SARS-The Toronto Experience

Transcription

1 SARS-The Toronto Experience Lecture given at the 13 th ECCMID 2003 on May 11 th by Prof. Donald E. Low Department of Microbiology University Health Network, Mount Sinai Hospital and University of Toronto Toronto, Ontario, Canada

2 The Outbreak

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4 Index Case (Mother) Case A (Son)

5 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.

6 Index Case (Mother) Case A (Son)

7 March 13 th, 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

8 Index Case (Mother) Case A (Son) (Father) (Son) (Daughterin-law) (Son)

9 Case B Index Case (Mother) Case A (Son)

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12 Case B Case B s wife 24 persons 9 persons Index Case (Mother) Case A (Son)

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18 Case B Case B s wife 24 persons 9 persons Case C Index Case (Mother) Case A (Son) 21 persons

19 Case B Case B s wife 24 persons 9 persons Case C Index Case (Mother) Case A (Son) 21 persons Case D 7 persons 15 persons

20 Figure 3. in Hospital A (N=72) Transmission of SARS in hospital C (N=7) Family A s physician 1 CC 4 members of family A 1 X-ray tech 1 HH 3 ICU nurses March 16, ER visitors 1 ER patient 5 HH 1 CC 3 EMS 3HH Index Case (died) Case A (died) Case B (died) Case B s wife (died) 1 physician 4 ER nurses Clinic nurse 1 Housekeeper 1 EMS 1 HH 2 ER nurses 2 ER nurses Case C (died) 1 ER patient 1 ER Clerk 1 visitor LEGEND 1 Housekeeper Case C s wife 1 physician 1 physician s clerk HH CC Case Household case Close contact case Transmission outside of Hospital A 1 CCU Clerk 6 CCU nurses 1 CCU patient ( 1 died) Transferred to Hospital B 3 HH 3 HH 1 HH Transferred to another hospital 1 coworker private sector 7 HCW 10HCW, 3V,2P

21 16/04/ Reported cases of SARS in cases linked to the BLD group March 20 to April 16, 2003 Health Care Worker BLD Family 23/03/03 25/03/03 27/03/03 29/03/03 31/03/03 02/04/03 04/04/03 06/04/03 08/04/03 10/04/03 12/04/03 14/04/03 Date of onset of symptoms 21/03/03 19/03/03 Number of cases

22 Clinical Disease

23 Clinical Features and Shortterm Outcomes of 144 Patients With SARS in the Greater Toronto Area (Booth et al. JAMA express)

24 Demographics Study population 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%) 1 Note: 3 patients contracted SARS while admitted to hospital for other conditions, they have been excluded from the subsequent analysis

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

26 Exposure Travel 3 (2.1%) Home 35 (24%) Hospital (77%) Hospital A 82 (74%) Hospital B 8 (7%) Hospital C 7 (6%) Other 14 (13%) *Note: 1 This group includes healthcare workers, patients and visitors.

27 Time from Exposure to Symptoms Median days from earliest known exposure 1 Prodrome 2 6 days (3-10) 3 Fever 7 days (4-10) Diarrhea 8 days (3-11) Cough/Dyspnea 9 days (5-12) Notes: 1 The number of days is based on history from the patient. 2 Prodrome includes headache, malaise, myalgia th and 75 th percentiles are shown in parentheses.

28 Course of Illness Initial 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.

29 How often is: Course of Illness: another view prodrome first? 74 (52%) fever first? 106 (74%) cough first? 51 (35%) diarrhea first? 9 (6%)

30 Course of Illness Seen 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: 1 25 th and 75 th percentiles are shown in parentheses

31 Reported Fever Nonprod. Cough Myalgia Dyspnea Headache Malaise Chills Diarrhea Nausea/Vomit Sore Throat Arthralgia Chest Pain Prod. Cough Dizziness Abd. Pain Rhinorrhea 49.3% 41.7% 35.4% 31.2% 27.8% 23.6% 19.4% 12.5% 10.4% 10.4% 4.9% 4.2% 3.5% 2.1% 69.4% 99.3% Percent with Symptom At Presentation

32 Physical Findings Tachycardia (>100bpm) 66 (46%) Tachypnea (RR>20) 53 (37%) Rales 37 (26%)

33 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%)

34 Laboratory Indices: Admission Median Value (25 th, 75 th Percentile) Normal range WBC 5.2 x 10 9 /L ( ) 4-11 Neutrophils 3.6 x 10 9 /L ( ) Lymphocytes 0.9 x 10 9 /L ( ) Platel ets 183 x 10 9 /L ( ) PTT 34.0 s ( ) INR 1.0 ( )

35 LDH Admission Median U/L ( ) No. abnormal 2 86/99 (87%) During Hospitalization 3 Median 630 U/L ( ) No. abnormal 2 115/123 (94%) Notes: 1 For all laboratory values the median and the 25 th and 75 th percentiles are presented. 2 Abnormal values are those > 190 U/L. 3 These values reflect the most abnormal values during hospitalization.

