterial gastroenteritis has not been fully established. Further studies of pathogenicity of these
EPEC
pathogens are needed.
EIEC
EAEC

Introduction and enteroaggregative E. coli [EAEC]) will be discussed in this review.

Infectious gastroenteritis is a leading cause of morbidity and mor-
tality worldwide. Gastroenteritis may be viral, bacterial, or parasitic in
origin. Although viruses cause the majority of such infections, ap-
proximately 15–20% of gastroenteritis is caused by bacteria.1 New
molecular diagnostic tools are increasing our knowledge of potential
causes of gastroenteritis. Identification of the specific etiology of gas-
troenteritis is helpful for individual patient targeted care and also for
public health measures such as outbreak investigation and other in-
fection control measures.
The limitations in detection of certain pathogens from stool by
traditional culture techniques have limited a complete understanding of
the possible pathogenic roles some of these pathogens play in gastro-
enteritis. Our knowledge of the true incidence of infection due to spe-
cific pathogens is likewise hindered. However, over the past several
decades, we have been gaining a better understanding of the patho-
genicity of certain bacterial pathogens that have been associated with
gastroenteritis. The role of Aeromonas spp., Plesiomonas shigelloides, and
the diarrheagenic pathotypes of Escherichia coli (enterotoxigenic E. coli
[ETEC], enteropathogenic E. coli [EPEC], enteroinvasive E. coli [EIEC],
Clinical presentation, pathophysiology, and diagnosis of these patho-
gens will be covered.
Multiplex molecular-based syndromic stool pathogen panels have
increased our knowledge of the roles various pathogens play in gas-
trointestinal (GI) diseases.2 These panels which are available through a
variety of commercial companies target some of the pathogens dis-
cussed in this review. The widespread use of molecular syndromic stool
testing in patients is changing our understanding of the roles of these
various agents in GI disease. However, detection of multiple positive
targets from specimens also leads to some difficulty in attributing dis-
ease to particular organisms. The role of multiplex molecular-based
syndromic stool pathogen panels is highlighted in discussion of each
pathogen.
Aeromonas spp.
Aeromonas spp. are Gram-negative rods within the family
Aeromonadaceae, which is distinct from the Enterobacteriaceae family.
Common inhabitants of aquatic ecosystems, aeromonads can lead to
infections after exposure to a water source. Transmission may occur by

E-mail address: schuetz.audrey@mayo.edu.

https://doi.org/10.1053/j.semdp.2019.04.012

0740-2570/ © 2019 Elsevier Inc. All rights reserved.

