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Toxoplasmosis during pregnancy
wide spread phobia
Dr Roli Gautam
MS
Assistant Professor
MedicityInstitute of Medical Sciences
Hyderabad,A.P., India,
Prof. Dr. Veena Agrawal
MS, MICOG, WHO Fellow U.S.A.
Prof. Obst.& Gynae
G. R. Medical College, Gwalior MP India
History
• Toxoplasma gondii is an obligate intracellular
protozoan .
• It derives its name from a North African rodent
the gondi, from which it was first isolated in
1908 .
• First case of a congenitally infected human baby
was reported in 1923
• Until 1969, life cycle of parasite was fully
elucidate with the discovery of its definitive host,
cats and other felines.
Toxoplasma gondii
Toxoplasmosis is the result of infection by Toxoplasma
gondii, an obligate intracellular protozoan parasite in the
phylum Apicomplexa.
The major forms of the parasite are:
• Oocysts (containing sporozoites), which are shed in the
feces.
• Tachyzoites, rapidly multiplying organisms found in the
tissues.
• Bradyzoites, slowly multiplying organisms found in the
tissues.
• Tissue cysts: walled structures, often found in the muscles
and central nervous system (CNS), containing dormant T.
gondii bradyzoites.
Oocyst
• Oocyst are formed as a results of
fertilization between male and female
gametocytes and are found in the epithelial
cells of the intestines of definitive host
• They are oval and 10-12 m in diameter
• Oocysts are excreted in the faeces of the cat,
contamination with which results in human
infection.
Trophozoites
• Trophozoites crescent shaped with one pointed end and the
other rounded end, and measure approximately 3-7m
• released from the ingested oocysts, invade epithelial cells
of the intestinal tract of the host
• Disseminate via blood and lymph to most of the organs.
• Invade all mammalian cells except nonnucleated
erythrocytes and are found extracellulary as well as
intracellularly in various organs.
• multiply in a host cell by a process known as endodyogeny
or internal budding.
• The rapidly proliferating trophozoites, as known as
techyzoites.
• The trophozoites are either eliminated by the immune
system of the host or by a drug or they are transformed into
cysts.
Tissue cysts
• Tissue cysts are 10-100  in diameter and contain
thousands of slowly multiplying forms of the
parasite, aptly known as bradyzoites.
• Formed within the host cells are early as 7 days
after the entry of trophozoites.
• Predominantly found in heart and skeletal muscles
and central nervous system.
• Known to persist within the tissue for the entire
life span of the host and are responsible for the
recrudescence of the infection, specially in
immuno-compromised hosts.
PARASITOLOGIC
CONSIDERATIONS
•
•
•
•
T. gondii has two of hosts:
a definitive host - like cats and other felines
an intermediate host - man and other .
It multiplies by sexual reproduction in the
definitive hosts, and by asexual
multiplication in definitive as well as
intermediate hosts.
• Oocysts are highly resistant to environmental
conditions and can remain infectious for as long
18 months in water or warm, moist soils. They do
not survive well in arid, cool climates.
• Tissue cysts can remain infectious for weeks in
body fluids at room temperature, and in meat for
as long as the meat is edible and uncooked.
• Tachyzoites aremore fragile and can survive in
body fluids for up to a day and in whole blood for
as longas 50 days at 4°C.
Source of infection
• Domestic cats
• Rodents (Rats)
• Contaminated soil (persist in environment if
moist)
• Farm animal (Cow, goat, sheep, rabbits)
Transmission of the infection
• Occur as a result of ingestion of occysts excreted in the
faeces of cats or by ingestion of udercooked meat
harbouring tissue cysts.
• Approximately 5-35% of pork, 9-60% of lamb and 0-9%
of beef contain T. gondii.
• Trans-placental transmission ot foetus from a mother
infected during pregnancy is also a common occurrence.
• In days of modern medicine, the odes of transmission have
attained a new perspective, like blood transfusion,
leucocyte transfusion and organ transplantation.
TRANSMISSION
A Diagram showing how infection
is transmitted to Non-Immune
Individuals
Immunity to Toxoplasma gondii
•
•
•
•
•
•
Active infection normally occur once
The risk is only from an infection caught for the first
time during pregnancy, or 2-3 months before
conception.
Acquired immunity is life long.
Parasite remains in body as latent infection in the form
of cyst in skeletal muscle, cardiac muscle and brain.
