Transcript Rubella Virus

Viral Infections of the Skin and
Mucus Membranes
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Maculopapular Rash
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Measles virus
Rubella virus
Parvovirus
Human Herpes 6
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Vesicular Rash
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Herpes simplex virus
Varicella zoster virus
Coxsakievirus
Measles
 Measles virus is a paramyxovirus
 Paramyxoviruses :
 Enveloped virus, ssRNA genome as a single piece.
 The family includes parainfluenza virus, mumps virus, measles virus
and respiratory syncytial virus.
 Parainfluenza and mumps virus have a surface hemagglutinin and
neuraminidase, while measles have a hemagglutinin, but not
neuraminidase.
 The virion structure includes:
 Spikes
 F protein
 Matrix protein M, below the envelope
 Only one serotype
Measles Disease
 Acute febrile illness, mostly in childhood
 Incubation period: 10 – 12 days
 Onset is flu-like: high fever, cough, conjunctivitis
 Koplik's spots: red spots with bluish-white centre on the buccal
mucosa
 1 – 2 days later, acute symptoms decline with appearance of a
widespread maculopapular rash
 Over 10 – 14 days, recovery is usually complete as the rash fades
Complications
 Giant cell pneumonia, more common in adults
 Otitis media
 Post-measles encephalitis
 Subacute sclerosing panencephalitis (SSPE):
 progressive and fatal degenerative disease
 within the infected cells, there is a defective form of the virus
which because it can not produce functional M protein, is not
released as complete virus from the cells.
Laboratory Diagnosis
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Most cases are diagnosed clinically
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NPA, immunofluorescence
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Epidemiology
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Control
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Transmission: person
to person by respiratory
droplets. Malnutrition
contributes to high
mortality.
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Live attenuated
vaccine, combined with
mumps and rubella
(MMR)
Administration:
between 12 – 18
months.
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Rubella (German Measles)
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Rubella Virus
Classified as togavirus
ssRNA virus with an envelope
pleomorphic in appearance, 50 – 60 nm in diameter
nucleocapsid is icosahedral in symmetry
ssRNA is infective and replication occurs in the
cytoplasm
three major polypeptides: C and envelope
glycoproteins E1 and E2
single serotype
Postnatal Rubella
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Incubation period: 12 – 21 days
Macular rash, appears first on the face, then
spreads to the trunk and limbs
Minor pyrexia, malaise and lymphadenopathy
with suboccipital nodes most commonly
enlarged and tender
Arthralgia is uncommon in children, but may
occur in up to 60% of adult females, involving
the fingers, wrists, ankles and knees
Encephalitis and thrombocytopenia are rare
complications
Pathogenesis
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Virus is transmitted by air-borne route
URT
Viremia
Skin, joints, placenta
cross the
barrier
Infect fetal differentiating cells
Early in pregnancy: this will cause congenital
abnormalities
Laboratory Diagnosis
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Clinical diagnosis is unreliable
Investigation by virus isolation is not indicated (unreliable
and time-consuming)
Serological diagnosis is the method of choice, detecting
rubella specific IgG and rubella specific IgM. These tests
are also used for screening to ascertain susceptibility
and whether rubella immunization is indicated.
Congenital rubella syndrome: serological testing for
specific IgM. Maternal IgM does not cross the placenta
so detection of specific IgM is diagnostic of intrauterine
infection
Control
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Attenuated live vaccine (MMR)
Seroconversion occurs in over 95%
Protection persists for more than 20 years
Administration in pregnancy is contra-indicated
Pregnancy should be avoided for the month
following vaccination
Human Parvovirus
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Only parvovirus B19 is
the cause of diseases
in humans
Genus: Erythrovirus
The Virus
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20 – 25 nm in diameter
icosahedral symmetry, no envelope
the capsid consists of two proteins, VP1 and VP2
specific viral receptors such as blood group P
antigen; explains narrow host range
infection is followed by life-long immunity
Genome: ssDNA
Replication
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Dependent on cellular factors expressed
transiently in the cell during late S or early G2
phase of mitosis.
