Biocontainment& The Pathogens of Concern

Ted Cieslak MDUniversity of Nebraska Medical Center

Omaha NE

Nebraska Medicine

1969

Nixon renounces biological warfare 

An investigator dies of Lassa Fever at Yale

Armstrong and Aldrin walk on the moon

Michael Crichton publishes The Andromeda Strain

High‐Level Containment Care:Influenced by Popular History

1967‐ ABL construction begun

1969‐ ABL repurposed as USAMRIID

1972 ‐ USAMRIID opened

1989 ‐ Reston outbreak

1992 ‐ Crisis in ‘Hot Zone’

1994 ‐ Hot Zone book debut

Biosafety Terminology:applies to microbiology laboratories

BSL‐1

– High School Lab

BSL‐2

– Hospital/Clinic Lab

BSL‐3

– State Health Lab

– Medical Center Lab

BSL‐4

– USAMRIID

– NMRC

– CDC

Co‐opting Terminology

BSL‐2– Conventional Hospital

BSL‐3– Negative Pressure Room

BSL‐3+– Emory, NIH, Nebraska– Bellevue (New York)?– St Patrick’s (Missoula)?

BSL‐4– The “Slammer”

BSL‐4 Care

The Downsideof BSL‐4‐like Care

• Intense training needs• Loss of tactile sense• Loss of auditory sense• Awkwardness & Clumsiness• Claustrophobia• Expense

Biosafety Levels

Biosafety Level Laboratory Clinical Correlate

BSL‐1 High School Biology Lab

BSL‐2 Hospital Laboratory Standard Room or Ward

BSL‐3 State Health Lab Isolation Room or Ward

*BSL‐3+ BCU

BSL‐4 CDC, USAMRIID The “Slammer”

*This terminology is not widely recognized

Biosafety terminology was NOT intended to apply to clinical facilities

Experts agree that BSL‐4 controls are not necessary in order to safely manage patients with diseases caused by BSL‐4 pathogens

Why Nebraska?

Central location

Offutt AFB/STRATCOM

Homeland Security – A new Federal agency

Monkey Pox – Healthcare Workers afraid to care for patients

SARS – Emerging diseases are a threat to Public Health

Active local Omaha community in Emergency Preparedness

Partnership

University of Nebraska Medical Center The Nebraska Medical Center Nebraska Department of Health and Human Services

The Nebraska Biocontainment Unit opened March 2005

Beyond the Biocontainment Units: ETCs & Assessment Hospitals

Beyond the Biocontainment Units: ETCs & Assessment Hospitals

Regional Ebola Treatment CentersTen; one for each DHHS RegionUniversity of Minnesota is the Region 5 ETC

Ebola Treatment CentersInitially 55Tier 1 Receiver Hospitals in Michigan

Detroit Receiving HospitalSt Joseph Mercy, YpsilantiSpectrum, Grand Rapids

Ebola Assessment HospitalsFrontline Healthcare Facilities

Ebola Treatment Centers

Nebraska Biocontainment Unit

Five (potentially double) patient rooms

Secure access

Separate air handling system

2 pass‐through autoclaves

Negative air pressure with 15‐20 air exchanges/hr

HEPA filtered exhaust air

HVAC System

Air handling system with negative 

pressure, 15‐20 air exchanges per 

hour

No recirculated air

Exhaust air is >25 feet from any of the 

building air intake areas.

All exhaust air  is HEPA filtered

Dual fan for redundancy

Isolation dampers can switch off air flow to either side if the fan fails

Exhaust Plumes go 60 feet high

HEPA Filter

Digital Environmental Information

Outside the Unit

Inside the Room

Outside the Care Rooms At the Nurse’s Station

Isopod ‐Negative pressure patient isolator for intra and inter‐hospital transportation

Bio‐Seal‐ For containment

Equipment

How Does OneTransport a Patient to a Biocontainment Unit?

High‐Level Containment Care:Two Components

1. Definitive Care– Emory– NIH– Bellevue– Nebraska

2. Transport– AIT (Army)– CCATT (AF)– Phoenix (CDC)

The Mobile Quarantine Facility:Apollo Missions 11, 12, 14

USAMRIID’s AIT

AIT Missions

1989‐ Ebola Reston– Dissected monkeys

1995‐ Glove Box– Dissected bomblets

1999‐ Bronx Zoo– Dissected birds

Air Force PIU/CCATT

The ISOPOD

Two Distinct Concepts

Envelope the Patient– AIT– Air Force PIU– ISOPOD

Envelope the Vehicle– CDC/Phoenix Air– Omaha Ambulance System

CDC’s MEDEVAC Project

CDC’s MEDEVAC Project

Transport Process

Transport Process

Ground transportation

Carter Lake, Iowa

Entering the Hospital

We are not sneaking in the back door of the Hospital at 3:00 am.This is a side door.

Which DiseasesWarrant Care in a Biocontainment Unit?

