the viral mechanisms for cell injury and death in rubella are not well understood for either

postnatal or congenital infection. following infection, the virus replicates in the respiratory
epithelium, the spreads to regional lymph nodes. viremia ensues and is most intense from 10
to 17 days after infection. viral shedding from the nasopharynx begins about 10 days after
infection and may be detected up to 2 weak following onset of the rash. the period of highest
communicability is from 5 days before to 6 days after the appearance of the rash.

the most important risk factor for severe congenital defects is the stage of gestation at the
time of infection. maternal infection during the fiirst 8 weak of gestation results in the most
severe and widespread defects. the risk for congenital defects has been estimated at 90 % fro
maternal infection before 11 weak of gestation, 33% at 11-12 weak,11% at 13-14 weak, and
24% at 15-16 weak. defects occuring after 16 weak of gestation are uncommon, even if fetal
infection occurs.

causes of cellular and tissue damage in the infected fetus may include tissue necrosis due to
vascular insufficiency, reduce cellular multipliction time, chromosomal breaks, and
production of a protein inhibitor causing mitotic arrests in certain cell types. the most
distinctive feature of congenital rubella is chronicity . once the fetus is infected early
gestatiton, the virus persist in fetal tissue until well beyond delivery. persistence suggests the
possibility of ongoing tissue damage and reactivation, most natably in the brain.

Clinical Manifestations

Postnatal infection with rubella is a mild disease not easily discernible from other viral
infections, especially in children. Following an incubation period of 14-21 days, a prodrome
consisting of low-grade fever, sore throat, red eyes with or without eye pain, headache,
malaise, anorexia, and lymphadenopathy begins. Suboccipital, postauricular, and anterior
cervical lymph nodes are most prominent. In children, the first manifestatiton of rubella is
usually the rash, which is variable and not distinctive. It begins on the face and neck as small
irregular pink macules that coalesce, and its spreads centrifugally to involve the torso and
extremities, where it tends to occur as discrete macules. About the time of onset of the rash,
examination of the oropharynx may reveal tiny, rose-colored lesions (forcheimer spots) or
petechial hemorrages on the soft palate. The rash fades from the face as it extends to the rest
of the body so that the whole body may not be involved at any fisrt time. The duration of the
rash is generally 3 days, and it usually resolves without desquamation. Subclinical infections
are common, and 25-40% of children may not have a rash.
Laboratory Findings

Leukopenia, neutropenia, and mild thrombocytopenia have been describe during

postnatal rubella.

Diagnose

Spesific diagnosis of rubella is important for epidemiologic reasons, for diagnosis

infection in pregnant women, and for confirmation of the diagnosis of congenital rubella. The
most common diagnostic test is rubella immunoglobulin M (IgM) enzyme immunosorbent
assay. As with any serologic test, the positive predictive value of testing decreases in
population with low prevalence of disease. Test should be performed in the context of a
supportive history of exposure or consintent clinical findings. The relative sensitivity and
specitifity of commercial kits used in most laboratories range from 96% to 99% and 86% to
97%, respectively. A caveat for testing of congenitally infected infants early in infacy is that
false-negative results may occur ing in these patients. In such patients, an IgM capture assay,
reverse transcriptase polymerase chain reaction (PCR) test, or viral culture should be
performed for confirmation.

Differential Diagnoses

Rubella may manifest as distinctive features suggesting the diagnosis. It is frequently

confused with other infections because it is uncommon, similar to other viral exanthematous
diseases, and demonstrates variability in the presence of typical findings. In severe prodrome
as well as shorter course allow for differentiation from measles. Other diseases frequently
confused with rubella include infections caused by adenoviruses, parvovirus B19 (erythema
infectiosum), Epstein-Barr virus, enteroviruses, and Mycoplasma pneumoniae.

Compligations

Complication following postnatal infection with rubella are infrequent and generally not life
threatening.

Postinfectious thrombocytopenia occurs in about 173,000 cases of rubella and

occurs more frequently among children and in girl. It manifests about 2 wk following the
onset of the ras as petecthiae, epistaxis, gastrointestinal bleeding, and hematuria. It is usually
self-limited.
 Arthritis following rubella occurs more commonly among adult, especially women.
It begins within 1 wk of onset of the exanthem and classically involves the small joins of the
hands. It also is self-limited and resolves within weeks without sequelse. There are
anaecdotal report and some serologic evidence linking rubella with rheumatoid arthritis, but a
true causal association remains speculative.

