Factsheet about plague

factsheet facts

1. Name and nature of infecting organism

Plague is caused by the bacillus Yersinia (Y.) pestis, belonging to the family of the Enterobacteriaceae. It evolved several thousand years ago from Y. pseudotuberculosis. Three phenotypically different biovars can be recognised and according to molecular data they correspond to phylogenetically distinct groups. The bacterium contains a toxin-producing plasmid that is responsible for its high lethality.   

Plague is a bacterial disease that has played an important role in the history of Europe. Three different plague pandemics have occurred in the past centuries, the latest one at the turn of the 19th century, and all with significant mortality worldwide. Plague has been absent from Europe for over half a century now, but is still widespread in the Americas, Africa and Asia. On an annual basis, a few thousands of cases are reported worldwide.

2. Clinical features

Infection with Yersinia pestis starts with flu-like symptoms but then rapidly progresses in serious illness, which differs according to the route of infection. Bubonic plague, the most common, has an incubation of 2–6 days, and is characterised by regional lymphadenopathy resulting from cutaneous or mucous membrane exposure. Buboes may occur in any regional lymph node sites, but the inguinal area is most commonly involved. If left untreated, 40–70% mortality has been recorded. Primary pneumonic plague has a short incubation of 1–3 days. It is the most fulminating form with chest pains, sputum production, difficulty in breathing and death within 24 hours after onset of disease. Septicaemic plague may be primary (2–6 days incubation) or the consequence of any form of plague. It leads to a progressive, overwhelming bloodstream infection with Y. pestis, resulting in a wide spectrum of pathological events and infection of other organs. Without prompt antibiotic treatment, pneumonic and septicaemic plagues are almost always fatal.

3. Transmission

3.1 Reservoir

The natural reservoirs for plague are rodents, which normally undergo a subclinical course of infection. Different species have different host competence and the reservoirs may differ between foci. Other rodent species, and other mammals, may act as multiplication hosts that develop serious disease and die of plague, increasing the speed of transmission. Black rats Rattus rattus are notorious as an intermediary between natural reservoir hosts and humans.
Seasonal patterns can be observed but differ between regions. Natural hosts may remain infectious for a long time, but peridomestic rodents usually die quickly and are infectious during the period they are ill.

3.2 Transmission mode

Transmission between rodents occurs through bites from infected fleas, and this is also the most common way in which humans are infected, leading to bubonic plague. Different flea species have a different vector capacity. Human-to-human transmission is rare in the case of bubonic plague, unless (human) flea densities are very high. Plague may also be acquired by ingestion of infectious (rodent) meat, by predators or humans.

Primary pneumonic plague follows inhalation of infectious droplets, produced by other patients or accidental hosts that developed pneumonic plague (e.g. cats that hunted infected rodents). Humans with pneumonic plague are most infectious during the last hours before death, and fast spreading epidemics with human-to-human transmission may occur.

3.3 Risk groups

Persons are more at risk when they come into close contact with wild rodents or their fleas in natural plague foci. Plague should be considered in symptomatic travellers coming back from risk areas.

4. Prevention measures

Plague can be avoided by reducing contact with wild rodents and their fleas, either through personal protection or by environmental sanitation including rodent and flea control. In natural foci, monitoring programmes should be set up so that control can be promptly initiated.
Medical staff should wear gloves and masks when nursing plague patients. There is no approved vaccine but antibiotics can be used as prophylaxis.

5. Diagnosis

Definitive diagnosis for plague is made through the isolation and identification of Yersinia pestis bacilli in clinical specimens or a diagnostic change in antibody titres in paired serum samples. Smears are coloured with Giemsa or Wayson stain and checked for the presence of bipolar staining Gram-negative bacilli. Culture of tissue samples (lymph nodes, liver, spleen, lung, bone marrow) can be done.

Acute-phase serum can be investigated in ELISA or (less common) direct immunofluorescence tests for the presence of antibodies against the specific Y. pestis F1-capsular antigen. Passive haemagglutination is an obsolete technique, neither sensitive nor specific. The ELISA can also be used for antigen detection. Small quantities of Y. pestis can be detected in PCR assays.
New optical fibre biosensor techniques for plague antigen and antibody detection are under development and have promising sensitivity and specificity characteristics but are not yet routinely available.

6. Management and treatment

Plague can be treated with antibiotics, with streptomycin, gentamicin or tetracyclines (doxycycline) being the most appropriate. Patients with pneumonic plague should be isolated and contacts of such patients should be traced and treated as soon as possible. In case of a large outbreak, mass distribution of ciprofloxacin has been suggested.

7. Key areas of uncertainty

Natural plague foci are poorly documented because they are only recognised when a human case emerges. The natural reservoirs and vectors are rarely known and there is no good understanding of the ecological conditions that facilitate transmission.

8. References

Stenseth NC et al. Plague: past, present, and future. PLoS Medicine 2008;5.
Tikhomirov E. Plague manual: epidemiology, distribution, surveillance and control. In: Dennis DT, Gage KL, Gratz N, Poland JD, Tikhonov I (eds.). Geneva : World Health Organisation 1999; p. 11–41.

WHO. International meeting on preventing and controlling plague: the old calamity still has a future. Weekly Epidemiological Record 14 July 2006;28:278–284.

Arntzen L, Frean JA. The laboratory diagnosis of plague. Belg J Zool 1997;127:91–96.
Chanteau S et al. Development and testing of a rapid diagnostic test for bubonic and pneumonic plague. Lancet 2003;361:211–216.

Wei H et al. Direct detection of Yersinia pestis from the infected animal specimens by a fiber optic biosensor. Sensors and Actuators B-Chemical 2007;123:204–210.

WHO. Interregional meeting on prevention and control of plague. Antananarivo, Madagascar, 1–11 April 2006. Geneva: World Health Organisation, Epidemic and Pandemic Alert and Response  2006; p. 1–65. Ref Type: Serial (book, monograph)

Mwengee W et al. Treatment of plague with gentamicin or doxycycline in a randomized clinical trial in Tanzania. Clin Infect Dis 2006;42:614–621.

Galimand M, Carniel E, Courvalin P. Resistance of Yersinia pestis to antimicrobial agents. Antimicrob Agents Chemother 2006;50:3233–3236.

Anisimov AP, Amoako KK. Treatment of plague: promising alternatives to antibiotics. J Med Microbiol 2006;55:1461–1475.

Titball RW, Williamson ED. Yersinia pestis (plague) vaccines. Expert Opinion Biol Ther 2004;4:965–973.

Gani R, Leach S. Epidemiologic determinants for modeling pneumonic plague outbreaks. Emerg Infect Dis 2004;10:608–614.