Plague (disease)

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Plague
Yersinia pestis fluorescent.jpeg
Yersinia pestis seen at 200× magnification with a fluorescent label.
Specialty Infectious disease
Symptoms Fever, weakness, headache [1]
Usual onset1–7 days after exposure [2]
Types Bubonic plague, septicemic plague, pneumonic plague [1]
Causes Yersinia pestis [2]
Diagnostic method Finding the bacterium in a lymph node, blood, sputum [2]
Prevention Plague vaccine [2]
Treatment Antibiotics and supportive care [2]
Medication Gentamicin and a fluoroquinolone [3]
Prognosis ≈10% risk of death (with treatment) [4]
Frequency≈600 cases a year [2]

Plague is an infectious disease caused by the bacterium Yersinia pestis . [2] Symptoms include fever, weakness and headache. [1] Usually this begins one to seven days after exposure. [2] There are three forms of plague, each affecting a different part of the body and causing associated symptoms. Pneumonic plague infects the lungs, causing shortness of breath, coughing and chest pain; bubonic plague affects the lymph nodes, making them swell; and septicemic plague infects the blood and can cause tissues to turn black and die. [2] [1]

Contents

The bubonic and septicemic forms are generally spread by flea bites or handling an infected animal, [1] whereas pneumonic plague is generally spread between people through the air via infectious droplets. [1] Diagnosis is typically by finding the bacterium in fluid from a lymph node, blood or sputum. [2]

Those at high risk may be vaccinated. [2] Those exposed to a case of pneumonic plague may be treated with preventive medication. [2] If infected, treatment is with antibiotics and supportive care. [2] Typically antibiotics include a combination of gentamicin and a fluoroquinolone. [3] The risk of death with treatment is about 10% while without it is about 70%. [4]

Globally, about 600 cases are reported a year. [2] In 2017, the countries with the most cases include the Democratic Republic of the Congo, Madagascar and Peru. [2] In the United States, infections occasionally occur in rural areas, where the bacteria are believed to circulate among rodents. [5] It has historically occurred in large outbreaks, with the best known being the Black Death in the 14th century, which resulted in more than 50 million deaths in Europe. [2]

Signs and symptoms

There are several different clinical manifestations of plague. The most common form is bubonic plague, followed by septicemic and pneumonic plague. [6] Other clinical manifestations include plague meningitis, plague pharyngitis, and ocular plague. [6] [7] General symptoms of plague include fever, chills, headaches, and nausea. [1] Many people experience swelling in their lymph nodes if they have bubonic plague. [1] For those with pneumonic plague, symptoms may (or may not) include a cough, pain in the chest, and haemoptysis. [1]

Bubonic plague

Swollen inguinal lymph glands on a person infected with the bubonic plague. The swollen lymph glands are termed buboes from the Greek word for groin, swollen gland: bubo. Plague -buboes.jpg
Swollen inguinal lymph glands on a person infected with the bubonic plague. The swollen lymph glands are termed buboes from the Greek word for groin, swollen gland: bubo.

When a flea bites a human and contaminates the wound with regurgitated blood, the plague-causing bacteria are passed into the tissue. Y. pestis can reproduce inside cells, so even if phagocytosed, they can still survive. Once in the body, the bacteria can enter the lymphatic system, which drains interstitial fluid. Plague bacteria secrete several toxins, one of which is known to cause beta-adrenergic blockade. [8]

Y. pestis spreads through the lymphatic vessels of the infected human until it reaches a lymph node, where it causes acute lymphadenitis. [9] The swollen lymph nodes form the characteristic buboes associated with the disease, [10] and autopsies of these buboes have revealed them to be mostly hemorrhagic or necrotic. [11]

If the lymph node is overwhelmed, the infection can pass into the bloodstream, causing secondary septicemic plague and if the lungs are seeded, it can cause secondary pneumonic plague. [12]

Septicemic plague

Septicemic plague resulting in necrosis PlagueTypes.jpg
Septicemic plague resulting in necrosis

