Author(s): Amanda Garcia-Williams, Kayla Vanden Esschert, Naeemah Logan

Infectious Agent

Shigellosis is an acute infection of the intestine caused by bacteria in the genus Shigella. There are 4 species of Shigella: S. dysenteriae, S. flexneri, S. boydii, and S. sonnei (also referred to as group A, B, C, and D, respectively). Several distinct serotypes are recognized within the first 3 species.

Transmission

Shigella is transmitted via the fecal–oral route, through direct person-to-person contact, or indirectly through contaminated food, water, or fomites. Transmission directly from one person to another or via fomite is likely the most common mode of transmission in high resource settings; foodborne and waterborne transmission are additional important transmission routes in both high- and low-resource settings. Spread of Shigella through both direct and indirect sexual contact has been widely reported, primarily among men who have sex with men (MSM). Shigellosis is highly contagious; as few as 10 organisms can cause infection. Humans are the primary natural reservoir, although nonhuman primates also can be infected.

Epidemiology

Shigella spp. are endemic to temperate and tropical climates. Shigellosis is caused predominantly by S. sonnei in high-income countries, whereas S. flexneri is prevalent in low- and middle-income countries. Infections caused by S. boydii and S. dysenteriae are less common globally. S. boydii is mostly restricted to the Indian subcontinent, and S. dysenteriae accounts for most Shigella spp. isolated in sub-Saharan Africa and South Asia.

Worldwide, Shigella is estimated to cause 80–165 million cases of disease and 600,000 deaths annually, and most cases and deaths are among children. Among shigellosis cases worldwide, approximately 20–119 million illnesses and 6,900–30,000 deaths are attributed to foodborne transmission. Foodborne transmission has been reported among travelers in multiple outbreaks, and tourists became ill after eating contaminated foods in hotels and on airplanes and cruise ships. Common food vehicles include cold salads, vegetables, lettuce, and herbs; meat and dairy items and hot dishes also have been implicated.

Numerous outbreaks have also been attributed to waterborne transmission, in both treated and untreated recreational water, and through ingesting contaminated drinking water. Outbreaks of shigellosis tend to occur in settings where sanitation and hygiene practices are inadequate; common settings include schools and daycare centers, private residences, and restaurants. Other populations with reported outbreaks of shigellosis include MSM, people experiencing homelessness, and people in refugee camps.

Shigella spp. have been detected in stool samples of 5%–18% of patients with travelers’ diarrhea, and studies in Australia and Canada found that 40%–50% of locally diagnosed shigellosis cases were associated with international travel. In the United States, ≈25% of sporadic cases of shigellosis are travel-associated, and Shigella spp. account for 13% of travel-associated enteric infections. In a study conducted among US travelers, most infections caused by S. dysenteriae (56%) and S. boydii (44%) were travel-associated, whereas infections caused by S. flexneri and S. sonnei were less often associated with travel (24% and 12%, respectively). In another study among US travelers, the risk for infection caused by Shigella spp. was greatest for people who had traveled to Africa, and then travelers to Central America, South America, and Asia. Infections caused by Shiga toxin–producing S. flexneri and S. dysenteriae have been reported repeatedly among travelers to Haiti and the Dominican Republic (Hispaniola).

Antimicrobial resistance is common in Shigella; resistant strains can be acquired during travel to areas of high endemicity. A systematic review of travel-associated Shigella infections from 139 countries showed that the percentage of antibiotic- resistant infections increased from 19% during 1990–1999, to 65% during 2000–2009. Moreover, most resistant Shigella spp. isolates originated from Asia (25%, excluding West Asia) and Central and South America (18%). The study also documented an increase in quinolone-resistant Shigella spp. from 30% during 1990–1999 to 53% during 2000–2009.