Highly Hazardous Communicable Diseases

AnthraxBotulism

BrucellaQ‐Fever

NorovirusMumps

Hazardous

Communicable

InfectiousEbola

Tularemia

Measles

Nipah

Highly Hazardous CommunicableDiseases: Preventable by Vaccine

• Measles• Polio• Rabies• Cholera• Smallpox

Ebola Vaccine

Potential Candidatesfor Admission to a BCU

Persons Infected With:

• BSL‐4 agents with person‐to‐person spread

• Other highly hazardous communicable pathogens

• Unknown diseases which appear highly hazardous– The “Andromeda Strain” problem

• Diseases with public assuredness concerns

The BSL‐4 PathogensFirst Four Groups cause VHF

• Filoviridae– Ebola– Marburg

• Arenaviridae– Lassa– Lujo– Guanarito– Junin– Machupo– Sabia

• Bunyaviridae– CCHF

• Flaviviridae*– RSSE & CEE– TBE Complex– Kyasanur Forest– Omsk

• Henipiviruses– Nipah– Hendra

• Orthopoxviruses– Variola

*Vector‐Borne; no known PTP transmission 

The Arenaviruses

Virus Disease

Old World Arenaviruses

Lassa Lassa Fever

Lujo

New World Arenaviruses

Guanarito Venezuelan HF

Junin Argentine HF

Machupo Bolivian HF

Sabia Brazilian HF

Chapare

Whitewater Arroyo

Other Highly Hazardous Communicable Pathogens

– Coronaviruses• SARS• MERS

– Orthopoxviruses• Monkeypox

– Highly Pathogenic Avian Influenza (HPAI)– Other novel & pathogenic influenza viruses– Pneumonic Plague– XDR‐TB

Mechanisms of Transmission

Contact or Fomites:EbolaMarburgLassaOther VHFsVariolaMonkeypox

Droplets:EbolaMarburg?NipahHendra?InfluenzaPlagueMonkeypox

Droplet Nuclei:VariolaXDR‐TBSARS?MERS?HPAI?

Courtesy of Mike Bray, NIAID

VHF Misperceptions

1. They all have the same features

2. They all spread easily3. They are easily

recognizable4. Bleeding is the primary

cause of death

Ebola spread in perspective

Clinical Features of the VHFs

Courtesy of Drs. Zaki & Peters

Distinguishing FeaturesAmong the VHFs

Hemorrhagic signs near the end of the first week‐ Bleeding doesn’t generally kill people; organ failure does

Bolivian Hemorrhagic Fever (Machupo)

Licensed Therapyand Prophylaxis

Ribavirin for Lassa Rx YF‐Vax for Yellow Fever Prevention

The Lethal VHFs

The Henipiviruses

Blue = NipahRed = Hendra

Nipah

The Orthopoxviruses:Smallpox

Smallpoxthe only Disease thus far Eradicated*

• Last natural V. major‐ 1975• Last natural V. minor‐ 1977• Two lab‐acquired cases‐ 1978• Declared eradicated‐ 1980• 1:10 deaths throughout history• 1:3 pediatric deaths• case fatality rate: 30%• >600,000,000 victims?• The weapon‐ Vaccine

“Ordinary Type” Smallpox

Meschede Smallpox Outbreak, 1969

From Wehrle et al. 1970

Index casePatient #8

Pt 8 visits evening of 3rd day, stood in lobby for 15 minutes – not permitted to visit because flu outbreak

Spread to 17 secondary cases on three floors– then 2 tertiary cases

Yugoslav Smallpox Outbreak, 1972

From Fenner, F. et al. 1988

Single traveler returning from Hajj to Mecca through Iraq. Over 140 cases of smallpox were documented.

Nearly 7 million doses of vaccine needed to bring the outbreak under control.

Human MonkeypoxDemocratic Republic of Congo

Human MonkeypoxWhy we care in Nebraska

• 2003 Midwest Outbreak• 71 reported cases• Traced to Gambian Rats

– Spread to Prairie Dogs• No mortality in US

– Traditionally, 1‐10% fatal• Widespread fear

– Some clinicians refused care

The Coronaviruses

229E

NL63

OC43

HKU1

SARS

MERS

Causes of theCommon Cold

SARS

• Produces severe lower respiratory illness• Appeared in China in 2002• No reported cases since 2004• There have been 8273 total cases recorded

– 775 deaths– 27 US cases (no deaths)

• Overall mortality was 9.6%

HemagglutininAllows the flu virus to adhere to the respiratory tract

NeuraminidaseAllows the flu virus to escape from respiratory cells after replication

Influenza Virus

Risk Factorsfor Novel Influenza or HPAI

• Pigs harbor human strains

• Pigs harbor avian strains

• Pigs thus serve as “mixing vessels”

• Antigenic shift occurs in the pig

• The fear: a new virus with human affinity and avian mortality

Origin of “Swine‐Origin”

H1N1Garten et alScience, 2009

Pneumonic Plague

Note the Rose‐colored ring around the neck

The Good Newsfor Biocontainment Personnel

• Smallpox Vaccine– Prevents Smallpox– Also prevents Monkeypox– Effective 4 days post‐exposure

• Antibiotics– Treat Plague– Can be given prophylactically

Tuberculosis

• Standard TB– Affects 1/3 of world– 1.5 million deaths/year– Contagious via droplet nuclei– Requires negative pressure room– Rx = INH + RIF + ETH + PZA

• MDR‐TB– Resistant to INH & RIF

• XDR‐TB– Resistant to INH & RIF +– Resistant to Quinolones or– Resistant to Aminoglycosides

Many believe that XDR‐TB should be managed in a BCU

The Andromeda Strain• Patients with unknown 

diseases could be admitted to a BCU or ETC

• At the time of their initial outbreaks, these could have been “Andromeda Strains”– Nipah– Hendra– SARS– MERS– Sin Nombre– Many others

Summary:“Enhanced” Precautions

Most VHFsSmallpox

Monkeypox

Ebola & MarburgNipah & HendraMonkeypoxInfluenzaPlague

SmallpoxSARS & MERS

XDR‐TB

The next lecture will detail these “enhanced” precautions

Questions?