Ebola and Highly Infectious Diseases

1. DANIEL BARNETT, MD, MPHJOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTHJEFFERSON CITY, MISSOURIMARCH 7, 2016

2. DisclaimerThe contents of this informational presentation solely represent my own views and perspectives, and not those of any institutional affiliation, including Johns Hopkins University.

3. Ebola and Highly Infectious Diseases

4. Public Health Emergency Preparedness System Health Care Delivery Systems Homeland Security and Public Safety Governmental Public Health Infrastructure Communities Employers and Business Academic The Media Source: IOM 2002

5. CBRNE • CBRNE • Chemical • Biological • Radiological • Nuclear • Explosive

6. Definition of Bioterrorism • A bioterrorism attack is the deliberate release of viruses, bacteria, or other germs (agents) used to cause illness or death in people, animals, or plants. • A bioweapon usually consists of: • Biological agent or toxin • Bacteria • Mycoplasma • Rickettsiae • Viruses • Yeasts • Fungi • Delivery system

7. What makes a BW attack different? • A BW attack will likely be covert – an attack will not be realized until symptoms begin to appear in victims – usually days to weeks after the attack. • Awareness of what has occurred will develop slowly: • Where did the attack occur? • Who was exposed? • What was the agent?

8. Biological Weapons Are Unique • The consequence of a biological weapon attack could be an epidemic. • The response required is fundamentally different from that demanded by natural disasters, conventional explosives, chemical terrorism, radiological terrorism or nuclear weapons.

9. Bioterror Weapons (CDC) - 1 • Category A - high priority - organisms that pose a risk to national security because they can be easily disseminated or transmitted from person to person, cause high mortality, and have the potential for major public health impact • Anthrax, botulism, plague, smallpox

10. Delivery Systems • Any device that can produce an effective aerosol can be fashioned into a BW delivery system: • Bombs/bomblets • Aircraft with spray tank • Truck-mounted sprayer • Crop duster • ABC fire extinguisher • Can of underarm deodorant

11. What is an Aerosol? • An aerosol is a suspension of liquid droplets or small particles in air. • To be effective, an aerosolized biological agent (i.e., bioaerosol) must be of the right size so that the particles will remain suspended in the air and will be inhaled into the lower lungs where infection takes place.

12. 5 Days Anthrax (inhalational) Botulism Plague (pneumonic) Smallpox Tularemia Hemorrhagic Fever Viruses Exposure Symptoms Incubation Period 1-7 days – can be longer 2-8 hours – can be days 1-6 days – (usually 2-4) 7-17 days 1-21 days (usually 2-5) 2-21 days Incubation Period • The time from exposure  onset of symptoms • Varies – depends on the particular agent, dose, underlying health status, etc.

13. Anthrax (inhalational) Botulism Plague (pneumonic) Smallpox Tularemia Hemorrhagic Fever Viruses Initial Diagnosis Clinical Presentation Clinical Presentation Clinical Presentation Clinical Presentation Clinical Presentation Clinical Presentation Initial Diagnosis • Diagnosis of infection with BW agents is generally made by clinical presentation of symptoms. • Confirmed by laboratory tests that can take days or weeks to complete. • Rapid, diagnostic, clinical tests are not currently available for most BW agents.

14. Anthrax (inhalational) Botulism Plague (pneumonic) Smallpox Hemorrhagic Fever Viruses Tularemia No Person to person spread? No No Yes Yes Seen in some VHFs Communicability • The ability of a disease to spread from person to person  contagious. • Not all BW agents can spread from person to person. • Usually requires close contact with infected person but not always.

15. Anthrax (inhalational) Botulism Plague (pneumonic) Smallpox Hemorrhagic Fever Viruses Tularemia Yes PEP Yes Yes Limited Yes Yes No – ribavirin in some cases Post-Exposure Prophylaxis • After a biological attack – can treatment prevent development of disease? • For some BW agents – post exposure prophylaxis is available. • Depends on the particular agent, dose, route of exposure, etc.

16. Anthrax (inhalational) Botulism Plague (pneumonic) Smallpox Hemorrhagic Fever Viruses Tularemia Antibiotics Treatment Antibiotics Antitoxin Antibiotics None after onset of symptoms Ribavirin in some cases Treatment • For many BW agents, there are treatments that can reduce the severity of disease. • Treatments are specific to the particular BW agent.

17. Anthrax (inhalational) Botulism Plague (pneumonic) Smallpox Hemorrhagic Fever Viruses Tularemia ~2% Lethality 20th Century – 89% (45% in 2001 attack) Uncertain – high w/o support ~14% with treatment ~30% Varies - <1% to 50-90% Lethality • The lethality of a biological attack (i.e., of those infected—how many will die) depends on a number of variables: • The particular agent used • Dose (how much exposed to) • Route of exposure • Underlying health status of victims (e.g. weakened immune system) • Size of the attack—ability to deliver healthcare

18. Anthrax (inhalational) Botulism Plague (pneumonic) Smallpox Hemorrhagic Fever Viruses Tularemia Yes Vaccine Yes No No Yes No Vaccination • Effective vaccines are available for some BW agents.

