GIDSAS Chotani, 2003 PART IV: The Disease. GIDSAS Chotani, 2003 SARS: What do we know so far? Viral...

GIDSAS

Chotani, 2003Chotani, 2003

PART IV: The DiseasePART IV: The Disease

GIDSAS


SARS: SARS: What do we know so far?What do we know so far?

Viral infection – a new mutation of Viral infection – a new mutation of coronaviruscoronavirus

Affects all age groups, highest number Affects all age groups, highest number of deaths have been among people of deaths have been among people with pre-existing chronic conditionswith pre-existing chronic conditions

Suspected to have originated in Suspected to have originated in Guandong, ChinaGuandong, China

Causes atypical pneumonia in infected Causes atypical pneumonia in infected patients.patients.

GIDSAS


Methods Of TransmissionMethods Of Transmission

Most frequent method of Most frequent method of transmission of coronavirus from transmission of coronavirus from person to person is droplet person to person is droplet transmissiontransmissionIf the sick person coughs or sneezes, If the sick person coughs or sneezes, the virus can be carried in saliva the virus can be carried in saliva droplets to people nearby, infecting droplets to people nearby, infecting themthemEnvironmental transmission from Environmental transmission from sewer/water, cockroach, and fomites sewer/water, cockroach, and fomites implicated implicated

GIDSAS


Wayne Stayskal, Tampa Tribune, 4/26/03

GIDSAS


Airborne TransmissionAirborne Transmission

Coronavirus family also has the Coronavirus family also has the property of surviving in dry air/surfaces property of surviving in dry air/surfaces for up to 3 hours.for up to 3 hours.In these conditions, the virus In these conditions, the virus crystallizes, and can float in the air like crystallizes, and can float in the air like dust.dust.It is suspected that the SARSIt is suspected that the SARS

virus can be transmitted in virus can be transmitted in this manner.this manner.

Schematic Schematic view of a view of a crystallized crystallized virus particlevirus particle

GIDSAS


Clinical manifestations and pathogenesis of Clinical manifestations and pathogenesis of coronavirus infectionscoronavirus infections

GIDSAS


Health authorities in Hong Kong are investigating whether cockroaches could spread

the deadly SARS virus

(AFP/File/Torsten Blackwood)

GIDSAS


Incubation PeriodIncubation Period

After the virus enters the body, it After the virus enters the body, it requires 3-10 days incubation period requires 3-10 days incubation period before the disease appears.before the disease appears.According to current data, infected According to current data, infected people do not pass on the virus to people do not pass on the virus to others during the incubation period.others during the incubation period.They become infectious only when They become infectious only when the first symptoms appear: cough, the first symptoms appear: cough, sneezing – which spread droplets sneezing – which spread droplets containing virus particles.containing virus particles.

GIDSAS


SymptomsSymptoms

Cough, nasal congestion, sneezingCough, nasal congestion, sneezing

High fever (39°C or higher)High fever (39°C or higher)

Severe muscle and joint painSevere muscle and joint pain

Difficulty in breathing – similar to Difficulty in breathing – similar to asthmaasthma

Continuous localized pain in the Continuous localized pain in the chest, which increases when taking chest, which increases when taking a breatha breath

GIDSAS


Case Definition - WHOCase Definition - WHO

Suspect caseSuspect case1.1. A person presenting after 1 November A person presenting after 1 November

2002(1) with history of:2002(1) with history of:high fever (>38 °C) high fever (>38 °C) AND AND cough or breathing difficulty cough or breathing difficulty AND AND one or more of the following exposures during one or more of the following exposures during the 10 days prior to onset of symptoms:the 10 days prior to onset of symptoms:

• close contact(2) with a person who is a suspect or close contact(2) with a person who is a suspect or probable case of SARS;probable case of SARS;

• history of travel, to an area with recent local history of travel, to an area with recent local transmission of SARStransmission of SARS

• residing in an area with recent local transmission of residing in an area with recent local transmission of SARSSARS

