Transcript Paramyxoviruses

Introduction
 The paramyxoviruses include the most important agents of
respiratory infections of under 5 years of age.(respiratory
syncytial virus and the parainfluenza viruses)
 They are causative agents of two of the most common
contagious diseases of childhood.(mumps and measles)
 All initiating 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.
aZoonotic
paramyxoviruses.
bHemolysin activity carried by F glycoprotein.
cHemagglutination and neuraminidase activities carried by HN glycoprotein of respiroviruses and
rubulaviruses; H glycoprotein of morbilliviruses lacks neuraminidase activity; G glycoprotein of
other paramyxoviruses lacks both activities.
dC, cytoplasm; N, nucleus.
Classification
• Paramyxoviridae
Paramyxovirinae
Pneumovirinae
•
The Paramyxoviridae family is divided into two subfamilies (and)
and seven genera, six of which contain human pathogens
(Respirovirus,
Rubulavirus,
Morbillivirus,
Henipavirusa,
Pneumovirus, Metapneumovirus)
Properties of Paramyxoviruses
Virion:Spherical,pleomorphic,150nm or more in diameter (helical nucleocapsid,
13–18 nm)
Composition: RNA (1%), protein (73%), lipid (20%), carbohydrate (6%)
Genome: Single-stranded RNA, linear, nonsegmented, negative-sense,
noninfectious, about 15 kb
Proteins: Six to eight structural proteins
Envelope: Contains viral glycoprotein (G, H, or HN) (which sometimes carries
hemagglutinin or neuraminidase activity) and fusion (F) glycoprotein; very
fragile
Replication: Cytoplasm; particles bud from plasma membrane
Outstanding characteristics:
Antigenically stable
Particles are labile yet highly infectious
PARAINFLUENZA VIRUS INFECTIONS
 Parainfluenza viruses cause common respiratory illnesses in persons of all
ages.
 They are major pathogens of severe respiratory tract disease in infants and
young children
 Involving only the nose and throat, resulting in a harmless "common cold"
syndrome.
 Infecting the larynx (‫ )حنجره‬and upper trachea, resulting in croup
(laryngotracheobronchitis)
 Characterizing Croup by respiratory obstruction due to swelling of the larynx
and related structures.
Pathogenesis & Pathology
 Types 1 and 2, may involve the larynx and upper trachea, resulting in
croup
 The infection may spread deeper to the lower trachea and bronchi,
resulting in pneumonia or bronchiolitis, especially with type 3, but at a
much lower frequency than that observed with RSV
 Reinfections with parainfluenza viruses are common.
The severe illness associated with type 3 occurs mainly in infants under
the age of 6 months. croup or laryngotracheobronchitis is more likely
to occur in older children, between ages 6 months and 18 months.
Factors involving in severity





both viral and host properties
Susceptibility of the protein to cleavage by different proteases,
Production of an appropriate protease by host cells,
Immune status of the patient
Airway hyperreactivity.
Patterns of lower respiratory tract
infections in infants and young children
with paramyxoviruses and other viruses.
Data from 25 years of surveillance (1976–
2001), involving 2009 children from birth
to age 5 years
Laboratory Diagnosis
a) ANTIGEN DETECTION (direct or
indirect immunoflorescence)
b) ISOLATION & IDENTIFICATION OF VIRUS (Nasal washes)
c) NUCLEIC ACID DETECTION
d) SEROLOGY
Epidemiology
 Parainfluenza viruses are a major cause of lower respiratory tract disease
in young children
 Type 3 is most prevalent parinfluenza, cause endemics during spring
 1 and 2 tend to cause epidemics during the fall or winter
 Parainfluenza viruses are transmitted by direct person-to-person contact
or by large-droplet aerosols
 Parainfluenza viruses are troublesome causes of nosocomial infection in
pediatric wards in hospitals.
Treatment & Prevention
 Contact isolation precautions
 gowning and hand washing by medical personnel.
 Ribavirin has been used with some benefit in treatment of
immunocompromised patients with lower respiratory tract
disease
 No vaccine
RESPIRATORY SYNCYTIAL VIRUS (RSV) INFECTIONS
 RSV is the most important cause of lower respiratory tract illness in
infants and young children
 Replication occurs initially in epithelial cells of the nasopharynx.
