sars

Slide1: 

Severe Acute Respiratory Syndrome Rowan Heath and Mike Sharland Paediatric Infectious Diseases Unit St George’s Hospital 23rd April 2003

SARS: 

SARS Epidemiology Case definitions Case reporting Infection control measures Pathogenesis Clinical features Investigations Management

Epidemiology: 

Epidemiology Outbreak dates back to 16th November 2002 Foshan City, Guangdong province, China 11th February 2003 305 cases reported in Guangdong, 5 deaths 26th February — 12th March 2003 Disease spreads to large number of health care workers in Hong Kong and Vietnam 12th March 2003 Global alert for Severe Acute Respiratory Syndrome (SARS)

The Hong Kong connection:Hotel M: 

The Hong Kong connection: Hotel M A B C D E F G H I J K L M Onset of symptoms Stayed at Hotel M February March

The Hong Kong connection:Hotel M: 

The Hong Kong connection: Hotel M A B C D E F G H I J K L M Onset of symptoms Stayed at Hotel M February March

The Hong Kong connection:Hotel M: 

The Hong Kong connection: Hotel M A B C D E F G H I J K L M Onset of symptoms Stayed at Hotel M February March

Slide7: 

Hotel M Hong Kong Guangdong Province, China A A Spread from Hotel M Reported as of March 28, 2003

Epidemiology: 

Epidemiology As of 21st April 2003, 3861 cases reported (217 deaths – 5.6%) Current “affected” areas Canada (Toronto) –132 cases (12 deaths) Singapore – 178 cases (1 death) China (Guandong, Beijing, Shanxi) – 1959 cases (86 deaths) Hong Kong – 1402 cases (94 deaths) Taiwan* Vietnam (Hanoi) USA* UK* (London) – 6 cases Phenomenom of “super-spreaders” *Limited local transmission and no international spread since 15/3/03 and no transmission except through close contacts

Case definitions (PHLS modified from WHO -updated 19/04/03): 

Case definitions (PHLS modified from WHO -updated 19/04/03) Suspect LOW case Person presenting after 1st February 2003 with sudden onset of fever > 38oC AND cough or dyspnoea AND travelled within 10 days of onset of symptoms to “affected” area with more than limited local transmission Suspect HIGH case Person presenting after 1st February 2003 with with sudden onset of fever > 38oC AND cough or dyspnoea AND had close contact with a probable SARS case from an “affected” area within 10 days of onset of symptoms Probable case A suspect (high or low) case WITH CXR findings of pneumonia and no response to standard antimicrobial treatment OR RDS OR death due to an unidentified respiratory illness with autopsy findings of RDS in a person who travelled to an “affected” area within 10 days of onset of symptoms 26th February — 12th March 2003 Disease spreads to large number of health care workers in Hong Kong and Vietnam 12th March 2003 Global alert for Severe Acute Respiratory Syndrome (SARS)

Case Reporting: 

Case Reporting Need to ensure good local communication eg GP to hospital, A&E to bleep holders, porters and wards (including PICU) and relevant consultants SARS surveillance began in UK 17/03/02 Suspect cases should be reported through local consultant CDC to CDSC at Colindale using reporting form (PHLS website) Probable cases should be telephoned to CDSC duty doctor on 020 8200 6868

Slide12: 

Infection Control Measures: Efforts to contain spread in community Locally Home quarantine (and masks) Hospital closures School closures Internationally Travel warnings Health Alert Notices Screening airline passengers

Infection Control Measures: Hospital: 

Infection Control Measures: Hospital If referred by GP, advise to use masks, notify A&E and see patient in closed room with no ventilation (perform all investigations including X-rays in room) If suspect or probable case (travel history on arrival in A&E), transfer immediately into closed room Strict infection control measures to be observed by all HCW –hand washing, gloves, gowns, goggles and high efficiency masks eg orange Fluidshield N95 particulate filter respirator or Shiloh Visimask +/- theatre caps

Infection Control Measures: Hospital: 

Infection Control Measures: Hospital If admitted, isolate in closed room (dedicated transfer route -patient to wear mask during transit) preferably with negative pressure ventilation eg Pinckney ward at St George’s or PICU HEPA cubicles (may be need to consider designated ward or hospital) For intubated patients, use closed suction system Daily and terminal disinfection of rooms and equipment with hypochlorite solution (1000 ppm)

Pathogenesis (ref’s: Peiris et al, The Lancet 08/04/03 & Ksiazek et al, NEJM 10/04/03): 

Pathogenesis (ref’s: Peiris et al, The Lancet 08/04/03 & Ksiazek et al, NEJM 10/04/03) SARS thought to be caused by a new coronavirus (may also be role for metapneumovirus) Coronaviruses (types 229E and OC43) normally cause mild URTIs in humans, but cause significant respiratory,GI, hepatic and neurological disease in animals Enveloped RNA virus survives for up to 3 hours outside host –method of transmission unclear ?fomite ?aerosol ??faecal/oral In patients with SARS, EM of blood, NPAs and throat swabs has shown typical halo/crown-like appearance –genetic analysis has revealed that this is a new coronavirus (whole genome has now been sequenced)

