SARS-The Toronto Experience - · PDF fileSARS-The Toronto Experience ... Notes: 1The number of...

SARS-The Toronto Experience

Lecture given at the 13th ECCMID 2003 on May 11th byProf. Donald E. Low

Department of MicrobiologyUniversity Health Network, Mount Sinai Hospital and

University of TorontoToronto, Ontario, Canada

The Outbreak

Index Case Case A(Mother) (Son)

• A ProMED-mail post

• Source: WHO Press Release 12 Mar 2003• Acute respiratory syndrome in Hong Kong SAR, Viet

Nam• ---------------------------------------------• WHO issues a global alert about cases of atypical

pneumonia• Cases of severe respiratory illness may spread to

hospital staff• Since mid February 2003, WHO has been actively

working to confirm reports of outbreaks of a severe form of pneumonia in Viet Nam, Hong Kong SAR, China, & Guangdong province in China.

Index Case Case A(Mother) (Son)

March 13th, 2003

• That morning:– phone call from physician at Scarborough Grace

Hospital (SGH) regarding an unusual cluster of unexplained illnesses in a Chinese family including two deaths

• That evening:– 4 family members assessed and admitted at

Mount Sinai Hospital with pneumonia

Index Case Case A(Mother) (Son)

(Son)

(Father) (Son) (Daughter-in-law)

Index Case Case A

Case B

(Mother) (Son)

Index Case Case A

Case B

Case B’swife

24 persons

(Mother) (Son)

9 persons

Index Case Case A

Case B

Case C

Case B’swife

9 persons

24 persons

21 persons

(Mother) (Son)

Index Case Case A

Case B

Case C

Case B’swife

9 persons

24 persons

21 persons

Case D

15 persons

7 persons

(Mother) (Son)

Case A(died)

Case B(died)

Case C(died)

4 members of family A

Family A’sphysician 1 CC

1 X-ray tech

3 ICU nurses

1 HH

3HH

3 EMS

March 16, 20037 ER visitors1 ER patient

5 HH1 CC

6 CCU nurses

3 HH1 CCU Clerk

1 physician1 physician’s clerk

3 HH

1 CCU patient( 1 died)

Transferred toanother hospital

1 physician

1 HH

Figure 3. Transmission of SARS in Hospital A (N=72)

2 ER nurses 2 ER nurses

1 ER Clerk

Case B’s wife(died)

4 ER nurses Clinic nurse

1 Housekeeper

1 HH

1 Housekeeper

1 EMS

LEGEND

Case

Household case

Close contact case

Transmission outsideof Hospital A

HH

Transferred toHospital B

Index Case(died)

Case C’s wife

1 coworker privatesector

CC

1 visitor1 ER patient

10HCW, 3V,2P

7 HCW

Transmission of SARS in hospital C (N=7)

Reported cases of SARS in cases linked to the BLD group March 20 to April 16, 2003

0

1

2

3

4

5

6

7

8

19/03

/0321

/03/03

23/03

/0325

/03/03

27/03

/0329

/03/03

31/03

/0302

/04/03

04/04

/0306

/04/03

08/04

/0310

/04/03

12/04

/0314

/04/03

16/04

/03

Date of onset of symptoms

Num

ber o

f cas

es

Health Care WorkerBLDFamily

Clinical Disease

Clinical Features and Short-term Outcomes of 144 Patients

With SARS in the Greater Toronto Area

(Booth et al. JAMA express)

DemographicsStudy population 1471

Median age 45 yrs (range 17-99)Female 88 (61%)Male 56 (39%)

Health care worker 73 (51%)Nurse 29 (40%)Physician 14 (19%)Other 30 (41%)

1Note: 3 patients contracted SARS while admitted to hospital for other conditions, they have been excluded from the subsequent analysis

Co-MorbiditiesDiabetes 16/144 (11%)COPD 2/144 (1%)Chronic renal failure 2/144 (1%)Cancer 9/144 (6%)Cardiac disease 12/144 (8%)

ExposureTravel 3 (2.1%)Home 35 (24%)Hospital1 111 (77%)

Hospital A 82 (74%)Hospital B 8 (7%)Hospital C 7 (6%)Other 14 (13%)

*Note: 1This group includes healthcare workers, patients and visitors.

Time from Exposure to Symptoms

Median days from earliest known exposure1

“Prodrome”2 6 days (3-10)3

Fever 7 days (4-10) Diarrhea 8 days (3-11)Cough/Dyspnea 9 days (5-12)

Notes: 1The number of days is based on history from the patient.2”Prodrome” includes headache, malaise, myalgia.325th and 75th percentiles are shown in parentheses.

