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Shigellosis

Chapter 172 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial · Chapter 172

Key Clinical Points

  1. Shigellosis is a clinical syndrome of fever, intestinal cramps, and frequent passage of small, bloody, mucopururulent stools caused by Shigella species.
  2. The human intestinal tract is the primary reservoir; high infectivity is evidenced by a very small inoculum (100 colony-forming units [CFU]) required for infection.
  3. S. dysenteriae type 1 produces Shiga toxin (A1-B5 structure), which inhibits protein synthesis via RNA N-glycosidase activity on 28S ribosomal RNA, potentially leading to Hemolytic-uremic syndrome (HUS).
  4. HUS is characterized by a diagnostic triad: microangiopathic hemolytic anemia (Hb <80 g/L), thrombocytopenia (<60,000/μL), and acute renal failure.
  5. Toxic megacolon results from severe inflammation of the colonic smooth-muscle layer, presenting with abdominal distention and specific radiographic findings like 'thumbprinting'.
  6. Reactive arthritis can occur weeks or months after S. flexneri infection in patients who are HLA-B27 positive.
  7. Antibiotic treatment is mandatory for all cases due to high transmissibility; fluoroquinolones (e.g., ciprofloxacin) are first-line despite rising resistance.
  8. Geographic distribution varies: S. flexneri predominates in less developed areas, while S. sonnei is more prevalent in emerging and industrialized nations.
  9. Diagnosis is confirmed by isolating Shigella from stool samples; treatment duration depends on the specific strain (e.g., 5 days for S. dysenteriae type 1).

EPIDEMIOLOGY

Shigellosis is a globally significant diarrheal disease with distinct geographic patterns. The human intestinal tract serves as the primary reservoir, with transmission primarily via the fecal-oral route.

• Transmission Routes: Fecal-oral (hand carriage), food/waterborne, and sexual contact. • Infectivity: High; 100 colony-forming units (CFU) can cause infection in experimental models. • Outbreak Settings: ◦ Day-care centers: attack rates 33–73%. ◦ Family clusters: 26–33% secondary cases. • Geographic Distribution: ◦ S. flexneri: Predominates in least developed areas. ◦ S. sonnee: Prevalent in emerging and industrialized nations. • Historical Context & Impact: ◦ ~165 million annual cases (1966–1997), with 69% in children <5 years. ◦ Significant contributor to stunted growth in endemic regions through exudative enteropathy and malnutrition.

Age and Nutritional Factors

• Pediatric Prevalence: Peak incidence in children due to lack of acquired immunity. • Adult/Elderly Trends: Decline in adults but a notable resurgence in elderly populations. • Socioeconomic Link: Strong association with poverty and poor hygiene, particularly in children <5 years post-weaning.

ETIOLOGY & PATHOPHYSIOLOGY

Shigella pathogenesis involves a complex virulence cascade:

• Pathogen Characteristics: ◦ Primary reservoir: Human intestinal tract (excretion highest in acute phase). ◦ S. dysenteriae type 1: Produces Shiga toxin (A1-B5 structure) with RNA N-glycosidase activity on 28S ribosomal RNA, inhibiting protein synthesis. • Virulence Cascade: 1. Gastric survival via low-pH resistance. 2. Watery diarrhea phase (ShET-1 toxin and mucosal inflammation). 3. Colonic invasion via M cells or crypt openings. 4. Intracellular survival: Type III secretion system-mediated cytoskeletal rearrangements, vacuole lysis, and cell-to-cell spread. 5. Inflammatory response: PMN recruitment, epithelial barrier disruption, and acute colitis. 6. Systemic translocation of Shiga toxin leading to HUS.

Mechanism of Invasion (Figure 172-1)

The Type III secretion system facilitates the entry of effector proteins (IpaA, IpaB, IpaC) into host cells. This triggers: ◦ Macrophage apoptosis. ◦ Activation of inflammatory cytokines (IL-1β, IL-8, IL-18). ◦ Disruption of epithelial permeability barrier by PMNs.

CLINICAL FEATURES

Clinical manifestations vary by host factors and serotype, progressing through four phases:

  1. Incubation (1–4 days)
  2. Watery diarrhea phase
  3. Dysentery phase (bloody mucopurulent stools, tenesmus)
  4. Postinfectious phase

Key Symptoms: • Fever: Up to 40–41°C in children. • Abdominal cramps and tenesmus. • Dehydration: Less common than in other diarrheal syndromes. • Severe cases: Toxic megacolon, HUS, bacteremia, altered consciousness.

