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Yersinia pestis/Plague

The plague is a bacterial infection caused by Yersinia Yersinia Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. Yersinia spp./Yersiniosis pestis (Y. pestis), which primarily infects rodents. The disease is transmitted to humans via a fleabite. Inhalation of infectious Infectious Febrile Infant droplets Droplets Varicella-Zoster Virus/Chickenpox and handling infected animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic or laboratory specimens are other means of transmission. The plague has 3 forms: bubonic (most common form), septicemic, and pneumonic. Bubonic plague results in swollen and tender lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy called buboes Buboes Chancroid in the inguinal area Inguinal area The external junctural region between the lower part of the abdomen and the thigh. Male Genitourinary Examination. Pneumonic and septicemic plague can arise as the primary presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor, but also can result from hematogenous Hematogenous Hepatocellular Carcinoma (HCC) and Liver Metastases spread from the bubonic disease. Diagnosis includes clinical history and findings, culture, polymerase chain reaction Polymerase chain reaction Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) ( PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR)), and serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus. The mortality rate Mortality rate Calculated as the ratio of the total number of people who die due to all causes over a specific time period to the total number of people in the selected population. Measures of Health Status is high, so prompt diagnosis and treatment with antibiotics are necessary.

Last updated: 14 Jan, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

General Characteristics

Basic features of Yersinia Yersinia Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. Yersinia spp./Yersiniosis pestis

Clinically relevant species and diseases

  • Associated species: Enteropathogenic Yersinia Yersinia Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. Yersinia spp./Yersiniosis cause yersiniosis Yersiniosis Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. Yersinia spp./Yersiniosis (discussed separately).
  • Associated disease: plague (“Black Death”)
    • Yersinia Yersinia Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. Yersinia spp./Yersiniosis pestis (Y. pestis) predominantly cause disease in rodents; humans are usually incidental hosts.
    • Forms:
      • Bubonic plague (most common)
      • Pulmonic plague
      • Septicemic plague

Epidemiology

Worldwide cases of the plague:

  • Majority of cases are from Africa.
  • Countries with the most prevalent cases:
    • Democratic Republic of the Congo
    • Madagascar
    • Peru
World plague map 2009

World map of plague cases reported to the World Health Organization (WHO), 2000–2009

Image: “World Plague Map – 2000 to 2009 – CDC” by the CDC. License: Public domain.

Plague in the United States:

  • Locations:
    • “4 Corners” (the junction point of New Mexico, Arizona, Colorado, and Utah)
    • West: California, southern Oregon, and western Nevada
  • Period with the most cases: May to October (People are outdoors, and rodents are plenty.)

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Pathogenesis

Reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli and transmission

  • Plague: zoonotic infection Zoonotic infection Diseases of non-human animals that may be transmitted to humans or may be transmitted from humans to non-human animals. Brucella/Brucellosis
  • Reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli: rodents, prairie dogs
  • Transmission: 
    • In areas with poor sanitary conditions and infestations of rats, the infection is acquired by a fleabite (the most common route). 
    • Handling of living or dead mammals 
    • Post-mortem examination of an infected body or laboratory handling of a specimen
    • Inhalation of infectious Infectious Febrile Infant droplets Droplets Varicella-Zoster Virus/Chickenpox (such as in bioterrorism Bioterrorism The use of biological agents in terrorism. This includes the malevolent use of bacteria; viruses; or other biological toxins against people, animals; or plants. Anthrax) can cause pneumonic plague.
  • Vector: Xenopsylla cheopis (the Oriental rat flea, the most efficient flea vector):
    • Y. pestis multiplies in the flea’s midgut Midgut Development of the Abdominal Organs after ingestion of a blood meal. 
    • Yersinia Yersinia Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. Yersinia spp./Yersiniosis aggregates can block the flea’s intestine.
    • The flea then regurgitates the bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology into the bite wound with each feeding.
    • In some cases, bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology are transmitted right after feeding on an infected host.