Course of IllnessInitial symptoms of SARS:

“Prodrome”1 and Fever 33 (23%)Fever alone 33 (23%)“Prodrome” alone 19 (13%)“Prodrome”, fever, and cough 16 (11%)Fever and cough 15 (11%)Cough alone 13 (9%)

Note: 1”Prodrome” includes headache, malaise, myalgia.

Course of Illness:another view

How often is: “prodrome” first? 74 (52%)fever first? 106 (74%)cough first? 51 (35%)diarrhea first? 9 (6%)

Course of IllnessSeen prior to admission 49 (34%)

ER 23 (52%)Clinic/Doctor’s office 18 (41%)Hospital 3 (7%)

Median time from first visit until admission 3 days (2-5)1

Note: 125th and 75th percentiles are shown in parentheses

RhinorrheaAbd. PainDizziness

Prod. CoughChest Pain

ArthralgiaSore Throat

Nausea/VomitDiarrhea

ChillsMalaise

HeadacheDyspneaMyalgia

Nonprod. CoughReported Fever

0 20 40 60 80 100

Percent with Symptom At Presentation

0 20 40 60 80 100

2.1%3.5%4.2%4.9%

10.4%10.4%

12.5%19.4%

23.6%27.8%

31.2%35.4%

41.7%49.3%

69.4%99.3%

Physical FindingsTachycardia (>100bpm) 66 (46%)

Tachypnea (RR>20) 53 (37%)

Rales 37 (26%)

Chest Radiograph Findings

At admission Progression during hospitalization

Normal 36 (25%) No change 15/36 (42%)

Unilateral 12/36 (33%)

Bilateral 9/36 (25%)

Unilateral infiltrate 66 (46%) No change 42/66 (64%)

Bilateral 24/66 (36%)

Bilateral infiltrate 42 (29%) - -

Pneumothorax 4 (3%)

Laboratory Indices: Admission

Median Value (25 th, 75thPercentile) Normal range

WBC 5.2 x 10 9 /L (3.6 -7.3) 4-11

Neutrophils 3.6 x 10 9 /L (2.4 -5.7) 2.0-7.5

Lymphocytes 0.9 x 10 9 /L (0.7 -1.3) 1.5-4.0

Platel ets 183 x 10 9 /L (147 -223) 150-400

PTT 34.0 s (29.7 -36.1) 28-40

INR 1.0 (1.0 -1.1) 0.8-1.2

LDHAdmission

Median1 396 U/L (219-629)No. abnormal2 86/99 (87%)

During Hospitalization3

Median 630 U/L (363-1156)No. abnormal2 115/123 (94%)

Notes: 1For all laboratory values the median and the 25th and 75th

percentiles are presented.2Abnormal values are those > 190 U/L.3These values reflect the most abnormal values during hospitalization.

Creatine KinaseAdmission

Median 157 U/L (70-310)No. abnormal1 43/109 (39%)

During HospitalizationMedian 370 U/L (208-959)No. abnormal1 64/118 (54%)

Note: 1Abnormal values are those >240 for males and > 150 for females.

3638

4042

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

Maximum Daily Temperature

Day of Hospitalization

Max

imum

Tem

pera

ture

(C)

144 144 142 138 133 119 100 78 63 55 47 41 34 26 23 16 10 7 4 3 3N=

Treatment

Treatment Proportion Cumulative % Cumulative %Receiving Started by Day 1 Started by Day 2

Ribavirin 126 (88%) 76% 91%

Steroids 58 (40%) 31% 40%

Antibiotics 137 (95%) 79% 94%

Ribavirin Therapy

Route of administrationIV 85 (67.5%)PO 4 (32.%)Both 37 (2.4%)

Median duration of treatment 6 (5-7) days

Outcomes1

Deaths 8/144 (6%)

Alive 136/144 (94%)

Discharged 103/144 (72%)

Still hospitalized 33/144 (23%)– 8 patients (6%) still ventilated

Note: 1Outcomes as of April 17 2003.

OutcomesOf the 8 deaths:

6/8 had diabetes (75%)

• One of the patients without diabetes had cancer• One patient had no medical co-morbidity other

than being a former smoker

(omitting dead)

Days from Hospital Admission

Prop

ortio

n St

ill in

Hos

pita

l

0 5 10 15 20 25 30

0.0

0.2

0.4

0.6

0.8

1.0

Time to Death

Days from Hospital Admission

Prop

ortio

n Al

ive

0 10 20 30

0.0

0.2

0.4

0.6

0.8

1.0

Time from Admission to Death

Days from Hospital Admission

Prop

ortio

n Al

ive

0 10 20 30

0.0

0.2

0.4

0.6

0.8

1.0

Age<60; n=11460+; n=30

Predictors of Poor Outcome

Poor outcome defined as: death, ventilation, or ICU admission

Incidence of poor outcome 30/144 (21%)

Univariate AnalysisVariable RR 95% CI P value1

Age 60 or greater 1.9 1.3-2.7 <0.001Ribavirin used 1.9 0.45-8.0 0.363Diabetes 5.4 2.5-11.5 <0.001Any co-morbidity2 4.4 2.1-8.9 <0.001

Note: 1P value calculated using Cox proportional hazards model.2Any co-morbidity includes diabetes, COPD, cancer, and

cardiac disease.

