Yersinia pestis infection overview

# Overview
Yersinia pestis infection, an infectious disease of animals and humans, is caused by enterobacteriaYersinia pestis, a bacterium. Human yersinia pestis infection takes three main clinical forms: pneumonic, septicemic, and the bubonic plague. All three forms are widely believed to have been responsible for a number of high-mortality epidemics throughout human history, including the Plague of Justinian in 542 CE and the black death, accounted for the death of at least one-third of the European population between 1347 and 1353 CE. It is demonstrated conclusively that these plagues originated in rodent populations in China. Plague is a zoonotic, primarily carried by rodents (notably rats) and spread to humans via fleas. Plague is notorious throughout history, due to the unprecedented scale of death and devastation it wrought. Plague is still endemic in some parts of the world. Bubonic plague should be differentiated from other causes of lymphadenopathy, such as streptococcal or staphylococcal lymphadenitis, infectious mononucleosis, cat-scratch fever, and tularemia.  Septicemic plague should be differentiated from non-specific sepsis syndrome and gram negative sepsis. Differential diagnosis for pneumonic plague includes infections that cause community-acquired pneumonia, such as pneumococcal or streptococcal pneumonia, viral pneumonia, hemophilus influenzae, and anthrax. Symptoms of plague may be differentiated by type: Bubonic, septicemic, and pneumonic. Although all 3 types share constitutional symptoms, key features differentiate them from one another. Not only do the 3 types differ in symptoms, but also in treatment and prognosis. Bubonic plague is characterized by the presence of painful and tender lymphadenopathy, called buboes. Less pathognomonic features are found in other types of plague, making their diagnosis more difficult. Septicemic plague follows the course, along with signs and symptoms, of a gram-negative bacilli and pneumonic plague presents with a virulent pneumonia. Antibiotic therapy is the mainstream of treatment. The drugs of choice are streptomycin or gentamicin, but tetracyclines, fluoroquinolones, and chloramphenicol are also effective.

# Historical Perspective
It is suggested that Yersinia pestis infection was a contributing factor in some of (though possibly not all) the European plagues. The earliest account describing a possible plague epidemic is found in I Samuel 5:6 of the Hebrew Bible (Tanakh). In this account, the Philistines of Ashdod were stricken with a plague for the crime of stealing the Ark of the Covenant from the Children of Israel. These events have been dated to approximately the second half of the 11th century BC.

# Classification
The classification of plague depends on the mode of infection and the clinical syndrome. Plague can be classified into bubonic plague, septicemic plague, or pneumonic plague.

# Pathophysiology
Plague can be transmitted from flea bites or the inhalation of aerosol from an individual who has plague pneumonia. Pathogenesis due to the Yersinia pestis infection of mammalian hosts, results from several factors including the bacteria's avoidance of normal immune system responses, such as phagocytosis and antibody production.

# Causes
Yersinia pestis (Y. pestis), a rod-shaped facultative anaerobe with bipolar staining (giving it a safety pin appearance) causes the infection in mammals and humans.  The bacteria maintain their existence in a cycle involving rodents and their fleas.  The genus Yersinia is gram-negative, bipolar staining coccobacilli, and, similarly to other Enterobacteriaceae, it has a fermentative metabolism. Y. pestis produces an antiphagocytic slime. The organism is motile when isolated, but becomes nonmotile in the mammalian host.

# Differential Diagnosis
The differential diagnosis for yersina pestis infection is dependent on the clinical syndrome (bubonic plague, septicimic plague, pneumonic plague, or pharyngeal plague).  Bubonic plague should be differentiated from other causes of lymphadenopathy, such as streptococcal or staphylococcal lymphadenitis, infectious mononucleosis, cat-scratch fever, and tularemia.  Septicemic plague should be differentiated from non-specific sepsis syndrome and gram negative sepsis.  The differential diagnosis for pneumonic plague includes infections that cause community-acquired pneumonia, such as pneumococcal or streptococcal pneumonia, viral pneumonia, hemophilus influenzae, and anthrax.

# Epidemiology and Demographics
Given its ability to cause serious pandemics, plague is one of the three diseases subject to the International Health Regulations, the other two being yellow fever and cholera.  From 1954 to 1997, plague affected 38 countries, with 80 613 cases and 6587 deaths. Between 2004 and 2009, the WHO reported that the number of cases of plague worldwide was 12,503, with 843 deaths, for a case-fatality rate of 6.7%.