36 Creatine Kinase Admission Median 157 U/L (70-310) No. abnormal 1 43/109 (39%) During Hospitalization Median 370 U/L ( ) No. abnormal 1 64/118 (54%) Note: 1 Abnormal values are those >240 for males and > 150 for females.

37 Maximum Daily Temperature Maximum Temperature (C) Day of Hospitalization N=

38 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%

39 Ribavirin Therapy Route of administration IV 85 (67.5%) PO 4 (32.%) Both 37 (2.4%) Median duration of treatment 6 (5-7) days

40 Outcomes 1 Deaths 8/144 (6%) Alive 136/144 (94%) Discharged 103/144 (72%) Still hospitalized 33/144 (23%) 8 patients (6%) still ventilated Note: 1 Outcomes as of April

41 Outcomes Of 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

42 (omitting dead) Days from Hospital Admission Proportion Still in Hospital

43 Time to Death Days from Hospital Admission Proportion Alive

44 Time from Admission to Death Proportion Alive Age <60; n= ; n= Days from Hospital Admission

45 Predictors of Poor Outcome Poor outcome defined as: death, ventilation, or ICU admission Incidence of poor outcome 30/144 (21%)

46 Univariate Analysis Variable RR 95% CI P value 1 Age 60 or greater <0.001 Ribavirin used Diabetes <0.001 Any co-morbidity <0.001 Note: 1 P value calculated using Cox proportional hazards model. 2 Any co-morbidity includes diabetes, COPD, cancer, and cardiac disease.

47 Multiple Regression Analysis a priori hypothesis of age and co-morbidities being associated with poor outcome Variable RR 95%CI P value 1 Diabetes Other co-morbidity Age 60 or greater Note: 1 P value calculated using Cox proportional hazards model. 2 Other co-morbidites include COPD, cancer, and cardiac disease.

48 Time from Admission to Poor Outcome Age < Days from Hospital Admission Proportion without Poor Outcome

49 Time from Admission to Poor Outcome Proportion without Poor Outcome Treatment Ribavirin-; n=18 Ribavirin+; n= Days from Hospital Admission

50 Time from Admission to Poor Outcome Proportion without Poor Outcome No comorbid illness; n=115 Other+/Diabetes-; n=13 Other-/Diabetes+; n=8 Other+/Diabetes+; n= Days from Hospital Admission

51 Conclusions 1. 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.

52 Conclusions 4. 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 % of patients have a normal CXR on admission.

53 Conclusions 8.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?

54 Conclusions 11. 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.

55 Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study (Peiris et al. Lancet, 2003:361)

56 Methods Between March 24 and 28, patients admitted from Amoy Gardens Followed prospectively All patients treated with ribavirin for 14 days and prednisolone for 13 days

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

58 Infection control for SARS

59 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)

60 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)

61 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

62 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

63 Managing Known SARS patients Room 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

64 Managing Known SARS Patients Reducing 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

65 Managing Known SARS Patients N95 mask Protective Barriers - 1 Face shield (fluid shield mask worn upside down) Cap/Hair cover Gown Double Glove

66 Managing Known SARS Patients N95 mask Protective Barriers - 2 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

67 Managing Known SARS Patients Protect face Protective Barriers - 3 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

68 Managing Known SARS Patients Removing 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

69 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

70 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

71 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

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

73 Removing Barriers At door to room, remove gloves, then gown

74 Removing Barriers Disinfect hands with alcohol handwash in the room

75 Removing Barriers Leave the room

76 Removing Barriers Disinfect hands

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

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

79 Removing Barriers Remove hair cover

80 Removing Barriers Disinfect hands

81 Protective Barriers Put on a clean N95 mask, a clean gown, and hair cover

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90 Heightened Awareness

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93 Toronto Area Probable and Suspect cases by source of infection May 5, 2003 Travel Non health care Health care settings 27-Feb Mar Mar Mar Mar Mar Mar Mar Mar Mar Mar Mar Mar Mar Mar Mar Mar Apr Apr Apr Apr Apr Apr Apr Apr Apr Apr Apr Apr Apr Apr Apr May May-03 Date of onset of first symptoms 23-Feb Feb-03 Number of cases (P & S)