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A.N. Schuetz
direct exposure to fresh water or brackish water with low salinity, or
through ingestion of contaminated water or foods. The most common
species linked with human infection include A. hydrophila complex, A.
caviae complex, and A. veronii complex. As the field of taxonomy grows,
new members of the Aeromonas genus are continually recognized. Many
of the same species that cause human disease are also pathogenic for
animals, fish, and reptiles.
Aeromonads cause gastroenteritis, ranging from acute watery diar-
rhea to dysentery or chronic gastrointestinal illness.3 White blood cells
and red blood cells are usually absent in the feces. Accompanying
symptoms include abdominal pain in the majority of patients; fever,
vomiting and nausea may also occur. Acute gastroenteritis is usually
self-limiting and does not routinely require antimicrobial therapy; ra-
ther, hydration and electrolyte support are the mainstays of treatment.
Pediatric patients may require antibiotic therapy if dehydration occurs.
Aeromonas may also cause extraintestinal disease such as bacteremia,
wound infections, urinary tract infections, and abdominal infections.3
Septicemia most often occurs in immunocompromised hosts with liver
disease or other immunocompromised states. Wound infections may be
due to trauma incurred during contact with water. Outbreaks of wound
infections have been reported with mud football tournaments in Aus-
tralia and after tsunami natural disasters.4,5 Use of medicinal leeches
(Hirudo medicinalis and Hirudo verbana) for enhanced wound healing –
hirudotherapy – is another risk factor. Leech therapy is used to enhance
blood circulation to surgical wound sites but can lead to an infected
wound.6 Leeches contain Aeromonas in their digestive tract, and
transmission to humans via their saliva may occur. Studies are un-
derway assessing whether infective complications following leech
therapy may be decreased by the use of antibiotic feeding by leeches,
thereby reducing symbiotic Aeromonas.7 Gastrointestinal infections as-
sociated with Aeromonas occur more often during the warmer months in
temperate climates, presumably due to increased recreational water
exposure during those times, but infections may occur year-round.3
Several virulence factors may contribute to pathogenicity, including
hemolytic toxins, flagella, and other enzymes.8 Aeromonas spp. are
generally resistant to ampicillin but show variable rates of susceptibility
to cephalosporins.9 In the Asia-Pacific region, ciprofloxacin suscept-
ibility rates have been decreasing over time according to resistance
surveys.10
The role of Aeromonas in GI disease has been debated. This con-
troversy is due to several factors, including limitations in the clinical
laboratory of diagnostic methods, lack of consistent reporting to public
health and other regulatory bodies, and an incomplete understanding of
the exact incidence of infection. In the 1980’s, isolation of Aeromonas
spp. from stool cultures collected from persons with diarrhea was be-
ginning to be reported.11 However, Aeromonas is not consistently rou-
tinely identified from stool specimens in clinical microbiology labora-
tories. The bacterial agents routinely screened in stool cultures include
Salmonella, Shigella, Campylobacter, and Shiga toxin-producing E. coli
O157:H7. Microbiology laboratories near coastal communities may also
routinely test for Aeromonas or Vibrio spp. in stool culture, but this
practice is not widespread. The chances of detecting Aeromonas im-
prove if the clinician specifies the suspected organism and the tech-
nologist seeks it out. Most Aeromonas organisms are oxidase positive,
indole positive, and beta-hemolytic on sheep blood agar (Fig. 1).
Screening of the blood agar plate with oxidase is helpful in identifying
Aeromonas spp. If a stool culture is requested, additional media targeted
at isolating Aeromonas, such as cefsulodin-irgasan-novobiocin (CIN)
agar, may also be used. Commercial biochemical identification panels
do not typically perform well in distinguishing Aeromonas spp. from
Vibrio spp., and unusual Aeromonas spp. remain difficult to identify by
these methods.12 However, identification of Aeromonas to the species
level from stool specimens is not clinically useful and not routinely
performed.13 Matrix-assisted laser desorption-time of flight mass spec-
trometry (MALDI-TOF MS) identifies Aeromonas spp. with a high degree
of certainty.14 The number of laboratories which routinely screen their
188
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Seminars in Diagnostic Pathology 36 (2019) 187–192
Fig. 1. Aeromonas sp. on sheep blood agar plate of stool specimen, demon-
strating creamy colonies and beta-hemolysis. Photo courtesy of Bacteriology
Laboratory of Mayo Clinic, Rochester, MN.
stool cultures for Aeromonas is unknown, particularly since Food and
Drug Administration (FDA)-cleared multiplex molecular-based syn-
dromic stool panels have replaced stool culture for bacterial pathogens
in many laboratories. Current FDA-cleared commercial multiplex mo-
lecular-based syndromic stool pathogen panels do not detect Aeromonas
(Table 1).
The proportion of diarrheal illness due to Aeromonas varies in the
literature, which is likely due to differences in patient populations
studied but also due to various detection approaches in stool specimens.
In a study of stool samples from 1286 persons over 14 years of age with
acute diarrhea in Beijing, China, Aeromonas was isolated in 98 (7.6%) of
stools using culture preceded by alkaline peptone water enrichment of
stool.15 Only 3/98 cases were polymicrobial (two patients with Vibrio
spp. and one with Salmonella typhimurium in addition to Aeromonas),
indicating a possible association with gastroenteritis. Aeromonas was
the likely cause of diarrhea in 12/863 (2%) patients in a study from
Spain, as assessed by stool culture.16 Investigators from India reported
that Aeromonas was the cause of diarrhea in 164/3501 (4.7%) of hos-
pitalized patients when culture of stool was performed.17 Overall,
Aeromonas is isolated from stool culture in 2 to 10% of cases according
to most reports from industrialized countries.18 Notably, culture ap-
proaches – particularly the use of alkaline peptone water enrichment of
stool before plating to media – vary across studies; therefore, direct
comparison of rates of recovery between populations is not possible.
Although not a common inhabitant of the normal GI microbiota,
Aeromonas can also be found in the stool of <1% to 4% of asympto-
matic individuals.3 Finally, the fact that laboratories and clinicians are
not routinely required to report infections due to Aeromonas to public
health laboratories likely contributes to an underestimation of the true
incidence of such infections. Differences in stool culture practices
amongst laboratories and difficulties in identification of Aeromonas
contribute to an incomplete understanding of the incidence of disease.
Some authors argue that the lack of a clonal outbreak of Aeromonas
infection and the short incubation time reported before putative in-
fection point towards its questionable role as a GI pathogen.3,19 An
outbreak of acute diarrheal disease due to Aeromonas has been docu-
mented; however, several Aeromonas species were involved in that
outbreak which was not clonal.20 In an effort to support Koch postulates
of infection, human volunteer challenge trials with A. hydrophila have
been undertaken but failed to lead to diarrhea in most volunteers.21 On
the other hand, some studies have shown that isolation of the organism
from feces and evidence of an immune response support its pathogenic
role in gastroenteritis.22 Various animal models of infection, such as
zebrafish larvae, are being explored to better understand the virulence
factors of Aeromonas, but a clear animal model of infection has not yet
A.N. Schuetz Seminars in Diagnostic Pathology 36 (2019) 187–192

