Innovative assays for high testing efficiency

Transcription

Elecsys® TORCH testing
cobas® modular platform
Flexible configurations for tailor made solutions
With the cobas modular platform (cobas 4000 and 6000 analyzer series and cobas 8000 modular analyzer series) Roche has
developed a platform concept based on a common architecture that delivers tailor-made solutions for diverse workload and testing
requirements. The cobas modular platform is designed to reduce the complexity of laboratory operation and provide efficient and
compatible solutions for network cooperation.
Flexible and intelligent solutions
•Multiple configurations with tailor-made solutions for higher
efficiency and productivity
•Consolidation of clinical chemistry and immunochemistry with
more than 200 parameters for cost and workflow improvements
•Future sustainability through easy adaptation to changing
throughput and parameter needs
cobas 8000 modular analyzer series
Large volume
<c 502>
<e 602>
<c 701>
cobas 6000 analyzer series
Mid volume
<c 501>
38 configurations
<c 702>
7 configurations
<e 601>
cobas 4000 analyzer series
Low volume
<c 311>
•Consistency of interaction with hardware, software and
reagents for less training and more staff flexibility
•Consistency of patient results due to a universal reagent
concept
<e 411>
3 configurations
Prenatal and perinatal TORCH testing1
The acronym TORCH was introduced in 1971 by Nahmias et al. to
group pathogens known to cause hazardous congenital infections,
namely toxoplasma, rubella, cytomegalovirus (CMV), and herpes
simplex virus (HSV). This list of prenatal infections is, however,
far from comprehensive, and should be supplemented with other
agents. Nowadays, there are many more infections representing
TORCH, such as:
• Toxoplasmosis
• Other: Treponema pallidum (syphilis), hepatitis B, hepatitis E,
Coxsackie virus, Epstein–Barr virus (EBV), human parvovirus,
varicella zoster and many more
• Rubella
• Cytomegalovirus (CMV)
• Herpes simplex virus (HSV)
Although some of these infections become chronic, they are usually asymptomatic in otherwise healthy adults. However, mothers
acquiring a primary infection during pregnancy have a high risk
of transmitting the pathogen to their embryo, which often has
devastating consequences for the unborn. The corresponding risk
in the case of secondary or reactivated infections is low.
TORCH screening is now widely requested by clinicians monitoring
infants and pregnant women for congenital, perinatal and neonatal
infections. The patient history, risk factors and local regulations
guide the screening procedure. These tests are performed mainly
in the first trimester of pregnancy, but suspect neonates may also
be tested. For most TORCH pathogens the initial screening test is
based on the detection of specific antibodies. The goals of TORCH
testing are to determine the mother’s immune status and to help
differentiate between acute and past infection in pregnancy. Preconception and antenatal screening play an important role in the
prevention of vertically transmitted infections.
Today, many sensitive and specific tests are available for serological diagnosis of these diseases. The major challenge in serodiagnosis is the combination of high sensitivity and high specificity,
although these features are mutually exclusive. To achieve a high
sensitivity, the early detection of infection and the recognition of
all pathogenic variants is mandatory. On the other hand, a high
specificity is required to avoid uncertainty and retesting for confirmation.
Toxoplasma gondii parasite2-12
Toxoplasma gondii is a ubiquitous intracellular parasite that can
affect virtually all warm-blooded vertebrates. Infections usually
lead to life-long persistence of the protozoon in muscle and nerve
tissues. According to rough estimates 25 – 50 % of the global
human population carry the parasite, with pronounced geographical and regional differences. Typical sources of infection are the
consumption of raw or undercooked meat and the uptake of free
spores released by cats into the environment.
Typical symptoms of an acute infection in otherwise healthy people
are an unspecific seroconversion disease and, rarely, intensified
headache, lymphadenopathy and muscle pain. Immunocompromized
persons will encounter much more severe, if not fatal, sequelae. In the
vast majority of cases chronic infection is asymptomatic subjectively.
However, there is increasing evidence that cerebral toxoplasma cysts
cause behavioral and other changes in the affected individual.
The primary hazard connected with toxoplasma infections is the
vertical transmission of the pathogen by a pregnant woman with
primary infection. 5 – 10 % of these pregnancies will abort spontaneously or terminate in miscarriage, another 8 – 10 % will result in
the birth of an infant with severe eye and/or brain damage and
10 – 13 % of the viable babies will suffer from visual handicaps.
Even if children are born without apparent symptoms, they may
still develop chorioretinitis or retard mentally in childhood or young
adulthood.
The incidence of primary toxoplasmosis during pregnancy in Western Europe is approximately 0.5 – 0.6 %, which, for example, is
significantly higher than the incidence of congenital hypothyroidism,
which affects 0.02 – 0.03 % of all viable born babies. It is for these
reasons that a pre-pregnancy or prenatal screening is considered
desirable, if not mandatory, in many countries and throughout large
parts of the population.
Toxoplasmosis screening is based on the evidence given by serological markers, namely Toxoplasma-IgG and IgM. In contrast with
many other infections, IgM antibodies can persist for years in
case of chronic disease, which complicates diagnosis significantly
and may require additional testing. The diagnostic strategies are
very different regionally and even locally. However, an algorithm as
shown below is reasonable. The testing and, if indicated, the monitoring of the pregnant woman, should start as soon as possible,
as therapeutic options become available.
Start
Perform
Toxo IgG/IgM tests
IgG neg.
IgM neg.
IgG pos.
IgM neg.
IgG neg.
IgM pos.
IgG pos.
IgM pos.
Toxo IgG
avidity
Intermediate
low
No
immunity
Acquired
immunity
Avoid
primary infection
Past
infection likely
Repeat testing
during pregnancy
Start
Beginning
infection
Unspecific
IgM
Toxo IgG
titer
stable
Repeat testing
~3 weeks later
Stop
Repeat IgG test
~3 weeks later
Start
Fig. 1: Suggested Toxoplasma gondii serologic diagnostic algorithm in immunocompetent individuals2, 8
Infection > 2
months before 1st
sample
high
Infection
> 4 months ago
Increasing
(2–4 fold
increase)
Recent infection
< 2 months before
1st sample
Further action
may be required
The suggested screening process starts with the demonstration of
specific Toxoplasma IgG and IgM. Four principal marker constellations may result:
IgG negative, IgM negative
This is the constellation seen in Toxoplasma-naïve individuals.
These women did not have contact with Toxoplasma in the past,
they do not have acquired immunity and can contract a primary
infection on each contact with the pathogen. They need special
medical attention and counseling. Repeated Toxoplasma testing is
recommended on a regular basis. They should refrain from eating
raw or undercooked meat, avoid cats and cat litter and also dogs.
They should strictly adhere to common hygiene measures and
should avoid eating unwashed raw fruits, vegetables and salads.
IgG positive, IgM negative
These women had contact with Toxoplasma in the past and
are now probably carriers of non-proliferative cysts. They have
acquired immunity and there is only a marginal, if any, risk of
vertical transmission and subsequent embryonic damage.
IgG negative, IgM positive
There are two scenarios that can lead to this constellation:
1. Beginning infection, before IgG seroconversion
2. Unspecific IgM
This situation can be resolved by repeating the tests with fresh
sample 3 weeks later. In the case of unspecific IgM, the result
should be the same as for the initial sample. In the case of a
beginning infection, IgG should be detectable by this stage.
IgG positive, IgM positive
This is the most difficult finding to interpret. In order to avoid being
misled by persisiting IgM or unspecific IgM, an IgG avidity test is
recommended at this point.
If the avidity is high, an infection has taken place more than 4
months ago. The IgM result is probably due to persisting IgM or
unspecific stimulation immune system. Timely screening can rule
out a risk for the unborn child.
If the avidity is low to borderline, there is a risk for the unborn.
An additional quantitative IgG test from a fresh sample taken
3 weeks after the first IgG test can be helpful when deciding
on patient management. If the IgG titer is stable, the infection
occurred more than 2 months before the first sampling. If the
IgG titer is increasing significantly, an infection younger than 2
months is possibly present, which translates into a high risk for
the embryo.
Rubella virus13-32
Virology
Rubella virus is the only known Rubivirus species and belongs to
the Togaviridae family. The RNA genome of Rubella virus codes
for 2 non-structural and 3 structural proteins, namely the capsid
protein C and the two envelop proteins E1 and E2. Its pathogenic
mechanism is not yet fully understood, although there is evidence
of a p53-dependent process. After replication and translation new
virus particles are assembled and leave the host cell by budding.
Transmission
Postnatally the virus is spread via airborne transmission. There is
no carrier state; the reservoir exists in infected people, who spread
the virus by droplets from the upper respiratory tract. A patient is
contagious from approximately from 1 week before to 1 week after
the symptomatic phase.
Prenatally the virus can be transmitted from a pregnant woman
with primary infection to the fetus through the placenta (vertical
transmission).
Nosography
Rubella, also known as German measles, is the disease caused by
Rubella virus. It is a typical childhood infection, usually with a mild,
if not subclinical, course. Normally, children recover from it within
1 – 3 days. In adults, the disease is often associated with more
pronounced manifestations, may last longer, but is self-limiting in
otherwise healthy people.
By contrast, primary infection of a pregnant women during the
first half of pregnancy and subsequent vertical transmission of the
virus is a serious event, often leading to miscarriages or congenital
rubella syndrome (CRS).
Acquired rubella
After an incubation of 2 – 3 weeks, during which the patient is
contagious, the typical exanthema will develop on the face, from
where it spreads over the trunk and limbs. Usually the itchy rash
fades away after 1 – 3 days.
Other symptoms include low fever (rarely above 38 °C), suboccipital and posterior cervical lymphadenopathy, joint pain (often
protracted in adults), headache and conjunctivitis. In about 20 %
of all cases small, red papules will develop on the soft palate
(Forchheimer’s sign).
Prenatal rubella virus transmission
Vertical transmission of rubella virus is a serious condition that
often has disastrous consequences for the fetus, which are more
severe when it occurs early in pregnancy. After passing the placenta the virus will infect the fetus, where it will stop cells from
developing or will destroy them.
Many women who contract rubella within the first trimester will either
have a miscarriage or a stillborn baby. Delivery is often premature
with babies having a low birth weight. If an infected baby survives
the birth barrier, it may present congenital rubella syndrome (CRS),
which includes blindness, deafness and congenital heart failure,
a patent ductus arteriosus (PDA) being the most frequent cause.
Furthermore, prenatal rubella infection may entail cerebral defects,
neonatal thrombocytopenia, anemia, hepatitis and skin lesions
known as “blueberry muffin lesions”.
Treatment
No direct treatment is available for rubella. Therapeutic efforts
focus on diminishing the discomfort associated with the disease. In
newborns with a prenatal rubella infection severe manifestations
are treated, if possible. For example, cataracts and congenital heart
failure are often managed by surgery.
Prevention
An effective vaccine is available against rubella virus, which
nowdays is usually given as part of the MMR vaccination. Every
woman of childbearing age should be immune to the virus, either
having had a previous infection or having been vaccinated. In
countries, where rubella vaccination is common, endemics have
been successfully interrupted. Occasional flare-ups result from virus
influx from countries without organised vaccination programs. Additionally, in a few European countries, there is resistance against vaccination in children from some parents, including MMR vaccination.
Virus in throat
Virus in bloodstream
IgG
IgM
1024
rash
64
32
16
50
8
Antibody titer
Virus isolation
[%]
100
4
0
8
6
4
Days before
2 1
1
2
4
6
8
10
12
Days after onset of rash
14
1
2
Months
1
2
3
10
0
Years
Fig. 2: Serological profile after rubella infection. Thomas L., Laboratory and diagnosis. Frankfurt: TH-Books 2009.
Diagnosis
The serological profile after a rubella virus infection is straightforward.
Shortly after infection the virus starts to proliferate in the upper
respiratory tract and is also detectable in blood. During this period
patients are contagious. Approx. 2 – 3 weeks after the infection the
typical exanthema and other symptoms evolve, followed by a rapid
elimination of the viral load and the development of a specific IgM
and IgG titer. During convalescence the IgM is usually completely
eliminated, although it can also persist for several months. IgG
remains elevated, normally for the rest of life, and protects against
reinfections.
1.A significant IgG titer without any other rubella indicators is
presumptive for immunity, either after a previous infection or
vaccination. These women are not at risk of a prenatal infection.
2.A low, marginal titer of IgG may indicate seroconversion at a
very early stage of infection, when IgM not yet detectable. If
observed during pregnancy, the IgG test should be repeated a
few weeks later with a fresh sample.
1.The patient did not have contact with Rubella virus in the past.
Such women are at risk of contracting an infection during
pregnancy. If not pregnant they should be vaccinated, if pregnant they require close monitoring.
