colds, flu and sars - malia

8/14/2019 Colds, Flu and SARS - Malia

1/53

Colds, Viruses &SARS:

Disease & Protection


2/53

UPPER RESPIRATORY TRACTINFECTIONS

Commonest cause of acute physical illness inthe developed world.

189 million days of absence from school and70 million days of absence from work.

110 million physician consultations, $2.9billion of OTC remedies.

Most common cause of inappropriate

antibiotic use (c. 40%). Total cost $40 billion per annum.

Fendrick AM. Arch Intern Med. 2003;163(4):487-94


3/53

The Common Cold Viruses

Rhinoviruses

Coronaviruses

Influenza

Parainfluenza viruses Respiratory syncytial virus (RSV) Human metapneumovirus (2001)


4/53

The Common Cold Viruses Rhinoviruses

Coronaviruses

Influenza

Parainfluenza viruses Respiratory syncytial virus (RSV)


5/53

RHINOVIRUSES

RNA viruses. Commonest causative agent of the

common cold accounting for 40 60%of colds.

Occur throughout the year but most

prevalent in September/October (80%of colds). >100 serotypes exist.


6/53

CLINICAL SYNDROMES CAUSED

BY RHINOVIRUS

CHILDREN ADULTS

Otitis media Sinusitis Bronchiolitis Asthma exacerbations Pneumonia COPD exacerbations Bronchitis


7/53


8/53


Coronaviruses

Influenza



9/53


Coronaviruses

Influenza



10/53

INFLUENZA

Influenza A main virus found inepidemics and pandemics.

Influenza B causes less severedisease than A.

Influenza C rare.


11/53

EPIDEMIOLOGY

Winter predominance in non-pandemicyears.

Causes considerable morbidity andmortality especially in the elderly andthose with chronic medical conditions.


12/53

Structure of Influenza Viruses

Neuraminidase

(9 subtypes)

Haemagglutinin(15 subtypes)

Viral RNA

Orthomyxovirus


13/53

ANTIGENIC SHIFT AND DRIFT

Antigenic drift minor changes in theinfluenza antigens and lead toepidemics.

Antigenic shift a major change in theantigenicity of the H and N proteins and

leads to pandemics.


14/53

Influenza A Pandemics1918 H1N1 (20 50 million deaths)1957 H2N21968 H3N21977* H1N1*Affected mainly young people born after 1957.

1997 H5N2 virus killed 6/18 humans infected inHong Kong - pandemic averted byslaughter of all chickens in Hong Kong?


15/53

0

10 000

20 000

30 000

40 000

50 000

60 000

70 000

0

200

400

600

800

1000

1200

1400

1600

1975 1980 1985 1990

4-weekly deaths 4-weekly influenza reports

Deaths Influenza A Influenza B

Epidemics have greater overall mortalitythan pandemics


16/53


Coronaviruses

Influenza



17/53

PARAINFLUENZA VIRUS

Similar spectrum of respiratory diseaseto RSV but less severe.

Mostly URTI but often complicated byotitis media.

15% of PIV infections involve the lower respiratory tract, commonestmanifestation is croup.


18/53


Coronaviruses

Influenza



19/53

Respiratory Syncytial Virus

Annual winter epidemics beginning inlate autumn in children and the elderly.

Can present with wide spectrum of disease severity from mild URTsymptoms only to severe lower

respiratory tract involvement . Most common cause of bronchiolitis.


20/53

Main cause of hospitalisation for respiratory tract disease in children.

Its role in adult disease has onlyrecently become appreciated. Significant cause of pneumonia and flu

especially in the elderly. High mortality rate in transplantpatients.


21/53

Shay et al J Am Med Assoc 1999;282:1440


22/53

IMMUNE RESPONSE TO

VIRUS INFECTION The immune response is essential to

clear virus infections.

In patients with impaired immunesystems virus infections are moresevere and infection with cold virusescan be fatal.

However the immune response canalso cause pathology.


