What is bubonic plague? |

Definition

Bubonic plague is a severe bacterial infection characterized by acute, local, necrotizing lymphadenitis (infection of the lymph glands). Bacteremia rapidly follows, then spreads to the spleen, liver, and other organs. Bubonic plague is the most common form of plague and has a mortality rate of 50 to 90 percent if not treated. If treated promptly and appropriately, the mortality rate is 5 to 15 percent.

Bubonic plague is one of the oldest diseases known and has been one of the most devastating in human history. It is widely regarded as a disease of mainly historical importance because it is now rare in developed countries and affects mainly poor and remote populations. However, reports of incidence have increased once again.

In Madagascar, Peru, and the Democratic Republic of the Congo, bubonic plague is a significant health concern. Adding to the new incidence rate is the discovery of antibiotic-resistant strains of the plague bacterium. The Centers for Disease Control and Prevention reports that as of 2015, an average of seven human cases develop each year in the United States, with the highest incidence occurring in the southwestern states of New Mexico, Arizona, and Colorado. According to the American Society of Tropical Medicine and Hygiene, between 2000 and 2009, more than 20,000 cases of humans infected with the plague were reported worldwide, with the following countries having the highest incidences (in order of most reported cases): DRC, Madagascar, Zambia, Uganda, Mozambique, Tanzania, China, Peru, Malawi, Indonesia, the United States, and Vietnam. The World Health Organization WHO) concedes that official data on the plague do not truly reflect incidence of plague, mainly because of a reluctance to report plague cases but also because of inadequate surveillance capabilities.

Causes

Bubonic plague is caused by the bacterium Yersinia pestis (formerly called Pasteurella pestis). Alexandre Yersin isolated the bacterium (germ) that causes plague. (The bacterium was named Y. pestis for Yersin.) He developed a treatment (an antiserum) to combat the disease and was the first to suggest that fleas and rats may have spread plague in the epidemic of 1894. Y. pestis is a nonmotile, non-acid-fast, non-spore-forming, gram-negative coccobacillus (bacterium) measuring 1.5 by 0.75 microns. The bacterium can be killed in less than ten minutes with sunlight, high temperatures, desiccation, ordinary disinfectants, and preparations containing chlorine.

Y. pestis is primarily an internal parasite of wild rodents. It is transmitted by rat fleas from wild rodents to domestic rats (Rattus norvegicus and especially R. rattus)
and then to humans (or directly from wild rodent to human). Y.
pestis reproduces rapidly in the wild rodent, which may then be
overcome with sepsis. A vector transmits it to a human from the wild
rodent. The vector is usually a rat flea of the species Xenopsylla cheopis, X. ramesis, or X.
nubica, although thirty different flea species have been identified as
carriers of plague; other vectors include ticks and
human
lice.

The vector takes a blood meal from the rodent, sucking up large amounts of Y. pestis bacteria, which then establish a colony in the stomachs and esophagi of some of these fleas. As a result, the flea cannot fit blood into its stomach and thus becomes extremely hungry. This extreme hunger drives the flea into intense blood-sucking (hematophagia). To avoid starvation, it will seek a blood meal from any nearby host, such as a human, rather than seek out a preferred rodent. This “blocked” flea will suck voraciously until it involuntarily regurgitates some of the blood it is sucking and some of the bacilli. As the flea feeds, it also defecates and thus excretes bacilli onto the human skin. The person scratches at the flea bite and thus deposits Y. pestis into his or her bloodstream.

As soon as a rodent that is infected with plague dies, its fleas leave for living hosts, humans often being the only nearby alternative. Under optimal conditions, vector fleas can live for six weeks, but they probably can transmit plague for about two weeks only. X. cheopis, the flea species most likely to transmit plague, flourishes in a dry, warm environment of about 60° to 77° Fahrenheit (20° to 25° Celsius). Bubonic plague can persist in relatively small rodent populations from which occasional human epidemics then arise.

Y. pestis probably evolved from the Central Asiatic plateau, the swathe of desert that reaches across Central Asia, the Middle East, and North Africa. It is rich with rodents and fleas that harbor and transmit plague. It is possible that these animals transferred Y. pestis from Central Asia to North Africa and subsequently to Central Africa.

The human flea (Pulex irritans) may be a transmitter of plague in some areas of Africa. However, human-to-human transmission of bubonic plague is uncommon because Y. pestis rarely produces in humans the level of sepsis needed for a flea to become blocked and thereby become a vector for bubonic plague.

Transmission can also occur when a person inhales plague-infected organisms
that have been released into the air. The inhalation form of the plague can be
aerosolized and used in acts of bioterrorism.