2.The patient is within the incubation period before seroconversion.
If indicated, the virus can be detected directly from blood by PCR
during this period. Otherwise, symptoms and seroconversion will
develop within a few weeks.
1.The patient is in the very early stages of infection, with IgM, but
not IgG, having already responded. If observed during pregnancy,
the test should be repeated a few weeks later with a fresh sample.
2.The IgM result may be unspecific. Again, the finding can be
clarified with a test performed with a sample taken a few weeks
later.
1.The patient is suffering from an acute infection, in particular
with preceding clinical signs. The serological finding can be
refined with a rubella IgG avidity test. If this constellation
occurs during pregnancy the embryo is at risk. To prove a fetal
infection, the virus can be confirmed by PCR in fetal blood (cordocentesis).
2.Without preceding clinical signs there is the possibility that the
IgM is unspecific. To refine this suspicion a rubella IgG avidity
test can be done.
Cytomegalovirus (CMV) 33-43
In immunocompromized patients a primary infection with CMV or
a reactivation has much more aggressive consequences. A CMVhepatitis may proceed fulminant, with the development of special
forms of retinitis and colitis. The outcome is not infrequently fatal.
A symptomatic CMV infection is an AIDS-defining event.
Cytomegalovirus (CMV), also known as human herpes virus 5
(HHV 5) belongs to the family of herpes viruses. It is one of the
world’s most widespread viruses with a regionally differing carrier
prevalence between 40 and close to 100 %. CMV is transmitted parenterally through body fluids, blood transfusion or organ
transplantation. Infection from person to person requires close
intimate contact. CMV can be transmitted sexually, vertically
before term, and perinatally. It is the most common viral cause of
birth defects in industrialized countries. Like all herpes viruses
CMV can persist latent within the body over long periods, with
the occurrence of recidivations.
The most sinister consequences can result after a primary infection
of a pregnant woman with vertical virus transmission to the unborn
child. Obviously, the incidence of this hazardous event depends on
the prevalence of acquired immunity in the community under consideration. For example, in the United States as many as 1 – 3 %
of all pregnant women will suffer a primary CMV infection before
term! And – what makes the story even worse – due to the mild
clinical course of the disease, most mothers won’t even notice that
they are acutely infected. 10 – 15 % of these women will give birth
to an affected baby with symptoms that may include:
In otherwise healthy people infection usually proceeds without
subjective symptoms or involves a mild seroconversion disease. A
sore throat is common. A few patients will develop more noticeable
symptoms such as infectious mononucleosis, glandular fever-like
syndrome, prolonged fever or even mild hepatitis. Recent research
is unveiling a more malicious side of CMV: Kidney cells infected
with CMV seem to produce renin, which directly interferes with the
RAA system, contributing to high blood pressure. Other authors
suggest that CMV infection of blood vessel endothelial cells may
be a major cause of atherosclerosis.
•low birth weight
•microcephaly
•seizures
•petechial rash
•moderate hepatosplenomegaly
•jaundice
Start
Perform
CMV IgG/IgM tests
IgG neg.
IgM neg.
IgG neg.
IgM pos.
IgG pos.
IgM neg.
IgG pos.
IgM pos.
low to borderline
High risk of
transmission
No
immunity
Beginning
infection
Avoid
primary infection
Repeat testing
during pregnancy
Repeat testing
~3 weeks later
low to borderline
Gestational
age
> 20 w
IgG
avidity
high
Acquired
immunity
Possibly
additional testing
IgG neg.
IgM neg.
Refer to 1st
trimester samples
Past
infection likely
Recidivation
possible
Maternal viremia
• Virus isolation
• Blood PCR
IgG pos. / IgM pos.
Low avidity
IgG pos.
IgM neg.
Fetal well-being
• Ultrasound
• MRI
IgG neg.
IgM pos.
Non-primary infection
low risk of
transmission
Invasive testing
• Amniocentesis
• Cordocentesis
Start
≤ 20 w
IgG
avidity
high
Stop
Fig. 3: Suggested CMV serologic diagnostic algorithm in immunocompetent individuals39-42
IgG pos. / IgM pos.
High avidity
Stop
The outcome can be fatal, but most infants will survive a congenital infection with state-of-the art supportive treatment. Nevertheless, 80 – 90 %
of these will develop later complications, including hearing loss, vision
impairment and varying degrees of mental retardation. There is significant morbidity. Another 5% - 10% of infants who are infected but without
symptoms at birth will subsequently have varying degrees of hearing and
mental or coordination problems. Perinatal or enteral transmission by
breast feeding will usually only cause mild, if any, disease in the infant.
An active vaccination is not available. A CMV-specific hyperglobulin
is mainly used to support treatment of patients with severe symptoms. The typically mild course of the disease does not make special
treatment necessary. In immunocompromized individuals anti-viral
treatment can be attempted. In case of pregnancy such treatment is
of course strictly contraindicated.
The initial lab diagnosis of CMV infection, either for screening purposes or if a concrete suspicion exists, is based on the detection of specific IgG and IgM antibodies against the virus. The age of an infection
can be estimated by IgG-avidity tests. IgM alone is not always reliable
for this purpose, as persisting IgM may also be present in case of a
non-acute infection due to recidivations or reinfections, unspecific
stimulation of immune system, etc. Confirmation is done with nucleic
acid tests, in the case of prenatal screening using fetal tissue (blood
or placenta).
No generally agreed screening algorithm is available for pregnancy
monitoring. The algorithm presented below is certainly the best
solution and covers all the aspects discussed above.
This is the constellation seen in CMV-naïve individuals. These women
did not have contact with CMV in the past, they do not have acquired
immunity and can contract a primary infection on each contact with the
pathogen. They need special medical attention and counseling. Repeated CMV testing is recommended on a regular basis during pregnancy.
Throughout the pregnancy, they should practice good personal hygiene,
especially hand washing with soap and water, after contact with diapers
or oral secretions (particularly with a child who is in day care).
There are two scenarios that can lead to this constellation:
1.Beginning infection, before IgG seroconversion
2.Unspecific IgM
This situation can be resolved by repeating the tests with fresh sample
3 weeks later. In the case of unspecific IgM, the result should be the
same as with the initial sample. In case of a beginning infection, IgG
should be detectable by this stage.
These women had contact with CMV in the past and have now
acquired immunity. There is only a marginal, if any, risk of vertical
transmission and subsequent fetal damage. However, recidivation
is possible, but is very unlikely to cause fetal morbidity.
This is the most difficult finding to interpret. The next step is to
determine IgG avidity. Depending on the corresponding gestational
age this result triggers different confirmation algorithms: If the gestational age is less than, or equal to, 20 weeks and avidity is high, it
is assumed that infection has occurred before conception. The initial
positive IgM finding is then attributed to a persisting response or
considered as unspecific. Further measures are not necessary.
If the gestational age is less than or equal to, 20 weeks and avidity is
low, the possibility that infection has occurred after conception cannot be ruled out. Additional confirmatory testing is recommended.
If the gestational age exceeds 20 weeks and the IgG avidity is low
to borderline, a fresh infection is possible and additional testing is
recommended.
If the gestational age exceeds 20 weeks and the IgG avidity is high,
then the CMV results from archived first trimester samples have to
be included in the diagnostic process.
If the first trimester samples are IgM and IgG positive with high avidity, an
acute infection can be excluded and further measures are not necessary.
If the first trimester samples are IgM negative and IgG positive, there
is probably a non-primary infection with a low risk of vertical transmission and further measures are not necessary.
In case of all other constellations in the first trimester samples an acute
infection cannot be excluded and further testing is recommended.
In order to avoid being misled by persisiting IgM, an IgG avidity test is
recommended at this point.
If the avidity is high, an infection has taken place more than 4 months
ago. The IgM result is probably due to persisting IgM. Timely screening can rule out a risk for the unborn child.
If the avidity is low to borderline, there is a risk for the unborn child.
An additional quantitative IgG test from a fresh sample taken 3 weeks
after the first IgG test can be helpful when deciding on patient management: If the IgG titer is stable, the infection occurred more than
2 months before the first sampling. If the IgG titer is increasing more
than twofold, an infection younger than 2 months is possibly present,
which translates into a high risk for the embryo.
Herpes simplex virus (HSV)44-57
Virology
Approximately 100 Herpes viruses have been identified to date,
8 of which are pathogenic in humans.
HSV 1 is mainly transmitted via social contacts during childhood, but also sexually later in life. Already by the end of puberty
high seroprevalences of specific antibodies are observed, which
increase only slightly later in life (Germany: 84 – 92 %).
Herpes Simplex Virus 1 (HSV 1) and Herpes Simplex Virus 2 (HSV 2)
are two closely related viruses, belonging to the family of Herpesviridae, subfamiliy Alphaherpesviridae, genus Simplexvirus. They are
human-specific. Like all herpes viruses they have a large doublestranded DNA genome that encodes more than 100 gene products.
The icosahedric capsid is embedded in approx. 20 different tegument proteins and covered with an outer envelope comprising at
least 10 shell proteins.
Transmission and prevalence
Postnatally the transmission is usually horizontal through close
contact with persons shedding virus. Not only secretions from
sores can contain virus, but also saliva or genital fluids. Transmission is likely when visible symptoms are present, but can also
occur from apparently asymptomatic patients.
HSV 2 is usually transmitted sexually by asymptomatic shedding. In
health-aware individuals the seroprevalence of specific antibodies
was found to be in the range of 3 – 23 % (US), while it was much
higher in patients with other venereal diseases (55 %) or prostitutes
(75 %).
Orofacial herpes manifestations are caused by HSV 1 in 80 %
of cases and by HSV 2 in the remaining 20 %. The figures are
reversed for genital herpes: HSV 1 accounts for 20 % and HSV 2
for 80 % of all cases.
Both viruses can also be transmitted vertically before birth (rare)
or perinatally during delivery. Such infections may have severe, if
not fatal, consequences for the fetus /newborn.
Neonate infection
at birth
(Sexual) transmission;
Neonate infection at birth
Symptomatic
virus shedding
Caused by
Asymptomatic
virus shedding
20 % HSV 1*
80 % HSV 2*
genital
Infection
Latency
Caused by
Reactivation
Virus dormant in nerve
ganglions
80 % HSV 1*
20 % HSV 2*
oro-facial
* distribution for Europe
Fig. 4: Incidence of congenital HSV 1 and 2 infections48, 49, 52, 56
stimuli
(e.g. stress UV-light,…)
Nosography
A primary infection with HSV is often associated with the development of painful watery blisters that release an infectious exudate.
Typical sites are the mouth, lips (Herpes labialis) or genitals (Herpes
genitalis). More severe sequelae of a primary infection are rare, but
possible and include herpetic whitlow, herpes gladiatorum, ocular
herpes, cerebral herpes with encephalitis, Mollaret’s meningitis,
Bell’s palsy and many other disorders.
After the acute symptoms have healed, the virus is not eliminated,
but the patient becomes a carrier with the infection being latent.
HSV 1 and 2 are neurotropic and neuroinvasive viruses that hide
from the immune system, entering the cell bodies of nerves.
Recent evidence suggests that – given a certain genetic setup – a
latent HSV 1 infection may even be an etiologic factor in the development of Alzheimer’ s disease.
Many carriers will suffer from sporadic reactivations. In such an
outbreak viruses leave the nerve cells and move via the axon to the
skin, where they proliferate causing painful sores.
If transmission occurs perinatally, the newborn will most likely be
infected. The undeveloped immune system is not able to fight the
virus effectively, and severe consequences such as skin, eye and
mouth involvement, herpes simplex encephalitis, pneumonitis, keratitis and other conditions may develop, possibly with a fatal outcome
or leading to irreversible morbidity. The risk of transmission is in the
range of 20 – 30 % in the case of maternal primary infection, which
is often asymptomatic. For recurrences in seropositive mothers the
risk is around 2 %.
Prenatal (intra-uterine) infection of the embryo is a comparably
rare event, but may have very severe sequelae, including a high
risk of spontaneous abortion, intra-uterine growth retardation,
premature birth, fetal damage, local disseminated neurologic morbidity, intravascular coagulopathy and others. The morbidity after
an HSV 2 infection is higher than after an HSV 1 infection.
In immunocompromized patients a Herpes infection easily generalizes with severe consequences for the patient.
Diagnosis
In otherwise healthy adults diagnosis is usually achieved by
assessment of the clinical picture. More sophisticated diagnostic
procedures, such as direct virus detection, genotyping and serological demonstration of specific antibodies, are indicated for
immunocompromized patients and in the field of obstetrics.
