3. Paramyxoviruses
• respiratory infections of infants and young children (respiratory
syncytial virus and the parainfluenza viruses) as well as the
causative agents of two of the most common contagious diseases
of childhood (mumps and measles).
• initiate infection via the respiratory tract
• Replication of the respiratory pathogens is limited to the
respiratory epithelia, whereas measles and mumps become
disseminated throughout the body and produce generalized
disease.
• pleomorphic
• The viral genome is linear, negative-sense, singlestranded,
nonsegmented RNA, about 15 kb in size
• all members of the paramyxovirus group are antigenically stable
4. • Classification
• genus Respirovirus contains two serotypes of human
parainfluenza viruses
• genus Rubulavirus contains two other parainfluenza
viruses as well as mumps virus
• Sendai virus of mice
• Newcastle disease virus, avian
5. • The Morbillivirus genus contains measles virus (rubeola)
of humans as well as canine distemper virus, rinderpest
virus of cattle, and aquatic morbilliviruses that infect
marine mammals.
• The Henipavirus genus contains zoonotic
paramyxoviruses
• Hendra and Nipah viruses, both indigenous to fruit bats,
are members of the genus.
• Respiratory syncytial viruses of humans and cattle and
pneumonia virus of mice constitute the genus
Pneumovirus.
6. Parainfluenza viruses
• Human PIVs 1 and 3 belong to the genus Paramyxovirus
• PIVs 2 and 4 belong to the genus Rubulavirus
• The PIVs are enveloped helical RNA viruses with two surface
antigens, hemagglutininneuraminidase (HN) antigen and the fusion
(F) antigen.
• respiratory epithelia
• may involve only the nose and throat, resulting in a harmless
“common cold” syndrome
• can survive up to 10 hours on surfaces
• cell culture
• IFA: confirmatory
• multiplex molecular diagnostic test: can differentiate the 3 major types
7. • types 1 and 2, may involve the larynx and upper trachea, resulting in
croup (laryngotracheobronchitis).
• Barking cough
• Croup is characterized by respiratory obstruction due to swelling of the
larynx and related structures.
• PIV-1 is the primary cause of croup (laryngotracheobronchitis) in
children.
• PIV-3 causes bronchiolitis and pneumonia in infants and is second in
importance only to RSV. fatal
• PIV-4 generally causes mild upper respiratory tract infections.
• Incubation period: 1–3 days
• virus shedding is about 1 week after onset of illness
• Type 3 may be excreted for up to 4 weeks after onset of primary illness.
•
8. • Diagnosis
• Antigens: direct or indirect immunofluorescence tests.
• best specimens for viral culture are aspirated secretions
and nasopharyngeal washes
• Inoculated into PMK cells or LLC-MK2 cells
• The viruses can be identified by hemadsorption using
guinea pig erythrocytes, IF, or EIA techniques.
• Aerosolized ribavirin can be used to treat infection
• No vaccines are available
• Natural infection stimulates appearance of IgA antibody in
nasal secretions and concomitant resistance to reinfection.
9. • Newcastle disease virus is an avian paramyxovirus that
produces pneumoencephalitis in young chickens and
“influenza” in older birds.
• In humans, it may produce inflammation of the conjunctiva.
• Recovery is complete in 10–14 days.
• Infection in humans is an occupational disease limited to
workers handling infected birds.
10. Respiratory Syncytial Virus
• Respiratory syncytial virus (RSV) is a member of the genus Pneumovirus.
• Fusion (F) protein: mediates host cell fusion into syncytial cells
• syncytia: hallmark of RSV infection
• RSV causes croup, bronchitis, bronchiolitis, and interstitial pneumonia.
• most significant cause of acute lower respiratory tract infection in children under
5yrs old.
• Infants: bronchiolitis, pneumomia, croup
• Children: upper respiratory infection
• late fall through early spring
• person to person by hand and respiratory contact
• Incubation period: 3–6 days.
• epithelial cells of the nasopharynx.
• Viral shedding may persist for 1–3 weeks from infants and young children,
whereas adults shed for only 1–2 days.
11. • Almost half of all infants are infected with RSV during their
first year of life, and by the age of 2 years, almost all have
been exposed to RSV.
• infection does not confer complete immunity
• The virus may be carried in the nares of asymptomatic
adults.
• Respiratory syncytial virus spreads extensively in children
every year during the winter season
• Outbreaks tend to peak in February or March in the
Northern Hemisphere.
• In tropical areas, respiratory syncytial virus epidemics
may coincide with rainy seasons.
12. • Diagnosis
• RSV can be identified in specimens from nasopharyngeal
swabs and washes by DFA or EIA.
• RSV grows readily in continuous epithelial cell lines, such as
HEp2, forming syncytia.
• Human heteroploid cell lines HeLa and HEp-2 are the most
sensitive for viral isolation.
• development of giant cells and syncytia in inoculated cultures
• It may take as long as 10 days for cytopathic effects to appear.
• It also grows in PMK and human diploid fetal cells.
• Once the CPE is detected, RSV can be identified using IF, EIA,
and serum neutralization tests.
• Rapid antigen detection kits are also available for RSV.
• FA stain
13. • Management
• The antiviral compound ribavirin is approved as a
treatment for patients with RSV.
