TOXOPLASMOSIS AND RUBELLA

IN PREGNANCY

Eka Dina I.
 TOXOPLASMOSIS
Toxoplasmosis caused by the protozoan
parasite Toxoplasma gondii that obligate
intracellular parasite, 3 forms:
1. Oocyst : only in cat feces
2. Tachyzoite (rapidly dividing form observed in
the acute phase of infection)
3. Bradyzoite (slow growing form observed
within tissue cysts)
Prevalence 10-50 % of adults aged 15-45
years
Incidence of maternal infection during
pregnancy : 1-8 per 1000
 Clinical
Manifestation
Asymptomatic
Nonspecific : fatigue, fever, headache,
malaise, myalgia and
lymphadenopathy
20 % population has toxoplasmic
retinochoroiditis, resulting in high
levels of visual impairment
 Fetal Infection
Risk fetal infection increases steeply with
advancing gestational age
Presence serological markers not associated
with greater severity of congenital infection
Abnormal findings : intrahepatic densities,
increased thickness and hyperdensity of the
placenta, ascites, pericardial and pleural
effusions
Sonographic findings : intracranial
hyperechogenic foci/calcifications and
ventricular dilatation poor prognostic signs
Table : Risk of Toxoplasma gondii congenital infection
(transmission) and development of clinical signs in
offspring before age 3 years, according to gestational age
at maternal seroconversion (Goldstein E., 2008)
Table : Possible Signs and Symptoms of
Congenital Toxoplasmosis in Infancy and Later in
Life (Jones J., 2003)
 Diagnosis
Diagnose : serological tests and PCR
Detection T. gondii antibodies :
to establish pregnant woman has been
infected
to determine infection acquired recently or
distant past
Prenatal diagnosis :
- to change prenatal treatment from
spiramycin to pyrimethamine-sulfonamide
combination
- to terminate the pregnancy
 Diagnosis
When pregnant woman found infected with T. Gondii
then determine whether the fetus is infected by
Polymerase chain reaction (PCR) in amniotic fluid
PCR is the best method for diagnosing fetal infection
PCR should be considered :
have serological test results diagnostic/highly
suggestive infection acquired during
gestation/shortly before conception
have evidence fetal damage by ultrasonographic
(ventriculomegaly/hepatic/brain calcifications)
significantly immunosuppressed and at risk
reactivation of their latent infection (except AIDS)
 Diagnosis
Ultrasound for women with
suspected/diagnosed acute infection
Presence fetal abnormalities :
hydrocephalus, brain/hepatic
calcifications, splenomegaly, ascites
Table : Laboratory tests available for diagnosis of
toxoplasmosis during pregnancy and the distinguishing
features between serological testing (Goldstein E., 2008)
If IgM and IgG positive at 13 weeks of
gestation, probability infection after
conception is 1-3 %
Although high IgG avidity is hallmark latent
infection, low avidity is not diagnostic of
acute infection because it can persist for
years in some women
IgG avidity shifts from low to high avidity at
5 months after infection
Combination positive IgM and negative IgG
result, with both tests positive 2 weeks
later, infection occurring 2 weeks before
the first positive IgM result
 Diagnosis
Detection acute infection can performed
by detection IgM positivity and or >
increase of IgG antibody titer
IgG antibodies appear within 1-2 weeks
after acquisition of parasite, peak at 68
weeks and may persist for 2 years
IgM antibodies detected in serum for
months or even years after primary
infection and not indicate acute infection
Table : Interpretation of results of serological tests for
toxoplasmosis (Goldstein E., 2008)
Figure : Guidelines for serological testing and management of
toxoplasmosis during pregnancy (Goldstein E., 2008)
Figure : Serological testing and management of toxoplasmosis
during pregnancy on the basis of results obtained at the Palo
Alto Medical Foundation Toxoplasma Serology Laboratory (PAMF-
TSL) (Goldstein E., 2008)
 Treatment
Table : Medicines used for pregnant women who have
suspected or confirmed Toxoplasma gondii infection
acquired during gestation (Goldstein E., 2008)
Figure : Approach for pregnant women who are suspected or
confirmed to have toxoplasmosis acquired during gestation
(Goldstein E., 2008)
Table : Frequency of clinical manifestations of congenital
toxoplasmosis in newborns from mothers treated with
spiramycin (Group 1) and from untreated mothers (Group
2)
 Terminaton of Pregnancy
and Prevention
Termination indicated if there is fetal
infection based on PCR performed in
reference laboratory and evidence of
intracranial abnormalities on fetal
ultrasound
Prevention of primary infection is
based upon avoidance of sources of
infection
Table : Primary Prevention Toxoplasma gondii infection
during pregnancy (Goldstein E., 2008)
 RUBELLA
Rubella (German measle) is
Togaviridae family and single-stranded
RNA virus
It easily crosses the placenta of
infected pregnant women
At first trimester causes miscarriage or
fetal death, or congenital rubella
syndrome (CRS)
Incidence 1.30/100 000 in the general
population and 0.00/100 000 in US
Route of Transmission
Humans are the only reservoir of
infection
Virus transmitted direct inter-human contact
via respiratory droplets
Virus may shed from 7 days before rash onset
to 57 days thereafter
Virus replicates in respiratory mucosa and
cervical lymph nodes, before reaching the
target organs via systemic circulation
Viremia

