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Plague and Other Yersinia Infections

Chapter 176 | Part 5: Infectious Diseases

KEY CLINICAL POINTS

  • Plague is a systemic zoonosis caused by Yersinia pestis, transmitted via flea bites or respiratory droplets, with high mortality if untreated.
  • Yersinia pestis evolves from Y. pseudotuberculosis via plasmid acquisition and gene inactivation, enabling flea-borne transmission.
  • Clinical manifestations include bubonic, septicemic, and pneumonic plague, with pneumonic plague having the highest fatality rate.
  • Treatment guidelines prioritize antibiotics like streptomycin, gentamicin, and fluoroquinolones, with prophylaxis for close contacts.
  • Global surveillance and prevention focus on rodent control, personal protective measures, and vaccine development.

1. DEFINITION & OVERVIEW

Plague is a systemic zoonosis caused by Yersinia pestis, primarily affecting rodents and transmitted to humans via flea bites or respiratory droplets. Other Yersinia species (e.g., Y. enterocolitica, Y. pseudotuberculosis) cause yersiniosis, an enteric infection linked to foodborne outbreaks.

Table 176-1: WHO Case Definitions of Plague

Suspected Case Probable Case Confirmed Case Not a Case
Clinical presentation suggestive of plague + epidemiological context Suspected case + F1 antigen detection/serology Suspected case + Y. pestis isolation/PCR Negative confirmatory tests

1.1 Global Considerations

Y. pestis is classified as a Tier 1 Select Agent due to its potential use as a bioterrorism weapon. Historical outbreaks (e.g., Black Death) and modern surveillance highlight its epidemiological significance. The WHO and CDC provide guidelines for case definitions and outbreak response.

2. EPIDEMIOLOGY

Plague is endemic in rural areas of Africa, Asia, and the Americas. Pneumonic plague has a 17% fatality rate with treatment, while untreated cases have 98% mortality. Risk factors include rodent exposure, tick bites, and contact with infected animals. Global surveillance reports 2886 cases (17% fatality) annually.

Table 176-2: Guidelines for the Treatment of Plague

Drug Daily Dose Interval (h) Route
Gentamicin 5 mg/kg (Adult)/4.5–7.5 mg/kg (Child) 24 IM/IV
Streptomycin 2 g (Adult)/30 mg/kg (Child) 12 IM
Levofloxacin 750 mg (Adult >50 kg)/16 mg/kg (Child <50 kg) 24 PO/IV
Ciprofloxacin 1500 mg (Adult)/30–45 mg/kg (Child) 12 PO/IV
Doxycycline 200 mg (Adult)/4.4 mg/kg (Child) 12 PO

2.1 Y. enterocolitica/Y. pseudotuberculosis

Y. enterocolitica causes 99% of yersiniosis, prevalent in Europe, with outbreaks linked to contaminated food. Y. pseudotuberculosis is less common but associated with mesenteric adenitis and pseudoappendicitis.

3. ETIOLOGY & PATHOPHYSIOLOGY

Y. pestis evolved from Y. pseudotuberculosis via plasmid acquisition (pla, ymt) and gene inactivation. It forms biofilms in flea midguts, enabling transmission. Pathogenesis involves type III secretion systems, F1 capsule, and virulence factors like Yops that inhibit immune responses.

3.1 Virulence Mechanisms

Y. pestis uses plasminogen activator (Pla) and F1 antigen for dissemination. The ymt gene enables biofilm formation in fleas, while Yops (Yersinia outer proteins) block phagocytosis and trigger apoptosis in immune cells.

4. CLINICAL FEATURES

Bubonic plague presents with lymphadenopathy (buboes), septicemic plague with systemic sepsis, and pneumonic plague with respiratory failure. Y. enterocolitica causes abdominal pain, mesenteric adenitis, and reactive arthritis. Pneumonic plague has a 17% mortality rate with treatment.

4.1 Forms of Plague

Bubonic (lymph node involvement), septicemic (systemic sepsis), and pneumonic (lung infection). Pneumonic plague is most lethal, with rapid progression to respiratory failure.

5. DIFFERENTIAL DIAGNOSIS

Differential diagnoses include tularemia, cat-scratch disease, tuberculosis, and Salmonella infections. Pneumonic plague must be distinguished from other respiratory pathogens, while yersiniosis overlaps with Salmonella and Shigella.

6. INVESTIGATIONS & DIAGNOSIS

Diagnosis involves PCR for F1 antigen, culture on CIN agar, and serology. Imaging (ultrasound, CT) detects buboes or abdominal involvement. Rapid diagnostic tests (F1RDT) are used in endemic areas.

Table 176-3: Guidelines for Plague Prophylaxis

Drug Daily Dose Interval (h) Route
Doxycycline 200 mg (Adult)/4.4 mg/kg (Child) 12 PO
Tetracycline 2 g (Adult)/40 mg/kg (Child) 6 PO
Levofloxacin 500–750 mg (Adult >50 kg)/16 mg/kg (Child) 24 PO

6.1 Laboratory Tests

Culture on CIN agar, PCR for F1/pla genes, and serology for anti-F1 antibodies. Blood tests show leukocytosis and elevated fibrinogen degradation products.

7. MANAGEMENT & TREATMENT

Antibiotics (streptomycin, gentamicin, fluoroquinolones) are first-line. Isolation for pneumonic plague, supportive care, and early treatment reduce mortality. Prophylaxis for close contacts and post-exposure prevention are critical.

7.1 Antimicrobial Therapy

Streptomycin (12 IM) is preferred for severe cases. Fluoroquinolones (levofloxacin 750 mg PO) are used for outpatient management. Doxycycline is effective for children ≥ 8 years.

8. PROGNOSIS & COMPLICATIONS

Untreated pneumonic plague has 98% mortality. Complications include septicemia, meningitis, and postinfectious arthritis. Early treatment reduces fatality to <1% in Sweden. Disseminated intravascular coagulation occurs in 20–30% of cases.

9. SPECIAL CONSIDERATIONS

Pregnancy: Antibiotics (e.g., doxycycline) are recommended to prevent maternal complications. Children: Risk of septicemia and require prompt treatment. Immunocompromised patients (e.g., diabetes, hemochromatosis) face higher mortality.

10. KEY POINTS & CLINICAL PEARLS

  • Pneumonic plague is the most lethal form, requiring immediate isolation and antibiotics.
  • F1 antigen detection and PCR are critical for rapid diagnosis.
  • Prophylaxis with doxycycline is recommended for close contacts.
  • Y. enterocolitica outbreaks are linked to contaminated food, with self-limiting diarrhea as the main presentation.
  • Vaccines (e.g., rF1-V subunit) are under development but not yet widely available.