20 chapter viruses associated with respiratory infections
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20 chapter viruses associated with respiratory infections. Department of pathogenic biology xie-shuixiang. ORTHOMYXOVIRUSES. pleomorphic influenza types A,B,C febrile, respiratory illness with systemic symptoms. ‘ FLU ’. True influenza

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20 chapterviruses associated with respiratory infections

Department of pathogenic biology

xie-shuixiang


ORTHOMYXOVIRUSES

  • pleomorphic

  • influenza types A,B,C

  • febrile, respiratory illness with systemic symptoms


‘FLU’

  • True influenza

    • influenza virus A or influenza virus B (or influenza virus C infections - much milder)

  • Febrile respiratory disease with systemic symptoms caused by a variety of other organisms often called ‘flu’


THE IMPACT OF INFLUENZAPANDEMICS

Deaths:


INFLUENZA VIRUS


Composition of Influenza Virus

1.Core

RNA: -ssRNA, 8 fragments

NP (nucleoprotein)

RNA dependent RNA polymerase

2. envelope

M protein

lipid envelope

sipke hemagglutinin(HA) 5

neuraminidase(NA) 1


HA - hemagglutinin

NA - neuraminidase

helical nucleocapsid (RNA plus

NP protein)

lipid bilayer membrane

polymerase complex

M1 protein

type A, B, C : NP, M1 protein

sub-types: HA or NA protein


Nomenclature

Host of origin

geographical origin

strain number

parentheses

antigenic description

of HA and NA

e.g. A/swine/Iowa/3/70(H1N1)

A/Hong Kong/1/68(H3N2)


Functions of Hemagglutinin

  • HA causes agglutination of red blood cells.

  • Viruses bind to the mucous membrane cells by HA1 interacting with membrane receptor.

  • Virus’ envelope fuse with cell membrane by HA2 forming a fusion pore.


S

S

cell enzymes

S

S

acid pH

S

S

HA protein - attachment, fusion


Functions of Neuraminidase

  • NA help the virus to permeate mucin and escape from “non-specific”inhibitor.

  • NA can increase the number of free virus particles, hence more virus spread from the original site of infection.

  • NA is important in the final stages of release of the new virus particle from infected cells.


NA protein - neuraminidase


ANTIGENIC DRIFT

  • Minor changes in antigens due to gene mutation in influenza virus.

  • HA and NA accumulate mutations

    • RNA virus

  • immune response no longer protects fully

  • sporadic outbreaks, limited epidemics


ANTIGENIC SHIFT

  • Major changes in antigens due to gene reassortment in influenza virus.

  • “new” HA or NA proteins

  • pre-existing antibodies do not protect

  • may get pandemics


INFLUENZA A PANDEMICS

Ryan et al., in Sherris Medical Microbiology


where do “new” HA and NA come from?

  • 15 types HA

  • 9 types NA

    • all circulate in birds

  • pigs

    • avian and human


where do “new” HA and NA come from?


why do we not have influenza B pandemics?

  • so far no shifts have been recorded

  • no animal reservoir known


TRANSMISSION

  • AEROSOL

    • 100,000 TO 1,000,000 VIRIONS PER DROPLET

  • 18-72 HR INCUBATION

  • SHEDDING


  • DECREASED CLEARANCE

  • RISK BACTERIAL INFECTION

  • VIREMIA RARE

Lycke and Norrby Textbook of Medical Virology 1983


RECOVERY

  • INTERFERON - SIDE EFFECTS INCLUDE:

    • FEVER, MYALGIA, FATIGUE, MALAISE

  • CELL-MEDIATED IMMUNE RESPONSE

  • TISSUE REPAIR

    • CAN TAKE SOME TIME


INTERFERON


antiviral state

antiviral state

antiviral state

antiviral state

INTERFERON


antiviral state

antiviral state

antiviral state

antiviral state

INTERFERON


antiviral state

antiviral state

antiviral state

antiviral state

INTERFERON


PROTECTION AGAINST RE-INFECTION

  • IgG and IgA

    • IgG less efficient but lasts longer

  • antibodies to both HA and NA important

    • antibody to HA more important (can neutralize)


SYMPTOMS

  • FEVER

  • HEADACHE

  • MYALGIA

  • COUGH

  • RHINITIS

  • OCULAR SYMPTOMS


CLINICAL FINDINGS

  • SEVERITY

    • VERY YOUNG

    • ELDERLY

    • IMMUNO-COMPROMISED

    • HEART OR LUNG DISEASE


PULMONARY COMPLICATIONS

  • CROUP (YOUNG CHILDREN)

  • PRIMARY INFLUENZA VIRUS PNEUMONIA

  • SECONDARY BACTERIAL INFECTION

    • Streptococcus pneumoniae

    • Staphlyococcus aureus

    • Hemophilus influenzae


DIAGNOSIS

  • ISOLATION

    • NOSE, THROAT SWAB

    • TISSUE CULTURE OR EGGS

  • SEROLOGY

  • RAPID TESTS

  • provisional - clinical picture + outbreak


VACCINE

  • ‘BEST GUESS’ OF MAIN ANTIGENIC TYPES

    • CURRENTLY

      • type A - H1N1

      • type A - H3N2

      • type B

      • each year choose which variant of each subtype is the best to use for optimal protection


