IS YOUR LABORATORY READY

EMERGING INFECTIOUS DISEASE

46 yo anesthetist assistant from Johannesburg

Fever day 1, Headache day 4, Works until day 5

Admitted to hospital Day 5 for suspected encephalitis

CSF workup normal, fever 103.5°

No recent history of travel or insect bites

Patient dies on Day 23 of il lness

CASE 1: SOUTH AFRICA

1996

41 yo Dutch woman referred by GP to hospital

Patient presented to GP with fever on July 5

Recent travel to Uganda June 5 -28

Travel group 7 Dutch tourists and 2 guides

Placed in hospital ward with 3 other patients

Malaria ruled out x 3-given antimicrobials

July 7, rapid deterioration with liver failure

Patient dies on July 11

CASE 2: NETHERLANDS

2008

January 4, 44 yo female with HA, fever, diarrhea N&V

Previous travel to Uganda, return on January 1

Self treated with ciprofloxacin x 2, developed rash

January 6-7 seen as outpatient treated with anti -emetics

Return to PCP January 8 with worsening symptoms

Admission to hospital with diagnosis of hepatitis ↑LFT’s

Negative leptospirosis, malaria, hepatitis, arbovirus, rickettsia

Workup for Ebola and Marburg VHF negative

Cholecystectomy for acalculous cholecystitis

Discharged on January 19

Patient read of death of Dutch patient 7/2008

CASE 2+: UNITED STATES

2008

10/2 --38 yo male returns from Dubai very il l

Patient was moderately il l on the Emirates flight

Travels home by private transport with friend

Admitted to hospital 3 hours later

Recent travel to Afghanistan to brother’s wedding

10/6 patient dies

CASE 3: GLASGOW, SCOTLAND

2012

May 18, 55 yo male fever, sore throat, fatigue

Travel history —no travel to West Africa

Patient sent home after non-diagnostic workup

May 21, patient returns to hospital, worsening symptoms

Patient transferred to second hospital, ?VHF

May 25, patient dies

CASE 4:NEW JERSEY

2015

Case 1: Ebola Viral Disease

Assisted with central line placement in physician from Gabon who had

no knowledge of Ebola exposure and who had self -treated for malaria

Case 2 and 2+: Marburg Hemorrhagic Fever

Visited Python cave, numerous bats, USA→ 260 contacts

Case 3: Crimean Congo Viral Hemorrhagic Fever

Endemic VHF

Case 4: Lassa Fever

False travel history; Liberia travel

EID CASE DIAGNOSES

All patients presented to a community hospital without a

biocontainment unit

The diagnosis at presentation was unknown

All patients had non-specific symptoms at presentation,

predominantly fever and malaise

Several patients were less than truthful with travel history

All patients had multiple contacts while sick

COMMONALITY IN EID CASES

All of the patients will have laboratory tests

Most will not be in isolation initially

Standard PPE will not be consistently employed

Blood will be transferred by ungloved hands and possibly by

pneumatic tube

Geography of travel and or exposures will determine infectious

disease differential diagnosis—truthfulness is paramount

SCENARIOS YOU CAN PREDICT WITH THE EID

PATIENTS

EMERGING INFECTIOUS DISEASE (EID)

GLOBAL AVIATION ROUTES

32 yo female with fever and headache

Recently returned from Australia

30 day adventure travel trip

Exposures?

Horses, camels, kangaroos, Tasmanian devil

Hiking and camping in the forest

Insect bites

EID CASE PRESENTS TO YOUR ED

Arthropod borne disease?

Hendra virus

Lyssa virus

Nipah virus

Japanese encephalitis

AUSTRALIAN TRAVELER

WHAT ARE THE POSSIBILITIES?

Picture: Locations of previous Henipavirus outbreaks (red stars –

Hendra virus; blue stars – Nipah virus) and distribution of

Henipavirus flying fox reservoirs (red shading – Hendra virus; blue

shading – Nipah virus)

OPPORTUNITIES FOR OUTBREAKS OF EID

Increases in travel, trade, and tourism

Zoonotic disease and human interaction in tourism

Animal pathogen spillover

Environmental changes resulting in new endemic regions

Refugee crises and population displacement

I l legal animal trade

Market for exotic animal products

Urbanization

Natural disasters in populated areas

WHAT’S A LAB TO DO?

