Sars

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Laboratory Diagnostics: 

Laboratory Diagnostics Bonna Cunningham, MS North Dakota Public Health Laboratory

SARS Testing* at CDC: 

SARS Testing* at CDC Antibody Tests Molecular Test Cell Culture * SARS serologic and molecular assays will be available at the NDPHL shortly (pending release by CDC).

Antibody Tests: 

Antibody Tests IFA and ELISA Reliable 21 days post onset of fever Antibodies detected as early as 14 days in some cases

Molecular Test: 

Molecular Test RT-PCR Positives reported Negatives repeated with more sensitive primers when available

Viral Culture: 

Viral Culture Respiratory secretions and blood Vero, Vero E6 support virus replication Other cell lines being evaluated

Interpreting Test Results: 

Interpreting Test Results Positive Indicates current or recent infection with the coronavirus. Negative Does not mean the patient does not have SARS. Diagnose on clinical evaluation and possible past exposure.

Potential SARS Specimens: 

Potential SARS Specimens Serum 5-10 ml blood in serum separator EDTA whole blood 5-10 ml Stool  10-50 cc NP swabs/OP swabs Dacron swab in viral transport

M4 Viral Transports Insert illustration: 

M4 Viral Transports Insert illustration

Location of M4 Viral Transports in North Dakota: 

Location of M4 Viral Transports in North Dakota Two M4 viral transports/swabs in each smallpox shipper Four shippers at each NDLRN Level A laboratory Four shippers at each District Health Unit Additional six M4 viral transports/swabs at each District Health Unit

Level A Labs Insert MAP: 

Level A Labs Insert MAP

District Public Health Units Insert MAP: 

District Public Health Units Insert MAP

Packaging and Shipping: 

Packaging and Shipping Follow IATA/DOT packaging regulations for Diagnostic Specimens* http://www.cdc.gov/ncidod/sars/packingspecimens-sars.htm * “Smallpox shippers” issued by NDDoH meet requirements

Smallpox Shippers (Insert Illustration): 

Smallpox Shippers (Insert Illustration) Contact the NDPHL for assistance Phone Number: 701.328.5262

Laboratory Biosafety: 

Laboratory Biosafety Establish protocols to protect laboratory workers Labeling suspected SARS cases Handling blood specimens for routine testing Handling specimens for microbiological analysis Define BSL-2 practices* Define BSL-3 practices* *Refer to CDC/NIH Biosafety in Microbiological and Biomedical Laboratories manual (BMBL): http://www.cdc.gov/od/ohs/biosfty/bmb14/bmb143s3.htm

Blood Specimens for Routine Testing: 

Blood Specimens for Routine Testing Use universal precautions Wear appropriate PPE Disposable gloves Lab coat Eye/face shields Use safe centrifugation practices

Centrifuging Protocols: 

Centrifuging Protocols Use sealed centrifuge cups or rotors Load and unload in BSC If sealed centrifuge cups and BSC not available Keep testing to a minimum Centrifuge separately Limit number of staff in room where centrifuge is located Use respiratory protection when unloading centrifuge N-95 mask Eye/face shields

BSL-2 Activities: 

BSL-2 Activities Exam/processing of formalin-fixed tissues Molecular analysis of extracted preps EM with glutaraldehyde-fixed grids Routine exam of bacterial/mycotic cultures Routine staining/analysis of fixed smears Packaging specimens for transport --Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with SARS, Department of Health and Human Services, Centers for Disease Control and Prevention, April 2, 2003

BSL-2 Activities/BSL-3 Practices: 

BSL-2 Activities/BSL-3 Practices Aliquoting/diluting specimens Inoculating bacterial/mycotic culture media Microbiology testing other than propagation of viral agents Nucleic acid extractions of untreated specimens Prep/fixing of smears for micro analysis --Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with SARS, Department of Health and Human Services, Centers for Disease Control and Prevention, April 2, 2003

BSL-3 Activities: 

BSL-3 Activities Viral cell culture Initial characterization of viral agents in cultures of SARS specimens --Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with SARS, Department of Health and Human Services, Centers for Disease Control and Prevention, April 2, 2003