Usually inactive and harmless.
Reactivation occurs only in immunocomproised
patients- Chemotherapy, Corticosteroid therapy,
Congenital immunodeficiendy deficiency, HIV/AIDS,
Patient having organ transplant
Disinfection
• oocysts are resistant to most disinfectants but can be
inactivated by iodine, formalin and ammonia.
• Can be destroyed within 10 minutes by temperatures
greater than 66°C (150°F), and can be killed with boiling
water.
• Tachyzoites and tissue cysts are susceptible to most
disinfectants, including l% sodium hypochlorite and 70%
ethanol.
• Tachyzoites are also inactivated at pH < 4.0.
• Freezing at –15°C for more than three days or –20°C for
more than 2days destroys a high percentage of the cysts.
Geographic Distribution
• Toxoplasmosis is found worldwide.
• Infections are particularly common in warm,humid
climates and at lower altitudes.
• Acc. to one estimate, over 500 million humans around the
world are infected with T. gondii. App 90% of the
population in France, 20 to 70% in the in the USA and
30% in the U K, 1.4% - 27% in India are infected
• Studies shown that 30% of 30-yr-olds and 50% of 70-yearolds have had a toxoplasmosis infection It is estimated that
only 15% of women booking in for antenatal care are
already immune. This leaves 85% of pregnant women still
at risk of contracting the infection - Tommy's, the baby charity
Incubation Period
• 10 to 23 days after ingesting contaminated
meat,
• 5 to 20 days after exposure to infected cats.
Clinical Signs –
In immunocompetent non-pregnant
individuals,
• usually asymptomatic.
• App 10-20% develop lymphadenitis or a mild, flulike syndrome
characterized by fever, malaise, myalgia, headache, sore throat,
lymphadenopathy and rash. In some cases, may mimic infectious
mononucleosis
• symptoms usually resolve without treatment within weeks to months,
although some cases may take up to a year.
• Severe symptoms, including myositis, myocarditis, pneumonitis and
neurologic signs including facial paralysis, severe reflex alterations,
hemiplegia and coma, are possible but rare.
• Ocular toxoplasmosis with uveitis, often unilateral, can be seen in
adolescents and young adults; this syndrome is often the result of an
asymptomatic congenital infection or the delayedresult of a postnatal
infection.
In immunosuppressed
patients
• Toxoplasmosis is often severe.
• Neurologic disease is the most common sign,
particularly in reactivated infections.
• Symptoms are:
– Encephalitis,
– Necrosis from multiplication of the parasite can cause
multiple abscesses in nervous tissue, with the
symptoms of a mass lesion.
– Chorioretinitis, myocarditis and pneumonitis
Toxoplasmosis during pregnancy
• Tox is a part of TORCH syndrome.
• It is not a cause of habitual abortion.
• Only pregnent women with primary active
infection leads to congenital tox.
• Development of active immunity once,
protects subsequent pregnancies.
Rate of Transmission
• Develop infection at least 6-9 months before
pregnancy – Pt immune – rare transmission
• within 2–3 months before conception - 1% or
below risk of transmission but a high risk of
miscarriage
• The first trimester - 15% chance but Severity of
disease in neonate is more
• Second trimester - 25% risk
• Third trimester - 65% chance but Severity of
disease in neonate is less usually asymptomatic
Congenital toxoplasmosis
The consequences of the infection of foetus can be very
different between subclinical to very serious.
-
-
Abortion or still birth.
Overt disease - Symptoms with classical triad.
Hydrocephalus
Intracranial calcification
Chorioretinitis
Sub clinical infection - Usually asymptomatic at birth
Later on develops hearing defects, visual defects,
mental retardation and learning disabilities, even
severe, life-threatening infections later in life, if
left untreated
• Up to 90 percent of
infected babies appear
normal at birth, 80 to 90
percent will develop sightthreatening eye infections
months to years after
birth. About 10 percent
will develop hearing loss
and/or
learning
disabilities,
60%
of
infected may suffer from
Long Term Sequella
Contd
• mild cases with only slightly diminished
vision. Ocular disease is usually bilateral;
• The most common symptom is
chorioretinitis but strabismus, nystagmus
and microphthalmia may also be seen.
• Infants infected late in gestation may have a
fever, rash, hepatomegaly, splenomegaly,
pneumonia or a generalized infection.