Virulence factors Virulence factors Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: toxins, biological and surface adhesion molecules that affect the ability of the microorganism to invade and colonize a host. Haemophilus

  • Lipopolysaccharide endotoxin Lipopolysaccharide endotoxin Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: Lipid A, core polysaccharide, and O-specific chains (O antigens). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. Yersinia spp./Yersiniosis: leads to systemic toxicity Toxicity Dosage Calculation in bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides
  • Type III secretion Secretion Coagulation Studies system: 
  • High-pathogenicity island High-pathogenicity island Yersinia spp./Yersiniosis (HPI)
    • Encodes for an iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements-scavenging siderophore, yersiniabactin Yersiniabactin Yersinia spp./Yersiniosis
    • Yersiniabactin Yersiniabactin Yersinia spp./Yersiniosis provides the bacterium the ability to take iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements molecules needed for growth and dissemination.
  • Virulence Virulence The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its virulence factors. Proteus regulation by temperature and calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes
    • Expression of Yersinia Yersinia Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. Yersinia spp./Yersiniosis virulence factors Virulence factors Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: toxins, biological and surface adhesion molecules that affect the ability of the microorganism to invade and colonize a host. Haemophilus is affected by temperature and free calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes
    • Physiologically, the mammalian host temperature is different from that of an insect.
    • Likewise, the calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes concentration is different in intracellular fluid Intracellular fluid The fluid inside cells. Body Fluid Compartments than in extracellular fluids. 
    • Yersinia Yersinia Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. Yersinia spp./Yersiniosis: able to adjust virulence factors Virulence factors Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: toxins, biological and surface adhesion molecules that affect the ability of the microorganism to invade and colonize a host. Haemophilus based on the above actions, with the life cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation continuing in the environment or host
  • Y. pestis:
    • pPCP1 (or pPst): plasmid with genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure for enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes with protease Protease Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene. HIV Infection and AIDS, coagulase Coagulase Enzymes that cause coagulation in plasma by forming a complex with human prothrombin. Coagulases are produced by certain staphylococcus and yersinia pestis. Staphylococci produce two types of coagulase: staphylocoagulase, a free coagulase that produces true clotting of plasma, and staphylococcal clumping factor, a bound coagulase in the cell wall that induces clumping of cells in the presence of fibrinogen. Staphylococcus, and fibrinolytic activity
    • pFra/pMT: encodes Fraction 1 capsular protein (has antiphagocytic function) and phospholipase D (facilitates survival in the flea’s midgut Midgut Development of the Abdominal Organs)

Disease process

Bubonic plague:

  • When a flea bites a human and contaminates the wound with regurgitated blood, the bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology are passed into the tissue.
  • Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology enter the dermal lymphatic system Lymphatic system A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs.
  • Subsequent effects of the infection: 
  • Lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy get overwhelmed and the infection passes to the bloodstream.

Pneumonic plague:

  • Arises from inhalation of highly contagious infected droplets Droplets Varicella-Zoster Virus/Chickenpox
  • Can result from hematogenous Hematogenous Hepatocellular Carcinoma (HCC) and Liver Metastases spread of bubonic plague
  • Rapidly progressive pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia with bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology prominent in the air spaces (segmental → lobar → bilateral lung involvement)

Septicemic plague:

  • Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology replicate in the bloodstream, spreading to other organs.
  • Travel to the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy produces secondary plague pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia. (Initially, the bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology are more prominent in the interstitium than in the air spaces.) 
  • Infection of the meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy ( meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis) and gastrointestinal tract can occur.
  • Progresses to:
    • Bacterial endotoxic shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock
    • Disseminated intravascular coagulation Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation ( DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation): clotting cascade, thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus with eventual bleeding from depletion of the clotting factors and platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology 
    • Ischemic necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage from poor perfusion 
    • Death
Transmission of y. Pestis

The transmission of Yersinia Yersinia Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. Yersinia spp./Yersiniosis pestis
Direct contact with rodents or flea bites give rise to bubonic plague while airborne transmission (human-to-human), either by coughing or sneezing Sneezing The sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. Rhinovirus, gives rise to pneumonic plague.

Image by Lecturio.

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Clinical Presentation

Bubonic plague

Plague buboes

Bubonic plague: swollen inguinal lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy on a person infected with the bubonic plague

Image: “Plague buboes Buboes Chancroid” by the CDC. License: Public domain.

