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Plague is the name given to infection with the bacteria called Yersinia pestis. The bacterium is a Gram negative bacillus and a member of the Enterobacteriaceae family. It is primarily a enzoonotic infection - a disease of rodents especially marmots but also black rats and squirrels amongst others.
Human infection most commonly results from being bitten by a rat flea called Xenopsylla cheopis. These fleas feed off the infected rodents and swallow the bacteria which then multiply in the fleas stomach. This makes the flea hungry and they then bite a human and vomit the bacteria into the bite. The flea dies of subsequent starvation as the bacteria in the stomach inhibits blood flow to the gut making them vomit when they eat.
Mode of transmission
- Bite from infected fleas
- Direct contact
Factors that lead to increased spread of Y. pestis include cold temperature, increased humidity and crowding.
The WHO document that between 1000-2000 cases are reported per year. In fact in 2003 nine countries reported 2118 cases of plague and 182 deaths from plague. These reports were from areas with endemic areas of plague eg subtropics and the tropics and more than 95% of these cases and deaths were reported from Africa.
There have been recent outbreaks of plague in India in 2002 and Algeria in 2003.
Outbreaks of Y. pestis occur whenever there is a loss of the normal host for the fleas eg if the rat population are affected by another illness increasing their mortality. The fleas then find another host to feed on eg humans.
Clinical Editor's note
Nov 2017 - Dr Hayley Willacy notes there has been a large outbreak of plague in Madagascar. As of 30 October 2017, 1,801 clinically compatible cases (suspected, probable and confirmed) had been reported across the country, of which 1,111 were clinically classified as pneumonic. In 2017 the season began earlier than usual, is predominantly pneumonic, and is affecting areas that do not usually experience outbreaks, including major urban centres. Pneumonic plague is transmissible from person to person. The probability of a case occurring in a person returning to the UK is very low; however, certain features of this outbreak increase the risk of infection to low-moderate for international travellers to, and those working in, Madagascar. Clinical and laboratory guidance has been developed for England.
Infection with Y. pestis begins with non-specific "flu-like" symptoms:
- Sudden onset chills
- Muscle ache
- Nausea and vomiting
- Swelling of lymph nodes
These usually follow an incubation period of 3-7 days.
Following this the infection can take on several forms (see below) but the three commonest are:
- Bubonic plague - this is the most common and usually follows a bite from a flea. The bacteria pass from the skin to local lymphatics and to local lymph nodes. The infection usually involves lymph nodes of the groin although the axillae and neck may also be effected. The bacteria replicate in the lymph node causing it to become enlarged and swollen and very tender, they are called buboes. Occasionally they may suppurate.
- Septicaemic plague - there is usually no evidence of lymph node involvement. The infection spreads into the blood and septic shock ensues. This may follow either a flea bite or direct contact on to broken skin. Patients may have bleeding from the skin and mucous membranes and haemorrhage into organs due to disseminated intravascular coagulation. They may also develop red tender nodules on the skin with a white centre. There may also be necrosis of blood vessels with purpura and gangrene. Symptoms can appear on the day and patients can die within 24 hours if not promptly treated.
- Pneumonic plague - This is the least common presentation of the three but is the most dangerous. The mortality and contagibility of pneumonic plague is very high. Lung infection can be primary from inhalation of droplets or secondary to advanced infection of the bubonic type. Pneumonic plague can be spread directly between humans and does not require a vector. The infection may present just as any bronchopneumonic illness with chest pain, cough, breathlessness and haemoptysis. Complications include disseminated intravascular coagulation, multi organ failure and acute respiratory distress syndrome. Chest X ray will show consolidation and pneumonic plague can progress rapidly to septicaemia. The incubation period can range from 2 hours to 4 days.
Other types of Y. pestis infection classified by WHO include cellulocutaneous plague, meningeal plague, pharyngeal plague, abortive plague, pestis minor and asymptomatic plague:
- Cellulocutaneous plague - this is rare and presents as infection of the skin.
- Meningeal plague - this is seen in children but is uncommon. It presents similar to other cases of meningitis and is thought to arise from incomplete treatment of other types of plague.
- Pharyngeal plague - this follows consumption of Y. pestis eg in food or inhalation and presents as tonsillitis with local lymphadenopathy.
- Pestis minor - presents with mild fever and lymphadenopathy and usually settles in a week.
- Other forms of plague described are asymptomatic plague and abortive plague.