Lymphatics ultimately drain into the bloodstream, so the plague bacteria may enter the blood and travel to almost any part of the body. In septicemic plague, bacterial endotoxins cause disseminated intravascular coagulation (DIC), causing tiny clots throughout the body and possibly ischemic necrosis (tissue death due to lack of circulation/perfusion to that tissue) from the clots. DIC results in depletion of the body's clotting resources so that it can no longer control bleeding. Consequently, there is bleeding into the skin and other organs, which can cause red and/or black patchy rash and hemoptysis/hematemesis (coughing up/ vomiting of blood). There are bumps on the skin that look somewhat like insect bites; these are usually red, and sometimes white in the centre. Untreated, the septicemic plague is usually fatal. Early treatment with antibiotics reduces the mortality rate to between 4 and 15 per cent. [13] [14] [15]

Pneumonic plague

The pneumonic form of plague arises from infection of the lungs. It causes coughing and thereby produces airborne droplets that contain bacterial cells and are likely to infect anyone inhaling them. The incubation period for pneumonic plague is short, usually two to four days, but sometimes just a few hours. The initial signs are indistinguishable from several other respiratory illnesses; they include headache, weakness, and spitting or vomiting of blood. The course of the disease is rapid; unless diagnosed and treated soon enough, typically within a few hours, death may follow in one to six days; in untreated cases, mortality is nearly 100%. [16] [17]

Cause

The Oriental rat flea (Xenopsylla cheopis) engorged with blood after a blood meal. This species of flea is the primary vector for the transmission of Yersinia pestis, the organism responsible for bubonic plague in most plague epidemics in Asia, Africa, and South America. Both male and female fleas feed on blood and can transmit the infection. Xenopsylla chepsis (oriental rat flea).jpg
The Oriental rat flea (Xenopsylla cheopis) engorged with blood after a blood meal. This species of flea is the primary vector for the transmission of Yersinia pestis, the organism responsible for bubonic plague in most plague epidemics in Asia, Africa, and South America. Both male and female fleas feed on blood and can transmit the infection.
A child bitten by a flea infected with the bacterium Yersinia pestis. Y. pestis, a member of the family Yersiniaceae, has caused the bite to become ulcerated. Ulceration of flea bite cause by yersinia pestis.jpg
A child bitten by a flea infected with the bacterium Yersinia pestis. Y. pestis, a member of the family Yersiniaceae, has caused the bite to become ulcerated.

Transmission of Y. pestis to an uninfected individual is possible by any of the following means: [18]

Yersinia pestis circulates in animal reservoirs, particularly in rodents, in the natural foci of infection found on all continents except Australia. The natural foci of plague are situated in a broad belt in the tropical and sub-tropical latitudes and the warmer parts of the temperate latitudes around the globe, between the parallels 55° N and 40° S. [18] Contrary to popular belief, rats did not directly start the spread of the bubonic plague. It is mainly a disease in the fleas ( Xenopsylla cheopis ) that infested the rats, making the rats themselves the first victims of the plague. Rodent-borne infection in a human occurs when a person is bitten by a flea that has been infected by biting a rodent that itself has been infected by the bite of a flea carrying the disease. The bacteria multiply inside the flea, sticking together to form a plug that blocks its stomach and causes it to starve. The flea then bites a host and continues to feed, even though it cannot quell its hunger, and consequently, the flea vomits blood tainted with the bacteria back into the bite wound. The bubonic plague bacterium then infects a new person and the flea eventually dies from starvation. Serious outbreaks of plague are usually started by other disease outbreaks in rodents or a rise in the rodent population. [19]

A 21st-century study of a 1665 outbreak of plague in the village of Eyam in England's Derbyshire Dales – which isolated itself during the outbreak, facilitating modern study – found that three-quarters of cases are likely to have been due to human-to-human transmission, especially within families, a much bigger proportion than previously thought. [20]

Diagnosis

Symptoms of plague are usually non-specific and to definitively diagnose plague, laboratory testing is required. [21] Y. pestis can be identified through both a microscope and by culturing a sample and this is used as a reference standard to confirm that a person has a case of plague. [21] The sample can be obtained from the blood, mucus (sputum), or aspirate extracted from inflamed lymph nodes (buboes). [21] If a person is administered antibiotics before a sample is taken or if there is a delay in transporting the person's sample to a laboratory and/or a poorly stored sample, there is a possibility for false negative results. [21]

