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Respiratory syncytial virus
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Dr.T.V.Rao MD
RESPIRATORY SYNCYTIAL VIRUS
DR.T.V.RAO MD 1
• In 1956, Morris and
colleagues initially isolated
RSV from chimpanzees
with upper respiratory tract
(URT) infections as the
causative agent of most
epidemic Bronchiolitis
cases. Subsequently,
Channock et al associated
this agent with Bronchiolitis
and LRT infection in infants
DISCOVERY OF
RESPIRATORY SYNCYTIAL VIRUS
DR.T.V.RAO MD 2
RESPIRATORY SYNCYTIAL VIRUS
• Respiratory syncytial virus (RSV) is a leading cause of severe respiratory infection in infants and children. RSV is an RNA virus whose genome encodes 10 proteins. The G protein is responsible for viral attachment to cells whilst the F protein promotes syncytia formation.
DR.T.V.RAO MD 3
DIFFERS FROM PARAMYXOVIRUS
• Unlike Paramyxovirus it does not posses Haemagglutinnins activity.
• Do not posses neuraminidase or hemolytic properties
• The size of nucelocapsid diameter is less than Paramyxovirus.
• RS virus are placed in a separate Genus Pneumovirus
DR.T.V.RAO MD 4
SERO TYPING OF RESPIRATORY
SYNCYTIAL VIRUS
• For all practical purposes there is only one serotype
• With the use of monoclonal antibodies that there are two subtypes A and B strains. .
DR.T.V.RAO MD 5
• Most common cause of bronchiolitis & pneumonia in children under 1
• 25-40% of children develop bronchiolitis or pneumonia during first RSV infection
• 31/1,000 under 1 yr. are hospitalized with RSV
• 2% will die
RSV FACTS
DR.T.V.RAO MD 6
INFECTS ANIMALS TOO
• RS virus infects cattle
and chimpanzees
• Both goats and sheep may be infected naturally
• Even rodents can be adopted after some adoption.
DR.T.V.RAO MD 7
RS VIRUS MAJOR CAUSE OF
RESPIRATORY INFECTIONS.
• Human respiratory
Syncytial virus (RSV)
was quickly determined to
be of human origin and
was shown to be the
leading worldwide viral
agent of serious
paediatric respiratory tract
disease.
DR.T.V.RAO MD 8
RESPIRATORY SYNCYTIAL
VIRUS (RSV)
• ssRNA enveloped virus.
• belong to the genus Pneumovirus of the Paramyxovirus family.
• Considerable strain variation exists, may be classified into subgroups A and B by monoclonal sera.
• Both subgroups circulate in the community at any one time.
• Causes a sizable epidemic each year.
DR.T.V.RAO MD 9
• Negative-strand RNA
virus
• Family Paramyxoviridae
• RSV season late fall to
early spring
• Peak in
January/February
• Incubation 4-5 days,
LRI between days 5-7
PATHOPHYSIOLOGY
DR.T.V.RAO MD 10
PROPAGATION OF RSV
• It can be propagated in
He La and Hep-2
cell culture lines.
• Highly labile virus and
promptly inactivated at
room temperatures
DR.T.V.RAO MD 11
MAJORITY OF CHILDREN ARE INFECTED
• Almost all children will
be infected with RSV
by their second
birthday.
• RSV causes
respiratory illness in
infants and young
children, and is the
most important cause
of Bronchiolitis. DR.T.V.RAO MD 12
PRESENTATION • Cold-like sx
• Audible wheezing
• SOB
• Anorexia
• Poor sleeping
• Irritability
• Vomiting
• Choking
DR.T.V.RAO MD 13
INVOLVEMENT OF ALVEOLI AND ALVEOLAR SPACE
- A SIGNIFICANT FEATURE
DR.T.V.RAO MD 14
MAJOR AREAS OF INFECTION IN RS VIRUSES
• Clinical diagnosis will be supported with presence of RS virus in the Nasopharynx and there is clinical evidence of lower respiratory tract involvement.