Risk assessment— what can your lab do safely

PPE training and skills development

Lab Drills with debriefing and alteration of lab SOP’s

Befriend your Public Health Department Colleagues

Insert the Lab Medical Director centrally in the communication

Presentation of Emerging Infectious Disease cases in

community hospital Emergency Departments is not preventable

BUT

Mitigation of risk of disease transmission in the laboratory can be

implemented, and treating the patient is crucial.

BIOCONTAINMENT LAB—NOT A REASONABLE

SOLUTION TO EID FOR COMMUNITY HOSPITAL

MONEY $$$$$$$$

PHYSICAL SPACE

EXPERTISE--- PPE

STAFFING

CONFIRMED DIAGNOSIS

Provide technical assistance

Ebola testing validated at Dallas LRN 10/2014

Provide personnel to assist with state and local public health

responses

Laboratorian from CDC

Epidemiologists for contact tracing

Public relations personnel

CDC LABORATORY RESPONSE NETWORK

MISSION: Maintain integrated national and international network of laboratories

that are fully equipped to respond quickly to acts of chemical or biological

threats, emerging diseases and other public health threats and emergencies.

Duty of an acute care facility

assess, rule out, and refer

Timeline to referral and disposition of PUI?

“Just in case” estimate— plan for 96 hours

SENTINEL LABORATORY

“The physician must be able to tell the

antecedents, know the present, and foretell

the future - must mediate these things, and

have two special objects in view with regard

to disease, namely, to do good or to do no

harm. “

Hippocrates

MMWR DECEMBER 12, 2014 / 63(49) ; 1175-117

CLINICAL INQUIRIES REGARDING EBOLA VIRUS DISEASE RECEIVED

BY CDC — UNITED STATES, JULY 9 –NOVEMBER 15, 20149

Among 33 recent travelers who tested negative for Ebola, alternative diagnoses

were available for 13, the most common being malaria (n = 5) and viral illnesses

(n = 4), including influenza. At least two persons who tested negative for Ebola

died from other causes. Based on reports from health departments and health

care providers, in several instances efforts to establish alternative diagnoses

were reported to have been hampered or delayed because of infection control

concerns. For example, laboratory tests to guide diagnosis or management (e.g.,

complete blood counts, liver function tests, serum chemistries, and malaria

tests) were reportedly deferred in some cases until there were assurances of a

negative Ebola virus test result. In other instances, radiologic studies, such as

computed tomography and ultrasound scans, or evaluation for noninfectious

conditions, such as severe hypertension and tachycardia, were reportedly

delayed while a diagnosis of Ebola was under consideration.

Chance favors the

prepared mind.

Louis Pasteur

BIOPREPAREDNESS --AMP MODEL

GETTING STARTED

Biorisk

Management

Assessment

→

←Performance

Mitigation

↑

Laboratory Biorisk Management,

2015 CRC Press

Encompasses specific risks during outbreaks as well as day-to-day operations

First considerations for working with a potentially

harmful microbe.

Precautions must be taken in the laboratory to

mitigate risk of transmission in daily operations.

•What physical spaces in the lab can be utilized?

negative air pressure room

closed centrifuge system

biosafety hood

•What protective equipment is available.

PPE- standard or high level

closed automated instrument systems

autoclave for waste disposal

•How would you contain the microbe to limit

contamination or accidental infection?

KNOW YOUR BUG!

Know your Lab Biosafety Level http://ABSA.org

LABORATORY BIOSAFETY LEVEL CRITERIA BIOSAFETY IN MICROBIOLOGICAL AND BIOMEDICAL LABORATORIES

Bacterial microorganisms

and safety classification

Although in the past

all risk assessment

was based on a rigid

risk and biosafety level

format, the new

biorisk protocols

incorporate the

traditional classes of

pathogen risk and BSL

information however,

do not rely solely on

these predetermined

risk classifications.

Route of transmission

Human-to-human or vector borne

Contact, droplet, airborne

Localization of infectious agent in the body

Which body fluids or tissues are infectious

Infectivity

High consequence pathogen?