Polymerase chain reaction (PCR) may also be used to diagnose plague, by detecting the presence of bacterial genes such as the pla gene (plasmogen activator) and caf1 gene, (F1 capsule antigen). [21] PCR testing requires a very small sample and is effective for both alive and dead bacteria. [21] For this reason, if a person receives antibiotics before a sample is collected for laboratory testing, they may have a false negative culture and a positive PCR result. [21]

Blood tests to detect antibodies against Y. pestis can also be used to diagnose plague, however, this requires taking blood samples at different periods to detect differences between the acute and convalescent phases of F1 antibody titres. [21]

In 2020, a study about rapid diagnostic tests that detect the F1 capsule antigen (F1RDT) by sampling sputum or bubo aspirate was released. [21] Results show rapid diagnostic F1RDT test can be used for people who have suspected pneumonic and bubonic plague but cannot be used in asymptomatic people. F1RDT may be useful in providing a fast result for prompt treatment and fast public health response as studies suggest that F1RDT is highly sensitive for both pneumonic and bubonic plague. However, when using the rapid test, both positive and negative results need to be confirmed to establish or reject the diagnosis of a confirmed case of plague and the test result needs to be interpreted within the epidemiological context as study findings indicate that although 40 out of 40 people who had the plague in a population of 1000 were correctly diagnosed, 317 people were diagnosed falsely as positive. [21] [22] [23]

Prevention

Vaccination

Bacteriologist Waldemar Haffkine developed the first plague vaccine in 1897. [24] [25] He conducted a massive inoculation program in British India, and it is estimated that 26 million doses of Haffkine's anti-plague vaccine were sent out from Bombay between 1897 and 1925, reducing the plague mortality by 50–85%. [24] [26]

Since human plague is rare in most parts of the world as of 2023, routine vaccination is not needed other than for those at particularly high risk of exposure, nor for people living in areas with enzootic plague, meaning it occurs at regular, predictable rates in populations and specific areas, such as the western United States. It is not even indicated for most travellers to countries with known recent reported cases, particularly if their travel is limited to urban areas with modern hotels. The United States CDC thus only recommends vaccination for (1) all laboratory and field personnel who are working with Y. pestis organisms resistant to antimicrobials: (2) people engaged in aerosol experiments with Y. pestis; and (3) people engaged in field operations in areas with enzootic plague where preventing exposure is not possible (such as some disaster areas). [27] A systematic review by the Cochrane Collaboration found no studies of sufficient quality to make any statement on the efficacy of the vaccine. [28]

Early diagnosis

Diagnosing plague early leads to a decrease in transmission or spread of the disease. [21]

Prophylaxis

Pre-exposure prophylaxis for first responders and health care providers who will care for patients with pneumonic plague is not considered necessary as long as standard and droplet precautions can be maintained. [7] In cases of surgical mask shortages, patient overcrowding, poor ventilation in hospital wards, or other crises, pre-exposure prophylaxis might be warranted if sufficient supplies of antimicrobials are available. [7]

Postexposure prophylaxis should be considered for people who had close (<6 feet), sustained contact with a patient with pneumonic plague and were not wearing adequate personal protective equipment. [7] Antimicrobial postexposure prophylaxis also can be considered for laboratory workers accidentally exposed to infectious materials and people who had close (<6 feet) or direct contact with infected animals, such as veterinary staff, pet owners, and hunters. [7]

Specific recommendations on pre- and post-exposure prophylaxis are available in the clinical guidelines on treatment and prophylaxis of plague published in 2021. [7]

Treatments

If diagnosed in time, the various forms of plague are usually highly responsive to antibiotic therapy. [6] [21] The antibiotics often used are streptomycin, chloramphenicol and tetracycline. Amongst the newer generation of antibiotics, gentamicin and doxycycline have proven effective in monotherapeutic treatment of plague. [6] [29] Guidelines on treatment and prophylaxis of plague were published by the Centers for Disease Control and Prevention in 2021. [7]

The plague bacterium could develop drug resistance and again become a major health threat. One case of a drug-resistant form of the bacterium was found in Madagascar in 1995. [30] Further outbreaks in Madagascar were reported in November 2014 [31] and October 2017. [32]

Epidemiology

Distribution of plague-infected animals 1998 World distribution of plague 1998.PNG
Distribution of plague-infected animals 1998