Infection of the placenta

Infection of fetal organs

 Diagnosis
Laboratory diagnosis based on
seroconversion of RV-IgG, RV-IgM and RV-
IgG avidity and detection rubella virus in
nasopharyngeal secretions by reverse
transcription/polymerase chain reaction
(RT-PCR) for as long as 2 weeks after
eruption and reduced by 4 days after rash
Patient seronegative another serology
test at 20 weeks of gestation if remain
seronegative offered vaccination after
delivery
 Diagnosis
RV-IgM appear within 3 days after the rash
and disappear in 4-12 weeks
It detected by ELISA (58 days after onset of
rash) and persist throughout life
It reach steady state from few days to few
weeks woman seropositive at first
screening test may have been infected few
weeks earlier
High RV-IgG titer not necessarily marker of
recent primary infection
IgM antibodies indicate acute infection and
disappear 45 weeks after acquisition of virus
Figure : Algorithm for the follow-up of women in contact with
suspected rubella cases or exposed to rash during pregnancy
( Bouthry E., 2014)
 Vaccination
Rubella vaccines well tolerated, adverse
effects are benign : fever (15%), rashes
(5%), transient lymphadenopathy/parotiditis,
febrile seizures, anaphylaxis,
thrombocytopenic purpura or encephalitis
Major goal vaccination is prevention of
congenital infection from rubella
Pregnancy remains contraindication to
rubella vaccination
Women advised precautions against
pregnancy for 1 month (28 days) after
vaccination
Signs and Symptoms
Asymptomatic
Prodromal illness : fever, malaise and
adenopathy
Complications : polyarthritis and
polyarthralgia
Maculopapular rash develops 1-3 days and
characterized by small pink papules,
atypical, scarlatiniform or purpuric

Figure : Rubella rash (Dr Wallach D. Cochin Hospital, Paris, France

Table : Common transient and permanent
manifestations in infants with congenital rubella
syndrome (Orenstein W., 2014)
 Rubella Re-Infection
Rubella re-infection is rubella infection in person
who already has rubella antibodies resulting from
documented natural rubella infection/successful
rubella immunization
Subclinical difficult to diagnose
Risk of transmission to the fetus is difficult to
determine
Risk of CRS : < 5%
Diagnosis :
- at least two previous laboratory reports antibodies
10 iu/ml
- single result antibodies 10 iu/ml obtained after
documented rubella vaccination
Congenital Rubella Syndrome
Pathogenesis :
Non-inflammatory necrosis in epithelium of chorion
and endothelial cells transported to fetal
circulation and fetal organs (eyes, heart, brain and
ears) thrombosis and ischemic lesions
Actin inhibited directly or indirectly in rubella
infection inhibition cell mitosis and development
organ precursor cells
Immune system might play role because interferon
and cytokines appear to be upregulated in rubella-
infected human fetal cells, which could disrupt
developing and differentiating cells and contribute
to congenital defects
Risks congenital infection and defects
depend on gestational age at infection
Fetal manifestations : classic triad of
cataracts, cardiac abnormalities and
sensorineural deafness
Table : Cases of congenital infection and
congenital defects after maternal rubella
infection at different stages of pregnancy ( Bouthry
E., 2014, adapted from Miller et al., 1982)
Prenatal diagnosis congenital infection
recommended when maternal infection
diagnosed and based on detection of
RV-IgM in fetal blood or detection of
viral genome in AF, fetal blood or
chorionic villus biopsies
Detection rubella virus in chorionic
villus biopsies reflects infection of villi,
not fetal infection
 Management
Depends on gestational age at onset of infection
< 18WG:
- fetus at high risk for infection and severe symptoms
- termination pregnancy could discussed and accepted
- detailed ultrasound examination and assessment of AF
viral RNA are recommended
- If prenatal diagnosis not performed, specific pediatric
examination must be performed in newborns, including
RV-IgM assays
> 18WG:
- pregnancy could continued with simple ultrasound
monitoring
- specific pediatric examination of the newborn and
testing for RV-IgM recommended
Ultrasound findings
Most common ultrasound
abnormalities : cardiac (septal defects)
and ocular defects (cataracts and
microphthalmia)

Figure : Fetal face at 19 WG (coronal view): microphthalmia and

hyperechoic lens; ophthalmic asymmetry (arrow; Dr O. Picone)
TERIMA KASIH