Is prophylaxis, vaccine, or treatment available

What laboratory testing might be necessary

RISK ASSESSMENT

FIRST IDENTIFY RISK GROUP OF PATHOGEN

THEN

1. Define the situation

2. Define the risks within the

situation

3. Characterize the risks

What work is occurring?

What can go wrong?

How likely is it to happen?

What are the consequences?

RISK GOVERNANCE

Risk is individual per institution and

depends on what mitigation is already

in place, as well pathogen, process,

work flow, and acceptable risk per

institution.

Acceptable risk may be dictated by an

institution, by local governance or

nationally.

Risk acceptability may vary with

emergency versus normal operations.

Each lab must do their own

homework! Workflow risk mitigation

RISK MITIGATION STRATEGY

Mitigation Controls Include: Elimination

Removal of biorisk—ie: no testing performed in core lab

Substitution

Options— ie: POC in patient room only

Engineering controls- primary and secondary

Equipment—BSC’s, closed automation, alarms, badge swipes, sensors

Intentional removal of hazardous material from the laboratory

Administrative controls

Who will conduct work

Training

Acceptable behaviors

Practices and Procedures

Policies, SOP’s

Personal protective equipment

What level of protection is necessary for each task

STRENGTHEN MITIGATIONS

SOP’s Personnel

Engineering

controls

If personnel do not--

Decontaminate appropriately

Leave air intake grill uncovered

No clutter

Dirty pipette disposal

UV light left on

Interrelated measures to optimize mitigation EXAMPLE: BSC provides

primary engineering control to

mitigate risk, but if SOP are

not thorough and personnel do

not follow procedures, risk will

not be mitigated as expected.

H i g h e n e r g y p r o c e d u r e s g e n e r a t e s m a l l e r d i a m e t e r a e r o s o l s Blending, mix ing with p ipet te, dropping samples, sonicat ion

1.0 -7.5 micrometer

L o w e r e n e r g y p r o c e d u r e s g e n e r a t e l a r g e r d r o p l e t s Centr i fuging, vor texing, sp i l l ing , shaking, p ipet t ing, pour ing, opening

>50 micrometer

Large droplets fa l l out of the a i r qu ickly contaminat ing work sur faces and equipment

Large droplets contaminate worker ’s hands, f ingers, and wr is ts

O n c e h a n d c o n t a m i n a t i o n h a s o c c u r r e d , p a t h o g e n s a r e e a s i l y t r a n s m i t t e d f r o m h a n d s t o m u c o u s m e m b r a n e s o n n o s e , e y e s a n d m o u t h . H a n d - t o - f a c e c o n t a c t ( H F C ) r o u t e o f e x p o s u r e i s p a r t i c u l a r l y i m p o r ta n t .

M i c r o b i a l a g e n t s h a n d l e d i n B S L - 2 a r e t r a n s m i t t e d b y i n g e s t i o n , p e r c u t a n e o u s i n j e c t i o n , o r d i r e c t c o n t a c t w i t h m u c o u s m e m b r a n e s r a t h e r t h a n b y i n h a l a t i o n i n m o s t c a s e s .

S t u d y o f 9 3 w o r k e r s f r o m 2 1 B S L - 2 l a b s , 5 6 % m a l e s , p r o f e s s o r s , p o s t do c s , r e s e a r c h f e l l o w s a n d a s s o c i a t e s , M D ’ s , g r a d u a t e s t u d e n t s .

S i t e s t o u c h e d → n o s e 4 4 % > f o r e h e a d 3 6 % > c h i n / c h e e k 1 2 . 5 % > m o u t h 4 % > e y e 1 . 7 %

7 2 % t o u c h e d t h e i r f a c e a t l e a s t o n c e , w i t h r a n g e o f 0 . 2 - 1 6 H F C / h r

LABORATORY GENERATED AEROSOLS

BIOSAFETY RISK

Eye and face protection should be mandatory for

pathogens with low infectious doses or agents with high

likelihood of direct contact transmission.

J Occupational and Environmental

Hygiene. Sept, 2014 625.-632.

Culture of biorisk management

Understand the science of implemented controls

Understand the consequences of failure to practice controls

Will not willingly circumvent engineering controls

Will not feel threatened by administrative controls

Institutional management must choose reliable employees

Physical competence

Trustworthiness

Mental competence

Emotional stability

Ability to uphold obligations for safety and integrity

STRENGTHEN MITIGATIONS

Personnel Behavior

Test orders: l imit testing/ timed/batch testing

Specimen collection: limit exposures

Specimen transport: no pneumatic tube

Processing of specimen(s): aerosolization?