Risk Factors

The main risk factor for bubonic plague is contact with rodents carrying infected fleas. This may occur through occupational or environmental exposure to rats, ferrets, rabbits, squirrels, marmots, gerbils, birds, prairie dogs, bobcats, and coyotes. More than two hundred different rodents and other species can serve as hosts. Recent flea bites and scratches or bites from infected domestic cats are also risk factors.

Risk factors may be heightened by environmental and cultural conditions. For example, the Alur ethnic group in the West Nile region store grain and livestock in the same structure where people sleep because of the possibility of theft. This, coupled with the cultural practice of gathering and sleeping in the home of a deceased for three or four days (as dictated by the belief that the deceased spirit lingers and should be recognized by surviving relatives and friends), may increase the risk of contracting plague. An unusually prolonged drought is another risk factor because it may force field rodents to seek food in buildings. Poverty, poor sanitation, and poor food-storage practices are also risk factors. Late diagnosis is a risk factor for the spread of bubonic plague because it limits the effectiveness of control measures.

Symptoms

The classic symptom of bubonic plague appears usually one to six days after exposure as a smooth and painful lymph gland swelling known as a bubo. A bubo is most commonly found in the groin but is also found in the armpits and neck. A bubo usually occurs at the site of the initial flea bite or scratch. Pain may occur at the site before the bubo appears. If the infected person survives, the bubo usually suppurates in one to two weeks because of secondary infection with pyogenic bacteria. It may then burst and leave a deep ulcer. Other symptoms of bubonic plague are malaise (a general ill feeling), myalgia (muscle aches and pain), high fever, chills, severe headache, nausea, vomiting, seizures, and prostration. Petechiae (purplish spots caused by small hemorrhages); ecchymoses (purple discoloration from ruptured blood vessels); bleeding into the tissues, which turns the tissue black; and bleeding from the gastrointestinal tract may also present. In its mild form, however, bubonic plague may not even confine a person to bed.

If left untreated, bubonic plague can became septicemic or pneumonic plague, which affect the blood stream and the lungs, respectively. In addition to the other symptoms of bubonic plague, shock may occur with septicemic plague or pneumonic plague. Pneumonic plague is characterized by respiratory symptoms such as cough, chest pain, thin or bloody mucus excretions, shortness of breath, and even respiratory failure. When someone has pneumonic plague, the disease can also transmit directly to another human through airborne droplets.

Screening and Diagnosis

A doctor will ask the patient about symptoms and medical history and will perform a physical examination. Diagnostic tests may include blood and urine samples, sputum samples, a chest X ray, a computed tomography (CT) scan, a magnetic resonance imaging (MRI) scan, and a bronchoscopy, in which a thin scope is used to look into the lungs. Laboratory confirmation includes cultures from samples of blood, sputum, and fluid from the bubo. Cultures require more than forty-eight hours to produce definitive results. If plague infection is discovered, an infectious disease specialist should be contacted for assistance.

Treatment and Therapy

One should immediately treat suspected bubonic plague with antibiotics and then initiate confirmatory laboratory work. Without prompt treatment, Y. pestis can multiply in the bloodstream or spread to the lungs so rapidly that it may lead to the more serious pneumonic plague. Persons with bubonic plague are often hospitalized and placed in isolation, however.

The standard treatment for bubonic plague is intramuscular streptomycin (1 gram twice daily for ten days). Less severe cases can be treated with 500 milligrams (mg) of oral tetracycline, four times daily. Chloramphenicol is a suitable alternative and is administered in divided doses of 50 mg per kilogram per day, either parenterally or, if tolerated, orally for ten days. Gentamycin is the preferred antibiotic for treatment during pregnancy because it is safe, because it can be administered either intravenously or intramuscularly, and because its concentrations in the blood can be monitored.

The three most effective drugs have potentially serious adverse events associated with use during pregnancy: streptomycin may be ototoxic and nephrotoxic to the fetus, tetracycline has an adverse effect on the developing teeth and bones of the fetus, and chloramphenicol carries a risk, albeit low, of gray baby syndrome or bone-marrow suppression. Sulfonamides have been used extensively in plague treatment; however, some studies have shown higher mortality, increased complications, and longer duration of fever with its use compared with treatment with streptomycin, tetracycline, or chloramphenicol.

