3. Pediatric S A R S

4. 11 JULY 2003 8 437 813 10% Case-fatality rate 32

6. 2/3 China mainland 1/2

7. TIMELINE

8. Guangdong Province, China

9. November 16, 2002 – February 14, 2003 305 cases and 5 deaths from unknown acute respiratory syndrome clinically consistent with atypical pneumonia (“chlamydial pneumonia”) ???? Anthrax, pulmonary plague, leptospirosis, avian influenza ??? Guangdong Province, China The Weekly Epidemiological Record (WER) 7/2003 The Weekly Epidemiological Record (WER) serves as an essential instrument for the rapid and accurate dissemination of epidemiological information on cases and outbreaks of diseases under the International Health Regulations and on other communicable diseases of public … Weekly Epidemiological Record (WER)

10. Hong Kong

11. February 14, 2003 9 th floor 64

12. February 15, 2003 Prince of Wales Hospital in Hong Kong

13. 12 9 th floor 04.03.2003

14. 9 dias pora Hong Kong

15. Effect of Travel and Missed Cases on the SARS Epidemic Spread from Hotel M, Hong Kong Hotel M Hong Kong Guangdong Province, China A A H,J A H,J Hong Kong SAR 95 HCW >100 close contacts United States 1 HCW I, L,M I,L,M K Ireland 0 HCW K Singapore 34 HCW 37 close contacts C,D,E C,D,E B B Vietnam 37 HCW 21 close contacts F,G Canada 18 HCW F,G 11 close contacts

16. March 7, 2003 Hanoi, Vietnam

17. Hanoi, Vietnam French Hospital Fever Dry cough Myalgia Sore throat 22 Bilateral pneumonia ARD 7 March 7, 2003

18. March 10, 2003 Prince of Wales Hospital in Hong Kong 138 cases 26

19. 78 TORONTO March 05, 2003 138 secondary and tertiary cases

20. Singapore

21. Probable cases of severe acute respiratory syndrome, by reported source of infection,* --- Singapore, February 25--April 30, 2003 Singapore 90

22. Cases Of Severe Respiratory Illness May Spread To Hospital Staff March 12-17, 2003 WHO issues a global alert about cases of atypical pneumonia

23. How the SARS coronavirus was discovered

24. Network for multicenter research into the etiology of SARS 11 laboratories in 9 contries

25. Modern communication technologies Real time data

26. E-mail Secure websites

27. Published at www.nejm.org April 10, 2003 (10.1056/NEJMoa030747 ) A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome Thomas G. Ksiazek, D.V.M., Ph.D., Dean Erdman, Dr.P.H., Cynthia Goldsmith, M.S., Sherif R. Zaki, M.D., Ph.D., Teresa Peret, Ph.D., Shannon Emery March 24, 2003

28. Published at www.nejm.org April 10, 2003 (10.1056/NEJMoa030747 ) Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome Christian Drosten, M.D., Stephan Günther, M.D., Wolfgang Preiser, M.D., Sylvie van der Werf, Ph.D., Hans-Reinhard Brodt, M.D., Stephan Becker

29. Phylogenetic tree of the SARS-associated coronavirus (Source: S. Günther, Department of Virology, Bernhard Nocht Institutel )

30. SARS-associated coronavirus (SARS Co-V) Glycoprotein spikes High error rate in RNA polymerase during replication

31. Coronaviruses, Hosts and Diseases Antigenic Group Virus Host Respiratory Enteric Other I HCoV-229E human X TGEV pig X PRCoV pig X FIPV cat X X X FECoV cat X CCoV dog X II HCoV-OC43 human X ?? MHV mouse X X X RCoV rat X X HEV pig X X BCoV cattle X X III IBV chicken X X TCoV turkey X * Coronaviruses are highly species-specific

