Understanding Congenital Infections: TORCH Pathogens and Clinical Features

1. CONGENITAL INFECTIONS Intrauterine and Perinatal Infetions

2. The major characteristics • Transplacentaltransmission • Variousagents: viruses, bacteria, parasites • A similarclinicalfeatures: • multi-organ infection

3. Pathogens TORCH: Toxoplasma, Rubella, Cytomegalovirus, Herpes simplex virus

4. Clinical features • Generalized disease of the fetus / newborn • Intrauterine growth restriction • Nonimmune hydrops (generalized edema) • Anemia, leucopenia, thrombocytopenia • Jaundice, hepto-splenomegaly • Chorioretinitis, encephalitis • Pneumonitis, myocarditis • Congenital malforamtions • Depending on the time of infection and the pathogen

5. CYTOMEGALOVIRUS

6. Cytomegalovirus • The most frequentcongenitalinfection • Infectioninpregnancy: 35% risk for fetus • earliergestation • mother’s primaryinfection • Reactivationoflatentmaternal CMV infection • alsomaycausefetalinfection • ~1% ofnewbornswithcongenital CMV infection More symptoms on birth

7. CMV Symptomatic disease on birth (10%) • Lowbirthweight for gestational age • Jaundiceandhepato-splenomegaly • Hepatitis (does not become chronic) • Blueberrymuffinrash • Leucocoria (chorioretinitis) • Microcephaly • intracerebralperiventricular calcifications • generally withno symptoms of encephalitis

8. CMV Blueberry muffin rash (intredermal hematopoesis) Anemia Leukopenia Tromocytopenia • mortality 10%

9. Asymptomatic infection • 90% asymptomatic on birth • but ~ 10% of them develop: • sensorineural hearing loos (SNHL) • chorioretinits • later in childhood: disorders of psychomotor development

10. CMV The so-called “asymptomatic" infections: • Chorioretinitis • Hearing loss May be the only consequences! Screeningis required! • Theymayaffect the child’s development

11. CMV Sensorineural hearing loss (SNHL) associated with congenital CMV infection 10.000 births/year 1% CMV infected 100 congenital CMV inections at birth 10% 90% 10 symptomatic newborns 90 asymptomatic newborns 10% SNHL 65% SNHL 15 Cases of SNHL 6 cases of SNHL 9 cases of SNHL

12. CMV Diagnosis • DNK urin, saliva, blood, CSF • Culture of virus • standard culture = several weeks • culture + monoclonal Ab detection = 24h • Serological tests • presence of IgM on birth = congenital infection

13. CMV Therapy • Ganciclovir • may halt the progression of hearing loss

14. TOXOPLASMOSIS

15. Toxoplasmosis Patogenesis • Usuallyduringmother’s primaryinfection • reactivation of latent infection - extremely rare • Transmission rate = overall 30-40% • earlier maternal infection =thelowerrisk for fetal infection • latermaternalinfection = hihgherrisk for fetal infection • becauseofbetterplacentalbloodflow • transmission rate near to birthterm ≈90%

16. Toxoplasmosis Symptoms • Severity of fetal disease • the earlier infection = the more severe simptoms • High risk period = 10-24 gestational week • Developed placental blood flow • Vulnerable fetal period

17. Toxoplasmosis “Asymptomatic” disease at birth In most newborns- with no obvious simptoms • But by detailed examinations can reveal: • Chorioretinitis • Intracerebral cortical calcifications • with inflammatory CSF finding • Signs of hydocephalus classic triad

18. Toxoplasmosis Symptomatic disease on birth: • Low birth weight • Jaundice (early, within 24h postnatally) • Hepato-splenomegaly • Maculopapular rash • Triad: choriretinitis, cerebral calcifications, hydocephalus • seizures are frequent High risk for permanent neurological sequellae

19. Diagnosis • Serologically • IgG seroconversion, or 4-fold rise • 1-2 months to achive peak • Presence of IgM, IgA or IgE confirms diagnosis • PCR • histological examination of the placenta

20. Other diagnostic procedures • ophthalmologic examination • hearing testing (Auditory Evoked Potentials) • CT of brain • LP: CSF examination

21. chorioretinitis calcifications hydrocefalus

22. Toksoplazma Therapy • Pyrimethamin + Sulfadiazin • 12 months • Therapy of infected pregnat women • if an infection is detected before birth

23. Toksoplazma Prevention • To prevent infection of pregnant women: • Cooking of food or freezing or below -200C • Thorough hand hygiene: • after preparing raw meat and vegetables • after contact with cats

24. rubella

25. Rubella Byweek 8 85% withcongenitaldefect first 4 weeks 40% spont. abortions/stillborns Week 9-12 50% withcongenitaldefect Week 13-16 35% withcongenitaldefect • Primary infection of mother • minor disease: fever + rash • Serious fetal disease

26. Rubella Aftergestationalweek 20 • congenitaldefects do notappear • but chronicinfection (inflammation) is possiblle • Affectedorgans • Eyes • Hearing • CNS

27. Rubella Clinical features • Congenital malforamtions • Genealised disease on birth • “Asymptomatic” infectionon birth

28. Rubella Congenital malformations • Cardiovascular • patent ductus ateriosus Botagli • pulmonary artery stenosis • ventricular and atrial septal defects • Eyes • Cataract, chorioretinitis, galucom • Hearing loos (SNHL) • Damage of CNS • microcephaly, mental retardation • spastic paralysis, ect...