• Ribavirin targets the viral mRNA
• The drug is administered in an aerosol for 3–6 days. Oral
ribavirin is not useful
• RSV immune for preexposure prophylaxis of susceptible
patients
• Prophylaxis
• Palivizumab is a monoclonal antibody indicated for
preventing RSV infection in infants of high risk of mortality
(e.g. ex-premature babies and children under 2 years of
age who have received treatment for bronchopulmonary
dysplasia or severe congenital heart disease).
• No vaccine is available for RSV.
15. Measles Virus
• The measles virus is an enveloped virus
• classified in the genus Morbillivirus.
• measles (rubeola)
• highly contagious and spreads by aerosol
• Incubation period :10–15 days, an average of two weeks
• attenuated vaccine is available and recommended for all
children
• Humans are the only natural hosts for measles virus
16. • sneezing, runny nose and cough, red eyes, and rapidly
rising fever.
• Initial replication takes place in the mucosal cells of the
respiratory tract; measles virus then replicates in the local
lymph nodes and spreads systemically.
• The virus circulates in the T and B cells and monocytes,
until eventually the lungs, gut, bile duct, bladder, skin, and
lymphatic organs are involved.
17. • Koplik spots, lesions on the oral mucosa consisting of
irregular red spots, with a bluishwhite speck in the center
generally appear 2 to 3 days before the rash and are
diagnostic.
• About 2 to 3 days later, a maculopapular rash appears on the
head and trunk.
• appears about day 14 just as circulating antibodies become
detectable
• Infection confers lifelong immunity.
• Symptomatic encephalitis develops in about 1:1000 cases
• A rare late complication of measles is subacute sclerosing
panencephalitis.
18. • Diagnosis
• Multinucleated giant cells with intranuclear inclusions are
seen in lymphoid tissues throughout the body (lymph
nodes, tonsils, appendix).
• nasopharynx and urine
• The virus grows on PMK cells, causing the formation of
distinctive spindle-shaped or multinucleated cells.
• Monkey or human kidney cells or a lymphoblastoid
cell line (B95-a) are optimal for isolation
• Virus isolates can be identified using serum neutralization,
EIA, or IF tests.
• IgM
19. • Treatment
• Measles virus is susceptible in vitro to inhibition by ribavirin, but
clinical benefits have not been proved.
• Measles vaccine
• is available in monovalent form and in combination with live
attenuated rubella vaccine (MR) and live attenuated rubella and
mumps vaccines (MMR).
• Pre-exposure
• Live attenuated measles vaccine as triple vaccine with mumps
and rubella (MMR) is recommended at 13–15 months with a pre-
school booster
• Post-exposure
• The MMR vaccine can be given within 72 hours of exposure as
post-exposure prophylaxis.
• Normal immunoglobulin should be given as post-exposure
prophylaxis to pregnant and immunocompromised patients or
those who present within 6 days of at-risk exposure.
20. Mumps Virus
• genus Rubulavirus
• Family Paramyxoviridae
• enveloped virus, with HN and F surface antigens.
• spread by droplets of infected saliva
• It causes an acute illness producing unilateral or bilateral
swelling of the parotid glands, although other glands such
as the testes, ovaries, and pancreas can be infected.
• long-lasting immunity .
• 10–21 days, average of about 2 weeks.
• Samples should be inoculated shortly after collection, as
mumps virus is thermolabile
21. • Pathogenesis
• Primary replication occurs in nasal or upper respiratory tract
epithelial cells.
• Viremia then disseminates the virus to the salivary glands
and other major organ systems.
• Virus is shed in the saliva from about 3 days before to 9 days
after the onset of salivary gland swelling.
• Virus frequently infects the kidneys and can be detected in
the urine of most patients.
• Viruria may persist for up to 14 days after the onset of clinical
symptoms.
• Acute parotitis
• When symptoms develop they comprise uni- or bilateral
parotid gland swelling (parotitis); other salivary glands may
also be involved.
22. • Complications
• Orchitis develops in young adult or adolescent males.
• It follows 4–5 days after parotitis (if present) and may
involve pain and swelling in one or both testes, which is
often accompanied by headache and fever.
• may raise testicular torsion as a differential diagnosis,
especially if mumps orchitis is not preceded by parotitis
(clinical mumps).
• Infertility is a rare occurrence, but testicular atrophy may
follow in about 30% of cases.
• Similarly inflammation of ovaries (oophoritis) may occur in
post-pubertal women, but this is much less common (5%).
• Rarely mumps pancreatitis may occur.
23. • Diagnosis
• infected saliva and swabs rubbed over the Stensen’s duct
• urine and CSF
• IF and EIA methods
• Monkey kidney cells are preferred for viral isolation
• viral isolation using shell vial cultures of Vero or LLC-MK2
cells to be more successful than with HEp2 or HeLa cell
lines
• cytopathic effects typical of mumps virus consist of cell
rounding and giant cell formation
• confirmed as mumps virus by hemadsorption inhibition, IF,
and EIA tests
24. • Immunity
• Immunity is permanent after a single infection.
• Antibodies to the HN glycoprotein (V antigen), the F
glycoprotein, and the internal nucleocapsid protein (S
antigen) develop in serum following natural infection.
• Interferon is induced early in mumps infection.
• In immune individuals, IgA antibodies secreted in the
nasopharynx exhibit neutralizing activity.
25. • Treatment
• There is no treatment. Treatment is supportive with pain-
killers etc.
• Prophylaxis
• Mumps vaccine: MMR