Table 1
Bacterial targets on commercially available Food and Drug Administration (FDA)-cleared gastrointestinal multiplex molecular panels.
Target BioFire® FilmArray® BD MAX™ Enteric BD MAX™ Great Basin Scientific Luminex xTAG® Verigene® Enteric
Gastrointestinal (GI) Panel Bacterial Panel (BD Extended Enteric Stool Bacterial Pathogens Gastrointestinal Pathogen Pathogens Test
(BioFire Diagnostics, Salt Life Sciences, Bacterial Panel* Panel (Vela Diagnostics, Panel (Luminex (Luminex
Lake City, UT) Sparks, MD) * Salt Lake City, UT) Corporation, Austin, TX)* Corporation, Austin,
TX)

Aeromonas spp. – – – – – –
Campylobacter spp. X⁎⁎ X⁎⁎⁎ – X⁎⁎⁎ X X
Clostridioides difficile X – – – X –
(toxins A/B)
EAEC X – – – – –
EIEC X X – – – –
EPEC X – – – – –
ETEC X – X – X –
Plesiomonas shigelloides X – X – – –
Salmonella spp. X X – X X X
Shigella spp. X X – X X X
Shiga toxins 1 & 2 – – – X – X
STEC X X – X⁎⁎⁎⁎ X⁎⁎⁎⁎
Vibrio spp. X – X – – X
Vibrio cholerae X – X – X –
Yersinia enterocolitica X – X – – X

STEC = Shiga toxin-producing E. coli; ETEC = enterotoxigenic E. coli; EPEC = enteropathogenic E. coli; EIEC = enteroinvasive E. coli; EAEC = enteroaggregative E.
coli; ND = not detected.
⁎
BD MAX panels and Luminex xTAG® panel are FDA-cleared for in vitro diagnostic (IVD) use.
⁎⁎
Includes Campylobacter jejuni, Campylobacter coli, and Campylobacter upsaliensis.
⁎⁎⁎
Includes C. jejuni and C. coli.
⁎⁎⁎⁎
E. coli O157.