Seroconversion in HSV 1 or 2 IgG during pregnancy involves a
risk of vertical transmission. Genital herpes sores during delivery
clearly suggest that a cesaerean section is advisable. However,
as asymptomatic virus shedding is also possible, the obstetrician
has to decide whether to perform a section in case of an existing
HSV 2 IgG titer.
The detection of specific IgM antibodies currently has no clinical
relevance. Primary infections may occur without an immediate IgM
response; on the other hand, the presence of an IgM-titer does not
necessarily prove a primary infection. IgM antibodies against HSV
may persist for months or years and may reappear again in the
case of reactivation.
Prophylaxis
No vaccination is available at this time.
The transmission of HSV 1 through social contacts during childhood
can not realistically be avoided. The sexual transmission of HSV can
only be suppressed by avoiding all skin-to-skin contacts. The use of
barrier methods reduces, but does not exclude transmission. As with
all sexually transmitted diseases, the use of condoms and dental
dams is highly recommended in non-monogamous relations. The
use of antiviral medication also helps to reduce the risk of transmission.
Treatment
There is currently no curative treatment available against Herpes
infections. A number of antiviral drugs (topic and atopic) can be
used to ameliorate the clinical consequences of virus reactivations.
Antivirals given as of gestational week 36 reduce the risk of viral
shedding during delivery.
Syphilis58-69
When Columbus returned from the West Indies, he had an unwanted,
morbid stowaway on board: Treponema pallidum ssp. pallidum – the
causative agent of syphilis. Syphilis has since spread around the
world, plaguing and killing humans. The advent of antibiotics brought
relief, but syphilis is now making a come-back.
Bacteriology
The infective agent causing syphilis is a bacterium belonging to
the order of Spirochaetales, family Spirochaetaceae, genus Treponema. Spirochaetales are gram-negative spirochetes (Greek: coiled
hair), which are extremely thin and can be very long. They have a
tightly coiled helical structure and are motile thanks to periplasmic
flagella. The genus Treponema comprises two species: pallidum
and carateum, the pallidum species being subdivided into three
subspecies: pallidum, endemicum and pertenue. These spirochetes
are too thin to be seen under a routine microscope, although darkfield microscopy will reveal them.
pertenue in yaws. Infection with T. pallidum ssp. pallidum is etiologic for syphilis. While pinta, bejel and yaws are non-venereal
diseases mainly seen in undeveloped tropical and subtropical
regions, syphilis is primarily a sexually, but also a vertically,
transmitted disease that is prevalent worldwide. Syphilis is also
known as Lues or French Disease.
T. pallidum ssp. pallidum is an intracellular pathogen, which cannot
be grown in cell-free cultures in vitro. It is quite sensitive in vitro
and can be killed by high temperatures (41 °C, 2 h), low temperatures (4 °C, 72 h), dryness, insecticides and changes in osmolality.
Transmission
Syphilis is mainly transmitted sexually, but also prenatally and
perinatally, in rare cases parenterally. With respect to sexual transmission, there is a 30% chance of acquiring disease after a single
exposure to an infected partner, but the transmission rate obviously also depends on the stage of the disease.
T. carateum causes a disease known as pinta, T. pallidum ssp.
endemicum is the infective agent in bejel and T. pallidum ssp.
Start
Nonreactive
<TP>-IgG
Reactive
equivocal
No
serological evidence
of infection
Nonreactive
Repeat
<TP>-IgG
Start
RPR
(quant.)
Reactive
Nonreactive
Early primary
syphilis cannot be
excluded
Retest in
2-4 weeks
Reactive or
equivocal
Presumptive
evidence of
•Current
infection
•Inadequately
treatment
infection
•Reinfection
Nonreactive
FTA-ABS
Reactive
Probably false
positive syphilis test
Probably syphilis
•Past infection
•Previous
treatment
•Late latent
•Late syphilis
Past infection
cannot be entirely
ruled out
Cross-reactivity with
other spirocheterelated antigens
cannot be excluded
Repeat
testing
Fig. 5: Suggested Syphilis serologic diagnostic algorithm in immunocompetent individuals69
Clinical history necessary for
interpretation
False positive
results cannot be
excluded
Correlate findings
with patient
symptoms and
treatment history
Stop
Disease stages of syphilis
In adults, syphilis proceeds in 3 stages (primary, secondary, tertiary
syphilis) separated by latent phases of various duration.
The pathogen enters the host through minor lesions in the skin and
then incubates for several weeks. During this period it multiplies
and spreads rapidly throughout the body via lymphatic and systemic
circulation. No general symptoms are involved at this stage.
The symptoms of primary syphilis appear 10-90 days (usually 3-4
weeks) after the initial contact: The host mounts an inflammatory
response at the site of inoculation, resulting in the hallmark syphilitic
lesion known as chancre. This ulceration is almost painless, a fact that
differentiates syphilis from other ulcerating diseases such as herpes.
High levels of Treponema are found in such ulcers. Within two months
the chancre will heal spontaneously, giving a false feeling of security.
2 – 10 weeks after the primary lesion, sometimes concomitantly with it,
secondary syphilis will arise. During this stage, many spirochetes are
spread throughout the body and a widely disseminated mucocutaneous
rash will develop, which is highly contagious. A generalized immunological response with severe subjective symptoms is usually associated
with this stage. Patients will suffer from pharyngeal pain, myalgia and
general lymphoadenopathy, and sometimes even more severe sequelae.
Following secondary syphilis the host enters a latent period. Within a period of approx. 4 years after the infection, secondary syphilis often flares up
again, albeit with milder manifestations. This so-called early latent phase
merges into late latent syphilis. This stage has no clear clinical symptoms
and lasts until symptoms of tertiary syphilis will develop.
Approx. 40 % of late latent patients will develop tertiary syphilis. This
stage is characterized by the development of granulomatous dermal
lesions (gummas), ranula, cardiovascular syphilis and neurosyphilis.
Neurosyphilis develops in about 15 % of untreated cases, usually more
than 5 years after the initial infection. It affects the central nervous
system and the spinal chord, possibly leading to dementia, seizures and
wasting. Meningitis due to Treponema may damage the brain parenchyma, resulting in progressive paralysis and impairment of the spinal
cord functions. Cardiovascular involvement appears 10-40 years after
initial infection with resulting myocardial insufficiency and death.
Congenital syphilis
The seroprevalence of T. pallidum during pregnancy is relatively low in
Western countries (0.02 % to 4.5 %), whereas it may be much higher
in other parts of the world. A dramatic increase in the incidence of
congenital syphilis is currently observed in rural areas of Eastern Europe
and Central Asia. There is a close correlation between the incidence
of primary and secondary syphilis in women and the incidence of
congential syphilis.
Syphilis can be transmitted vertically from a seropositive mother to
the fetus, usually during the 2nd and 3rd trimesters. T. pallidum will
widely disseminate in the unborn leading to septicemia, often with the
consequence of abortion or neonatal mortality. Children surviving the
birth barrier can suffer from mental or physical problems later in life.
Early congenital syphilis, which develops within few years after birth,
is associated with symptoms such as rhagades, syphilitic pemphigus,
syphilitic rhinitis and osteochondritis. Late congenital syphilis can
develop during early adolescence of late childhood and manifests
itself in the form of e.g. inner ear hearing loss, parenchymatous
keratitis, Hutchinson’s teeth (Hutchinson’s triad), gumma and central
nervous system lesions.
WHO estimates that maternal syphilis causes, each year, 460,000
abortions or stillbirths, 270,000 cases of congenital syphilis, and
270,000 premature or low-birth-weight babies.
Prophylaxis and treatment
There is no vaccination available to protect from syphilis. Since syphilis is a sexually transmitted disease, practising the rules of safer sex
protects against transmission. However, since T. pallidum can enter
through any breaches in the skin, the use of barrier methods does not
provide complete protection (e.g. syphilitic whitlow). Syphilis can be
treated effectively with antibiotics, namely penicillin or tetracycline.
Diagnosis
Accurate diagnosis of syphilis is essential as it is an important health
problem worldwide. The incidence is on the rise again in Western
countries, particular in big cities and other hotspots. The latent phases
of syphilis proceed without subjective symptoms, and each case that
remains undiscovered involves the risk of serious consequences,
including stillbirths, congenital syphilis, further sexual or parenteral
transmission, tertiary syphilis. On the other hand, if properly diagnosed
a patient can be treated effectively.
The diagnosis of symptomatic primary and secondary syphilis is
often straightforward and is based on the clinical picture. Serological tests are only required for confirmation. Non-symptomatic
syphilis can only be diagnosis by laboratory tests. Basically, three
procedures are available:
1.Direct demonstration of T. pallidum ssp. pallidum by dark field
microscopy or PCR
2.Treponemal antibody tests (HetIA, HIA, agglutination)
3.Non-treponemal tests (VDRL, RPR, HIA, agglutination)
In order to overcome the specificity shortcomings of the assays,
treponemal and non-treponemal tests are often done together. A positive antibody titer indicates prior exposure to T. pallidum, while nontreponemal tests are particularly well suited for therapy monitoring.
Glossary
Anemia
Reduction in the ability of blood to transport
oxygen. May be due to a reduction in the
concentration of intact hemoglobin, hematocrit or the number of intact erythrocytes.
Avidity
Avidity is a measure of the stability of
immune complexes, including the affinities of
paratope-epitope interactions and statistical
properties due to multipoint binding.
Capsid
A complex, usually symmetric, protein structure that coats the viral genome.
Cataract
Clouding of the crystalline lens or its envelope, possibly up to total opacity.
Cervical
Concerning the neck.
Chorioretinitis
Simultaneous inflammation of the conjunctiva
and the choroid.
Coagulopathy
Pathological impairment of blood coagulation.
Colitis
Inflammation of the colon.
Conjunctivitis
Inflammation of the conjunctiva.
Contagious
Capable of transmitting disease.
Curative
Tending to overcome disease and promote
recovery.
Dissemination
Spreading.
Ductus arteriosus
Prenatal shunt between the aorta and the
pulmonary artery.
Encephalitis
Inflammation of the brain.
Endemic
An infection in a population that is maintained without the need for external inputs.
Envelope
Found in some viruses: A protein layer that
covers the capsid, often faking a cellular
membrane.
Enteral
Uptake of nutrients, medication or an infective agent via the intestine.
Exanthema
Acutely occurring rash.
Exudate
Secretion usually caused by inflammation.
Flagellum
A tail-like part of a bacterium employed to
gain motility.
Fulminant
Beginning suddenly, proceeding fiercely and
rapidly.
Genome
The total of inheritable cellular information,
coded in strands of nucleic acids.
Gumma
Rubber-like hardened nodule, usually of the
skin, that develops during tertiary syphilis.
Hepatosplenomegaly Simultaneous enlargement of liver and
spleen.
Horizontal transmissionTransmission of a pathogen between members of the same species that are not in a
parent-child relationship.
Hutchinson’s triad
Complex of three symptoms that often occur
secondarily to congenital syphilis: inner ear
hearing impairment, keratitis, dental deformations.
Iatrogenic
Caused by medical actions.
Icosahedral symmetry Most common symmetry of virus capsids. An
icosahedron is a body encompassed by 20
identical triangles.
Immunocompromized Patients who have a weakened, impaired or
inoperative immune system. May be iatrogenic (e.g. immunosuppressive therapy) or
acquired (e.g. AIDS).
Incidence
Number of new occurrences of a certain
condition in a given population during a
given time period.
Keratitis
Inflammation of the cornea.
Latent infection
Equilibrium between host and pathogen. The
pathogen is present but is controlled by the
host’s immune system and does not cause
subjective disease.
Lymphadenopathy
Pathological swelling of lymph nodes.
Meningitis
Inflammation of the membranes covering the
brain and the spinal chord.
Microcephaly
Developmental abnormality presenting as a
skull with a significantly reduced volume.
MMR
Mononucleosis
Measles – Mumps – Rubella.
Disease caused by infection with EpsteinBarr Virus.
Morbidity
The presence of disease or illness.
Mucocutaneous zone Transition area from mucosa to skin.
Myalgia
Muscle pain.
Naïve (pathogen)
Not having had any contact with a particular
pathogen in the past.
Neuroinvasive
Entering nerve cells.
Neurotropic
A virus that infects only, or preferentially,
nerve cells.
Nosography
Systematic description of diseases.
Oro-facial
Related to the mouth and the face.
Osteochondritis
Painful inflammation of the bone or cartilage
in a joint.
p53
Protein found in many malignant, but also
in benignly proliferating, cells. It appears to
play a role in the regulation of the cell cycle,
where it controls the activity of a number of
genes.
Papule
Circumscribed, solid elevation of skin with no
visible fluid.
Parenchyma
The functional part of an organ.
Pemphigus
Blistering autoimmune disease that affects
the skin and mucous membranes.
