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CDC/James Gathany . COMMON COLD MOST COMMON CAUSES RHINOVIRUSES ( MEMBERS OF THE PICORNAVIRIDAE ) CORONAVIRUSES - many other viruses as well. CDC/James Gathany . Paramyxovidae (paramyovirus family) HPIV 1-4 human parainfluenza virus RSV respiratory syncytial virus hMPV

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COMMON COLD

MOST COMMON CAUSES

RHINOVIRUSES

(MEMBERS OF THE PICORNAVIRIDAE)

CORONAVIRUSES

- many other viruses as well

CDC/James Gathany


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Paramyxovidae (paramyovirus family)

HPIV 1-4

human parainfluenza virus

RSV

respiratory syncytial virus

hMPV

human metapneumovirus

Adenoviridae (adenovirus family)

adenoviruses

Respiratory viruses


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PARAMYXOVIRUSES

HN/H/G glycoprotein

SPIKES

pleomorphic

F glycoprotein

SPIKES

helical nucleocapsid (RNA plus

NP protein)

lipid bilayer membrane

polymerase

complex

M protein


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PARAMYXOVIRUS FAMILYSURFACE GLYCOPROTEINS

GENUS

GLYCOPROTEINS

TYPICAL MEMBERS

PARAMYXOVIRUS SUBFAMILY

Paramyxovirus

HN, F

HPIV1, HPIV3

Rubulavirus

HN, F

HPIV2, HPIV4, mumps virus

Morbillivirus

H, F

measles virus

PNEUMOVIRUS SUBFAMILY

Pneumovirus

G, F

respiratory syncytial virus

Metapneumovirus

G, F

human metapneumovirus


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Human parainfluenza virusesHPIV 1, 2, 3 and 4

  • FOUR SEROTYPES

    • HPIV 1, 2, 3 and 4

  • INFECTION

    • aerosol, person to person and fomites

      • unstable, but can survive on surfaces for a few hrs

    • highly contagious

    • susceptible to soap and water, alcohol based disinfectants, etc.

    • incubation 1-7 days


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EPIDEMIOLOGY”Iceberg phenomenon”

Classical disease presentation

Mild clinical disease

Asymptomatic infection but infectivity (+)


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Human parainfluenza viruses DISEASE

  • usually see as upper respiratory tract infections

    • one of causes ‘common cold’

    • coryza - inflammation nasal mucous membranes

      • ->congestion, headache, runny nose

    • fever

    • pharyngitis

  • however can be more serious as spreads down respiratory tract

    • croup, bronchitis, bronchiolitis, pneumonia

    • highest % of serious disease due to HPIV is seen in young children

    • second to respiratory syncytial virus in importance for lower respiratory tract disease in very young

  • can cause disease in adults (reinfections occur) – usually mild

  • reinfections in adults can sometimes be severe

    • especially elderly and immunocompromised – bronchiolitis, pneumonia

  • viremia is rare for HPIV

  • very rarely parotitis, meningitis, encephalitis



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Human parainfluenza virusesCROUP

  • laryngotracheitis or laryngotracheobronchitis

  • primarily in young

    • usually <6 yrs

  • HPIV is most common cause of croup

  • other viruses also cause croup

  • fever, cough, hoarseness, stridor

  • outbreaks most often associated with HPIV1 and HPIV2

  • HPIV3 – sporadic cases

  • humidification, racemic epinephrine, steroids (some cases)


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Human parainfluenza viruses

  • DIAGNOSIS

    • viral culture (shell vial cultures)

http://www.lhsc.on.ca/lab/MICRO/virology/vir_cult.htm


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Human parainfluenza viruses DIAGNOSIS

  • viral culture (shell vial assays)

    • detect with fluorescent antibodies, hemadsorption

  • direct detection virus in respiratory secretions (first week of symptoms)

    • immunoassays or PCR

  • serology

    • rise of IgG in paired specimens or high levels IgM


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Human parainfluenza viruses TREATMENT

  • no antiviral therapy

  • supportive

  • usually self-limited

  • various treatments for croup


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Human parainfluenza viruses EPIDEMIOLOGY

  • restricted to humans, important and ubiquitous

    • most people have had all types of HPIV by 5yrs of age

  • reinfections throughout life

    • usually less severe, may be symptomatic or asymptomatic

    • asymptomatic infections can be infectious

  • usually shed for ~1 week

    • immunocompromised individuals with lower respiratory tract disease may shed for weeks

  • antigenically stable

  • HPIV 1 and 2 tend to be in fall

  • HPIV2 tends to be biennial

  • HPIV 3 throughout year, but especially spring and summer

  • HPIV 4

    • less often recognized, usually milder infections

      • less common cause of croup, bronchiolitis


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Human parainfluenza viruses PREVENTION

