1-10-19
Serologic Testing for Rubella and CRS (Cong
RubellaSndrome)- Low Prevalence Setting.
IgM and IgG Detection
Although rubella was officially declared to
be eliminated from the United States in 2004, ongoing rubella activity in
many other countries can result in sporadic U.S. cases or outbreaks. Detection
of specific IgM antibodies in a serum sample collected within the first few
days after rash onset can provide presumptive evidence of a current or recent
rubella virus infection.
The optimum time-point for collection of serum is
five days after the onset of symptoms (fever and rash) when >90% of cases
will be IgM positive.
On the day of rash onset only about 50% of cases
are IgM positive. Therefore, if serum collected less than five days after onset
is negative, a second sample would be necessary to confirm/rule out rubella.
The anti-rubella IgG status is determined for every serum received at CDC for
rubella testing to aid in case classification.
The
interpretation of rubella laboratory results must always take into account
relevant clinical and epidemiological data.
IgG Avidity Detection
Since no assay is 100% specific, serologic
testing of non-rubella cases using any assay will occasionally produce false
positive IgM results. In countries such as the United States where endemic
circulation of rubella has been eliminated, most suspected cases are not
rubella.
Rash and
fever illnesses are more likely due to a number of other rash–causing illnesses
such as parvovirus B19, enteroviruses such
as coxsackie viruses and echoviruses, or human herpesvirus–6 (roseola).\The
presence of rheumatoid factor can also result in a false positive IgM.
What is meant by IgM positivity ? IgM reactivity
It is important to distinguish IgM reactivity caused by primary infection from
that caused by IgM persistence or cross-reactivity with other antigens,
especially in pregnant women. The measurement of rubella IgG antibody avidity can be used to
distinguish between recent infection and remote rubella infection.
Antibody avidity (the overall strength of
binding between the antigen and antibody) increases with time; this is known as
maturation of the immune response. As the immune response
matures, low avidity antibodies are replaced with high avidity antibodies.
These avidity differences can be detected by using protein denaturants such as
diethylamine (DEA) in the washing step of an enzyme-linked immunoassay (EIA)
for rubella IgG. In acute rubella virus infections, specific, low-avidity IgG
lasts for up to three months after appearance of the IgG response. The presence
of high avidity antibodies, which develop by about three months after
infection, provides evidence of remote infection. The cut-off between low and
high avidities has to be established by using standardized sera and a
particular EIA kit.
For pregnant women, avidity testing is most
useful in early pregnancy to help rule out a rubella infection in the first
trimester, when the risk of congenital defects due to rubella is highest.
It is not as useful in late pregnancy because avidity will be high by the third
trimester if infection occurred in the first trimester.
Serological testing for congenital rubella
syndrome (CRS)
Congenital Rubella
Syndrome (CRS), which can occur when a woman is
infected with rubella during a pregnancy, consists of a variety of possible
birth defects including cataracts, hearing loss, heart defects, developmental
disabilities, and low birthweight. CRS was eliminated from the United States in
2004, but cases can still be imported by pregnant women who contract rubella in
an endemic country. In rare cases, CRS can occur in the United States when
susceptible pregnant women are exposed to imported rubella cases.
CRS cases can be diagnosed in newborns and young
infants using detection of rubella IgM. Suspected cases should be tested as
close to birth as possible and again at 1 month of age if the initial IgM test
is negative. At 3 months of age, approximately 50% of cases would still have
detectable rubella IgM in their serum. Additionally, the presence of rubella
IgG in an infant after the decline of maternal antibodies (9 months of age) and
the absence of vaccination or exposure to rubella will confirm CRS.
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