been definitively established.23
In brief, most evidence supports the role of Aeromonas in gastro-
intestinal disease, while rare studies refute these observations.3 Future
studies delineating the differences in pathogenicity and clinical disease
associations among various Aeromonas spp. will aid in an understanding
of disease. Recovery of Aeromonas from stool is hindered by a lack of
clear diagnostic approaches. The absence of Aeromonas from current
multiplex molecular-based syndromic stool pathogen panels also slows
our understanding of the role this organism plays, as many laboratories
are adopting these multiplex syndromic panels and no longer per-
forming stool culture.
Plesiomonas shigelloides
Plesiomonas shigelloides is the only species within the genus
Plesiomonas and is a member of the Enterobacteriaceae family. Similar to
Aeromonas, P. shigelloides is a common inhabitant of freshwater and
estuarine water (i.e., transition between fresh and maritime waters)
environments. The range of P. shigelloides in non-human hosts is wider
than that of Aeromonas, as they may also be found in amphibians, fish,
birds, and mammals. It is an emerging cause of water- and foodborne
infections leading to diarrhea in humans but likely only rarely causes
disease in non-human hosts.
Gastroenteritis due to P. shigelloides varies from a secretory or wa-
tery diarrhea to more severe dysentery-like symptoms.24 Diarrhea may
also be subacute or chronic in nature. Disease may occur at any age.
Seasonality of disease due to P. shigelloides has been noted, with higher
rates of infection in summer months in temperate and tropical or sub-
tropical climates. Transmission most often occurs by consumption of
contaminated seafood (most commonly shellfish) or uncooked food, or
by consumption of contaminated freshwater. Foreign travel is the
second major risk factor associated with gastroenteritis due to P. shi-
gelloides. Travel to Latin America and the Caribbean, and South and
Southeast Asia has been associated with such infections.25,26 Im-
munocompromised individuals are at higher risk of developing gas-
troenteritis as a result of exposure, and disease severity is also higher in
these patients. Rarely, extraintestinal infections due to P. shigelloides
may occur, such as meningitis or bacteremia. Wound infections due to
P. shigelloides are not encountered which differs from Aeromonas. Its
pathogenicity and virulence factors are not well understood.
As with Aeromonas, isolation of P. shigelloides from stool cultures of
patients suffering from gastroenteritis was first described in the
1980’s.27 Although the role of P. shigelloides in human GI disease was
once controversial, most sources now consider this organism to be an
established enteropathogen.28 Clinical and epidemiologic studies have
linked the presence of P. shigelloides in stool with diarrheal symptoms,
histopathologic evidence of colitis on biopsy, and endoscopic find-
ings.29 Case-controlled studies and outbreak investigations have sup-
ported the role of P. shigelloides in gastroenteritis.30,31 Establishment of
virulence by in vitro experimental settings with animal models and
human volunteers have been successful in supporting P. shigelloides as a
likely agent of gastroenteritis; however, not all studies are conclusive of
its pathogenic role.32
One of the top five causes of gastroenteritis in some countries, P.
shigelloides may be detected in stool culture alongside other well-es-
tablished enteric pathogens.30 In a retrospective study of 197 cases of
culture-proven P. shigelloides gastroenteritis infections, concurrent in-
fection with other common stool pathogens such as Salmonella, Cam-
pylobacter jejuni, Shigella, or Vibrio were reported in 27 (16%) pa-
tients.24 Thus, P. shigelloides may not be the causative agent of disease
when co-detected with more well-established enteric pathogens. Less
than 1% of asymptomatic individuals carry P. shigelloides.33 Carriage
rates in some studies are slightly higher based on exposures in the
natural environment. In asymptomatic individuals assessed in Thailand,
P. shigelloides was recovered by stool culture in 25/367 (6.8%) per-
sons.34 As with Aeromonas, acute gastroenteritis due to P. shigelloides
does not typically require antimicrobial therapy and usually responds to
hydration therapy. P. shigelloides is generally susceptible to most anti-
microbials, with the exception of ampicillin and other penicillins.30
Detection of P. shigelloides in the clinical laboratory can be achieved
by a variety of methods. In stool cultures, P. shigelloides is not routinely
identified in clinical microbiology laboratories, although some labora-
tories may screen stool cultures routinely for P. shigelloides during
certain seasons. The chances of detecting P. shigelloides are higher if the
clinician specifies this organism when ordering the culture. P. shi-
gelloides produces non lactose-fermenting, non sucrose-fermenting

189

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A.N. Schuetz Seminars in Diagnostic Pathology 36 (2019) 187–192

Fig. 3. Colonies of E. coli O157:H7 on sorbitol MacConkey agar of a stool

specimen. Photo courtesy of Bacteriology Laboratory of Mayo Clinic, Rochester,
MN.