NDDoH Website: 

NDDoH Website http://www.health.state.nd.us/disease/SARS

Slide21: 

Burleigh Oliver Dunn Slope Bowman Billings Golden Valley Stark Hettinger Adams Sioux Grant Mercer Morton Mountrail Williams McKenzie Divide Burke McHenry McLean Ward Renville Bottineau Kidder Dickey Emmons McIntosh Stutsman Logan La Moure Sargent Richland Barnes Ransom Cass Ramsey Eddy Wells Sheridan Foster Rolette Pierce Benson Towner Nelson Steele Griggs Traill Grand Forks Cavalier Walsh Pembina North Dakota Laboratory Response Network 12 8 9 9 7 6 5 1 2 13 14 15 16 Level-A Laboratories 1. Mercy Hospital, Williston 2. Trinity Med. Cen., Minot 3. USAFB, Minot 4. Presentation Hospital, Rolla 5. Mercy Hosp, Devils Lake 6. USAFB, Grand Forks 7. Altru Hospital, Grand Forks 8. Innovis Health Center, Fargo 9. MeritCare Med Cen., Fargo 10. VA Medical Center, Fargo 11. Dakota Clinic, Fargo 12. Mercy Hosp., Valley City 13. Health Care Hosp., Jamestown 14. MedCenter One, Bismarck 15. St. Alexius Med. Cen., Bismarck 16. St. Joseph Hospital, Dickinson 17. West River Reg. Med. Center, Hettinger NDPHL 3 4 17 10 11 Level-B/C Laboratory North Dakota Public Health Laboratory (NDPHL)

Severe Acute Respiratory Syndrome (SARS): 

Larry A. Shireley, MS, MPH State Epidemiologist North Dakota Department of Health Severe Acute Respiratory Syndrome (SARS)

CDC SARS Case Definition April 10, 2003: 

Onset since February 1, 2003 Measured temperature ≥ 100.50F Respiratory Illness* AND Travel within 10 days of symptoms onset to: Peoples’ Republic of China, Hong Kong, Hanoi, Viet Nam or Singapore OR Close contact within 10 days of symptoms onset to: Suspected SARS case Respiratory illness & travel to above areas * WHO definition requires radiographic evidence of infiltrates consistent with pneumonia or respiratory distress syndrome CDC SARS Case Definition April 10, 2003

Epidemiology: 

Epidemiology Transmission Person – Person Health Care Workers Community Transmission United States – Primarily related to travel Primarily adults – 25 – 70 Uncommon < 15 years old

Epidemiology: 

Epidemiology Most Cases Resolve ~90%+ day 6-7 Mortality ~ 4 % United States Cases less severe Reasons? Cultural? Medical care? Other co-infection?

SARS Time Line: 

SARS Time Line November 16, 2002 Index Case – Guangdong, China (Reported Feb 14, 2003) Feb 11, 2003 - First Case Reports from China Feb 21 Hong Kong hotel outbreak Feb 28, 2003 – Viet Nam reports cases Global Alert – March 12, 2003 March 14 – Canada reports cases March 15 – WHO Travel Advisory March 24 – Link to coronavirus April 3 – CDC Travel Advisory April 4 – Executive Order - Quarantine

Suspected Cases Worldwide (April 12, 2003): 

Suspected Cases Worldwide (April 12, 2003) Total Cases 2,960 Deaths 119 Number of Countries 19

Suspected SARS Cases by Country April 12, 2003: 

Suspected SARS Cases by Country April 12, 2003

Suspected SARS Cases by Country April 12, 2003 (cont): 

Suspected SARS Cases by Country April 12, 2003 (cont)

Reported Suspect Cases of SARS United States through April 10, 2003: 

5 RI 1 CT 4 NJ 3 MA 5 35 21 5 1 5 1 2 7 1 3 1 1 6 3 2 3 HI 5 5 NH 1 6 14 VT 2 5 11 1 1 Reported Suspect Cases of SARS United States through April 10, 2003

Characteristics of US SARS Cases* As of April 9, 2003: 