Shipping of specimen(s): category A, who is trained?

Reporting: who and how? Logs

Medical staff communication: timely, who?

Waste and decontamination: city, county, state laws

STANDARD SOP’S FOR EID

STAFF AND ENVIRONMENTAL

RISK MITIGATION

Minimize test menu—disease dependent

Control test timing- Nursing colleagues

Control number of lab staff exposed

Provide written specimen collection guidance

Medical director should be involved with clinicians to guide

lab test utilization

This requires a medical director to interact with the clinical

team to determine necessity with a view towards acceptable

risk for lab staff.

TEST MENU CONTROLS

RISK MITIGATION

Ebola Test Menu recommendations:

CBC Malaria ABO Rh

Basic Metabolic panel Respiratory Panel Blood gas

PT/INR Blood cultures Urinalysis

LFT’s including bilirubin Rapid Strep Mg, Phos,

TRANSMISSION AND DECONTAMINATION

Viruses 7(12), 2014.

EBOV is shed in many body fluids

during acute illness but risk of

transmission from fomites is low.

Only fomite samples grossly

contaminated with blood were EBOV

PCR +. This suggests that fomites are

not frequent modes of transmission.

JID 2007:196 (Sup 2) 142.

EBOLA VIRAL DISEASE TRANSMISSION

Viruses, 7(12)2014

Initial PPE Recommendations Direct Care

Metamorphosis – Is More Better?

Exceeding PPE recommendations may actually increase the

rate of exposure.

Unfamiliar doffing techniques = self contamination

Extra gear can increase anxiety

Awkward movement, curtails activities

Train frequently, actual donning and doffing performance

Train only those who are willing volunteers for high level PPE

Always have a PPE buddy

PPE CONTROVERSY

MORE IS BETTER---NOT ALWAYS!

Ann Intern Med. 2014;161(10):751-752.

PPE

Overkill?

High risk?

The Dallas Ebola event demonstrated how a laboratory facility

without a biocontainment lab could implement risk mitigation

measures to ensure the safety of the laboratory staff and lab

environment while providing excellent diagnostic care for the

Ebola stricken patients.

Flexibility and adaptability are paramount in daily operations

Use of elimination and substitution controls were used as well

as primary engineering controls, administrative measures,

new and revised procedures and PPE training.

Personnel were volunteers, carefully chosen

OPTIMIZE BIORISK MITIGATION

Heroic phase— action heroes and ADRENALINE

Honeymoon phase—people pull together united

Fatigue/Conflict– every man for himself, blame

PTSD/Recovery– lessons learned, anxiety situations

MAKE SURE TO

1. Set boundaries, send people home

2. Emphasize teamwork

3. Provide guidance and emotional support

EMOTIONAL RESPONSES TO CRISIS

•Create opportunities to express concern

•Inspire personal safety

•Provide resources for response

•Address loss of revenue/liability

•Control speed of information flow

•Anticipatory guidance

•Answer queries :family’s safety

HEALTHY LAB ENVIRONMENT

IN CRISIS

Listen to staff concerns

Address the science--factual, candid, uncertainty

Update, be visible, be transparent

Frequent updates build trust and manage expectations

Open communications dispel rumors

Rumors in your own lab and in the community

Social support—personal stories

Psychosocial consequences can be extremely stressful

Thank your staff—

Laboratorians, the unrecognized heroes

CRISIS COMMUNICATION

EARLY AND OFTEN

As laboratory scientists, healthcare workers, and

humanitarians we have a moral duty to aid the sick and dying,

albeit with minimal risk to ourselves.

This can be accomplished by careful consideration of the risks,

with implementation of biosafety controls and protection.

Globalization has introduced many new as yet undiscovered

diseases as well as environmental and anthropogenic changes

that allow ancient or well known diseases to become endemic in

new global regions.

We cannot remove ourselves as laboratory scientists from the

risk of encountering an emerging infectious disease, thus we

must be prepared to encounter them but kept safe.

Bev Dickson, 2014 USA Ebola Event Participant