Lessons learn from sars the etiology pathology and clinical features of sars
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Lessons Learn from SARS The Etiology ,Pathology and Clinical Features of SARS. Nantong Medical College The Department of Pathology Chen Li. Introduction.

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Lessons learn from sars the etiology pathology and clinical features of sars

Lessons Learn from SARSThe Etiology ,Pathology and Clinical Features of SARS

Nantong Medical College

The Department of Pathology

Chen Li


Lessons learn from sars the etiology pathology and clinical features of sars

Introduction

SARS is a condition of unknown cause that has recently been recognized in patients in Asia , North America , and Europe . This report summarizes the initial epidemiologic findings , pathologic description , clinical and diagnostic findings.


Lessons learn from sars the etiology pathology and clinical features of sars

  • An outbreak of atypical pneumonia, referred to as severe acute respiratory syndrome (SARS) and first identified in Guangdong Province, China, has spread to several cities and countries. The severity of this disease is such that the mortality rate appear to be 3 to 6%. A number of laboratories worldwide have undertaken the identification of the causative agent.


Lessons learn from sars the etiology pathology and clinical features of sars

  • Medical personnel , physicians ,nurses and hospital workers are among those commonly infected . Sadly,Dr. Carlo Urbani,the 46-year-old WHO physician and infectious disease specialist whose work defined SARS(Ferbruany 28),and died on March 29 of SARS .


The who issued a global alert sars

The WHO issued a global alert SARS

  • The first time on march 12

  • The second time on march 15

  • The third time on march 27

  • The international society are taking actions to SARS. The virus has been identified to be coronavirus by the cooperation of laboratories all over the world. The target has been aimed, and the actions are undertaken. This is a battle without fire.


Lessons learn from sars the etiology pathology and clinical features of sars

1. Etiology

On march 24 ,scientists at the CDC in USA and in Hong Kong announced that a new coronavirus had been isolated from patients with SARS.

This coronavirus(COV) has been named publicly by the WHO and member laboratories as “SARS virus”.

This is a novel virus that is not closelt related to any of the known clusters of coronaviruses.


Lessons learn from sars the etiology pathology and clinical features of sars

SARS virus

completely newcoronavirus


Lessons learn from sars the etiology pathology and clinical features of sars

  • The National Microbiology Laboratory in Canada obtained the Tor2 isolated from a patient in Toronto, and succeeded in growing a coronavirus-like agent in African Green Monkey Kidney (Vero E6) cells.

  • This virus was purified and its RNA genome extracted and sent to the British Columbia Centre for Disease Control in Vancouver for genome sequencing by the Genome Sciences Centre at the BC Cancer Agency.


Lessons learn from sars the etiology pathology and clinical features of sars

  • The coronaviruses are members of a family of enveloped viruses that replicated in the cytoplasm of animal host cells. They are distinguished by the presence of a single-stranded plus sense RNA genome approximately 30 kb in length that has a 5’ cap structure and 3’ polyA tract. Upon infection of a host cell, the 5’ most open reading frame (ORF) of the viral genome is translated into a large polyprotein that is cleaved by viral-encoded proteases to release several nonstructural proteins including an RNA-dependent RNA polymerase (Rep) and ATPase helicase (Hel). These proteins in turn are responsible for replicating the viral genome as well as generating nested transcripts that are used in the synthesis of the viral proteins. The mechanism by which these subgenomic mRNAs are made is not fully understood.


Lessons learn from sars the etiology pathology and clinical features of sars

SARS virus

completely newcoronavirus


Lessons learn from sars the etiology pathology and clinical features of sars

SARS virus structure

S(spite protein)

M(membrane protein)

E(small membrane protein)

HE(hemagglutinin eaterase)

N(nucleocapsid protein)

RNA genome

Some small nonstructure ORFs


Lessons learn from sars the etiology pathology and clinical features of sars

SARS virus in EM

60-220nm


Lessons learn from sars the etiology pathology and clinical features of sars

The SARS genomic sequence has been deposited into Genbank (Accession AY274119.3 , Apr. 18 03, Canada)


Lessons learn from sars the etiology pathology and clinical features of sars

The nucleotide position ,associated ORF and putative transcription regulatory sequences(TRSs).


