Pneumonic Plague

Yersinia pestis[1]

Pneumonic plague is one of the three types of plague caused by the Yersinia pestis (Y. pestis) bacteria, which is associated with a serious lung infection.


Presentation

The symptoms of pneumonic plague typically occur within two to three days of bacterial exposure. Infected individuals will develop severe headaches, tachycardia, chills and fever along with a cough that produces clear sputum that may contain blood in later stages. Over the time, the cough may become foamy and bright red followed by hyperventilation and labored breathing. After symptoms develop the majority of mortalities will occur within two days if no treatment is provided. Transmission of pneumonic plague, which is extremely contagious, is through inhalation of waterborne droplets from an infected person. Transmission of primary pneumonic plague is rare and usually associated with observed in individuals that encounter a human or cat with pneumonic plague or laboratory personnel. Typically, pneumonic plague develops secondary to the septicemic or bubonic plague that spreads through the blood into the lungs.

There is a concern of bioterrorism-associated with the plague due to its ability to spread through direct inhalation of the Y. pestis pathogen.

Workup

A plague diagnosis is confirmed through microscopic examination of infected sputum, blood or lymph node pus. Infected patient samples may also be cultured in a laboratory and blood may contain antibodies for the pathogen which can also be detected in a laboratory. Polymerase chain reaction (PCR) may be performed to rapidly identify genes from the Y. pestis genome in patient samples. To specifically diagnose pneumonic plague physicians will perform chest x rays.

Treatment

Immediate treatment after contracting the plague dramatically decreases mortalities to lower than five percent. The most common antibiotic used to treat the plague is streptomycin which is administered intramuscularly for a minimum of 7 days (alternatively for at least three days after fever subsides). A number of alternative antibiotics, such as ciprofloxacin, doxycycline, and gentamicin, have also been shown to be effective. A quarantine is needed for patients with pneumonic plague to reduce the risk of spreading the infection through airborne droplets. This quarantine includes limiting patient contact and the use of personal protective equipment (PPE), including gloves, gown, face and eye protection, for all personnel that comes within two meters of the patient.

Prognosis

Appropriate and timely treatment along with the type of plague greatly influence the outcome of patients with the plague [5]. The highest mortality rates are observed in individuals infected with the pneumonic plague which has a 100% mortality rate if untreated and a 50% rate when treated. Mortality rates from bubonic plague vary widely from 50 to 90% if untreated and only 10 to 20% if treated and the mortality rates associated with septicemic plague are around 20 to 25%. Individuals who spend much of their time outdoors, such as hunters, miners, and tourists, may have a higher chance of acquiring the plague. There is no link between gender and chances of acquiring the plague but individuals below the age of 20 are more likely to become infected.

Etiology

Bubonic and septicemic plague are more common than pneumonic plague and may be acquired by humans that are bitten by plague-ridden fleas. The bubonic and septicemic forms of plague are not passed directly from human to human. Untreated bubonic and septicemic plague may spread through the blood to the lungs which may result in a secondary plague infection or pneumonic plague. This highly virulent form of plague can be passed from an infected human directly to another human by way of inhalation of airborne water droplets [1] [2]. This direct spread of pneumonic plague results in a primary infection [1] [2].

Epidemiology

In the United States, Y. pestis infections are rare, averaging around 10 to 15 per year, and they are typically isolated to certain areas in the Western states. From 1994 to 1999 there were 49 individuals that reported plague infections from five western states, including Utah, Colorado, Arizona, New Mexico, and California. Of those 49 cases, there were three mortalities caused by the plague. Another outbreak with 13 cases of Y. pestis infection which occurred in 2006 in the western states of California, Colorado, New Mexico and Texas that led to two confirmed mortalities. One reason for the low incidence of plague in the US is the limited human presence in the rural areas where the Y. pestis is commonly found. Another reason for the low incidence may be due to the fact that Y. pestis has been classified as a Category A bioterrorism agent by the Center for Disease Control and Prevention (CDC).

Classically, rabbits, prairie dogs, and squirrels have been shown to harbor Y. pestis. However, domestic cats have been shown to transmit the plague. Indeed, in the western US from 1977 to 1998 cats were responsible for 8% of all human plague cases (23 cases) [3]. Interestingly, in cases where the plague was spread by cats, the disease was spread through inhalation leading to primary pneumonic plague more commonly than bubonic or septicemic plague and increased mortality rates were observed due to delayed diagnosis and treatment [3].

