Emerging Infections


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Emerging Infections and Bioterrorism Lecture

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Emerging Infections

  1. 1. Emerging Infections and Bioterrorism<br />Jeffrey Gehring, MD<br />Department of Emergency Medicine<br />February 12, 2009<br />
  2. 2. Goals and Objectives<br />Introduction of emerging and re-emerging infections<br />Introduction to potential agents of bioterrorism<br />
  3. 3. Emerging and Re-Emerging Infectious Diseases<br />Fall into one of three categories<br />1. Diseases that have not previously affected humans (SARS)<br />2. Diseases that occurred previously, but only affected a small number of people (Ebola)<br />3. Diseases that have occurred previously, but have only recently been determined to be caused by distinct infectious agents (Lyme disease)<br />Slaven, Stone, and Lopez. Infectious Diseases Emergency Department Diagnosis and Management. McGraw-Hill Companies, Inc., 2007<br />
  4. 4.
  5. 5. Severe Acute Respiratory Syndrome (SARS)<br />Previously unknown disease entity<br />Causative virus is a coronavirus: SARS coronavirus (SARS-CoV)<br />Coronaviridae is second most common cause of the common cold<br />First emerging infection of the 21st century<br />
  6. 6. SARS<br />“Near” Pandemic between November 2002 and July 2003<br />8,096 known infected cases with 774 deaths<br />9.6% fatality rate (as compared to annual influenza fatality rate of 0.6%)<br />Originated in Guandong province of China<br />Spread to 37 countries around the world<br />Epidemic controlled by July 5, 2003<br />
  7. 7. SARS<br />Pathophysiology<br />Spread by respiratory droplets<br />2-7 day asymptomatic incubation period<br />Incubation followed by 3-7 days of fever, malaise myalgia, headache, and anorexia (much like influenza)<br />Dry cough, SOB, progressive hypoxia and respiratory failure<br />Patients most contagious late in the illness course which accounts for high incidence of healthcare workers infected<br />
  8. 8. SARS<br />Diagnosis<br />History and physical exam suggestive of influenza or other respiratory tract infections (Non-specificity makes diagnosis difficult; reliance on trends)<br />Contact with someone diagnosed with SARS within 10 days<br />Travel to regions affected with SARS<br />Imaging<br />CXR abnormal in 60% of cases initially.<br />CXR, when abnormal, reveals patchy interstitial infiltrates<br />Lower lung fields affected preferentially as disease progresses<br />
  9. 9. SARS<br />Laboratory Testing<br />None available during acute illness<br />ELISA able to detect antibodies 21 days after illness<br />Treatment<br />Largely supportive<br />Isolation in negative pressure rooms<br />Complete barrier precautions<br />Quarantine<br />Anecdotal reports of effectiveness of ribavirin and steroids, but some research shows detrimental effects<br />Some feel most serious damage is caused by overreaction of the immune system<br />Chinese researchers have developed a vaccine that has been tested on 36 individuals with 24 showing immunity<br />
  10. 10. West Nile Virus<br />
  11. 11. West Nile Virus<br />First discovered in Uganda’s West Nile district in 1937<br />First outbreak in the United States started in New York in August, 1999<br />Belongs to the Flaviviridae family of viruses that also includes dengue fever virus<br />Mainly infects birds which are the reservoir<br />Disease spread to humans by mosquitoes (Primarily the Culex species)<br />In 2007 there were 3,630 cases with 124 deaths (Less than 4% fatality which is probably an overestimate because most cases are not severe)<br />Elderly and patients with history of organ transplantation are most at risk<br />
  12. 12. West Nile Virus<br />Three different effects on humans<br />Asymptomatic infection<br />West Nile Fever (mild febrile syndrome)<br />West Nile meningitis or encephalitis<br />Febrile stage <br />has incubation of 2-8 days followed by headache, fever/chills, and other “flu” like symptoms.<br />Resolution of symptoms in 7-10 days<br />West Nile Meningitis/Encephalitis<br />Signs and symptoms of meningitis or encephalitis<br />May present as flaccid paralysis with progressive limb weakness over 48hrs<br />
  13. 13. West Nile Virus<br />Diagnosis<br />CSF analysis<br />WNV – specific IgM antibodies detected with enzyme-immunoasay<br />Serum tests more useful if acute and convalescent samples taken<br />Treatment<br />Supportive<br />No vaccine available<br />Avoidance of mosquito bites<br />
  14. 14. Influenza<br />
  15. 15. Influenza<br />“It killed more people in twenty-four weeks than AIDS has killed in twenty-four years, more in a year than the Black Death killed in a century.” John M. Barry. The Great Influenza. Penguin Books, Ltd. 2005<br />Approximately a third of the population was infected in the 1918-1919 pandemic with estimated deaths between 50 and 100 million people<br />Fatality rate was greater than 2.5%<br />
