Toxoplasmosis in pregnancy


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Toxoplasmosis in pregnancy

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Toxoplasmosis in pregnancy

  1. 1. Benha University Hospital, EGYPT E mail: elnashar53@hotmail. com TOXOPLASMOSIS IN PREGNANCY Aboubakr Elnashar
  2. 2. DEFINE Disease caused by an obligate intracellular parasite;T. gondii HISTORY •Wolf & Cowen (1937): congenital Toxoplasmosis •Sabin & Feldman (1948): dye test Aboubakr Elnashar
  3. 3. PREVALENCE • Depend on: 1. Age: seroconversion increases by 1% /y 2. Eating habits 3. Exposure Aboubakr Elnashar
  4. 4. U.K Egypt Germany USA France Sero +ve 25% 30% 35% 50% 75% Seroconversion in pregnancy 0.2% ? 0.6% 0.6% 1% Acute infection complicates 1-5 ‰ of pregnancies Aboubakr Elnashar
  5. 5. Aboubakr Elnashar
  6. 6. Bradyzoite Bradyzoite Tachyzoite Bradyzoite Sporozoite Tachyzoite Bradyzoite Aboubakr Elnashar
  7. 7. FORMS 1. Oocyst: excreted in farces of cats, sporulate in the soil to form sporocyst. 2. Tissue cyst: latent form, contain bradyzoites, represent chronic stage, persist for life in humans Aboubakr Elnashar
  8. 8. 3. Tachzoites: invasive form, multiplies intracellularly, found in tissues in acute stage or during reactivation of the chronic infection spread in blood & lymph, disappear with development of the normal immune response Aboubakr Elnashar
  9. 9. TRANSMISSION OF INFECTION 1. ORAL: Tissue cysts: 10 % of lamb, 25 % of pork, beef, poultry. Pork and lamb carry a higher risk of infection than beef or poultry. Oocyst: 30 - 80 % of cats (low parasite dose) 2.TRANSPLACENTAl: Primary acute infection during pregnancy Maternal parasitaemia [Tachyzoites] (limited to 3 W): Placentitis: Fetal infection 3 . BLOOD or LEUCOCYTES TRANSFUSION (Tachyzoites) or ORGAN TRANSPLANTATION (Tissue cysts): (Rare) Aboubakr Elnashar
  10. 10. Soil contact (cat feces):17% Eating infected meat: 65% Cook et al BMJ 2000;321:142-147(Multicenteric) [Evidence level 3] Inadequately cooked meat is the main risk factor Aboubakr Elnashar
  11. 11. CLINICAL PICTURE Aboubakr Elnashar
  12. 12. Immunocomptent •Mild & self-limited •I.P :1-3 w •90 %: asymptomatic •10 %: lymphadenitis (painless, cervical LN), fever, sore throat, rash lymphocytosis, atypical lymphocytes •DD: flu, inf. mononucleosis Immunocompromised •Severe, fulminate, CNS, Eye Immunodeficient •Fatal, CNS, Eye, heart &lung Aboubakr Elnashar
  13. 13. Congenital toxoplasmosis •Effects: 67 % uninfected 2 % IUFD 31 % infected : Before pregnancy: 0% 1st mo: 1 % (usually abortion) 2nd&3rd mo: 17 % 9 th mo: 90% Aboubakr Elnashar
  14. 14. •Incidence of fetal infection: greater in late pregnancy •Severity of fetal infection: greater in early pregnancy • Cl. forms: Triad 1 Attenuated: chroretinitis, microphthalmia, hypotonia 2. Serious: 10% IC calcification, icterus, encephalopathy 3. Latent: convulsions, hydrocephalus, chorioretinitis Aboubakr Elnashar
  15. 15. Transmission risk (mother to fetus) Severity of Damage to fetus 15% 25% 65% Most less least 1st Trimester 2nd Trimester 3rd Trimester [Evidence level 3] Foulon et al. A.J. of Obst&Gynecology 1999;180:410–5 Hydrocephalus. Intracranial calcification, Retinochoroiditis 60% 20% 5% Transmission To The Fetus Aboubakr Elnashar
  16. 16. As in rubella, toxoplasmosis 1. Is dangerous for the fetus only if the initial infection occurs during pregnancy 2. Infection confers lasting immunity (Fields,1990) Aboubakr Elnashar
  17. 17. INVESTIGATIONS Aboubakr Elnashar
  18. 18. Parasite isolation Parasite detection Serology Histology Other Lymph adenopathy IgG IgM Excision biopsy Pregnancy IgG IgM IgG Avidity Fetus Am F Bl cells Bl cells IgM IgA Total IgM LFT Neonate Placenta Bl cells Bl cells Seq IgG IgM IgA Radiology of the brain Ocular disease Ocular fluids IgG Local Ab Ocular examination Aboubakr Elnashar