All parvoviruses require dividing cells for
replication
Clinical Diseases
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Rash illness (Erythema infectiosum)
 Erythematous maculopapular rash
 Common in children aged 4 – 11 years
 Very similar to rubella
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Joint disease
 80% in adult females
 10% in childhood cases
 arthritis involving small joints of the hands with wrists,
knees and ankles affected in some cases
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Aplastic crisis
A transient acute event which complicates chronic
hemolytic anemia
Fall in hemoglobin
Disappearance of reticulocytes from peripheral blood
Erythropoiesis cessation lasts for 5 – 7 days
Symptoms of worsening anemia
B19 infection is responsible for 90% of the cases
Occurs most commonly in children with sickle cell
anemic
B19 in the immunocompromized
 Persistent infection that leads to persistent anemia
Laboratory Diagnosis
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Virus detection
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Serum,
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detecting viral antigens using ELISA
detecting viral genome using nucleic acid hybridization
and PCR
Antibody detection
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Recent infection can be diagnosed by detecting
B19-specific IgM or increasing amounts of specific
IgG.
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Epidemiology
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Endemic throughout the
year in temperate
climates
Transmission occurs by
respiratory route
High-titre viremia enables
transmission by blood
Congenital transmission
(vertical)
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Treatment
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Most cases are mild and
self-limiting
Aplastic crisis: blood
transfusion
Immunosuppressed:
blood transfusion and
human normal
immunoglobulin
Intrauterine infection:
intrauterine blood
transfusion
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Human Herpesvirus 6 (HHV 6)
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Sequence analysis revealed two variants:
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HHV 6A: no clear disease association
HHV 6B: exanthema subitum or roseola infantum
Roseola Infantum
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The disease is common between 6 months and 3
years
Sudden onset of fever
Throat congestion and cervical lymphadenopathy
Widespread macular rash occurs in 10% of the
cases
Some cases are associated with HHV-7 infection
HHV-6 and -7, both infect T lymphocytes
Vesicular Rash
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Herpes simplex virus
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Varicella zoster virus
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Coxsakievirus
Herpes Simplex Viruses
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Ubiquitous virus, infecting the majority of world’s
population
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Two types: HSV-1 and HSV-2
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Type 1 is associated primarily with mouth, eye and
CNS
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Type 2 is found mostly in the genital tract
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Transmission: direct contact
Herpes Simplex Structure
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Icosahedral virus
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Lipoprotein envelope,
derived from the nuclear
membrane
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Genome: linear, ds DNA
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Replicate in the nucleus
HSV Glycoproteins
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At least 11 glycoproteins are known
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Three are essential for production of
infectious virus:
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gB and gD : penetration into the cells
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gH:
release of the virus
Pathogenesis
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Primary Infection
The typical lesion is the vesicle; ballooning degeneration of
intra-epithelial cells. The roof of the vesicle breaks down,
forming ulcer
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During the replication phase at the site of entery in the
epithelium, virus particles enter through the sensory nerve
endings and transported along the axon to the nerve body
(neurone) in the sensory (dorsal root) ganglion by
retrograde axonal flow. Latent infection occurs in the
survived neurons that still harbor the viral genome
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Antibodies reduce the severity of the infections, although it
does not prevent recurrences.
Latent Infection
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About 1% of cells in the affected ganglion carry
the viral genome.
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Viral DNA exists as free circular episomes (20
copies / cell).
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Latency-associated transcripts (LAT) are present
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HSV-1: causes latency in trigeminal ganglion
HSV-2: causes latency in sacral ganglion
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Reactivation
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Known triggers for recurrences are accompanied by
a local increase in prostaglandin levels and
depression of cell-mediated immunity.
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Reactivation can be induced by
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UV light
Fever
Trauma
Stress
Interval between the stimulus and lesion appearance
is 2 – 5 days.
Clinical Features
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Oral infection
Acute febrile gingivostomatitis in preschool children
Vesicular lesions ulcerate rapidly
Skin infections
Herpetic whitlow: primary lesion on the fingers or
thumb of the toddler with herpetic stomatitis, due to
autoinoculation. It also occurs as accidental
inoculation in health care workers.
Eczema herpeticum: severe form of cutaneous
herpes. It may occur in children with atopic eczema.
Clinical Features
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Eye infection
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Conjunctivitis or keratoconjunctivitis associated with corneal
ulceration. This will result in corneal scarring and vision
impairment.
The majority are caused by HSV-1
Most patients with recurring eye disease are aged over 50 years
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CNS infection
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The most likely route of infection is central spread from
trigeminal ganglion
HSV encephalitis
 CSF collected in the acute stage should be used for PCR
amplification of HSV DNA.
 More commonly due to HSV-1
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Clinical Features
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Genital tract infection
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Both types can infect genital tract, but HSV-2 is more
common. The lesions are vesicular at first but
rapidly ulcerate
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Male: affects the glans and shaft of the penis
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Female: affects the labia and vagina or cervix
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Fever and malaise are accompanied by regional
lymphadenopathy, urethritis and vaginal discharge
Clinical Features
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Recurrent genital herpes
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Can be as frequent as six or more episodes a year.