Encephalitis is the most serious complication of postnatal rubella. It occurs in 2

forms: a postinfectious syndrome following as a neurodegenerative disorder years following
rubella.

Postifectious encephalitis is uncommon, occurring in 1/5,000 cases of rubella. It

appers within 7 days after onset of the rash, consisting of headache, seizures, confusion, focal
neurologic signs, and ataxia. Fever may recrudesce wuth the onset of neurologic symptoms.
Cerebrospinal fluid (CSF) may be normal or have a mild mononuclear pleocytosis and/or
elevated protein concentration. Virus is rarely, if ever, isolated from CSF or brain, suggesting
a noninfectious pathogenesis. Most patients recover completely, but mortality rates of 20%
and long-term neurologic sequelae have been reported.

Progressive rubella panencephalitis (PRP) is an extremely rare complication of

either acquired rubella or CRS. It has an onset and course smiliar to those of the subacute
sclerosing panencephalitis (SPPE) associated with meales (Chapter 238). Unlike in the
postinfectious form of rubella encephalitis, however, rubella virus may be isolated from brain
tissue of the patient with PRP, suggesting an infectious pathogenesis, albeit a “slow” one.
The clinical findings and course are undistinguishable from those of SPPE and transmissible
spongiform encephalopathies (Chapter 270). Death occurs 2-5 yr after onset.

Other neurologic syndromes rarely reported with rubella include Guillain-Barre

syndrome and peripharel neuritis. Myocarditis is a rare complication.

Congenital Rubella Syndrome

In 1994 an ophthalmologist first described a syndrome of cataracts and congenital heart

disease that he correctly associated with rubella infection in the mother during early
pregnancy. Shortly after the first description, hearing loss was ecognired as a common
finding afren associated with min cephaly. In 1964-1965 a pandemic of rubella eccurred, wih
20,000 cases ceported in the USA leading to S11,000 this experience emerged the expanded
definiion of C included numerous other transjent or permanent abnormalit ous or therapcutic
abortions and 2.100 neonazal dexth Fro RS tha Nerve deafness is the single most common
finding among rare infants with CRS. Moit infants have sone degree of intrantere growth
restriction. Retinal findings descrnbed as salt-and-pe retinopathy are the most commion
oqular abnormality but hs ittle early ettect on vision. Unidaeral or ilatecal cataracts are th
most serious eye finding occurring in about a third of inanits (g 239-4) Cardiac shnormalities
occur m half of the childnn infected doring the 1st 8 wk of gostation. Paten: dacts aterome in
the most frequently reported cardiac defect, followed by lessi of the pulmonary anmeries and
valrular disease Intestiial pors monitis leading to death in some cases has bes reported. Neu
rologic abnormalities ar buth Meningenxephalitis is present in 10.20 % of CRS and inay
perist for up to 12 mo, Longc tidinal tol through 912 yr of intants without initial recardation
reveakd e common and may grx follos resive development of addinional sensory, motirs and
belas abnormalities, including hearing loss and autian.PRP aso been rocognized rarely ahes
CRS Suhseqe growth retardation and uleinate shos tatue have been reported. In a minority of
cases, rare reports of immunologic deficiency syndrome have also been described. A variety
of late- onset manifestation of CRS have been recognized. In addition to PRP, they include
diabetes mellitus (20%), thyroid dysfunction (5%), and glaucoma and visual abnormalities
associated with the retinopathy, which had previously been considered benign.

TREATMEN

There is no specific treatment available for either acquired rubella or CRS.

SUPPORTIVE CARE

Postnatal rubella is generally a mild illness that requires no care beyond antipyretics and
analgesics, intravenous immunoglobulin or corticosteroids can be considered for server,
nonremitting thrombocytopenia.

Management of children with CRS is more complex and requires pediatric, cardiac,
audiologic ophtalmologic, and neurologic evaluation and follow-up bacause many
manifestationsmay not be readily apparent initially or may women whith time. Hearing
screening is of special importance, because early intervention may improve outcomes in
children with hearing problems due to CRS.

PROGNOSIS

Postnatal infection with rubella has an excellent prognosis. Long term outcome of CRS are
less favorable and somewhat variable. In an australian cohort evaluated 50 years after
infection, many had chronic conditions but most were married and had made good social
adjustments. A cohort from new york from the mid 1960s epidemic had less favorable
outcomes, with 30%leading normal lives, 30% in dependent situations but functional, and
30% requiring institutionalization and continouns care.

