Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Emerging Infections

2,998 views

Published on

Emerging Infections and Bioterrorism Lecture

Published in: Health & Medicine
  • Be the first to comment

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 />

×