Severe Acute Respiratory Syndrome (SARS)

1. Severe Acute Respiratory Syndrome (SARS) Prof. Pushpa Raj Sharma Department of Child Health Institute of Medicine 30.04.03

2. Severe Acute Respiratory Syndrome (SARS): Epidemiology • A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. • 11 February, 2003: 305 cases and 5 death.

4. HOTEL M IN HONGKONGFebruary 21 HCW: Hong Kong 95 Vietnam 37 Ireland 0 Singapore 34 United State 1 Severe Acute Respiratory Syndrome

5. Severe Acute Respiratory Syndrome (SARS) • Fever followed by rapidly progressive respiratory compromise is the key complex of signs and symptoms from which the syndrome derives its name.

6. SARS Case Definition (April 23) • Suspected case: • Measured temperature greater than 100.40F (greater than 38 0 C AND • One or more clinical findings of respiratory illness (e.g. cough, shortness of breath, difficulty in breathing, or hypoxia) AND • Travel within 10 days of onset of symptoms to an area with documented or suspected community transmission of SARS) OR close contact within 10 days of onset of symptoms with a person known to be a SARS suspect.

7. SARS Case Definition • Probable case: • Radiographic evidence of pneumonia or respiratory distress syndrome. • Autopsy findings consistent with respiratory distress syndrome without an identifiable cause.

8. Severe Acute Respiratory Syndrome (SARS)Reported Probable Cases 5050 321

11. SARS: Timeline of an Outbreak Nov. 16, 2002 -- The first case of an atypical pneumonia in the Guangdong province in China. Feb. 26, 2003 -- First cases of unusual pneumonia reported in Hanoi, Vietnam. Feb 28, 2003 -- World Health Organization officer Carlo Urbani, MD, examines an American businessman with an unknown form of pneumonia in a French hospital in Hanoi, Vietnam.

12. March 10, 2003 -- Urbani reports an unusual outbreak of the illness, which he calls sudden acute respiratory syndrome or SARS, to the main office of the WHO. He notes that the disease has infected an usually high number of healthcare workers (22) at the hospital. March 11, 2003 -- Outbreak of a mysterious respiratory disease is reported among healthcare workers in Hong Kong. March 12, 2003 -- WHO issues a global alert about a new infectious disease of unknown origin in both Vietnam and Hong Kong.

13. March 17, 2003 -- An international network of 11 leading laboratories is established to determine the cause of SARS and develop potential treatments. March 24, 2003 -- CDC officials present the first evidence that a new strain of a virus most frequently associated with upper respiratory infections and the common cold in humans called The corona virus might be likely cause of SARS. March 29, 2003 -- Carlo Urbani, who identified the first cases of SARS, dies as a result of the disease.

14. April 9, 2003 -- WHO investigative team gives initial report on Guangdong outbreak. The team found evidence of "super spreaders“ who were capable of infecting as many of 100 persons. April 16, 2003 -- A new form of a corona virus never before seen in humans is confirmed as the cause of SARS according to Koch's postulates, which are four specific conditions that must be met for a pathogen to be confirmed as a causal agent of disease.

15. 28th April 2003 WHO has removed Viet Nam from the list of affected areas, making it the first country to successfully contain its SARS outbreak. The change in Viet Nam’s status Follows 20 consecutive days (the duration of two incubation periods) since the last new case was detected.

19. Severe Acute Respiratory Syndrome (SARS) Demography Travel 94%

20. Corona viruses were first isolated from chickens in 1937 Paramyxoviridae human meta pneumovirus Coronaviridae novel corona virus of SARS

21. Severe Acute Respiratory Syndrome (SARS) Corona of spikes Made of S glycoprotein(red) Cell envelop derived from Host cell (green) Core (purplish) M protein caries the genetic material (RNA)