Pneumonic plague

  • In primary plague pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia, symptoms start within 2–3 days of exposure Exposure ABCDE Assessment.
  • The initial signs are indistinguishable from several other respiratory illnesses: 
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
    • Weakness
  • After 24 hours, cough, hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis, and shortness of breath Shortness of breath Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea follow. 

Septicemic plague

  • The initial presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor in a minority of cases: septic shock Septic shock Sepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status. Sepsis and Septic Shock without lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy/bubo
  • Risk factors for septicemia (for all Yersinia Yersinia Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. Yersinia spp./Yersiniosis spp.):
    • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus
    • Iron overload Iron overload An excessive accumulation of iron in the body due to a greater than normal absorption of iron from the gastrointestinal tract or from parenteral injection. This may arise from idiopathic hemochromatosis, excessive iron intake, chronic alcoholism, certain types of refractory anemia, or transfusional hemosiderosis. Hereditary Hemochromatosis or hemochromatosis Hemochromatosis A disorder of iron metabolism characterized by a triad of hemosiderosis; liver cirrhosis; and diabetes mellitus. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. Hereditary Hemochromatosis
  • Hemorrhage occurs in other organs, with tissue vasculature occluded by thrombi:
    • Purpuric lesions
    • Hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis/ hematemesis Hematemesis Vomiting of blood that is either fresh bright red, or older ‘coffee-ground’ in character. It generally indicates bleeding of the upper gastrointestinal tract. Mallory-Weiss Syndrome (Mallory-Weiss Tear) 
    • Gangrene Gangrene Death and putrefaction of tissue usually due to a loss of blood supply. Small Bowel Obstruction in ears, fingers, and toes
  • Difficult to diagnose, especially in a sporadic Sporadic Selective IgA Deficiency presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor without bubo

Diagnosis

Diagnostic tools

  • Clinical history and findings:
    • Travel to endemic areas
    • Animal contact
    • Occupational exposure
    • Suggestive symptoms and examination
  • Smear and culture:
    • Specimens:
      • Buboes: needle aspiration of affected lymph node(s)
      • Lungs: sputum, bronchial/tracheal aspirate 
      • Blood
      • Cerebrospinal fluid
    • Bipolar staining (“safety pin” shape) in Wright’s, Giemsa’s, or Wayson’s stains 
    • Fluorescent antibody stains targeting the capsular F1 antigen Capsular F1 antigen Yersinia spp./Yersiniosis
    • Specimen cultured in blood agar Blood agar Nocardia/Nocardiosis, MacConkey agar MacConkey agar Yersinia spp./Yersiniosis plates, and brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification–heart infusion broth
    • Yersinia Yersinia Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. Yersinia spp./Yersiniosis-specific culture medium: cefsulodin Cefsulodin A pyridinium-substituted semisynthetic, broad-spectrum antibacterial used especially for pseudomonas infections in debilitated patients. Yersinia spp./Yersiniosis, irgasan Irgasan Yersinia spp./Yersiniosis, and novobiocin ( CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer) agar
  • Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus: A titer of > 1:16 is suggestive of the plague.
  • Specific polymerase chain reaction Polymerase chain reaction Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) ( PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR))
Yersinia pestis fluorescent

Yersinia Yersinia Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. Yersinia spp./Yersiniosis pestis: under microscopy, dyed with fluorescent stain

Image: “ Yersinia Yersinia Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. Yersinia spp./Yersiniosis pestis fluorescent” by the CDC/Courtesy of Larry Stauffer, Oregon State Public Health Laboratory. License: Public domain.

Additional tests

  • Laboratory tests:
    • Complete blood count: may show leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus with left shift; in some, may have leukopenia; thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia in DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation
    • Metabolic panel: Multi-organ involvement may show renal and hepatic function abnormalities.
    • Elevated fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis degradation products and prolonged prothrombin Prothrombin A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Hemostasis times in septicemia
  • Imaging studies: chest X-ray Chest X-ray X-ray visualization of the chest and organs of the thoracic cavity. It is not restricted to visualization of the lungs. Pulmonary Function Tests in pneumonic plague
Chest x-ray pneumonic plague

A patient with pneumonic plague
A chest X-ray Chest X-ray X-ray visualization of the chest and organs of the thoracic cavity. It is not restricted to visualization of the lungs. Pulmonary Function Tests shows increased pulmonary markings, with thick interlobar pleura Pleura The pleura is a serous membrane that lines the walls of the thoracic cavity and the surface of the lungs. This structure of mesodermal origin covers both lungs, the mediastinum, the thoracic surface of the diaphragm, and the inner part of the thoracic cage. The pleura is divided into a visceral pleura and parietal pleura. Pleura: Anatomy in a patient who presented with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, cough, and dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea after exposure Exposure ABCDE Assessment to a herding dog.

