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Virology
Dr.Bara H.Hadi
Measles , Mumps, Rubella
Measles (Rubeola) Virus Infection
One of the most infectious childhood diseases known. Humans are the natural host. Caused by
the measles virus which is a paramyxovirus, genus Morbillivirus. It is 100–200 nm in diameter,
with a core of single-stranded RNA. Two membrane envelope proteins are important in
pathogenesis. They are the F (fusion) protein, which is responsible for fusion of virus and host
cell membranes, viral penetration, and hemolysis, and the H (hemagglutinin) protein, which is
responsible for adsorption of virus to cells. There is only one antigenic type of measles virus.
Although studies have documented changes in the H glycoprotein, these changes do not appear
to be epidemiologically important (i.e., no change in vaccine efficacy has been observed).
Measles virus is rapidly inactivated by heat, light, acidic pH, ether, and trypsin. It has a short
survival
time
(less
than
2
hours)
in
the
air
or
on
objects
and
surfaces.
Pathogenesis & Immunity:
 Virus infects URT cell lining where it multiplies locally, the infection then spreads to the
regional lymphoid tissues &then multiply there (primary Viremia).
Virology
Dr.Bara H.Hadi
 Secondary Viremia seeds the epithelial surfaces of the body including skin, respiratory
tract, conjunctiva where focal replication occurs. Virus replicates in certain lymphocytes
which aid in dissemination throughout the body.
 Skin rash: due to cytotoxic T cells attacking the measles virus-infected vascular
endothelial cells in the skin.
 Antibody-mediated vasculitis( so that specific antibodies coincide with appearance of
rash).
 Virus shedding from infected person start 4days prior to and 4 days after the appearance
of rash.
 Both neutralizing antibodies- IgG &cell mediated Immunity are involved during viremic
stage of measles.
Clinical features:
1- Incubation period: 8-12 days may lasts up to3 wks in adults.
2- Prodromal phase: last for (2-4 days) this phase is characterized by high grade fever,
running nose, dry cough, sore throat, conjunctivitis (virus may be excreted during this
phase) in tears, nasal secretions, urine and blood.
3- Koplik's spots -raised bright red macules or ulcer with white centers on the buccal
mucosa opposite the lower molar (It’s a valuable diagnostic sign) and it appears 2 days
before the rash.
4- Eruption phase: (last for 5-8 days) a characteristic light pink, discrete maculopapules
that coalesce to form blotches, rash appear on face to the chest, the trunk and then
proceeds gradually down the limbs. Rash become brownish in 5-10 days.
The disease is more extensive in this stage with generalized virus infection in lymphoid
tissues and skin, it’s more severe in malnourished children, AIDS & TB.
Modified Measles: occur in partially immune persons,such as infant with residual
maternal anibodies. I.P is prolonged, diminished prodromal symptoms, koplik’s spots are usually
absent and rash is mild.
Complications :
1-bronchopneumonia (giant cell pneumonia,croup&bronchitis )
2- Otitis media (with or without secondary bacterial infections).
Virology
Dr.Bara H.Hadi
3- Conjunctivitis and corneal ulcer
4- Encephalitis ~1:1000 cases, 10% mortality rate,40% with permanent sequalae (deafness
&MR)
5-Subacute schlerosing pan encephalitis (SSPE) a rare late and fatal complication of measles
with incidence of about 1:300,000 cases occurs several years after measles, slow
viral(conventional) infection in which the virus multiplies in the brain, resulting in
neurodegenerative disease. It’s usually fatal within 1-3 years after onset.
6-progressive measles inclusion body encephaltitis.
7-Measles in pregnant women resulting in stillbirth
8-Atypical measles following taken a killed vaccine, Occurs only in adult; infrequent
Laboratory diagnosis of measles:

Most diagnoses are made on clinical grounds; presence of koplik’s spot provides a
definitive diagnosis.

If laboratory diagnosis is necessary, it can be done by :-

Isolation of virus in a cell culture

A positive serologic test for measles IgM

Demonstrating rise in antiviral antibody titer of greater than four-fold.