Characteristics of US SARS Cases* As of April 9, 2003 135 (81%) Adults 154 (93%) Travel to endemic area 9 (5%) Household contact to SARS 3 (2%) Health Care Workers 60 (36%) Hospitalized >24 hours 33 (20%) Radiographic abnormalities *166 cases

Number of Suspected Cases of SARS by Exposure Category and Date of Illness Onset United States, 2002: 

Number of Suspected Cases of SARS by Exposure Category and Date of Illness Onset United States, 2002 CDC, MMWR April 11, 2003

Number and Percentage of Reported SARS Cases by Selected Characteristics United States, 2003 : 

Number and Percentage of Reported SARS Cases by Selected Characteristics United States, 2003 * N = 166. †To mainland China, Hong Kong, Hanoi, or Singapore. § As of April 9, no deaths of SARS patients have been reported in the United States. ¶ Respiratory distress syndrome. CDC, MMWR April 11, 2003

Keys to Control: 

Keys to Control Early recognition and treatment of cases Stringent Infection Control Procedures in Hospitals and Clinics Prompt Reporting of Suspected Cases Investigation & Contact Tracing Public Awareness and Education

SARS Severe Acute Respiratory Syndrome: 

SARS Severe Acute Respiratory Syndrome Clinical Issues “We've never faced anything on this scale with such a global reach.” -Dr. David Heymann, World Health Organization

SARS Background: 

SARS Background 26 Feb 03 1st case Hanoi WHO official - Dr. Carlo Urbani died 29 Mar 03 SARS

SARS Background Case 1: 

SARS Background Case 1 Disease symptom onset Feb. 15 Traveled from Guangdong Province to Hong Kong Hotel M Feb 21 Died Feb 23 4 health care workers and 2 family contacts, and 10 hotel guests developed disease

SARS Background Case 2: 

SARS Background Case 2 Admitted to a Hanoi hospital Feb 26 Travel to Hong Kong Hotel M Respiratory failure requiring ventilatory support Evacuated to Hong Kong; died March 12 59 contacts developed disease

Chain of Transmission at Hotel M - Hong Kong 2003: 

MMWR March 28, 2003 / 52(12);241-248 Chain of Transmission at Hotel M - Hong Kong 2003

Slide41: 

MMWR April 4, 2003 / 52(13);269-272

Slide42: 

MMWR March 28, 2003 / 52(12);241-248

Hong Kong study of 50 cases www.thelancet.com 8 Apr 03: 

Hong Kong study of 50 cases www.thelancet.com 8 Apr 03

Predictors of “severe” SARS in Hong Kong www.thelancet.com 8 Apr 03: 

Predictors of “severe” SARS in Hong Kong www.thelancet.com 8 Apr 03 DM Chronic active hepatitis Cardiomopathy HTN

Predictors of “severe” SARS www.thelancet.com 8 Apr 03: 

Predictors of “severe” SARS www.thelancet.com 8 Apr 03 Method of contact Travel to china HCW Hospital visit Household contact Social contact P = 0.09

Predictors of “severe” SARS www.thelancet.com 8 Apr 03: 

Predictors of “severe” SARS www.thelancet.com 8 Apr 03 Duration of symptoms before admission ~ 5 days Temperature on admission 38.8 WBC Initial lymphocyte 0.66 vs .85 Thrombocytopenia Impaired LFT’s 11 vs. 6 P=0.04 P = 0.01

Predictors of “severe” SARS www.thelancet.com 8 Apr 03: 

Predictors of “severe” SARS www.thelancet.com 8 Apr 03

Slide48: 

Hong Kong

Slide49: 

Hong Kong

Demography Hong Kong: 

Demography Hong Kong Total 138 Female 72 HCW 69 Doctors 20 Nurses 34 Allied health workers 15 Medical Students 16 Patients 19 Relatives 34

Common Symptoms Hong Kong: 

Common Symptoms Hong Kong

Slide52: 

Hong Kong

Serum Chemistry Hong Kong: 

Serum Chemistry Hong Kong Elevated LDH 71% Elevated CPK 32% median 126 U/L, range: 29-4644 Elevated ALT 23% Hypokalemia 25% Hyponatremia 20%