Lessons learn from sars the etiology pathology and clinical features of sars

The feature of the Tor2 genome sequence (Canada)


Lessons learn from sars the etiology pathology and clinical features of sars

The SARS genomic sequence has been deposited into Genbank (Accession AY278554, Apr.18 03, USA)


Lessons learn from sars the etiology pathology and clinical features of sars

Make a comparison beteen tow SARS genomic sequence

USA

29727nt

Canada

29736nt

GenBankAY278554


Lessons learn from sars the etiology pathology and clinical features of sars

attachment

engulfenment

lost envelope

early protein synthesis

nucleotide synthesis

later protein synthesis

encapisula assemble

release


Lessons learn from sars the etiology pathology and clinical features of sars

Human coronaviruses surivival time

229E---6 days in suspension

3 hours after drying on surfaces

OC43---<1hour after drying on surfaces

SARS virus---4-5 days on drying plastic film

5 days in excrements

10 days in urine

15 days in blood


Lessons learn from sars the etiology pathology and clinical features of sars

Extinct Cov

High tempreture 56c 90min or 75c 30min

Ultraviolet 30 min

Other disinfectants handling effectively


Lessons learn from sars the etiology pathology and clinical features of sars

Comparison of previously 3 groups CoV

  • Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of CoVs

Cov are divided into three serotypes,

The SARS virus is the fouth ?


Lessons learn from sars the etiology pathology and clinical features of sars

The purpose of studying genome sequence

  • The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using PCR and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.


About metapneumovirus

About metapneumovirus

  • In addition, a novel coronavirus was isolated from vero cell cultures of SARS patiens and metapneumovirus was also identified . Futher studies are currently being completed to help determine whether the human metapneumovirus and novel coronavirus, either alone or in combination ,are the cause of SARS or whether other thus far undetected pathogens are possibly responsible .The possibility that coinfection of either virus with another agent may be responsible for SARS cannot be excluded.


Lessons learn from sars the etiology pathology and clinical features of sars

Conclusion

  • SARS virus(coronavirus), a single-stranded plus sense RNA.

  • SARS virus are stable but a few variforms

  • SARS virus has long period survival

  • The genome sequencing of the virus has been finished

  • Different from previously found coronaviruses.

  • The largest enveloped virus is difficult to be cultured in vitro.

  • May be the animals sources?----fruit fox


Lessons learn from sars the etiology pathology and clinical features of sars

2. Pathology

Severe exudate and tansudate inflammation congestion,edema and formation of hyline membrane


Lessons learn from sars the etiology pathology and clinical features of sars

highly reactive blood vessels (Cap)

Capillary highly dilatation and congestion

RBC transudation

Virus inclusion


Lessons learn from sars the etiology pathology and clinical features of sars

syncytial giant cells pneumonia

Scanty interstitial inflammatory-cell infiltrates


Lessons learn from sars the etiology pathology and clinical features of sars

Multinucleated syncytial giant cells and abundant foamy macrophages,no conspicuous viral inclusions

in lung of SARS patient


Lessons learn from sars the etiology pathology and clinical features of sars

Special staining for virus

Diffuse alveolar damage with proliferation of Alveolar epithelial typeⅡ

Virus inclusion (Macchiavell staining )


Lessons learn from sars the etiology pathology and clinical features of sars

Immunohistochemical staining of SARS-associated Cov-infected cells

Immunoalkline phosphatase with napthol-fast red substrate and hematoxylin counterstain (FAF X250)


Lessons learn from sars the etiology pathology and clinical features of sars

The immuno-fluorescent staining for virus


Lessons learn from sars the etiology pathology and clinical features of sars

Lung solidification


Lessons learn from sars the etiology pathology and clinical features of sars

diffuse alveolar damage and no infection evidence

Intraalveolar and interstitial mononuclar cells suggesting a possible viral cause were also noted , but no viral inclusion were seen .