29. Rubella Patent ductus arteriosus Microcephaly Cataract

30. Rubella Symptomatic infectionon birth:generalised newborn disease • Low bith weight • Jaundice, hepatosplenomegaly • Thrombocytopenia • Purpuric (blueberry muffin) rash • Penumonitis • Menignoencephalitis

31. Rubella “Asymptomatic” infectionon birth • Often lower birth weight • Later may become apparent • SNHL • glaucoma, cataract • CNS damage: • Behavioral disorders • Mental retardation

32. Rubella Diagnosis Postnatally: • Serology - detectionofantibodies • IgM- evidenceoffetalinfection • producedonlybychild • IgG- Initially can be maternal • later only child’s IgGremain • Viral culture (throat, urine,blood, CSF …)

33. Rubella Dijagnosis Prenatally • Viral culture of amniotic fluid • RNA hybridization from biopsied chorionic vill

34. Rubeola Prevention • MPR vaccine (liveattenuated) • during 2ndyear of life • at the beginning elementary school • Pregnant women - not to vaccinate: • viraemia and fetal infection is possible • 3 mo. after vaccination pregnancyshould be avoided CAUTION: virus is exretedbyvariousbodyfluids for ≈ 1 year - Keepchildawayfromunvaccinatedpregnantwoman -

35. HERPES SIMPLEX VIRUS type 1 and 2

36. HSV Epidemiology • 90% of HSV infections occurs during delivery • HSV-2 in 80% of cases • Most often symptoms of genital herpes are absent • mother’s primary infection = high risk of trassmision • recurrent genital heres = low risk of trasmission

37. Pathogensis • Intrauterine infection (rare) • Transplacental trasmission from viremic mother • dissemination to multiple organs • CNS- most freqently affected

38. HSV Pathogenesis • Intrapartal infection • source: vaginal secretions • entrance: conjunctiva or respiratory mucosa • Local infection • dissemination • hematogenusly in to various organs • by retrograde axonal transport to CNS Symptomsusuallydevelopewithin 7 pospartaldays

39. HSV Clical features from Mild disease • vesicles or scarring of skin / mucous membranes …. to severe disease • generalized (disseminated) disease • encephalitis as the only manifestation • pneumonia as the only manifestation

40. HSV Disseminated disease • hepatitis, myocarditis, pneumonia, encefalitis • chorioretinitis, keratoconjunctivitis • rash (vesicles, bullae) in 70% • facilitate diagnosis

41. Diagnosis • Specimens: • swabs and aspirates of vesicles, conjunctiva, nasopharynx, rectum • blood, CSF, urine, stool, • Methods • Viral culture • PCR – evidence of viral DNA

42. Therapy • Aciclovir IV

43. Prevention: depending on circumstances of infection • Primaryinfectionofmother • risk for child = 50% • immediatelyintroduceacyclovir therapy for mother!! • Recurrentgenital herpes • obtainswabs for viraldignosis • if symptoms are present - introduce acyclovir to child • otherwise - justfollowup

44. Syphilis

45. Transmission • Hematogenous (transplacental) • the most common • Contact with mother’s chancre during birth • rare

46. Timing of sympomatic disease • Symptomatic at birth • Late neonatal onest • Within 5 weeks postpartum • Late onset • After 2 years of age

47. Symptomatic infection at birth • Stillbitrh • Generalised neonatal disease • Low birth weight, hepato-splenomegaly • Nonimmune hydrops + hemolytic anemia • Neutropenia and thromocytopenia

48. Late neonatal onset • Osteohondritis (metaphysitis), periostitis (new bone) • Rash: maculopapular desquamtive • Syphilitic rhinitis (hemorrhagic) • Hepatitis, lymphocytosis • Keratitis • CSF: pleocytosis + proteinorachia

49. Late onset: ≥2 years after birth Hutchinson triad: • Interstitial keratitis • 8th n. damage (deafness) • Hutchinson teeth Spaced apart and noched incisors

50. Late onset: othersymptoms 2. Mulberry molars 1. Saddle nose enamel coups of the permanent 1st molar 3. Bowing of the shins • Clutton joints: • painless swelling of the joints • most commonly knees