Perinatal
Period between the 24th week of gestation
and the 7th day after birth.
Periplasm
see periplasmic space.
Periplasmic space
The space between the inner cytoplasmic
membrane and the external outer membrane
of certain bacteria.
Persistent IgM Specific IgM persisting after convalescence
from an acute infection.
Petechial rash
Bleeding from capillaries in the skin or
mucosa leading to multiple pinhead-sized
hematomas.
Pharyngeal
Related to the throat.
Pneumonitis
Inflammation of the lung.
Posterior
Located toward the back.
Prevalence
Number of occurrences of a certain condition
in a given population.
Primary infection
First infection of a patient with a given pathogen.
Proliferative
Growing, propagating.
RAAS
Renin-angiotensin-aldosterone system.
Ranula
Cyst beneath the tongue, caused by retained
saliva.
Recidivation
Relapse or recurrence of a disease.
Replication
Multiplication of genetic material, usually a
genome.
Rhagades
Deep fissures of the skin
Sequela
Complication of an acute condition.
Septicemia
Presence of pathogens in the bloodstream
leading to sepsis.
Seroconversion
The point in time when a serological marker
(usually an antibody) becomes detectable
after an infection.
Seropositive
Describes a sample (or patient) that contains
a detectable titer of a serological marker.
Seroprevalence
The prevalence of a serological marker in a
given population.
Suboccipital
The location between the skull and the first
cervical vertebra.
Tegument proteins
Viral proteins located between the nucleocapsid and the envelope.
Thrombocytopenia
Platelet count below 50,000 per μL.
Translation
Synthesis of proteins based on information
provided by genes.
Unspecific IgM IgM not directed against a pathogenic
epitope.
Venereal diseases
Sexually transmitted diseases such as syphilis
and gonorrhea.
Vertical transmission Transmission of a pathogen from mother to
child.
References
TORCH
1 Stegmann, B.J., Carey, J.C. (2002). TORCH infections: Toxoplasmosis, Other (syphilis, varicellzoster, prarvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes infections. Curr Women’s
Health Rep 2(4), 253-8.
Toxoplasmosis
For overall reviews see:
2 Remington, J.S., McLeod, R., Desmonts, G. (2001). Toxoplasmosis. In: J.S. Remington & J.O. Klein
(ed.), Infectious Diseases of the Fetus and Newborn Infant, 5th ed., Philadelphia: W.B. Saunders,
pp. 205-346.
3 Montoya, J.G., Liesenfeld, O. (2004). Toxoplasmosis. Lancet 363:1965-76.
For Toxoplasmosis in pregnancy see:
4 Thulliez, P. (2001). Maternal and foetal infection. In: Joynson DHM, Wreghitt TG (ed.), Cambridge:
Cambridge University Press, pp. 193-213.
5 Wong, S.Y., Remington, J.S. (1994). Toxoplasmosis in pregnancy. Clin Infedt Dis 18: 853-62.
For Toxoplasmosis in immunocompromized patients see:
6 Luft, B.J., Remington, J.S. (1992). Toxoplasmic encephalitis in AIDS. Clin Infect Dis 15: 211-22.
7 Khalifa, K.E.S., Roth, A., Roth, B., Arasteh, K.N., Janitschke, K. (1994). Value of PCR for Evaluating
Occurrence of Parasitemia in immunocompromised Patients with Cerebral and Extracerebral
Toxoplasmosis. J Clin Microbiol 32, 2813-9.
For persisting IgM see:
8 Meek, B., van Gool, T., Gilis, H., Peek, R. (2001). Dissecting the IgM antibody response during the
acute and latent phase of toxoplasmosis. Diagn Microbiol Infect Dis 41, 131-7.
9 Bobic, B., Sibalic, D., Djurkovic-Djakovic, O. (1991). High levels of IgM Antibodies Specific for
Toxoplasma gondii in Pregnancy 12 Years after Primary Toxoplasm Infection. Gynecol Obstet
Invest 31, 182-4.
For toxoplasmosis and behavioural changes see:
10 Holliman, R.E. (1997). Toxoplasmosis, Behavior, and Personality. Journal of Infection 35, 105-10.
11 Lafferty, K.D. (2006). Can the Common Brain Parasite, Toxoplasma gondii, Influence Human
Culture? Proc R Soc B. 273, 2749-55.
12 Berdoy, M., Webster, J.P., Macdonald, D.W. (2000). Fatat Attraction in Rats Infected with Toxoplasma gondii. Proc Biol Sci 267(1452), 1591-4.
Rubella
13 Banatvala, J.E., Brown, D.W.G. (2004). Rubella. Lancet 363, 1127-37.
14 Best, J.M., Banatvala, J.E. (2000). Rubella. In: Zuckerman, A.J., Banatvala, J.E., Pattison, J.R. (ed.),
Principles and Practice of Clinical Virology, Hoboken: John Wiley & Sons, Ltd., 387-418.
15 Best, J.M., Cooray, S., Banatvala, J.E. (2005). Rubella, 960-92. In: Topley und Wilson’s Microbiology and Microbial Infections, Vol. 2, Virology, Chapter 45.
For rubella in pregnancy see:
16 Wesselhoeft, C. (1949). Rubella and congenital deformities. NEJM 240(7), 258-61.
17 Hanshaw, J.B., Dudgeon, J.A., Marshall, W.C. (1985). Viral diseases of the fetus and newborn.
Philadelphia: W.B. Saunders.
18 Cooper, L.Z., Alford, C.A. (2001). Rubella. In: Remington JS, Klein JO (ed.), Infectious Diseases of
the Fetus & Newborn Infant, 5th ed. Philadelphia: W.B. Saunders, 347-388.
19 Pustowoit, B., Lieber, U.G. (1998). Predictive Value of Serological Tests in Rubella Virus Infection
during Pregnancy. Intervirology 41, 170-7.
20 Siegel, M., Fuerst, H.T., Guinee, V.F. (1971). Rubella epidemicity and embryopathy. Results of a
long-term prospective study. Am J Dis Child 121(6), 469-73.
21 Edlich, R.F., Winter, K.L., Long, W.B., Gubler, K.D. (2005). Rubella and congenital rubella (German
measles). J Long Term Eff Med Implants 15(3), 319-28.
22 Atreya, C.D., Mohan, K.V., Kulkarni, S. (2004). Rubella virus and birth defects: molecular insights
into the viral teratogenesis at the cellular level. Birth Defects Res Part a Clin Mol Teratol 70(7), 431-7.
23 De Santis, M., Cavaliere, A.F., Straface, G., Caruso, A. (2006). Rubella infection in pregnancy.
Reprod Toxicol 21(4), 390-8.
24 Weisinger, H.S., Pesudovs, K. (2002). Optical complications in congenital rubella syndrome.
Optometry 73(7), 418-24.
25 Freij, B.J., South, M.A., Sever, J.L. (1988). Maternal rubella and the congenital rubella syndrome.
Clin Perinatol 15(2), 247-57.
26 Lee, J.Y., Bowden, D.S. (2000). Rubella virus replication and links to teratogenicity. Microbiol Rev
13(4), 571-87.
For rubella virus see:
27 Frey, T.K. (1994). Molecular biology of rubella virus. Adv Virus Res 44, 69-160.
For rubella vaccination see:
28 Skendzel, L. (1996). Rubella Immunity. Defining the Level of Protective Antibody. Am J Clin Pathol
106, 170-4.
29 Watson, J.C., Hadler, S.C., Dykewicz, C.A., Reef, S., Phillips, L. (1998). Measles, mumps, and
rubella-vaccine use and strategies for elimination of measles, rubella, and congenital rubella
syndrome and control of mumps: recommendations of the Advisory Commettee on Immunization
Practices (ACIP). MMWR Recomm Rep 47(RR-8), 1-57.
30 Reef, S.E., Frey, T.K., Theall, K. (2002). The changing epidemiology of rubella in the 1990s: on the
verge of elimination and new challenges for control and prevention. JAMA 287(4), 464-72.
31 Plotkin, S.A. (2001). Rubella eradication. Vaccine 19(25-26), 3311-9.
32 Atkinson, W., Hamborsky, J., McIntyre, L., Wolfe, S. (eds) (2010). Epidemiology and Prevention
of Vaccine-Preventable Diseases, 10th ed. Chapter 12: Rubella; Centers for Disease Control and
Prevention. http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/rubella.pdf
[Accessed 02-September-2010]
Cytomegalovirus
33 Revello, M.G., Gerna, G. (2008). Expert Opin Med Diagn 2(5), 547-63.
34 Revello, M.G., Gerna, G. (2002). Clin Microbiol Rev 15(4), 680-715.
For CMV in pregnancy see:
34 Revello, M.G., Gerna, G. (2002). Diagnosis and Management of Human Cytomegalovirus Infection
in the Mother, Fetus, and Newborn Infant. Clin Microbiol Rev 15(4), 680-715.
36 Munro, S.C., Hall, B., Whybin, L.R. et al. (2005). Diagnosis of and Screening for Cytomegalovirus
Infection in Pregnant Women. J Clin Microbiol 43(9), 4713-18.
37 Lazzarotto, T., Gabrielli, L., Lanari, M., et al. (2004). Congenital Cytomegalovirus Infection. Recent
Advances in the Diagnosis of Maternal Infection. Hum Immunol 65, 410-5.
38 Guerra, B., Simonazzi, G., Banfi, A. (2007). Impact of diagnostic and confirmatory tests and prenatal counseling on the rate of pregnancy termination among women with positive citomegalovirus
immunoglobulin M antibody titers. Am J Obstet Gynecol 196, 221-3.
For diagnostic and screening procedures of CMV see:
39 Munro, S.C., Hall, B., Whybin, L.R. et al. (2005). J Clin Microbiol 43(9), 4713-8.
40 Lazzarotto, T., Gabrielli, L., Lanari, M. et al. (2004). Hum Immunol 65, 410-415.
41 Guerra, B., Simonazzi, G., Banfi, A. et al. (2007). Am J Obstet Gynecol 196, 221-223.
42 Duff, P. (2007). A thoughtful algorithm for the accurate diagnosis of primary CMV infection in
pregnancy. Am J Obstet Gynecol 196, 196-197.
For CMV in immunocompromized patients see:
43 Ljungman, P. (2004). Risk of cytomegalovirus transmission by blood products to immunocompromised patients and means for reduction. Brit J Haematol 125,107-16.
Herpes simplex virus
44 Marre, R., Mertens, T., Trautmann, M., Vanek, E. (2000). Klinische Infektiologie. München Jena,
pp. 578ff, 596ff, 189ff.
45 Hahn, H., Falke, D., Kaufmann, S.H.E., Ullmann, U. (2005). Medizinische Mikrobiologie und Infektiologie, 5th ed. Heidelberg: Springer, 610ff.
46 Mims, C., Dockrell, H.M. et al. (2006). Medizinische Mikrobiologie / Infektiologie, 2nd ed.
München: Elsevier.
For signs and symptoms of infection see:
47 Daniels, C.A., LeGoff, S.G. (1975). Shedding of infectious virus/antibody complexes from vesicular
lesions of patients with recurrent herpes labialis. Lancet 20(2), 524-8.
48 Malvy, D. et al. (2007). Epidemiology of orofacial herpes simplex virus infections in the general
population in France: results of the HERPIMAX study. J Eur Acad Dermatol Venereol 21(10),
1398-403.
49 Anderson, B.J. (2003). The epidemiology and clinical analysis of several outbreaks of herpes
gladiatorum. Med Sci Sports Exerc 35(11), 1809-14.
50 Sanderson, I.R. et al. (1987). Eczema herpeticum: a potentially fatal disease. Br Med J 294(6573),
693-4.
51 Cordero-Coma, M. (2007). Herpetic retinitis. Herpes 14(1), 4-10.
52 Maertzdorf, J. et al. (2001). Herpes simplex virus type 1 (HSV-1)-induced retinitis following herpes simplex encephalitis: indications for brain to eye transmission of HSV-1. Ann Neurol 49(1),
104-6.
53 Klein, A., Lefebvre, P. (2007). Three consecutive episodes of acute retinal necrosis due to herpes
simplex 1 over twelve years following herpetic encephalitis. Ocul Immunol Inflamm 15(5), 411-3.
54 Murakami S. et al. (1996). Bell’s palsy and herpes simplex virus: Identification of viral DNA in
endoneurial fluid and muscle. Ann Intern Med 124(1), 27-30.
55 Wakisaka, H. et al. (2002). Demyelination associated with HSV-1-induced facial paralysis. Exp
Neurol 178(1), 68-79.