DR.T.V.RAO MD 15
IMMUNITY HELPS IN RECOVERY
• The surface glycoproteins also evoke a host-derived
antibody response following an infection. A primary
RSV infection produces a weak humoral antibody
response that does not differ with the severity of the
disease. These responses are responsible for ending
the infection and eliminating the virus, but do not
appear to impart long-term immunity. In fact, it is only
with reinfection that the antibody response is
enhanced. If the infection reaches the LRT, a T cell-
mediated response is generated.
DR.T.V.RAO MD 16
CLINICAL FEATURES • The peak incidence is in
those under 1 year of age.
• The most serious illness manifest with Bronchiolitis in young babies
• Leads to hyperinflation of lungs secondary to bronchiolar inflammation acting as a on way valve.
DR.T.V.RAO MD 17
PATIENTS WITH RESPIRATORY SYNCYTIAL VIRUS (RSV) MAY
PRESENT WITH THE FOLLOWING SYMPTOMS:
• Fever (typically low-
grade)
• Cough
• Tachypnea
• Cyanosis
• Retractions
• Wheezing
• Rales
DR.T.V.RAO MD 18
• Inhibition of certain
interferon's
• Involvement of innate
immune system
• Interleukins and
chemokine's
• Coinfection with other
respiratory viruses
SEVERITY OF RSV INFECTION IS
DETERMINED BY:
DR.T.V.RAO MD 19
• Interferon's believed to have antiviral properties
• NS1 & NS2 inhibit IFN-alpha/beta
• Inhibition of IFN-gamma causes enhanced IgE production
INHIBITION OF INTERFERON'S
DR.T.V.RAO MD 20
CAN BE LIFE THREATENING
• The RS viral infection
is potentially in those
with or congenital
heart disease
Bronchopulmonary
dysplasia defects, or in
those who are
Immunosupressed or
Immunodeficient.
DR.T.V.RAO MD 21
SUDDEN INFANT DEATH SYNDROME
( SIDS )
• RS virus has been
recovered from some
victims of the Sudden
infant death syndrome
• Although it may have
been contributed to death,
other factor are also
significantly contributed.
DR.T.V.RAO MD 22
• The majority of infected
present with clinical
features of Bronchiolitis
• In majority of cases
recovery is complete.
• In older children, and adults
the virus cause minor
illness,
• Reinfections are common
and in adults may cause
no more than cold
ACTIVE CLINICAL MANIFESTATIONS
DR.T.V.RAO MD 23
RS VIRUS INFECTIONS CAN
PREDISPOSE TO….
Some reports suggest the infection can predispose to Chronic respiratory tract disease, Asthma,Bronchectasis etc
Several studies in progress to prove the predisposition
with RS virus
DR.T.V.RAO MD 24
• Rhinovirus contributes
to increased severity in
children with
bronchiolitis
• Metapneumovirus
(hMPV) enhances or
mimics symptoms of
RSV bronchiolitis
• 70% were confected w/
hMPV & required
admission to PICU
CO - INFECTION
DR.T.V.RAO MD 25
• There are upcoming reports of severe illness with some fatalities in old people’s homes as well as in elderly living in a community
• The under diagnosis can be attributed lack of confirming Virological diagnosis in adults and elderly.
RS VIRUS CAN INFECT OLD AGED
GROUPS
DR.T.V.RAO MD 26
• Attending child care
centers.
