and Panpanit 1987). ReA after shigellosis is rare: in studies of Israeli soldiers with acute diarrheal illnesses, 336 cases of shigellosis were documented from 1993 to 1997 in the field units under surveillance, and none of the subjects developed ReA or ankylosing spondylitis (Bloom et al. 1994).

The most conclusive evidence regarding the incidence of ReA due to Shigella infection comes from the recent population-based study of Hannu et al. (2005). Of 278 patients with Shigella-positive stool cultures, 7% had ReA, and an additional 2% developed other reactive musculoskeletal symptoms; one of the 597 controls had ReA. In the Shigella-positive patients, the odds ratio for developing ReA was 16.2 (95% CI, 2.1-123.9). Some 36% of the ReA patients were HLA-B27-positive. Several additional studies and case reports support the findings of Hannu et al. (Chen et al. 2002; Davies et al. 1969; Finch et al. 1986; Lauhio et al. 1988; Neithercut et al. 1984; Noer 1966; Sieper et al. 1993; Simon et al. 1981).

The committee concludes that there is sufficient evidence of an association between Shigella infection and reactive arthritis (ReA), if the ReA is manifested within 3 months of the infection. Most cases of ReA will be manifested within 1 month of the infection.

Hemolytic Uremic Syndrome

Acute shigellosis may lead to hemolytic uremic syndrome (HUS), a life-threatening disease that afflicts primarily young children and the elderly (Ilnyckyj et al. 2003; Okhuysen et al. 2004). HUS is defined as a clinical triad of hemolysis, thrombocytopenia, and renal dysfunction. It is usually manifested within 6-10 days of the onset of shigellosis; more rarely, people with shigellosis-associated HUS can come to clinical attention as late as 30 days after the onset of enteritis (Nathoo et al. 1995; Parsonnet and Griffin 1993).

Shiga toxins produced by some Shigella strains (particularly S. dysenteriae) cause HUS by damaging endothelial cells, especially in the kidneys. The damage leads to microangiopathy, which results in microangiopathic hemolytic anemia, renal failure, and systemic illness.

There have been many published cases of HUS that occurred after shigellosis. For example, HUS occurred after Shigella infection in two of 42 US tourists to Mexico in 1988 (Parsonnet et al. 1989), 40 of 320 (12%) patients in Bangladesh admitted to a hospital (Rahaman et al. 1975), nine of 241 (4%) patients in Bangladesh (Koster et al. 1978), and seven of 36 (19%) patients in South Africa (Bloom et al. 1994).

The committee concludes that there is sufficient evidence of an association between Shigella infection and hemolytic uremic syndrome (HUS), if HUS is manifested within 1 month of the infection. Most cases of HUS will be manifested within 10 days of the infection.

BRUCELLOSIS

Human brucellosis is a chronic intracellular infectious process that involves Brucella spp. and the human reticuloendothelial system. The process may harm any organ in the human body. Up to 10% of people infected with brucellae may develop chronic disease, which is often due to relapses after partial therapy or to disease progression after undiagnosed and untreated acute disease. Although brucellosis occurs sporadically in many countries, it is endemic in areas of southwest and south-central Asia. The committee discusses below the clinical spectrum of



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