Published on October 23, 2007
Slide1: JON ROSENBERG INFECTION CONTROL AND HEALTHCARE EPIDEMIOLOGY DIVISION OF COMMUNICABLE DISEASE CONTROL CALIFORNIA DEPARTMENT OF HEALTH SERVICES EXPERIMENTAL SARS VACCINES WORK ON ANIMALS June 26, 2004 SARS Outline: Outline Brief history and epidemiology Etiology and reservoir Clinical presentation Laboratory issues Infection control issues – later talk Surveillance for SARS now In the beginning….Guangdong Province, China: In the beginning…. Guangdong Province, China November 2002-January 2003 – Clusters of atypical pneumonia seen in provincial hospitals February 10 –Officials report that 300 people affected with 5 deaths, “illness effectively treated and controlled” Feb 14 – The Chinese CDC reports the situation is “under control and not as serious as rumors” Feb 21 – Patient A travels to Hong Kong, leading to a global outbreak of SARS Guangdong in Retrospect: Guangdong in Retrospect Large number of early cases worked in kitchens or wildlife markets 42.8% of SARS cases without a credible history of exposure worked in kitchens although there was no significant history of direct contact with domestic animals or birds 40% of the wild animal traders, 20% of the wild animal butchers 5% of the vegetable traders were seropositive for SARS-CoV (none ill) Global spread of SARS: Global spread of SARS Hanoi, Vietnam (Patient B) - Dr. Carlos Urbani described first cases of SARS to WHO, leading to WHO issuing Global Alert on 3/12. Of 63 documented cases, 63% occur in HCW, including Dr. Urbani. Singapore (Patients C, D and E) – initial outbreaks noted in HCWs; >200 people subsequently infected, which led to large scale mandatory quarantines being instituted. Toronto, Canada (Patient F) - > 250 cases from nosocomial transmission within 3 large hospitals before strict infection control practices were instituted. 40% of cases were in HCWs. Hong Kong (Patients A, H and J) - initial outbreak in HCWs lead to community transmission with >1700 cases and mandatory quarantines in “holiday camps”. March 12, 2003: March 12, 2003 WHO issues a global alert: Atypical pneumonia with rapid progression Unidentified cause, presumed infectious Antibiotics and antivirals not effective Health workers at greatest risk Spreading internationally within Asia and to Europe and North America March 15, 2003: March 15, 2003 WHO issues a rare emergency travel advisory to be aware of a new severe acute respiratory syndrome, or SARS. Travelers are asked to avoid nonessential travel to Hong Kong, Singapore, and Hanoi, Vietnam. March 23 - Toronto, Canada and Beijing and Shanxi provinces, China added to the list. Workers Disinfecting Streets in Gangzhou : Workers Disinfecting Streets in Gangzhou SARS Reproduction Number: SARS Reproduction Number California SARS Surveillance: California SARS Surveillance Sunday, March 16 Chris Cahill e-mail and draft guideline Monday, March 17 Established call system Tuesday, March 18 Guidelines distributed Reinforcements needed for call system Slide15: At least six SARS cases in California reported Severe respiratory disease called less deadly than initially reported By Paul Elias Associated Press Thursday, March 20, 2003 - SAN FRANCISCO -- At least six California residents are suspected of having the mystery illness that is confounding medical experts around the world. Federal officials announced Thursday an increase in the number of suspected U.S. cases, from 11 to 13, and the number is expected to rise. Slide16: Posted on Fri, Mar. 21, 2003 3 in Bay Area may have new illness CALIFORNIA LEADS U.S. WITH 6 POSSIBLE CASES By Julie Sevrens Lyons Mercury News Three Bay Area residents are believed to be infected with a deadly mystery illness linked to Asian travel, giving California the dubious distinction of being the U.S. state with the most suspected cases. Suspect Case Definition: Suspect Case Definition Respiratory illness of unknown etiology with onset since February 1, 2003, and: · Temperature > 100.4 °F (> 38° C) AND · One or more findings of respiratory