Toxoplasmosis during pregnancy

A.Kurdi Syamsuri

Toxoplasma gondii

Toxoplasmosis is the result of infection by Toxoplasma gondii.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.

Trophozoites

• 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.

• Domestic cats

• Rodents (Rats)

• Contaminated soil (persist in environment if moist)

• Farm animal (Cow, goat, sheep, rabbits) 

Source of infection

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

• 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

Immunity to Toxoplasma gondii

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 immunosuppressedpatients

• 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

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

Congenital toxoplasmosis

• Up to 90 percent of infected babies appear normal at birth, About 10 percent will develop hearing loss and/or learning disabilities, 60% of infected may suffer from Long Term Sequella

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 .

Criteria for Screening

• 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.

•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

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

Blood test procedure flow chart

blood test

positivesample sent to lab for further testing

negative

positive tocurrent infection

positive toprevious infection

not immune

expert adviceabout risks andfurther action

immunenot at riskfrom toxo

take precautionsbecause preg

could be at riskfrom toxo

treatment

scans/furthertests to see if baby

is infected

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

Avidity Test

• avidity test is an additional confirmatory diagnostic tool in the TSP for those patients with a positive and/or equivocal IgM .

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

• 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.

Ultrasoundsigns 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

• 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

TreatmentTreatment

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

• 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 :

Treatment of pregnant women

Medications

• .

Drug Toxo during pregnancy

Remarks

Spiramycin 6-9 MIU/day in 2 or 3 divided doses for 3 wks followed by 2 wks intervals until parturition

safest amongst the antitoxoplasma agents

Pyrimethamine in combination with sulphonamides

After 16 weeks -pyrimethamine 25 mg/day with sulphadiazine 1-2 gm gid alternating with the cycles of spiramycin 6-9 MIU/day for 3 weeks until parturition

Pyrimethamine is teratogenic. used in pregnancy only if potential benefit justifies the risk to foetus.

Drug Congenital toxoplasmosis

Spiramycin 0.15-0.30 MIU/Kg/day for 12 months

Pyrimethamine in combination with sulphonamides

15 mg/square metre or 1 mg/kg/day (maximum 25 mg/day), with sulphadiazine or 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,

ThanksThanksThankThankss