Globally about 600 cases are reported a year. [2] In 2017, the countries with the most cases include the Democratic Republic of the Congo, Madagascar and Peru. [2] It has historically occurred in large outbreaks, with the best known being the Black Death in the 14th century which resulted in more than 50 million dead. [2] In recent years, cases have been distributed between small seasonal outbreaks which occur primarily in Madagascar, and sporadic outbreaks or isolated cases in endemic areas. [2]

In 2022 the possible origin of all modern strands of Yersinia pestis DNA was found in human remains in three graves located in Kyrgyzstan, dated to 1338 and 1339. The siege of Caffa in Crimea in 1346, is known to have been the first plague outbreak with following strands, later to spread over Europe. Sequencing DNA compared to other ancient and modern strands paints a family tree of the bacteria. Bacteria today affecting marmots in Kyrgyzstan, are closest to the strand found in the graves, suggesting this is also the location where plague transferred from animals to humans. [33]

Biological weapon

The plague has a long history as a biological weapon. Historical accounts from ancient China and medieval Europe details the use of infected animal carcasses, such as cows or horses, and human carcasses, by the Xiongnu/Huns, Mongols, Turks and other groups, to contaminate enemy water supplies. Han Dynasty General Huo Qubing is recorded to have died of such contamination while engaging in warfare against the Xiongnu. Plague victims were also reported to have been tossed by catapult into cities under siege. [34]

In 1347, the Genoese possession of Caffa, a great trade emporium on the Crimean peninsula, came under siege by an army of Mongol warriors of the Golden Horde under the command of Jani Beg. After a protracted siege during which the Mongol army was reportedly withering from the disease, they decided to use the infected corpses as a biological weapon. The corpses were catapulted over the city walls, infecting the inhabitants. This event might have led to the transfer of the Black Death via their ships into the south of Europe, possibly explaining its rapid spread. [35]

During World War II, the Japanese Army developed weaponized plague, based on the breeding and release of large numbers of fleas. During the Japanese occupation of Manchuria, Unit 731 deliberately infected Chinese, Korean and Manchurian civilians and prisoners of war with the plague bacterium. These subjects, termed "maruta" or "logs", were then studied by dissection, others by vivisection while still conscious. Members of the unit such as Shiro Ishii were exonerated from the Tokyo tribunal by Douglas MacArthur but 12 of them were prosecuted in the Khabarovsk War Crime Trials in 1949 during which some admitted having spread bubonic plague within a 36-kilometre (22 mi) radius around the city of Changde. [36]

Ishii innovated bombs containing live mice and fleas, with very small explosive loads, to deliver the weaponized microbes, overcoming the problem of the explosive killing the infected animal and insect by the use of a ceramic, rather than metal, casing for the warhead. While no records survive of the actual usage of the ceramic shells, prototypes exist and are believed to have been used in experiments during WWII. [37] [38]

After World War II, both the United States and the Soviet Union developed means of weaponising pneumonic plague. Experiments included various delivery methods, vacuum drying, sizing the bacterium, developing strains resistant to antibiotics, combining the bacterium with other diseases (such as diphtheria), and genetic engineering. Scientists who worked in USSR bio-weapons programs have stated that the Soviet effort was formidable and that large stocks of weaponised plague bacteria were produced. Information on many of the Soviet and US projects is largely unavailable. Aerosolized pneumonic plague remains the most significant threat. [39] [40] [41]

The plague can be easily treated with antibiotics. Some countries, such as the United States, have large supplies on hand if such an attack should occur, making the threat less severe. [42]

See also

Related Research Articles

<span class="mw-page-title-main">Black Death</span> 1346–1353 pandemic in Eurasia and North Africa

The Black Death was a bubonic plague pandemic occurring in Western Eurasia and North Africa from 1346 to 1353. It is the most fatal pandemic recorded in human history, causing the deaths of approximately 40% to 60% of Europe's population peaking in Europe from 1347 to 1351. Bubonic plague is caused by the bacterium Yersinia pestis spread by fleas, but during the Black Death it probably also took a secondary form, spread by person-to-person contact via aerosols, causing pneumonic plague.

A human pathogen is a pathogen that causes disease in humans.

