Lecture 8. anthrex, plague

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Lecture 8. anthrex, plague

  1. 1. Especially dangerous infections Sorokhan V.D., MD, PhD Bukovinian State Medical University Department of infectious diseases and epidemiology
  2. 2. Definition <ul><li>Anthrax is an acute disease caused by the bacteria Bacillus anthracis . The name 'anthrax' comes from the Greek word for 'coal', because of the black skin lesions developed by victims with a cutaneous anthrax infection . Anthrax is one of the oldest diseases of grazing animals such as sheep and cattle. Anthrax is mentioned by Homer , and Hippocrates . </li></ul>
  3. 3. Definition <ul><li>Bacillus anthracis can form spores that are able to survive in harsh conditions for extremely long periods of time-even decades or centuries. Such spores can be found on all continents. When spores are inhaled, ingested, or come into contact with a skin lesion on a host they may reactivate and multiply rapidly. </li></ul>
  4. 4. History <ul><li>Until the twentieth century, anthrax infections killed hundreds and thousands of animals and people each year in Europe, Asia, Africa, and Australia. Infection of humans can result from contact with infected animal hides, wool, leather or contaminated soil. Anthrax is now fairly rare in humans, although it still regularly occurs in cattle , sheep , and goats . </li></ul>
  5. 5. Etiology <ul><li>Bacillus anthracis is a rod-shaped, Gram-positive , aerobic bacterium, about 1 by 9 micrometers in size and is usually straight but may be slightly curved. The ends of the bacilli are truncated, not rounded. </li></ul>Gram-positive anthrax bacteria (purple rods) in cerebrospinal fluid sample. If present, a Gram-negative bacterial species would appear pink. (The other cells are white blood cells ).
  6. 6. <ul><li>Anthrax bacilli tend to form into long chains. B. anthracis produces a capsule that is easily visualized using a methylene blue . </li></ul>Polychrome methylene blue stain of Bacillus anthracis. Image courtesy of Anthrax Vaccine Immunization Program Agency, Office of the Army Surgeon General, United States. Etiology
  7. 7. Epidemiology <ul><li>Occupational exposure to infected animals or their products (such as skin, wool, and meat) is the usual pathway of exposure for humans. Workers who are exposed to dead animals and animal products are at the highest risk, especially in countries where anthrax is more common. Many workers who deal with wool and animal hides are routinely exposed to low levels of anthrax spores but most exposures are not sufficient to develop anthrax infections. Presumably, the body's natural defenses can destroy low levels of exposure. These people usually contract cutaneous anthrax if they catch anything. </li></ul>
  8. 8. Epidemiology <ul><li>Anthrax can enter the human body through the intestines (ingestion) , lungs (inhalation) , or skin (cutaneous) and causes distinct clinical symptoms based on its site of entry. Occupational exposure to infected animals or their products (such as skin, wool, and meat) is the usual pathway of exposure for humans. Workers who are exposed to dead animals and animal products are at the highest risk, especially in countries where anthrax is more common. </li></ul>
  9. 9. Pathophysiology <ul><li>Anthrax is primarily a disease of cattle, sheep, goats, and horses. In cutaneous anthrax, a malignant pustule develops at the infection site. This pustule is a central area of coagulation necrosis (ulcer) surrounded by a rim of vesicles filled with bloody or clear fluid. A black eschar forms at the ulcer site. Extensive edema surrounds the lesion. </li></ul>
  10. 10. Pathophysiology <ul><li>The organisms multiply locally and may spread to the bloodstream or other organs (eg, spleen) via the efferent lymphatics. Dissemination from the liver, spleen, and kidneys back into the bloodstream may result in bacteremia. In bacteremic anthrax, hemorrhagic lesions may develop anywhere on the body. Bacteremic anthrax with hematogenous spread most commonly follows inhalation anthrax. </li></ul>
  11. 11. Pathology B . anthracis remains in the capillaries of invaded organs, and the local and fatal effects of the infection are due, in large part, to the toxins elaborated by B . anthracis. Histopathology of mediastinal lymph node showing mediastinal necrosis. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
  12. 12. Pathology Histopathology of mediastinal lymph node showing a microcolony of Bacillus anthracis on Giemsa stain. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia. Anthrax in the spore stage can exist indefinitely in the environment. Optimal growth conditions result in a vegetative phase and bacterial multiplication. Secondary hemorrhagic intestinal foci of anthrax result from B . anthracis bacteremia.
