Respiratory viruses (other than influenza virus)

CDC/James Gathany

COMMON COLD MOST COMMON CAUSES RHINOVIRUSES ( MEMBERS OF THE PICORNAVIRIDAE ) - many other viruses as well

Respiratory viruses Paramyxoviridae (paramyxovirus family) HPIV 1-4 –human parainfluenza virus RSV –respiratory syncytial virus hMPV –Human metapneumovirus Adenoviridae (adenovirus family) adenoviruses

GENUSGLYCOPROTEINSTYPICAL MEMBERS ParamyxovirusHN, FHPIV1, HPIV3 RubulavirusHN, FHPIV2, HPIV4, mumps virus MorbillivirusH, Fmeasles virus PneumovirusG, Frespiratory syncytial virus MetapneumovirusG, Fhuman metapneumovirus PARAMYXOVIRUS SUBFAMILY PNEUMOVIRUS SUBFAMILY Paramyxoviruses – surface glycoproteins

M protein helical nucleocapsid (RNA plus NP protein) HN/H/G glycoprotein SPIKES polymerase complex lipid bilayer membrane F glycoprotein SPIKES Paramyxoviruses pleomorphic

Parainfluenza Virus SS (-) RNA virus (15kb) 4 serotypes: 1, 2, 3, 4 (type 4 – 4a and 4b)

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 –incubation 1-5 days

HPIV -disease URI - one of causes ‘common cold’ - congestion, headache, runny nose, fever, pharyngitis, croup LRI –Croup, bronchitis, bronchiolitis, pneumonia –serious disease due to HPIV in young children Elderly and IC – severe LRI viremia is rare in HPIV.

Airway narrowing in croup

HPIV and croup laryngotracheitis or laryngotracheobronchitis primarily in young - usually <6 yrs HPIV is most common cause of croup fever, cough, hoarseness outbreaks most often associated with HPIV1 and HPIV2 HPIV3 /4 – sporadic cases

HPIV – Lab diagnosis viral culture - detect with IF Direct detection Ag /nucleic acids in resp. secretions –ELISAs or PCR

HPIV -Rx no antiviral therapy supportive usually self-limited

Epidemiology ”Iceberg phenomenon” Classical disease presentation Mild clinical disease Asymptomatic infection but infectivity (+)

HPIV – Epidemiology restricted to humans, ubiquitous –most people have had all types of HPIV by 5yrs of age reinfections throughout life –usually milder, may be symptomatic or asymptomatic antigenically stable

HPIV – prevention No vaccine Passive maternal antibodies may help in first few months Hand and surface hygiene

Respiratory syncytial virus

GENUSGLYCOPROTEINSTYPICAL MEMBERS ParamyxovirusHN, FHPIV1, HPIV3 RubulavirusHN, FHPIV2, HPIV4, mumps virus MorbillivirusH, Fmeasles virus PneumovirusG, Frespiratory syncytial virus MetapneumovirusG, Fhuman metapneumovirus PARAMYXOVIRUS FAMILY SURFACE GLYCOPROTEINS PARAMYXOVIRUS SUBFAMILY PNEUMOVIRUS SUBFAMILY

2 major strains –group A and group B (G protein differences) Respiratory syncytial virus (RSV)

infections –aerosol, person-to-person and fomites Can survive on inanimate surfaces for a few hrs –virtually all children have been infected by 2yrs of age incubation period –a few days to a week infects respiratory epithelial cells – cell to cell spread RSV infections

RSV- disease common cause upper respiratory tract infections –runny nose, cough, sore throat, headache, fever –co-infection with bacteria - rare –complications - otitis media (up to 40%) 25% of primary infections result in LRI – bronchiolitis, viral pneumonia

RSV- risk factors for severe disease Age (especially if less than 6 months) Pre-term birth Preexisting respiratory conditions Immunodeficiency

RSV – Lab diagnosis rapid antigen assay – ICT Virus isolation – cell culture PCR –especially useful in older children and adults when viral load is usually lower and so antigen detection or viral isolation less reliable serology –used for epidemiology ; not diagnosis

RSV- Rx no specific antivirals -ribavirin- not used routinely, may be considered in life threatening situations supportive care

RSV- prevention No vaccine Passive immunization –for high-risk children –monoclonal antibody against F protein –monthly IM injections during the RSV season –not effective in treatment of infection

RSV- prevention Hand 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

Human metapneumovirus (hMPV) GENUSGLYCOPROTEINSTYPICAL MEMBERS ParamyxovirusHN, FHPIV1, HPIV3 RubulavirusHN, FHPIV2, HPIV4, mumps virus MorbillivirusH, Fmeasles virus PneumovirusG, Frespiratory syncytial virus MetapneumovirusG, Fhuman metapneumovirus PARAMYXOVIRUS FAMILY SURFACE GLYCOPROTEINS PARAMYXOVIRUS SUBFAMILY PNEUMOVIRUS SUBFAMILY

Human metapneumovirus (hMPV) only recently (2001) recognized common – probably 15% of childhood colds –commercial tests only recently available

hMPV- Disease Disease - similar to RSV/ HPIV most children infected by age 5 reinfections common upper respiratory tract - common cold, croup lower respiratory tract - bronchiolitis /pneumonia (especially in infants)

hMPV - epidemiology Worldwide humans only source of infection Not fully understood

Adenoviruses linear, double stranded DNA non-enveloped –stable in environment icosahedral

Fiber protein – virus attachment protein - determines host cell specificity Infect epithelial cells lining the mucus membranes –respiratory, GI, urinary tract –enter via epithelium, replicate and spread to lymphoid tissue Viremia occurs Secondary involvement of viscera Adenoviruses - pathogenesis

Acute infection latent/occult –virus remains in cell – seen in lymphoid tissue oncogenic transformation (animals only) Adenoviruses - pathogenesis

Human Adenoviruses 51 human serotypes (1-51) Classified into six subgroups (A-F) members of a subgroup often cause similar spectrum of disease –enteric adenoviruses are in subgroup F (40,41)

Human Adenoviruses SubgroupSerotypeClinical syndromes A31Infantile gastroenteritis ?? B3, 7, 21Upper respiratory disease, pneumonia C1, 2, 5Hemorrhagic cystitis, nephritis D8,19,37Epidemic conjuctivitis E4Upper respiratory disease, pneumonia F40, 41Infantile gastroenteritis

Human adenoviruses Transmission aerosols, fomites Secretions – respiratory, tears, fecal/oral

Human adenoviruses- infection and virus shedding incubation – up 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 adenoviruses Disease LRI URI Diarrhea Conjunctivitis Cystitis

Adenovirus infections in Immunocompromised hosts Disseminated, severe and often fatal infections New infection Reactivation of latent virus Prolonged infections with prolonged viremia and viral shedding

Human adenoviruses Lab diagnosis antigen testing in body fluids - very rapid cell culture PCR