Lecture on Shigellosis Pathogenesis and Treatment

Shigellosis Pathogenesis

• Causative Agent: Shigella causes invasive diarrhea.
• Site of Infection: Primarily affects the colon, particularly the rectal mucosa.
• Entry Mechanism:
  • Enters colonic enterocytes and M cells (microfold cells) in the colonic mucosa.
  • M cells are significant for clinical infection, as seen in rectal biopsies.
• Bacterial Secretion System:
  • Uses a Type 3 secretion system to inject effector proteins into host cells.
  • Induces micropinocytosis by rearranging the host cell cytoskeleton to engulf bacteria.
• Infection Process:
  1. Bacteria are taken up by phagocytosis, release into host cytoplasm.
  2. Actin filaments form a tail for bacterial movement.
  3. Bacteria move through cytoplasm, passing into protrusions on the cell surface.
  4. These protrusions are endocytosed by adjacent cells, spreading the bacteria.
  5. Bacteria are released into the cytoplasm of new cells.
• Evasion and Immunity:
  • By staying in cytoplasm, Shigella avoids phagolysosomal fusion and host defenses.
  • Natural infection leads to immunity; endemic infections are more common in children.

Clinical Manifestations

• Symptoms:
  • High fever, abdominal cramps, bloody mucoid diarrhea.
  • Incubation: 1-3 days, average 2 days.
  • Stool frequency: 8-10 per day, potentially up to 100.
• Types of Infection:
  • Shigella sonnei: Mild disease with watery diarrhea.
  • Shigella dysenteriae 1 and Shigella flexneri: Dysentery with bloody diarrhea.

Intestinal Complications

• Proctitis and Rectal Prolapse: Inflammation can lead to these conditions in children.
• Toxic Megacolon and Intestinal Obstruction: Severe complications that can arise.
• Colonic Perforation: Rare but severe consequence.

Systemic Complications

• Bacteremia: More common in children under 5 years.
• Neurologic Disease: Includes seizures, mainly in children under 15.
• Hemolytic Uremic Syndrome (HUS): Leading cause of acute renal failure in children, associated with Shiga toxin-producing bacteria.

Diagnosis

• Symptoms: Suspect Shigella with bloody stools, cramps, and tenesmus with fever.
• Microscopy: Presence of WBCs and RBCs in stool.
• Stool Culture: Primary method, with stool samples preferred over rectal swabs.
• Molecular Diagnostics: PCR can detect specific DNA sequences.

Treatment

Adults

• Antimicrobial Resistance: Rising resistance makes susceptibility testing crucial.
• Supportive Therapy: Oral rehydration is critical; avoid antimotility drugs.
• Antibiotic Treatment:
  • Empiric therapy suggested with antibiotics reducing fever/diarrhea duration.
  • Choice based on susceptibility testing, with fluoroquinolones as an option.

Children

• Hydration and Electrolyte Correction: Essential for managing gastroenteritis.
• Avoid Antimotility Drugs: They may prolong illness.
• Parenteral Therapy: Recommended for severe cases, with ceftriaxone and azithromycin as options.

Prevention

• Hygiene: Frequent handwashing with soap and water.
• Sexual Precautions: Avoid sexual activity until two weeks post-diarrhea resolution.

Diagnostic Imaging and Tests

• Triple Sugar Iron Agar: Used to identify non-lactose fermenting bacteria like Shigella.
• Motility Testing: Differentiates motile from non-motile strains.
• Urea Slant Testing: Differentiates Shigella from other bacteria.

Conclusion

• Important to be aware of antimicrobial resistance and employ proper hygiene and prevention strategies to control the spread of Shigellosis.