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What health professionals need to know about plague

Plague is a zoonotic disease caused by the bacteria Yersinia pestis, found in small mammals and their fleas. Yersinia pestis, which is a Gram-negative bacillus, is also considered a potential biological warfare agent.

Plague can be severe, with a case-fatality rate of 40 to 70% for the bubonic type. It is almost always fatal for the pneumonic and septicemic forms if left untreated. Early diagnosis and treatment are essential due to the rapid course of the disease.

Plague is an ancient disease and has caused widespread pandemics with high mortality affecting most of the continents except Oceania. It was known as the "Black Death" during the fourteenth century, causing more than 50 million deaths in Asia, Africa and Europe.

Reservoir and Vectors

Yersinia pestis circulates in animal reservoirs, particularly in rodents, principally rats and sylvatic ground squirrels such as:

  • marmots
  • susliks and
  • prairie dogs

Rabbits, camels, carnivores, and domestic cats may also be infected.  Cats can also develop pneumonic plague.

Vectors include fleas, especially the rat flea (Xenopsylla cheopsis) and possibly the human flea (Pulex irritans).

Transmission

The plague bacteria can be transmitted to humans in 3 ways:

Flea bites

The bite of an infected flea is the most common route of transmission and leads to bubonic plague. People and animals that visit places where rodents have recently died from plague are at risk of being infected from flea bites. Dogs and cats may also bring plague-infected fleas into the home.

Contact with contaminated fluid or tissue

People can be infected directly from a plague-infected rodent or other animal while handling, skinning or cutting up the meat. The plague agent penetrates the human through skin lesions or through the mucous membranes of the mouth, nose or eyes. This form of exposure most commonly results in bubonic or septicemic plague.

Infectious droplets

When primary bubonic plague develops into secondary pneumonic plague, airborne droplet transmission of the infective agent may take place. It does so via the respiratory route, leading to primary pneumonic plague among close contacts. Transmission of these droplets is the only way that plague can spread between people.

Infection through direct contact with objects contaminated with sputum from pneumonic plague patients can lead to the development of bubonic plague.

Clinical manifestations

Clinical manifestation depends on the route of infection. It usually presents in 3 forms:

  • bubonic
  • septicaemic and
  • pneumonic

Bubonic plague

This is the most common form of plague and is caused by the bite of an infected flea. Plague bacillus, Y. pestis, enters at the bite and travels through the lymphatic system to the nearest lymph node, where it replicates itself.

The lymph node then becomes inflamed, tense and painful and is called a "bubo". At advanced stages of the infection the inflamed lymph nodes can turn into suppurating open sores. Buboes may occur in any regional lymph node sites including:

  • cervical
  • axillary
  • popliteal
  • inguinal
  • epitrochlear
  • pharyngeal
  • post-auricular
  • supraclavicular

There is no human to human transmission of bubonic plague.

The incubation period ranges from 2 to 7 days for bubonic plague. Patients typically experience a sudden onset of illness characterized by:

  • fever
  • malaise
  • headache
  • shaking chills and
  • pain in the affected regional lymph nodes

Septicaemic plague

This form occurs when infection spreads through the bloodstream. It may result from flea bites and from direct contact with infective materials through cracks in the skin. Advanced stages of the bubonic form of plague will also lead to direct spread of Y. pestis in the blood.

In the septicimic form, Y. pestis spreads through the blood-stream usually affecting the lungs, ending in fatal endotoxic shock and disseminated intravascular coagulation (DIC), which can lead to:

  • arteriolar thrombosis
  • haemorrhage in
    • skin
    • serosal surfaces
    • organ parenchyma

Sometimes it results in acral cyanosis and tissue necrosis.

Pneumonic or lung-based plague

This is the most virulent and least common form of plague. Typically, the pneumonic form is caused by advanced bubonic plague spreading to the lungs. However, a person with secondary pneumonic plague may form aerosolized infective droplets and transmit plague via droplets to other humans.

The incubation period is usually 1 to 4 days. Disease typically manifests by the sudden onset of:

  • chills
  • fever
  • headache
  • body pains
  • weakness and
  • chest discomfort

As the disease rapidly progresses other symptoms become prominent:

  • cough
  • sputum production
  • increasing chest pain
  • dyspnea
  • hypoxia and
  • haemoptysis

Death usually follows if specific antibiotic therapy is not begun within 18 to 24 hours of disease onset. 