Prevention and Outcomes

Killed bacteria began to be used in plague vaccines in 1896. However, the vaccine licensed for use in the United States was a whole-cell bacterial vaccine, inactivated with formaldehyde and preserved in phenol. The primary series consisted of three doses: the first dose at the initial visit, the second dose one to three months later, and the third dose five or six months later. Booster doses could be given at six-month intervals if exposure continued. Common side effects included mild pain, erythema (redness), and induration (hardening) at the injection site. Fever, headache, and malaise were more common and more severe following repeated doses. Rare side effects included difficulty in breathing or swallowing; hives; itching, especially of soles or palms; reddening of skin, especially around ears; swelling of eyes, face, or inside of nose; and unusual, sudden, and severe tiredness or weakness. The plague vaccine was not very effective, however.

In 2000, the United States began working with Great Britain and Canada in sharing information about plague vaccine. In 2005, the three countries agreed to pool their resources to create a vaccine that combines the existing vaccine for the bubonic plague with a new kind of protection from the pneumonic plague. As of 2015, no plague vaccine was available to the public. In 2008, researchers from the Institut Pasteur in Paris used the less virulent ancestor to Y. pestis, Y. pseudotuberculosis, to try to develop a potentially safer, more efficient, and less expensive live oral vaccine. As of 2015, their efforts to create a stable, safe live vaccine remained ongoing.

Because human plague is rare in most parts of the world, there is no need to vaccinate anyone other than those at particularly high risk of exposure—namely, laboratory and field personnel working with or in proximity to Y. pestis. This intramuscular vaccine is not indicated for most travelers to countries reporting cases, particularly those traveling only to urban areas with modern hotel accommodations.

If a person is diagnosed with plague, most countries require that a governmental health agency be notified. Particularly if pneumonic plague is suspected, the person is kept in strict isolation until the disease is controlled with antibiotics. It is imperative that those who have been in close contact with an infected person be traced, identified, and evaluated. Infected persons might also be put under observation or given preventive antibiotic therapy (with a tetracycline, chloramphenicol, or one of the effective sulfonamides), depending on the degree and timing of contact. Antibiotics can also be given for a brief period to people who have been exposed to the bites of potentially infected rodent fleas or who have handled an animal known to be infected. People who must be present in an area where a plague outbreak is occurring can protect themselves for two to three weeks by taking antibiotics.

Many cities, especially in the United States, have instituted rodent-control programs because rodents also carry rabies and other deadly diseases. In rural areas, eliminating wild-rodent harborage and food sources and clearing brush, rock piles, and junk puts distance between rodents and the home. Ridding pet dogs and cats of fleas regularly prevents the fleas from jumping to other pets. Applying insect repellents, if available, to clothing and skin to prevent flea bites is advisable, as is wearing gloves when handling potentially infected animals. Keeping floors clean and occasionally pouring boiling water on a dirt floor and not sleeping on it is helpful.

In Africa, plague control is often reactive, not proactive, because of a lack of resources for surveillance. Plague control that targets rodents in Africa has focused on trapping, burning homes, and dusting homes and rodent burrows with powdered insecticide or other poisons such as dichloro-diphenyl-trichloroethane (DDT) powder followed by anticoagulant bait. Many countries employ rigorous disinfection routines for ships, docks, and aircraft because transportation of infected rodents aboard transcontinental vehicles has led to earlier pandemics.

Bibliography

Bahmanyar, M., and D. C. Cavanaugh. Plague Manual. Geneva: World Health Organization, 1999.

Borchert, Jeff N., Jeff J. Mach, and Timothy J. Linder. “Invasive Rats and Bubonic Plague in Northwest Uganda.” In Managing Vertebrate Invasive Species, edited by G. W. Witmer, W. C. Pitt, and K. A. Fagerstone. Fort Collins, Colo.: National Wildlife Research Center, 2007.

Cook, Gordon C., and Alimuddin I. Zumla, eds. Manson’s Tropical Diseases. 22d ed. Philadelphia: Saunders/Elsevier, 2009.

"Fast Facts on Plague in the 21st Century." ASTMH. Amer. Soc. of Tropical Medicine & Hygiene, n.d. Web. 29 Dec. 2015.

Findlay, John, and Drew Shrewsbury. A History of Bubonic Plague in the British Isles. New York: Cambridge University Press, 2005.

Jong, Elaine C., and Russell McMullen, eds. Travel and Tropical Medicine Manual. 4th ed. Philadelphia: Saunders/Elsevier, 2008.

Mandell, Gerald L., John E. Bennett, and Raphael Dolin, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. New York: Churchill Livingstone/Elsevier, 2010.

Marquardt, William C., ed. Biology of Disease Vectors. 2d ed. New York: Academic Press/Elsevier, 2005.

National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Vector-Borne Diseases (DVBD). "Plague: Frequently Asked Questions." CDC. Centers for Disease Control and Prevention, 14 Sept. 2015. Web. 29 Dec. 2015.