For statistical data see:
56 Hellenbrand, W., Thierfelder, W. et al. (2005). Seroprevalence of herpes simplex virus type 1
(HSV-1) and type 2 (HSV-2) in former East and West Germany, 1997-1998. Eur J Clin Microbiol
Infect Dis 24(2), 131-5.
For herpes simplex virus see:
57 Coriell, L.L., Rake, G. et al. (1950). Electron microscopy of herpes simplex. J Bacteriol 59(1), 61-68.
Syphilis
58 WHO: Focus Syphilis (2004). Nature Microbiology Reviews 2, 448-9.
59 Pickering, L.K. (ed.) (2006). Syphilis, 631-44. In: Red Book, Elk Grove Village, IL:American Academy of Pediatrics.
60 Centers for Disease Control and Prevention (2010). CDC Fact Sheet Syphilis. http://www.cdc.gov/
std/syphilis/syphilis-fact-sheet-press.pdf
61 Centers for Disease Control and Prevention (2010). Primary and Secondary Syphilis – United
States, 2003 – 2004. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5510a1.htm
For symptoms and course see:
62 Dylewski, J., Duong, M. (2007). The rash of secondary syphilis. CMAJ 176(1), 33-5.
63 Clark, E.G., Danbolt, N. (1964). The Oslo study of the natural course of untreated syphilis: An
epidemiologic investigation based on a re-study of the Boeck-Bruusgaard material. Med Clin
North Am 58, 613.
For prevention and treatment of syphilis see:
64 Centers for Disease Control and Prevention (2010). How can Syphilis be Prevented?
http://www.cdc.gov/std/Syphilis/STDFact-MSM-Syphilis.htm#prevent
65 Centers for Disease Control and Prevention (2006). Sexually Transmitted Diseases Treatment
Guidelines. MMWR 55(RR-11): 24-32.
For statistical data see:
66 WHO: WHO Disease and injury country estimates 2004 (2010).
http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html
67 Fairley, C.K., Hocking, J.S., Medland, N.(2005). Syphilis back on the rise, but not unstoppable.
Medical Journal of Australia 183(4), 172-3.
68 Fenton, K.A., Nicoll, A., Kinghorn, G. (2001). Resurgence of syphilis in England: time for more
radical and nationally coordinated approaches. Sex Transm Infect 77(5), 309-10.
For diagnostic and screening procedures of CMV see:
69 College of American Pathologists, USA (2007).
http://www.cap.org/apps/docs/cap_today/feature_stories/0807SyphilisChart.pdf
COBAS, COBAS C, COBAS E, LIFE NEEDS ANSWERS
and ELECSYS are trademarks of Roche.
©2011 Roche
06479367001 b 0311 -
Roche Diagnostics Ltd.
CH-6343 Rotkreuz
Switzerland
www.cobas.com
Based on recombinant antigens and specific assay formats like µ-capture and DAGS (double antigen sandwich), Roche has
been continuously developing innovative TORCH assays. These assays enable the reliable and early diagnosis of infections in
prenatal screening and the recognition of opportunistic infections in immunocompromized patients.
Elecsys TORCH IgM µ-capture assays: Proven performance
•Advanced sensitivity for earlier diagnosis
•High specificity in routine and in possibly cross-reactive samples
•Good discrimination between acute and past infections due to less reactivity to persistent IgM 1,2 for diagnostically more
conclusive results and less unnecessary retesting
•Smart interference blocking concept for less interferences
… for early and reliable diagnosis of acute infections
Elecsys TORCH IgG DAGS assays: Unique assay design
•High specificity without compromizing sensitivity: sensitivity
up to 9% better than competitive assays 3 resulting in less
unnecessary serological follow-ups
Relative specificity
•Clear discrimination of negative and positive results for
less retesting 4
Relative sensitivity
Elecsys
Frequency
Immulite
Axsym
Access II
Vidas
0
10
20
30
40
50
60
70
80
90
160
140
120
100
80
60
40
20
0
cut-off ≥1.0 U/mL
136
133
118
75
54
40
38
29
4
3 2 0 0 0 0 0 0 0 0 0 0 0 0 1 0
0.0
0.2 0.4
0.6
0.8
1.0
1.2
1.4
1.6 1.8
2.0
100
500
0.1
0.3
0.5
0.7
0.9
1.1
1.3
1.5
1.7
1.9
50
250
Elecsys® CMV-IgG [U/mL]
100
Fig. 1: Elecsys® Toxo IgG – Excellent specificity with best-in-class sensitivity
at the same time 3
grayzone
Fig. 2: Distribution of Elecsys® CMV IgG values in daily routine samples
(n=633) 2
•High precision and good reproducibility with accurate quantification for an easy follow-up of antibody concentration during seroconversion
… for accurate
Elecsys assessment of the immune status and reliable monitoring
Immulite
Elecsys TORCH
assays: High workflow efficiency
Axsym
•Integration
into routine testing with efficiency, cost and workflow improvement without compromizing performance
Access II
•Outstanding SWA consolidation degree with >200 parameters for clinical
and immunochemistry including many
realtivechemistry
specificity
Vidas
relative sensitivity
innovative markers
0
10
20
30
40
50
60
70
80
90
100
•Broad infectious disease menu with a complete hepatitis panel (A, B and C), HIV and TORCH
•Operational efficiency: highly automated systems (e.g. autodilution), short turn around times, less retesting and confirmation testing
due to high sensitivity and specificity of the TORCH assays, wide measuring ranges
•Broad range of system platforms for every lab size with consistent patient results
…for streamlined lab organization with efficiency and cost gains
COBAS, LIFE NEEDS ANSWERS and ELECSYS
are trademarks of Roche.
All other trademarks are the property of their respective owners.
References
©2011 Roche
2 Revello, M.G., et al. (2009). Evaluation of fully automated assays for the detection of Cytomegalovirus
CH-6343 Rotkreuz
Switzerland
www.cobas.com
3 Maudry, A. et al. (2009). Bicentric evaluation of six anti-toxoplasma immunoglobulin G (IgG) automated
1 Grangeot-Keros, L., et al. (2010). Innovative Elecsys CMV IgM assay design using recombinant
antigens reduces significantly the detection of mature anti-CMV IgM antibodies. ECCMID conference. Vienna, Austria.
IgM and IgG antibodies on the Elecsys immunoassay system. ECCMID conference. Helsinki, Finland.
immunoassays and comparison to the Toxo II IgG western blot, Clin Vaccine Immunol. 16(9). 1322-6.
4 Köhler, S. et al. (2008). Evaluation of Fully Automated Assays for the Detection of Anti-Toxoplasma IgM
and IgG Antibodies on the Elecsys® Immunoassay System. Toxoplasma Centennial Congress. Brazil.
Elecsys® Toxo IgG
Electro-chemiluminescence immunoassay (ECLIA)
for the quantitative in-vitro determination of
IgG-antibodies against Toxoplasma gondii in
serum and plasma
Indication
Toxoplasmosis is a common infection caused by the protozoon Toxoplasma gondii. The infection is mainly acquired by ingestion of food
or water that is contaminated with mature oocysts shed by cats or by undercooked meat containing tissue cysts. In healthy individuals
primary, acute infection is mostly a subclinical or even asymptomatic process and turns chronic, usually persisting silently for life. However, reactivation in immunocompromized people is frequently associated with severe clinical consequences. In case of primary maternal
infection with T. gondii during pregnancy the parasite can be transmitted vertically. Possible consequences include miscarriage, still birth,
malformations, inflammations, sensorial defects, retardations. If not present at birth they may develop later in life. With gestational
age the probability of fetal infection increases, while the risk of severe clinical manifestations decreases. Early drug therapy in acute
infection during pregnancy can prevent or ameliorate congenital damage. The diagnosis of T. gondii infection usually starts with the
detection of anti-Toxoplasma IgG and IgM antibodies. The presence of IgG-antibodies is indicative of an acute or chronic infection.
The diagnosis of acute acquired infection during pregnancy is established by a seroconversion or a significant rise in antibody titers
(IgG and/or IgM) in serial samples. Often a Toxoplasma IgG avidity test is performed to collect additional information.
Test principle: one-step double antigen sandwich (DAGS) assay (testing time 18 min)
Ru
Ru
Biotinylated
recombinant SAG1
Sample
anti-SAG1 IgG
Ruthenylated
recombinant SAG1
Step 1 (9 minutes):
10 μL of the patient sample are incubated with a
mix of biotinylated and ruthenylated monomeric
SAG1. In the presence of corresponding IgG antibodies, double
antigen sandwich immune comBiotinylated
recombinant
SAG1 antibodies do not
plexes are formed.
IgM-class
form stable immune complexes with a monomeric
antigen due to their typically low paratope
affinity.
9 min
Ru
Ru
Sample
anti-SAG1
IgG
9 min
Ruthenylated
recombinant
SAG1
Ru
9 min
Ru
Measurement
Streptavidin-coated
microparticle
Step 2 (9 minutes):
After the addition
of streptavidincoated paramagnetic
microparticles,
the
Strepatvidin
particlecomplexes bind
DAGS
to the solid phase via
biotin-streptavidin. Ru
Step 3 (measurement):
The reagent mixture is transferred to the measuring
cell, where the microparticles are fixed to the electrode
surface by magnetic action. The unbound substances
are subsequently removed. Luminescence is then
induced by applying a voltage and measured with a
photomultiplier. The signal yield depends on the properties
of the antibodies in the sample.
9 min
Measurement
Ru
Elecsys® Toxo IgG test characteristics
Testing time
18 min
Test principle
One-step double antigen sandwich assay
Calibration
2-point
Traceability
3rd international standard /(TOXM), NIBSC, UK
Interpretation
Non-reactive: <1 IU/mL
Indeterminate: ≥1 – 30 IU/mL
Reactive: ≥30 IU/mL
Sample material
Serum, Li-heparin, K3-EDTA, Na-citrate plasma
Sample volume
10 μL
Total imprecision (NCCLS)
cobas e 411 analyzer, Elecsys® 2010 analyzer: 2.7 – 4.0 %
cobas e 601 / e 602 module, E170:
3.0 – 5.7 %
100 % (n = 317)
99.5 % (n = 192)
100 % (n = 220)
100 % (n = 188)
99.8 % (n = 626)
98.8 % (n = 242)
100 % (n = 159)
99.0 % (n = 202)
97.8 % in a collective of 226 potentially cross-reacting samples
Analytical specificity
Suggested Toxoplasma gondii serologic diagnostic algorithm in immunocompetent individuals
Start
Perform
Toxo IgG/IgM tests
IgG neg.
IgM neg.
IgG pos.
IgM neg.
IgG neg.
IgM pos.
IgG pos.
IgM pos.
Toxo IgG
avidity
Intermediate
low
No
immunity
Acquired
immunity
Avoid
primary infection
Past
infection likely
Beginning
infection
Repeat testing
~3 weeks later
Stop
COBAS, COBAS E, LIFE NEEDS ANSWERS
©2011 Roche
CH-6343 Rotkreuz
Switzerland
www.cobas.com
Repeat IgG test
~3 weeks later
Infection
> 4 months ago
Increasing
(2–4 fold
increase)
Toxo IgG
titer
stable
Repeat testing
during pregnancy
Start
Unspecific
IgM
Infection > 2
months before 1st
sample
•Remington, J.S., McLeod, R., Desmonts, G.
Recent infection
< 2 months before
1st sample
Further action
may be required
Start
References
high
Order information
(2001). Toxoplasmosis, 205-346. in J.S. Rem-
Elecsys® Toxo IgG
100 tests
04618815
ington & J.O. Klein (ed.), Infectious Diseases
PreciControl
Toxo IgG 1 & 2
8 x 1 mL each
04618823
of the Fetus and Newborn Infant, 5th ed., W.B.
Saunders, Philadelphia, Pa.
•Meek, B., van Gool, T., Gilis, H., Peek, R. (2001).
Diluent Universal
16 mL
11732277
Dissecting the IgM antibody response during
Diluent Universal
32 mL
03183971
CalSet vials, empty
2 x 56
11776576
the acute and latent phase of toxoplasmosis.
Diagn Microbiol Infect Dis 41: 131-7.