illness (e.g. cough, shortness of breath, or difficulty breathing) AND · Travel within 10 days of onset to an area with SARS transmission OR · Close contact with a suspect SARS case within 10 days of onset Probable Case Definition: Probable Case Definition A suspect case with: · Radiographic evidence of pneumonia or respiratory distress syndrome OR · Autopsy findings consistent with respiratory distress syndrome without an identifiable cause California by July 17, 2003: California by July 17, 2003 Cases: 79 (23 Probable, 56 Suspect) Distribution: 23 counties – LA (13), S. Clara (8), S. Mateo (8), Alameda (5), Contra Costa (3), Orange (3), Sacramento (3), SF (3) Age: Median 39 years (Range 1-85 years) Gender: 56% Male Race/Ethnicity: 60% Asian, 33% White Hospitalized: 41% (1 ventilated) Exposure: 96% Travel, 4% Household Cases: Worldwide/United StatesNovember 2002 through Sept. 30, 2003: Cases: Worldwide/United States November 2002 through Sept. 30, 2003 Worldwide: 8,098 cases reported 774 deaths (overall fatality rate = 9.6%) US: Suspect = 134 Probable = 19 Laboratory confirmed = 8 (CA = 2) All cases imported Laboratory Acquired Case 1: Laboratory Acquired Case 1 September 9 –Singapore Environmental Health Institute laboratory researcher confirmed SARS Conducting research on the West Nile virus in laboratory was also conducting research using active SARS coronavirus Cross-contamination of West Nile virus samples with SARS virus in laboratory source of infection Both viruses detected in research specimen Laboratory Acquired Case 2: Laboratory Acquired Case 2 44-year-old researcher, screening antiviral drugs National Defense University, Taipei Virus samples closed cabinet using attached gloves. Transporting chamber attached to cabinet to transfer waste materials to an autoclave for sterilization. On 6 December, liquid waste spilled into chamber. Unable to reach the material through the attached gloves, sprayed area with alcohol and waited 10 minutes. Thinking it had been disinfected, opened the transporting chamber door to finish cleaning up. Laboratory Acquired Case 2: Laboratory Acquired Case 2 Left for conference Singapore 7 December Returned to Taiwan 10 December and fell ill Admitted to hospital on 16 December. Taiwan and Singapore quarantined a total of 90 people, no secondary cases. Laboratory Acquired Outbreak: Laboratory Acquired Outbreak During April 22-29, the Chinese Ministry of Health reported 9 cases of SARS 7 were from Beijing , and two from Anhui Province , located in east-central China 2 of the 9 patients graduate students at the National Institute of Virology Laboratory Laboratory was closed on April 23, investigated. 2 cases close personal contact with one student Mother (died), nurse provided care student Remaining 5 cases close contact with nurse 2 additional laboratory workers reported July, SARS-like illnesses early February 2004, recent + SARS antibodies SARS Crisis Topples China Lab Chief: SARS Crisis Topples China Lab Chief Director Li Liming resigned after a report by a panel of experts blamed China's most recent outbreak on a series of flaws at the National Institute of Virology in Beijing. Many details about the incident and the lab's operating procedures remain hidden. Science, 2 July 2004 Four Community Cases China: Four Community Cases China 40-year-old director of hospital and practicing physician in Guangzhou, onset January 7 20-year-old woman restaurant worker Guangdong Province onset December 25, 2003 32-year-old man Guangdong Province onset December 16, 2003 35-year-old business man from the Guangdong Province onset December 31, 2003 Four Community Cases China: Four Community Cases China All four patients recovered No contact ill Source not determined Samples collected from cages that housed civets at restaurant where waitress worked positive for SARS-CoV The Etiology: The Etiology March 21 – Hong Kong and CDC culture virus March 23 – CDC announces coronavirus April 13 – A Canadian lab sequences genome April 14 - The CDC publishes its own