• Older siblings in preschool
or school
• Exposure to environmental
pollutants (eg, cigarette
smoke)
• Multiple birth sets
(especially triplets or
greater)
• Minimal breastfeeding
MANY FACTORS HAVE BEEN ASSOCIATED WITH
INCREASED RISK OF ACQUIRING RSV DISEASE,
DR.T.V.RAO MD 27
OTHER CONTRIBUTING FACTORS IN
RESPIRATORY SYNCYTIAL VIRUS INFECTION
• Premature children , especially birth at less than 35 weeks' gestation
• Age younger than 3 months at time of infection
• Chronic lung disease
• Congenital heart disease
• Toxic appearance at time of presentation
• Respiratory rate more than 70 per minute in room air
• Atelectasis and/or pneumonitis on chest radiography
• Oxygen less than 95% on room air
• Doctorrao’s ‘e’ learning series
DR.T.V.RAO MD 28
RS VIRUS DO NOT WITHSTAND FREEZING
• The virus is
relatively fragile
and may not
survive even snap
–freezing at -700c • Specimens for isolation
should not be frozen
DR.T.V.RAO MD 29
RAPID DIAGNOSIS IN RS VIRAL
INFECTIONS
• In acute phase of illness, a Rapid diagnosis in > than 1 hour by Immunofluorescence with conjugated monoclonal antibodies with adequate number of desquamated respiratory cell is reliable.
• However antigen detection and culture methods are good for diagnosing RS virus infection in infants and young children.
DR.T.V.RAO MD 30
SEROLOGY • Serological
assessment using complement fixation is generally not helpful.
• Immunoassays for G and F proteins may offer more reliable serological tests, in adults where other options are limited. DR.T.V.RAO MD 31
MOLECULAR METHODS IN RESPIRATORY
SYNCYTIAL VIRAL DETECTION
• The emerging
molecular methods
such as reverse
transcription-
polymerase chain
reaction, either for a
single virus or
multiplexed to detect a
panel of viruses
DR.T.V.RAO MD 32
• A supportive management
with tube feeding in cases of
difficulty in suckling
• Use of oxygen if indicated.
• Ribavirin is a
specific antiviral drug, proved
to effective when given as a
small particle aerosol although
it is apparently not effective
intravenous infusion.
TREATMENT
DR.T.V.RAO MD 33
INDICATION FOR CHEMOTHERAPY
• The chemotherapy with Ribavirin is expensive and its recommended use is confined to those babies who are at risk from rampant RS virus, because they have congenital heart or lung abnormalities
• The use os Hyper immune RS virus immunoglobulin and humanized monoclonal antibodies have become available for treatment and prevention of RS infection. In view of higher costs they are warranted in selected infants born with low birth weight or preexisting Bronchopulmonary dysplasia
DR.T.V.RAO MD 34
• Mostly symptomatic
• Salbutamol MDI drug of choice
• Also use epinephrine, ipratropium bromide, & oral steroids only if hospitalized
SUPPORTING TREATMENT
DR.T.V.RAO MD 35
EPIDEMICS AND SEASONAL VARIATION
• In temperate climates in both the northern and southern hemisphere, RS virus causes a substantial winter epidemic every year.
• In tropical regions the epidemics manifest in hot periods of summer.
• However sporadic cases occur throughout the year
• The RS virus produces infections all over the world
DR.T.V.RAO MD 36
• More likely to suffer
recurrent infections
• Many have recurrent
acute otitis media
• Many likely to be
hospitalized with
another episode of
acute respiratory
distress
MORBIDITY & MORTALITY
DR.T.V.RAO MD 37
• Adolescents suffer from allergic asthma, allergic rhino conjunctivitis, & more sensitive to inhaled allergens
• More likely to have asthma, bronchial reactivity to methacholine, and reduced lung function
• RSV ind. risk factor for reduced FEV% (FEV1/FVC)
MORBIDITY & MORTALITY
DR.T.V.RAO MD 38
• Male infants
• Age & birth month of infant
• Crowding & day care attendance
• Secondhand smoke
ENVIRONMENTAL &
DEMOGRAPHICS
DR.T.V.RAO MD 39
VACCINE - FAILURES • A formalin inactivated
crude, whole virus vaccine was tried in 1960, but failed to produce immunity in the recipients
• The difficulties in preparing safe vaccine for RSV lie with young and immunologically immature recipients.
• Yet to date there is no safe vaccine available for universal use
D oc t o r r ao ’s ‘ e ’ lea r n ing se r ies
DR.T.V.RAO MD 40
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DR.T.V.RAO MD 41
• Created by Dr.T.V.Rao MD for ‘e’ learning
resources for Microbiologists in
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DR.T.V.RAO MD 42