19. Ebola & Other (Re-)Emerging Infectious Diseases

20. Twenty-First Century Public Health Preparedness Challenges • Natural disasters • Technological disasters • Terrorism • Emerging Infectious Diseases

21. Key Transformative Events – September 11, 2001 to Present

22. Major drivers of EIDs Woolhouse, M. E. J., & Gowtage-Sequeria, S. (2005). Host Range and Emerging and Reemerging Pathogens. Emerging Infectious Diseases, 11(12), 1842–1847.

23. Relevance to YOU Global trends in the drivers of disease emergence will impact the United States Detecting and responding to EID events locally is essential to protecting state and national health

24. Key Underpinning Themes • EIDs are part of the all-hazards preparedness • EIDs fit centrally in “public health preparedness system” framework • EIDs follow maxim that “all disasters begin locally” • EIDs are part of cyclical nature of readiness and response • EID preparedness is vital part of public health agency organizational culture

25. EBOLA Photo: http://www.cnn.com/2014/09/12/health/ebola-airborne/

26. 2014-2016 Ebola Epidemic:Cases and Deaths1 Largest Ebola Outbreak in History 1 Total cases include probable, suspected, and confirmed cases. Reported by WHO using data from ministries of health. Adapted From: CDC slides for healthcare workers: http://www.cdc.gov/vhf/ebola/healthcare-us/index.html

27. Info at http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/united-states-imported-case.html. Ebola Cases in the U.S. • Diagnosed in the United States in 4 people: • 1 (the index patient) who traveled to Dallas, Texas from Liberia • Patient died October 8, 2014 • 2 healthcare workers who cared for the index patient • 1 recovered and released from NIH Clinical Center October 24, 2014 • 1 recovered and released from Emory University Hospital in Atlanta October 28, 2014 • 1 medical aid worker who traveled to New York City from Guinea • Recovered and released from Bellevue Hospital in New York City November 11, 2014

28. Ebola Cases in the U.S. • 6 health workers and 1 journalist have been infected with Ebola virus while in West Africa and transported to hospitals in the United States. • 1 of the health workers died on November 17, 2014, after being transported from Sierra Leone to Nebraska Medical Center Adapted from CDC slides for healthcare workers: http://www.cdc.gov/vhf/ebola/healthcare-us/index.html 28

29. Numbers in Perspective 28,639 infected; 11,316 dead

30. Ebola Virus Characteristics • Filovirus (Filoviradae) • Includes Ebola virus and Marburg virus • Cause severe hemorrhagic fever in humans and nonhuman primates • High case fatality rate (25% to 90%) • Five species of Ebola virus: • Tai Forest, Sudan, Zaire, Bundibugyo, Reston (no clinical disease in humans) • Fruit bats (Pteropodidae) are natural reservoir • Nonhuman primates can become infected and show clinical signs Info at: http://www.cdc.gov/vhf/ebola/about.html Photo: http://www.cdc.gov/vhf/virus-families/filoviridae.html

31. Virus Transmission Natural reservoir in nature: Bats Hunted by humans for income and food Small numbers of primary cases Human-to-human transmission: Close contact with blood, secretions, organs or other body fluids and with contaminated fomites Ebola outbreaks in non-human primates

32. Human-to-Human Transmission • Infected persons are not contagious until onset of symptoms • Infectiousness of body fluids increases as patient becomes more ill • Remains from deceased infected persons are highly infectious • Human-to-human transmission of Ebola virus via inhalation (aerosols) has not been demonstrated Adapted from CDC slides for healthcare workers: http://www.cdc.gov/vhf/ebola/healthcare-us/index.html

33. Pathogenesis • Direct infection of tissues • Immune dysregulation • Hypovolemia and vascular collapse • Electrolyte abnormalities • Multi-organ failure, septic shock • Disseminated intravascular coagulation (DIC) and coagulopathy Adapted from CDC slides for healthcare workers: http://www.cdc.gov/vhf/ebola/healthcare-us/index.html

34. Clinical Presentation and Course • Incubation period 2-12 days; average 8-10 days • Initial signs and symptoms include: • Fever, severe headache, muscle pain, weakness Photo: http://img.rt.com/files/news/2c/46/40/00/000_ts-par7952010.si.jpg • Within 5 days of initial signs progression to: • Diarrhea, vomiting, abdominal (stomach pain), and hemorrhagic signs (18% of cases) including petechiae, ecchymosis/bruising, and mucosal hemorrhage • Patients with fatal disease usually develop more severe signs early during infection. Death due to multi-organ failure and septic shock Adapted from CDC slides for healthcare workers: http://www.cdc.gov/vhf/ebola/healthcare-us/index.html