sequence, with 15 additional nucleotides April 16 - Koch’s postulate is fulfilled (Rotterdam) Coronavirus in cell culture Coronavirus immunofluroescence assay Coronavirus organization Molecular Evolution of the SARS Coronavirus During the Course of the SARS Epidemic in China: Molecular Evolution of the SARS Coronavirus During the Course of the SARS Epidemic in China Initial phase rapid mutation at specific hotspots Caused amino acid changes in the virus spike protein required for host cell adhesion Middle phase “super-spreader events" Hong Kong Amino acid substitutions rate slowed. Late phase strong purifying selection Implications for preemptive control strategies and development of therapeutics and vaccines Science, 303:1666-1669, 12 March 2004 Animal Reservoir?: Animal Reservoir? Animal Testing: Animal Testing Sequencing: an additional 29 base-pair sequence in palm civet coronaviruses Of human SARS-CoV in GenBank, only one has the additional 29 nucleotide sequence Chinese ferret badger, cynomolgus macaques, fruit bats, snakes and wild pigs also positive Pet dogs and cats at Amoy Gardens infected and dogs, cats, ferrets experimentally infected Accidental hosts or reservoirs?: Accidental hosts or reservoirs? Clinical Aspects of SARS: Clinical Aspects of SARS Incubation period 2-10 days Fever, chills/rigors, headache, myalgias, malaise first, and THEN Respiratory symptoms (3-7 days after onset) Usually pneumonia, but not always present at onset No proven effective therapy SARS in Children: SARS in Children Nonspecific and mild illness in young children Clinical, laboratory, and radiologic features indistinguishable from common respiratory pathogens Adolescents more similar to adults Low risk of transmission Need further investigation of subclinical illness, transmission using serological tests SARS in Pregnancy: SARS in Pregnancy No reported cases of vertical transmission Hong Kong 10 women SARS during pregnancy (WHO Consensus Document) 6 required ICU, 4 ventilated, 3 died 1 maternal death and 4 spontaneous abortions among 5 first trimester pregnancies Two maternal deaths among 5 late pregnancies, all 5 infants survived (Shek et al, Pediatrics 112: 4 October 2003) SARS Transmission: SARS Transmission Probable major modes Droplet (within 3 feet) Contact Direct Fomite Airborne transmission Role of aerosol-generating procedures ? Fecal-oral Transmission efficiency may vary Virus Survival: Virus Survival The SARS virus can survive… 4 days in diarrheal stool (2 days in normal stool) 2 days on surfaces 1 day in urine The SARS virus can be killed by… Formaldehyde, 75% ethanol, acetone, 10% bleach Laboratory Assays for SARS: Laboratory Assays for SARS Detection of virus Isolation (culture) Detection of viral RNA (PCR) Detection of SARS-specific antibody Real-time RT-PCR: Real-time RT-PCR Conventional vs Real-time RT-PCR (TaqManTM) increased sensitivity (1-10 transcript copies) increased speed/throughput quantitative reduced risk of amplicon contamination Multiple genetic targets nucleocapsid and polymerase genes amplification of 2 of the 3 targets required for a positive test Real-time RT-PCR: Real-time RT-PCR Potential for false negative results low titer virus in early respiratory secretions Potential for false positive results contamination from previously amplified DNA cross-contamination between specimens Positive test result considered provisional until confirmed by independent testing Negative test result does not rule out SARS and should not affect patient management decisions Serology – Current EIA: Serology – Current EIA Serology appears to be highly specific no reactions with other documented CoV infections (OC43 and 229E) no reactions with “normal” blood donors (U.S. and Hong Kong populations) Serology can be positive in as few as 8 to 10 days after onset of symptoms Serology cannot be considered negative until >28 days after onset of symptoms Serology - New Assays: Serology - New Assays Native virus vs recombinant antigens nucleocapsid, spike, and membrane proteins