Y. pestis can be best identified in culture of infected tissues or fluids, for example, blood, sputum or bubo aspirates. Rapid dipstick tests, immunoassays and polymerase chain reaction methods are only available in some states.
The mainstay of treatment is antibiotics. However, there are no trials comparing the efficacy of individual antibiotics. All patients need strict isolation as should close contacts. Traditionally the following have been used:
- Streptomycin - reduces mortality rate to 4-15% when given parenterally.
- Gentamicin - is considered as a second line parenteral treatment and success rates may be similar to streptomycin.
- Fluoroquinolones - these are as efficacious as aminoglycosides and tetracyclines in experimental induced plague and can be given orally.
- Chloramphenicol - may be better in plague meningitis as it crosses the blood brain barrier, however this has not been confirmed and the drug is associated with toxicity eg bone marrow failure.
- Tetracycline (not in children) and doxycycline - these have been used in the treatment and prophylaxis of plague.
Doxycycline or ciprofloxacin are probably first line in pregnant patients. Children can be treated with streptomycin or gentamicin.
Resistance of plague to antibiotics can also occur - eg, tetracycline resistance and quinolone resistance; these reports are very rare.
The untreated mortality of plague is high especially for pneumonic plague where it approaches 95% and septicaemic plague which is fatal without therapy. Untreated bubonic plague has a mortality of 30-75%. With treatment the overall mortality rate is reduced to 4-15%.
A vaccination had previously been developed (a formaldehyde-killed whole bacille vaccine) but this did not prevent plague effectively and thus is not recommended in the setting of outbreaks[2, 6]. The vaccinations are really only used for prophylaxis in high risk groups such as, laboratory staff who will be handling plague infected tissue. The following preventive measures need to be considered:
- Surveillance of disease and thus awareness of areas where plague is active.
- Precautions against flea bites - good hygiene and sanitation.
- Education of persons likely to be involved in handling carcasses that may be infected with plague to wear appropriate clothing eg gloves.
- Use of licensed insecticides to kill fleas in outbreaks of plague.
- Rat control measures.
- Strict isolation of patients who are infected and avoidance of contact with infected patients especially those with pneumonic plague.
- Persons bitten by fleas during an outbreak.
- Persons exposed to tissues or fluids from animals infected with the plague.
- Persons living in a house where a patient developed bubonic plague.
- Persons in close contact with those suspected of pneumonic plague.
Advice to travellers
- Avoid contact with rodents
- Use of insect repellents on skin and clothes
- Hand washing
- If in close contact with suspected or confirmed case - use gloves and face masks
- Seek prompt medical advice if fever develops or lymphadenopathy
History and future of plague
The organism responsible for plague was isolated in 1892 by Alexandre Yersin. The organism was originally named Pasteurella pestis but this was changed to Yersinia pestis in 1962. The discovery of the flea as the vector for plague was made in 1898 by Paul-Louis Simond.
Plague epidemics have been described for ages, as early as the 11th century B.C. However more infamous is the Black death which occurred in the mid-14th century and claimed the lives of more than 230 million persons.
There have been worldwide concerns that plague could be used in biological warfare. The Y. pestis infection would be primarily pneumonic plague that is the result of aerosol based mechanisms of release.
Advice for practitioners during plague outbreak or plague bioterrorism
- High index of suspicion eg extra number of patients presenting with pneumonia.
- Use gloves, face masks and gowns if available.
- Notify authorities as soon as possible.
- Initiate antibiotic therapy within 24 hours to reduce mortality.
- Isolate patients - this may mean isolation within the patients own home if other facilities not available. Infected patients may need to be grouped together.
- Sterilise all equipment. If this is not possible equipment needs to be disposed of effectively.
Further reading and references
Perry RD, Fetherston JD; Yersinia pestis--etiologic agent of plague. Clin Microbiol Rev. 1997 Jan10(1):35-66.
Inglesby TV, Dennis DT, Henderson DA, et al; Plague as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA. 2000 May 3283(17):2281-90.
Plague fact sheet No. 267; World Health Organization, Feb 2005
Bossi P, Tegnell A, Baka A, et al; Bichat guidelines for the clinical management of plague and bioterrorism-related plague. Euro Surveill. 2004 Dec 159(12):E5-6.
Plague: epidemiology, outbreaks and guidance; Public Health England (Nov 2017)
Calhoun LN, Kwon YM; Salmonella-based plague vaccines for bioterrorism. J Microbiol Immunol Infect. 2006 Apr39(2):92-7.
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