enterohemorrhagic strains and cause bloody diarrhea and hemorrhagic

colitis through the production of Shiga toxins 1 or 2. There are various
serotypes of STEC which can lead to disease, most notably E. coli
Fig. 2. Hektoen enteric agar with colonies of Plesiomonas shigelloides (colorless/
O157:H7. However, there are over 150 different types of non-O157
slight green colonies; thick arrow) and normal enteric flora (yellow colonies; STEC strains which have been associated with diarrhea or hemolytic
thin arrow) from stool specimen. uremic syndrome, including O104:H4 which led to an outbreak of he-
morrhagic colitis in Germany in 2011.37 In the United States, O157:H7
is the most commonly isolated STEC strain, but non-O157:H7 serotypes
colonies on enteric media and is easy to differentiate from normal stool
are increasingly recognized as causes of outbreaks and illness.38 E. coli
microbiota on culture (Fig. 2). It grows on CIN media but not on
O157:H7 is the only serotype which is readily diagnosed in stool cul-
thiosulfate-citrate-bile salts-sucrose media. The only oxidase-positive
ture, and it is a routine component of stool culture. Colonies of E. coli
member of the Enterobacteriaceae family, P. shigelloides may be detected
O157:H7 do not ferment sorbitol on sorbitol MacConkey agar and thus
in stool culture by assessing for oxidase positive colonies on blood agar.
remain colorless (Fig. 3). Antimicrobial therapy for diarrhea due to E.
Manual or automated biochemical-based commercial identification
coli O157:H7 likely increases the risk of hemolytic uremic syndrome
systems perform variably in identification of P. shigelloides.35 MALDI-
and should be avoided. The role of STEC in disease has been firmly
TOF MS accurately identifies P. shigelloides.36 P. shigelloides is included
established. The clinical presentation and virulence factors of the other
as a target currently in one FDA-cleared multiplex molecular-based
E. coli pathotypes ETEC, EPEC, EIEC, and EAEC are examined in greater
syndromic stool pathogen panel (Table 1). Commercial FDA-cleared
detail (Table 2). All diarrheagenic pathotypes of E. coli are transmitted
molecular multiplex syndromic panels for gastroenteritis target a
via the fecal-oral route.
variety of the organisms listed in this review, as well as other bacterial,
ETEC is an important cause of diarrhea in resource-limited settings,
viral, and/or parasitic targets which are more clearly associated with
particularly among young children. It is also a frequent cause of tra-
clinical disease. Current FDA-cleared stool panels include the BioFire®
veler's diarrhea. Severity of disease ranges from self-limited watery
FilmArray® Gastrointestinal (GI) Panel (BioFire Diagnostics, Salt Lake
diarrhea to severe cholera-like illness consisting of profuse watery
City, UT), BD MAX™ Enteric Bacterial Panel and Extended Enteric
diarrhea without blood or mucus. These strains colonize the small in-
Bacterial Panel (BD Life Sciences, Sparks, MD), the Great Basin Scien-
testine and produce a heat-labile enterotoxin and/or a heat-stable en-
tific Stool Bacterial Pathogens Panel (Vela Diagnostics, Salt Lake City,
terotoxin. The true incidence of disease is difficult to ascertain, as di-
UT), the Luminex xTAG® Gastrointestinal Pathogen Panel (Luminex
agnosis in clinical laboratories is achieved by molecular detection. Prior
Corporation, Austin, TX), and the Verigene® Enteric Pathogens Test
to the availability of multiplex molecular-based syndromic stool pa-
(Luminex Corporation) (Table 1). The BD MAX™ panels and the Lu-
thogen panels in routine clinical microbiology laboratories, diagnosis
minex xTAG® panel are FDA-cleared for in vitro diagnostic (IVD) use.
was obtained generally through public health or reference laboratories
In brief, as the use of multiplex syndromic stool panels increases, the
which utilized specialized methods for toxin detection. Pathogenicity of
role of P. shigelloides as a true agent of gastroenteritis may become
ETEC is well established by epidemiologic and case-control studies.39
clearer. However, the lack of this target on some multiplex syndromic
Infections due to EPEC also occur more commonly in resource-
panels and the difficulty in identifying the organism by culture methods
limited settings and in children younger than two years of age. EPEC
may also prevent a complete understanding of the true incidence of
strains cause watery diarrhea, occasionally accompanied by fever and
disease due to P. shigelloides.
mucus in the stool. They remain an important cause of infant diarrhea
in South America, sub-Saharan Africa, and Asia but no longer represent
Diarrheagenic pathotypes of Escherichia coli: enterotoxigenic E. important causes of gastroenteritis in North America and Europe.40
coli, enteropathogenic E. coli, enteroinvasive E. coli, and EPEC localizes to the small intestine, are not invasive, and do not
enteroaggregative E. coli produce Shiga toxins or enterotoxins. They are defined by their ad-
herence in cell culture, and by the “attaching and effacing” effect they
E. coli is a Gram-negative rod which is a normal inhabitant of the GI demonstrate on enterocytes (i.e., epithelial cells lining the small intes-
tract. There are several strains of diarrheagenic E. coli, including shiga tine).41 Diagnosis is achieved by molecular methods, and such strains
toxin-producing E. coli (STEC), enterotoxigenic E. coli (ETEC), en- cannot be reliably identified by culture methods. Thus, the disease
teropathogenic E. coli (EPEC), enteroinvasive E. coli (EIEC), and en- burden due to EPEC has not been well understood in past. Its role in
teroaggregative E. coli (EAEC). STEC strains are also referred to as the

