++
The organism has
a large animal reservoir, including cattle, sheep, swine, dogs,
cats, horses, rodents, and lagomorphs. Streams, lakes, and drinking
water have all been contaminated.
++
Yersinia enterocolitica has been isolated from
humans worldwide, but most commonly in cooler climates. The organism
has a large animal reservoir, including cattle, sheep, swine, dogs,
cats, horses, rodents, and lagomorphs. Streams, lakes, and drinking
water have all been contaminated. The most common mode of transmission
is ingestion of contaminated food, milk, or water.3 Occasional outbreaks
have been reported within families or institutions. Common source
outbreaks have been traced to raw milk, contaminated pasteurized
milk, and foods prepared with contaminated water. Person-to-person
transmission has not been conclusively proven but probably occurs.
Seasonal isolation rates of Yersinia indicate that
it is more prevalent as a cause of enteritis in winter months in
the United States.4,5 Most reported cases have
been from Canada, Europe, and the United States. Clustering of infections
during fall and winter has been reported in northern Europe.1 Because
pigs are often infected, persons who eat or handle pork are at risk
of getting infected. Diarrheal illness in infants caused by Y
enterocolitica 0:3 in the United States is associated with
household preparation of raw pork intestines (chitterlings).6 In
one study 20 (62%) of 32 children with Y enterocolitica diarrheal
illness had been exposed to raw pork intestines in the 2 weeks before
onset. Affected infants were probably exposed to infection by their caretakers
who were cleaning the chitterlings while caring for the infants.African
American infants have the highest incidence of infection in the
United States.7 Among 142 pediatric patients with Y
enterocolitica enteritis, 141 were black, 85% were
under age 1, and 84 presented during November to January.7 Rarely,
severe infections have been transmitted from blood transfusions.8 Some
blood donors may occasionally have transient occult Y enterocolitica bacteremia
at the time of donation, and the organism can multiply to high concentrations in
refrigerated blood. One instance of perinatal transmission has been
reported.
++
The frequency of isolation of Y enterocolitica from
stools of patients with diarrhea is reported to be 1% to
3% in a number of studies. In one Canadian report, it was
recovered in 2.8% of stool cultures from 6364 children
with diarrheal illnesses over a 15-month period. It was isolated
less often than Salmonella, but more commonly than Shigella, in
this series.9 In one US study, Y enterocolitica was
recovered in 1.3% of stool cultures of 10,570 children
with diarrheal illness during a 7-year period. It accounted for
12.6% (142 of 1120) of all bacterial enteric pathogens. Yersinia infection
during the study period was comparable to Campylobacter,
but lower than Salmonella or Shigella.7 In
a pediatric multicenter study in the United States, Y enterocolitica was
recovered from 1% of stool specimens. The yield was comparable
to that of Shigella and Campylobacter, but
less than that of Salmonella. One other study found
no isolates in more than 1000 stool samples, but specimens were
processed only from May to November and not during the winter months.
++
Yersinia enterocolitica is an invasive organism
and causes disease by tissue destruction. Pathogenic properties
include chromosomally mediated effects such as invasion attachment to
host cells, iron complexing and uptake, and enterotoxin production.
Plasmid-mediated mechanisms include production of outer membrane
antigens, calcium dependency for growth, and autoagglutination.
Invasion and penetration of the mucosa occurs in the ileum, followed
by multiplication in Peyer patches.
++
Drainage into the mesenteric lymph nodes can lead to systemic
infection or mesenteric adenitis. The enterotoxin produced by Y
enterocolitica appears to play a minor role in causing
disease because diarrheal illness can occur in the absence of enterotoxin
production. In addition, the toxin appears to be produced only at
temperatures lower than 30°C. The plasmid-mediated outer membrane
antigens are associated with bacterial resistance to opsonization
and neutrophil phagocytosis.
