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 case-fatality ratio of 30 to 60 percent. If treated promptly and appropriately, the mortality rate is 5 to 15 percent.

ANATOMY OR SYSTEM AFFECTED: Glands, lymphatic system, skin

ALSO KNOWN AS: Black Death, plague

Incidence

Bubonic plague is one of the oldest diseases known and has been one of the most devastating in human history, perhaps most infamously in the medieval pandemic known as the Black Death. It is widely regarded as a disease of mainly historical importance because it is now rare in developed countries and affects mainly poor, remote populations. However, reports of new cases increased notably in the twenty-first century, drawing fresh attention from epidemiologists. Adding to the concern is the discovery of antibiotic-resistant strains of the plague bacterium.

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, primarily in the following countries (in order of most reported cases): the Democratic Republic of the Congo (DRC), Madagascar, Zambia, Uganda, Mozambique, Tanzania, China, Peru, Malawi, Indonesia, the United States, and Vietnam. The US Centers for Disease Control and Prevention stated in 2021 that between one thousand and two thousand global cases were reported each year, but noted that this estimate was likely low. The CDC also reported that an average of seven human plague cases developed each year in the United States, with the highest incidence occurring in the southwestern states of New Mexico, Arizona, and Colorado as well as parts of Nevada, Oregon, and California.

The World Health Organization (WHO) concedes that official data do not truly reflect the incidence of bubonic plague, mainly because of a reluctance to report plague cases but also because of inadequate surveillance capabilities. Notable outbreaks were reported in Madagascar in 2017 and in the DRC in 2020.

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 Hong Kong 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 mainly transmitted from wild rodents to domestic rats (Rattus norvegicus and especially R. rattus) by rat fleas. Y. pestis reproduces rapidly in rodents, which may then be overcome with sepsis. While a rodent can transmit the bacteria directly to a human, more commonly it is transmitted by a vector. 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. (Some studies have suggested that the human body louse, as well as fleas, may have played a major role in the spread of the Black Death.)

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 their bloodstream.

As soon as a rodent that is infected with plague dies, its fleas leave for living hosts, including humans if they are 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.

DNA analysis has suggested that Y. pestis probably evolved from the Central Asiatic plateau, the swathe of desert that reaches across Central Asia, the Middle East, and North Africa. From there it spread widely over thousands of years. Most research has focused on rats and rat fleas as the primary vectors for plague in humans. However, various other theories about the disease's historical spread (and especially the various waves of the Black Death) have also been raised, and experts continue to debate the issue.

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 person 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 become septicemic or pneumonic plague, which affect the bloodstream 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, and was withdrawn from use in the US.

In 2000, the United States began working with Great Britain and Canada in sharing information about plague vaccines. In 2005, the three countries agreed to pool their resources to create a vaccine combining the existing vaccine for the bubonic plague with a new kind of protection from the pneumonic plague. In 2008, researchers from the Institut Pasteur in Paris used a less virulent ancestor to Y. pestis, Y. pseudotuberculosis, to try to develop a potentially safer, more efficient, and less expensive live oral vaccine. Using the knowledge gained from the development of COVID-19 vaccine, researchers at Oxford University began Phase 1 trials in 2022 for a vaccine that would deliver a portion of the bacteria's genetic code to individuals, preventing serious illness.

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 historically contributed to pandemics.

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