Plague

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    Last updated: September 2022

     

     

    Plague is a zoonosis caused by the Gram-negative bacillus Yersinia pestis that affects many wild and domestic mammals, particularly rodents.

    Plague is transmitted to man by infected animals (direct contact or inhalation of their respiratory secretions), the bite of a flea of infected animals, or inhalation of respiratory secretions of individuals with pneumonic plague.

    Natural foci of infection include Africa, Asia, North and South America, and parts of Europe.

     

    Bubonic plague is the most common form, usually resulting from the bite of an infected flea. Without prompt treatment, the bacteria may be disseminated by haematogenous route, producing a more severe form (see below) with a high mortality rate.

    The following forms of plague may be primary or secondary to bubonic plague:

    • Pneumonic plague can rapidly progress to respiratory distress, shock, and death without prompt treatment.
    • Septicaemic plague is a fulminant illness that can progress to disseminated intravascular coagulation, respiratory distress, shock, and death.
    • Plague meningitis is a rare but very severe form of plague.

    Clinical features 

    See table below.

     

    Main differential diagnoses include:

    Laboratory

    • Collect pre-treatment specimens: lymph node aspirate (bubonic plague), sputum (pneumonic plague), blood (septicaemic plague), or cerebrospinal fluid (plague meningitis).
    • Send specimens a Citation a. Transportation of specimens in 0.9% sodium chloride requires a cold chain (failing that, a temperature below 30 °C), triple packaging and UN3373 label. to reference laboratory for:
      • Rapid diagnostic test for detection of F1 capsular antigen of Y. pestis
      • PCR 
      • Culture of Y. pestis and drug suceptibility test
    • In all cases, rapid test for malaria in endemic regions (and antimalarial treatment if needed, see Malaria, Chapter 6).

    Management

    • Start empiric antibiotic treatment for 10 to 14 days as soon as plague is suspected, before results of diagnosis tests are available. 
    • A combination of 2 antibiotics from different classes is recommended in severe disease, plague meningitis, and pregnant women.
    • Follow national recommendations according to antibiotic resistance patterns if known. For information: see table below.

    Treatment of suspected cases

    Forms of plague Clinical features Antibiotic treatment [1] Citation 1. Nelson CA, Meaney-Delman D, Fleck-Derderian S, Cooley KM, et al. Antimicrobial treatment and prophylaxis of plague: recommendations for naturally acquired infection and bioterrorism response. MMWR Recomm Rep 2021;70(No. RR-3):1-27.
    https://www.cdc.gov/mmwr/volumes/70/rr/rr7003a1.htm?s_cid=rr7003a1_w [Accessed 25 January 2022]
    Bubonic
    • Fever, chills, malaise, headache 

    AND 

    • Lymph node (bubo), painful, usually inguinal, (one or more) 

    Children (including < 8 years) and adults:

    doxycycline PO:

    • Under 45 kg: 4.4 mg/kg (max. 200 mg) on D1, then 2.2 mg/kg (max. 100 mg) 2 times daily
    • 45 kg and over: 200 mg on D1, then 100 mg 2 times daily

    or

    gentamicin IM or IV: (a) Citation a. Streptomycin IM may be an alternative to gentamicin (except in pregnant women):
    Children: 15 mg/kg (max. 1 g) every 12 hours
    Adults: 1 g every 12 hours

    • Children: 4.5 to 7.5 mg/kg once daily
    • Adults: 5 mg/kg once daily

    or

    ciprofloxacin PO:

    • Children: 15 mg/kg 2 to 3 times daily (max. 750 mg 2 times daily or 500 mg 3 times daily)
    • Adults: 750 mg 2 times daily
    Pneumonic
    • Fever, chills, malaise, headache 

    AND  

    • Dyspnea, chest pain, productive cough with purulent or blood-stained sputum 
    • Respiratory distress or failure and sepsis in severe or advanced, untreated disease

    Children and adults:

     