Multiple Regression Analysis• a priori hypothesis of age and co-morbidities being associated

with poor outcome

Variable RR 95%CI P value1

Diabetes 3.1 1.4-7.2 0.01Other co-morbidity2 2.5 1.1-5.8 0.03Age 60 or greater 1.4 0.95-2.1 0.09

Note: 1P value calculated using Cox proportional hazards model.2Other co-morbidites include COPD, cancer, and cardiac disease.

Time from Admission to Poor Outcome

Days from Hospital Admission

Prop

ortio

n w

ithou

t Poo

r Out

com

e

0 5 10 15 20 25 30

0.0

0.2

0.4

0.6

0.8

1.0

Age<6060+

Time from Admission to Poor Outcome

Days from Hospital Admission

Prop

ortio

n w

ithou

t Poo

r Out

com

e

0 5 10 15 20 25 30

0.0

0.2

0.4

0.6

0.8

1.0

TreatmentRibavirin-; n=18Ribavirin+; n=126

Time from Admission to Poor Outcome

Days from Hospital Admission

Prop

ortio

n w

ithou

t Poo

r Out

com

e

0 5 10 15 20 25 30

0.0

0.2

0.4

0.6

0.8

1.0

No comorbid illness; n=115

Other+/Diabetes-; n=13

Other-/Diabetes+; n=8

Other+/Diabetes+; n=8

Conclusions1. The majority of cases were acquired in hospital

(healthcare workers, patients and visitors) and most of those occurred in one hospital before intensive respiratory precautions were instituted for both patients and their contacts.

2. Fever is very close to the first symptom in almost everyone.

3. Rhinorrhea is not a common presenting symptom of SARS.

Conclusions4. Many patients were evaluated and sent home prior

to admission to hospital (perhaps because the signs and symptoms are so non-specific).

5. The most useful feature on physical exam is elevated temperature.

6. The current WHO, CDC, and Health Canada definitions of suspect SARS exclude 11% of patients who have fever, contact and pulmonary infiltrates with NO respiratory symptoms.

7. 25% of patients have a normal CXR on admission.

Conclusions8.The hallmark laboratory findings are

lymphopenia and elevated LDH.

9.Many patients also demonstrate low calcium, phosphate, magnesium, and potassium levels and elevated CK on admission to hospital.

10.The pre-existing electrolyte abnormalities tend to get worse in hospital.? 2° to Ribavirin and other therapies?

Conclusions11. Ribavirin is associated with many side effects,

especially hemolysis and transaminitis.

12. Diabetes and other co-morbidities are independently associated with poor outcome.

13. Based on short-term outcome data (30 days), the vast majority (94%) of people survive SARS.

Clinical progression and viral load in a community outbreak

of coronavirus-associated SARS pneumonia: a prospective study

(Peiris et al. Lancet, 2003:361)

Methods

• Between March 24 and 28, 2003 75 patients admitted from Amoy Gardens

• Followed prospectively• All patients treated with ribavirin for 14

days and prednisolone for 13 days

Results

• All but one patient became afebrile within 48 hours, but fever recurred in 64 (85%) of patients by 8-9 days

Infection control for SARS

How is SARS spread?• MOST OFTEN spread by contact and or droplet

– That is, touching a patient or their secretions directly (and then touching your face), or having droplets from their breathing, speaking, coughing etc. land on your hands or face

• Other possible routes– Airborne (breathing same air without N95 mask)– Contact with contaminated environment– Re-aerosolization of droplets (eg. When mask

removed, or with toilet flushing or bed sheets shaken out)

How can we prevent transmission? I

• Ensure that all patients who might have SARS are rapidly identified and managed in precautions

• Minimize the opportunities for exposure of staff/other patients to SARS patients

• Minimize the number of droplets the patient produces (eg. minimize coughing, vomiting)

How can we prevent transmission? II

• Control air flow and air exchanges • Use N95 masks to protect against possibility of

airborne spread • Use barriers to prevent direct contact and droplet

contact• Handle patient area (eg. Linens) and remove

barriers so as to prevent re-aerosolization• Repeated, thorough cleaning of the environment