Re-infection with wild virus occurs postnatally in both individuals who were previously
infected with wild –virus rubella and in vaccinated individuals. Re-infection is defined
serologically as a significant increas in igG antibody level and/ or an IgM respons. Hearing
screening is of special importance, because carry prevention may improve outcomes in
children with hearing lems due to CRS.

Prognosis

Postnatal infection with rubella has an excellent prognosis. Longterm outcomes of

CRS are less favorable and somewhat variable. In an Australian cohort evaluated 50 year
after infection, many had chronic conditins but most were married and had made good social
adjustments. A cohort from New York from the mid-1960sepidemic had less favorable
outcomes, with 30 % leading normal lives, 30 % in dependent situations but functional, and
30 % requiring institutionalizatiion and continous care.

Re-infection with wild virus occurs postnatally in both individuals who were
previously infected with wild-virus rubella and in vaccinated individuals. Re-infection is
defined serologically as a significant increase in IgG antibody level and/or an IgM response
in an individual who has a documented preexisting rubella-spesific IgG above an accepted
cutoff. Re-infection may result in an anamnestic IgG response, an IgM and IgG response, or
clinical rubella. There have been 29 reports of CRS following maternal re-infection in the
literature. Re-infection with serious adverse outcomes to adults or children is rare and of
unknown significance.

Prevention

Patients with postnatal infection should be isolated from susceptible individuals for 7
days after onset of the rash. Standard plus droplet precautions are recommended for
hospitalized patients. Children with CRS may excrete the virus in respiratory secretions up to
1 year of age, so contact precautions should be maintained for them until then, unless
reported cultures of urine and pharyngeal secretions have negative results. Similiar
precautions apply to patients with CRS with regard to attendance in school and out-of-home
child are.

Exposure of susceptible pregnant women poses a potential risk to the fetus. For
pregnant women exposed to rubella, a blood specimen should be obtained as soon as possible
for rubella IgG-spesific antibody testing; a frozen aliquot also should be saved for later testig.
If the rubella antibody test is negative, a second specimen should be obtained 2-3 weak later
and tested concurrently with the saved specimen. If both of these test negative, 3rd specimen
should be obtained 6 weak afterexposure and tested concurrently with. 3rd specimens test
negative, infection has not accured. A negative first specimen and positive test result in either
the second or 3rd specimen indicate that seroconversion has occured in the mother,
suggesting recent infection. Counseling should be provided about the risks and benefits of
termination of pregnancy. The routine use of immune globulin for susceptible pregnant
women exposed to rubella is not recommended and is considered only if termination of
pregnancy is not an option because of maternal preferences. In such circumstances, immune
globulin 0.55 mL/kg IM may be given with the understanding that prophylaxis may reduce
the risk for clinically apparent infection but does not guarantee prevention of fetal infection.

Vaccination

Rubella vaccine in the USA consists of the attenuated RA 27/3 strain that is usually
administered in combination with measles and mumps (MMR) or also with varicella
(MMRV) in a 2-dose-regimen at 12-15 mo and 4-6 year of age. If theoritically may be
effective as postexposure prophylaxis if administered within 3 days of exposure. Vaccine
should not be administered to severely immunocompromised patients (e.g., transplant
recipients). Patients with Hiv infection who are not severely immunocompromised may
benedit from vaccianation. Fever is not a contraindication, but if a more serious illness is
suspected, immunization should be delayed. Immune globulin preparations may inhibit the
serologic response to the vaccine. Vaccine should not be administered during pregnancy. If
pregnancy occurs within 28 days of immunization, the patient should be consuled on the
theoritical risks to the fetus. Studies 0f >200 women who had been inadverently immunized
with rubella vaccine during pregnancy showed that none of their offspring developed CRS.
Therefore, interruption of pregnancy is probably not warranted.

Adverse reactions to rubella vaccination are uncommon in children. MMR

administration is associated with fever in 5-15 % of vaccine and rash in about 5%. Arthralgia
and arthritis are more common following rubella vaccination in adults. Approxing mately
25% of postpubertal women experience arthralgia, and 10% experience arthritis. Peripheral
neuropathies and transient thrombocytopenia may also occur.

As part of the worldwide effort to eliminate endemic rubella virus transmission and
occurrence of CRS, maintaining high population immunity through vaccination coverage and
high quality intergrated measles-rubella surveillance have been emphasized as being vital to
its success.