PediatricPediatricS A R SS A R S

11 11 JULY 2003JULY 2003

8 437 813

10% Case-fatality rate

32

2/3China mainland

1/2

TIMELINETIMELINE

Guangdong Province, ChinaGuangdong 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)

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, ChinaGuangdong Province, China

Hong Kong

February 14, 2003

9th floor

64

February 15, 2003

Prince of Wales Hospital Prince of Wales Hospital in Hong Kongin Hong Kong

12

9th floor

04.03.2003

9

diasdiasporapora

Hong Kong

Hotel MHong Kong

Guangdong Province,

China A

A

H,JA

H,J

Hong Kong SAR

95 HCW

>100 close contacts

United States

1 HCW

I, L,M

I,L,M

K Ireland

0 HCWK

Singapore

34 HCW

37 close contacts

C,D,E

C,D,E

B

B

Vietnam

37 HCW

21 close contacts

F,G

Canada

18 HCWF,G

11 close contacts

Effect of Travel and Missed Cases on the SARS Epidemic

Spread from Hotel M, Hong Kong

March 7, 2003 Hanoi, Vietnam

Hanoi, VietnamFrench Hospital

FeverDry coughMyalgiaSore throat

22

Bilateral pneumonia ARD7

March 7, 2003

March 10, 2003Prince of Wales Hospital Prince of Wales Hospital

in Hong Kongin Hong Kong

138 cases138 cases

2626

78

TORONTO

March 05, 2003

138 secondary 138 secondary and tertiaryand tertiarycasescases

Singapore

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

Singapore

90

WHO issues a global alert about cases of atypical pneumonia

Cases Of Severe Respiratory Illness May Spread To Hospital Staff

March 12-17, 2003

How the SARS coronavirus was discovered

Network for multicenter research into the etiology of SARS

11 laboratories in 9 contries

Modern communication technologies

Real time data

E-mail

Secure websites

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

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

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

SARS-associated coronavirusSARS-associated coronavirus (SARS Co-V) (SARS Co-V)

Glycoprotein spikesHigh error rate in RNA polymerase during replication

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 XTCoV turkey X

* Coronaviruses are highly species-specific

The genome sequence of The genome sequence of SARSSARS Co-V reveal that the novel Co-V reveal that the novel agent does not belong to any of the known groups of agent does not belong to any of the known groups of coronaviruses. It is neither a mutant, nor a recombinant coronaviruses. It is neither a mutant, nor a recombinant between known Co-V (Ludwig et all. 2003)between known Co-V (Ludwig et all. 2003)

X1

X2

X3

X4 X5

NME

20,001 30,000

0.5

1.0

1.5

2.02.53.0

4.05.06.0

9.0

25,000

S

RNA 6

1 2 3kB

RNA 5

RNA 4

RNA 3

RNA 28.3 kb

4.5 kb

3.4 kb

2.5 kb

1.7 kb

SORF 1b

ORF 1a NM

EA

BC

1 5,000 10,000 15,000 20,000 25,000 30,000

SARS-CoV Genome OrganizationSARS-CoV Genome Organizationand mRNA Synthesisand mRNA Synthesis

Crossing the species barrier…Crossing the species barrier…

… … and jumped from another speciesand jumped from another species

Tracking the origin of SARS coronavirusTracking the origin of SARS coronavirus

Guangdong, ChinaGuangdong, China

The food markets of Guangdong provinceThe food markets of Guangdong province

5% of the first 5% of the first 900 SARS 900 SARS patients in China patients in China were food were food handlers and handlers and chefschefs

RestaurantsRestaurants

Guangdong, ChinaGuangdong, China

Antibodies to SARS Co-VAntibodies to SARS Co-V

Masked palm civet Masked palm civet (Paguma larvata)(Paguma larvata)

Palm civet -Palm civet -special special ceremonial dish ceremonial dish in Chinain China

Racoon dogRacoon dog

and Chinese ferret badgersand Chinese ferret badgers

special dish in Guangdong provincespecial dish in Guangdong province

rearing, slaughter, preparation of these rearing, slaughter, preparation of these animals – animal-to-human transmissionanimals – animal-to-human transmission