# Risk Factors
Risk factors for plague include living in rural areas, near animals such as rodents, or in houses where sanitation is poor. People who deal frequently with animals, such as veterinaries, are at higher risk for infection with Yersinia pestis.

# Screening
Screening is not recommended for patients at risk of contracting plague. However, all suspected cases should be confirmed and reported to the World Health Organization upon discovery.

# Natural History, Complications and Prognosis
The complications of Yersina pestis infection are dependent on the clinical syndrome (bubonic plague, septicimic plague, pneumonic plague, or pharyngeal plague).  Bubonic plague can be complicated by septicemia, pneumonia, or meningitis.  The complications of septicemic plague include gangrene of distal upper and lower extremities and tip of the nose due to small vessel thrombosis, disseminated intravascular coagulopathy (DIC), and adult respiratory distress syndrome (ARDS).  The complications of pneumonic plague are septicemia, abscess formation, and cavitation.  If plague patients are not administered specific antibiotic therapy, the disease can progress rapidly to death. Approximately 14% (1 in 7) of all plague cases in the United States are fatal.

# Diagnosis

## History and Symptoms
Symptoms of plague may be differentiated by type: Bubonic, septicemic, and pneumonic. Although all 3 types share constitutional symptoms, key features differentiate them from one another. Not only do the 3 types differ in symptoms, but also in treatment and prognosis. Bubonic plague is characterized by the presence of painful and tender lymphadenopathy, called buboes. Less pathognomonic features are found in other types of plague, making their diagnosis more difficult. Septicemic plague follows the course, along with signs and symptoms, of a gram-negative bacilli and pneumonic plague presents with a virulent pneumonia.

## Physical Examination
Apart from the presence of buboes, which are tender lymph nodes in patients infected with bubonic plague, the physical examination findings are not specific to plague. Nonetheless, physical examination is crucial to evaluate for the presence of target organ damage or the progression and worsening of infection burden in these patients.

## Laboratory Findings
Following a thorough history and physical exam, patients suspected to be infected by the plague, such as a patient presenting with fever living in an endemic region, require a confirmation of the initial diagnosis.  Bubonic plague is diagnosed by gram stain and culture of aspirated material from suppurative lymph nodes. Collection of blood specimens, lymph node aspirates from buboes, sputum samples, and tracheal swabs are needed before the administration of antibiotics. Additionally, cerebrospinal fluid (CSF) collection is required in cases suspected to have meningeal complications of plague.  In the United States, reporting of suspicious cases and sending collected material to specialized labs with expertise in Plague testing and to the State Health Department are mandatory procedures.

## Chest X-Ray
A chest x-ray is required in patients suspected to have plague, especially those with pneumonic plague. Findings on chest x-ray may reveal the true burden of pulmonary disease when there are minimal findings on auscultation during physical examination.

# Treatment

## Medical Therapy
When a diagnosis of human plague is suspected upon clinical and epidemiological grounds, appropriate specimens for diagnosis should be obtained immediately and the patient should be started on specific antimicrobial therapy prior to a definitive answer from the laboratory. The drugs of choice are streptomycin or gentamicin, but tetracyclines, fluoroquinolones, and chloramphenicol are also effective.  The regimens should be adjusted depending on the patient's age, medical history, underlying health conditions, and allergies.  Upon evidence of pneumonia, suspect plague patients should be placed in isolation and managed under respiratory droplet precautions.

## Primary Prevention
The plague may be prevented by the administration of prophylactic therapy and implementation of hospital and public risk reduction measures. Post-exposure prophylaxis is indicated in persons with known exposure to plague, such as close contact with a pneumonic plague patient or direct contact with infected body fluids or tissues. There is a vaccine available for professionals who work in laboratories with the bacteria, or who study infected rodents.

## Cost-Effectiveness of Therapy
Without treatment, the plague can cause serious illness or death. With adequate antibiotic treatment the mortality rate is about 8-10%. Therefore the treatment of plague may be considered cost-effective.

## Future or Investigational Therapies
Current research aims to develop new and less invasive vaccines that protect from airborne infection of Yersinia pestis.