Prenatal Management
•
•
•
•
•
Screening for Toxo during pregnancy
Frequent Antenatal visits
Surveillance for Fetal growth & health
Ultrasound for signs of foetal infection
PCR on an amniotic fluid sample when infection
in utero is suspected
• Foetal blood sampling has now been abandoned at
the expense of amniocentesis with PCR and
mouse inoculation of amniotic fluid
Prenatal Management
• Routine neonatal screening for toxoplasmosis
identifies congenital and early subclinical
infections. Treatment may reduce the severe long
term sequelae
• The diagnosis of congenital toxoplasmosis is
confirmed by demosntrating the presence of T.
gondii in blood, body fluid or specific IgM
antibodies
• Special hearing and eye exams will be done, as
well as a sonogram or CAT scan of his head and
other tests as needed
Criteria for Screening
•Ideally all women of child-bearing age should
know their serological status before conception.
•Once the maternal serological status is known,
screening is necessary
•As maternal infection is most often clinically
silent, repeated serological testing is the only way
to diagnose all acute infections
• All the these facts proof that myth that toxoplasmosis
causes recurrence abortion or BOH are wrong. It is not
mandatory to do screening in all the patients.
• As Toxo is not very common,Screening should be
only in patient
– "High effluent society“
– Non vegetarians
– eating habits and hygiene practices have been clearly
identified as risk factors.
– Immunocompromised patient
• Mothers who tested positive before the pregnancy
do not need monitoring
• Mothers who tested negative should be monitored
until term to avoid missing a clinically silent
infection
Diagnosis of toxoplasmosis
• May be established by
– Serological tests,
– Polymerase chain reaction (PCR),
– Histological demonstration of the parasite
and/or its antigens (i.e. immunoperoxidase
stain),
– Or isolation of the organism
Serodiagnosis
• Presence of IgM antibodies or a four fold rise in
IgG titres at 2-3 wks interval indicates a relatively
recent infection.
• Significant levels of IgM antibodies indicate infection acquired within the past 3 months.
• IgG antibodies usually appear within 1 to 2 wks of
infection, peak within 1 to 2 months, fall at
variable rates, and usually persist for life
• The titer does not correlate with the severity of
illness
Specific Toxoplasma Antibody Tire : Some interpretations
Antibody Titre
IgM
IgM-IFA > 1:80
IgM-ELISA > 1:256
IgG
IFA/Dye IgG and IgM
Single high titre Rising titers at
IFA > 1:1000
3 week interval
IFA/Dye Titre < 1:1000
IgM-IFA/ELISA Negative
Recent Acute
Probably Recent Definite Recent
Exclude Recent
Infection
Acute Infection
Acquired Infection
Acute Infection
Blood test procedure flow chart
blood test
positive
negative
sample sent to lab for further testing
positive to
current infection
positive to
previous infection
expert advice
about risks and
further action
immune
not at risk
from toxo
treatment
scans/further
tests to see if baby
is infected
not immune
take precautions
because preg
could be at risk
from toxo
Serological Tests
• IgM test
– Determine recent infection or in the distant past.
– Significant potential of misinterpretation of +ve result,
should be confirmed by other tests.
– Kits often have low specificity
– IgM antibodies can persist for months to more than one
year.
– Persistence of these IgM antibodies does not appear to
have any clinical relevance
IgA Antibodies
• IgA antibodies may be detected in sera of acutely
infected adults and congenitally infected infants
using ELISA or ISAGA methods.
• May persist for many months to more than one
year.
• Of little additional assistance for diagnosis of the
acute infection in the adult.
• Has increased sensitivity of IgA assays over IgM
assays hence useful for diagnosis of congenital
toxoplasmosis
IgE Antibodies
• Detectable by ELISA in sera of acutely
infected adults, congenitally infected
infants, and children with congenital
toxoplasmic chorioretinitis.
• The duration of IgE seropositivity is less
than with IgM or IgA antibodies and hence
appears useful as an adjunctive method for
identifying recently acquired infections
confirmatory test, the Toxoplasma
Serological Profile (TSP)
• TSP, differentiate between recently acquired and
chronic infection, is superior to any single
serological test.
• TSP consist of – Sabin-Feldman Dye Test (DT)
– double sandwich IgM ELISA or IgM-immunosorbent
(IgM-ISAGA) , IgA ELISA, IgE ELISA,
– and AC/HS test.
