4/23/15

Ebola Update: One Year Later…

Catherine Liu, MD

Associate Professor, Department of Medicine, Division of, Infectious Diseases, University of California San Francisco

Medical Director, Hospital Epidemiology and Infection Control, UCSF

Disclosures

• None

1 4/23/15

West African Ebola Outbreak: How Did it Begin? • Dec 2013: 1st case in Guinea • March 2014: WHO nofied of outbreak in Guinea • July 2014: CDC releases first health advisory regarding Ebola epidemic • August 2014: WHO declares epidemic a “public health emergency of internaonal concern”

Background

• Member of Filoviridae family • Natural reservoir - ? Fruit bats • Named aer Ebola river in DRC • 5 species: – Zaire (1976) – Sudan (1976) – Reston (1989) – imported monkeys from Philippines – Cote d’Ivoire/ Tai Forest (1994) – Bungibugyo (2007)

2 4/23/15

What is Ebola Virus?

• Single-stranded RNA virus, Filoviridae family • Natural reservoir unknown ? Fruit bats • Named aer the Ebola river in the DRC • 5 species: – Zaire (1976) – Sudan (1976) – Cote d’Ivoire/ Tai Forest (1994) – Reston (1989) – primate pathogen – Bundibugyo (2007)

2014 West African Ebola Outbreak

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2014 West Africa Outbreak – Why did it Happen? An Old Disease in A New Context

Deforestation

“The increase in Ebola outbreaks since 1994 is frequently associated with drasc changes in forest ecosystems in tropical Africa” – 2012 study in Journal of Veterinary Research

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Bushmeat Consumption

Transmission During Burial Ceremonies for Dead

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Spread of Infection from Movement of People

Inadequate Medical Personnel (1 doctor per 100,000 population)

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Ebola Disease Progression

RECOVERY or

Massive fluid losses (5-10 L/day*) Prolonged convalescence if survive *Dr. Bruce Ribner, IDWeek Update 2014

Diagnosis of Ebola

• PCR most sensive – May take 3 days aer symptom onset to reach detectable levels – TAT 12-24 hrs • ReEBOV Rapid Angen – Approved by WHO 2/15, FDA EUA 2/15 – TAT 15 minutes – ê sensivity vs PCR – Other rapid tests under development

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How is Ebola Transmied?

• Direct contact (through broken skin or mucous membranes, i.e. eyes, nose mouth) – With blood or bodily fluids (saliva, mucus, vomit, urine, feces) from an infected person – Sharps injuries (contaminated needles or syringes) – With bIood or bodily fluids from infected animals (bats, primates, bushmeat) • Indirect contact (uncommon) – With infected person’s blood or bodily fluids via a contaminated object (i.e. soiled linens)

8 4/23/15

Airborne Transmission of Ebola?

CONTROL MONKEYS

Transmission due to aerosolizaon of infected droplets from pressure washing of cages

EXPERIMENTALLY INFECTED MONKEYS

Jaax, et al., Lancet 1995

Recent Studies Show No Evidence of Airborne Transmision • Infected macaques died on day 6 – Virus detected in blood, 0.3 m oral/ nasal/ rectal swabs • Uninfected macques followed for 28 days – Oral, rectal, nasal swabs – Blood samples

Infected macaques Uninfected • No evidence of infecon macaques – Viral PCR negave – Ebola IgM and IgG negave

Alimon et al Scienfic Rep 2014

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How Contagious is Ebola?

R0 = average # of people that one sick person will infect

10 4/23/15

When during Ebola infecon does transmission occur? • Not contagious unl symptom onset • Infecvity increases as paent becomes more ill – No pts managed by MSF contracted disease from an infected contact during early febrile phase of illness – No secondary cases in Dallas when pt inially presented despite lack of PPE – No secondary cases in NY – Remains from deceased infected persons are highly infecous

Survival Outside Host

• Survives on dry surfaces for several hours • Survives in bodily fluids (ie blood) for several days at room temperature • Easily inacvated by hospital-grade disinfectants including bleach • Emory hospital: “...environmental tesng in the [two] paent rooms had no detecon of viral RNA and included many high touch surfaces such as bed rails and surfaces in the bathroom...” (Dr. Bruce Ribner)

11 4/23/15

What are current treatment opons for Ebola? • There is no approved treatment for Ebola

• Mainstay of treatment is intensive supporve care (intravenous fluids, electrolyte repleon, blood transfusion, pressors, oxygen, empiric anbiocs for secondary bacterial infecon)

• Experimental drugs and vaccines under development

Experimental Drugs and Vaccines

Drug/ Vaccine Mechanism of Acon Clinical Trials?

Favipravir Approved in Japan for Rx of influenza 2014 Noncontrolled trial in Guinea 12/14, prelim results 69 pts ↓ mortality Brincidofovir RNA polymerase inhibitor, being studied in RCT Liberia launched adenovirus 1/2/15, trial halted 2/1/15 slow enrollment ZMapp 3 monoclonal anbodies targeng Ebola virus RCT Liberia launched glycoprotein, 8/10 US treated pts survived. 2/27/15 TKM-Ebola Small interfering (siRNA) drug Phase 1 safety study launched in US human volunteers

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Experimental Drugs and Vaccines

Drug/ Vaccine Mechanism of Acon Clinical Trials?

Convalescent Plasma from Ebola survivors in Monrovia RCT launched in 12/14 in Plasma Sponsored by Bill&Melinda Gates Foundaon Liberia Therapy in collaboraon with WHO Convalescent Plasma from Ebola survivors in Guinea RCT launched in 12/14 Plasma Sponsored by EU, Wellcome Trust, and MSF Therapy Convalescent Plasma from Ebola survivors in Sierra Leone RCT TBD Plasma Sponsored by Sierrra Leone Acon Group Therapy NIAID/ GSK Uses chimpanzee adenovirus type 3 as vector Phase III launched Vaccine Liberia 2/15 (CAd3-EBOZ) NIH/ Merck/ Vesicular stomas virus vector Phase III launched NewLink Liberia 2/15, Guinea (VSV-EBOV) 3/15

Ebola Outbreak: Current Status

• Overall decline in number of new cases, but geng to zero remains a challenge • Lessons learned from success stories in Nigeria, Senegal, and Mali • 12 cases treated in the US; 2 deaths • Unintended consequences: – Disrupon of immunizaon services, access to care/ treatment for malaria

13 4/23/15

UCSF Ebola Response: Key Planning Areas • Screening and Triage Protocols • Isolaon Unit • Staffing and Training • Exercises and drills • PPE selecon and acquision • External Agencies • Communicaon

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Screening and Triage

Ask, Mask, Isolate, Communicate

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14 4/23/15

Screen to Idenfy “Person Under Invesgaon” “In the last 21 days have you traveled to Guinea, Liberia or Sierra Leone OR had contact with an Ebola paent?”

Yes

“Do you have fever, headache, weakness, muscle pain, voming, diarrhea, stomach No pain, unusual bleeding or bruising?”

Yes

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Biocontainment Center

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Staffing and Training

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PPE Donning Checklist

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PPE Doffing Checklist

Lessons Learned From Ebola

• Investment in global outbreak response system, public health infrastructure, disease surveillance, R&D needed • Humility is wise when dealing with an unfamiliar communicable infecous disease • Muldisciplinary coordinaon and communicaon at all levels key • Dedicated team of providers for repeated training on PPE, scenario/workflows facilitates local preparedness efforts

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