 Virus may spread into the lower respiratory tract and cause
bronchiolitis and pneumonia.
 Bronchiolitis is the distinct clinical syndrome associated with this
virus
 Respiratory syncytial virus is an important cause of otitis media
Epidemiology
 Respiratory syncytial virus is distributed worldwide and is
recognized as the major pediatric respiratory tract pathogen
 RSV is the most common cause of viral pneumonia in children
under age 5 years but may also cause pneumonia in the
elderly or in immunocompromised persons.
 Spread by large droplets and direct contact
Laboratory Diagnosis
a) ANTIGEN DETECTION
b) ISOLATION & IDENTIFICATION OF VIRUS
c) NUCLEIC ACID DETECTION
d) SEROLOGY
Treatment
Depends primarily on supportive care.
Ribavirin administered in an aerosol for 3–6
days
Mumps Virus Infections
 Mumps is an acute contagious disease characterized by nonsuppurative
enlargement of one or both salivary glands (90% are both).
 Mumps virus mostly causes a mild childhood disease, but in adults
complications including meningitis and orchitis are fairly common.
 More than one-third of all mumps infections are asymptomatic.
Pathogenesis & Pathology
 Humans are the only natural hosts for mumps virus.
 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.
Clinical Findings
 Majority of infections in children under 2 years of age.
 The most characteristic feature of symptomatic cases is swelling of
the salivary glands (Parotitis, 20-70%)
 The incubation period may range from 2 to 4 weeks but is typically
about 14–18 days.
 Symptoms:
 Nonspecific prodrome of low-grade fever, headache,
malaise, myalgias
 Lower respiratory tract illness, especially preschoolaged children
Mumps Complications:
Unvaccinated Persons
• Common
• Meningitis – 5-15% of cases
• Orchitis – 20%-30% of cases in post-pubertal males
(rarely sterility)
• Uncommon
•
•
•
•
Pancreatitis
Encephalitis
Deafness
Death
Mumps Epidemiology
• Transmission
– Route: person-to-person (respiratory secretions, e.g. saliva),
respiratory droplets, fomites
– Closer contact is necessary for transmission of mumps than
for transmission of measles or varicella.
• Risk of disease: > 50% reported cases 5-9 yrs but shift to younger
children with child care
• Seasonality: Peak late winter and spring
Mumps Diagnosis
• Laboratory (validation)
• Isolation
• PCR
• Serologic
– IgG
– IgM
Measles (Rubeola) Virus Infections
 Measles
highly infectious disease characterized by fever, respiratory
symptoms, and a maculopapular rash.
.
Pathogenesis & Pathology
 Humans are the only natural hosts
 Viral replication begins in the respiratory epithelium
 Multinucleated giant cells with intranuclear inclusions are seen in lymphoid tissues
throughout the body (lymph nodes, tonsils).
 The virus-specific immune response is detectable when the rash appears.
 The rash develops as a result of interaction of immune T cells with virus-infected
cells in the small blood vessels and lasts about 1 week.
 Involvement of the central nervous system is common in measles.
 progressive measles inclusion body encephalitis may develop in patients with
defective cell-mediated immunity.
Timing of neurologic complications of measles. PIE, postinfectious encephalomyelitis (also
called acute disseminated encephalomyelitis); MIBE, measles inclusion body encephalitis;
SSPE, subacute sclerosing panencephalitis. Encephalitis occurs in about one out of every 1000
cases of measles, whereas SSPE is a rare late complication that develops in about one out of
300,000 cases.
SSPE( subacute sclerosing panencephalitis )
A rare late complication of
measles
This fatal disease is caused by virus that remains in the body after
acute measles infection
Clinical Findings
The prodromal phase is characterized by fever, sneezing, coughing, running nose, redness of
the eyes, Koplik spots, and lymphopenia
 The rash starts on the head and then spreads progressively to the chest, the trunk, and
down the limbs
 The most common complication of measles is otitis media (5–9% of cases)
 Pneumonia is the most common life-threatening complication of measles, caused by
secondary bacterial infections
 Pulmonary complications account for more than 90% of measles-related deaths
.
