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Respiratory viruses (other than influenza virus)

Respiratory viruses (other than influenza virus)

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Respiratory viruses(other than influenza virus)

CDC/James Gathany

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

GENUS GLYCOPROTEINS TYPICAL MEMBERS

Paramyxovirus HN, F HPIV1, HPIV3Rubulavirus HN, F HPIV2, HPIV4, mumps virusMorbillivirus H, F measles virus

Pneumovirus G, F respiratory syncytial virusMetapneumovirus G, F human metapneumovirus

PARAMYXOVIRUS SUBFAMILY

PNEUMOVIRUS SUBFAMILY

Paramyxoviruses – surface glycoproteins

M protein

helical nucleocapsid (RNA plusNP protein)

HN/H/G glycoprotein SPIKES

polymerasecomplex

lipid bilayer membrane

F glycoprotein SPIKES

Paramyxovirusespleomorphic

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

Respiratory syncytial virus

GENUS GLYCOPROTEINS TYPICAL MEMBERS

Paramyxovirus HN, F HPIV1, HPIV3Rubulavirus HN, F HPIV2, HPIV4, mumps virusMorbillivirus H, F measles virus

Pneumovirus G, F respiratory syncytial virusMetapneumovirus G, F human 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)

GENUS GLYCOPROTEINS TYPICAL MEMBERS

Paramyxovirus HN, F HPIV1, HPIV3Rubulavirus HN, F HPIV2, HPIV4, mumps virusMorbillivirus H, F measles virus

Pneumovirus G, F respiratory syncytial virusMetapneumovirus G, F human 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

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

• 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 AdenovirusesSubgroup Serotype Clinical syndromes

A 31 Infantile gastroenteritis ??

B 3, 7, 21 Upper respiratory disease, pneumonia

C 1, 2, 5 Hemorrhagic cystitis, nephritis

D 8,19,37 Epidemic conjuctivitis

E 4 Upper respiratory disease, pneumonia

F 40, 41 Infantile 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 adenovirusesDisease

• 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