  16. 16. Influenza<br />Caused by an RNA virus in the family Orthomyxoviridae<br />Two types: Influenza A and Influenza B<br />Influenza A subdivided based on two surface antigens<br />Hemagglutinin (H)<br />Neuraminidase (N)<br />The 1918 pandemic was caused by H1N1, and all subsequent pandemics are descendents of the H1N1 except for human infection caused by avian viruses such as H5N1<br />Reemerges each year due to anigenicdrift which is caused by point mutations during replication, whereas antigenic shift is a major change in the virus leading to novel hemagglutinin or neuraminidase proteins.<br />
  17. 17. Avian Influenza<br />Wild birds are the host of influenza A<br />January 2003: influenza A (H5N1) reported in Asian poultry<br />Greater than one million birds died or were killed due to the disease<br />Humans infected by this highly virulent strain, but humans not highly contagious at this time<br />Fear is of coinfectionwith an avian strain and a highly contagious human strain which could lead to genetic realignment<br />
  18. 18. Avian Influenza<br />Diagnosis <br />Symptoms show spectrum of typical influenza infection to acute respiratory distress<br />CXR nonspecific<br />Suspect in any person with contact with poultry or people in an affected region and a temperature greater than 38° C with cough, sore throat, or SOB<br />Nasopharyngeal swab for influenza A<br />Virus isolation only biosafety level 3+ facility<br />
  19. 19. Avian Influenza<br />Treatment<br />Supportive measures<br />Two classes of antivirals<br />M2 inhibitors (amantadine and rimandadine) H3N2 has shown 91% resistance in 2005. Always ineffective against influenza B<br />Neuraminidase inhibitors: Oseltamivir (Tamiflu) and zanamivir (Relenza) have been shown to be beneficial with no known resistance<br />
  20. 20. Bioterrorism<br />Characteristics of bioterrorism weapons<br />Mortality<br />Ease of dissemination<br />Transmissible<br />Ability to cause panic and social disruption<br />
  21. 21. Anthrax<br />
  22. 22. Anthrax<br />First disease with a definite microbial origin established by Robert Koch in 1876<br />First disease with a vaccine created by Louis Pasteur in 1881<br />Investigated as a biological weapon by 5 countries<br />Former Soviet Union is known to have created weaponized anthrax with antibiotic resistant strains<br />Used as biological weapon in October of 2001 when 22 cases of clinical anthrax were caused by contaminated mail<br />
  23. 23. Anthrax<br />Bacillus anthracis is an aerobic, gram-positive, non-motile spore former<br />Zoonosis which occurs in mammas such as sheep, goats, cattle, and horses<br />Infection is caused by endospores which enter the body through the skin/mucosa or through inhalation<br />Spores are infectious, but bacilli are not—so no known cases of human to human transmission<br />
  24. 24. Anthrax<br />Pathophysiology<br />Three routes of infection<br />Cutaneous<br />Inhalation<br />Gastrointestinal<br />95% of naturally occurring cases are cutaneous<br />Three factors are the leading causes of virulence<br />Edema toxin: calmodulin-dependent adenylatecyclase that leads to cell edema<br />Lethal toxin: zinc metalloprotease which inhibits cell and cytokine response and causes the release of TNF and IL-1B which leads to toxicity and sudden death<br />Capsule Production: inhibits phagocytosis of vegetative forms<br />
  25. 25. Anthrax<br />Cutaneous Anthrax<br />Incubation period of 3-5 days<br />Bacterial proliferation and toxin release cause local edema and necrosis<br />Begins a pruriticmacule or papule which ruptures causing a necrotic ulcer <br />Antibiotics don’t help with cutaneous manifestation, but help prevent systemic spread<br />20% mortality if left untreated, but death rare if treated<br />
  26. 26. Anthrax <br />Gastrointestinal Anthrax<br />Rare<br />Caused by ingestion of undercooked contaminated meat<br />Two forms: abdominal or oropharyngeal<br />Abdominal type: N/V, bloody diarrhea, abdominal pain, hematemesis, shock and death<br />Oropharyngeal: edema, lymphadenopathy, sepsis, death<br />
  27. 27. Anthrax<br />Inhalation Anthrax<br />“Wool sorters’ Disease”<br />Rapid onset of symptoms in 2-3 days post-exposure<br />Spores ingested by macrophages and carried to mediastinallymphnodes leading to hemorrhagic mediastinitis<br />Not considered true pneumonia<br />Biphasic clinical syndrome<br />Initial phase is a non-specific flu-like illness<br />Second phase represented by severe sepsis, MODS and death usually within 3 days<br />
  28. 28. Anthrax<br />Diagnosis<br />Clinical suspicion<br />Widened mediastinum on CXR (hemorrhagic mediastinitis), pleurual effusions <br />Gram stain of peripheral blood (Gram positive bacilli) or of vesicular fluid<br />CSF Gram stain and culture (Up to 50% of patients with inhalation anthrax will have meningitis)<br />
  29. 29. Anthrax<br />Treatment<br />Recognition<br />Early initiation of antibiotics: ciprofloxacin, clindamycin, rifampin, doxycycline<br />Triple antibiotic coverage recommended<br />Corticosteroids?<br />Barrier precautions<br />No documented cases of person-person spread<br />No need for exposure prophylaxis for ED staff<br />Vaccine is available<br />