23/53

Two broad types of immune response: Innate immunity (non-specific). Adaptive immunity (specific). The 2 work in combination to prevent

and resolve virus infections.


24/53

INNATE IMMUNITY

Physical factors: - airway epithelium,mucus, cilia.

Soluble factors: - antibacterial peptides(defensins), enzymes (lysozyme) IgA. Cells: - macrophages, NK cells,

neutrophils. The innate response is early but non-

specific.


25/53

Innate immunity to virus

infections


26/53

Mucus

Innate Immunity to virus

infections

MannoseBinding Lectin


27/53

ADAPTIVE IMMUNITY

Cellular response: - cytotoxic Tlymphocytes.

Humoral response: - antibody. Response is later than the innate

response but specific. Has memory!


28/53

Specific immunity to virusinfections: antibodies

B Cell


29/53

CD8 + T cell immunity to

respiratory viruses

PerforinFAS Ligand


30/53

INNATE ACQUIRED

VIRUS

NK CELLS

NEUTROPHILS MACROPHAGES

T LYMPHOCYTES

DENDRITICCELL

B LYMPHOCYTES

ANTIBODY

CYTOTOXICITYIFN-

IFN-

DAY 3 DAY 4 DAY 7


31/53

Normal immunity to respiratory virusesis complex involving innate and specific

defences. Immunity must be balanced to produce

effective viral clearance without

excessive immunopathology. Imbalance either way leads to disease.


32/53

Virus Entry

Immune Mediators

Glandular secretion

CytokinesHistamineLeukotrienesProstaglandins

{

LymphocytesEosinophilsNeutrophils

Production of symptoms

Vascular leakage

Upper andlower airway

inflammation

Granule proteinsCytokinesMediators

Replication

MEDIATORS OF THE IMMUNE RESPONSE


33/53

HISTAMINE

Induces sneezing and rhinorrhea. Firstgeneration H1 antihistamines reduce

cold symptoms but second generationnon-sedating anti-histamines do not.

Induces vasodilatation blocked by -adrenoceptor agonists.


34/53

PROSTAGLANDINS

Lipid mediators synthesised by theenzyme cyclo-oxygenase (COX).

Induce sneezing, sore throat and coughbut not nasal blockage/rhinorrhea.

Non-steroidal anti-inflammatory drugs(NSAIDs) aspirin, ibuprofen inhibitCOX.


35/53

INTERFERON-

Intra-nasal interferon has little effect onalleviating symptoms. Probably

because the inflammatory cascade hasbeen triggered.

However when administered

prophylactically can reduce risk of acquiring a cold by 60%


36/53

COMBINED ANTIVIRAL-ANTIMEDIATOR TREATMENT FOR

THE COMMON COLD

The greatest benefit in cold symptoms

is seen with a combination of chlorpheniramine, ibuprofen andinterferon.

Gwaltney JM Jr J Infect Dis. 2002 Jul 15;186(2):147-54.


37/53

IMMUNITY TO SPECIFIC

VIRUSES Immunity to specific viruses depends on

a combination of humoral and cell-

mediated immunity. The relative contribution of each varies

in different viral infections.

Immune responses may contribute tothe disease pathogenesis.


38/53

RHINOVIRUSES

Antibodies responsible for mostprotection against viral re-infection.

However antibodies are serotype-specific.

Cell-mediated immunity does have arole as different severity of symptoms is

seen in subjects with the same antibodytitre infected with rhinovirus.


39/53

INFLUENZA

Antibodies to HA protective againstinfection.

Antibodies to NA do not preventinfection but reduce spread of the virus. Antibody response is subtype specific

so antigenic drift results in virus escape. Cytotoxic T cells essential for clearance

of virus.


40/53

RSV

High frequency of recurrent infections. Immunity is neither complete nor long-

lasting. Both antibody and cellular components

involved. Immunopathology believed to contribute

to disease severity.


41/53

IMMUNE PATHOLOGY

CAUSED BY RSV VACCINE Trials of formalin-inactivated RSV

vaccine in 1966-67.