Sabin-Feldman Dye Test (DT).
• DT is a sensitive and specific neutralization
test in which live organisms are lysed in the
presence of complement and the patient's
IgG T. gondii-specific antibody
Contd:
• A positive DT establishes that the patient has been
exposed to the parasite.
• A negative DT essentially rules out prior exposure
to T. gondii (unless the patient is
hypogammaglobulinemic).
• in a few patients, IgG antibodies might not be
detected within 2 to 3 weeks after the initial
exposure.
• In rare cases of toxoplasmic chorioretinitis and
toxoplasmic encephalitis in immunocompromised
patients have been documented in patients
negative for T. gondii-specific IgG antibodies.
Differential agglutination (AC/HS)
• uses two antigen preparations that express antigenic
determinants found in early acute infection (AC antigen) or
in the later stages of infection (HS).
• Ratios of titers using AC versus HS antigens are
interpreted as acute, equivocal, non-acute patterns of
reactivity or non-reactive.
• The acute pattern may persist for one or more years
following infection.
• This test is useful in helping differentiate acute from
chronic infections but is best used in combination with a
panel of other tests (e.g.: the TSP).
Avidity Test
• The functional affinity of specific IgG antibodies is
initially low after primary antigenic challenge and
increases during subsequent weeks and months.
• Protein-denaturing reagents including urea are used to
dissociate the antibody-antigen complex.
• The avidity result is determined using the ratios of
antibody titration curves of urea-treated and untreated
serum
• avidity test is an additional confirmatory diagnostic tool in
the TSP for those patients with a positive and/or equivocal
IgM test or acute and/or equivocal pattern in the AC/HS
test.
Polymerase Chain Reaction (PCR)
• Used to detect T. gondii DNA in body fluids and tissues.
• Used to diagnose congenital, ocular, cerebral and
disseminated toxoplasmosis.
• PCR performed on amniotic fluid has revolutionized the
diagnosis of fetal T. gondii infection
• PCR has allowed detection of T. gondii DNA in brain
tissue, cerebrospinal fluid (CSF), vitreous and aqueous
fluid, bronchoalveolar lavage (BAL) fluid, urine, amniotic
fluid and peripheral blood
Histologic Diagnosis
• A rapid and technically simple method is the
detection of T. gondii in air-dried, Wright-Giemsastained slides of centrifuged sediment
• The presence of multiple tissue cysts near an
inflammatory necrotic lesion probably establishes
the diagnosis of acute infection or reactivation of
latent infection.
• It is often difficult to demonstrate tachyzoites in
conventionally stained tissue sections. The
immunoperoxidase technique, which uses antisera
to T. gondii, has proven both sensitive and specific
Isolation of T. gondii
• Isolation of T. gondii by mouse inoculation
from blood or body fluids establishes that
the infection is acute.
Ultrasound
signs of foetal infection
• Cerebral ventricular dilatation, usually symmetrical and
bilateral- poor prognostic sign
• starts in the posterior horns of the lateral ventricles and
leads, sometimes in the space of a few days, to
hydrocephalus
• Intracranial densities are found less frequently. - well
correlated with the presence of chorioretinitis at birth.
• Hyperechogenic foetal bowel
• Placental thickening with a“frosted glass” aspect,
• hepatosplenomegaly and hepatic densities, pleural and
pericardic effusions and ascites
Ultrasound
Myths & Facts
• Foetal ultrasound is essential to the management of
gestational infection and its role is both diagnostic and
prognostic.
• Signs of foetal infection are present in about 65% of
pregnancies when infection occurred in the first trimester
and in 20% in the second trimester
• cannot be used as a screening tool as it detects only major
signs of infection
• Ultrasound signs of foetal infection after a negative
amniocentesis is also of value in indicating a second
sampling as a few foetuses are infected after the timeof
prenatal diagnosis,
• Following a negative amniocentesis, scans
should be performed monthly.
• When amniocentesis is positive scans
should be performed fortnightly
• Repeated scans are mandatory during an at
risk pregnancy.
HYDROCEPHALUS
INTRACRANIAL CALCIFICATION
CHORIORETINITIS
Treatment
Non-pregnant women desirous of
pregnancy:
•
•
•
If IgM is positive, they should conceive
after it becomes negative and until IgG
titres should be stable and less than or
equal to 1:1000.