<i>Yersinia pestis</i> Species of bacteria, cause of plague

Yersinia pestis is a gram-negative, non-motile, coccobacillus bacterium without spores that is related to both Yersinia enterocolitica and Yersinia pseudotuberculosis, the pathogen from which Y. pestis evolved and responsible for the Far East scarlet-like fever. It is a facultative anaerobic organism that can infect humans via the Oriental rat flea. It causes the disease plague, which caused the Plague of Justinian and the Black Death, the deadliest pandemic in recorded history. Plague takes three main forms: pneumonic, septicemic, and bubonic. Yersinia pestis is a parasite of its host, the rat flea, which is also a parasite of rats, hence Y. pestis is a hyperparasite.

<span class="mw-page-title-main">Pneumonic plague</span> Severe lung infection

Pneumonic plague is a severe lung infection caused by the bacterium Yersinia pestis. Symptoms include fever, headache, shortness of breath, chest pain, and coughing. They typically start about three to seven days after exposure. It is one of three forms of plague, the other two being septicemic plague and bubonic plague.

<span class="mw-page-title-main">Tularemia</span> Infectious disease caused by the bacterium Francisella tularensis

Tularemia, also known as rabbit fever, is an infectious disease caused by the bacterium Francisella tularensis. Symptoms may include fever, skin ulcers, and enlarged lymph nodes. Occasionally, a form that results in pneumonia or a throat infection may occur.

<span class="mw-page-title-main">Septicemic plague</span> Human disease caused by Yersinia pestis

Septicemic plague is one of the three forms of plague, and is caused by Yersinia pestis, a gram-negative species of bacterium. Septicemic plague is a systemic disease involving infection of the blood and is most commonly spread by bites from infected fleas. Septicemic plague can cause disseminated intravascular coagulation and is always fatal when untreated. The other varieties of the plague are bubonic plague and pneumonic plague.

<span class="mw-page-title-main">Bacterial pneumonia</span> Disease of the lungs

Bacterial pneumonia is a type of pneumonia caused by bacterial infection.

<span class="mw-page-title-main">Third plague pandemic</span> Bubonic plague pandemic, beginning 1855

The third plague pandemic was a major bubonic plague pandemic that began in Yunnan, China, in 1855. This episode of bubonic plague spread to all inhabited continents, and ultimately led to more than 12 million deaths in India and China, and at least 10 million Indians were killed in British Raj India alone, making it one of the deadliest pandemics in history. According to the World Health Organization, the pandemic was considered active until 1960 when worldwide casualties dropped to 200 per year. Plague deaths have continued at a lower level for every year since.

<span class="mw-page-title-main">Yersiniosis</span> Human disease

Yersiniosis is an infectious disease of the gastrointestinal tract caused by bacteria of the genus Yersinia other than Y. pestis. Most cases of yersiniosis in humans are caused by Y. enterocolitica, with a small minority being caused by Y. pseudotuberculosis. Rarely, other species of the genus can cause yersiniosis.

<span class="mw-page-title-main">Bubo</span> Inflammation of the lymph nodes

A bubo is adenitis or inflammation of the lymph nodes and is an example of reactive lymphadenopathy.

<span class="mw-page-title-main">Bubonic plague</span> Human and animal disease

Bubonic plague is one of three types of plague caused by the bacterium Yersinia pestis. One to seven days after exposure to the bacteria, flu-like symptoms develop. These symptoms include fever, headaches, and vomiting, as well as swollen and painful lymph nodes occurring in the area closest to where the bacteria entered the skin. Acral necrosis, the dark discoloration of skin, is another symptom. Occasionally, swollen lymph nodes, known as "buboes", may break open.

Theories of the Black Death are a variety of explanations that have been advanced to explain the nature and transmission of the Black Death (1347–51). A number of epidemiologists from the 1980s to the 2000s challenged the traditional view that the Black Death was caused by plague based on the type and spread of the disease. The confirmation in 2010 and 2011 that Yersinia pestis DNA was associated with a large number of plague sites has led researchers to conclude that "Finally, plague is plague."

<span class="mw-page-title-main">Plague vaccine</span>

Plague vaccine is a vaccine used against Yersinia pestis to prevent the plague. Inactivated bacterial vaccines have been used since 1890 but are less effective against the pneumonic plague, so live, attenuated vaccines and recombinant protein vaccines have been developed to prevent the disease.