  13. 13. Pathology Primary intestinal anthrax predominantly affects the cecum and produces a local lesion similar to the lesion produced in the cutaneous form. Oropharyngeal anthrax is a variant of intestinal anthrax and occurs in the oropharynx after ingesting meat products contaminated by anthrax. Histopathology of large intestine showing marked hemorrhage in the mucosa and submucosa. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
  14. 14. Pathology Histopathology of the large intestine showing submucosal thrombosis and edema. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia. Inhalation anthrax occurs after inhaling spores into the lungs. Spores are ingested by alveolar macrophages and are carried to the mediastinal lymph nodes. Anthrax in the lungs does not cause pneumonia , but it does cause hemorrhagic mediastinitis and pulmonary edema. Hemorrhagic pleural effusions frequently accompany inhalation anthrax.
  15. 15. Clinic <ul><li>Cutaneous anthrax develops 1-7 days (usually 2-5) after skin exposure and penetration of B. anthracis spores. </li></ul>Anthrax skin lesion Cutaneous anthrax
  16. 16. Clinic <ul><li>Note the black eschar. </li></ul><ul><li>Courtesy of American Academy of Dermatology. </li></ul><ul><li>Courtesy of Gorgas Course in Clinical Tropical Medicine. </li></ul><ul><li>This form most commonly affects the exposed areas of the upper extremities and, to a lesser extent, the head and neck. </li></ul>
  17. 17. Clinic <ul><li>Hematogenous dissemination occurs in 5-10% of untreated cases. </li></ul>Seven-month-old infant with anthrax.
  18. 18. Clinic <ul><li>Cutaneous anthrax begins as a pruritic papule that enlarges within 24-48 hours to form an ulcer surrounded by a satellite bulbus/lesion edematous halo. </li></ul>Skin lesions of anthrax on neck. Image courtesy of the Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
  19. 19. Clinic <ul><li>The cutaneous anthrax lesion is usually approximately 2-3 cm in diameter and has a round, regular, and raised edge. </li></ul>Note the hemorrhage that is associated with cutaneous anthrax lesions. The early ulcer has a moist base. Courtesy of American Academy of Dermatology.
  20. 20. Clinic <ul><li>Regional lymphadenopathy of the nodes draining the infected area may occur. The cutaneous anthrax ulcer is characteristically pruritic but not painful. </li></ul>Note the central ulcer and eschar. Courtesy of American Academy of Dermatology.
  21. 21. Clinic Cutaneous anthrax. Image courtesy of Anthrax Vaccine Immunization Program Agency, Office of the Army Surgeon General, United States. The membrane or exudate of the ulcer contains numerous anthrax bacilli.
  22. 22. Clinic <ul><li>Anthrax with facial edema. </li></ul><ul><li>Courtesy of American Academy of Dermatology. </li></ul>The anthrax ulcer and surrounding edema evolve into a black eschar within 7-10 days and last for 7-14 days before separating and leaving a permanent scar.
  23. 23. Clinic <ul><li>The edema surrounding the ulcer may persist through the eschar stage. </li></ul>An example of a central ulcer and eschar with surrounding edema. Courtesy of American Academy of Dermatology with permission from Boni Elewski, MD.
  24. 24. Clinic <ul><li>Lymphadenopathy associated with cutaneous anthrax may persist long after disappearance of the ulcer/eschar. </li></ul>Skin lesion of anthrax on face. Image courtesy of the Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
  25. 25. Clinic <ul><li>If the lesions of cutaneous anthrax affect the neck, neck swelling due to edema and enlarged cervical lymph nodes may impinge on the trachea and cause stridor and respiratory distress and, if severe, may be accompanied by asphyxiation. </li></ul>Fourth patient with cutaneous anthrax in New York City, October 2001. This dry ulcer was present. Photo used with permission of the patient. Courtesy of American Academy of Dermatology. Courtesy of Sharon Balter of the New York City Department of Health.
