Plague is acute febrile disease due to infection of Yersinia pestis. Plague is one of the most virulent bacterial infections known to occur in humans, although completely curable by appropriate antibiotics. If not treated with appropriate antibiotics the case fatality rate of plague is very high.

Types of plague:

There are three clinical types of plague namely bubonic, septicemic, and pneumonic plague.

Transmission of Plague:

Plague is transmitted by most commonly by bite of flea infected with Yersinia pestis. Plague can also be transmitted by direct contact with infected materials (such as animal tissue) and by droplet infection, as in case of pneumonic plague.

If there is outbreak of Yersinia pestis among rodent hosts, the rodents die in large numbers and infected fleas in search of new host bite humans to cause plague.

Yersinia pestis:

It is the causative agent for plague which is a gram-negative coccobacillus and belongs to the family Enterobacteriaceae. Yersinia pestis is non spore forming, microaerophilic, nonmotile, oxidase and urease negative and biochemically unreactive which has only recently evolved from Yersinia pseudotuberculosis as suggested by recent genomic analysis.

Global scenario of plague:

Yersinia pestis, the causative agent for plague has established enzootic cycles in rural areas of Asia, Africa, and the Americas and in limited rural foci in southeastern Europe near the Caspian Sea, in resistant wild rodents and their fleas, which is maintaining the cycle. Humans are accidental host. Ground squirrels, prairie dogs, and chipmunks also act as host.

Presently reported case fatality rate of plague is approximately 7%.

In the United States approximately 5-10 cases of plague occur every year (due to flea bite), generally in New Mexico, Arizona, Colorado, and California.

Plague and International health regulations:

National authorities are required to report any case of plague to the WHO (World Health Organization) according to international health regulation.

Clinical features of Plague:

The onset of fever is rapid in plague. Death can occur from shock and multiple-organ failure, if not treated promptly and adequately. Three different clinical types of plague can have different clinical features.

Bubonic plague:

The incubation period of bubonic plague is 2-6 days. Bubonic plague is characterized by rapidly developing fever (temperature may be more than 38 degree Centigrade) with chills; generalized weakness, headache, muscle pain, joint pain etc. are also seen. With 24 hours of flea bite, the lymph node proximal to the bite site becomes tender and painful (called “bubo”). Most commonly femoral and inguinal nodes are involved, as the commonest site of flea bite is leg. The pain and tenderness of “bubo” increase progressively and due to severe pain the patient limits movement, and guard against palpation and pressure of the bubo. The areas surrounding bubo becomes edematous, and the overlying skin becomes erythematous, warm, and tense.

Sometimes the flea bite mark as papule, pustule, or ulcer (sometimes ulcer may be covered by eschar) can be demonstrated by inspecting skin distal to the bubo.

Secondary plague pneumonia may occur in some cases of bubonic plague, which manifest clinically as diffuse interstitial pneumonitis with scanty sputum production and as a result less infectious.

Septicemic plague:

In septicemic plague, septicemia occurs without bubo. Diagnosis of septicemic plague is generally made only after positive blood culture for Yersinia pestis. Septicemia may be accompanied by gastrointestinal symptoms such as nausea, vomiting, diarrhea, and abdominal pain and make diagnosis difficult. Other signs of septicemic plague include hypotension, renal shutdown, obtundation, shock and DIC (Disseminated Intravascular Coagulation) manifested as petechiae, ecchymoses, bleeding from puncture wounds and orifices. ARDS (Adult Respiratory Distress Syndrome) can sometimes occur in septicemic plague.

Pneumonic plague:

The incubation period of pneumonic plague is 1-7 days and it is the most serious and life threatening form of plague. Another serious problem with pneumonic plague is its communicability, as it can be transmitted from patients to other persons by droplet infection (other two clinical forms are not transmissible).

The onset of symptoms of pneumonic plague is sudden and includes fever with chills, headache, muscle pain, generalized weakness, and dizziness. Respiratory signs and symptoms of pneumonic plague are tachypnea (high respiratory rate or fast breathing) and dyspnea (difficulty in breathing), cough with sputum (sputum is most often watery or mucoid, frothy and may contain blood). Chest pain, respiratory distress, cardiopulmonary insufficiency, and circulatory collapse may occur. Liquefaction necrosis and cavitation may occur in the involved lobes of lungs.

Complications of Plague:

Complications of plague include meningitis and pharyngitis (minor). Meningitis is a rare complication of plague and generally occurs in bubonic plague. The common cause of plague meningitis is inadequate treatment, such as treatment with bacteriostatic (to Y. pestis) antibiotics tetracycline. The symptoms of plague meningitis are fever, headache, meningismus etc.

Treatment of plague:

Untreated cases of bubonic plague are more than 50% fatal and almost 100% fatal in case of pneumonic and septicemic plague. At present due to easy availability of highly effective antibiotics has reduced fatality of plague drastically and most of the deaths are due to delays in seeking treatment, delays in the institution of treatment, incorrect treatment or misdiagnosis. Rapid diagnosis and institution of adequate antibiotic therapy can give dramatic results.

The drug of choice in treatment of plague is streptomycin (at the dose of 2 gram intramuscularly every 12 hourly or 30 mg per kg body weight in children). Gentamicin (at the dose of 3-5 mg for adults and 6-7 mg per kg body weight in children every 8 hourly) also gives excellent result and preferred now-a-days due to easy availability. Other antibiotics that can be used for treatment of plague include tetracyclines (doxycycline), chloramphenicol, trimethoprim-sulfamethoxazole etc. Chloramphenicol can be used for treatment of plague meningitis, pleuritis, and myocarditis due to its superior tissue penetration.

The duration of antibiotic treatment is for 7-10 days or for minimum 3 days after fever subsides and there is clinical improvement. Initial treatment should be with IV (intravenous) antibiotics and can be switched over to oral regimen if there is clinical improvement. Patient of plague should be closely monitored. The buboes may need surgical drainage.

US National bioterrorism-response protocol recommends use of gentamicin, ciprofloxacin, and doxycycline as first line treatment or postexposure prophylaxis in the event of a bioterrorist attack using Y. pestis.

Prevention of plague:

The most important aspect of prevention of plague is surveillance, education, and environmental management. Individuals at risk (living, working, and those who participate in outdoor recreational activities in plague enzootic areas) should take protective measures such as avoidance of sick or dead animals, use of insect repellents, insecticides, and protective clothing (if there is risk of exposure to rodents' fleas), wearing of gloves when handling animal carcasses and if possible avoid plague enzootic areas.

Short term antibiotic prophylaxis is recommended in persons who had close contact with confirmed or suspected pneumonic plague patient. In the event of bioterrorist attack using Y. pestis wearing of masks that block droplets is recommended.

Improvement of environmental sanitation in residential and occupational areas is an important step in prevention of plague. Rodent food (garbage, pet food) and habitats (brush piles, junk heaps, woodpiles) should be eliminated. Use of insecticides to control fleas (dusting and spraying of rodent burrows) is important. In plague endemic areas residents should be advised to keep their pets free of flea.

Killed, whole-cell plague vaccine is available in some countries (not available in US). The plague vaccine is indicated among laboratory personnel who routinely worked with Y. pestis and individuals who come in regular contact with wild rodents and their fleas in plague endemic areas. A new and improved vaccine using recombinant F1 and V antigens is going to be available soon.