Lessons learn from sars the etiology pathology and clinical features of sars

Lesions in other organs

Multifocal hemorrhage and necrosis

Proliferation of histocytes in the surrounding tissue

phagocytosis of histocytes


Lessons learn from sars the etiology pathology and clinical features of sars

Conclusion

1. Diffuse alveolar damage

2. Severe exudate and tansudate but no infection evidence in lung

3. Proliferation of Alveolar epithelial typeⅡ

4. Syncytial giant cells pneumonia

5. Hyline membrane formation

6. Lung solidification

7. The main cause of death is the progressing respiratory failure caused by lung damaging, which also have relationships with immuno-pathological change of the patients.


Lessons learn from sars the etiology pathology and clinical features of sars

3. Clinical Features

1. Epidemiology (contact and influential area)

2. Symptoms and signs (fever, dry cough ,myolgia ,

diarrhea and the number of viruses in sputum is

>100M/ml)

3. Laboratory tests: WBC↓,LC ↓ (CD4+ ↓,CD8+↓)

4. X-ray: patches and confluent air-space opacification

5. No effective to antibiotics,partially effective to

hormone.


Lessons learn from sars the etiology pathology and clinical features of sars

X-rayappearance


Lessons learn from sars the etiology pathology and clinical features of sars

X-rayappearance


Lessons learn from sars the etiology pathology and clinical features of sars

SARS has spread rapidly becouse during the incubation period , which appears to be between 1 day and 11 days.With a median of about 5 days, patients can transmit the disorder to others.


Lessons learn from sars the etiology pathology and clinical features of sars

The statistical data of WHO appear the mortabity rate :

age mortabity rate

<24 year-old <1%

25-44year-old 6%

45-64 year-old 15%

>65 year-old >50%


Lessons learn from sars the etiology pathology and clinical features of sars

Review X-ray appearance of

15 SARS cases


Lessons learn from sars the etiology pathology and clinical features of sars

Case 1 : 29 year old symptomatic female with

normal radiographic appearance


Lessons learn from sars the etiology pathology and clinical features of sars

Case 2: A 31-year-old health-care worker presented with

2-day history of fever, chills and myalgia

Figure 1 - CXR at the time of diagnosis showed ill-defined air space opacification in right lower zone

Figure 2 - CXR after 3 days showed partial resoulation of consolidative changes in right lower zone. There is a new finding of ill-defined air space opacification in left lower zone

Figure 3 - CXR after another 4 days showed progressive resolution of the changes in both lower zones


Lessons learn from sars the etiology pathology and clinical features of sars

Case 3: A 34-year-old presented with 3-day history of

fever, chills and malaise

Figure 1 - CXR (7 days after admission) showed ill-defined air space opacification in periphery of right lower zone

Figure 3 - CXR (after another 4 days) showed marked resolution of the consolidative changes in both lungs after treatment

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


Lessons learn from sars the etiology pathology and clinical features of sars

Case 4: A 34-year-old health care worker presented

with fever, chills and myalgia for 2 days

Figure 1 - CXR showed ill-defined air-space opacity in periphery of left upper and mid zones

Figure 3 - CXR (after another 7 days) showed resolution of radiographic changes after successful treatment

Figure 2 - CXR (after 5 days) showed progressive air-space opacities in both lungs


Lessons learn from sars the etiology pathology and clinical features of sars

Case 5: 52-year-old symptomatic female from Virginia

15 MARCH 2003(On presentation to A&E)

19 MARCH 2003

20 MARCH 2003


Lessons learn from sars the etiology pathology and clinical features of sars

Case 6: 24-year-old Filipino nursing aid from nursing

home with one week history of fever,

dry cough and myalgia

Day 7 - Patient became hypoxic & required subsequent intubation. CXR showed bilateral widespread air-space infiltrates

Day 1 - CXR showed subtle left lower zone air-space infiltrates

Day 5 - CXR showed left lower zone consolidation became more obvious


Lessons learn from sars the etiology pathology and clinical features of sars

Case 7: 30-year-old worker with one week history of fever, dry cough and myalgia

Fig 3: (day 5 after onset of symptoms)Air-space opacification in the periphery of middle lobe abutting the superior aspect of the horizontal fissure

