Mr. Wilson, a 37-year-old man, decides to take his two children (Steven, age 5, and Linda, age 12) to Sweden to visit his parents, who are dairy farmers living just outside the town of Malmö. The children enjoy helping their grandparents care for the numerous domestic animals on the farm and love the home-cured meat and fresh raw milk served to them. Their father, on the other hand, is not a big fan of animals, raw milk, or home-cured meats, so he avoids them all whenever possible. Everything is fine until both children become ill 9 days after the family's arrival in Sweden. Steven develops a watery, mucoid diarrhea with occasional flecks of blood, a low-grade fever, and a diffuse abdominal pain, all of which resolve spontaneously after 4 days. Linda's episode begins in a similar fashion, but worsens after 3 days, when her pain localizes in the right lower quadrant and becomes associated with high fever and leukocytosis. She is brought to the hospital, where a tentative diagnosis of acute appendicitis is made. During surgery her appendix is found to be normal, but the terminal ileum is inflamed, with many enlarged mesenteric lymph nodes. Stool cultures were done when Linda was admitted, but they were incubated at 25(C for several days before culturing. By the time the lab reports its results, Linda has made a nearly complete recovery.

Question 7.1: What do you think the lab reported?

The children clearly had some type of acute gastroenteritis. The fact that both children were exposed to domestic animals and consumed home-cured meat and raw milk suggests some sort of zoonotic disease. One of the cases mimicked acute appendicitis, something that is not seen with most gastrointestinal infections. The fact that the infections occurred in Scandinavia is also suggestive. Specific lab tests would be required to confirm it (because the symptoms are not overly definitive), but the most likely diagnosis to explain this particular combination of facts would be yersinosis. In fact, the lab identified the causative agent in both cases as Yersinia enterocolitica.

Question 7.2: How did the children acquire their infections?

Yersinosis is a bacterial zoonosis (uncommon in the U.S.) caused by infection with either of two enteropathogenic Yersinia species: Y. enterocolitica and Y. pseudotuberculosis. Reservoir hosts of these two bacteria include swine and other wild and domestic animals. Most Y. enterocolitica infections are caused by strains associated with domestic mammals. Infection of humans usually occurs via the oral route, in contaminated foods or raw milk. Either the home-cured meat or the raw milk probably served as the source of infection in this case. The incidence rate of Y. enterocolitis infection is highest in Scandinavia and some other northern European countries, although this observation may be in part an artifact of underrecognition in other countries.

Question 7.3: How does this causative agent produce disease?

A large dose of bacteria (possibly >109 cells) must be swallowed to initiate an infection. After an incubation period of 1-11 days (average of 5 days), Y. enterocolitica invades the ileal epithelium, is translocated via M cells into the lamina propria, and finally enters the Peyer's patches, where it replicates. The bacterium then drains into the mesenteric lymph nodes, which undergo hyperplasia and from which the bacteria can be distributed systemically. The mesenteric lymph nodes become severely swollen and matted, and they occasionally can be detected on physical examination as a tender right lower quadrant mass. Intestinal inflammation (most often in the distal ileum) develops and may be accompanied by mucosal ulcerations and shedding of PMNs and red blood cells into the intestinal lumen.

Y. enterocolitia contains a plasmid that is essential for virulence because it codes for at least six outer membrane proteins that act as virulence factors. Some of these proteins confer properties such as cytotoxicity; resistance to phagocytosis by PMNs; and the ability to suppress the host's expression of tumor necrosis factor (, to cause monocyte apoptosis, to interfere with platelet aggregation and host complement activation, and to dephosphorylate host proteins. A chromosomal gene (inv) encodes for the surface protein invasin, which is required for yersinial invasion of nonphagocytic host cells (e.g., epithelial cells) and which facilitates the translocation of bacteria across the intestinal epithelium. Y. enterocolitica also produces superantigens, enterotoxin, and endotoxin, but the role of these compounds in pathogenesis (if any) has yet to be identified.

Question 7.4: What complications may be associated with this disease?

Although not a complication per se, the syndrome of mesenteric adenitis and terminal ileitis (in the absence of diarrhea) is very easily confused with appendicitis. Unnecessary appendectomies are carried out in about 10% of these cases, and the surgical incisions sometime become infected with Y. enterocolitica. Rare (and sometimes fatal) complications of yersinosis include diffuse inflammation, ulceration, hemorrhage, and necrosis of the small bowel and colon; intestinal perforation; peritonitis; ascending cholangitis; mesenteric vein thrombosis; diverticulitis; toxic megacolon; and ileocecal intussusception. Acute pharyngitis and pharyngotonsilitis, with or without cervical adenitis or intestinal illness, are less common but potentially lethal manifestations of Y. enterocolitica, especially in adults. In Scandinavia, about 10% of the cases that occur in adults are followed by reactive arthritis, which most frequently affects the knees and ankles.

Question 7.5: Who is most susceptible to this disease?

All age groups are susceptible, but the majority of Y. enterocolitica infections occur in children aged 1 to 4. There is a modest predilection for males in this age group. Mesenteric adenitis and terminal ileitis are most common among older children and young adults. Risk factors include chronic liver disease, malignancy, diabetes mellitus, immunosuppressive therapy, malnutrition, advanced age, and other factors.

Question 7.6: How can this disease be treated?

Most uncomplicated cases of yersinial enteritis, enterocolitis, mesenteric adenitis, and terminal ileitis are self-limiting. Treatment is symptom-based and supportive. The effectiveness of antimicrobial agents in the treatment of these diseases has not been established. Antibiotic treatment is usually reserved for cases with septicemia, metastatic focal infections, etc.