32. The genome sequence of SARS Co-V reveal that the novel agent does not belong to any of the known groups of coronaviruses. It is neither a mutant, nor a recombinant between known Co-V (Ludwig et all. 2003) X1 X2 X3 X4 X5 N M E 20,001 30,000 0.5 1.0 1.5 2.0 2.5 3.0 4.0 5.0 6.0 9.0 25,000 S RNA 6 1 2 3 kB RNA 5 RNA 4 RNA 3 RNA 2 8.3 kb 4.5 kb 3.4 kb 2.5 kb 1.7 kb S ORF 1b ORF 1a N M E A B C 1 5,000 10,000 15,000 20,000 25,000 30,000 SARS-CoV Genome Organization and mRNA Synthesis

33. Crossing the species barrier… … and jumped from another species

34. Tracking the origin of SARS coronavirus Guangdong, China

35. The food markets of Guangdong province 5% of the first 900 SARS patients in China were food handlers and chefs

36. Restaurants Guangdong, China

37. Antibodies to SARS Co-V Masked palm civet (Paguma larvata)

38. Palm civet - special ceremonial dish in China

39. Racoon dog and Chinese ferret badgers special dish in Guangdong province

41. rearing, slaughter, preparation of these animals – animal-to-human transmission 13%

42. How Severe Acute Respiratory Syndrome (SARS) spread: Hospitals and airplanes

43. April 23, 2003 Autbreaks show sings of peaking

44. Transmission The SARS Co-V is not easily transmissible (tQ 2.1-3.3; flu tQ > 20) droplets

45. Close community: healthcare workers, military populations, travel groups, religious gathering, or funerals with close interactions (kissing, hugging). Superspreaders ? Transmission

46. March 30, 2003 Amoy Garden 10/35

47. Amoy Garden

48. Amoy Garden

49. Hospitals -incubator for SARS

50. Hospitals -incubator for SARS In Toronto, Singapore Hong Kong 80% of cases were associated with healh care exposure

51. Hospitals -incubator for SARS Hospital staff seems to be at highest risk

52. Total SARS Cases and % Healthcare Workers by Location Total No. SARS cases % HCW % HCW

53. The world – “global vilage” 83 000 000 visitors to China each year

54. “ Peripatetic” – acquiring infection in one part of the world, but being diagnosed in another

56. Person- to - person transsmision: within two rows of seats

57. An unsuspected SARS case with transmission to health care workers could shut down in a short period of time any health care system within days, resulting in an economic and public relation disaster

58. Clinical findings No help in making diagnosis

59. 50%

61. Symptoms Commonly Reported By Patients Presenting with SARS Symptom Range (%) Fever 95-100 Cough 57-100 Dyspnea 20-100 Chills/Rigor 73-90 Myalgias 20-83 Headache 20-70 Diarrhea 10-67 Nausea/Vomiting 10-24 ( Rhinorrhea) 5-25 ( Sore Throat) 5-25

62. Common Clinical Findings in Patients with SARS Range (%) Finding 17-34 70-95 30-50 40-60 20-30 70-94 30-40 Laboratory Leukopenia Lymphopenia Thrombocytopenia Prolonged aPTT Increased ALT Increased LDH Increased CPK 38-90 60-83 Physical Examination Rales/Rhonci Hypoxia

68. Day 5 - CXR showed left lower zone consolidation became more obvious. Day 7 - Patient became hypoxic & required subsequent intubation. CXR showed bilateral widespread airspace infiltrates . Changi General Hospital, Singapore Courtesy of Dr Augustine Tee 24-year-old Filipino nursing aid from nursing home with one week history of fever, dry cough and myalgia Day 1 - CXR showed subtle left lower zone airspace infiltrates

69. Figure 1 - CXR (7 days after admission) showed ill-defined air space opacification in periphery of right lower zone Figure 2 - CXR (2 days later) showed progression of air space opacification in right lower zone and a new finding of similar changes in left mid and lower zones after initial treatment Figure 3 - CXR (after another 4 days) showed marked resolution of the consolidative changes in both lungs after treatment Case 1: A 31-year-old health-care worker presented with 2-day history of fever, chills and myalgia.