  19. 19. Appear Maximum Disappear Ig M Ig G 1week 2 weeks Few months ± few years (6 mo to 6 yr) Not disappear Individuals who have recovered from prior toxoplasmosis may demonstrate Anamnestic spike in IgG titer during subsequent episodes of other infections. -ve IgM excludes acute infection 1 month 2 month Aboubakr Elnashar
  20. 20. Diagnosis of acute infection 1. IgG: dye test > 1/ 1000. The gold standard test (sensitive & specific) IFA > 1/ 512 Titer Increase 4 folds over 3 w Seroconversion Avidity: low 2. IgM: ELISA. Remains high for many yr after acute infection IFA > 1/ 80. Remains elevated for 6 mo after acute infection, then rapidly drops. More useful than ELISA ISA > 6 The presence of IgM is suggestive but not diagnostic. 3. IgA or IgE: more sensitive than IgM Aboubakr Elnashar
  21. 21. Negative Negative No serological evidence of infection Negative Positive Possible acute infection or false-positive IgM result Positive Negative Infection for more than 1 year. Positive Positive Possible recent infection within the last 12 months. IgG IgM Report/Interpretation for All Except Infants Equivocal IgG or IgM: obtain a new specimen for both IgG and IgM testing. Aboubakr Elnashar
  22. 22. IgG Neg: Not infected, retest/ 1-3 ms for seroconversion Pos: Infected Neg: Infected for >1 y Pos: Infection within last 2 ys or false positive IgM IgG avidity High: Infected at >12 ws previously low: Recent infection possible Obtain 2nd sample 2 ws after 1st; send both samples to toxoplasma reference lab for confirmation before any intervention.Aboubakr Elnashar
  23. 23. The IgG avidity test Discriminate between past and recently acquired infection. Avidity (functional affinity) of toxoplasma- specific IgG antibodies. Following an antigenic challenge, the antibodies produced usually have a low average affinity. During the course of the immune response, there is maturation of antibody affinity that increases progressively over weeks or months. The avidity tests are helpful primarily to rule out that a patient’s infection occurred within the prior 4 to 5 months. This is most useful in pregnant women in their first months of gestation who have a positive test for both IgG and IgM toxoplasma antibodies. Aboubakr Elnashar
  24. 24. Diagnosis of fetal infection 1. U/S No findings: 80% Specific findings: Hydrops, Ventriculomegaly (mild symmetrical to severe hydrocephalus), Intracranial calcifications (periventricular) Non specific findings: ascites, hepatomegaly, liver calcification, pericardial /pleural effusion, oligohydramnios, IUGR, placental thickness Aboubakr Elnashar
  25. 25. 2. Amniocentesis or cordocentesis . IgM . High eosinophil count, LFT & low platelet count . PCR: sensitive & specific . Inoculation to mice or tissue culture Aboubakr Elnashar
  26. 26. Aboubakr Elnashar
  27. 27. •Depends upon: prevalence rate & economic issues. Cost benefit ratio •Obligatory in: France, Austria, Belgium. •Not done in UK, Egypt. In USA (precomceptional) In France (prenuptial) NICE (2003): Routine antenatal serological screening for toxoplasmosis should not be offered because the harms of screening may outweigh the potential benefits. [B] Aboubakr Elnashar
  28. 28. •ACOG (2000): SCREENING in: -High-risk persons Who eat undercooked meat (pork, lamb) Who clean litter boxes. Who garden without glove. Who have had a recent mononucleosis-type like illness -U/S findings suggestive of toxoplasmosis: hydrocephalus intracranial calcifications Microcephaly fetal growth retardation Ascites Hepatosplenomegaly [C] Aboubakr Elnashar
