Yersinia pestis is a Gram-negative non-motile, non-spore-forming coccobacillus measuring approximately 1.5 μm x 0.75 μm, capable of both aerobic and anaerobic growth. The pathogen can remain viable for days in water or moist soil and can resist drying if protected by mucus or other substances but is killed by a few hours of direct exposure to sunlight.
During the 1990s there were human outbreaks in Africa, Asia, and South America and sporadic cases in many countries, including the USA. Known historically as the Black Death and still a serious problem, it is limited to sporadic cases where adequate surveillance and modern public health measures are practised.
The pathogen is present in animal reservoirs, particularly in wild rodents, in endemic foci worldwide, with the exception of Australia.
Mode of transmission
Plague is transmitted between rodents and to other animals via fleas, consumption of infected animal tissues or, possibly, contaminated soil or respiratory droplet exposures. In endemic rural areas, plague typically occurs sporadically among persons who come in contact with wild rodent hosts of Y. pestis and their fleas. Outbreaks affecting large numbers of people can occur in cities when plague infects populations of urban rodents, particularly the black rat, Rattus rattus, and the brown rat, Rattus norvegicus.
The most common form of the disease in humans, bubonic plague, is spread mainly by the bite of fleas regurgitating plague bacteria from infected rodents or by entry of the pathogen from infected fleas through a skin lesion. If the lungs become infected, as may occasionally occur in patients with the bubonic form, a much more virulent form, pneumonic plague, ensues and can be transmitted directly from person to person by droplet infection.
The incubation period is 2–6 days in bubonic plague and somewhat less for the pneumonic form.
Initial symptoms may be nonspecific, with sudden onset of fever, chills, malaise, myalgia, nausea, sore throat and headache. Cases acquired by aerosol inhalation would probably present as primary pneumonia, possibly accompanied by bloody cough. Infection spreads from the inoculation site via the lymphatics to regional nodes, which become swollen and painful (buboes). In a minority of cases, the pathogen enters the bloodstream giving rise to plague septicaemia.
Haematogenous spread of the pathogen to the lungs causes the pneumonic form of the disease, which then can spread directly from person to person by droplet infection. As the disease progresses, patients experience shock, delirium and coma. Untreated bubonic plague has a case-fatality rate as high as 60%, while untreated pneumonic plague is almost always fatal. Less common forms are plague meningitis and plague pharyngitis.
Strong suggestive evidence of Y. pestis in sputum, blood or material aspirated from a bubo is provided by observation of Gram-negative ovoidal bacilli that stain preferentially at their ends with Giemsa or Wayson’s stains, although such bipolar distribution of stain may not always be clearly evident or specific. The bacillus may be identified by direct fluorescent antibody stain for the Y. pestis capsular antigen, by lysis by specific bacteriophage and by PCR. Various serological methods are also available.
Biosafety Level 2 practices, equipment and facilities are recommended for all activities involving infective clinical materials and cultures. Biosafety Level 3 should be used for activities in which there is a high potential for aerosol or air droplet production or for work with antimicrobial-resistant strains and infected fleas.
Medical management and public health measures
Emphasis must be placed on preventing epidemic spread. For patients with pneumonic plague, strict precautions against airborne droplet spread are essential, including patient isolation and wearing of surgical masks by patients and caregivers. Patients with confirmed pneumonic plague may be placed together in shared rooms if private rooms are not available.
For patients with any type of plague, standard precautions must be taken against contamination from discharges and contaminated articles, including hand washing and the wearing of gloves, gowns and face protection. If indicated, flea control measures should be instituted.
Plague vaccines are available worldwide but are not recommended for immediate protection in outbreak situations. Vaccination is recommended only for high-risk groups, e.g. health workers and laboratory personnel who are constantly exposed to the risk of contamination. Preventive vaccination with killed or live attenuated Y. pestis is moderately effective against bubonic but not against pneumonic plague. With killed vaccine, protection is relatively short-lived (3–12 months) and periodic revaccination is necessary.
Vaccination is of little use during a plague outbreak, as at least a month is needed for immunity to build up and recommendations for administration of killed bacteria vaccines include an initial injection and two booster injections over a period of 6 months.
As with various other pathogens, massive infection can overcome vaccine-conferred immunity. Persons in close contact with pneumonic plague patients or who are likely to have been exposed to infected fleas, have had direct contact with body fluids or tissues of an infected mammal, or for any other reason are suspected to have been exposed to the pathogen should receive antimicrobial prophylaxis for a week after the last suspected exposure.
Doxycycline and ciprofloxacin are recommended for such use.
Antimicrobial therapy is effective if begun early in the disease and continued for at least 3 days after body temperature returns to normal. Streptomycin is the historical drug of choice but is not immediately available everywhere. Gentamicin is considered to be an acceptable alternative to streptomycin, based on in vitro and animal experiments, and on limited clinical observations in humans.
Tetracyclines are effective against plague, and are widely used for treatment and prophylaxis. Doxycycline, administered twice daily, is preferred for oral treatment because of its ready gastrointestinal absorption. Chloramphenicol has been used to treat various forms of plague, including plague pneumonia, and is recommended for treatment of plague meningitis because of its ability to cross the blood–brain barrier.
Fluoroquinolones have demonstrated efficacy in treating plague in animal experiments. Ciprofloxacin was observed to be at least as efficacious as aminoglycosides and tetracyclines in studies of mice with pneumonic plague.
In vitro studies show activity of several fluoroquinolones to be equivalent to or greater than that of the aminoglycosides or tetracyclines. Several sulfonamides (sulfathiazole, sulfadiazine, sulfamerazine and trimethoprim–sulfamethoxazole) have been used successfully for the treatment and prophylaxis of plague.
Data indicate, however, that sulfonamides are less effective than streptomycin or tetracycline, particularly for pneumonic plague.
Sulfisoxazole should not be used because of its rapid renal excretion. Penicillins, macrolides and cefalosporins are thought not to be clinically efficacious and are not recommended for treatment of plague.
Multidrug resistance imparted by a transferable plasmid has been reported in a single clinical isolate, as has plasmid-mediated streptomycin resistance. Antimicrobial resistant strains have been developed in the laboratory.