71. HRCT Features of SARS Multiple confluent areas of consolidation in the middle lower and both lower lobes Ill-defined consolidation with air-bronchogram in apical segment of right lower lobe

75. Currently, there are no specific clinical or laboratory findings which can distinguish with certainty SARS from other respiratory illnesses at the time of presentation Early recognition will depend on the astute clinician’s ability to combine clinical and epidemiologic features !

76. SARS is biphasic illness 85% of patients developed fever and diarrhea after a mean of 9 days

77. SARS is biphasic illness 12% - pneumo mediastinum 20% - ARDS

78. Risk factors for adverse outcome Older age (61 – 80) Cfr 43% vs 13,2% HB s Ag carriage

80. Infection Control

86. SARS has no specific symptoms, no early diadnostic test, no specific treatment, and no vaccine

87. The SARS outbreak was controlled by old-fashioned aggressive infection control techniques

88. Pediatric S A R S

89. April 29, 2003; Lancet: Hon et al The first report on SARS in children

90. Young children develop milder form of the disease with less-aggressive clinical course than in teenagers and adults

91. Children: reservoir for many respiratory diseases (flu, RSV…) Children: massive exposure (kissing…) infected without clinical presentation Children: absence of mortality

92. SARS: where are the pediatric cases? Philip A. Brunell Chief Medical Editor May 2003 To date there is no evidence to support the thesis that there is widespread unrecognized illness in children. At this time, it is safe to say that our pediatric patients with respiratory illnesses without an epidemiologic link do not have SARS. That does not means we should stop looking.

93. Section of Pediatric Emergency Medicine Pediatric SARS Lance Brown, MD MPH FACEP Does it strike anyone else as odd that SARS is a viral pneumonia that strikes adults harder than kids? The worldwide numbers from the May 21, 2003 World Health Organization tally show 7,956 cases, 4,085 individuals who have recovered from the disease, and 666 deaths. The United States is officially listed as having 66 cases and no deaths. Unfortunately, I could not find specific numbers for children in either the CDC or WHO Web sites. The percentage of cases involving children has been reported to be 2% in Canada , 2.4% in Sinapore , and 14% in the United States . What I would really like to see is the Chinese pediatric data. There are a few possibilities including: 1) children get the disease, but it is manifests itself so mildly that the children don't come to medical attention; 2) children have more resistance to getting the infection for some reason; 3) children just haven't been exposed as often as adults; 4) bad data ; 5) luck

94. Clinical features among SARS children

95. Laboratory features among SARS children Lowest lymphocyte count

96. Treatment among SARS children i.v. ribavirin Ventilatory support Oxygen requirement

97. Severe acute respiratory syndrome in children: experience in a regional hospital in Hong Kong. Chiu WK, Cheung PC, Ng KL, Ip PL, Sugunan VK, Luk DC, Ma LC, Chan BH, Lo KL, Lai WM. Department of Pediatrics and Adolescent Medicine, United Christian Hospital, Kwun Tong, Hong Kong. chiuwkv1@netvigator.com Pediatr Crit Care Med. 2003 Jul;4(3):279-83 .

99. 2 -year-old boy presenetd with febrile convulsion and cough. CXR in admission showed air-space opacities in left mid and lower zone.

100. 5-year-old girl presented with fever for 4 days. CXR showed air-space opacity in left lower zone.

101. 6-year-old girl presented with fever, runny nose and cough. CXR in admission showed focal air-space consolidation in left upper zone.

102. Chapter 10 : Pediatric SARS Bernd Sebastian Kamps, Christian Hoffmann Clinical Manifestation

103. Treatment

104. The reason why children with SARS fare better than adults and adolescents is unclear

105. SARS: Here to stay? SARS: Preparing for the future?