Pathogenesis (ref’s: Peiris et al, The Lancet 08/04/03 & Ksiazek et al, NEJM 10/04/03): 

Pathogenesis (ref’s: Peiris et al, The Lancet 08/04/03 & Ksiazek et al, NEJM 10/04/03) Mechanism of disease unclear new coronavirus found to have cytopathogenic effect in Vero E6 cells and FRhK-4 cells (surprising as known viruses are notably fastidious) viral inclusion bodies have not been found in open lung biopsies, instead diffuse alveolar damage and hyaline membrane formation suggesting cytokine mediated damage

Pathogenesis (ref’s: Peiris et al, The Lancet 08/04/03 & Ksiazek et al, NEJM 10/04/03): 

Pathogenesis (ref’s: Peiris et al, The Lancet 08/04/03 & Ksiazek et al, NEJM 10/04/03) Testing antibody tests eg serum for ELISA-reliable detection from day 21; AND indirect immunofluorescence-reliable detection from day 10 reverse transcriptase PCR (blood, respiratory secretions, faeces etc.)-primers have been developed and a kit is available from WHO network laboratories, tests are specific but lack sensitivity cell culture is only means of showing live virus (virus replication), but it is very difficult requiring co-culture with well characterised cell lines

Pathogenesis (ref’s: Peiris et al, The Lancet 08/04/03 & Ksiazek et al, NEJM 10/04/03): 

Pathogenesis (ref’s: Peiris et al, The Lancet 08/04/03 & Ksiazek et al, NEJM 10/04/03) University of Hong Kong conducted review of 50 patients with probable SARS (aged 23-74 yrs) admitted to 3 hospitals 26/02/03- 26/03/03 All patients had NPAs and acute serum samples, some had paired sera and faeces -immunofluorescene and culture for conventional respiratory pathogens performed A coronavirus was isolated in 2 patients (co-cultured with FRhK-4 cells) -open lung biopsy & NPA 45/50 SARS cases and no controls (40 NPAs & faecal samples & 80 serum samples from patients with other respiratory diseases and 200 serum samples from blood donors) had evidence of infection with a coronavirus by serology( all 32 cases with paired sera had seroconversion or at least a four-fold increase in antibody titres) and reverse-transcriptase PCR (22/44 NPAs & 10/18 faecal samples)

Clinical Features (ref: Peiris et al,The Lancet 08/04/03): 

Clinical Features (ref: Peiris et al,The Lancet 08/04/03) Incubation period is 2-11 days (usually 2-7) Initially fever, chills or rigors(74%), headache(20%), malaise(50%), myalgia(54%) –coryza relatively uncommon (24%) After 3-7 days, a dry non-productive cough develops(62%) and/or dyspnoea(20%) (diarrhoea and anorexia in a few patients) Approx. 10-20% cases require ventilation (more in Hong Kong case series 19/50) All Hong Kong case series patients had radiological pulmonary infiltrates, but auscultatory findings only present in 38%

Investigations: 

Investigations Patients with mild illness should have serum sent at presentation and on day 21 as a minimum (in Hong Kong FBC recommended as well) Patients with moderate/ severe illness should have pulse oximetry ( blood gases not necessary) and a CXR and blood sent for culture, PCR and serology (and at 21 days) and an NPA to exclude RSV, adenovirus, influenza A & B, and parainfluenza 1,2 & 3 as well as for coronavirus studies (mark samples SARS) Other useful microbiological samples include urine for pneumococcal antigen and faeces and conjunctival swabs Other useful tests include FBC (and differential), LFTs (abnormal transaminases) and CPK (often raised early on) Lymphopenia occurs early in the disease; at the peak of the illness, a low WCC and Plts 50-150 seen in 50% of cases

Management: 

Management Supportive care as necessary eg oxygen, ventilation, fluids and feeding Empirical treatment suggested by Hospital Authority, Hong Kong antibacterial coverage for typical and atypical agents for 7-14 days eg a beta-lactam or cephalosporin (co-amoxiclav/ cefotaxime) and a macrolide ( po azithromycin/ iv erythromycin). broad spectrum antiviral agent eg iv ribavarin 8mg/kg 8hrly for 7-14 days depending on response (oseltamavir has also been used) (inform pharmacy early) iv hydrocortisone 4mg/kg 8hrly with gradual weaning once there is clinical improvement (use methylprednisolone in severe cases) monitor FBC, reticulocyte count, blood glucose and potassium (consider anti-ulcer prophylaxis)

Key Messages: 

Key Messages Thankfully for paediatricians, no reports of major outbreaks in children yet Although the aetiology of SARS may now be known, vaccine development will take a long time and there is no specific treatment available The “super-spreader” phenomenom has not been adequately explained Strict infection control measures are vital to prevent further expansion of this pandemic

Whenever you see a child with a fever and flu-like or respiratory symptoms,take a travel history, and think is this SARS?: 

Whenever you see a child with a fever and flu-like or respiratory symptoms, take a travel history, and think is this SARS?