IgM positive titres and rising IgG titres
mean recent infection.
If these women are asymptomatic, no
treatment required.
Avoiding toxoplasmosis
• only eat meat which has been thoroughly
cooked (i.e. with no trace of blood or
pinkness)
• avoid raw cured meat, like Parma ham
• wash hands, chopping boards and utensils
thoroughly after preparing raw meat
• wash all fruit and vegetables thoroughly to
remove all traces of soil
• don’t drink unpasteurised goats’ milk or eat
dairy products made from it
• wear gloves when gardening and wash
hands and gloves afterward
• if you eat while gardening wash your hands first,
and try to avoid gardening in areas which may
have been soiled with cat faeces
• cover children’s sandpits to prevent cats using
them as litter boxes
• remove faeces from cat litter tray every day
wearing rubber gloves and wash gloves and hands
afterwards – or have someone else do this
• do not handle lambing ewes and do not bring
lambs into the house
Treatment of pregnant women
•
Spiramycin is drug of choice can be given before 26 weeks
no teratogenic effects
•
If fetus is infected there can be replaced by or addition of
Sulfadiazine + pyrimethamine
•
Clindamycin or Dapson : If patient has sulfa drug allergy.
•
Higher dose therapy, continue for 4-6 weeks.
•
Lower dose maintenance therapy given there after :
Medications
• Medicine for toxoplasmosis is only needed when the
infection affects an unborn baby (fetus) or someone with a
very weak immune system.
• diagnosed with toxoplasmosis during pregnancy, treat with
antibiotics.
• antibiotic treatment reduces the chances of transmission to
fetus
• fetus becomes infected (diagnosed using amniocentesis),
another antibiotic replaces or is added. This treatment
lessens the severity of fetal toxoplasmosis and related
problems after birth.
• If newborn has toxoplasmosis, will have antibiotics for the
first year of life. This is needed to lower the risk of brain
damage and blindness from the infection.
Contd:
• Spiramycin collects in the placenta, the site where
the Toxoplasma gondii parasites travel to the fetus.
• Antibiotic treatment during pregnancy (given to
the mother) may not cure an infected fetus.
However, it greatly reduces the risk and severity
of fetal brain and eye damage. Foulon W, et al. (2000).
• Infected infants who are not treated with
antibiotics after birth can develop increasingly
severe infection during the first 20 years of life.
This can lead to mental retardation, eye damage,
and sometimes blindness.
Contd:
• Studies show that although treatment after
birth may not reverse all the damage that
occurred before birth, it will greatly reduce
a baby's risk of developing new problems
during infancy and beyond.
Drug
Spiramycin
Toxo during
pregnancy
6-9 MIU/day in 2 or 3
divided doses for 3 wks
followed by 2 wks
intervals until parturition
Pyrimethamine After 16 weeks in combination pyrimethamine 25
with
mg/day with
sulphonamides sulphadiazine 1-2 gm gid
alternating with the
cycles of spiramycin 6-9
MIU/day for 3 weeks
until parturition
Remarks
safest amongst the
antitoxoplasma
agents
Pyrimethamine is
teratogenic. used in
pregnancy only if
potential benefit
justifies the risk to
foetus.
Drug
Spiramycin
Congenital toxoplasmosis
0.15-0.30 MIU/Kg/day for 12
months
Pyrimethamine 15 mg/square metre or 1 mg/kg/day
in combination (maximum 25 mg/day), with
with
sulphadiazine or
sulphonamides trisulphapyrimidine, 50-100
mg/kg/day alternation with the
cycles of spiramycin 0.15-0.3
MIU/kg/day for 3 wks for 12
months
Conclusion
• Toxoplasmosis remains a serious disease although recent
advances in diagnosis and treatment have greatly
ameliorated the prognosis for the affected infants.
• Routine screening is currently controversial
• If IgM +ve or 3-4 fold increase in IgG, start Spiramycin
• When infection in utero is documented, using PCR on an
amniotic fluid, Add or replace a combination of
pyrimethamine and sulfadiazine with folinic acid
supplementation to antibiotic.
• Infected infants should be treated postnatally up to one
year of age with the same drugs,
Education programmes may be
preventing acquisition of toxo cases,
only routine screening of all
pregnant women or all newborn
infants at birth would prevent or
detect a higher proportion of
congenital infections.
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