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DANIEL BARNETT, MD, MPH JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH JEFFERSON CITY, MISSOURI MARCH 7, 2016 Disclaimer The contents of this informational presentation solely represent my own views and perspectives, and not those of any institutional affiliation, including Johns Hopkins University. Ebola and Highly Infectious Diseases Public Health Emergency Preparedness System Health Care Delivery Systems Communities Academic Source: IOM 2002 Homeland Security and Public Safety Governmental Public Health Infrastructure Employers and Business The Media CBRNE • CBRNE – Chemical – Biological – Radiological – Nuclear – Explosive 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 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? 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. 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 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 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. Incubation Period • The time from exposure onset of symptoms 5 Days Exposure Symptoms • Varies – depends on the particular agent, dose, underlying health status, etc. Anthrax Incubation Period Botulism Plague (inhalational) (pneumonic) 1-7 days – can 2-8 hours – be longer can be days 1-6 days – (usually 2-4) Smallpox 7-17 days Tularemia 1-21 days (usually 2-5) Hemorrhagic Fever Viruses 2-21 days 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. Anthrax Botulism (inhalational) Initial Clinical Diagnosis Presentation Plague Smallpox Tularemia Clinical Presentation Clinical Presentation (pneumonic) Clinical Presentation Clinical Presentation Hemorrhagic Fever Viruses Clinical Presentation 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. Anthrax Botulism (inhalational) Person to person spread? No Plague Smallpox Tularemia (pneumonic) No Yes Yes No Hemorrhagic Fever Viruses Seen in some VHFs 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. Anthrax Botulism (inhalational) PEP Yes Plague Smallpox Tularemia (pneumonic) Yes Limited Yes Yes Yes Hemorrhagic Fever Viruses No – 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. Anthrax Botulism (inhalational) Treatment Antibiotics Plague Smallpox Tularemia (pneumonic) Antitoxin Antibiotics None after onset of symptoms Antibiotics Hemorrhagic Fever Viruses Ribavirin in some cases 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 Anthrax Botulism (inhalational) Lethality 20th Century – 89% (45% in 2001 attack) Plague Smallpox Tularemia (pneumonic) Uncertain – high w/o support ~14% with treatment ~30% ~2% Hemorrhagic Fever Viruses Varies - <1% to 50-90% Vaccination • Effective vaccines are available for some BW agents. Anthrax Botulism (inhalational) Vaccine Yes Plague Smallpox Tularemia (pneumonic) No No Yes Yes Hemorrhagic Fever Viruses No Ebola & Other (Re-)Emerging Infectious Diseases 19 Twenty-First Century Public Health Preparedness Challenges • Natural disasters • Terrorism • Technological disasters • Emerging Infectious Diseases 20 Key Transformative Events – September 11, 2001 to Present 21 Major drivers of EIDs RANK DRIVER 1 Changes in land use or agricultural practices 2 Changes in human demographics and society 3 Poor population health (e.g., HIV, malnutrition) 4 Hospitals and medical procedures 5 Pathogen evolution (e.g., antimicrobial drug resistance, increased virulence) 6 Contamination of food sources or water supplies 7 International travel 8 Failure of public health programs 9 International trade 10 Climate change Woolhouse, M. E. J., & Gowtage-Sequeria, S. (2005). Host Range and Emerging and Reemerging Pathogens. Emerging Infectious Diseases, 11(12), 1842–1847. 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 Key Underpinning Themes 1. EIDs are part of the all-hazards preparedness 2. EIDs fit centrally in “public health preparedness system” framework 3. EIDs follow maxim that “all disasters begin locally” 4. EIDs are part of cyclical nature of readiness and response 5. EID preparedness is vital part of public health agency organizational culture Photo: http://www.cnn.com/2014/09/12/health/ebola-airborne/ EBOLA 2014-2016 Ebola Epidemic: Cases and Deaths1 Largest Ebola Outbreak in History Reporting Date Guinea Confirmed Cases Total Deaths 28 Dec 15 3,804 3,351 2,536 Sierra Leone 7 Feb 16 14,124 8,706 3,956 Liberia 14 Jan 16 10675 3160 4809 Italy 20 May 15 1 1 0 United Kingdom 29 Dec 14 1 1 0 Nigeria 15 Oct 14 20 19 8 Spain 27 Oct 14 1 1 0 Senegal 15 Oct 14 1 1 0 United States 24 Oct 14 4 4 1 Mali 23 Nov 14 8 7 6 28,639 15,251 11,316 TOTAL 1 Total Cases (Suspected, Probable, and Confirmed) 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 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 Info at http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/united-states-imported-case.html. 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 Numbers in Perspective 28,639 infected; 11,316 dead 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 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 nonhuman primates 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 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 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 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 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 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/ 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) 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 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 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 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 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/evaluatingpatients/evaluating-travelers.html • If patient has both exposure and symptoms, know initial steps to take Photo: http://www.cnn.com/2016/02/02/health/zika-virus-sexual-contact-texas/ MOSQUITO-BORNE DISEASES: FOCUS ON ZIKA 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: Distribution of Mosquitoes 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 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/ Imported Dengue Cases 2015 CDC ArboNET http://diseasemaps.usgs.gov/mapviewer/ Locally Transmitted Dengue Cases 2015 CDC ArboNET