The spread of the plague from human to human in the US is extremely rare and since 1924 there has only been one such case. In 2014, a man in Colorado with respiratory symptoms tested positive for Y. pestis. Upon further examination it was revealed that a recently deceased dog owned by the man also tested positive for Y. pestis along with three individuals that were in contact with the dog [4]. Of the four individuals infected with the plague in this outbreak, one was suspected to be from human to human transmission [4]. The North American Pacific coast and the southwestern US are thought to have the largest number of animals carrying the plague, primarily in uninhabited regions.

Developing countries of Asia and Africa, especially Zaire, India, Malawi and Mozambique along with Peru, have the highest number of plague cases in the world. In the five-year period between 1990 and 1995, there were an estimated 12,998 confirmed cases of Y. pestis infection. Zimbabwe, Peru, Uganda, Tanzania, Vietnam, India, Madagascar, Congo, Mozambique, China, and Myanmar were among the countries with more than 100 individuals infected with the plague during that period. Zambia and Malawi have also experienced outbreaks and Brazil has a number of geographical foci of plague infection in the northeastern regions that have semi-arid environments. In 2003 the World Health Organization (WHO) reported that 2,118 cases of plague were confirmed in 9 countries, with greater than 98% of those cases and mortalities associated with plague in Africa. The only continent that is thought to be plague-free is Australia.

Sex distribution
Age distribution

Pathophysiology

The bacteria responsible for the plague, Y. pestis, are a non-spore-forming, nonmotile, gram-negative, pleomorphic species that have a cell wall made of the endotoxin lipopolysaccharide (LPS). LPS along with other pathogenic factors, fibrinolysin, and coagulase, initiate the pathophysiology associated with the plague. The life cycle of Y. pestis begins its first phase in fleas and completes its second phase in humans.

The blockage phenomenon is one hypothesis that explains the virulence of Y. pestis. This bacterium is able to survive in the gastrointestinal tract of fleas due to the phospholipase D enzyme that is encoded by a plasmid and prevents the destruction of the organism by digestive juices [6]. According to the blockage hypothesis once the Y. pestis multiply to form a mass in the flea midgut they form jagged teeth-like structures called proventriculus that extend through the stomach into the esophagus [7]. This causes a blockage that will eventually lead to starvation of the flea, however, in this blocked state the flea will desperately attempt to attain nutrition from hosts by repeated biting and subsequently releasing the Y. pestis the host bloodstream [8]. This hypothesis does not fully explain how epidemics persists, therefore, other mechanisms of virulence must exist [9].

The second phase of the Y. pestis begins once it enters the hosts (usually humans) blood stream. Once in the blood stream, these bacteria travel to the lymph nodes where they are engulfed by phagocytes and begin a stage of intracellular reproduction [10]. The specific lymph node affected by Y. pestis will have a high bacterial presence, necrosis, abnormal architecture and lysed phagocytes which release the bacterium allowing the colonization of other organs. Along with being spread through infected flea bites, the plague can be spread through handling plague-ridden carcasses, being bitten or scratched by an infected cat, through inhalation of airborne droplets from humans or dogs and from contact with plague containing aerosols [11] [12].

Prevention

Prophylactic prevention includes using flea repellents and managing rodent infestations. If patients are traveling to areas known to have a plague epidemic, prophylactic antibiotics may be administered. If a patient comes in contact with an individual with pneumonic plague, doctors should closely monitor their temperatures every four to six hours. Additionally, doctors should prescribe antibiotics to avoid the development of an infection. Sulfamethoxazole or trimethoprim may be administered to children and ciprofloxacin or doxycycline should be administered to adults.

Summary

Compared to the bubonic plague, pneumonic plague is rarer and more virulent. Although they are both caused by the same pathogen (Y. pestis), pneumonic plague infects the respiratory system whereas bubonic plague affects the lymphatics. The third form of plague, septicemic plague, occurs in the circulatory system. Bubonic plague infections often precede the pneumonic form of plague which occurs secondary to spread of bubonic plague through the blood to the lungs. Unlike bubonic plague which requires an animal vector, pneumonic plague is spread directly from person to person through inhalation of airborne water droplets from infected individuals. The severity of pneumonic plague is highlighted by the 100% mortality rate in untreated individuals. With appropriate treatment mortality rates of pneumonic plague drop upto 50%.

Patient Information

The pneumonic plague is the respiratory version of the bubonic and septicemic plague which are all caused by the bacteria Yersinia pestis (Y. pestis). Plague infections are most commonly transmitted to humans through flea bites, however, the pneumonic plague may be passed from human to human through inhalation of airborne droplets that are expelled by infected individuals. Developing countries that have overcrowding, unsanitary conditions and rodent infestations are among the areas that present the highest risk for contracting the plague. Historically, the plague (known as the black death at the time) was responsible for millions of deaths each year but currently there are only a few thousand cases reported each year with the majority of these cases in Africa. Other than Africa, the plague is most common in Asia and South America. Although there are only 10 to 25 cases of plague reported in the US each year, the highest numbers of plague infested animals are found in the Midwestern states of the US. Without rapid treatment, plague can cause death within a few days.