22. Coronavirus List of Species in the Genus Group 1. Human coronavirus 229E [X69721] (HCoV-229E) 03.019.0.01.008. Porcine epidemic diarrhea virus [Z35758] (PEDV) 03.019.0.01.010. Transmissible gastroenteritis virus [Z24675] (TGEV) 03.019.0.01.010. Transmissible gastroenteritis virus [Z34093] 03.019.0.01.010. Transmissible gastroenteritis virus [D00118] 03.019.0.01.010. Transmissible gastroenteritis virus [X06371] 03.019.0.01.010.    (Porcine transmissible gastroenteritis virus) 03.019.0.01.010.01.001.001.      Porcine respiratory virus (PRCoV) Group 2 03.019.0.01.006. Human coronavirus OC43 (HCoV-OC43) 03.019.0.01.007. Group 3 species 03.019.0.01.001. Infectious bronchitis virus [M95169] (IBV) 03.019.0.01.001.    Turkey coronavirus (TCoV) Tentative Species in the Genus 03.019.0.81.013. Rabbit coronavirus Novel corona virus of SARS

23. The SARS virus has been mutating rapidly in Hong Kong: Mortality rate

24. The microbiologists at the Chinese University discovered four strains of the virus, all with different genomic sequencing

25. Severe Acute Respiratory Syndrome (SARS): Evidence • Corona virus supportive evidence: Tissue Culture Electron microscopy Microarray technology Indirect immunofluorescencent antibody PCR • Metapneumovirus

26. Severe Acute Respiratory Syndrome (SARS): Proposed Name for Virus • Dr. Carlo Urbani 46 yr old WHO physician and infectious disease specialist died on March 29 of SARS • The name Urbani SARS-associated coronavirus is proposed for the virus.

27. Pathogenesis • Clinically, most infections cause a mild, self-limited disease (classical 'cold' or upset stomach), but there may be rare neurological complications. • SARS is a form of viral pneumonia where infection encompasses the lower respiratory tract.

28.  Pathogenesis • They are transmitted by aerosols of respiratory secretions, by the faecal-oral route, and by mechanical transmission. Most virus growth occurs in epithelial cells. Occasionally the liver, kidneys, heart or eyes may be infected, as well as other cell types such as macrophages. In cold-type respiratory infections, growth appears to be localized to the epithelium of the upper respiratory tract.

29.  Pathogenesis • These viruses infect a variety of mammals & birds. The exact number of human isolates are not known as many cannot be grown in culture. In humans, they cause: Respiratory infections (common), including Severe Acute Respiratory Syndrome (SARS) Enteric infections (occasional - mostly in infants <12 months) Neurological syndromes (rare)

30.  Pathogenesis • Coronavirus infection is very common and occurs worldwide. The incidence of infection is strongly seasonal, with the greatest incidence in children in winter. Adult infections are less common. The number of coronavirus serotypes and the extent of antigenic variation is unknown. Re-infections appear to occur throughout life, implying multiple serotypes (at least four are known) and/or antigenic variation, hence the prospects for immunization appear bleak.

31. SARS Virus • Survived as long as 24 hours in the environment. • Finding of virus in faeces. • Occasionally linked with pneumonia in humans, specially with immunocompromised. • Can cause severe illness in animals. • Incubation period: 2-7 days • CDC/WHO Network is performing studies for further information.

32. SARS Clinical Picture (Hong Kong) • The most common symptoms included fever (in 100 percent of the patients); chills, rigors, or both (73.2 percent); and myalgia (60.9 percent). Cough and headache were also reported in more than 50 percent of the patients. Other common findings were lymphopenia (in 69.6 percent), thrombocytopenia (44.8 percent), and elevated lactate dehydrogenase and creatine kinase levels (71.0 percent and 32.1 percent, respectively). • 78.3% had abnormal chest radiographs

33. SARS: Clinical feature (Canada) • The most common presenting symptoms were fever (in 100 percent of cases) and malaise (in 70 percent), followed by nonproductive cough (in 100 percent) and dyspnea (in 80 percent) associated with infiltrates on chest radiography (in 100 percent). Lymphopenia (in 89 percent of those for whom data were available), elevated lactate dehydrogenase levels (in 80 percent), elevated aspartate aminotransferase levels (in 78 percent), and elevated creatinine kinase levels (in 56 percent) were common.

35. Clinical outcomes (n= 138) • 32.2% admitted to ICU for respiratory failure. Mechanical ventilatory support 13.8% • Dramatic increase in lung opacity with hypoxaemia at a median of 6.5 days. • By 21 days 5 patients died (crude mortality 3.2%)

36. Factors predictive of ICU admission and death • Advanced age. • Male sex • High peak creatinine kinase • High lactate dehydrogenase • High initial absolute neutrophil count • Low serum sodium level

37. Postmortem Findings • Gross consolidation of lungs • Diffuse alveolar damage. (early phase) • Cellular fibromyxoid organizing exudates in air spaces (organizing phase) • Scanty lyphocytic infiltrate in the interstitium. No evidence of the involvement of other organs.