GIDSAS



Suspect case (Suspect case (continuedcontinued))2. A person with an unexplained acute 2. A person with an unexplained acute

respiratory illness resulting in death after respiratory illness resulting in death after 1 November 2002,(1) but on whom no 1 November 2002,(1) but on whom no autopsy has been performed autopsy has been performed AND one or more of the following AND one or more of the following exposures during to 10 days prior to onset exposures during to 10 days prior to onset of symptoms:of symptoms:

close contact,(2) with a person who is a close contact,(2) with a person who is a suspect or probable case of SARS;suspect or probable case of SARS;history of travel to an area with recent local history of travel to an area with recent local transmission of SARStransmission of SARSresiding in an area with recent local residing in an area with recent local transmission of SARS transmission of SARS

GIDSAS



Probable caseProbable case1.1. A suspect case with radiographic A suspect case with radiographic

evidence of infiltrates consistent with evidence of infiltrates consistent with pneumonia or respiratory distress pneumonia or respiratory distress syndrome (RDS) on chest X-ray (CXR).syndrome (RDS) on chest X-ray (CXR).

2.2. A suspect case of SARS that is positive A suspect case of SARS that is positive for SARS coronavirus by one or more for SARS coronavirus by one or more assays.assays.

3.3. A suspect case with autopsy findings A suspect case with autopsy findings consistent with the pathology of RDS consistent with the pathology of RDS without an identifiable cause.without an identifiable cause.

GIDSAS



Exclusion criteriaExclusion criteriaA case should be excluded if an A case should be excluded if an alternative diagnosis can fully explain alternative diagnosis can fully explain their illness. their illness.

GIDSAS


Case Definition - CDCCase Definition - CDC

Suspected Case:Suspected Case:Respiratory illness of unknown Respiratory illness of unknown etiology with onset since February 1, etiology with onset since February 1, 2003, and the following criteria:2003, and the following criteria:Measured temperature greater than Measured temperature greater than 100.4° F (greater than 38° C) AND100.4° F (greater than 38° C) ANDOne or more clinical findings of One or more clinical findings of respiratory illness (e.g. cough, respiratory illness (e.g. cough, shortness of breath, difficulty shortness of breath, difficulty breathing, hypoxia, or radiographic breathing, hypoxia, or radiographic findings of either pneumonia or acute findings of either pneumonia or acute respiratory distress syndrome) ANDrespiratory distress syndrome) AND

GIDSAS


Case Definition - CDCCase Definition - CDC

Travel† within 10 days of onset of Travel† within 10 days of onset of symptoms to an area with documented symptoms to an area with documented or suspected community transmission or suspected community transmission of SARS (see list below; excludes areas of SARS (see list below; excludes areas with secondary cases limited to with secondary cases limited to healthcare workers or direct household healthcare workers or direct household contacts)contacts)ORORClose contact* within 10 days of onset of Close contact* within 10 days of onset of symptoms with either a person with a symptoms with either a person with a respiratory illness who traveled to a respiratory illness who traveled to a SARS area or a person known to be a SARS area or a person known to be a suspect SARS case.suspect SARS case.

GIDSAS


Atypical PneumoniaAtypical Pneumonia

Atypical pneumonia: the tissue Atypical pneumonia: the tissue surrounding the alveoli swells, surrounding the alveoli swells, collapsing the alveoli, reducing the collapsing the alveoli, reducing the blood supply to the area, and blood supply to the area, and obstructing the oxygen transfer. Chest obstructing the oxygen transfer. Chest X-ray shows a fuzzy shadow without X-ray shows a fuzzy shadow without clear boundaries.clear boundaries.

GIDSAS


TypicalTypicalPneumoniaPneumonia

AtypicalAtypicalPneumoniaPneumonia

PneumoniaPneumonia

GIDSAS


Frontal CXR in a 46 y/o male. An obvious area of air space shadowing (arrows) on the left side.

Ref: Lee et al. A major Ref: Lee et al. A major outbreak of Severe Acute outbreak of Severe Acute Respiratory Syndrome in Respiratory Syndrome in Hong Kong. NEJM April 7, Hong Kong. NEJM April 7, 20032003

GIDSAS


Follow-up CXR showed progression of the disease, with multiple, bilateral areas of involvement.