++
One unique property of Y enterocolitica is its
inability to chelate iron. Iron is an essential factor for growth
of most bacteria. Bacteria produce and release iron-binding chelators known
as siderophores that extract iron from transferrin. Yersinia
enterocolitica does not produce siderophores but has receptors
for them and can utilize siderophores produced by other bacteria
including the gastrointestinal flora (eg, deferoxamine produced
by Streptomyces pilosus). Iron overload substantially
increases the pathogenicity of the organism, perhaps through attenuation
of the bactericidal activity of the serum. However, to establish extraintestinal
infection, an exogenous siderophore (eg, a chelating agent such
as deferoxamine) or excess iron is required. It is for this reason
that Y enterocolitica bacteremia and other systemic
infections are more often seen in patients with iron overload and
those receiving chelation therapy including patients with thalassemia
major with hemosiderosis and some patients with sickle-cell disease.10,11
+++
Clinical Manifestations
++
Infection with Y enterocolitica may result in a
variety of clinical presentations that, to some extent, are dependent
on the age and physical state of the host. The most common clinical syndrome
is acute enteritis illness resulting in diarrhea (98%),
fever (88%), abdominal pain (65%), and vomiting
(38%). The mean duration of diarrhea is 2 weeks (range
1–28 days). Blood and mucus are found in the stool in 25% to
50% of the children. This clinical presentation is seen
most frequently in children younger than age 5 years.7,9 Most
enteric infections are benign and self-limited; however, intra-abdominal
complications occur in a small percentage of patients and include
diffuse ulceration, intestinal perforation, peritonitis, intussusception,
toxic megacolon, and mesenteric vein thrombosis. Rarely, patients
may develop a chronic illness with intermittent diarrhea. In older
children and adolescents, Y enterocolitica infection
is more likely to present with pseudoappendicitis syndrome (mesenteric
adenitis).13 Clinical manifestations include fever
and diffuse abdominal pain that subsequently localizes to the right
lower quadrant. Nausea, anorexia, and vomiting may occur. Guarding
and rebound tenderness are common; leukocytosis is frequently present. Appendectomy
is often performed on these patients; however, at laparotomy the
appendix is normal or slightly inflamed with mesenteric adenitis
and terminal ileitis. The organism can be cultured from the ileum
as well as the mesenteric nodes. The pain usually resolves gradually
over a period of 1 to 2 weeks.
++
Septicemia with Y enterocolitica is the major
complication of enteric infection in the very young and in those
with iron overload syndromes. One report indicated that 28% of children
younger than age 3 months with Y enterocolitica enteritis
developed sepsis.7
++
Conditions that seem to predispose to septicemia with this organism
include liver disease; hemochromatosis; diabetes mellitus; malnutrition;
immunosuppressive therapy; iron overdose; iron overload states such
as transfusion-dependent blood dyscrasias (sickle-cell diseases, β-thalassemia,
aplastic anemia); and chelation therapy. Septicemia can lead to
metastatic sites of infection including hepatic and/or
splenic abscesses.
++
Adults with Yersinia infection are more susceptible
to 2 manifestations that are presumed to be immunologically mediated:
arthritis and erythema nodosum.14 In Scandinavia,
reactive arthritis following Y enterocolitica infection in
adults occurs in about 10% of patients. The initial symptoms
may include an acute diarrheal illness with fever and abdominal
pain followed in 1 to 2 weeks by an aseptic arthritis. This most
commonly involves the knees or ankles, but the small joints of the
hands and feet can be affected. Reiter syndrome with reactive arthritis,
urethritis, and conjunctivitis/uveitis is seen in 10% of
these patients. The synovial fluid may contain a few hundred to 63,000
white cells per cubic millimeter with predominance of polymorphonuclear
leukocytes. Cultures of the joint fluid are sterile, but Y
enterocolitica antigen has been detected in immune complexes
within the affected joints. Reactive arthritis is more common in
individuals who are HLA B27 positive. The illness lasts 1 to 4 months,
but can persist for more than a year. Erythema nodosum is seen as
a postinfectious syndrome primarily in middle-aged women. In Scandinavia,
it occurs in 15% to 20% of patients with Yersinia infection.
The lesions, usually located on the lower extremities, appear within
a few days to several weeks after the intestinal infection and disappear within
a month. Erythema nodosum may be associated with fatigue and fever.
++
Other occasional manifestations of infection with Y enterocolitica include
exudative pharyngitis (with or without gastrointestinal manifestations),
pneumonia, lung abscess, endocarditis, urinary tract infection,
cutaneous abscess, and conjunctivitis. The atypical presentations
are associated with serotypes other than 0:3, 0:8, and 0:9.