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Attacks are milder and shorter than first episodes
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HSV-1 genital infection recurs less often than HSV-2
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Either type is capable of transmission from mother to infant.
Transplacental passage has been recorded but is very rare.
Ascending infection from the cervix is more significant
especially when the membranes are ruptured prematurely.
Laboratory Diagnosis
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Isolation of HSV in cultures of human diploid fibroblast
cells. Growth is rapid. CPE includes rounded, ballooned
cells in foci and giant cell formation
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Detection of viral antigens in cell (by
immunofluorescence), scraped from the base of lesions
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Detection of amplified viral DNA by PCR in CSF
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Giant cell formation
induced by Herpes
simplex infection
Treatment
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Acyclovir: inhibits viral DNA synthesis
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Acute HSV infections
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Latency is not eradicated by this agent
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Prophylactic to prevent reactivation in the
immunocompromized (transplant recipients)
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Available for topical, oral and intravenous route
Varicella Zoster Virus
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Two forms
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Primary infection is a generalized eruption (chicken pox)
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Reactivation is localized to one or few dermatomes
(shingles, Varicella Zoster)
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Only one antigenic type
Pathogenesis of Chicken Pox
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Children, vesicular skin eruption
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Virus enters through URT or conjunctiva
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The virus causes viremia
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The vesicles lie in the middle of the epidermis. The fluid
becomes cloudy with the influx of leucocytes. These
pustules dry up, scabs form and desquamate.
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Lesions in all stages are present at any time while new
ones are appearing.
Pathogenesis of Varicella Zoster
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VZV stays latent in the sensory ganglia
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Reactivation can occur at any age but the rate is much
increased in persons aged 60 years or over.
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Zoster is usually limited to one dermatome; in adults
most commonly in the thoracic or upper lumbar region.
Clinical Features
Chicken Pox
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Incubation period: 14 – 15 days
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The patient is infectious for 2 days before and up to 5
days after onset
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The rash is most dense on the trunk and head
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Macules ---- Papules ---- Vesicles ----
Pustules
Chicken Pox
Complications
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Secondary bacterial infection (commonest)
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Pneumonia
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CNS
 cerebellar ataxia syndrome
 acute encephalitits
Herpes Zoster
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Reactivated VZV infection
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Localized eruption, unilateral, typically confined to one
dermatome
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Prodromal paraesthesia and pain in the area supplied by
affected nerve are common before skin lesions develop
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Postherpetic neuralgia
 Most common complication of zoster
 50% risk in patients aged over 60 years
 pain persisting for 1 month or more after the rash
Herpes Zoster
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Ophthalmic zoster
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Involvement of ophthalmic division of the trigeminal
nerve
corneal ulceration, stromal keratitis
permanent scarring and loss of sight
Laboratory Diagnosis
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Early vesicular lesions are the best diagnostic material
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Virus isolation takes from 5 days to 3 weeks
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More rapid detection is possible with centrifugationenhanced cultures (shell vials)
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Direct immunofluorescence
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VZV DNA amplification by PCR
Treatment
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Acyclovir
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Given to high-risk of complication
 Neonates (first 3 weeks of life)
 Ophthalmic zoster
 Immunocompromized
Epidemiology
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Spread: respiratory route, in winter and early spring
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Varicella is highly infectious to susceptible close contacts
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Mortality is high in normal adults, particularly smokers
who develop pneumonia
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Zoster is associated with decreased T cell function:
 Old age
 Pre-AIDS phase
 Organ transplant recipients
Control
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Passive immunization: varicella zoster immunoglobulin
(VZIG):
 Neonates
 Non-immune pregnant contacts
 Immunocompromized contacts
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A live attenuated vaccine, IM injection
Coxsackieviruses
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Picornavirus
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Icosahedral, positive sense, linear, ssRNA
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Two groups: A and B
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Group A:
 Herpangina (vesicular pharyngitis)
 Hand – Foot – and – Mouth disease
 Acute hemorrhagic conjunctivitis
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Group B:
 Pleurodynia (epidemic myalgia)
 Myocarditis
 Meningoencephalitis
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Herpangina
 Severe febrile pharyngitis
 The pharynx is usually hyperemic and discrete
vesicles occur on the posterior half of the palate,
pharynx, tonsils or tongue
 Self-limited and most frequent in small children
Hand – Foot – and – Mouth disease
 Oral and pharyngeal ulcerations
 Vesicular rash on the palm and soles
Hand – Foot – and – Mouth disease