GIDSAS


Subsequent CXR shows improvement of bilateral lung opacities after therapy


GIDSAS


A High-Resolution CT Scan Showing the Characteristic A High-Resolution CT Scan Showing the Characteristic Ground-Glass Abnormality in a Subpleural Location, the Ground-Glass Abnormality in a Subpleural Location, the

Anterior Segment of the Right Upper Lobe.Anterior Segment of the Right Upper Lobe.There is no cavitation. A convenient ional CT scan did not show There is no cavitation. A convenient ional CT scan did not show

pleural effusion or lymphadenopathypleural effusion or lymphadenopathy

Ref: Lee et al. A major outbreak of Severe Acute Respiratory Ref: Lee et al. A major outbreak of Severe Acute Respiratory Syndrome in Hong Kong. NEJM April 7, 2003Syndrome in Hong Kong. NEJM April 7, 2003

GIDSAS


SARS Interpretation of SARS Interpretation of laboratory results - WHOlaboratory results - WHO

Positive SARS diagnostic test findings Positive SARS diagnostic test findings

1.1. Confirmed positive PCR for SARS virus:Confirmed positive PCR for SARS virus:

at least 2 different clinical specimens at least 2 different clinical specimens (eg nasopharyngeal and stool) OR (eg nasopharyngeal and stool) OR

the same clinical specimen collected on the same clinical specimen collected on 2 or more days during the course of the 2 or more days during the course of the illness (eg 2 or more nasopharyngeal illness (eg 2 or more nasopharyngeal aspirates) ORaspirates) OR

2 different assays or repeat PCR using 2 different assays or repeat PCR using the original clinical sample on each the original clinical sample on each occasion of testingoccasion of testing

GIDSAS


SARS Interpretation of SARS Interpretation of laboratory results - WHOlaboratory results - WHO

Positive SARS diagnostic test findings Positive SARS diagnostic test findings

2.2. Seroconversion by ELISA or IFA:Seroconversion by ELISA or IFA:negative antibody test on acute serum negative antibody test on acute serum followed by positive antibody test on followed by positive antibody test on convalescent serum ORconvalescent serum OR

four-fold or greater rise in antibody titre four-fold or greater rise in antibody titre between acute and convalescent phase sera between acute and convalescent phase sera tested in parallel tested in parallel

3.3. Virus isolation:Virus isolation:Isolation of SARS-CoV in cell culture from any Isolation of SARS-CoV in cell culture from any specimen with PCR confirmation using a specimen with PCR confirmation using a validated method.validated method.

GIDSAS


LaboratoryLaboratoryStatus of laboratory tests currently Status of laboratory tests currently under development under development

Antibody tests: Antibody tests: • ELISA (Enzyme Linked ImmunoSorbant ELISA (Enzyme Linked ImmunoSorbant

Assay) detects antibodies in the serum of Assay) detects antibodies in the serum of SARS patients reliably as from day 21 after SARS patients reliably as from day 21 after the onset of clinical symptoms and signs.the onset of clinical symptoms and signs.

• Immunofluorescence Assays detect Immunofluorescence Assays detect antibodies in serum of SARS patients after antibodies in serum of SARS patients after about day 10 of illness onset. This is a about day 10 of illness onset. This is a reliable test requiring the use of fixed SARS reliable test requiring the use of fixed SARS virus, an immunofluorescence microscope virus, an immunofluorescence microscope and an experienced microscopist. Positive and an experienced microscopist. Positive antibody tests indicate that the patient was antibody tests indicate that the patient was infected with the SARS virus.infected with the SARS virus.

GIDSAS


LaboratoryLaboratoryStatus of laboratory tests Status of laboratory tests currently under development currently under development

Molecular tests (PCR) Molecular tests (PCR) • PCR can detect genetic material of the SARS PCR can detect genetic material of the SARS

virus in various specimens (blood, stool, virus in various specimens (blood, stool, respiratory secretions or body tissue)respiratory secretions or body tissue)

• Primers, which are the key pieces for a PCR Primers, which are the key pieces for a PCR test, have been made publicly available by test, have been made publicly available by WHO network laboratories on the WHO web sit. WHO network laboratories on the WHO web sit.

• The primers have since been used by The primers have since been used by numerous countries around the world. numerous countries around the world.