13%13%

How Severe Acute Respiratory Syndrome (SARS)

spread: Hospitals and airplanes

April 23, 2003 Autbreaks show sings of peaking

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

droplets

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

Transmission

March 30, 2003 Amoy Garden

10/35

Amoy GardenAmoy Garden

Amoy GardenAmoy Garden

Hospitals -Hospitals -incubator incubator for SARSfor SARS

Hospitals -incubator for SARSHospitals -incubator for SARS

In Toronto, SingaporeIn Toronto, SingaporeHong KongHong Kong80% of cases were associated 80% of cases were associated with healh care exposurewith healh care exposure

Hospitals -incubator for SARSHospitals -incubator for SARS

Hospital staff seems to be at highest riskHospital staff seems to be at highest risk

Total SARS Cases and % Total SARS Cases and % Healthcare Workers by Healthcare Workers by

LocationLocation

0

1000

2000

3000

4000

5000

6000

Vietnam Singapore Canada Taiwan Hong Kong China

0

20

40

60

80

100

To

tal N

o. S

AR

S c

ase

s

% HCW

% H

CW

The world – The world – “global vilage”“global vilage”

83 000 000 visitors to China each year83 000 000 visitors to China each year

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

Person- to - person transsmision:Person- to - person transsmision:within two rows of seatswithin two rows of seats

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

Clinical findingsClinical findings

No help in making diagnosisNo help in making diagnosis

50%50%

Clinical Aspects of (SARS) *

• Incubation period 2-10 days– Median 4-6– Rarely up to 14 days?

• Onset of fever, chills/rigors, headache, myalgias, malaise– Fever may resolve prior to respiratory symptoms– Diarrhea has been a prominent feature of early illness in

some

• Respiratory symptoms often begin 3-7 days after symptom onset, peak in second week– 30% have respiratory symptoms at onset

* 138 cases of SARS at Prince of Wales Hospital in HongKong

Symptoms Commonly Reported By Patients Presenting with SARS

Symptom Range (%)Fever 95-100Cough 57-100Dyspnea 20-100Chills/Rigor 73-90Myalgias 20-83Headache 20-70Diarrhea 10-67

Nausea/Vomiting 10-24 (Rhinorrhea) 5-25 (Sore Throat) 5-25

Common Clinical Findings in Patients with SARS

Finding Range (%)

Physical Examination

Rales/Rhonci

Hypoxia

38-90

60-83

Laboratory

Leukopenia

Lymphopenia

Thrombocytopenia

Prolonged aPTT

Increased ALT

Increased LDH

Increased CPK

17-34

70-95

30-50

40-60

20-30

70-94

30-40

Radiographic Features of SARSRadiographic Features of SARS

• Infiltrates develop on chest radiograph in Infiltrates develop on chest radiograph in nearly 100% of laboratory confirmed casesnearly 100% of laboratory confirmed cases– At presentation, CXR normal in up to 30%At presentation, CXR normal in up to 30%

• How soon do abnormalities appear?How soon do abnormalities appear?– 66% abnormal by day 366% abnormal by day 3– 97% abnormal by day 797% abnormal by day 7– 100% abnormal by day 10100% abnormal by day 10

Wong. Radiology 2003;228:401-6.Wang. Proceedings of International Science Symposium on SARS. Beijing, China, 2003Xue. Chin Med J 2003;116:819-822Zhao. J Med Microbiol 2003;52:715-20.Rainer. BMJ 2003;326:1354-8.

Radiographic Features of SARSRadiographic Features of SARS

• InfiltratesInfiltrates– initially

focal, often peripheral lower lobes

Radiographic Features of SARSRadiographic Features of SARS

• InfiltratesInfiltrates– initially

focal, often peripheral lower lobes

– interstitial

Radiographic Features of SARSRadiographic Features of SARS

• Infiltrates

•Infiltrates

–75% progress to involve multiple lobes or both lungs

Radiographic Features of SARSRadiographic Features of SARS

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

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.

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.

