Download Severe Acute Respiratory Syndrome (SARS)

Severe Acute Respiratory
Syndrome (SARS)
Prof. Pushpa Raj Sharma
Department of Child Health
Institute of Medicine
30.04.03
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.
China's Ministry of Health on Sunday
afternoon reported a total of 2,914 cases of
severe acute respiratory syndrome (SARS) on
the Chinese mainland by 10:00 a.m. April 27.
Of the total, 1,299 patients had been
discharged from hospitals upon recovery and
131 had died.
HOTEL M IN
HONGKONG
February 21
HCW:
Hong Kong
Vietnam
Ireland
Singapore
United State
Severe Acute Respiratory Syndrome
95
37
0
34
1
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.
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.
SARS Case Definition
• Probable case:
– Radiographic evidence of pneumonia
or respiratory distress syndrome.
– Autopsy findings consistent with
respiratory distress syndrome without
an identifiable cause.
Severe Acute Respiratory
Syndrome (SARS)Reported
Probable Cases
5050
321
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.
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
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.
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.
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.
Severe Acute Respiratory Syndrome (SARS)
Demography
80
70
60
50
40
30
20
10
0
Travel 94%
0-4 years
5-17 years
18-64 years
65+
Corona viruses were first isolated from chickens in 1937
Paramyxoviridae
human meta pneumovirus
Coronaviridae novel corona virus of SARS
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)
•
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)
Novel corona virus of SARS
The SARS virus has been mutating
rapidly in Hong Kong: Mortality rate
12
10
8
6
4
2
0
March
April
May
The microbiologists at the Chinese University
discovered four strains of the virus,
all with different genomic sequencing
Severe Acute Respiratory Syndrome
(SARS): Evidence
• Corona virus supportive evidence:
Tissue Culture
Electron microscopy
Microarray technology
Indirect immunofluorescencent antibody
PCR
• Metapneumovirus
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.
Pathogenesis
• Clinically, most infections cause a mild, selflimited 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.
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 coldtype respiratory infections, growth appears to be
localized to the epithelium of the upper
respiratory tract.
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)
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.
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.
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
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.
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%)
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
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.
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
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.
Severe Acute Respiratory Syndrome
(SARS): Treatment
• Empirical therapy most commonly
included antibiotics, oseltamivir, and
intravenous ribavirin.
• Mechanical ventilation was required in
five patients.
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.
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
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
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
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
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.
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]
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
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
3. Additional Therapy for SARS
• Corticosteroids
• Oral ribavirin
•Oseltamivir
•IVIG
Severe Acute Respiratory Syndrome
(SARS) Further Research
• Anti viral compounds
Therapeutic
Prophylactic
• Vaccine development
Summary of SARS
•
•
•
•
•
Causative agent: Corona virus (Urbani SARS)
Incubation period: 2-7 days (10 days)
Mode of spread: Droplet
Commonest age group: 25-70 years.
Fever, respiratory illness, myalgia are common
symptoms. Respiratory failure is high.
• Adverse outcome: high LDH, high absolute
neutrophil count.
• Preventive measures are important.
Is SARS really a threat?
• 40,000 Nepalese children die annually
from pneumonia.
• 8000 children die each day from
waterborne diseases in world.
• Malaria is alive and well and killing more
than 3000 African children every day.
• 1918 influenza epidemic, an acute
infection like SARS, which killed about
40 million people worldwide.
Severe Acute Respiratory Syndrome
References: (www.nejm.org.)
•Novel Corona virus Associated with Severe Acute
Respiratory Syndrome
T.G. Ksiazek and Others
•A Major Outbreak of Severe Acute Respiratory Syndrome
in Hong Kong
N. Lee and Others
•Identification of Severe Acute Respiratory Syndrome in
Canada
SM Poutanen and Others
•Editorial: Faster . . . but Fast Enough? Responding to the
Epidemic of Severe Acute Respiratory Syndrome
J.L. Gerberding
•WWW.cdc.gov/ncidod/sars/clinicians.htm
Thank you