The 1994 plague in India was an outbreak of bubonic and pneumonic plague in south-central and western India from 26 August to 18 October 1994. 693 suspected cases and 56 deaths were reported from the five affected Indian states as well as the Union Territory of Delhi. These cases were from Maharashtra, Gujarat, Karnataka, Uttar Pradesh, Madhya Pradesh and New Delhi. There are no reports of cases being exported to other countries.

<span class="mw-page-title-main">Cat-scratch disease</span> Human disease

Cat-scratch disease (CSD) or felinosis is an infectious disease that most often results from a scratch or bite of a cat. Symptoms typically include a non-painful bump or blister at the site of injury and painful and swollen lymph nodes. People may feel tired, have a headache, or a fever. Symptoms typically begin within 3–14 days following infection.

<span class="mw-page-title-main">Sylvatic plague</span> Infectious bacterial disease

Sylvatic plague is an infectious bacterial disease caused by the plague bacterium that primarily affects rodents, such as prairie dogs. It is the same bacterium that causes bubonic and pneumonic plague in humans. Sylvatic, or sylvan, means 'occurring in woodland,' and refers specifically to the form of plague in rural wildlife. Urban plague refers to the form in urban wildlife.

<span class="mw-page-title-main">Urban plague</span> Infectious disease affecting rodents

Urban plague is an infectious disease among rodent species that live in close association with humans in urban areas. It is caused by the bacterium Yersinia pestis which is the same bacterium that causes bubonic and pneumonic plague in humans. Plague was first introduced into the United States in 1900 by rat–infested steamships that had sailed from affected areas, mostly from Asia. Urban plague spread from urban rats to rural rodent species, especially among prairie dogs in the western United States.

<span class="mw-page-title-main">1924 Los Angeles pneumonic plague outbreak</span> Disease outbreak in Los Angeles, California

The 1924 Los Angeles pneumonic plague outbreak was an outbreak of the pneumonic plague in Los Angeles, California that began on September 28, 1924, and was declared fully contained on November 13, 1924. It represented the first time that the plague had emerged in Southern California; plague outbreaks previously surfaced in San Francisco and Oakland. The outbreak killed 30 people and infected several more. Public health officials credited the lessons learned from the San Francisco outbreak with saving lives, and swiftly implemented preventative measures, including hospitalization of the sick and all their contacts, a neighborhood quarantine, and a large-scale rat eradication program. The epicenter of the plague was in the Macy Street District, primarily home to Mexican immigrants. Racism against Mexican Americans tainted the reaction to the plague, an issue not made public until the outbreak concluded. This outbreak was the last instance of aerosol transmission of the plague and the last major plague outbreak in the United States.

<span class="mw-page-title-main">21st century Madagascar plague outbreaks</span> Outbreaks of plague in Madagascar during the 21st century

Madagascar has experienced several outbreaks of bubonic and pneumonic plague in the 21st century. In the outbreak beginning in 2014, 71 died; in 2017, 202 died. Smaller outbreaks occurred in January 2008, and December 2013.

The Neolithic decline was a rapid collapse in populations between 5000 and 6000 years ago during the Neolithic period in western Eurasia. The specific causes of that broad population decline are still debated. While heavily populated settlements were regularly created, abandoned, and resettled during the Neolithic, after around 5400 years ago, a great number of those settlements were permanently abandoned. The population decline is associated with worsening agricultural conditions and a decrease in cereal production. Other suggested causes include the emergence of communicable diseases spread from animals living in close quarters with humans.

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  33. ↑ "Origin of Black Death finally found in bacteria from Kyrgyzstan graves".
  34. ↑ Schama, S. (2000). A History of Britain: At the Edge of the World? 3000 BC-AD 1603, BBC Worldwide, London, p. 226.
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  36. ↑ Daniel Barenblatt, A Plague upon Humanity, HarperCollins, 2004, pp. 220–221
  37. ↑ "Japan's Secret Biological Weapons Program". Damn Interesting. Retrieved 2020-05-29.
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  42. ↑ Tamparo C, Lewis M (2011). Diseases of the Human Body. Philadelphia, PA: F.A. Davis Company. p. 70. ISBN   9780803625051.

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