Elecsys® Toxo IgM
for the qualitative in-vitro determination of
IgM-antibodies against Toxoplasma gondii in
serum and plasma
Indication
Toxoplasmosis is a common infection caused by the protozoon Toxoplasma gondii. The infection is mainly acquired by ingestion of food
or water that is contaminated with mature oocysts shed by cats or by undercooked meat containing tissue cysts. In healthy individuals
primary, acute infection is mostly a subclinical or even asymptomatic process and turns chronic, usually persisting silently for life. However, reactivation in immunocompromized people is frequently associated with severe clinical consequences. In case of primary maternal
infection with T. gondii during pregnancy the parasite can be transmitted vertically. Possible consequences include miscarriage,
still birth, malformations, inflammations, sensorial defects, retardations. If not present at birth they may develop later in life. With
gestational age the probability of fetal infection increases, while the risk of severe clinical manifestations decreases. Early drug
therapy in acute infection during pregnancy can prevent or ameliorate congenital damage. The diagnosis of T. gondii infection usually starts with the detection of anti-Toxoplasma IgG and IgM antibodies. The presence of Toxo IgM antibodies is presumptive of an
acute, recent or reactivated Toxoplasma infection. The diagnosis of acute acquired infection during pregnancy is established by a
seroconversion or a significant rise in antibody titers (IgG and/or IgM) in serial samples. Often a Toxoplasma IgG avidity test is
performed to collect additional information.
Test principle: μ-capture assay (testing time 18 min)
Ru
Ru
Ru
Sample
anti-Toxo
IgM
Ru
Ruthenylated
recombinant
polymeric SAG1
Step 1 (9 minutes):
10 μL of the patient sample are
prediluted and incubated with
ruthenylated recombinant polymeric SAG1. Anti-Toxo IgM forms
a stable immune complex with this
antigen due to multipoint binding.
9 min
Ru
Biotinylated
anti-human-IgM
Step 2 (9 minutes):
Streptavidin-coated paramagnetic microparticles
are bound to the immune
complex via biotinylated
anti-human-IgM.
Ru
Ru
9 min
Ru
Ru
Measurement
Streptavidin-coated
microparticle
The reagent mixture is transferred to the measuring cell, where
the microparticles are fixed to the electrode surface by magnetic
action. The unbound substances are subsequently removed.
Luminescence is then induced by applying a voltage and measured with a photomultiplier. The signal yield depends on the
properties of the antibodies in the sample.
Elecsys® Toxo IgM test characteristics
Testing time
18 min
Test principle
μ-capture assay
Cut-off
Automatically calculated from 2 calibrators
Interpretation
Non-reactive: <0.8 COI
Indeterminate: ≥0.8 – 1.0 COI
Reactive: ≥1.0 COI
Sample material
Serum, Li-heparin, K3-EDTA, Na-citrate plasma
Sample volume
10 μL
Total imprecision
cobas e 411 analyzer, Elecsys® 2010 analyzer: 2.5 - 5.4 %
1.6 - 2.4 %
95.3 % (n = 170)
98.8 % (m = 84)
98.9 % (n = 602)
99.7 % (n = 295)
Suggested Toxoplasma gondii serologic diagnostic algorithm in immunocompetent individuals
Start
Perform
Toxo IgG/IgM tests
IgG neg.
IgM neg.
IgG pos.
IgM neg.
IgG neg.
IgM pos.
IgG pos.
IgM pos.
Toxo IgG
avidity
Intermediate
low
No
immunity
Acquired
immunity
Avoid
primary infection
Past
infection likely
Beginning
infection
Repeat testing
~3 weeks later
Stop
©2011 Roche
CH-6343 Rotkreuz
Switzerland
www.cobas.com
Repeat IgG test
~3 weeks later
Infection
> 4 months ago
Increasing
(2–4 fold
increase)
Toxo IgG
titer
stable
Repeat testing
during pregnancy
Start
Unspecific
IgM
Infection > 2
months before 1st
sample
•Remington, J.S., McLeod, R., Desmonts, G.
Recent infection
< 2 months before
1st sample
Further action
may be required
Start
References
high
Order information
(2001). Toxoplasmosis, 205-346. in J.S. Rem-
Elecsys® Toxo IgM
100 tests
04618858
ington & J.O. Klein (ed.), Infectious Diseases
PreciControl
Toxo IgM 1 & 2
8 x 0.67 mL
each
04618866
•Meek, B., van Gool, T., Gilis, H., Peek, R. (2001).
Diluent Universal
16 mL
11732277
Dissecting the IgM antibody response during
Diluent Universal
32 mL
03183971
CalSet vials, empty
2 x 56
11776576
of the Fetus and Newborn Infant, 5th ed., W.B.
Saunders, Philadelphia, Pa.
the acute and latent phase of toxoplasmosis.
Diagn Microbiol Infect Dis 41: 131-7.
Elecsys® Rubella IgG
IgG-antibodies against rubella virus in
serum and plasma
Indication
Rubella virus causes German measles, a mild rash disease which commonly occurs during childhood. Postnatal infection is
rarely associated with complications. However, primary infection mainly during early pregnancy is a serious condition, as vertical
transmission of the virus may cause miscarriages or congenital rubella syndrome (CRS). CRS includes blindness, deafness,
congenital heart disease and mental retardation. Today’s vaccination programs have considerably reduced the incidence of
acute rubella and CRS. The presence of IgG antibodies to rubella virus indicates a previous exposure either by vaccination or
prior rubella infection and suggests immunity. Seroconversion of specific rubella antibodies or a significant rise of the IgG titer
strongly supports the diagnosis of acute rubella infection. The quantitative determination of specific IgG is used to determine
the immune status to rubella.
Test principle: one-step double antigen sandwich (DAGS) assay / g-capture assay (testing time 18 min)
Sample
anti-rubella IgG
Biotinylated E1
Ruthenylated E1
Streptavidin-coated
microparticle
Ru
Ru
Ru
9 min
9 min
Measurement
Ru
Biotinylated antihuman-IgG antibody
Rubella-like Ruthenylated
particle
anti-rubella Ab-fragment
Step 1 (9 minutes):
incubated with monoclonal antihuman IgG antibody, rubella-like
particles (RLP), a ruthenylated
monoclonal anti-rubella antibody
(Ab) fragment, biotinylated E1
and ruthenylated E1.
Step 2 (9 minutes):
After the addition of streptavidin-coated paramagnetic
microparticles, the immune
complexes bind to the solid
phase via biotin-streptavidin.
Ru
Ru
The reagent mixture is transferred to the measuring cell,
where the microparticles are fixed to the electrode surface by
magnetic action. The unbound substances are subsequently
removed. Luminescence is then induced by applying a voltage
and measured with a photomultiplier. The signal yield depends
on the rubella IgG titer in the sample.
Elecsys® Rubella IgG test characteristics
Testing time
18 min
Test principle
One-step double antigen sandwich assay (DAGS) g-capture assay
Calibration
2-point
Traceability
1st international standard, human anti-rubella Ig RUBI-1-94 (NIBSC)
Interpretation
Non-reactive: <10 IU/mL
Reactive: ≥10 IU/mL
Sample material
Serum, Li-heparin, K 3-EDTA, Na-citrate plasma
Sample volume
10 μL
Total imprecision
cobas e 411 analyzer, Elecsys® 2010 analyzer: 3.4 – 6,4 %
cobas e 601 / e 602 module, E170: 3.2 – 4.3 %
100 % (n = 514)
99.9 % (n = 978)
100 % (n = 120)
100 % (n = 20)
97.4 % (n = 38)
100 % (n = 18)
100 % (n = 78)
100 % (n = 769)
Serological profile after rubella infection
Virus in throat
IgG
IgM
1024
rash
64
32
16
50
8
4
0
8
6
4
2 1
1
Days before
2
4
6
8
10
12
14
1
2
1
Months
2
3
10
0
Years
Order information
©2011 Roche
CH-6343 Rotkreuz
Switzerland
www.cobas.com
Elecsys® Rubella IgG
100 tests
04618793
PreciControl Rubella IgG 1 & 2
8 x 1 mL each
04618807
Diluent Universal
16 mL
11732277
Diluent Universal
32 mL
03183971
CalSet vials, empty
2 x 56
11776576
Antibody titer
Virus isolation
[%]
100
Elecsys® Rubella IgM
IgM-antibodies against rubella virus in
serum and plasma
Indication
Rubella virus causes German measles, a mild rash disease which commonly occurs during childhood. Postnatal infection is
rarely associated with complications. However, primary infection mainly during early pregnancy is a serious condition, as vertical
transmission of the virus may cause miscarriages or congenital rubella syndrome (CRS). CRS includes blindness, deafness,
congenital heart disease and mental retardation. Today’s vaccination programs have considerably reduced the incidence of
acute rubella and CRS. The presence of IgM antibodies to rubella virus usually indicates an acute infection, but may also be
unspecific or persistent. Seroconversion of specific rubella antibodies strongly supports the diagnosis of acute rubella infection.
Sample
anti-rubella IgM
Ruthenylated
anti-rubella
Ru
9 min
Biotinylated
anti-human-IgM
Rubella-like
particle
Step 1 (9 minutes):
prediluted and incubated with
biotinylated anti-human IgM
and rubella-like particles (RLP).
Anti-rubella IgM forms stable
immune complexes with RLPs
due to multipoint binding.
Ru
9 min
Measurement
Streptavidin-coated
microparticle
Step 2 (9 minutes):
Ruthenylated rubella-specific
antibodies are added together
with streptavidine-coated
paramagnetic microparticles.
The antibodies bind to free
sites on the RLP, while the
microparticles are bound to
the complex via the biotin on
the capture antibody.
on the properties of the antibodies in the sample.
Elecsys® Rubella IgM test characteristics
Testing time
18 min
Test principle
μ-capture assay
Cut-off
Interpretation
Reactive: ≥1.0 COI
Sample material
Serum, Li-heparin, K 3-EDTA, plasma
Sample volume
10 μL
Total imprecision
cobas e 601 / e 602 module, E170: 2.7 – 10.9 %
Sensitivity in early acute infection (< 30 days)
80 % (n = 84)
96 % (n = 25)
98.7 % (n = 554)
99.0 % (n = 993)
98.99 % in 390 potentially cross-reacting samples
Serological profile after rubella infection
Virus in throat
IgG
IgM
1024
rash
64
32
16
50
8
4
0
8
6
4
2 1
1
Days before
2
4
6
8
10
12
14
1
2
1
Months
2
3
10
0
Years
Order information
©2011 Roche
CH-6343 Rotkreuz
Switzerland
www.cobas.com
Elecsys® Rubella IgM
100 tests
04618831
PreciControl Rubella IgM 1 & 2
4 x 1 mL each
04618840
Diluent Universal
16 mL
11732277
Diluent Universal
32 mL
03183971
CalSet vials, empty
2 x 56
11776576
Antibody titer
Virus isolation
[%]
100
Elecsys® CMV IgG
IgG-antibodies against CMV in serum and plasma
Indication
Cytomegalovirus (CMV) is a herpes virus that is ubiquitous in all human populations. Transmission occurs mainly through
incorporation of virus-loaded body fluids. The global prevalence of seropositive adults ranges from 40 – 100 %. In healthy
individuals primary, acute infection is mostly a subclinical or even asymptomatic process and turns latent. Reactivation in
immunocompromized people is frequently associated with severe clinical consequences. In case of primary maternal infection
with CMV during pregnancy the virus can be transmitted vertically. Consequences include severe fetal damage, growth and
mental retardations, jaundice and CNS abnormalities. If unsuspicious at birth, hearing defects or cognitive deficits may develop
later in life. There is currently no generally accepted therapy available. The diagnosis of CMV infection usually starts with the
detection of anti-CMV IgG and IgM antibodies. The detection of CMV IgG antibodies is an indicator of a past infection. The
time of infection can roughly be estimated by a CMV IgG avidity test. Seroconversion in CMV IgG shows a recent infection.
Test principle: one-step double antigen sandwich (DAGS) assay (testing time 18 min)
Streptavidin-coated
microparticle
Sample
anti-CMV IgG
Ru
Biotinylated
recombinant
pp150, pp28, p52, p38
9 min
Ru
9 min
Ru
Measurement
Ruthenylated
recombinant
pp150, pp28, p52, p38
Step 1 (9 minutes):
20 μL of the patient sample are incubated with a mix
of biotinylated and ruthenylated monomeric CMV
antigens. In the presence of corresponding IgG antibodies, double antigen sandwich immune complexes
are formed. Following a statistical distribution these
sandwiches can carry biotin and the ruthenium label
simultaneously. IgM-class antibodies do not form
stable immune complexes with a monomeric antigen
due to their typically low paratope affinity.
Step 2 (9 minutes):
After the addition
of streptavidincoated paramagnetic
microparticles, the
DAGS complexes bind
to the solid phase via
biotin-streptavidin.
The reagent mixture is transferred to the measuring cell, where the microparticles are fixed
to the electrode surface by magnetic action.
The unbound substances are subsequently
removed. Luminescence is then induced
by applying a voltage and measured with a
photomultiplier. The signal yield depends on
the properties of the antibodies in the sample.