VACCINE

  • inactivated

  • egg grown

  • sub-unit vaccine for children

  • reassortant live vaccine approved 2003

    • for healthy persons (those not at risk for complications from influenza infection) ages 5-49 years


live vaccine development

adapted from

Treanor JJ Infect. Med. 15:714


TREATMENT - DRUGS

  • RIMANTADINE (M2)

    • type A only, needs to be given early

  • AMANTADINE(M2)

    • type A only, needs to be given early

  • ZANAMIVIR (NA)

    • types A and B, needs to be given early

  • OSELTAMIVIR (NA)

    • types A and B, needs to be given early


  • NA protein - neuraminidase

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    OTHER TREATMENT

    • REST, LIQUIDS, ANTI-FEBRILE AGENTS (NO ASPIRIN FOR AGES 6MTHS-18YRS)

    • BE AWARE OF COMPLICATIONS AND TREAT APPROPRIATELY


    CORONAVIRUSES

    COLDS AND  SARS


    Severe acute respiratory syndrome (SARS)


    SARS Coronavirus, SARS CoV

    • Severe Acute Respiratory Syndrome(SARS)

    • 2002/11


    SARS symtom

    • Droplet or osculation

    • Latent period:2~12d,usually4~5d

    • Centralization in family and hospital apparently


    Biological properties

    • 60-130nm,envelope with spikes

    • +ssRNA,29.7KB,14 ORF:RNApolymer- ase、S、E、M、N

    • Vero cell--CPE

    • Infected quadrumana –typical SARS symptom


    SARS Genome


    Transmission and Epidemiology


    Chinese SARS epidemiology


    Diagnosis

    • Mainly depend on the clinic and epidemiologic data

    • Pathogen diagnosis

      • Isolation and identification of virus

      • RT-PCR

      • Immunofluorescence、ELISA

    • P3 laboratory

    • Pathogen diagnosis is immature


    Prevention

    • SARS CoV比普通CoV抵抗力强,室温下痰、粪便、尿中可稳定存活1~2d

    • 对温度敏感,37oC存活4d,56oC存活90m,75oC30m

    • 对含氯消毒剂、过氧乙酸及UV均敏感,

    • WHO推荐中效以上的消毒剂,如过氧乙酸


    Pathologic cytoarchitectural changes indicative of diffuse alveolar damage, as well as a multinucleated giant cell with no conspicuous viral inclusions.


    Paramyxoviridae

    -ssRNA


    measles (rubeola)

    Koplik's spots on mucosal membranes

    Maculopapular rash (extends from face to extremities)


    Measles virusmeasles (rubeola)


    SUB-ACUTE SCLEROSING PANENCEPHALITIS (SSPE)

    • Very rarely (7 in 1,000,000 cases)

    • 1-10 years after initial infection.

    • progressive, fatal disease.

    • defective forms of the virus in the brain


    Histopathology of measles pneumonia.  Giant cells.

    Lab Diagnosis


    Prevention

    MMR

    • (mumps, measles, rubella) vaccine contains live, attenuated forms of all three of these viruses.


    MUMPS VIRUSMumps 

    • British "to mump" - to grimace or grin, from the appearance of the patient as a result of parotid gland swelling.

    • (Note: Other agents can also cause parotitis).


    • very contagious


    RESPIRATORY SYNCYTIAL VIRUS

    spherical or pleomorphic enveloped viruses (100-350 nm) with single-stranded, negative sense linear RNA


    Infection of cells results in syncytiumformation

    Upper respiratory infection (‘bad cold’) in older children and adults

    Lower respiratory infection- Bronchiolitis and/or pneumonia may occur after  the upper respiratory infection

    Severe infections occur in infants (2-6m)


    Others


    ADENOVIRUS

    • non-enveloped

    • linear double-stranded (ds) DNA

    • Icosahedral capsid,

    • capsomeres

      hexons;

      at the vertices are 12 pentons, from which a fiber with a terminal knob projects. This complex is toxic to cells - causing rounding and death of cells through inhibition of protein synthesis.


    • Eye

      Epidemic Keratoconjunctivitis (EKC), acute follicular conjunctivitis, pharyngoconjunctival fever

    • Respiratory system

      Common cold (rhinitis), pharyngitis (with or without fever), tonsillitis, bronchitis, pharyngoconjunctival fever, acute respiratory disease (LRI)

    • Genitourinary

      Acute hemorrhagic cystitis

    • Gastrointestinal

      Gastroenteritis.


    Rash

    Congenital rubella

    cataracts

    RUBELLA


    RUBELLA (GERMAN MEASLES) VIRUS

    • Togavirus

    • +ssRNA

    • Fetal damage

    • live vaccine (attenuated strain)


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