  26. 26. Clinic <ul><li>Inhalation anthrax begins abruptly, usually 1-3 days (range, 1-60 d) after inhaling anthrax spores that are 1-5 µm in diameter. This form presents initially with nonspecific symptoms, including a low-grade fever and a nonproductive cough. </li></ul>Inhalational anthrax, mediastinal widening Inhalation anthrax
  27. 27. Clinic <ul><li>The appearance on chest radiograph or CT scan may suggest the diagnosis, especially if other predisposing disorders that might result in a widening mediastinum (eg, dissecting aortic aneurysm, bacterial mediastinitis) are absent. </li></ul>Chest radiograph showing widened mediastinum resulting from inhalation anthrax. Image courtesy of P.S. Brachman, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
  28. 28. Clinic <ul><li>Intestinal anthrax </li></ul><ul><ul><li>Ingesting B. anthracis spores may cause intestinal anthrax 2-5 days following ingestion. </li></ul></ul><ul><ul><li>Patients with intestinal anthrax report nausea, vomiting, malaise, anorexia, abdominal pain, hematemesis, and bloody diarrhea, which are accompanied by fever. </li></ul></ul><ul><ul><li>Patients with intestinal anthrax may have severe abdominal pain, hematemesis, and/or bloody diarrhea. </li></ul></ul><ul><ul><li>Multiple anthrax ulcerative lesions are found throughout the GI tract secondary to hematogenous spread. </li></ul></ul>
  29. 29. Differential Diagnoses <ul><li>Cutaneous anthrax </li></ul><ul><li>Physicians must differentiate cutaneous anthrax from : </li></ul><ul><li>bubonic plague </li></ul><ul><li>tularemia </li></ul><ul><li>primary syphilis </li></ul><ul><li>community-acquired pneumonia </li></ul><ul><li>b acterial mediastinitis </li></ul><ul><li>dysentery </li></ul>
  30. 30. Laboratory Studies <ul><li>The preferred diagnostic procedure for cutaneous anthrax is staining the ulcer exudate with methylene blue or Giemsa stain. </li></ul><ul><li>In patients with cutaneous anthrax who have fever and systemic symptoms that suggest extracutaneous spread, blood culture may be indicated. </li></ul><ul><li>The diagnosis of cutaneous anthrax is usually suggested by the characteristic appearance of skin lesions. </li></ul>
  31. 31. Treatment <ul><li>The preferred agent used to treat nonbioterrorist anthrax is penicillin. Penicillin is the preferred agent to treat inhalational anthrax and anthrax meningitis. Use meningeal doses for inhalational anthrax because meningitis is often also present. </li></ul><ul><li>For bioterrorist anthrax, use doxycycline for 1-2 weeks. </li></ul>
  32. 32. Treatment <ul><li>Penicillin: 4 million U IV q4h </li></ul><ul><li>Doxycycline: 100 mg PO/IV q12h for 60 d </li></ul><ul><li>Amoxicillin : 500 mg PO q8h </li></ul><ul><li>Ampicillin : 2 g IV q4h </li></ul><ul><li>Ciprofloxacin:500 mg PO q12h for 60 d </li></ul><ul><li>Levofloxacin:500 mg PO/IV q24h for 60 d </li></ul>
  33. 33. Complications <ul><li>Patients with cutaneous anthrax have a persistent circular scar at the point of eschar formation. </li></ul><ul><li>Patients with inhalation, oropharyngeal, or cutaneous (neck) anthrax may develop an airway obstruction. </li></ul><ul><li>Patients with septicemic anthrax may develop overwhelming toxicity or shock. </li></ul><ul><li>Patients with inhalation anthrax also often develop hemorrhagic leptomeningitis. </li></ul>
  34. 34. Plague
  35. 35. Definition <ul><li>Plague is an acute, contagious, febrile illness transmitted to humans by the bite of an infected rat flea. The cause is the plague bacillus, a rod-shaped bacteria referred to as Yersinia pestis. Yersinia is named in honor of Alexander Yersin, who successfully isolated the bacteria in 1894 during the pandemic that began in China in the 1860s. </li></ul>
  36. 36. History <ul><li>Plague has caused large-scale epidemics, thereby changing the course of history in many nations. The first pandemic was believed to have started in Africa and killed 100 million people over a span of 60 years. In the Middle Ages, plague killed approximately one fourth of Europe's population. The pandemic that began in China in the 1860s spread to Hong Kong in the 1890s and was subsequently spread to Africa, Asia, and South America. In the early twentieth century, plague epidemics accounted for about 10 million deaths in India. </li></ul>
  37. 37. Etiology <ul><li>Y . pestis is a nonmotile, non - spore-forming, pleomorphic, gram-negative coccobacillus. The bacteria elaborate a lipopolysaccharide endotoxin, coagulase, and a fibrinolysin, which are the principal factors in the pathogenesis of this disease. </li></ul>Wayson stain showing the characteristic &quot;safety pin&quot; appearance of Yersinia pestis, the plague bacillus. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
  38. 38. Epidemiology <ul><li>Domestic and urban rats are the most important reservoirs for the plague bacillus, but field mice, cats, camels, prairie dogs, rabbits, and squirrels can be important animal reservoirs as well. </li></ul>The prairie dog is a burrowing rodent of the genus Cynomys. It can harbor fleas infected with Yersinia pestis, the plague bacillus. Image courtesy of the Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