Elecsys® CMV IgG test characteristics
Testing time
18 min
Test principle
One-step double antigen sandwich assay (DAGS)
Calibration
2-point
Interpretaton
Non-reactive: <0.5 U/mL
Indeterminate: 0.5 – 1.0 U/mL
Reactive:
≥1 U/mL
Sample material
Serum, Li-heparin, K 2-EDTA, K 3-EDTA, plasma
Sample volume
20 μL
Total imprecision
3.2 – 4.5 %
Agreement with a commercially available method
98.9 % (n = 532)
96.8 % (n = 616)
99.4 % (n = 520)
Suggested CMV serologic diagnostic algorithm in immunocompetent individuals
Start
Perform
CMV IgG/IgM tests
IgG neg.
IgM neg.
IgG neg.
IgM pos.
IgG pos.
IgM neg.
IgG pos.
IgM pos.
≤ 20 w
IgG
avidity
high
low to borderline
High risk of
transmission
No
immunity
Beginning
infection
Avoid
primary infection
Repeat testing
during pregnancy
Repeat testing
~3 weeks later
IgG
avidity
high
low to borderline
Acquired
immunity
Possibly
additional testing
IgG neg.
IgM neg.
Refer to 1st
trimester samples
Past
infection likely
Recidivation
possible
Maternal viremia
• Virus isolation
• Blood PCR
IgG pos. / IgM pos.
Low avidity
IgG pos.
IgM neg.
Fetal well-being
• Ultrasound
• MRI
IgG neg.
IgM pos.
low risk of
transmission
Invasive testing
• Amniocentesis
• Cordocentesis
Start
Gestational
age
> 20 w
Stop
References
©2011 Roche
•Lazzarotto, T., Gabrielli, L., Lanari, M., et al. (2004).
CH-6343 Rotkreuz
Switzerland
www.cobas.com
•Guerra, B., Simonazzi, G., Banfi, A., et al. (2007).
•Munro, S.C., Hall, B., Whybin, L.R., et al. (2005).
J Clin Microbiol 43(9): 4713-8.
Hum Immunol 65: 410-415.
Am J Obstet Gynecol 196: 221-223.
•Duff, P. (2007). A thoughtful algorithm for the
accurate diagnosis of primary CMV infection in
pregnancy. Am J Obstet Gynecol 196: 196-197.
IgG pos. / IgM pos.
High avidity
Stop
Order information
Elecsys® CMV IgG
100 tests
04784596
PreciControl
CMV IgG 1 & 2
8 x 1 mL each
04784600
Diluent Universal
16 mL
11732277
Diluent Universal
32 mL
03183971
CalSet vials, empty
2 x 56
11776576
Elecsys® CMV IgM
IgM-antibodies against CMV in serum and plasma
Indication
Cytomegalovirus (CMV) is a herpes virus that is ubiquitous in all human populations. Transmission occurs mainly through
incorporation of virus-loaded body fluids. The global prevalence of seropositive adults ranges from 40 – 100 %. In healthy
individuals primary, acute infection is mostly a subclinical or even asymptomatic process and turns latent. Reactivation in
immunocompromized people is frequently associated with severe clinical consequences. In case of primary maternal infection
with CMV during pregnancy the virus can be transmitted vertically. Consequences include severe fetal damage, growth and
mental retardations, jaundice and CNS abnormalities. If unsuspicious at birth, hearing defects or cognitive deficits may develop
later in life. There is currently no generally accepted therapy available. The diagnosis of CMV infection usually starts with the
detection of anti-CMV IgG and IgM antibodies. Samples being reactive for IgM antibodies indicate an acute, recent or reactivated
infection. A positive IgM result in combination with a low avidity index for IgG is an indication of a primary CMV infection within
the last 4 months. Seroconversion to CMV IgM also establishes the diagnosis of a recent CMV infection.
Sample
anti-CMV IgM
Ru
Ru
9 min
Biotinylated
anti-human-IgM
Step 1 (9 minutes):
10 μL of the patient sample
are prediluted and incubated
with biotinylated anti-humanIgM.
Ru
Ru
Ruthenylated
recombinant multimeric
pp150, p52
Step 2 (9 minutes):
Ruthenylated multimeric pp150
and p52 is added together with
streptavidine-coated paramagnetic microparticles. Anti-CMV
IgM forms stable immune complexes with these antigens due
to multipoint binding which are
bound to the solid phase via
biotin-straptavidin.
9 min
Ru
Ru
Measurement
Streptavidin-coated
microparticle
on the properties of the antibodies in the sample.
Elecsys® CMV IgG test characteristics
Testing time
18 min
Test principle
μ-capture assay
Cut-off
Interpretaton
Reactive:
≥1.0 COI
Sample material
Serum, Li-heparin, K 2-EDTA, K 3-EDTA, plasma
Sample volume
10 μL
Total imprecision
3.8 – 6.1 %
Sensitivity
93.0 % (n = 114)
96.5 % (n = 57)
91.2 % (n = 34)
93.1 % (n = 29)
92.3 % (n = 52)
Specificity in routine samples
98.8 % (n = 501)
97.1 % (n = 591)
97.0 % (n = 507)
92.3 % in 413 potentially cross-reacting samples
Start
Perform
CMV IgG/IgM tests
IgG neg.
IgM neg.
IgG neg.
IgM pos.
IgG pos.
IgM neg.
IgG pos.
IgM pos.
≤ 20 w
IgG
avidity
high
low to borderline
High risk of
transmission
No
immunity
Beginning
infection
Avoid
primary infection
Repeat testing
during pregnancy
Repeat testing
~3 weeks later
IgG
avidity
high
low to borderline
Acquired
immunity
Possibly
additional testing
IgG neg.
IgM neg.
Refer to 1st
trimester samples
Past
infection likely
Recidivation
possible
Maternal viremia
• Virus isolation
• Blood PCR
IgG pos. / IgM pos.
Low avidity
IgG pos.
IgM neg.
Fetal well-being
• Ultrasound
• MRI
IgG neg.
IgM pos.
low risk of
transmission
Invasive testing
• Amniocentesis
• Cordocentesis
Start
Gestational
age
> 20 w
Stop
References
©2011 Roche
•Lazzarotto, T., Gabrielli, L., Lanari, M., et al. (2004).
CH-6343 Rotkreuz
Switzerland
www.cobas.com
•Guerra, B., Simonazzi, G., Banfi, A., et al. (2007).
•Munro, S.C., Hall, B., Whybin, L.R., et al. (2005).
J Clin Microbiol 43(9): 4713-8.
Hum Immunol 65: 410-415.
Am J Obstet Gynecol 196: 221-223.
•Duff, P. (2007). A thoughtful algorithm for the
accurate diagnosis of primary CMV infection in
pregnancy. Am J Obstet Gynecol 196: 196-197.
IgG pos. / IgM pos.
High avidity
Stop
Order information
Elecsys® CMV IgM
100 tests
04784618
PreciControl
CMV IgM 1 & 2
8 x 1 mL each
04784626
Diluent Universal
16 mL
11732277
Diluent Universal
32 mL
03183971
CalSet vials, empty
2 x 56
11776576
CMV IgG Avidity
for the determination of the avidity of IgG
antibodies to CMV in human serum and plasma
Indication
Sample being reactive for anti-CMV IgG and IgM may indicate an acute, recent or reactivated infection. Since symptomatic congenital
infection in the fetus is mostly due to intrauterine transmission following primary maternal infection, differential diagnosis of primary
versus recurrent infection, unspecific IgM or persistence of CMV-specific IgM antibody is crucial for the management of such a
pregnancy. Antibodies produced at an early stage during primary response have lower antigen avidity than those produced at a later
stage. Since low avidity is encountered up to approx. 18–20 weeks after the onset of symptoms in immunocompetent patients and
is subject to interindividual variation, avidity testing should be performed at an early stage of gestation. A low-avidity anti-CMV IgG
detected before the 16th–18th week of pregnancy, together with a positive anti-CMV IgM, is strong evidence of a recent primary
infection, whereas a high avidity index would be considered a good indicator of past infection. A high avidity result later in gestation
cannot rule out a primary infection at an earlier stage of the pregnancy.
Reference - Test principle: one-step double antigen sandwich assay (DAGS, assay time 18 min)
Sample high avidity Biotinylated recombinant
CMV-specific antigens
anti-CMV IgG
Streptavidin-coated
microparticle
Ru
Ru
9 min
Sample low avidity
anti-CMV IgG
9 min
Ru
Ru
Ru
Ru
Measurement
Ru
Ru
Ru
Ruthenylated recombinant
Step 1 (9 minutes):
20 μL of the patient sample are incubated with a mix of
biotinylated and ruthenylated monomeric CMV antigens.
Double antigen sandwich immune complexes are formed
in the presence of corresponding IgG antibodies.
The reagent mixture is transferred
to the measuring cell, where the
microparticles are fixed to the electrode surface by magnetic action.
Step 2 (9 minutes):
After the addition of streptavidincoated paramagnetic microparticles,
the DAGS complexes bind to the solid
phase via biotin-streptavidin.
Avidity - Test principle: one-step double antigen sandwich assay under chaotropic conditions (DAGS, assay time 18 min)
Sample high avidity
anti-CMV IgG
Biotinylated recombinant
Chaotropic reagent
Streptavidin-coated
microparticle
Ru
9 min
Ru
Sample low avidity
anti-CMV IgG
9 min
Sample low avidity
early anti-CMV IgG
Ru
Ru
Ru
Ruthenylated
recombinant
Sample low
avidity
early anti-CMV IgG
Ru
Ru
Measurement
CMV-specific antigen
Step 1 (9 minutes):
50µL of the patient sample are mixed with 50µL of DilCMVAv. 20 μL of the diluted patient sample are incubated with a mix of biotinylated and ruthenylated monomeric CMV antigens. Double
Biotinylated
recombinant recombinant
Sample high
avidity
Strepatvidin-coated
Strepatvidin-coated
Biotinylated
Sample
high
avidity
antigen
sandwich
immune
complexes are formed
in the presence microparticle
of high-avidity
IgG antibodies.
CMV-specific
antigens
anti-CMV IgG
microparticle
Ru
CMV-specific
antigens
anti-CMV IgG
IgG of low avidity cannot form stable immune-complexes under the prevailing conditions.
Ru
Ru
Ru
9 min
Ru
Ru
9 minu
R
9 min
Ru
Ru
Ru
Step 2
(9 minutes):
See above
9 min
Ru
Step 3
(measurement):
See above
Ru
Measurement
Measurement
Ru
Ru
Ru
Ru
Result calculation
The analyzer automatically calculates the analyte concentration of each sample in U/mL for both measurements (reference measurement
and DilCMVAv treated measurement). Calculation of avidity [Avi %]:
result DilCMVAv treated measurement [U/mL]
Avidity [Avi %] =
x 100 %
result reference measurement [U/mL]
CMV IgG Avidity test characteristics
Assay time
2 x18 min (in parallel)
Test principle
One-step double antigen sandwich assay (DAGS) under various buffer
conditions
Calibration
2-point
Interpretation
Low avidity: <45.0 Avi %
Grey zone: 45.0 – 54.9 Avi %
High avidity: ≥55.0 Avi %
Sample material
Serum, Li-heparin, K 2-, K 3-EDTA plasma
Sample volume
1x 20 μL and 1x 50 µL
Intermediate imprecision
1.5 – 3.8 %
Clinical sensitivity [95% confidence limit]
96.1 % [89.0-99.2]n = 77, diagnostic
93.4 % [86.9-97.3]n = 106, pregnant
Clinical specificity [95% confidence limit]
90.9 % [78.3-97.5]n = 44, diagnostic
100.0 %[93.0-100] n = 51, pregnant
Start
Perform
CMV IgG/IgM tests
IgG neg.
IgM neg.
IgG neg.
IgM pos.
IgG pos.
IgM neg.
IgG pos.
IgM pos.
low to borderline
High risk of
transmission
No
immunity
Beginning
infection
Avoid
primary infection
Repeat testing
during pregnancy
Repeat testing
~3 weeks later
low to borderline
Gestational
age
> 20 w
IgG
avidity
high
Acquired
immunity
Possibly
additional testing
IgG neg.
IgM neg.
Refer to 1st
trimester samples
Past
infection likely
Recidivation
possible
Maternal viremia
• Virus isolation
• Blood PCR
IgG pos. / IgM pos.
Low avidity
IgG pos.
IgM neg.
Fetal well-being
• Ultrasound
• MRI
IgG neg.
IgM pos.
low risk of
transmission
Invasive testing
• Amniocentesis
• Cordocentesis
Start
≤ 20 w
IgG
avidity
high
Stop
IgG pos. / IgM pos.
High avidity
Stop
COBAS, COBAS E and LIFE NEEDS ANSWERS
are trademarks of Roche.