http://diseasemaps.usgs.gov/mapviewer/ Chikungunya in the U.S. • Prior to 2006, rarely identified in US travellers • 2006-2013: Average of 28 travel-associated cases in US per year • Late 2013, local transmission of the virus in Caribbean countries and US territories • 2014: First local transmission in continental US- Florida, 12 cases • Became a nationally notifiable disease in 2015 Info at: http://www.cdc.gov/chikungunya/index.html Risk of local transmission in U.S. Linked to distribution: Image: http://www.cdc.gov/chikungunya/resources/vector-control.html The Zika Virus • Flavivirus (Flaviviridae) – Other Flaviviruses include West Nile virus, dengue virus, and yellow fever virus Photo: http://www.cdc.gov/media/dpk/2016/dpk-zika-virus.html The Recent Emergence of Zika Virus • Initially isolated from a rhesus monkey in the Zika forest in Uganda- 1947 • Sporadic cases in SE Asia and Sub-Saharan Africa • Major epidemics in French Polynesia, New Caledonia, the Cook Islands, and Easter Island 2013 and 2014 • First case in Western Hemisphere detected in Brazil May 2015 – Total in 2015: 440,000 to 1.3 million cases • Since then 39 countries have reported local transmission Info at: http://www.cdc.gov/chikungunya/index.html Zika in the U.S. Florida #1: 16 travel associated cases As of Feb 10, 2016 •Continental US: – Travel associated cases: 52 – Locally acquired: 0 •US Territories – Travel associated cases: 1 – Locally acquired: 9 Image: http://www.cdc.gov/zika/geo/united-states.html Clinical Presentation • 1 in 5 people infected will become ill • Incubation period not known, likely to be a few days to 1 week • Remains in blood for 1 week, longer in some individuals • Acute onset of fever with maculopapular rash, arthralgia, or conjunctivitis- similar to dengue and chikungunya • Symptoms are mild, lasting several days to 1 week • Severe disease requiring hospitalization is uncommon and case fatality is very low • Rare cases of Guillain-Barre syndrome reported in patients following Zika infection Info at: http://www.cdc.gov/zika/hc-providers/clinicalevaluation.html Zika and Microcephaly? Photo: http://www.nbcnews.com/slideshow/brazil-blames-virus-birth-defects-newborns-n496986 Microcephaly • Diagnosis: – During pregnancy with ultrasound, late in 2nd trimester or early in 3rd – After birth- head circumference • Lifelong condition – No known cure or standard treatment – Range from mild to severe • Associated Problems: – Seizures, developmental delay, intellectual disability, problems with movement and balance, feeding problems, hearing loss, vision problems Info at: http://www.cdc.gov/ncbddd/birthdefects/microcephaly.html Microcephaly: Known Causes • Infections during pregnancy: rubella, toxoplasmosis or cytomegalovirus • Severe malnutrition • Exposure to harmful chemicals such as alcohol, certain drugs, or toxic chemicals • Interruption of blood flow to baby’s brain during development • Incidence in US: 2-12 babies per 10,000 live births http://www.cdc.gov/ncbddd/birthdefects/microcephaly.html Zika and Microcephaly: the evidence BRAZIL •October 2015 to January 2016: – 3,935 suspected cases of microcephaly; 508 confirmed cases – Prior to this ~150 cases/year •Case studies – Mother terminated pregnancy at 29 weeks due to abnormal ultrasound. Microcephaly on autopsy. Virus found in fetal brain tissue on RT-PCR – 2 pregnant women with clinical symptoms and abnormal ultrasounds: virus found in amniotic fluid- Can be spread from pregnant women to fetus REF: Mlakar J et al. (2016). Zika Virus Associated with Microcephaly. New England Journal of Medicine at http://www.nejm.org/doi/full/10.1056/nejmoa1600651 Calvet G et al. (2016). Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. The Lancet DOI: http://dx.doi.org/10.1016/S1473-3099(16)00095-5 CDC Recommendations • Pregnant women in any trimester should consider postponing travel anywhere Zika is spreading • See CDC’s Zika Travel Information Page for up-todate travel recommendations – http://wwwnc.cdc.gov/travel/page/zika-information • If you MUST travel, strictly follow steps to prevent mosquito bites – http://wwwnc.cdc.gov/travel/page/avoid-bug-bites CDC Recommendations • All women who have traveled to an area with Zika should talk to their healthcare provider, even if they don’t feel sick • All pregnant women with travel history should be tested • Especially important if the woman develops a rash, joint pain, or red eyes during the trip or within 2 weeks after For Healthcare Providers: http://www.cdc.gov/zika/hc-providers/index.html CDC Interim Guidelines, 2016 • For Health Care Providers Caring for Pregnant Women and Women of reproductive Age with Possible Zika Virus Exposure • For the Prevention of Sexual Transmission of Zika Virus • For Healthcare Providers Caring for Infants and Children with Possible Zika Virus Infection http://www.cdc.gov/zika/hc-providers/index.html FDA Guidelines on Blood Donation • In areas without active Zika transmission, donors at-risk for Zika virus infection should defer blood donation for 4 weeks • At-risk: – Those with symptoms suggestive of Zika in past 4 weeks – Those who have had sexual contact with a person who has traveled to, or resided in, an area with active Zika transmission during the prior three months – Those who have traveled to areas with active transmission of Zika virus in the past 4 weeks Info at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm486359.htm FDA Guidelines on Blood Donation • In areas with active Zika transmission, FDA recommends that Whole Blood and blood components for transfusion be obtained from areas of the U.S. without active transmission Info at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm486359.htm Funding Acknowledgment Funding for this conference/training was made possible (in part) by the Centers for Disease Control and Prevention (CDC) under the grant number TP000531-032, PT12-1201 HPP and PHEP Cooperative. The views expressed in written conference materials or publication and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services, nor does the mention of trade names, commercial practices or organizations imply endorsement by the U.S. Government. Special Acknowledgement • Cassidy Rist, DVM, MPH Thank You • Questions? [email protected] 410-502-0591