Congenital Infections

Transcription

1 Congenital Infections The elephant in the room Fetal Medicine Old and New Dr JL van der Merwe AOG 2014

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3 Originally TORCH complex Toxoplasmosis Other [T. pallidum] Rubellavirus Cytomegalovirus (CMV) Herpes implex Virus (HV) Now also perpetrators. Parvovirus B19 Varicella-zoster virus Hep B Plasmodium HIV Mycobacterium tuberculosis Listeria Monocytogenes, Enterovisuses, Borrelia burgdorferi (Lyme Disease)

4 Transmission Routes

5 Transmission Timing

6 Manifestation influenced by Mode of acquisition Maternal immunity Timing (gestation) Effect of pathogen on organogenesis Fetal genetics Teratogens: Varicella, Rubella CMV, HV Influenza

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8 D0 : Maternal Infection - Viraemia, Bacteraemia, Paracitaemia?Clinical ymptomatology D1-7: Nonspecific (fever, chills headache myalgia) D5-21: pecific (rash, arthritis, pharyngitis, meningitis (up to 21d) D5-24: Transmission (1-3w) Fetal Infection from D1 Fetal Affection - ultrasound features (weeks - months) Pathogenesis Neonatal presentation

9 D0 : Maternal Infection - Viraemia, Bacteraemia, Paracitaemia?Clinical ymptomatology D1-7: Nonspecific (fever, chills headache myalgia) D5-21: pecific (rash, arthritis, pharyngitis, meningitis (up to 21d) D5-24: Transmission (1-3w) Fetal Infection from D1 Fetal affection - Ultrasound features (weeks - months) Pathogenesis Neonatal presentation

10 Maternal Immunity Virulence organism everity of disease Gestational age Pathogenesis

11 ? Foreign graft placenta immunological barrier Immature immunologic mechanism Persistence of organism Pathogenesis

12 Placental damage Pathogenesis

13 Progressive tissue destruction Toxoplasmosis yphilis Rubella CMV HV Pathogenesis

14 Pathogenesis

15 Pathogenesis

16 Pathogenesis

17 Pretest Probability and detection Pos Predictive Value Neg Predictive Value Prevalence

18 Primary Prevention

19 Current antenatal screening Test Purpose Action HIV antibody To enable measures to be taken to reduce vertical transmission. If positive, ARVs and screening OI. yphilis To detect active infection. If reactive, treat with penicillin Urine culture Treatment of asymptomatic UTI If asymptomatic bacteriuria, treat and repeat culture Hep B surface antigen Rubella IgG To determine chronic carriers. To determine susceptibility If positive, administer hepatitis B Ig and vaccine to infant at birth If negative, MMR before conception / postpartum.

20 CMV Primary Prevention detect seronegative women (IgG -) Avoid high risk (children under 6y, sharing utensils) Good hygiene Primary screening not recommended No vaccine is available In seropositive women,? distinguish between primary nonprimary infection or determine the timing No evidence - antiviral drug treatment of primary infection Although fetal infection detected, no way to predict outcome

21 Toxoplasmosis Primary Prevention detect seronegative women (IgG -) Avoid high risk (undercooked / cured meat, soil-contaminated fruit / vegetables) Primary screening not recommended creen IgM and/or IgG avidity IgM false positive rate (10-13m post after infection) erial IgG titres - lab reproducibility problems IgM + and IgG ; both positive two weeks later can be useful Although treatment decrease significant CN affect

22 Assess risk profile What to do? Inform of risks of exposure Educate on preventative measures Vaccinations Hand hygiene Food (deli meats, soft cheese, unwashed veg) Cat litter boxes Avoid contact with sick people, wild pets, toddlers

23 econdary Prevention

24 Presentation Maternal Features Contact with known infection History of suggestive infection

25 Diagnosis

26 Diagnosis erology Prim infection = seroconversion Probable recent if IgM + WITH low IgG avidity Recurrent infection: pecific IgG + without IgM before pregnancy NOW significant increase IgG + titre

27 Diagnosis Avidity Test Abs avidity indicates -strength of multivalent Abs binding to multivalent antigen Low avidity <30% - suggests primary infection (<3 months) High avidity >70% - suggests infection of >4m ago

28 Prognosis Number of cases Transmission Toxo Transmission CMV Transmission Rubella everity of infection Gestation

29 Tertiary Prevention

30 Fetal Presentation Maternal Features Contact with known infection History of suggestive infection Ultrasound Abnormalities Ventriculomegaly, Calcifications, echogenic bowels, Hepato- / plenomegaly, Hydrops fetalis

31 Antenatal Ultrasound Infection Congenital toxoplasmosis Congenital syphilis Congenital rubella syndrome Congenital cytomegalovirus Congenital varicella syndrome Main Features of yndrome Microcephaly, hydrocephalus, intracranial calcifications, ascites Hepatosplenomegaly, ascites Cataracts, cardiac malformations (eg, patent ductus arteriosus, pulmonary artery hypoplasia), microcephaly, hepatosplenomegaly IUGR, microcephaly, hypotonia, intracranial calcifications Atrophy of extremities, microcephaly, cataracts, microphthalmia

32 Ultrasound Features

33 Ultrasound Features Example Ventricular dilatation (A), hyperechogenicity of the ventricular wall (B).

34 Ultrasound Features

35 Ultrasound Features

36 Ultrasound Features

37 Diagnosis - Fetal U Features - yndromes Amniocentesis (after 20w) Viral culture 100% specific ( false-negative) Viral DNA isolation PCR both sensitive and specific Cordocentesis FB Detection of viral PCR, IgM, or viral culture Together with hematologic, immunologic, and enzymatic measurements