The most devastating form of plague is the pneumonic plague which arises when the bacteria Y. pestis colonize the lungs. Not only is this form of the disease associated with the highest mortality rates the pneumonic plague is also highly contagious due to its ability to spread directly from person to person. Pneumonic plague may be transmitted when an uninfected individual inhales air that contains airborne water droplets containing Y. pestis which were expelled in an infected individual's cough. Pneumonic plague may also develop in untreated individuals with primary bubonic or septicemic plague once the bacteria travel through the bloodstream into the lungs.

After infection with Y. pestis symptoms of the plague occur very rapidly. These symptoms may include; dyspnea, cough with blood and sputum, chest pain, fever, weakness and severe headaches. A number of tests can be performed to determine whether an individual is infected with the plague causing Y. pestis. To diagnose pneumonic plague physicians will use an endoscope.

Untreated pneumonic plague has a 100% mortality rate which can occur within one day of symptom onset. Mortality rate goes to 50% with appropriate treatment. If physicians suspect a plague infection they will administer antibiotics before receiving a definitive diagnosis. Along with antibiotics, patients will receive oxygen therapy and fluids. In severe cases, breathing support may be necessary. Due to the highly contagious nature of the plague health care workers must be extremely cautious to prevent acquiring the plague. Development of a fever should be closely monitored in anyone suspected of coming into contact with an individual with the pneumonic plague.

The best way to prevent acquiring the plague is by reducing the exposure to fleas and individuals infected with the plague. To reduce the chances of acquiring the plague it is important to control rodent populations, remove wood and debris piles from around the house, use of insect repellent when outside and use of flea prevention on pets. It is important to contact a physician when someone comes in contact with fleas during an outbreak of plague. Vaccines are available but their effectiveness is unclear.

Self-assessment

Ask Question


5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.

References

  1. Inglesby TV, Dennis DT, Henderson DA, et al. Plague as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA. 2000; 283:2281–90
  2. Kool JL. Risk of person-to-person transmission of pneumonic plague. Clin Infect Dis. 2005; 40:1166–72.
  3. Gage K, Lance S, Dennis D, et al. Human plague in United States: A review of cases from 1988-1992 with comments on likelihood of increased plague activity. Border Epidemiol Bull. 1992; 1:19.
  4. Runfola JK, House J, Miller L, et al. Outbreak of Human Pneumonic Plague with Dog-to-Human and Possible Human-to-Human Transmission - Colorado, June-July 2014. MMWR Morb Mortal Wkly Rep. 2015; 64(16):429-34.
  5. Prentice MB, Rahalison L. Plague. Lancet. 2007; 369(9568):1196-207.
  6. Hinnebusch BJ, Rudolph AE, Cherepanov P, et al. Role of Yersinia murine toxin in survival of Yersinia pestis in the midgut of the flea vector. Science. 2002; 296(5568):733-5.
  7. Jarrett CO, Deak E, Isherwood KE, et al. Transmission of Yersinia pestis from an infectious biofilm in the flea vector. J Infect Dis. 2004; 190(4):783-92.
  8. Hinnebusch BJ, Perry RD, Schwan TG. Role of the Yersinia pestis hemin storage (hms) locus in the transmission of plague by fleas. Science. 1996; 273(5273):367-70.
  9. Eisen RJ, Bearden SW, Wilder AP, et al. Early-phase transmission of Yersinia pestis by unblocked fleas as a mechanism explaining rapidly spreading plague epizootics. Proc Natl Acad Sci U S A. 2006; 103(42):15380-5.
  10. Pujol C, Bliska JB. Turning Yersinia pathogenesis outside in: subversion of macrophage function by intracellular yersiniae. Clin Immunol. 2005; 114(3):216-26.
  11. Crook LD, Tempest B. Plague. A clinical review of 27 cases. Arch Intern Med. 1992; 152(6):1253-6.
  12. Runfola JK, House J, Miller L, et al. Outbreak of Human Pneumonic Plague with Dog-to-Human and Possible Human-to-Human Transmission - Colorado, June-July 2014. MMWR Morb Mortal Wkly Rep. 2015; 64(16):429-34.

Media References

  1. Yersinia pestis, Public Domain

Languages