  30. 30. Smallpox<br />
  31. 31. Smallpox<br />Estimated to have caused 300 million deaths in the 20th century<br />Up to 80% mortality in non-immune populations<br />Last recorded natural case in Somalia in 1977. Routine vaccination in the US stopped in 1972<br />Two known sources of the virus<br />CDC in Atlanta<br />Russian State Research Center of Virology and Biotechnology in Koltsovo, Russian Federation<br />Humans are only known host with no known animal reservoir<br />Mortality estimates are 20-40% in unvaccinated individuals and 1-3% in vaccinated individuals<br />
  32. 32. Smallpox<br />DNA virus of the orthopox virus genus <br />Variola major<br />Variola minor (milder form less associated with morbidity and mortality)<br />Transmission is person to person by respiratory droplets and through infectious fomites<br />People are infectious from onset of rash until resolution of all lesions<br />
  33. 33. Smallpox <br />Pathophysiology<br />3-4 days of asymptomatic to nonspecific symptomatic viremia follows initial exposure<br />Second cycle of viremia occurs at 7-17 days post-exposure, and is marked by signs and symptoms of toxemia<br />Rash follows second phase by 48hrs<br />Death occurs 1-2 weeks after onset of illness<br />Classically described as acute fever followed by rash in 1-2 days<br />
  34. 34. Smallpox<br />Rash<br />First noted on oral mucosa, pharynx, followed by head, face, proximal extremities, distal extremities and trunk<br />Involvement of palms and soles<br />Initially maculopapular and then progresses to vessicles in 1-2 days, and become umbilicated in another 1-2 days<br />Pustules scab over in an additional 2 days<br />Scabs slough off in 8-17 days<br />All lesions in one area of the body are in the same stage of development which distinguishes it from varicella<br />
  35. 35. Smallpox<br />Diagnosis<br />Initial diagnosis is clinical<br />High clinical suspicion<br />Confirmation by electron microscopy<br />Culture and PCR (only available at CDC)<br />Treatment<br />Supportive<br />Cidofivir shows in vitro activity<br />Negative pressure isolation<br />Patient contact only by vaccinated individuals<br />Clothing is potential fomite carrier<br />Quarantine<br />Vaccine available<br />
  36. 36. Plague<br />
  37. 37. Plague<br />“Black Death”<br />Three pandemics with a deaths exceeding 100 million people<br />First used as a biologic weapon in the Crimean War in 1346<br />Used as a biologic weapon by Japan in World War II by aerial dropping of infected fleas on Chinese villages<br />Former Soviet Union created large quantities of genetically engineered Y. pestis that could be delivered by aerial munitions<br />Disease is endemic to 17 western states<br />
  38. 38. Plague<br />Pathophysiology<br />Yersiniapestis: gram negative, non-motile, coccobacillus<br />“Safety Pin” appearance<br />Virulence due to multiple plasmid encoded proteins<br />Natural reservoir is rats, prairie dogs, chipmunks, and multiple other animals<br />Transmission is by bite of infected flea <br />Three principle forms<br />Bubonic (84% of cases with 14% mortality)<br />Septicemic (13% of cases with 22% mortality)<br />Primary Pneumonic (2% of cases with 57% mortality)<br />Bacteria transported to regional lymph nodes and created classic “bubo”<br />
  39. 39. Plague<br />Untreated infection will lead to systemic involvement with resultant septicemia<br />Systemic spread to the lungs results in “secondary” pneumonic plague<br />About 13% of people present with systemic infection without adenopathy (primary septicemic plague) with about twice the mortality<br />Primary pneumonic plague results from direct inhalation of infected particles which is more virulent than secondary pneumonic plague—this is the form feared in a bioterrorism attack<br />
  40. 40. Plague<br />Aerosolized plague would result in a rapidly progressive primary pneumonic plague or septicemic picture<br />Bubonic plague presents after 1-8 days incubation period (Could present if infected fleas used as bioterror threat)<br />Initial symptoms non-specific<br />Follow rapidly by painful adenopathy at location near inoculation site<br />Bubos differentiated by other diseases by rapid onset, extremely painful, absence of lymphangitis, and toxicity<br />Septicemia in 2-6 days if left untreated<br />
  41. 41. Plague<br />Common complication is DIC which leads to acral ischemia and gangrene—”Black Death”<br />Primary pneumonic plague has incubation of 1-6 days, and is the most deadly form of the disease<br />Diagnosis<br />Clinical suspicion<br />Rapidly progressive adenitis or severe pneumonia and sepsis in normally healthy individuals<br />Blood cultures, cultures of bubos<br />CBC often markedly elevated especially in children (50,000-100,000)<br />DIC<br />Nonspecific CXR<br />
  42. 42. Plague<br />Treatment<br />Streptomycin, tetracycline, doxycycline (FDA approved)<br />Gentamicin appears equally effective in animal models<br />Chloramphenicol effective, especially in cases of meningitis<br />Respiratory precautions<br />Vaccine available<br />
  43. 43. On The Bright Side<br />