  29. 29. •Indications of screening during pregnancy (Bader et al,1997) 1. Symptoms suggestive of acute infection 2. Exposure to the organism during pregnancy 3. Residence or migration to high prevalence areas e.g. France 4. Infection with HIV Aboubakr Elnashar
  30. 30. Preconceptional: IgG +ve No further tests -ve IgG/ 4-8 W during pregnancy First antenatal visit: IgG -ve IgG/4-8 w +ve Acute infection +ve IgM titer high Acute infection -ve or low Past infection Aboubakr Elnashar
  31. 31. TREATMENT Aboubakr Elnashar
  32. 32. Indications: •Pregnancy •Immunocompromised or immunodeficient •Severe persistent symptoms •Serious damage of vital organs •Infection acquired via blood transfusion Mode of action: Non of the drugs is effective against the encysted form slowing down multiplication of tachozites Aboubakr Elnashar
  33. 33. Aim during pregnancy: 1. Prevention of localization in the placenta 2. Prevention or modification of neonatal infection By 60% (Holfeld et al, 1994) No effect on intracranial or occular lesions (Gras et al, 2001) Effectiveness is less if infection acquired in late pregnancy or tt is delayed. Aboubakr Elnashar
  34. 34. Pyrimethamine & S. diazine combination Pyrimethamine • Mode of action: inhibit production of dihydrofolate reductase & synthesis of DNA,RNA & proteins •Side effects: teratogenic in first trimester bone marrow depression •How to avoid side effects: not used in 1st trimester CBC/4d folonic ac (yeast tab 8 tab/4d)Aboubakr Elnashar
  35. 35. S. diazine •Other types of sulpha: S. pyrimidine, S. pyrazine, S. methazine. • Side effects: crystalluria haematuria rash neonatal hyper bilirubinemia at term • How to avoid side effects: Maintain high urinary flow not used at term. Aboubakr Elnashar
  36. 36. •Dose & duration Non pregnant Pyrim: loading dose: 2 mg/ k/d x 2 d Maintenance dose: 1 mg/ k/d x 4 - 6 w S. diazine: Loading dose: 50 mg /k then 100 mg / k /d 4 divided doses Pregnant 1 st trimester: S. diazine (50 - 100 mg /k /d) 2nd & 3rd trimester: S. diazine + Pyrim.(0.5 -1 mg /k /d)X4 w At term: Pyrim. Aboubakr Elnashar
  37. 37. Spiramycin • Mode of action: macrolide cross placental barrier poorly. intracellular toxoplasmicidal •Side effects: n. & vomiting, diarrhea, allergic skin reaction •Dose: (T= 1.5 million iu= 0.5 gm) # 3 gm in 4 divided doses X 3 w on & 2 w off till term # If f. infection is confirmed: Pyrim. & S. diazine X 3 w then spiramycin x 3 w & so on till delivery Aboubakr Elnashar
  38. 38. •Therapeutic abortion is not recommended 1. Risk of transmission to the f. is low 2. Treatment can prevent f. infection as the parasite takes 4-8 w to cross placenta Aboubakr Elnashar
  39. 39. Aboubakr Elnashar
  40. 40. Prevention of maternal infection (primary prevention) •Kill tissue cysts in the meat : heat 60c freeze at -20 or -6 for 24 h •Avoidance of oocytes from cats : Hand wash, Wear gloves, Wash fruits & vegetables Dry heat or boiling water Avoid contamination with cats Prevent infection of cats • Avoid blood or blood products with toxoplasmosis Aboubakr Elnashar
  41. 41. Prevention of congenital infection (secondary prevention) •Preconceptional screening •Diagnosis & treatment of acute infection during pregnancy •Avoid infection during pregnancy Tertiary Prevention: Early detection and treatment of neonatal disease Aboubakr Elnashar
  42. 42. Aboubakr Elnashar
  43. 43. •Toxoplasmosis is not a cause of habitual abortion. •Routine screening should consider the cost benefit ratio. •If IgG is +ve before pregnancy: No need for retesting or treatment. No fear of congenital infection. •Only primary acute infection can lead to fetal infection which occurs in 33%. •Acute infection is diagnosed if IgM is high or IgG avidity is low. •+ve IgG or +ve IgM is not diagnostic of acute infection. Aboubakr Elnashar
  44. 44. Thanks Aboubakr Elnashar