Transcript Ebola and Highly Infectious Diseases

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