Identification of measles virus RNA from a clinical specimen by PCR
Transmission:
Measles virus transmitted through respiratory droplets but this virus can also infect via the eye
and multiply in the conjunctivae. Viremia following primary local multiplication results in
widespread distribution to many organs.
Hematogenus transplacental transmission when occur during pregnancy.
Treatment & Prevention:
No antiviral drug, only supportive treatment; the use of vitamin A is useful to prevent blindness
due to measles.
Live attenuated vaccine, Trivalent live attenuated vaccine (MMR) usually given to 15 months
of age
Virology
Dr.Bara H.Hadi
Killed vaccines should not be used
Human Immunoglobulin given to modify the disease if given early in incubation period to
unimmunized pt., neonates and pregnant women.
Ribavirin; measles is susceptible in vitro to this drug with not proved clinical benefit.
Mumps Virus Infection :Mumps virus is a paramyxovirus. There is one serotype of the virus and in an affected patient it
can be found in most body fluids including cerebro-spinal fluid, saliva, urine and blood. The
virus can be grown in cell cultures and in eggs. The name comes from the British word "to
mump", that is grimace or grin. This results from the appearance of the patient as a result of
parotid gland swelling although other agents can also cause parotitis. Clinically, mumps is
usually defined as acute unilateral or bilateral parotid gland swelling that lasts for more than two
days with no other apparent cause.
Pathogenesis :
Humans are the only natural hosts for mumps virus. The virus is acquired by respiratory droplets.
It replicates in the nasopharynx and regional lymph nodes. After 12 to 25 days a viremia occurs,
which lasts from 3 to 5 days. During the viremia, the virus spreads to multiple tissues, including
the meninges, and glands such as the salivary, pancreas, testes, and ovaries. Involvement of the
parotid gland is not an obligatory step in infectious process . The incubation period of mumps is
14 to 18 days (range, 14 to 25 days).Virus is shed in the saliva from about 2 days before to 9
days after the onset of salivary gland swelling. About one third 1/3 of infected individuals do not
exhibit obvious symptoms(in apparent infections)
but are equally capable of transmitting
infection.
Transmission :
Mumps is spread through airborne transmission or by direct contact with infected droplet nuclei
or saliva.
Virology
Dr.Bara H.Hadi
Clinical Features :
The prodromal symptoms are nonspecific, and include myalgia, anorexia, malaise, headache, and
low-grade fever.
Parotitis is the most common manifestation and occurs in 30% to 40% of infected persons.
Parotitis may be unilateral or bilateral, and any combination of single or multiple salivary glands
may be affected. Parotitis tends to occur within the first 2 days and may first be noted as earache
and tenderness on palpation of the angle of the jaw. Symptoms tend to decrease after 1 week and
usually resolve after 10 days. As many as 20% of mumps infections are asymptomatic. An
additional 40% to 50% may have only nonspecific or primarily respiratory symptoms.
Complications :
 Central nervous system (CNS) involvement :-In the form of aseptic meningitis is
common, occurring asymptomatically in 50% - 60% of patients. Symptomatic meningitis
(headache, stiff neck) occurs in up to 15% of patients and resolves without sequelae in 3
to 10 days. Adults are at higher risk for this complication than are children, and boys are
more commonly affected than girls (3:1 ratio). Parotitis may be absent in as many as 50%
of such patients. Encephalitis is rare
 Orchitis (testicular inflammation) is the most common complication in postpubertal
males. It occurs in as many as 50% of postpubertal males, usually after parotitis, but it
may precede it, begin simultaneously, or occur alone. It is bilateral in approximately 30%
of affected males. There is usually abrupt onset of testicular swelling, tenderness, nausea,
vomiting, and fever. Pain and swelling may subside in 1 week, but tenderness may last
for weeks. Approximately 50% of patients with orchitis have some degree of testicular
atrophy, but sterility is rare.
 Oophoritis (ovarian inflammation) occurs in 5% of postpubertal females. It may mimic
appendicitis. There is no relationship to impaired fertility.
 Pancreatitis is infrequent, but occasionally occurs without parotitis; the hyperglycemia is
transient and is reversible.
 Deafness caused by mumps virus occurs in approximately 1 per 20,000 reported cases.
Hearing loss is unilateral in approximately 80% of cases and may be associated with
Virology
Dr.Bara H.Hadi
vestibular reactions. Onset is usually sudden and results in permanent hearing
impairment.
 Electrocardiogram changes compatible with myocarditis are seen in 3%–15% of patients
with mumps, but symptomatic involvement is rare. Complete recovery is the rule, but
deaths have been reported.
 Other less common complications of mumps include arthralgia, arthritis, and nephritis.
Laboratory Diagnosis :
 The diagnosis of mumps is usually suspected based on clinical manifestations.
 Isolation and identification of virus from clinical specimens (saliva, CSF, urine ) .
 Serology is the simplest method for confirming mumps virus infection and enzyme
immunoassay (EIA), is the most commonly used test. EIA is widely available and is more
sensitive than other serologic tests. It is available for both IgM and IgG.
Treatment ,Prevention and Control:
 There is no specific therapy.
 Immunization with attenuated live mumps virus vaccine .