Testing and Diagnosis

Plague should be suspected in any patient with clinical signs and symptoms of plague and a recent history of travel to a plague endemic area.

Clinical specimens should be collected immediately. These include:

  • aspirates from suspected buboes
  • whole blood
  • sputum
  • cerebrospinal fluid

Throat specimens are not ideal since they are not sterile and can be overgrown by other bacteria. Blood and lymph aspirates are preferred.

Diagnostic tests include: 

  1. Isolation and identification of Y. pestis from clinical specimens:
    1. microscopic examination: visualization of bipolar-staining, ovoid, Gram-negative organisms with a “safety pin” appearance permits a rapid presumptive diagnosis of plague
    2. culturing the organism from blood, sputum and bubo aspirates for a definitive diagnosis
  2. Serologic tests for the Y. pestis F1 antigen confirm the diagnosis by a four-fold rise in antibody titer in patient serum if culture is inconclusive
  3. Molecular detection targeting genetic sequences specific to Y. pestis
  4. Antimicrobial susceptibility testing as per Clinical and Laboratory Standards Institute (CLSI M45 Standards)

Treatment

Plague is treatable through prompt, appropriate medical care.

Appropriate antimicrobial treatment should start as soon as plague is suspected, within 18 hours of onset, to reduce complications and deaths:

  • Use your clinical judgement and adjust the antibiotic dependent on patient’s:
    • age
    • medical history
    • underlying health conditions or
    • allergies
  • Antibiotics of choice include streptomycin and gentamycin:
    • Second-line agents include:
      • tetracycline,
      • fluoroquinolones
      • sulphonamides and
      • chloramphenicol (in cases of plague meningitis)
  • If fever reappears or persists after antibiotic treatment, infected buboes may need to be surgically drained.
  • Prophylaxis antibiotic therapy for possible contacts:
    • close contacts with very sick pneumonic plague patients may need to be assessed and possibly placed under observation. Preventive antibiotic therapy may also be given, depending on the type and timing of personal contact.

Surveillance in Canada

Plague is subject to the International Health Regulations (2005) and is notifiable to the World Health Organization (WHO).

While plague is rare in Canada, it is a nationally notifiable disease (Case Definition for Plague). This means that the provinces and territories need to notify only confirmed cases of disease up to federal level on an urgent basis.

You are required to report cases either directly or via your local public health authority to your provincial or territorial public health authority. They in turn notify the Public Health Agency of Canada. Refer to your provincial/territorial health system for further details.

Epidemiology

In Canada, human cases of plague are very rare. The last case was reported in 1939.

From 2010 to 2015, the WHO reported 3248 cases  worldwide, including 584 deaths. Globally, plague is present in:

  • South America
  • large areas of Asia
  • the western part of North America and
  • central, eastern and southern Africa

Since the 1990s most human cases have occurred in Africa, with epidemic recurrences in Madagascar. There has been a large shift in case load from Asia to Africa, with more than 90% of cases occurring in Africa. The most common form is bubonic plague, but outbreaks of pneumonic plague still occur.  It is possible that plague is more common in Africa as poor rural communities live in close proximity to rodents. Rodents are widely hunted and eaten in plague-endemic areas.

Most human cases in the United States have occurred in two regions:

  • Northern New Mexico, northern Arizona, and southern Colorado; and
  • California, southern Oregon, and far western Nevada

In recent decades, the US has reported an average of 7 human plague cases each year with the range being 1 to 17 cases per year.

Plague affects all age groups, though 50% of cases occur in ages 12 to 45. It affects both men and women.

For more information

  • Gratz N. (1999) “Plague Manual Epidemiology, Distribution, Surveillance and Control”.  WHO Report, Geneva
  • Butler T. “Plague and other yersinia infections”. In: Greenough WB III, Merigan TC. (Eds): Current Topics in Infectious Disease. New York, Plenum, 1983, 71-92..
  • Neerincks SB, et al. (2008) “Geographic distribution and ecological niche of plague in sub-Saharan Africa”.  Int J Health Geog 7:54
  • Stenseth NC, et al. (2008) “Plague: past, present and future”.  PLoS Med 5(1): e3
  • Wertheim, H.F.L. (2012) Atlas of Human Infectious Diseases, Wiley-Blackwell,Oxford pp.82-83.
  • WHO – Plague
  • Plague in the United States
  • Ontario Ministry of Health And Long Term care- Diseases:Plague
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