Slide54: 

Hong Kong

Slide55: 

Hong Kong

Slide56: 

It is important to to consider other pathogens: influenza etc

CXR Resolution Hong Kong: 

CXR Resolution Hong Kong In 7 days median duration: 82% of patients had 25% resolution of chest shadows 69% of patients had 50% resolution of chest shadows

Lessons Learned: 

Lessons Learned Early high dose steroid is worthy Ribivirin may be beneficial Don’t use nebulizer Don’t use non-invasive positive pressure ventilation Chest physiotherapy may help

Identification of Severe Acute Respiratory Syndrome in Canada : 

Identification of Severe Acute Respiratory Syndrome in Canada published at www.nejm.org on March 31, 2003 ER, 2 meters away Diabetic Diabetic, died at home

Severe Acute Respiratory Syndrome in Canada: 

Severe Acute Respiratory Syndrome in Canada published at www.nejm.org on March 31, 2003 No SARS contact

Clinical Features of the Canadian Patients with SARS at Presentation: 

Clinical Features of the Canadian Patients with SARS at Presentation published at www.nejm.org on March 31, 2003

Summary of the 20 cases published at www.nejm.org on March 31, 2003: 

Summary of the 20 cases published at www.nejm.org on March 31, 2003 Incubation period 1 to 11 days median 5 days Fever 100% Most patients: Rigor, nonproductive cough, dyspnea, hypoxia, malaise, and headache Lung crackles and dullness on percussion

Summary of the 20 cases published at www.nejm.org on March 31, 2003: 

Summary of the 20 cases published at www.nejm.org on March 31, 2003 Lymphopenia Elevated transaminases Hypoxia CXR and CT scans Similar to interstitial pneumonia Progressive bilateral air space disease

Summary of the 20 cases published at www.nejm.org on March 31, 2003: 

Summary of the 20 cases published at www.nejm.org on March 31, 2003 Majority of cases suggest droplet transmission Index cases Family members HCW’s failure to follow infection controls Fourth - and fifth generation of cases Will blur epidemilogical links

Summary of cases: 

Summary of cases Increase morbidity and mortality advance age comorbidities e.g. DM Ribivirin and prednisone early may be of benefit

Recommended Protocol for Clinical Treatment: 

Recommended Protocol for Clinical Treatment Community acquired pneumonia protocol 1. R/O influenza 2. Consider atypicals 3. Ribaviran and Prednisone 4. No aerosolized procedures

Prognosis of SARS: 

Prognosis of SARS ~ 3 - 4% mortality 6% survive but prolong, complicated course 90% recover

Coronavirus Etiology of SARS ?: 

Coronavirus Etiology of SARS ?

Coronavirus in culture: 

Coronavirus in culture

Serological Evidence of Coronavirus: 

Serological Evidence of Coronavirus Found in multiple geographic areas Hong Kong - 9 pts USA - 1 Bangkok - 1 Singapore - 4 Seropositivity occurs ~ 11 to 24 days after onset

Multiple Methods Point to Coronavirus: 

Multiple Methods Point to Coronavirus

Genetic Evidence for Coronavirus: 

Genetic Evidence for Coronavirus

Coronavirus Etiology of SARS ?: 

Coronavirus Etiology of SARS ? Increase confidence in Coronavirus New case definition anticipated To include laboratory test criteria International testing of antiviral compounds Vaccine research underway

SARS Unresolved Issues: 

SARS Unresolved Issues ? Airborne transmission extensive spread within buildings in Asia Fomite transmission Coronavirus can survive in the environment for a few hours Coronavirus found in animal stools No proven, successful population based strategy prevention

SARS Optimism for future control: 

SARS Optimism for future control Effective coronavirus vaccines in animals Novel antiviral drugs may be found Infection control measures work

Infection Control: 

Infection Control

Administrative: 

Administrative Communication Educate Policies & procedures Enforcement

Personal Protective Measures : 

Personal Protective Measures Mask Gloves and gowns Eye protection Hand hygiene

Principles: 