38. SARS in Children Infants and young children Primary symptoms     fever > 38ฐC (oral or tympanic) or rectal equivalent cough, respiratory distress, tachypnea Additional symptoms, which may precede primary symptoms  lethargy, irritability           loss of appetite

39. Older children • Primary symptoms •   as in infants and young children • Additional symptoms, which may precede primary symptoms •  loss of appetite headache, malaise, fatigue,myalgias [even in the hours to day prior to onset of fever] diarrhea, confusion. • In some cases, the headache may resolve, and fever, chills and shakes start shortly after. Respiratory symptoms may not start for 2-3 days later. Some patients have a period of improvement when fever resolves for 24-36 hours, then fever returns and symptoms worsen.

40. Severe Acute Respiratory Syndrome (SARS): Treatment • Empirical therapy most commonly included antibiotics, oseltamivir, and intravenous ribavirin. • Mechanical ventilation was required in five patients.

41. Severe Acute Respiratory Syndrome (SARS): Treatment All patients received corticosteroid and ribavirin therapy a mean (+/-SD) of 9.6+/-5.42 days after the onset of symptoms, and eight were treated earlier with a combination of beta-lactams and macrolide for 4+/-1.9 days, with no clinical or radiological efficacy.

42. MANAGEMENT OF SARS PAEDIATRIC PATIENT • Hospitals must follow infection control guidelines: • masking of patients (sugical mask) accompanying • individuals are to wear N95 mask or equivalent • e.g. PCM 2000 • Staff protection with N95 masks, eye protection, • gowns and gloves isolation of patient in a negative • pressure room is preferred [ if not available, use a single room with door closed] • Frequent handwashing continues to be critical

43. INVESTIGATIONS • Selected investigations are intended to determine the cause of the respiratory illness. Test for viral, bacterial and other usual respiratory pathogens Identify common pathogens circulating in the community which may be responsible for the illness

44. INVESTIGATIONS • Bloodwork: • blood cultures X 2 • CBC, diff, AST, ALT, bilirubin, alkaline phosphatase, LDH, CPK, urea, creatinine, electrolytes • other diagnostic tests as indicated by patients condition

45. INVESTIGATIONS • Respiratory samples: NP swab #1: rapid antigen detection for respiratory viruses, viral cultures, viral PCR ETT aspirate or Auger suction: SARS investigation throat swab #1: Group A strep throat swab #2: Mycoplasma PCR • Blood for serology: 1.   One clotted tube[5 cc] labelled “SARS serology” • Stool: 1.       For viral electron microscopy

46. TREATMENT • At present, the most effective therapeutic regimen is not known. The following recommendations are based on clinical experience to date. The choice may change if any positive laboratory tests are forthcoming.

47. Clinically SUSPECT Cases • TREAT AS YOU WOULD FOR DISEASES OTHER THAN SARS • For fever with no focus, sepsis, otitis media, pharyngitis, meningitis. Antibiotics may therefore include amoxycillin po, ceftriaxone iv and/or a po macrolide, as indicated for community acquired infections • No ribavirin • Antibiotic therapy will be modified if specific pathogen is identified [ie non-SARS]

48. Clinically PROBABLE Cases: Cover typical and atypical causes of pneumonia, and potential viral causes of this unknown illness. 1.  General Therapy TREAT AS YOU WOULD FOR DISEASES OTHER THAN SARS These patients by definition will have community acquired pneumonia, Ceftriaxone (iv ) and a macrolide po

49. 2.  SARS Specific Therapy The efficacy of ribavirin in treating SARS is not known but if ribavirin is being started, use intravenous ribavirin. Loading dose of 33 mg/kg X 1 [max 2 grams/dose]; followed 6 hours later by 16 mg/kg/dose q6h for 4 days [max 1 gram/dose]; followed 8 h later by 8mg/kg/dose q8h [max 500 mg/dose] for 3 to 6 days depending on clinical course

50. 3.   Additional Therapy for SARS • Corticosteroids • Oral ribavirin • Oseltamivir • IVIG