Fig 2: (day 4 after onset of symptoms)Confluent air-space opacification in left lower zone

Fig 1: (day 3 after onset of symptoms)Ill-defined air-space opacification in right lower zone


Lessons learn from sars the etiology pathology and clinical features of sars

Case 8: A 38-year-old doctor presented

with fever, chills and myalgia for 2 days

Fig1: (day 2 after onset of symptoms)Middle lobe air-space opacity obscuring part of right heart border

Fig 2: (day 3 after onset of symptoms)Ill-defined opacity in left lower zone

Fig 3: (day 4 after onset of symptoms)Bilateral lower zones air-space opacities in para-cardiac areas after successful treatment.


Lessons learn from sars the etiology pathology and clinical features of sars

Case 9: 26 year old symptomatic male

Fig 1: (day 4 after onset of symptoms)Peripheral segmental air-space opacification in right upper lobe

Fig 2: (day 5 after onset of symptoms)Patchy peripheral opacities involving both lower lobes

Fig 3: (day 6 after onset of symptoms)Multi-focal ill-defined air-space opacities in both lower and right upper zones


Lessons learn from sars the etiology pathology and clinical features of sars

Case 10: 23 year old symptomatic female

Fig 1: (day 4 after onset of symptoms)Peripheral patchy opacification in right upper and left lower zones

Fig 2: (day 5 after onset of symptoms)Patchy air-space opacification in both mid and lower zones

Fig 3: (day 7 after onset of symptoms)Multi-focal diffuse air-space opacities in both lungs


Lessons learn from sars the etiology pathology and clinical features of sars

Case 11: 57year old symptomatic retire worker

Fig 1: (day 5 after onset of symptoms)Multi-focal confluent areas of air-space opacities in both lungs

Fig 2: (day 6 after onset of symptoms)Diffuse and widespread consolidative changes in both lungs (patient is intubated)


Lessons learn from sars the etiology pathology and clinical features of sars

Case 12: 46year old symptomatic man

A follow-up chest radiograph showed progression of the disease , with mulotiple, bilateral ateas of involvement.

A subsequent chest radiograph shows improvement of bilateral lung opacities after therapy.

An obvious area of air-space shadowing on the leftside


Lessons learn from sars the etiology pathology and clinical features of sars

Case 13-15:children’s SARS

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

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

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


Lessons learn from sars the etiology pathology and clinical features of sars

Conclusion

  • Respiratory difficult (>30times/min)

  • Hypoxmia

  • Abnormal chest radiographs show air-space consolidation in either unilateral multifocal or Bilateral involvement, which progressing more than 50% within 48 hours

  • Shock

  • Chest X-ray features separated from clinical features.

  • The diagnosis must dependent on clinical features


Lessons learn from sars the etiology pathology and clinical features of sars

The results of research on SARS may give some hints to the clinical therapy

  • The main pathological change of severe SARS is the exudate and transudate inflammation with hyline membrane formation, which suggests the proper time and large dose of hormone therapy is helpful to ease the ARDS.

  • Considering the possibility of correlative infections, the correlative therapy should be conducted in clinics.

  • The damage immuno-organs suggests the applying of immuno-enhancing and regulating agents is helpful.

  • Antibody treatment and proteose


Lessons learn from sars the etiology pathology and clinical features of sars

It is becoming quite clear that SARS is an infectious disease.

Although progress has been extraordinarily rapid because of unprecedented worldwide scientific cooperation , there is still a lot to be learned.


Lessons learn from sars the etiology pathology and clinical features of sars

Emerging global microbial threats

Lessons learn from SARS

  • Importance of strong national and international collaborations and partnerships

  • Enhancing global infectious disease surveillance

  • Rebuilding domestic public health capacity

  • Developing optimal diagnostic tests

  • Effective therapy need for new antimicrobial drugs

  • Educating and training multidisciplinary workforce

  • Vaccine approaches, development and production


Lessons learn from sars the etiology pathology and clinical features of sars

thank you very much!


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