Image: “PMC4759734_12879_2016_1403_Fig2_HTML” by Li YF, Li DB, Shao HS HS Hypertrophic scars and keloids are raised, red, and rigid (3 rs) scars that develop during cutaneous wound healing and are characterized by a local abnormal proliferation of fibroblasts with over-production of collagen. Over-expression of growth factors and decreased production of molecules that promote matrix breakdown appear to be involved in the etiology. Hypertrophic and Keloid Scars, Li HJ, Han YD. License: CC BY 4.0.

Management

Treatment

  • High mortality rate Mortality rate Calculated as the ratio of the total number of people who die due to all causes over a specific time period to the total number of people in the selected population. Measures of Health Status with delay of or without treatment
  • Antibiotics: aminoglycosides Aminoglycosides Aminoglycosides are a class of antibiotics including gentamicin, tobramycin, amikacin, neomycin, plazomicin, and streptomycin. The class binds the 30S ribosomal subunit to inhibit bacterial protein synthesis. Unlike other medications with a similar mechanism of action, aminoglycosides are bactericidal. Aminoglycosides ( gentamicin Gentamicin Aminoglycosides)
  • Alternatives:
    • Doxycycline/ tetracycline Tetracycline A naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis. Drug-induced Liver Injury
    • Streptomycin (ototoxic and nephrotoxic; not widely available) 
    • Levofloxacin Levofloxacin The l-isomer of ofloxacin. Fluoroquinolones, moxifloxacin Moxifloxacin A fluoroquinolone that acts as an inhibitor of DNA topoisomerase II and is used as a broad-spectrum antibacterial agent. Fluoroquinolones, ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones
    • Chloramphenicol Chloramphenicol Chloramphenicol, the only clinically relevant drug in the amphenicol class, is a potent inhibitor of bacterial protein synthesis by binding to the 50S ribosomal subunit and preventing peptide bond formation. Chloramphenicol is a broad-spectrum antibiotic with wide distribution; however, due to its toxicity, its use is limited to severe infections. Chloramphenicol
  • Droplet isolation of the infected patient (until pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia has been ruled out or > 48 hours of treatment)
  • Post- exposure Exposure ABCDE Assessment prophylaxis Prophylaxis Cephalosporins:
    • Exposure Exposure ABCDE Assessment to plague: close contact with a patient who has pneumonic plague or direct contact with infected tissue/fluids
    • Give doxycycline or levofloxacin Levofloxacin The l-isomer of ofloxacin. Fluoroquinolones
    • For pregnant women or children: Give trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim sulfamethoxazole Sulfamethoxazole A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. Sulfonamides and Trimethoprim.

Prevention

  • Vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination
    • Not available in the United States
    • Used in military personnel deployed in endemic areas
  • Use of proper personal protective equipment Personal protective equipment Specialized clothing or equipment worn for protection against health hazards. Personal protective equipment may include masks; respiratory protective devices; head protective devices; eye protective devices; ear protective devices; protective clothing; and protective footwear. Leptospira/Leptospirosis in high-risk occupations
  • Sanitation Sanitation The development and establishment of environmental conditions favorable to the health of the public. Hepatitis E Virus measures and rodent control
  • In outdoor activities: use of insect repellent Insect repellent Substances causing insects to turn away from them or reject them as food. St. Louis Encephalitis Virus, insecticide, and protective clothing