Rubella Virus Infection
Rubella (which means "little red" and
is also known as German measles)
was originally thought to be a variant
of measles. It is a mild disease in
children and adults, but can cause
devastating problems if it infects the
fetus, especially if infection is in the
first few weeks of pregnancy. Rubella
virus is the only member of the
Virology
Dr.Bara H.Hadi
Rubivirus genus of the Togavirus family. Unlike most Togaviruses it is not arthropod-borne, but
is acquired via the respiratory route. It is an enveloped (toga=cloak), non-segmented, positive
sense, RNA virus and replicates in the cytoplasm. Its nucleocapsid has icosahedral symmetry
.There is only one major antigenic type.
Postnatal Infection:
Pathogenesis and Pathology:
Neonatal, childhood and adult infections occur through the mucosa of URT . Initial viral
replication probably occurs in RT, followed by multiplication in cervical lymph nodes. Viremia
after 7-9 days and last until the appearance of antibodies on about day 13-15 .The development
of antibodies coincides with the appearance of rash. After the rash appear ,the virus remains
detectable only in the nasopharynx where it may persist for several weeks.
Clinical features:
Postnatal rubella is often asymptomatic but may result in a generally mild, self-limited illness
characterized by rash, lymphadenopathy, and low-grade fever. As is the case for many viral
diseases, adults often experience more severe symptoms than do children. In addition,
adolescents and adults may experience a typical mild prodrome that is not seen in infected
children; this occurs 1 to 5 days before the rash and characterized by headache, malaise, and
fever.
The typical picture of rubella includes a maculopapular rash that appears first on the face and
neck and quickly spreads to the trunk and upper extremities and then to the legs. It often fades on
the face while progressing downwards. The lesions tend to be discrete at first, but rapidly
coalesce to produce a flushed appearance. The onset of rash is often accompanied by low-grade
fever. Although the rash usually lasts 3 to 5 days (hence the term “3-day measles”), the
associated fever rarely persists for more than 24 hours.
Postnatal rubella usually resolves without complication. However, a number of studies report
that as many as one-third of adult women with rubella experience self-limited arthritis of the
extremities and/or polyarthralgia; such effects are rare in children or men. Other complications of
Virology
Dr.Bara H.Hadi
rubella, reported with much less frequency than arthritis, include encephalitis and
thrombocytopenic purpura.
Congenital Infection:
Maternal viremia associated with rubella infection during pregnancy may result in infection of
placenta and fetus. Only limited number of fetal cells become infected. The growth rate of
infected cells is reduced, resulting in fewer numbers of cells in affected organs at birth and
hypoplastic organ development and so structural anomalies in the newborn. Timing of the fetal
infection determines the extent of teratogenic effect. The earlier in pregnancy infection occurs ,
the
greater the damage to the fetus. Rubella infection can
also result in stillbirth and
spontaneous abortion.
Clinical features :Clinical features of congenital rubella syndrome can be divided into three
main categories: Transient effect in infants .
 Permanent manifestation that may be apparent at birth or become recognized during the
first year.
 Developmental abnormalities that appear and progress during childhood and adolescence.
The classic triad of congenital rubella syndrome includes cataracts, heart defects, and deafness.
Infants may also display transient symptoms of growth retardation ,rash ,hepatosplenomegaly,
jaundice ,and meningoencephalitis. CNS involvement is more global with mental retardation
,balance and motor skills problems, progressive rubella panencephalitis.
Diagnosis :
The occurrence of the typical rash and lymphadenopathy may suggest the diagnosis of rubella.
Laboratory diagnosis of rubella is typically made by using serologic studies (i.e., detection of
IgM and/or fourfold antibody rises). The presence of specific IgM antibodies indicates recent
rubella infection. Specific IgG antibodies in healthy individuals demonstrate immunity to
rubella.
Virology
Dr.Bara H.Hadi
Antibodies are detectible by a variety of methods including : hemagglutination inhibition,
ELISA, and indirect immunofluorescent immunoassay.
Virus can be readily recovered in cell cultures from respiratory tract secretions and, in infants
with congenital infection, from urine, cerebrospinal fluid, and blood. Presence of virus in
inoculated cultures can be recognized by viral interference or immunoperoxidase staining assays.
Congenital rubella in the neonate is diagnosed by virus isolation or serologic testing. The
affected neonate has circulating antibodies, including transplacentally acquired maternal IgG
antibody and actively produced fetal and neonatal IgM antibody.
Prevention and Tretment:
A live vaccine (attenuated strain) is available. The vaccine virus is grown in human diploid
fibroblasts. Since there is only one serotype, a univalent attenuated vaccine can provide lifelong
immunity. It is important that women are vaccinated prior to their first pregnancy. The vaccine is
contraindicated for pregnant women, but when unwittingly used, no problems have been seen. If
the patient is pregnant and seronegative, the pregnancy should be monitored carefully and the
patient vaccinated postpartum. There is no specific treatment. Supportive care should be used.