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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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slide3
COMMON COLD

MOST COMMON CAUSES

RHINOVIRUSES

(MEMBERS OF THE PICORNAVIRIDAE)

CORONAVIRUSES

- many other viruses as well

CDC/James Gathany

respiratory viruses
Paramyxovidae (paramyovirus family)

HPIV 1-4

human parainfluenza virus

RSV

respiratory syncytial virus

hMPV

human metapneumovirus

Adenoviridae (adenovirus family)

adenoviruses

Respiratory viruses
slide5
PARAMYXOVIRUSES

HN/H/G glycoprotein

SPIKES

pleomorphic

F glycoprotein

SPIKES

helical nucleocapsid (RNA plus

NP protein)

lipid bilayer membrane

polymerase

complex

M protein

slide6
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 parainfluenza viruses hpiv 1 2 3 and 4
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
slide8
EPIDEMIOLOGY”Iceberg phenomenon”

Classical disease presentation

Mild clinical disease

Asymptomatic infection but infectivity (+)

human parainfluenza viruses disease
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
human parainfluenza viruses croup
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)
human parainfluenza viruses
Human parainfluenza viruses
  • DIAGNOSIS
    • viral culture (shell vial cultures)

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

human parainfluenza viruses diagnosis
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
human parainfluenza viruses treatment
Human parainfluenza viruses TREATMENT
  • no antiviral therapy
  • supportive
  • usually self-limited
  • various treatments for croup
human parainfluenza viruses epidemiology
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
human parainfluenza viruses prevention
Human parainfluenza viruses PREVENTION
  • no vaccine
  • passive maternal antibodies may help in first few months
  • hand, nose and surface hygiene
respiratory syncytial virus
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

respiratory syncytial virus rsv
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
respiratory syncytial virus rsv infection
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
respiratory syncytial virus rsv20
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
respiratory syncytial virus disease
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
respiratory syncytial virus severe lrt disease
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
respiratory syncytial virus treatment
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
respiratory syncytial virus diagnosis
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
slide25
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/

respiratory syncytial virus prevention
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
respiratory syncytial virus prevention27
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
human metapneumovirus hmpv
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)
human metapneumovirus hpmv
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

human metapneumovirus hpmv disease
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?
human metapneumovirus hpmv epidemiology
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
human metapneumovirus hpmv diagnosis
Human metapneumovirus (hPMV)DIAGNOSIS
  • antigen detection
    • commercially available
  • PCR, culture
    • not yet commercially available
human metapneumovirus hpmv treatment
Human metapneumovirus (hPMV)TREATMENT
  • supportive
    • hydration
    • respiratory monitoring and management
human metapneumovirus hpmv prevention
Human metapneumovirus (hPMV)PREVENTION
  • hand, nose and surface hygiene
  • similar hospital infection control practices as for RSV
adenoviruses
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

slide36
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
adenoviruses37
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
adenoviruses38
Adenoviruses
  • Infect mucoepithelial cells
    • respiratory, GI and GU tracts
  • Enter via epithelium, replicate and spread to lymphoid tissue
  • Viremia occurs
  • Secondary involvement of viscera
adenoviruses types of infection
Adenovirusestypes of infection
  • lytic
    • mucoepithelial cells
  • latent/occult
    • virus remains in cell – seen in lymphoid tissue
  • oncogenic transformation (animals only)
human adenoviruses
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)
human adenoviruses41
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.

human adenoviruses transmission
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)
human adenoviruses infection and shedding
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%)
human adenoviruses44
Human adenoviruses

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

human adenoviruses disease
Human adenovirusesDISEASE
  • common cold (coryza, fever, headache, malaise)
  • pharyngitis
  • bronchitis
  • pneumonia
  • diarrhea
  • conjunctivitis
  • pharyngoconjunctival fever
  • cystitis
  • rash
  • neurologic disease
slide46
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
human adenoviruses epidemiology
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
human adenoviruses diagnosis
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
human adenoviruses treatment
Human adenoviruses TREATMENT
  • supportive care
    • most infections mild
  • for life threatening infections (immunocompromised patient)
    • cidofovir
human adenoviruses prevention
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