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A.N. Schuetz
Table 2
Classification of diarrheagenic Escherichia coli strains.
Strain Clinical disease Virulence
STEC Watery diarrhea Shiga toxin
Hemorrhagic colitis
Hemolytic uremic syndrome
ETEC Watery diarrhea Heat-labile enterotoxin
Traveler's diarrhea Heat-stable enterotoxin
Colonizing fimbriae allow attachment to intestinal epithelial cells
EPEC Watery diarrhea (primarily in infants) Adherence in cell culture
EIEC Watery diarrhea Invasion of epithelial cells
Dysentery
EAEC Watery diarrhea Enterotoxins
Traveler's diarrhea Cytotoxins
Persistent diarrhea in children Adherence in cell culture
STEC = Shiga toxin-producing E. coli; ETEC = enterotoxigenic E. coli; EPEC = enteropathogenic E. coli; EIEC = enteroinvasive E. coli; = enteroaggregative E. coli.
disease has been established based on studies of immune responses,
disease association, and studies of virulence factors.39
EIEC causes watery diarrhea through invasion of the epithelial cells
of the colon, although EIEC strains do not produce enterotoxins.
Abdominal cramps, malaise, tenesmus, and fever may accompany
diarrhea, and rarely will progress to bloody diarrhea or dysentery. EIEC
are closely related to Shigella.42 As with EPEC and other diarrheagenic
strains of E. coli, EIEC cannot be distinguished from non-pathogenic E.
coli in routine culture. Infections due to EIEC are rare in the U.S.43 Until
recently, diagnosis was only achievable through molecular or other
methods performed at reference or public health laboratories.
First described in the 1980’s, EAEC causes epidemic and sporadic
diarrhea among children and adults in developing and developed
countries.44 It has been associated with traveler's diarrhea, as well as
persistent infant diarrhea. The consistency of the stool is watery with
mucus, but it may also be bloody. EAEC is found within the intestines
and produces enterotoxins and cytotoxins. Its name was derived from
its ability to adhere to certain cells in cell culture in a pattern resem-
bling stacked bricks.45 As with many of the other E. coli strains dis-
cussed in this section, EAEC cannot be distinguished from non-patho-
genic E. coli by routine stool culture and diagnosis relies upon
molecular or other advanced methods. Distinct from several other
diarrheagenic pathotypes of E. coli, EAEC strains are not as clearly as-
sociated with disease. In a matched case-control study in Africa and
Asia, there was no clear association with diarrhea when an in-house
multiplex PCR of stool targeting various genes of diarrheagenic E. coli
pathotypes was used.46 In a U.S. study of 1267 children in Tennessee,
there was no significant difference between prevalence of EAEC strains
in cases versus controls (17/857 [2%] vs. 15/410 [4%], respectively;
OR 0.52, range 0.26–1.07).47 Current evidence supports the possibility
that EAEC more often is associated with asymptomatic carriage than
with diarrhea.
In a study of the BioFire GIP, which can detect STEC, EPEC, ETEC,
EIEC, and EAEC diarrheagenic pathotypes of E. coli, two or more pa-
thogens were detected in 116/709 (16%) of stool samples.48 Of the
samples positive for two or more pathogens, 98/116 (84%) were po-
sitive for either EPEC or EAEC. The percentages of EPEC (45.7%) and
EAEC (61.5%) associated with coinfection have been high in other
studies as well.49 Since laboratories have not historically tested for
several of these pathotypes such as EPEC and EAEC, laboratories and
clinicians are faced with the difficulty of assigned clinical relevancy to
these pathogens.
Conclusions
In summary, the increasing use of multiplex molecular-based syn-
dromic stool pathogen panels in routine clinical microbiology labora-
tories may aid in a better understanding of the roles P. shigelloides and
the various diarrheagenic pathotypes of E. coli play in gastroenteritis.
191
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Seminars in Diagnostic Pathology 36 (2019) 187–192
Site of infection Strength of evidence in role of disease
Small intestine High
Colon
Small intestine High
Small intestine Moderate
Colon Moderate
Small intestine Low
Colon
However, not all commercial systems include such targets, so disease
incidence remains unclear. Nevertheless, most evidence clearly sup-
ports P. shigelloides and some diarrheagenic pathotypes of E. coli in-
cluding STEC and EPEC and perhaps EPEC and EIEC as true pathogens
in gastroenteritis. On the other hand, pathogenicity of EAEC and
Aeromonas spp. is not currently well established in the literature and
requires further study. The limitations of routine stool culture methods
in detecting Aeromonas, P. shigelloides, ETEC, EPEC, EIEC, and EAEC
also limit our understanding. Further studies assessing the clinical sig-
nificance of such pathogens need to be performed. Additionally, de-
tection methods for these various pathogens should be developed for
possible routine assessment by clinical laboratories when gastro-
enteritis is suspected.
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