Typhoid fever, also referred to as enteric fever, is caused by Salmonella typhi and Salmonella paratyphi. It affects up to 30 million individuals worldwide each year. Infection by S. typhi is more common in endemic areas, where children and adolescents are most often affected. By contrast, S. paratyphi predominates in travelers and those living in developed countries. Humans are the sole reservoir for S. typhi and S. paratyphi, and transmission occurs from person to person or via contaminated food or water. Gallbladder colonization may be associated with gallstones and a chronic carrier state. Acute infection is associated with anorexia, abdominal pain, bloating, nausea, vomiting, and bloody diarrhea followed by a short asymptomatic phase that gives way to bacteremia and fever with flulike symptoms. It is during this phase that detection of organisms by blood culture may prompt antibiotic treatment and prevent further disease progression. Cultures are positive in 90% of cases during the febrile phase Without such treatment, the febrile phase is followed by up to 2 weeks of sustained high fevers with abdominal tenderness that may mimic appendicitis. Rose spots, small erythematous maculopapular lesions, are seen on the chest and abdomen. Systemic dissemination may cause extraintestinal complications including encephalopathy, meningitis, seizures, endocarditis, myocarditis, pneumonia, and cholecystitis. Patients with sickle cell disease are particularly susceptible to Salmonella osteomyelitis.
Like S. enteritidis, S. typhi and S. paratyphi are taken up by M cells and then engulfed by mononuclear cells in the underlying lymphoid tissue. Thus, infection causes Peyer patches in the terminal ileum to enlarge into plateau like elevations up to 8 cm in diameter. Mucosal shedding creates oval ulcers oriented along the long axis of the ileum. However, unlike S. enteritidis, S. typhi and S. paratyphi can disseminate via lymphatic and blood vessels. This causes reactive hyperplasia of draining lymph nodes, in which bacteria-containing phagocytes accumulate. In addition, the spleen is enlarged and soft with pale red pulp, obliterated follicular markings, and prominent phagocyte hyperplasia. Randomly scattered small foci of parenchymal necrosis with macrophage aggregates, termed typhoid nodules, can be found in the liver, bone marrow, and lymph nodes. Definitive diagnosis depends on positive blood cultures. Serologic tests are of limited utility, especially in endemic areas unless rising titers of antibodies can be demonstrated.
Pseudomembranous colitis, generally caused by C. difficile, also is referred to as antibiotic-associated colitis or antibiotic-associated diarrhea. While antibiotic-associated diarrhea also may be caused by other organisms such as Salmonella, C. perfringens type A, or Staphylococcus aureus, only C. difficile causes pseudomembranous colitis. It is likely that disruption of the normal colonic microbiota by antibiotics allows C. difficile overgrowth. Almost any antibiotic may be responsible; the most important determinants of the disease are frequency of use and the effect on colonic microbiota. Toxins released by C. difficile cause the ribosylation of small GTPases, such as Rho, and lead to disruption of the epithelial cytoskeleton, tight junction barrier loss, cytokine release, and apoptosis.
MORPHOLOGYFullydevelopedC. difficile–associatedcolitisisaccompaniedbyformationofpseudomembranes (