Principles Hypertransmitters - some patients Protection of patients, staff, visitors Prevent spread in the facility and community Target all modes of transmission until SARS epidemiology is understood Protect facilities so routine care is not impaired

Triage for SARS in Ambulatory Care: 

Triage for SARS in Ambulatory Care Targeted screening Currently: Travel history Contact with a person with SARS Air travel to a country with SARS Fever and or respiratory symptoms www.cdc.gov/ncidod/sars/triage_interim_guidance.pdf

Triage for SARS in Ambulatory Care: 

Triage for SARS in Ambulatory Care Evaluate in a separate assessment area If SARS suspected: Patient wears a surgical mask HCW applies Airborne and Contact Precautions N95 if available; at least a surgical mask Gloves Gown Eye protection Negative pressure if available

Respiratory Protection: 

Respiratory Protection Patient Cover coughs with tissue or hand Surgical mask Hand hygiene Healthcare Workers N95 PAPR Surgical mask if respirator not available

Engineering measures : 

Engineering measures Control of ventilation Control of traffic Security

Aerosolizing Procedures for SARS: 

Aerosolizing Procedures for SARS Evaluate patients for SARS before: Aerosolized medication treatments Sputum induction Bronchoscopy Airway suctioning Endotracheal intubation Perform only if medically necessary Use Airborne Precautions as per TB www.cdc.gov/ncidod/sars/pdf/aerosolinfectioncontrol-sars.pdf

Visitor Restrictions: 

Visitor Restrictions Symptomatic close contacts of SAR patients should not enter facility. Screening. Educate visitors about precautions if visiting a SARS patient.

Post-mortem: 

Post-mortem Standard Precautions Gown N95, N100, or PAPR (preferred for aerosolizing procedures) Autopsy Minimum 12 ACH and negative pressure Prevent percutaneous injury Dispose of PPE carefully www.cdc.gov/ncidod/sars/pdf/sarsautopsy.pdf

Patients with suspected SARS and Household Contacts: 

Patients with suspected SARS and Household Contacts Limit interactions outside the home until 10 days after resolution of symptoms Hand hygiene Gloves Patient covers coughs with tissue or mask Do not share utensils, towels, bedding Clean surfaces with disinfectant Household contacts do not limit activity outside the home if asymptomatic www.cdc.gov/ncidod/sars/pdf/ic-closecontacts-sars.pdf

Exposure Management: 

Exposure Management Definitions Exposure:Travel from areas with documented or suspected community transmission of SARS Close Contact having cared for having lived with having direct contact with respiratory secretions and/or body fluids

Slide100: 

www.cdc.gov/ncidod/sars/pdf/exposuremanagement-sars.pdf

Exposure Management in Healthcare: 

Exposure Management in Healthcare Transmission associated with unprotected exposure Exclude from duty if symptomatic within 10 days of exposure to SARS. Continue until 10 days after resolution of symptoms. Screen exposed daily for fever and respiratory symptoms. Facilities with SARS patients: educate workers about symptoms passive surveillance www.cdc.gov/ncidod/sars/pdf/exposureguidance.pdf

School Children Exposed to SARS: 

School Children Exposed to SARS No symptoms-do not exclude from school but monitor symptoms Fever or respiratory symptoms within 10 days of exposure Stay home; if no progression to SARS, then return to school If progresses to SARS, precautions continued until 10 days after resolution Alternative housing for students in dorms, etc. www.cdc.gov/ncidod/sars/pdf/exposurestudents.pdf

Advice for Travelers: 

Advice for Travelers Know about SARS in the travel area Do not go to China, Hong Kong, Singapore or Hanoi unless necessary. No advisories about Canada. Current immunizations. Hand hygiene; bring alcohol hand rubs Seek medical attention if ill www.cdc.gov/ncidod/sars/pdf/travel_advice.pdf

SARS Infection Control at Altru Phase 1: 

SARS Infection Control at Altru Phase 1 Identify and rapidly isolate initial patients Signs at entry: passive screening First contacts screen for travel and SARS exposure EOD: active screening SARS Call Center Use existing negative pressure rooms Education

Summary: 

Summary Use epidemiology Passive and active screening Use standard, airborne, and contact precautions

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