GIDSAS


LaboratoryLaboratory

Status of laboratory tests currently Status of laboratory tests currently under development under development

Molecular tests (PCR) Molecular tests (PCR) • A ready-to-use PCR test kit containing primers and A ready-to-use PCR test kit containing primers and

positive and negative control has been developed. positive and negative control has been developed. • Testing of the kit by network members is expected to Testing of the kit by network members is expected to

quickly yield the data needed to assess the test’s quickly yield the data needed to assess the test’s performance, in comparison with primers developed by performance, in comparison with primers developed by other WHO network laboratories. other WHO network laboratories.

• Existing PCR tests are very specific but lack sensitivity. Existing PCR tests are very specific but lack sensitivity. That means that negative tests can’t rule out the That means that negative tests can’t rule out the presence of the SARS virus in patients. Various WHO presence of the SARS virus in patients. Various WHO network laboratories are working on their PCR protocols network laboratories are working on their PCR protocols and primers to improve their reliability.and primers to improve their reliability.

GIDSAS


LaboratoryLaboratory

Status of laboratory tests currentlyStatus of laboratory tests currently

under development under development Laboratories performing SARS specific PCR tests Laboratories performing SARS specific PCR tests should adopt strict criteria for confirmation of should adopt strict criteria for confirmation of positive results, especially in low prevalence positive results, especially in low prevalence areas, where the positive predictive value might be areas, where the positive predictive value might be lower:lower:

The PCR procedure should include appropriate The PCR procedure should include appropriate negative and positive controls in each run, which negative and positive controls in each run, which should yield the expected results: should yield the expected results:

1 negative control for the extraction procedure and 1 1 negative control for the extraction procedure and 1 water control for the PCR run water control for the PCR run

GIDSAS


LaboratoryLaboratoryStatus of laboratory tests currentlyStatus of laboratory tests currentlyunder development under development

Laboratories performing SARS specific PCR tests Laboratories performing SARS specific PCR tests should adopt strict criteria for confirmation of should adopt strict criteria for confirmation of positive results, especially in low prevalence positive results, especially in low prevalence areas, where the positive predictive value might be areas, where the positive predictive value might be lower:lower:

1 positive control for PCR and extraction and a parallel 1 positive control for PCR and extraction and a parallel sample to each patient test reaction spiked with a weak sample to each patient test reaction spiked with a weak positive control to detect substances inhibitory to PCR positive control to detect substances inhibitory to PCR (inhibition control) (inhibition control) If a positive PCR result has been obtained, it should be If a positive PCR result has been obtained, it should be confirmed by: confirmed by:

• repeating the PCR starting from the original sample repeating the PCR starting from the original sample AND AND

• amplifying a second genome regionamplifying a second genome regionOR OR

• having the same sample tested in a second having the same sample tested in a second laboratory.laboratory.

GIDSAS


LaboratoryLaboratoryStatus of laboratory tests Status of laboratory tests currently under development currently under development

3 Cell culture3 Cell culture• Virus in specimens (such as respiratory Virus in specimens (such as respiratory

secretions, blood or stool) from SARS secretions, blood or stool) from SARS patients can also be detected by infecting patients can also be detected by infecting cell cultures and growing the virus. cell cultures and growing the virus.

• Once isolated, the virus must be identified Once isolated, the virus must be identified as the SARS virus with further tests. Cell as the SARS virus with further tests. Cell culture is a very demanding test, but the culture is a very demanding test, but the only means to show the existence of a live only means to show the existence of a live virus.virus.

GIDSAS


TreatmentTreatmentHospitalized patients have been Hospitalized patients have been administered antibiotics, alone or in administered antibiotics, alone or in combination therapy without any clinical combination therapy without any clinical improvementimprovementIV Ribavirin (antiviral) + high-dose IV Ribavirin (antiviral) + high-dose corticosteroids have been responsible corticosteroids have been responsible for some clinical improvement of for some clinical improvement of critically ill patients in Hong Kongcritically ill patients in Hong KongIntensive & good supportive care with Intensive & good supportive care with and without antivirals has also improved and without antivirals has also improved prognosisprognosis

Date post:	11-Jan-2016
Category:	Documents
Upload:	melissa-fleming
View:	212 times
Download:	0 times

GIDSAS Chotani, 2003 PART IV: The Disease. GIDSAS Chotani, 2003 SARS: What do we know so far? Viral...

Documents