Toxoplasmosis during pregnancy wide spread phobia

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Toxoplasmosis during pregnancy wide spread phobia
Dr Roli Gautam MS Assistant Professor MedicityInst
itute 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
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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.

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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.
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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.

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Trophozoites
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• 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.

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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.

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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.

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• 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 4C.

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Source of infection

• Domestic cats
• Rodents (Rats)
• Contaminated soil (persist in environment if
  moist)
• Farm animal (Cow, goat, sheep, rabbits) 

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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.

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TRANSMISSION
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A Diagram showing how infection is transmitted to
Non-Immune Individuals
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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

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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 66C (150F), 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 lt 4.0.
• Freezing at 15C for more than three days or
  20C for more than 2days destroys a high
  percentage of the cysts.

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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-year-olds 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

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Incubation Period

• 10 to 23 days after ingesting contaminated meat,
• 5 to 20 days after exposure to infected cats.

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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.

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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

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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.

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Rate of Transmission

• Develop infection at least 6-9 months before
  pregnancy Pt immune rare transmission
• within 23 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

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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
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• Up to 90 percent of infected babies appear normal
  at birth, 80 to 90 percent will develop
  sight-threatening 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

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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.

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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

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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

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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.

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• 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

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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

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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

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• Specific Toxoplasma Antibody Tire Some
  interpretations
• Antibody Titre
• IgM IgG IFA/Dye IgG and IgM
• IgM-IFA gt 180 Single high titre Rising titers
  at IFA/Dye Titre lt 11000
• IgM-ELISA gt 1256 IFA gt 11000 3 week
  interval IgM-IFA/ELISA Negative
• Recent Acute Probably Recent Definite
  Recent Exclude Recent
• Infection Acute Infection
  Acute Infection Acquired Infection

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Blood test procedure flow chart
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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

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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

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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

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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.

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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

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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.

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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).

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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.

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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

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Histologic Diagnosis

• A rapid and technically simple method is the
  detection of T. gondii in air-dried,
  Wright-Giemsa-stained 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

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Isolation of T. gondii

• Isolation of T. gondii by mouse inoculation from
  blood or body fluids establishes that the
  infection is acute.

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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 afrosted glass
  aspect,
• hepatosplenomegaly and hepatic densities, pleural
  and pericardic effusions and ascites

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UltrasoundMyths 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,

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• 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.

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• HYDROCEPHALUS

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INTRACRANIAL CALCIFICATION
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CHORIORETINITIS
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Treatment
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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 11000.
• IgM positive titres and rising IgG titres mean
  recent infection.
• If these women are asymptomatic, no treatment
  required.

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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
• dont drink unpasteurised goats milk or eat
  dairy products made from it

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• 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 childrens 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

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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
  

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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.

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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.

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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.

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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,

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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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