  39. 39. Epidemiology <ul><li>The most important vector for transmission of plague is the rat flea, Xenopsylla cheopis . Ticks and human lice have been identified as possible vectors. Humans are accidental hosts in the natural cycle of this disease. </li></ul><ul><li>Human-to-human transmission is rare except during epidemics of pneumonic plague. </li></ul>Oriental rat flea ( Xenopsylla cheopis ), the primary vector of plague, engorged with blood. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
  40. 40. Epidemiology <ul><li>Risk factors </li></ul><ul><li>Flea bite </li></ul><ul><li>Contact with a patient or a potential host </li></ul><ul><li>Contact with sick animals or rodents </li></ul><ul><li>Residence in an endemic area of plague </li></ul><ul><li>Presence of a food source for rodents in the immediate vicinity of the home </li></ul><ul><li>Camping, hiking, hunting, or fishing </li></ul><ul><li>Occupational exposure </li></ul><ul><li>Direct handling or inhalation of contaminated tissue or tissue fluids </li></ul>
  41. 41. Epidemiology <ul><li>Plague is worldwide in distribution, with most of the human cases reported from developing countries. </li></ul>1998 world distribution of plague. Image courtesy of the Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
  42. 42. Pathophysiology <ul><li>When a rat flea ingests a blood meal from an animal infected with Y . pestis, the coagulase of the bacteria causes the blood to clot. The bacilli multiply in the blood clot, and the flea inoculates thousands of these bacilli into a host's skin during subsequent blood meals. The bacilli migrate to the regional lymph nodes, are phagocytosed by the polymorphonuclear cells and mononuclear phagocytes, and multiply intracellularly. Involved lymph nodes show dense concentrations of plague bacilli, destruction of the normal architecture, and medullary necrosis. With subsequent lysis of the phagocytes, bacteremia can occur and may lead to invasion of distant organs in the absence of specific therapy. </li></ul>
  43. 43. Pathology <ul><li>Histopathology of lung in fatal human plague -fibrinopurulent pneumonia. </li></ul><ul><li>Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga. </li></ul>
  44. 44. Pathology <ul><li>Histopathology of lung showing pneumonia with many Yersinia pestis organisms (the plague bacillus) on a Giemsa stain. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga. </li></ul>
  45. 45. Pathology <ul><li>Histopathology of spleen in fatal human plague. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga. </li></ul>
  46. 46. Pathology <ul><li>Histopathology of lymph node showing medullary necrosis and Yersinia pestis, the plague bacillus. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga. </li></ul>
  47. 47. Pathology <ul><li>Histopathology of liver in fatal human plague. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga. </li></ul>
  48. 48. Pathology <ul><li>Focal hemorrhages in pancreas in fatal human plague. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga. </li></ul>
  49. 49. Clinical <ul><li>Bubonic plague </li></ul><ul><li>This is the most common presentation of plague. </li></ul><ul><li>The incubation period varies but usually ranges 2-6 days. </li></ul><ul><li>There is a sudden onset of high fever, chills, and headache. </li></ul>Swollen lymph glands, termed buboes, are a hallmark finding in bubonic plague. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
  50. 50. Clinical <ul><li>Bubonic plague </li></ul><ul><li>Patients with this type also experience body aches, weakness, abdominal pain, and/or diarrhea. </li></ul><ul><li>Painful, swollen lymph glands (buboes) arise, usually in the groin (most common site), axilla, or neck. </li></ul>Acral necrosis of the nose, the lips, and the fingers
  51. 51. Clinical <ul><li>Axillary, and cervical buboes are almost always seen in cat-associated plague. </li></ul><ul><li>Without intervention, this stage may lead to secondary pneumonic plague or meningitis or may disseminate and manifest as a sepsis picture. </li></ul>Acral necrosis of the toes
  52. 52. Clinical <ul><li>Meningeal plague is characterized by fever, headache, and nuchal rigidity. </li></ul><ul><li>Buboes are common in meningeal plague. </li></ul><ul><li>Axillary buboes are associated with an increased incidence of the meningeal form. </li></ul>Erythematous, eroded, crusting, necrotic ulcer at the primary inoculation site
  53. 53. Clinical <ul><li>Pharyngeal plague results from ingestion of the plague bacilli. </li></ul><ul><li>Patients experience sore throat, fever, and painful cervical lymph nodes. </li></ul>Ecchymoses at the base of the neck in a girl with plague. The bandage is over the site of a prior bubo aspirate. These lesions are probably the source of the line from the children's nursery rhyme, &quot;ring around the rosy.&quot; Courtesy of Jack Poland, PhD, Centers for Disease Control and Prevention (CDC), Fort Collins, Colo.