38 Prognosis onographic abnormalities: Associated abnl / extent No guarantee of normal fetus/infant if absent Fetal blood parameters: specific IgM, viral load, biochemical, haematological Viral load in amniotic fluid

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40 pecific Infections

41 Rubella Mother: Isolate virus from throat / blood Paired serological samples IgG +, IgM + (Recent infection /reinfection) - Repeat 2w IgG -, IgM (usceptibility) Repeat if < 3w since contact, < 7d since onset) IgG -, IgM + Possible recent infection IgG +, IgM Past infection /immunisation

42 Rubella Fetal Risk T % transmission 80% abnl (multiple organ damage, miscarraige) Congenital rubella syndrome Transient abnormalities: Permanent abnormalities: cataract, glaucoma, CV, deafness, microcephaly, MR T2 25% abnl (±100% hearing impairment/ ±50% eye abnl) >16w - Fetal affectation rare Late abnormalities: Risk of fetal infection 1-4 wks 5-8 wks 9-12 wks > 12 wks

43 CMV High risk groups for primary CMV Day care workers (11% incidence per year) erologic testing recommended for: Parents with child in day care (incidence of %/y) History suggestive Exposure to known CMV Cannot be eradiated! (Reactivation and reinfection common) Immunocompromised Abnormalities on routine antenatal ultrasound

44 CMV Prim infect % transm. Reinfection - 1-2% transm. T1: severe sequelae (deafness and mental retardation) 10-20% infected infants: sensorineural hearing loss, ocular damage, impairment of cognitive / motor function Primary Maternal Infection 1st trimester 3rd trimester Congenital Infections ymptoms at birth evere handicaps

45 CMV Diagnosis Ultrasound [detect typical features, sensitivity % Amniocentesis [for PCR + culture] 4-6w after infection 45 % sensitive If < 20 weeks % sensitive if > 20 weeks gestation. pecificity up to 100 %. Viral loads of >10 3 copies/ml =symptomatic fetal infection (sens 70%) Fetal blood sampling CMV- IgM > 20 weeks % sensitive evere congenital CMV Consider TOP experimental protocols with IV ganciclovir / Valganciclovir

46 Parvovirus B19 Childhood viral exanthem erythema infectiosum (Fifth disease or "lapped cheek disease") Transmision: Transplacental up to 30% Fetal loss about 9% (T2) Overall fetal loss rate 1/60 [<20w up to 17%] Risk of Fetal Infection 1-12 wks wks > 20 wks

47 Parvovirus B19 Fetal Affectation FB: Aplastic anaemia Direct cadriomyopathy NIHF (nonimmune hydrops fetalis) IUFD 1-12w after infection Fetal serology can be false negative PCR (best) Fetus 1-2w review for 3m signs of hydrops MCA PV

48 Toxoplasmosis Protozoan, Toxoplasma gondii [intracellular patasite] 70% 60% 50% 40% 30% 20% 10% Transplacental Toxoplasma and Congenital Infection Fetal T1 Miscarraige Chorioretinits (blindness), encephalitis (micro-,hydrocephaly and calcifications), jaundice 0% T1 T2 T3 Transmission evere symptoms

49 Toxoplasmosis Investigations Ultrasound (>20w) - IUGR, ventriculomegaly, intracranial calcifications, or ascites Amniocentesis (4w after maternal) PCR and / or culture If U and AF negative - still consider treatment Infected mothers piramycin (1.5 grams every 12 hours) to prevent fetal infection 60% reduction Infected fetus Pyrimethamine and sulfadiazine with folinic acid (Leukovorin) TOP

50 Varicella-Zoster Virus Primary infection - chickenpox Highly infectious 10% respiratory complications Herpes zoster ("shingles") Not cause congenital /neonatal varicella Transplacental passage of antibodies [mother] T2 and T3 Fetal infection rate 25% 2% - 10% fetuses develop VZV embryopathy 6-12 weeks - limb abn 16 to 20 weeks - eye and brain Later less frequent & severe

51 Varicella-Zoster Virus Management Infected mothers: VZIG does not protect the fetus Antiviral agent - acyclovir 5-10mg/kg IVI 8hly x 7d Women exposed - VZIG 125 U/10kg IMI (max 625 U) Women infected last few days of gestation - born within 2-4 days after the onset 20% risk for neonatal varicella - develop progressive varicella Administration of VZIG most valuable

52 Herpes implex HV persist in latent state, resurfacing at any time Mostly acquired during delivery Primary infection - 33 to 50% transmission Recurrent disease - 1 to 3% transmission Primary HV infection: Miscarriage Disseminated hepatitis, encephalitis,death PTL Perinatal infection Manifests during 1 st month

53 Herpes implex Effects 3 major categories seen localized skin, eye and mouth infection encephalitis with or without skin, eye, and mouth disease disseminated infection [irritability, seizures, respiratory distress, jaundice, bleeding diathesis, and shock] CN infections chorioretinits, meningitis, encephalitis, MR

54 Herpes implex Management Caesarean section if primary, first episode, or recurrent HV lesions present in labour Infants - cultures of nose, mouth, urine, and stool [24 48h] If any maternal cultures are positive or if disease is apparent Diagnosed new-borns - isolated to prevent nosocomial transmission Treatment include acyclovir IV (20 mg/kg/dose) q8 hours for 14 to 21 days

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