safety, standardization, and sensitivity need to rule out cross-reactions with other human coronaviruses IgM assays IgM antibodies may be detectable earlier in the course of infection Transient response Neutralization and other immunological markers Specimen Selection and Timing: Specimen Selection and Timing Respiratory tract specimens LRT > URT Sputum > NP aspirates > NP/OP swabs More sample Multiple samples Others specimens Blood, plasma Stool Timing of specimen collection Slide45: Log10 copies/ml Days after onset Slide47: Seroconversion Peiris J et al, Lancet 2003;361:1767-72 % Seroconverting 28 days Alternative Diagnostic Testing: Alternative Diagnostic Testing Schrag SJ et al. SARS surveillance in the United States during the Emergency Public Heath Response, March-July, 2003. Alternative Diagnostic Testing: Alternative Diagnostic Testing California Viral and Rickettsial Disease Laboratory > 200 respiratory specimens from 106 patients Alternative pathogens found in 24% of patients: Influenza A: 19 Influenza B: 1 RSV: 3 Parainfluenza: 2 Infection Control in Hospitals: Infection Control in Hospitals Isolation Airborne Precautions (N-95 respirator, negative pressure room) Contact Precautions (gloves, gown) Eye protection Hand hygiene Environmental cleaning Journalists looked through a window at patients in an isolation ward of a hospital in Beijing: Journalists looked through a window at patients in an isolation ward of a hospital in Beijing SARS in India – Source Control: SARS in India – Source Control 84 cases of SARS linked to 6 family members in Toronto Hospital: 84 cases of SARS linked to 6 family members in Toronto Hospital CMAJ • AUG. 19, 2003; 169 Died at home B&C in ER, then isolated Visited while ill Ill wife visited, Difficult intubation Not isolated 16 HCW 7 visitors 16 HCW 1 patient 119 cases in other hospitals from transferred patients with unrecognized SARS 3 HCW New SARS Surveillance: New SARS Surveillance Every patient hospitalized with radiographic evidence of pneumonia should be asked : In 10 days prior to onset of symptoms: Have you returned from travel to China, Hong Kong or Taiwan or had close contact with any ill person returning from those places? Are you employed as a healthcare worker? Have you had close contact with a person recently diagnosed with pneumonia for which an alternative pathogen has not been identified? If yes, isolate and report to LHD After 3 days without dx consider SARS SARS Surveillance – Fall 2003: SARS Surveillance – Fall 2003 Every patient hospitalized with radiographic evidence of pneumonia should be screened with the following questions: In 10 days prior to onset of respiratory symptoms: Have you returned from travel to China, Hong Kong or Taiwan or had close contact with any person returning from those places who is ill with a respiratory infection? Are you employed as a healthcare worker? Have you had close contact with a person(s) recently diagnosed with pneumonia for which an alternative pathogen has not been identified? CSTE Case DefinitionNovember 2003: CSTE Case Definition November 2003 Based on clinical, epi and lab criteria Clinical: early, mild to moderate, and severe respiratory illness Epi: Possible exposure, likely exposure Lab: Serology, RT-PCR Exclusion Criteria: alternative diagnosis, negative serology >28 d, case based on subsequently excluded case. Case classification: SARS Reports Under Investigation SARS Co-V Disease (Probable and Confirmed) ReportingCDHS to CDC: Reporting CDHS to CDC Data entered in the SARS database can be uploaded to the CDC Surveillance System Eliminates the need for traditional disease reporting mechanisms CDC can provide information back to CDHS through electronic downloads The Future?: The Future? Slide59: Vietnam: 10 Dead In Human Cases Of Bird Flu By LAWRENCE K. ALTMAN (NYT) Published: January 13, 2004, Tuesday Nine children and an adult have died in Hanoi since October from a rare strain of avian influenza that usually spreads from birds to people, the World Health Organization said.