Identification/management of patients

• Fever surveillance in patients– All patients with fever assessed for SARS risk,

maintained in SARS precautions

• Fever/symptom surveillance in staff– Occupational health assessment of staff with

fever, myalgias, new cough

Managing Known SARS patientsRoom Placement/Entry

• Airborne isolation rooms or SARS unit (negative pressure, at least 6 air exchanges per hour)

• Only essential staff enter room/unit• Minimize time in room • Minimize time within six feet of patient

– HCW position to avoid droplets in front of patient’s face• Minimize amount of direct contact with patient• Do not go into patient’s bathroom unless

essential for patient care

Managing Known SARS PatientsReducing Droplets

• Medical management to reduce cough• Medical management to reduce nausea and

prevent vomiting• No nebulizer treatments• Supply oxygen dry; by nasal prongs if

possible• Patient to wear surgical mask at all times

when HCW are in the room• Handle bed linens to avoid creating aerosols

Managing Known SARS PatientsProtective Barriers - 1

• N95 mask • Face shield (fluid shield mask worn

upside down)• Cap/Hair cover• Gown• Double Glove

Managing Known SARS PatientsProtective Barriers - 2

• N95 mask– Ensure fits on face– Comfortable enough so that does not need

adjustment while garbed• Ensure overlap between gloves and gown cuff• Double glove

– Wear first pair for direct contact with patient, then remove

– If top pair of gloves contaminated (eg cleaning vomit), remove and replace

Managing Known SARS PatientsProtective Barriers - 3

• Protect face– Consciously keep hands away from

face/head/neck while in room– Ensure hair is tied or clipped back so that

hands do not move to adjust• Do not check pager, or answer phone

while in room

Managing Known SARS PatientsRemoving Barriers - 4

• At door to room, remove gloves, then gown• Disinfect hands with alcohol handwash in the room• Leave the room• Disinfect hands• Remove hair cover• Hold the mask/face shield by the edge of the face shield

and lift it up over your head• Remove N95 mask, by holding at the bottom and lifting it

up over your head• Disinfect hands• Put on a clean N95 mask, then a clean gown

High risk activities

• Intubation• Noninvasive positive pressure ventilation• Manual bagging• Nebulized medication administration• Use of Venturi mask• Tracheal and oropharyngeal suction• Nasopharyngeal aspiration / throat swab• Percussion chest physiotherapy

High risk activities (cont’d)• Manual bagging

– Avoid where possible; minimize time• Tracheal and oropharyngeal suction

– Always used closed suction• Nasopharyngeal aspiration / throat swab

– Use nasal, not NP swab– Perform swab with mask over mouth, and

tissues at hand for the patient

Intubation for SARS patients

• Elective intubation preferred• Negative pressure, well ventilated room• Minimize number of people in room• Most experienced staff members only• Protective gear, as usual, with addition of PAPR • Avoid manual bagging• Perform procedure that is safe for patient, while

minimize cough and other droplet producing effects/procedures

Protective Barriers: N95 masks, face shields, gown and gloves

Removing Barriers

At door to room, remove gloves, then gown

Removing Barriers

Disinfect hands with alcohol handwash in the room

Removing Barriers

Leave the room

Removing Barriers

Disinfect hands

Removing Barriers

Hold the face shield by the edge of the face shield and lift it up over your head

Removing Barriers

Remove N95 mask, by holding at the bottom and lifting it up over your head

Removing Barriers

Remove hair cover

Removing Barriers

Disinfect hands

Protective Barriers

Put on a clean N95 mask, a clean gown, and hair cover

Heightened Awareness

Toronto Area Probable and Suspect cases by source of infectionMay 5, 2003

0

2

4

6

8

10

12

23-F

eb-0

325

-Feb

-03

27-F

eb-0

301

-Mar

-03

03-M

ar-0

305

-Mar

-03

07-M

ar-0

309

-Mar

-03

11-M

ar-0

313

-Mar

-03

15-M

ar-0

317

-Mar

-03

19-M

ar-0

321

-Mar

-03

23-M

ar-0

325

-Mar

-03

27-M

ar-0

329

-Mar

-03

31-M

ar-0

302

-Apr

-03

04-A

pr-0

306

-Apr

-03

08-A

pr-0

310

-Apr

-03

12-A

pr-0

314

-Apr

-03

16-A

pr-0

318

-Apr

-03

20-A

pr-0

322

-Apr

-03

24-A

pr-0

326

-Apr

-03

28-A

pr-0

330

-Apr

-03

02-M

ay-0

304

-May

-03

Date of onset of first symptoms

Num

ber o

f cas

es (P

& S

)TravelNon health careHealth care settings