    If mild disease:

    gentamicin IM or IV (a) Citation a. Streptomycin IM may be an alternative to gentamicin (except in pregnant women):
    Children: 15 mg/kg (max. 1 g) every 12 hours
    Adults: 1 g every 12 hours
    (as above)

    or

    ciprofloxacin PO (as above) or IV (b) Citation b. Use ciprofloxacin IV when oral route is not possible:
    Children: 10 mg/kg (max. 400 mg) every 8 or 12 hours
    Adults: 400 mg every 8 hours

     

    If severe disease:

    gentamicin + ciprofloxacin (as above)

    or, if not available, gentamicin + doxycycline (as above)

     

    After clinical improvement, change to ciprofloxacin or doxycycline PO (as above).

    Septicaemic
    • Frequently no localizing symptoms or signs
    • Gastrointestinal disturbances (abdominal pain, vomiting, diarrhoea, etc.) often present

    As severe pneumonic plague

    Meningitis (c) Citation c. If plague meningitis develops, add chloramphenicol to the existing regimen, and continue the combined regimen for an additional 10 days. Signs of meningitis.

    Children and adults:

    chloramphenicol IV:

    • Children 1 to 12 years: 25 mg/kg (max. 1 g) every 8 hours  
    • Children 13 years and over and adults: 1 g every 8 hours

    + ciprofloxacin PO or IV (as above)

    or, if not available,

    gentamicin + ciprofloxacin (as above)

    Treatment in pregnant women

    • Bubonic, pneumonic, and septicaemic plague: gentamicin IM or IV (as above) + ciprofloxacin PO (500 mg 3 times daily) or IV (as above)
    • Plague meningitis: chloramphenicol IV + ciprofloxacin PO (500 mg 3 times daily) or IV (as above)​​

    Infection prevention and control (in hospitals)

    • Bubonic plague: no isolation, standard precautions (handwashing, gowns, gloves, eye protection, etc.) with respect to lymph node aspiration or discharge and other body fluids.
    • Pneumonic plague: isolation (in single room if possible), standard precautions, plus, for 48 hours after the start of antibiotic treatment, droplet precautions (medical mask for healthcare workers and for patients during contact). Only for aerosol-generating procedures, airborne precautions (FFP2 or N95 respirators) for health workers exposed to aerosols.
    • Elimination of fleas (e.g. bedding, clothing, corpse): refer to the guide Public health engineering, MSF.

    Post-exposure prophylaxis of contacts

    In the event of contact (distance less than 2 meters without appropriate personal protective equipment) with a pneumonic plague patient or direct contact with infected body fluids or tissues of any plague patient and within one week after the end of exposure:
    doxycycline PO for 7 days
    Children: 2.2 mg/kg (max. 100 mg) 2 times daily
    Adults (including pregnant women): 100 mg 2 times daily
    or
    ciprofloxacin PO for 7 days
    Children: 20 mg/kg (max. 750 mg) 2 times daily
    Adults: 500 to 750 mg 2 times daily 

    Pregnant women: 500 mg 3 times daily

    Prevention

    • Flea vector control, sanitation and rodent reservoir control, refer to the guide Public health engineering, MSF.
    • Vaccination against plague is indicated for laboratory technicians handling rodents or working with Y. pestis and is not a method for controlling an epidemic.

     

    Footnotes
    • (a)Transportation of specimens in 0.9% sodium chloride requires a cold chain (failing that, a temperature below 30 °C), triple packaging and UN3373 label.
    • (a) Streptomycin IM may be an alternative to gentamicin (except in pregnant women):
      Children: 15 mg/kg (max. 1 g) every 12 hours
      Adults: 1 g every 12 hours
    • (b)Use ciprofloxacin IV when oral route is not possible:
      Children: 10 mg/kg (max. 400 mg) every 8 or 12 hours
      Adults: 400 mg every 8 hours
    • (c)If plague meningitis develops, add chloramphenicol to the existing regimen, and continue the combined regimen for an additional 10 days.
    References