  • no vaccine

  • passive maternal antibodies may help in first few months

  • hand, nose and surface hygiene


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Respiratory syncytial virus

PARAMYXOVIRUS FAMILYSURFACE GLYCOPROTEINS

GENUS

GLYCOPROTEINS

TYPICAL MEMBERS

PARAMYXOVIRUS SUBFAMILY

Paramyxovirus

HN, F

HPIV1, HPIV3

Rubulavirus

HN, F

HPIV2, HPIV4, mumps virus

Morbillivirus

H, F

measles virus

PNEUMOVIRUS SUBFAMILY

Pneumovirus

G, F

respiratory syncytial virus

Metapneumovirus

G, F

human metapneumovirus


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Respiratory syncytial virus (RSV)

  • 2 major strains

    • group A and group B (G protein differences)

    • multiple genotypes of each strain

    • currently not clear how these affect the clinical picture


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Respiratory syncytial virus (RSV)INFECTION

  • infections

    • aerosol, person-to-person and fomites

      • virus unstable, but can survive for an hour or so on hands, and on inanimate surfaces for a few hrs

    • easily spread (infants may have 10 million pfu/ml in nasal secretion)

    • virtually all children have been infected by 2yrs of age

    • primary infections are usually symptomatic

    • reinfections are common – may be symptomatic or asymptomatic

  • incubation period

    • a few days to a week

    • recovery takes a week or two

  • virus shedding

    • a few days to a week

    • 3-4 weeks in infants or immune suppressed individuals


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Respiratory syncytial virus (RSV)

  • virus confined to respiratory tract

  • infects respiratory epithelial cells

  • mucosal edema

  • increased mucin production

  • cell necrosis

  • obstruction by mucin/cell debris

  • host immune response contributes to pathology

  • cell mediated immunity important for recovery


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Respiratory syncytial virusDISEASE

  • common cause upper respiratory tract infections

    • runny nose, cough, sore throat, headache, fever, malaise, loss appetite

    • co-infection with bacteria usually not a problem except otitis media common

  • 25% of primary infections result in lower respiratory tract infections – bronchiolitis, viral pneumonia

    • commonest cause of bronchiolitis

    • if previously healthy, only a few individuals with bronchiolitis need hospitalization

    • re-infections usually not associated with LRT disease

  • but...reinfections can be associated with LRT disease

    • risk factors include immunosuppression, cardiopulmonary disease


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Respiratory syncytial virusSEVERE LRT DISEASE

  • risk factors for severe disease

    • age (especially if less than 6 months)

    • preterm birth

    • heart disease

    • pulmonary hypertension

    • lung disease of prematurity

    • immunodeficiency


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Respiratory syncytial virusTREATMENT

  • no specific antivirals

  • supportive care

    • hydration

    • assessment and management of respiratory status

    • ribavirin

      • not used routinely, may be considered in life threatening situations


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Respiratory syncytial virusDIAGNOSIS

  • rapid antigen assay

  • isolation (shell vial culture)

  • PCR

    • especially useful in older children and adults when viral load is usually lower and so antigen detection or viral isolation less reliable

      • not widely available yet

  • serology

    • usually used for epidemiology rather than diagnosis


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Respiratory syncytial virusEPIDEMIOLOGY

  • worldwide distribution

  • restricted to humans

  • US ~3000 deaths per yr

  • In USA usually late winter, early spring

    • earlier in Florida

  • timing helps to determine when to give prophylaxis to high-risk children

  • timing varies from year to year

    • surveillance system in US

  • http://www.cdc.gov/Features/dsRSV/


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    Respiratory syncytial virusPREVENTION

    • No vaccine

      • passive immunization is available for high-risk children

    • Hand, nose and surface hygiene

    • Nosocomial infections common

      • need to be especially rigorous when high risk patients involved

        • pediatric wards, neonatal units, transplantation units, etc.

        • gloves, gowns, masks, goggles; isolation and cohort nursing


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    Respiratory syncytial virusPREVENTION

    • palivizumab (Synagis®)

      • humanized monoclonal antibody

      • for high-risk children

      • monthly IM injections during the RSV season

      • not effective in treatment of infection


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    PARAMYXOVIRUS FAMILYSURFACE GLYCOPROTEINS

    GENUS

    GLYCOPROTEINS

    TYPICAL MEMBERS

    PARAMYXOVIRUS SUBFAMILY

    Paramyxovirus

    HN, F

    HPIV1, HPIV3

    Rubulavirus

    HN, F

    HPIV2, HPIV4, mumps virus

    Morbillivirus

    H, F

    measles virus

    PNEUMOVIRUS SUBFAMILY

    Pneumovirus

    G, F

    respiratory syncytial virus

    Metapneumovirus

    G, F

    human metapneumovirus

    Human metapneumovirus (hMPV)


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    Human metapneumovirus (hPMV)

    • only recently (2001) recognized

    • common – probably 15% of childhood colds

      • commercial tests only recently available

    • serogroup A and group B, each group has 2 subgroups based on genotype

      • all 4 circulate

        Note: can get co-infections with more than one respiratory virus


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    Human metapneumovirus (hPMV)DISEASE

    • pathophysiology very similar to RSV

    • most children infected by age 5

      • reinfections common

    • upper respiratory tract

      • common cold, croup

    • often complicated by otitis media

    • lower respiratory tract

      • bronchiolitis (may be involved in 10-15% cases in infants)

      • pneumonia

    • possible fatal pneumonia in bone marrow and lung transplants?