Likewise, in the United States, infection with quinolone-resistant Shigella spp. has been linked to international travel. Bowen et al. identified a large outbreak of ciprofloxacin-resistant shigellosis in San Francisco after international travel, primarily to the Dominican Republic, Haiti, and India. Similarly, Grass et al. analyzed Shigella infections using linked data collected during 2004–2014 from the Foodborne Diseases Active Surveillance Network (FoodNet) and National Antimicrobial Resistance Monitoring System (NARMS). The authors found that international travel was associated with a 6-fold higher odds of infection with quinolone-resistant Shigella.

Resistance to third- and fourth-generation cephalosporins is less common but has also been documented in the United States and is more common in South and East Asia. Additionally, reduced susceptibility to azithromycin and ciprofloxacin has been documented among MSM in several countries, including the United States. Finally, widespread and extensive resistance to former first-line agents, including ampicillin, cotrimoxazole, and nalidixic acid, exists.

Clinical Presentation

Illness typically begins 1–2 days after exposure with symptoms lasting 5–7 days. Disease severity varies according to species. S. dysenteriae serotype 1 (Sd1) is the agent of epidemic dysentery and often causes severe illness, whereas S. sonnei commonly causes milder, nondysenteric diarrheal illness. Shigella of any species can cause severe illness among people with compromised immune systems.

Shigellosis is characterized by watery, bloody, or mucoid diarrhea, fever, and stomach cramps. Tenesmus is also a common symptom. Illness in immunocompetent people is usually mild and self-limited. Occasionally, patients experience intestinal or extraintestinal complications, including intestinal perforation, seizures (in young children), and invasive focal infections. Postinfectious manifestations, including reactive arthritis, and hemolytic-uremic syndrome (HUS), can occur weeks after infection. HUS is associated with Shiga toxin–producing Shigella strains, particularly Sd1.

Diagnosis

To confirm the diagnosis of shigellosis, perform a stool culture. Conduct antimicrobial susceptibility testing for patients who might require antimicrobial treatment. Rapid PCR-based diagnostic tests for Shigella are now increasingly available in the United States. This method cannot determine whether viable Shigella organisms are present in stool, however, and does not yield an isolate for susceptibility testing or for public health investigation and control. As such, if Shigella is detected using a PCR assay, consider performing reflex culture and susceptibility testing.

If additional diagnostic support is required, consult a clinical laboratory first. Testing performed at the Centers for Disease Control and Prevention, if appropriate, should be arranged through the state or county public health department. Shigellosis is a nationally notifiable disease in the United States.

Treatment

Shigellosis usually resolves within 5–7 days with supportive care alone; antimicrobial treatment given early in the course of illness can, however, shorten the duration of symptoms and of carriage (asymptomatic shedding of the organism in the stool). Consider antimicrobial treatment for patients with severe disease or those with compromised immune systems. Antimicrobial treatment can also be considered for patients working in occupations where their risk of transmitting Shigella to others is high (e.g., childcare workers, food handlers, health care workers) or to limit transmission in outbreak settings.

Whenever possible, use antimicrobial susceptibility results to direct antibiotic therapy. If empiric therapy is indicated, current clinical guidelines recommend azithromycin, ciprofloxacin, or ceftriaxone as first-line options. Given widespread resistance to commonly used first- and second-line agents, review local resistance trends and pertinent sexual and travel history before initiating empiric therapy. In the United States, populations at increased risk for multidrug-resistant Shigella infections include international travelers, people experiencing homelessness, MSM, and people infected with HIV. Information on antimicrobial resistance among shigellosis cases in the United States is available at https://wwwn.cdc.gov/narmsnow. Additional discussion of symptomatic management can be found in Sec. 2, Ch. 6, Travelers’ Diarrhea.

Prevention

No vaccines are available for Shigella. The best defense against shigellosis is thorough, frequent handwashing; strict adherence to standard food and water safety precautions (see Sec. 2, Ch. 8, Food & Water Precautions); and minimizing fecal–oral exposures during sexual activity by using barriers during sex, washing the genitals and anal area before and after sex, and washing sex toys after use. When soap and water are not available, travelers can use alcohol-based hand sanitizers. Sec. 2, Ch. 6, Travelers’ Diarrhea, contains general recommendations to prevent diarrhea while traveling.

CDC website: Shigella