  54. 54. Pneumonic plague <ul><li>Pneumonic plague is highly contagious and transmitted by aerosol droplets. </li></ul><ul><li>This is often secondary to bubonic or septicemic plague. However, primary pneumonic plague may be seen in laboratory workers, individuals exposed to an infected person, or those who have been exposed to a cat with pneumonic plague. </li></ul><ul><li>There is an abrupt onset of fever and chills, accompanied by cough, chest pain, dyspnea, purulent sputum, or hemoptysis. </li></ul><ul><li>Buboes may or may not be associated with pneumonic plague. </li></ul><ul><li>The ability for plague to be spread by aerosols makes Y . pestis a potential agent of bioterrorism. </li></ul>
  55. 55. Septicemic plague <ul><li>Septicemic plague is observed in elderly patients and causes a rapid onset of symptoms. </li></ul><ul><li>Patients experience nausea, vomiting, abdominal pain, and diarrhea. </li></ul><ul><li>Patients exhibit a toxic appearance. </li></ul><ul><li>Buboes are uncommon in septicemic plague. </li></ul><ul><li>Septicemic plague carries a high mortality rate and is associated with disseminated intravascular coagulation (DIC), multiorgan failure, and profound hypotension. </li></ul><ul><li>Plague initially occurred as a flea-borne septicemic disease. However, over its evolutionary course, it acquired the plasminogen activator gene, giving rise to the bubonic form of disease. </li></ul>
  56. 56. Differential Diagnoses <ul><li>Acute Renal Failure </li></ul><ul><li>Bacterial Pharyngitis </li></ul><ul><li>Anthrax </li></ul><ul><li>Bacterial Pneumonia </li></ul><ul><li>Brucellosis </li></ul><ul><li>Catscratch Disease </li></ul><ul><li>Rocky Mountain Spotted Fever </li></ul><ul><li>Cellulitis </li></ul><ul><li>Bacterial Sepsis </li></ul><ul><li>Disseminated Intravascular Coagulation </li></ul><ul><li>Systemic Inflammatory Response Syndrome </li></ul><ul><li>Tularemia </li></ul><ul><li>B-Cell l ymphoma </li></ul><ul><li>Typhus </li></ul><ul><li>Malaria </li></ul><ul><li>Septic Shock </li></ul>
  57. 57. Laboratory Studies <ul><li>Blood culture results are often positive for </li></ul><ul><li>Y . pestis in patients with bubonic plague and septicemic plague. Y . pestis may be observed on a peripheral blood smear. </li></ul><ul><li>Lymph node aspirates often demonstrate </li></ul><ul><li>Y . pestis . In patients with pharyngeal plague, Y . pestis is cultured from throat swabs. </li></ul><ul><li>Gram stain of sputum often reveals </li></ul><ul><li>Y . pestis . </li></ul>
  58. 58. Other Tests <ul><li>Direct immunofluorescence testing of fluid or cultures may aid in rapid diagnosis. </li></ul><ul><li>A passive hemagglutination test (performed on serum from a patient in acute or convalescent stages) with a 4-fold or greater increase in titer suggests plague infection. </li></ul>
  59. 59. Treatment <ul><li>Streptomycin sulfate – Dosing : 1 g IV/IM q12h for 7-14 d or continue for 5-7 d once patient is afebrile; not to exceed 2 g/d . </li></ul><ul><li>Gentamicin – Dosing : 2 mg/kg IV loading dose with normal renal function; then, 1.7 mg/kg IV q8h for 10 d . </li></ul><ul><li>Doxycycline – Dosing : 100 mg PO/IV q12h . </li></ul><ul><li>Chloramphenicol - Dosing : 500 mg PO/IV q6h . </li></ul>
  60. 60. Complications <ul><li>Acute respiratory distress syndrome </li></ul><ul><li>Chronic lymphedema from lymphatic scarring </li></ul><ul><li>Disseminated intravascular coagulation </li></ul><ul><li>Septic shock </li></ul><ul><li>Superinfections of the buboes by Staphylococcus and Pseudomonas species </li></ul>
  61. 61. Prognosis <ul><li>Untreated patients with plague have a mortality rate of approximately 50%; however, with appropriate therapy, the mortality rate drops to approximately 5%. </li></ul>
  62. 62. Thank you for your attention!

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