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    Human metapneumovirus (hPMV)EPIDEMIOLOGY

    • worldwide

    • humans only source of infection

    • hPMV season has similar timing to RSV season

    • incubation period: few days to a week


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    Human metapneumovirus (hPMV)DIAGNOSIS

    • antigen detection

      • commercially available

    • PCR, culture

      • not yet commercially available


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    Human metapneumovirus (hPMV)TREATMENT

    • supportive

      • hydration

      • respiratory monitoring and management


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    Human metapneumovirus (hPMV)PREVENTION

    • hand, nose and surface hygiene

    • similar hospital infection control practices as for RSV


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    Adenoviruses

    • linear, double stranded DNA

    • non-enveloped

      • stable in environment

    • icosahedral

    • first isolated from adenoidal tissue

    http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/em_adeno.gif


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    Adenovirus- Properties

    • Stable in the environment

    • Relatively resistant to various disinfectants

      • Alcohol, detergents, chlorhexidine

    • Stable in GI tract- can withstand low pH, bile acids and proteolytic enzymes


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    Adenoviruses

    • Fiber protein – virus attachment protein

      • determines host cell specificiy

    • Virus -> nucleus

      • replicates DNA in nucleus

      • assembles nucleocapsid in nucleus

        • nuclear inclusion bodies

    • Released by cell lysis


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    Adenoviruses

    • Infect mucoepithelial cells

      • respiratory, GI and GU tracts

    • Enter via epithelium, replicate and spread to lymphoid tissue

    • Viremia occurs

    • Secondary involvement of viscera


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    Adenovirusestypes of infection

    • lytic

      • mucoepithelial cells

    • latent/occult

      • virus remains in cell – seen in lymphoid tissue

    • oncogenic transformation (animals only)


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    Human Adenoviruses

    • Approx 51 human serotypes (1-51)

    • Classified into six subgroups (A-F) based on hemagglutination patterns, hexon antigenicity and sequence

      • members of a subgroup often cause similar spectrum of disease

      • enteric adenoviruses are in subgroup F (40,41)


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    Human Adenoviruses

    Remaining serotypes are infrequently isolated or not clearly associated with disease.

    * Association with gastroenteritis not as firmly established as with types 40 and 41.


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    Human adenoviruses TRANSMISSION

    • person-to-person, aerosols, fomites

    • respiratory secretions, tears, fecal/oral

    • stable in environment

      • not very susceptible to many disinfectants

      • underchlorinated swimming pools, shared towels

      • under sterilized medical equipment (eye exam equipment, etc)


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    Human adenoviruses infection and shedding

    • incubation period few days to a couple of weeks

    • virus shedding usually highest during acute phase

      • may continue to shed at lower levels for a long time (months)

      • high rate of transmission to other family members (up to 50%)


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    Human adenoviruses

    Timecourse - Respiratory infectionSource- Medical Microbiology- Murray, Rosenthal, Kobayshi and Pfaller


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    Human adenovirusesDISEASE

    • common cold (coryza, fever, headache, malaise)

    • pharyngitis

    • bronchitis

    • pneumonia

    • diarrhea

    • conjunctivitis

    • pharyngoconjunctival fever

    • cystitis

    • rash

    • neurologic disease


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    Adenovirus infections in Immunocompromised hosts

    • Disseminated, severe and often fatal infections

    • Due to new infection or reactivation of latent virus

    • Prolonged infections with prolonged viremia and viral shedding

    • Necrotizing pneumonia, hepatitis, rash, DIC, CNS involvement


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    Human adenoviruses EPIDEMIOLOGY

    • human

    • asymptomatic infections common

    • reinfections common

    • crowding and stress can be risk factor

      • military basic trainees – may see in up to 10% in first week

      • daycare centers


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    Human adenoviruses DIAGNOSIS

    • antigen testing in some body fluids

      • can be very rapid

    • cell culture (shell vial)

      • prolonged shedding (especially in feces) so may mean that not cause of current disease

      • virus isolated from URT from site associated with disease may be more relevant to current disease

      • not applicable for enteric types 40, 42

    • PCR


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    Human adenoviruses TREATMENT

    • supportive care

      • most infections mild

    • for life threatening infections (immunocompromised patient)

      • cidofovir


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    Human adenoviruses PREVENTION

    • good hygiene

      • take into account that virus fairly stable

    • take care to thoroughly decontaminate medical equipment

    • adequate chlorination of swimming pools

      • to reduce risk pharynoconjunctival fever

    • use disposable or adequately sterilized items in ophthalmic practice

      • to reduce risk epidemic keratoconjunctivitis

    • no vaccine

      • one for military recruits no longer made


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