•Computed tomography more sensitive than conventional radiography

–Ground glass opacification

–Peripheral lower lobes

HRCT

Multi-focal peripheral consolidation in posterior basal segments of both lower lobes and an area of ground-glass opacification in left lingular segment

Radiographic Features of SARSRadiographic 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

HRCT HRCT Features of SARSFeatures of SARS

Laboratory Diagnosis of Laboratory Diagnosis of SARSSARS

• SARS CoV testing – Virus detectionSARS CoV testing – Virus detection– RNA detection by RT-PCR or real time RNA detection by RT-PCR or real time

PCRPCR

Focus Technologies $298Focus Technologies $298

Laboratory Diagnosis of Laboratory Diagnosis of SARSSARS

• SARS CoV testingSARS CoV testing– Antibody detection (Serology) Antibody detection (Serology)

ImunofluorescenceImunofluorescence

Laboratory Diagnosis of SARSLaboratory Diagnosis of SARS

• Ability to detect SARS CoV early in Ability to detect SARS CoV early in illness limitedillness limited– Low titer of virus in early specimensLow titer of virus in early specimens

• < 50% positive by PCR 1< 50% positive by PCR 1stst week week• Testing multiple specimens may improve Testing multiple specimens may improve

ability to diagnoseability to diagnose– Respiratory, stool, serum/plasmaRespiratory, stool, serum/plasma– Stool may be bestStool may be best

• Antibody response can take up to 28 Antibody response can take up to 28 daysdays

• Detectable as early as 10-14 daysDetectable as early as 10-14 days

Currently, there are Currently, there are no specific no specific clinical or laboratory findings which clinical or laboratory findings which can distinguish with certainty SARS can distinguish with certainty SARS from other respiratory illnessesfrom other respiratory illnesses at at the time of presentationthe time of presentation

Early recognition will depend on the Early recognition will depend on the astute clinician’s ability to astute clinician’s ability to combine combine clinical and epidemiologic featuresclinical and epidemiologic features!!

SARS is biphasic illnessSARS is biphasic illness

85% of patients developed fever and 85% of patients developed fever and diarrhea after a mean of 9 daysdiarrhea after a mean of 9 days

SARS is biphasic illnessSARS is biphasic illness

12% - pneumo12% - pneumomediastinummediastinum

20% - ARDS20% - ARDS

Risk factors for adverse outcomeRisk factors for adverse outcome

Older ageOlder age

(61 – 80)(61 – 80)

Cfr 43% Cfr 43% vs 13,2%vs 13,2%

HB s Ag HB s Ag carriagecarriage

Treatment of Patients with SARS –no data

• Potential Therapies Requiring Further Investigation– Empiric antibacterial therapy 14 days– Ribavirin 10-14 days– ?other antiviral agents– Immunomodulatory agents

• Corticosteroids 21 days or pulse• Interferons• Others? Vaccine?

1111

Infection Control Infection Control

Infection Control

• Isolation

Institutional Quarantine

Infection Control Infection Control – Hand hygiene

Infection Control

– Contact Precautions

(gloves, gown)

Eye protection

Infection Control Infection Control

– Environmental cleaning

Infection Control – Airborne Precautions (N-95 respirator,

negative pressure)

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

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

PediatricPediatricS A R SS A R S

April 29, 2003; Lancet: Hon et al

The first report on SARS in children

Young children develop milder form of the disease

with less-aggressive clinical course than in teenagers and adults

Children: reservoir for many respiratory diseases (flu, RSV…)

Children: massive exposure (kissing…) infected without clinical presentation

Children: absence of mortality

SARS: where are the pediatric cases?Philip A. BrunellChief 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.

Section of Pediatric Emergency Medicine

Pediatric SARSLance 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

Clinical features among SARS childrenClinical features among SARS children

LaboratoryLaboratory features among SARS children features among SARS children

Lowest lymphocyte countLowest lymphocyte count

TreatmentTreatment among SARS children among SARS children

i.v. ribavirini.v. ribavirin

Ventilatory supportVentilatory support

Oxygen requirementOxygen requirement

 

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):279-83Pediatr Crit Care Med. 2003 Jul;4(3):279-83 ..

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

5-year-old girl presented with fever 5-year-old girl presented with fever for 4 days. CXR showed air-space for 4 days. CXR showed air-space

opacity in left lower zone.opacity in left lower zone.

6-year-old girl presented 6-year-old girl presented with fever, runny nose with fever, runny nose

and cough. CXR in and cough. CXR in admission showed focal admission showed focal air-space consolidation air-space consolidation

in left upper zone.in left upper zone.

Chapter 10: Pediatric SARS

Bernd Sebastian Kamps, Christian Hoffmann

Clinical Manifestation

TreatmentTreatment

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

SARS: Here to stay?SARS: Here to stay?

SARS: Preparing for SARS: Preparing for the future?the future?