Immunity
There is only one antigenic type of measles virus
Infection confers lifelong immunity
Measles immune responses are involved in disease pathogenesis
 Local inflammation causes the prodromal symptoms, and specific cell-mediated immunity
plays a role in development of the rash
.
Natural history of measles infection. Viral replication begins in the respiratory epithelium and spreads to monocytemacrophages, endothelial cells, and epithelial cells in the blood, spleen, lymph nodes, lung, thymus, liver, and skin and to the
mucosal surfaces of the gastrointestinal, respiratory, and genitourinary tracts. The virus-specific immune response is
detectable when the rash appears. Clearance of virus is approximately coincident with fading of the rash.
Laboratory Diagnosis
 Antigen & Nucleic Acid Detection
Measles antigens can be detected directly in epithelial cells from respiratory secretions, the
nasopharynx, conjunctiva, and urine. Antibodies to the nucleoprotein are useful because that
is the most abundant viral protein in infected cells.
Detection of viral RNA by RT-PCR is a sensitive method that can be applied to a variety of
clinical samples for measles diagnosis
Isolation & Identification of Virus
Nasopharyngeal and conjunctival swabs, blood samples, respiratory secretions, and urine
collected from a patient during the febrile period are appropriate sources for viral isolation.
 Serologic confirmation of measles infection
Epidemiology
 The virus is highly contagious, there is a single serotype, there is no animal reservoir , and
inapparent infections are rare.
 Transmission occurs predominantly via the respiratory route .
 Measles is endemic throughout the world.
.
Treatment, Prevention, & Control
 Vitamin A decreasing the mortality and morbidity
 Ribavirin,
A highly effective and safe attenuated live measles virus vaccine a (monovalent form)
 Measles vaccine is available in and in combination with live attenuated rubella vaccine
(MR)
 live attenuated rubella and mumps vaccines (MMR), and live attenuated varicella vaccine
(MMRV)
Rubella (German Measles) Virus
 Rubella (German measles; 3-day measles) is an acute febrile illness with rash and
lymphadenopathy
 Affects children and young adults
 It is the mildest of common viral exanthems
 Infection during early pregnancy may result congenital malformations and mental
retardation
Electron micrograph of rubella
Classification
 A member of the Togaviridae family
 The sole member of the genus Rubivirus
 Classified into two clinical groups
Postnatal Rubella
Congenital Rubella Syndrome
Postnatal Rubella
 Neonatal, childhood, and adult infections occur through the mucosa of the
upper respiratory tract
 In 20–50% of cases, primary infection is subclinical.
Clinical Findings
 Rubella usually begins with malaise, low-grade fever, and a morbilliform rash
appearing on the same day
 The rash starts on the face, extends over the trunk and extremities, and
rarely lasts more than 3 days
 Transient arthralgia and arthritis are commonly seen in adults, especially
women
 Rare complications include thrombocytopenic purpura and encephalitis.
Congenital Rubella Syndrome
Maternal viremia during pregnancy may result in infection of the placenta and
fetus
the earlier in pregnancy infection occurs, the greater the damage to the fetus
Inapparent maternal infections can also result in fetal death and spontaneous
abortion
Symptomes: cataracts, cardiac abnormalities, and deafness, microcephaly, rash,
hepatosplenomegaly, jaundice, and meningoencephalitis
Laboratory Diagnosis
Isolation & Identification of Virus
specific laboratory studies
Nucleic Acid Detection
Serology
Nasopharyngeal or throat swabs taken 6 days before and after onset of
rash are a good source of rubella virus
Epidemiology
a peak incidence in the spring
Epidemics occur every 6–10 years, with explosive pandemics
every 20–25 years
Infection is transmitted by the respiratory route
 rubella is not as contagious as measles
Treatment, Prevention, & Control
 Rubella is a mild, self-limited illness, and no specific treatment is indicated
 It can be prevented by :
 The vaccine is available as a single antigen or combined with measles and mumps
vaccine
 The primary purpose of rubella vaccination is to prevent congenital rubella infections
 Immune globulin intravenous (IGIV) injected into the mother does not protect the
fetus against rubella infection