Did the Fetus catch it?

Transcription

1 Did the Fetus catch it? Dr Ilse Erasmus Fetal Medicine Centre of Excellence Morningside Hospital

2 Fetal infections in 15 minutes Mega ZIP

3 Huge healthcare burden: $ 2Bn

4 You will be alerted by: Clinical suspicion Maternal Sero - Conversion Abnormal Ultrasound Confirm Fetal Infection

5 TORCH Toxoplasma gondii Other Syphilis Rubella virus Cytomegalovirus Herpes simplex virus Pathogens Involved Other continued and expanding. Varicella Parvovirus B19 HIV AIDS Enteroviruses (Coxsackie) Hepatitis B * Lysteria Monocytogenes Lyme disease Mycobacterium Tuberculosis Adenovirus

6 Antibody response VL> 1000 copies 1 st exposure 2 nd exposure X4 IgG -ve IgM -ve IgG -ve IgM +ve IgG +ve IgM +ve Avidity Low IgG +ve IgM -ve Avidity High IgG +ve IgM +ve Avidity High

7 Avidity of IgG

8 Rubella ss RNA virus Togaviridae Humans Primary Infection Latent or Chronic in CRS

9 Rubella Congenital Rubella Syndrome: CRS CNS: Microcephaly, Mental handicap Eyes: Cataracts, Retinitis Blindness Cardiac: VSD,PDA,PS Gregg syndrome 1941

10 Rubella Congenital Rubella Syndrome: CRS Immediate clinical signs: Active viral infection IUGR Thrombocytopenic purpura (Blueberry Muffin Rash) Hepatosplenomegaly Bone lesions Late sequelae: Latent viral infection & Immune complexes damage Sensorineural deficits Deafness Autism Endocrine disorders Diabetes Thyroid disfunction

11 Rubella Seroprevalence! Seroconversion 0.1-2% Primary Infections 85-95% Risks Occupation Small Children 4% Epidemics

12 Rubella Enders Lancet 1984 Fetus infected Placenta 90% 60% 24% 100% 1 st T 2 nd T 3 rd T Fetus affected 100% 24% 0% CRS >16w Deafness

13 Rubella Ultrasound findings IUGR CNS Microcephaly Eyes Cataracts Face Micrognathia, Cleft Palate Cardiac Anomalies Septal defects ASD, VSD, TOF PDA PS Placental calcification

14 Rubella Diagnosis IgM -ve IgG -ve IgM +ve IgG - ve IgM +ve IgG +ve Avidity Low IgM +ve IgG +ve Avidity Intermediate IgM +ve IgG +ve Avidity High IgM -ve IgG +ve Avidity High No Immunity High Suspicion Retest Wait for IgG Grey zone Old Infection No risk Immunity

15 Rubella Management Routine Serology Screen First Trimester Or 10 days after exposure Seronegative IgG - IgM Risk Counsel Regarding avoiding infection Monthly bloods Immune IgG + IgM Fetus risk Reassure First Trimester infection IgG+ IgM + Low Avidity Confirm infection Counsel re TOP Vaccinate post delivery If Sero-conversion If no sero-coversion during pregnancy Reassure Vaccinate post delivery

16 CMV DNA virus Herpesviridae 5 strains Humans Primary Infection Latency & Reactivation Secondary infection Immunocompromised Transplant Patients

17 CMV Congenital infection: Immediate clinical signs of CID: Severe IUGR Seizures Spastic Ventriculomegaly Microcephaly Moderate Thrombocytopenia Anemia Hepatosplenomegalys Myocarditis Pneumonitis Late sequelae: CNS:mental retardation, epilepsy Eye:blindness chorioretinitis and optic atrophy Ear:deafness sensorineural

18 CMV Middle High Socio Economic Seroprevalence Low Socio Economic Seroprevalence! 50-60%! 70-85% G2P! Occupation daycare worker, nurse, paediatrician Small Children- chreche??? seroconversion

19 CMV Type of maternal Infection Primary Maternal Infection 1-4% 96% Periconceptual Post Conception Reactivation 30-40% secrete virus Or Different Strain 5 Fetal Infection 50 % Fetal Infection 0.2%

20 CMV Fetus infected Placenta 50% 36% 45% 77% 1 st T 2 nd T 3 rd T 20-30% Fetus affected Earlier Less but more severe Later More but less severe

21 CMV Fowler et al 1992 Enders et al 2001 Primary Infection Symptomatic 10% Asymptomatic 90% Severe Moderate 5-10% 5-10% NND 30% Sequelae 60% Sequelae 5-15% Normal

22 CMV Diagnosis IgM -ve IgG -ve IgM +ve IgG - ve IgM +ve IgG +ve Avidity Low IgM +ve IgG +ve Avidity Intermediate IgM +ve IgG +ve Avidity High IgM -ve IgG +ve Avidity High No Immunity High Suspicion Retest Wait for IgG Grey zone Fetal risk? 2.5% Old Infection No risk Immunity? Beware of early infections may only present!!2 nd 3 rd trimester

23 CMV Ultrasound findings IUGR CNS Microcephaly Hydrocephaly (tissue destruction) Cerebellar Atrophy Eyes Chorioretinitis Oligohydramnios Echogenic kidneys Ascites, Hydrops Calcifications (echogenicities): Brain periventricular Retinal - chorioretinitis Hepatic Bowel Placenta