++
Diagnosis of Y enterocolitica infection should be
made by isolating the organism from appropriate clinical specimens
such as stools and sometimes from mesenteric lymph nodes or peritoneal
fluid specimens. When infection with Y enterocolitica is
suspected, the laboratory should be instructed to culture specifically
for this organism. Although Y enterocolitica can
grow on commonly used enteric media, growth is slow and can be overlooked
by concomitant growth of multiple isolates of normal flora. The
use of selective media such as agar containing cefsulodin, irgasan,
and novobiocin (CIN) is more effective than routine enteric media
for recovery of the organism from stools. Cold enhancement in phosphate-buffered
saline may also increase the yield of cultures from contaminated
specimens.
++
When the organism cannot be cultured, but Yersinia is
suspected, serologic testing may be of benefit. Tube agglutination
test is the standard assay; however, enzyme-linked immunoassays
(ELISA) and radioimmunoassays have also been developed. Titer determinations
are available through commercial laboratories for the most common
serotypes. Agglutinin titers rise 1 week after onset of symptoms
and reach a peak in the second week of illness. The usefulness of
serologic testing, however, is limited by cross-reactions between Y
enterocolitica and Brucella abortus, Rickettsia,
Salmonella sp, and Morganella morganii.
Children younger than age 1 year are also less likely to develop
serologic response than are older children. In addition, some populations
may have a high seroprevalence in healthy individuals. An agglutinin
titer greater than 1:128, in the appropriate clinical setting, is
considered presumptive evidence of infection.
++
In vitro testing indicates that Y enterocolitica is
susceptible to trimethoprim-sulfamethoxazole, aminoglycosides, chloramphenicol,
tetracycline, third-generation cephalosporins, and the quinolones.
Strains are often resistant to penicillins, ampicillin, first-generation cephalosporins,
and most second-generation cephalosporins.15 Despite
the in vitro testing, the effectiveness of antibiotics in the treatment of
uncomplicated gastroenteritis or mesenteric adenitis (pseudoappendicitis
syndrome) has not been established. In one pediatric trial, trimethoprim-sulfamethoxazole
was compared to placebo in 34 patients with gastroenteritis; treatment
did not show any significant clinical or bacteriologic benefit.
However, the study was limited by the small number of patients and
the initiation of treatment late in the course of the illness.16 Uncontrolled
data suggest some benefit of therapy in patients with prolonged
symptoms.
++
Immunocompromised patients with enterocolitis, patients with
septicemia, and those with focal extraintestinal infections should
be treated with antimicrobial therapy. Although there are no controlled
clinical comparisons of antimicrobials in the treatment of severe Y
enterocolitica infections in human beings, doxycycline
and gentamicin were promising in a mouse model. Trimethoprim-sulfamethoxazole
(or doxycycline in older patients) can be used for focal disease.
Third-generation cephalosporins, often in combination with an aminoglycoside,
were shown to have a successful outcome in the treatment of patients
with extraintestinal infection such as septicemia. Selection of
appropriate antimicrobial treatment should ultimately be guided
by the clinical response of the patient and antimicrobial susceptibility
results. Treatment of septicemia in patients with iron overload
should include temporary discontinuation of desferrioxamine chelation
therapy. Recent data indicate that the third-generation cephalosporin
cefotaxime is effective in the treatment of Y enterocolitica bacteremia
in children.7 Antibiotic treatment has no effect
in patients with postinfectious syndromes.
++
Attention to appropriate handling and cooking of pig products,
especially intestines, should decrease the risk of infection associated
with these food items. Consumption of uncooked meat should be avoided.
Refrigeration of cooked meat for prolonged periods of time before
consumption should be avoided because Y enterocolitica grows
at refrigerator temperature.
++
Patients and at-risk individuals should be instructed about appropriate
hygiene methods and signs and symptoms of infection.
++
Outbreaks of illness owing to Y enterocolitica are
often foodborne and should receive prompt and thorough investigation.
++
Careful handwashing and enteric precautions are required for
a prolonged period following infection. In one Canadian report,
the duration of excretion of Y enterocolitica in
the stool ranged from 14 to 97 days (mean 42 days). Spread of the
organism occurred in 27 of 57 families studied.9