When infected with RSV the vaccinatedchildren had more severe illness and 2died.

Intense inflammatory infiltrate seen inthe lungs.

Still no vaccine for RSV.


42/53

THE SPREAD OF SARSNovember 2002: New type of severe atypical pneumonia in

Guangdong

21 st Feb 03: Prof. Liew came from Guangdong, booked intothe Metropole

23rd

Feb: Admitted to Kwong Wah hospital: warned staff!(at least 70 hospital staff infected)

23 rd Feb: Jonnie Chang flew to Hanoi26 th Feb: Admitted to hospital with fever. Examined byCarlo Urbani, who alerted WHO (Dr Urbani and 3 other staff died, and 63 were infected)

Canadian visitor to the Metropole returned to Toronto

(infected her son; both died)


43/53

SARS: Clinical course Incubation period average: 4 days

Fever 99% Sputum 20%Chills 74% Shortness of breath 20%Myalgias 52% Diarrhoea 15%Cough 43% Sore throat 14%Headache 33%

Recurrent fever in 85%

Case fatality rate: often in 3rd

or 4th

week. Around 12% overall, 43% in over 60s Strongly related to age/intercurrent illness 26% required ITU admission.


44/53

Amoy Gardens Hong Kong

33 floor apartmentblocks

41% of 321 casesconcentrated in Block E,units 7 and 8

66% of cases reporteddiarrhoea

Cracked sewage pipesin kitchens

Contamination of U-traps in bathroom floors

Droplets may havespread when fan in use


45/53

CORONAVIRUSES

Two known human coronaviruses(15 30% of colds).

Widespread in domestic animals(enteric, lung, liver etc)

RNA genome 27-30 kb

(largest RNA virus)

SARS coronavirusCompletely novel genetically


46/53

Points of Interest

Spreads fast in hospital wards Does not respect international

boundaries Fit, healthy people affected Strong suggestion of immunopathology

Break in fever - delayed second phase Possible response to steroids


47/53

Protective Measures Reported byInfected and Non-Infected Staff (Lancet

2003; 361: 1519-20)

.047227 (94%)10 (77%)Hand-washing

.00683 (34%)0 (0%)Gowns

.364117 (48%)4 (31%)Gloves

.0001169 (70%)2 (15%)Masks

p valueNon-infectedstaff (n=241)

Infected staff (n-13)

Protectivemeasures


48/53

Animal Reservoir?

Beijing - no SARS-like coronaviruses in 732animals from 54 wild and 11 domesticspecies in southern China, including palmcivets.

Hong Kong - related viruses have so far beenfound in about half-a-dozen species includingwild civet.

Against the advice of the WHO restrictions onthe sale of wild animals in markets in Chinahave been lifted.


49/53

Civet cat: nocturnal animal related to mongoose.


50/53

SARS: Global effort, spread and effects

SARS does not respect national borders. Speed of spread of information is unprecedented.

Scientific discovery has been extremely fast. Very large negative economic impact on tourism,

travel and trade.

May have devastating impact on poor countrieswith insufficient infrastructure.


51/53

The Future? First recognized as a global threat in mid-March

2003, SARS was successfully contained in less thanfour months.

On 5 July 2003, WHO reported that the last humanchain of transmission of SARS had been broken.

While much has been learned including discovery of a new coronavirus (SARS-CoV), our knowledgeabout SARS coronavirus infection remains limited.

Resurgence of SARS remains a distinct possibilityand does not allow for complacency.


52/53

KEY POINTS Colds are caused by a number of different

respiratory viruses. Usually mild self-limiting illness but can have

more serious consequences.

Efficiently cleared by the immune system butthe large number of viruses and their capacityto change means recurrent infectioninevitable.

The emergence of SARS is an illustration of how new pathogens can emerge and howrapidly worldwide spread can occur.


53/53

ACKNOWLEDGEMENTS

PRFOESSOR PETER OPENSHAW

PROFESSOR SEBASTIAN JOHNSTON

colds, flu and sars - malia

Documents