24 CMV Ultrasound findings

25 CMV Ultrasound findings Perivascular Inflammation Candlestick echogenicities Guibaud et al

26 CMV Ultrasound findings Placenta thick and calcified

27 CMV Ultrasound findings Echogenic Bowel Hepatic calcifications Guibaud et al

28 CMV Ultrasound findings Ascites Pleural Effusions

29 Grangeot Keros Valloup-Fellous Lereus Ville Yves Ville CMV Management Maternal Seroconversion Abnormal Ultrasound Confirm Fetal Infection Amniocentesis > 21 week >7 weeks from primary infection PCR for CMV CMV PCR + And N Scan: Serial Ultrasound scans And 3 rd trimester MRI Treatment? 94%PPV CMV PCR - Fetus Not infected beware of late 3 rd trimester infection CMV PCR + Fetus infected and affected counsel on severity

30 CMV Treatment ARV s Reduces Viral load in fetus after 1-12 weeks of infection Expensive R per week!!!!

31 CMV Treatment

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33 CMV Treatment HIG Benefit 200IU RCT No Benefit

34 CMV Prevention Screen in pregnancy for maternal antibodies not currently recommended

35 Parvovirus B19 ssdna virus Parvoviridae Erythrovirus Human parvovirus B19 Infects P Antigen and kills erythrocyte precursors Transient Aplastic crisis Immunocompromised Pre-existing haematology disease Myocarditis 5 th Disease

36 Parvovirus B19 Seroprevalence Seroconversion! 15-40% 1-3% Risks Occupation Small Children Epidemics 10%

37 Parvovirus Oepkes et al Prenatal Diagnosis 2011 Fetus infected Placenta 33-51% 1 st T 2 nd T 3 rd T Fetus affected 15% 10% 2.3% Death 4-6w post inf w Hydrops 4% 7% if < 20w CNS damage

38 Parvovirus Diagnosis IgM -ve IgG -ve IgM +ve IgG - ve IgM +ve IgG +ve Avidity Low IgM +ve IgG +ve Avidity Intermediate IgM +ve IgG +ve Avidity High IgM -ve IgG +ve Avidity High High Suspicion Retest Wait for IgG Grey zone Not Immuun? Beware IgM drops quickly Possible False Negative results If suspicion do Maternal B19 PCR Old Infection No risk Immunity

39 Parvovirus Management Normal Ultrasound Monitor for fetal anemia MCA V Max Maternal Seroconversion CVS Amniocentesis Fetal blood Parvo PCR + Abnormal Ultrasound Fetal Anemia Hydrops MCA V max >1.5 <32w >32w Fetal Blood Transfusion Oepkes et al Prenatal Diagnosis 2011 Anemia Resolving Consider delivery

40 PARVOVIRUS B19 Ultrasound findings NT Edema

41 Parvovirus B19 Ultrasound findings MCA V Max >1.5 Hydrops

42 Toxoplasmosis Domain: Eukaryota Phylum: Apicomplexa Genus: Toxoplasma Species: Toxoplasma gondii Protozoan Parasite Obligate Intracellular Contaminated Food and Water Pregnancy Immunocompromised Neurobehavioral

43 Toxoplasmosis

44 Toxoplasmosis Congenital Toxoplasmosis: Enchephalitis Chorioretinitis Jaundice Majority have at least one of the following by age 3: Hydrocephalus Intracranial calcification Neurological damage Chorioretinitis

45 Toxoplasmosis Seroprevalence 9.6% Seroconversion 19.6% Geographical location 4-19% WHO Risks Ingestion Occupation

46 Toxoplasmosis Fetus infected Placenta 5% 20% 80% 1 st T 2 nd T 3 rd T Fetus affected 65% 45% 20%

47 Toxoplasmosis Diagnosis IgM -ve IgG -ve IgM +ve IgG - ve IgM +ve IgG +ve Avidity Low IgM +ve IgG +ve Avidity Intermediate IgM +ve IgG +ve Avidity High IgM -ve IgG +ve Avidity High No Immunity Highs suspicion Retest wait for IgG? Beware: IgM + can persist for Months to years Need further confirmation Old Infection No risk Immunity

48 Toxoplasmosis US CNS Ventriculomegaly Hydrochephalus Eyes Chorioretinitis Widespread Calcifications Brain Chorioretinal Hepatic Placenta Placenta Thick

49 Toxoplasmosis Intracranial calcifications Thick Placenta

50 Toxoplasmosis Ultrasound findings Hepatic calcifications, Ascites

51 Toxoplasmosis Management Serology Routine Screen First Trimester Seronegative IgG - IgM - Counsel Regarding avoiding infection Monthly bloods Seropositive old infection IgG + IgM <18 weeks Fetus risk >18w Can t be so sure Repeat bloods 1-3 weeks Seroconversion IgG+ IgM+ Fetus infection risk Amiocentesis >18w PCR + Start Treatment Suspect Seroconversion IgG IgM + First Trimester infection IgG+ IgM+ Ultrasound Normal Treatment Abnormal Scan If Seroconversion Unchanged IgG IgM + Positive IgM does not mean much Treat as seronegative Montoya Remington 2008

52 Toxoplasmosis in pregnancy Management 1T trimester infection: Treatment aims to prevent transmission of parasite to fetus Spiramycin: statt and continue to term Macrolide antibiotic Does not cross placenta 1g (3M IU) q8h {max 3g or 9M IU/24h} If fetal infection is confirmed >18w: Pyrimethamine 50mg /day * + Sulphadiazine 3g/day + Folic acid alternating 3 weekly with Spiramycin Evidence for effectiveness of treatment and RCT s is lacking

53 Toxoplasmosis Prevention Screen in pregnancy for maternal antibodies not currently recommended in RSA

54 Thank you for your attention