©2011 Roche
CH-6343 Rotkreuz
Switzerland
www.cobas.com
References
• Munro, S.C., Hall, B., Whybin, L.R., et al. (2005). J Clin Microbiol 43(9), 4713-4718.
• Lazzarotto, T., Gabrielli, L., Lanari, M., et al. (2004). Hum Immunol 65, 410-415.
• Guerra, B., Simonazzi, G., Banfi, A., et al. (2007). Am J Obstet Gynecol 196, 221-223.
• Duff, P. (2007). A thoughtful algorithm for the accurate diagnosis of primary CMV infection in
pregnancy. Am J Obstet Gynecol 196, 196-197.
Elecsys® HSV-1 IgG
for the in-vitro determination of IgG antibodies
to Herpes Simplex Virus type 1 (HSV-1)
Indication
Herpes simplex virus 1 (HSV-1) is mainly transmitted via social contacts during childhood, but also sexually later in life. The prevalence
of HSV-1 infections in the general population is estimated to be around 70-90%. A primary infection with HSV is often associated
with the development of painful watery blisters that release an infectious exudate. Typical sites are the mouth, lips (herpes labials)
or genitals (herpes genitalis). Recurrent skin lesions are the hallmark of HSV pathogenesis. Orofacial herpes manifestations are
usually caused by HSV-1, whereas genital herpes is mainly caused by HSV-2. HSV-1 and HSV-2 can also be transmitted vertically
before birth or perinatally during delivery. Such infections may have severe, if not fatal, consequences for the fetus/newborn. Subclinical viral shedding and unrecognized infections seem to be major factors in transmission.
Test principle: Double antigen sandwich assay (DAGS, testing time 18 min)
Streptavidin-coated
microparticle
Sample
anti-HSV-1
Ru
Biotinylated
HSV-1 antigen
9 min
Ru
9 min
Ru
Measurement
Ruthenylated
HSV-1 antigen
Step 1 (9 minutes):
20 μL of the patient sample are incubated
with a mix of biotinylated and ruthenylated HSV-1 antigens. Double antigen
sandwich immune complexes are formed
in the presence of corresponding antibodies.
Step 2 (9 minutes):
After the addition of streptavidin-coated
paramagnetic microparticles, the DAGS
complexes bind to the solid phase via
The reagent mixture is transferred to
the measuring cell, where the microparticles are fixed to the electrode surface
by magnetic action. The unbound substances are subsequently removed by
ProCell. Luminescence is then induced
by applying a voltage and measured with
a photomultiplier.
!
Elecsys® HSV-1 IgG characteristics
Analyzer compatibility
cobas e 601 module, cobas e 602 module, cobas e 411 analyzer,
MODULAR ANALYTICS E170, Elecsys® 2010 analyzer
Assay time
18 min
Test principle
DAGS assay
Cut-off
automatically calculated from 2 calibrators
Sample material
Serum, Li-heparin plasma, K2-EDTA plasma, K3-EDTA plasma
Sample volume
20 μL
Total imprecision
1.6 – 2.2 %
Expected values
Gray-zone:
≥0.6 - <1.0 COI
Reactive:
≥1.0 COI
Quality control procedure
For quality control, use Elecsys® PreciControl HSV. The controls 1 and
2 should be run as single determinations at least once every 24 hours
when the test is in use, once per reagent kit, and after every calibration.
On-board stability
28 days
Elecsys® HSV-1 IgG key perfomance data
B.Sexually active adults (n = 300)
Elecsys
Elecsys
Comparator
Comparator
A.Pregnancy screening (n = 400)
Elecsys
Comparator
100.0 %
Relative
specificity
92.4 %
95.6 %
Relative
sensitivity
100.0 %
0
10
20
30
40
50
60
70
80
90
100
100.0
100.0
% %
Relative
Relative
specificity
specificity
92.692.6
% %
99.499.4
% %
Relative
Relative
sensitivity
sensitivity
100.0
% %
100.0
0 10
0 10
20 20
30 30
40 40
50 50
60 60
70 7080 80
90 90100 100
Frozen samples analyzed by commercially available HSV-1 IgG assays were tested with the HSV-1 IgG Elecsys®. Resolution of
discordant samples was done using a commercially available immunoblot assay. Gray-zone samples as well as inconclusive
samples (i.e. concordant results with Elecsys® HSV-1 IgG and comparison method but discordant immunoblot results) were
excluded from calculation.
Elecsys
Relative
specificity
Comparator
HSV 1
100.0 %
92.4 %
HSV 2
99.7 %
99.19 %
HSV 1
Relative
sensitivity
COBAS, COBAS
HSV 2E, LIFE NEEDS ANSWERS, ELECSYS
and MODULAR are trademarks of Roche.
©2011 Roche
0 10
CH-6343 Rotkreuz
Switzerland
www.cobas.com
20
30
40
50
60
70
95.6 %
100.0 %
92.6 %
92.6 %
80
90
100
Order information
Elecsys
Comparator
Elecsys® HSV-1 IgG
100 tests
HSV 1
®
Elecsys
PreciControl HSV
For 4 x 3 mL
Relative
specificity
Control
Set Vials, empty
2 x 56
HSV 2
Relative
sensitivity
05572185 190
100.0 %
05572207 92.6
190 %
03142949 12299.6 %
100.0 %
HSV 1
HSV 2
86.9 %
0 10
20
30
40
50
60
70
80
99.4 %
100.0 %
100.0 %
90
100
Elecsys® HSV-2 IgG
for the in-vitro determination of IgG antibodies
to Herpes Simplex Virus type 2 (HSV-2)
Indication
Herpes simplex viruses 2 (HSV-2) are usually transmitted sexually by asymptomatic shedding and account for approximately 80%
of all cases of genital herpes. The prevalence of HSV-2 infections in the general population is estimated to be around 17-25%, but
can be higher in specific risk groups like AIDS-patients and female sex workers. HSV-2 infection is a risk factor for HIV transmission
and is associated with an increased risk of acquisition of HIV. Neonatal herpes has the most severe implications and is usually
acquired during the intrapartum period through exposure in the genital tract. Subclinical viral shedding and unrecognized infections
seem to be major factors in transmission. Genital HSV infection is frequently not recognized and diagnosis based on the clinical
presentation alone has a low sensitivity. Type-specific serologic tests allow the identification of silent carriers of HSV-2 infection in
patients with or without pre-existing antibodies to HSV-1.
Test principle: Double antigen sandwich assay (DAGS, testing time 18 min)
Streptavidin-coated
microparticle
Sample
anti-HSV-2
Ru
Biotinylated
HSV-2 antigen
9 min
Ru
9 min
Ru
Measurement
Ruthenylated
HSV-2 antigen
Step 1 (9 minutes):
20 μL of the patient sample are incubated
with a mix of biotinylated and ruthenylated
HSV-2 antigens. Double antigen sandwich
immune complexes are formed in the
presence of corresponding antibodies.
Step 2 (9 minutes):
After the addition of streptavidin-coated
paramagnetic microparticles, the DAGS
complexes bind to the solid phase via
The reagent mixture is transferred to
the measuring cell, where the microparticles are fixed to the electrode surface
by magnetic action. The unbound substances are subsequently removed by
ProCell. Luminescence is then induced
by applying a voltage and measured with
a photomultiplier.
Elecsys® HSV-2 IgG characteristics
Analyzer compatibility
cobas e 601 module, cobas e 602 module, cobas e 411 analyzer,
MODULAR ANALYTICS E170, Elecsys® 2010 analyzer
Assay time
18 min
Test principle
DAGS assay
Cut-off
automatically calculated from 2 calibrators
Sample material
Serum, Li-heparin plasma, K2-EDTA plasma, K3-EDTA plasma
Sample volume
20 μL
Total imprecision
1.8 – 2.0 %
Expected values
Gray-zone:
≥0.51 - <1.0 COI
Reactive:
≥1.0 COI
Quality control procedure
For quality control, use Elecsys® PreciControl HSV. The controls 1 and
2 should be run as single determinations at least once every 24 hours
when the test is in use, once per reagent kit, and after every calibration.
On-board stability
28 days
Elecsys® HSV-2 IgG key perfomance data
Elecsys
Elecsys
Comparator
Comparator
Elecsys
Comparator
99.7 %
Relative
specificity
99.2 %
92.6 %
Relative
sensitivity
10
20
30
40
50
60
70
80
90
100.0
% %
100.0
100.0
100.0
% %
Relative
Relative
sensitivity
sensitivity
92.6 %
0
99.699.6
% %
Relative
Relative
specificity
specificity
100
86.986.9
% %
0 10
0 10
20 20
30 30
40 40
50 50
60 60
70 7080 80
90 90100 100
Frozen samples analyzed by commercially available HSV-2 IgG assays were tested with the HSV-2 IgG Elecsys®. Resolution of
discordant samples was done using a commercially available immunoblot assay. Gray-zone samples as well as inconclusive
samples (i.e. concordant results with Elecsys® HSV-2 IgG and comparison method but discordant immunoblot results) were
excluded from calculation.
Order information
COBAS, COBAS E, LIFE NEEDS ANSWERS, ELECSYS
©2011 Roche
CH-6343 Rotkreuz
Switzerland
www.cobas.com
Elecsys® HSV-2 IgG
100 tests
Elecsys® PreciControl HSV
For 4 x 3 mL
05572207 190
Control Set Vials, empty
2 x 56
03142949 122
05572193 190
Elecsys® HSV-1 IgG and HSV-2 IgG
immunoassays
Type-specific assays for reliable diagnosis
and assessment of the immune status
Elecsys® HSV-1 IgG and HSV-2 IgG
immunoassays
Type-specific assays for reliable diagnosis
and assessment of the immune status
HSV-1 is mainly transmitted via social contacts during childhood, but also sexually later in life. Its prevalence in the general
population is around 70-90%. HSV-2 is usually transmitted sexually and has a prevalence of around 17-25% in the general
population. However, prevalence can be much higher in specific risk groups like AIDS-patients and female sex workers. Orofacial
herpes manifestations are usually caused by HSV-1, whereas genital herpes is mainly caused by HSV-2. HSV-1 and HSV-2 can
also be transmitted vertically before birth or perinatally during delivery. Such infections may have severe, if not fatal, consequences for the fetus/newborn. Subclinical viral shedding and unrecognized HSV-infections seem to be major factors in transmission.
Type-specific assays for reliable differentiation between HSV-1 and HSV-2
Two Elecsys® HSV IgG assays available:
•One for the detection of HSV-1 IgG and one for the detection of HSV-2 IgG
•Only type-specific serologic tests allow the identification of silent carriers infected with one subtype with or without
pre-existing antibodies to the other subtype
Advantages:
•Asymptomatic HSV-2 patients can be educated to recognize symptomatic disease
•HSV-2 transmission can be reduced by education of patients
•Allows treatment that is specific for either HSV-1 or HSV-2 infection
High specificity for less retesting in clinical routine and pregnancy screening
Comparator
Elecsys
Elecsys
Comparator
Comparator
Elecsys
Relative
specificity
Relative
sensitivity
HSV 1
100.0 %
92.4 %
HSV 2
99.7 %
99.2 %
HSV 1
95.6 %
100.0 %
92.6 %
92.6 %
HSV 2
0 10
20
30
40
50
60
70
80
90
100.0
% %
100.0
92.692.6
% %
HSVHSV
1 1
Relative
Relative
specificity
specificity
HSVHSV
2 2
HSVHSV
1 1
Relative
Relative
sensitivity
sensitivity
HSVHSV
2 2
100
99.699.6
% %
100.0
% %
100.0
99.499.4
% %
100.0
% %
100.0
100.0
% %
100.0
86.986.9
% %
0 10
20 20
30 30
40 40
50 50
60 60
70 7080 80
90 90
100 100
0 10
The word “relative” refers to comparing the results of the Elecsys® HSV-1 IgG and HSV-2 IgG assays with those of comparator assays. Resolution of discordant
samples was done using a commercially available immunoblot assay. Gray-zone samples as well as inconclusive samples were excluded from calculation.
Completing Roche´s TORCH portfolio
The comprehensive assay menu for consolidated pregnancy testing
Elecsys® 2010 analyzer, MODULAR ANALYTICS E170, cobas e 411 and cobas e 601 analyzers
Toxo IgG
Toxo Avidity*
CMV IgM
Rubella IgG
HSV-1 IgG
Toxo IgM
CMV IgG
CMV Avidity
Rubella IgM
HSV-2 IgG
*under development
COBAS, COBAS E, LIFE NEEDS ANSWERS, ELECSYS
©2011 Roche
CH-6343 Rotkreuz
Switzerland
www.cobas.com

Innovative assays for high testing efficiency

Transcription

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