Complications

• Toxic Megacolon: ◦ Pathophysiology: Severe inflammation of colonic smooth-muscle layer. ◦ Clinical features: Abdominal distention and tenderness. ◦ Radiographic findings: Marked transverse colon dilation, thumbprinting (from mucosal edema), loss of haustral pattern, and pseudopolyps. ◦ Other findings: Pneumatosis coli (occasional) or pneumoperitoneum (if perforation occurs). • Hemolytic-uremic syndrome (HUS): ◦ Trigger: Shiga toxin in developing countries. ◦ Diagnostic triad: 1. Microangiopathic hemolytic anemia (Hb <80 g/L) 2. Thrombocytopenia (<60,000/μL) 3. Acute renal failure (elevated creatinine). • Reactive Arthritis: ◦ Risk factors: S. flexneri infection in HLA-B27-positive individuals. ◦ Timing: Weeks or months post-infection. ◦ Triad: Arthritis, urethritis, conjunctivitis.

DIAGNOSTIC APPROACH

Definitive diagnosis requires pathogen isolation from fecal samples.

  1. Sample Collection: ◦ Preferred: Rectal swabs during acute phase. ◦ Media: Buffered glycerol saline or Cary-Blair medium.
  2. Culture (Gold Standard): ◦ Method: Prompt inoculation onto selective media (Hektoen, Salmonella-Shigella agar). ◦ Incubation: 12–18 hours. ◦ Morphology: Non-lactose fermenting colonies (0.5–1 mm), convex, translucent, smooth surface.
  3. Microscopic Examination: ◦ Shigella identification: High PMN counts in each field. ◦ Entamoeba histolytica differentiation: Erythrophagocytic trophozoites with few PMNs.

Differential Diagnosis

• Invasive bacterial pathogens: Salmonella, Campylobacter jejuni, Yersinia enterocolitica, Clostridium difficile. • Parasitic infections: Entamoeba histolytica (erythrophagocytic trophozoites with few PMNs). • Inflammatory bowel disease: Crohn's disease, ulcerative colitis (distinguished by travel history).

MANAGEMENT & TREATMENT

Antibiotic therapy is essential for all cases due to high transmissibility.

  1. First-line Therapy: Fluoroquinolones (e.g., ciprofloxacin).
  2. Second-line Options: Cephalosporins, β-lactams, azithromycin.
  3. Treatment Duration: ◦ Non-dysenteriae Shigella: 3 days. ◦ S. dysenteriae type 1: 5 days. ◦ Immunocompromised patients: 7–10 days.
  4. Clinical Outcomes: ◦ Effective therapy leads to improvement within 48 hours and reduces risk of complications/mortality.

Antibiotic Regimens (Table 172-1)

• Ciprofloxacin: ◦ Children: 15 mg/kg PO BID ×3 days ◦ Adults: 500 mg PO BID ×3 days • Pivmecillinam: ◦ Children: 20 mg/kg PO QID ×5 days ◦ Adults: 100 mg PO QID ×5 days ◦ Limitations: Cost, frequent dosing, emerging resistance, no pediatric formulation. • Ceftriaxone: ◦ Children: 50–100 mg/kg IM once daily ×2–5 days ◦ Limitation: Efficacy not validated. • Azithromycin: ◦ Children: 6–20 mg/kg PO once daily ×1–5 days ◦ Adults: 1–1.5 g PO once daily ×1–5 days ◦ Limitation: Efficacy not validated.

PROGNOSIS

Clinical outcomes vary by patient factors:

• General Prognosis: ◦ Self-limiting in 90% of cases (1 week without treatment). ◦ Rapid resolution with appropriate therapy (3–7 days) with no sequelae. • High-risk groups: Children <5 years (especially malnourished), elderly patients. • Mortality Risk Factors: ◦ Nonbloody diarrhea. ◦ Moderate-severe dehydration. ◦ Bacteremia. ◦ Absence of fever. ◦ Rectal prolapse.

Special Considerations

• Genetic Factors: IRAK-4 deficiency linked to severe infections. • Global Health Impact: 99% of cases in developing nations; major contributor to child stunting.

Reference Tables

Harrison's 22e, p.1324

ANTIMICROBIAL
AGENT		 TREATMENT SCHEDULE LIMITATIONS
CHILDREN ADULTS
First-Line
Ciprofloxacin 15 mg/kg 500 mg
2 times per day for 3 days, PO
Second-Line
20 mg/kg 100 mg
4 times per day for 5 days PO
50–100 mg/kg —
Once a day IM for 2–5 days
6–20 mg/kg 1–1.5 g
Once a day for 1–5 days PO