Differential Diagnosis

  • Anthrax Anthrax Anthrax is an infection caused by the bacterium Bacillus anthracis, which usually targets the skin, lungs, or intestines. Anthrax is a zoonotic disease and is usually transmitted to humans from animals or through animal products. Symptoms depend on which organ system is affected. Anthrax: an infection caused by Bacillus Bacillus Bacillus are aerobic, spore-forming, gram-positive bacilli. Two pathogenic species are Bacillus anthracis (B. anthracis) and B. cereus. Bacillus anthracis. Cutaneous anthrax Cutaneous anthrax Bacillus presents with small blisters that become ulcers with a black eschar. In inhalational anthrax Anthrax Anthrax is an infection caused by the bacterium Bacillus anthracis, which usually targets the skin, lungs, or intestines. Anthrax is a zoonotic disease and is usually transmitted to humans from animals or through animal products. Symptoms depend on which organ system is affected. Anthrax, chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain and dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea occur. Bloody diarrhea Bloody diarrhea Diarrhea, abdominal pain Abdominal Pain Acute Abdomen, and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia are noted in gastrointestinal anthrax Gastrointestinal anthrax Bacillus. History, PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR), and culture help with the diagnosis. Antimicrobial treatment and antitoxin are given for systemic anthrax Anthrax Anthrax is an infection caused by the bacterium Bacillus anthracis, which usually targets the skin, lungs, or intestines. Anthrax is a zoonotic disease and is usually transmitted to humans from animals or through animal products. Symptoms depend on which organ system is affected. Anthrax.
  • Cat scratch disease: an infection caused by Bartonella Bartonella Bartonella is a genus of gram-negative bacteria in the family Bartonellaceae. As a facultative intracellular parasite, Bartonella can infect healthy people as well as act as an opportunistic pathogen. Bartonella species are transmitted by vectors such as ticks, fleas, sandflies, and mosquitoes. B. henselae is the most common of the 3 species known to cause human disease. Bartonella henselae, a gram-negative bacillus Bacillus Bacillus are aerobic, spore-forming, gram-positive bacilli. Two pathogenic species are Bacillus anthracis (B. anthracis) and B. cereus. Bacillus. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship usually present with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, and tender lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy after being bitten or scratched by a cat. Symptomatic treatment is recommended, with azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides given for severe illness.
  • Tularemia: a rare infection caused by Francisella tularensis Francisella Tularensis Aminoglycosides acquired by contact with animal tissue, from ticks Ticks Blood-sucking acarid parasites of the order ixodida comprising two families: the softbacked ticks (argasidae) and hardbacked ticks (ixodidae). Ticks are larger than their relatives, the mites. They penetrate the skin of their host by means of highly specialized, hooked mouth parts and feed on its blood. Ticks attack all groups of terrestrial vertebrates. In humans they are responsible for many tick-borne diseases, including the transmission of rocky mountain spotted fever; tularemia; babesiosis; african swine fever; and relapsing fever. Coxiella/Q Fever, or from biting flies. Infection manifests as a papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes, followed by fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, and suppurative lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy. Tularemia may have multi-organ involvement. Diagnosis is by the culture of blood and infected tissue. Treatment is with antibiotics.
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia: an infection of the lung parenchyma most commonly caused by bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology (most common: Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pneumoniae) or viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology. Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia is community acquired (CAP) in 80% of the cases. Diagnosis is based on a clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor of fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, cough, dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, rales Rales Respiratory Syncytial Virus, and consolidation Consolidation Pulmonary Function Tests on chest X-ray Chest X-ray X-ray visualization of the chest and organs of the thoracic cavity. It is not restricted to visualization of the lungs. Pulmonary Function Tests. Atypical pneumonia Atypical pneumonia Mycoplasma may present with milder symptoms and less remarkable imaging. 

References

  1. Prentice, M.B. (2018). Plague and other yersinia infections. In Jameson J, et al. (Ed.)  Harrison’s Principles of Internal Medicine, 20th ed. McGraw-Hill.
  2. Stout, J., Sexton, D., & Bloom, A. (2020). Clinical manifestations, diagnosis, and treatment of plague (Yersinia pestis infection). UpToDate. Retrieved Jan 5, 2021, from https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-treatment-of-plague-yersinia-pestis-infection
  3. Stout, J., Sexton, D., & Bloom, A. (2020). Epidemiology, microbiology and pathogenesis of plague (Yersinia pestis infection). UpToDate. Retrieved Jan 6, 2021, from https://www.uptodate.com/contents/epidemiology-microbiology-and-pathogenesis-of-plague-yersinia-pestis-infection

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