35. Examples of Hemorrhagic Signs Hematemesis Bleeding at IV Site Gingival Bleeding Adapted From: CDC slides for healthcare workers: http://www.cdc.gov/vhf/ebola/healthcare-us/index.html

36. Clinical Management • No FDA-approved medicines (e.g. antiviral drug) are available • Supportive, but Aggressive therapies: • IV fluids, electrolyte repletion, correction of acid-base derangements • Symptomatic treatment of fever and gastrointestinal symptoms • Avoid NSAIDS • Multisystem organ failure may require: • Maintain oxygen status +/- mechanical ventilation • Correction of coagulopathy • Renal replacement therapy • Treat other infections if they occur Adapted from CDC slides for healthcare workers: http://www.cdc.gov/vhf/ebola/healthcare-us/index.html

37. Vaccine Trials • Combined Phase 2 and 3 clinical trials to assess safety and efficacy of the rVSV-ZEBOV candidate Ebola vaccine • Sierra Leone, Guinea and Liberia • Other vaccines trials underway with different candidates • CDC: http://www.cdc.gov/vhf/ebola/strive/qa.html AND • WHO: http://www.who.int/medicines/emp_ebola_q_as/en/

38. Other Therapeutics • Limited human clinical trial data • Convalescent blood and plasma • Novel therapeutic medications • Monoclonal antibodies (Zmapp) • RNA-based drugs (Favipiravir) • Small antiviral molecules (Tekmira)

39. Sample Submission • CDC has developed interim guidance for laboratory and healthcare personnel who collect or handle specimens • Appropriate steps for collecting, transporting, and testing specimens from patients suspected to be infected with Ebola • Specimens should NOT be shipped to CDC without consultation with CDC and local/state health departments Information available at: http://www.cdc.gov/vhf/ebola/healthcare-us/laboratories/index.html

40. Recovery • People who recover develop antibodies that last for 10 years, possibly longer • Unknown if immune for life or if they can become infected with different species of Ebola • After recovery, Ebola can be found in some body fluids, including semen (3 to 9 months) • Long term sequelae have been described Info at: http://www.cdc.gov/vhf/ebola/treatment/index.html

41. Potential Sequelae of Ebola • Musculoskeletal: weakness, pain in joints, muscles and chest- 50-75% of survivors • Ocular: uveitis, cataracts, retinal and optic nerve disease • Auditory: tinnitus and hearing loss reported in > 25% of survivors. Causal link remains to be determined WHO Interim Guidance: Clinical care for survivors of Ebola virus disease http://apps.who.int/iris/bitstream/10665/204235/1/WHO_EVD_OHE_PED_16.1_eng.pdf?ua=1

42. Potential Sequelae of Ebola • Neurological: Headache, memory impairment, peripheral neuropathy, and tremors are common • RARE: Relapse due to persistent virus in ‘immunologically privileged sites’: eye, CNS, testicles WHO Interim Guidance: Clinical care for survivors of Ebola virus disease http://apps.who.int/iris/bitstream/10665/204235/1/WHO_EVD_OHE_PED_16.1_eng.pdf?ua=1

43. Evaluating Patients in US for Ebola • CDC encourages all U.S. healthcare providers to assess patients for: • International Travel within last 21 days, or • Contact with someone with confirmed Ebola, and • Fever or other symptoms of Ebola • CDC has developed documents to facilitate these evaluations: • http://www.cdc.gov/vhf/ebola/healthcare-us/evaluating-patients/evaluating-travelers.html • If patient has both exposure and symptoms, know initial steps to take

45. MOSQUITO-BORNE DISEASES: FOCUS ON ZIKA Photo: http://www.cnn.com/2016/02/02/health/zika-virus-sexual-contact-texas/

46. Emerging Mosquito-Borne Diseases in the Western Hemisphere • Dengue virus • 4 serotypes: DENV-1, DENV-2, DENV-3, DENV-4 • Chikungunya virus • Zika virus All are transmitted by mosquitoes: Aedesaegypti and Aedesalbopictus

47. Distribution of AedesMosquitoes Distribution of the occurrence database for Ae. aegypti (A) and Ae. albopictus (B) plotted on the underlying prediction surface REF: Kraemer MUG et al. (2015). The global distribution of the arbovirus vectors Aedes aegypti and Ae. albopictus. eLife, DOI: http://dx.doi.org/10.7554/eLife.08347

48. Dengue in the U.S. • Endemic in US territories of Puerto Rico, American Samoa, Guam, Northern Mariana Islands, and US Virgin Islands • 2009-2010: First outbreak on continental US since WWII occurred in Key West, FL • Majority of cases diagnosed in US are imported • Small numbers of locally acquired cases occur in South Florida counties each year Info at: http://www.cdc.gov/dengue/

49. Imported Dengue Cases 2015 CDC ArboNET http://diseasemaps.usgs.gov/mapviewer/

50. Locally Transmitted Dengue Cases 2015 CDC ArboNET http://diseasemaps.usgs.gov/mapviewer/