CONGENITAL INFECTIONS

1. CONGENITAL INFECTIONS Dr.M.VENKATESH Nagarcoil

2. Definition • Infections transmitted any time during gestation excluding the last 5 to 7 days. • Common infections acquired in utero are a. CMV b. Rubella c. Toxoplasma gondii d. Treponema Pallidum e. HIV f. Human parvovirus B19

3. Clinical Features

4. Clinical Features - Contd..

5. Diagnostic Approach • Family and maternal History • Birth weight • Medical Problems of siblings • Maternal illness • Drug use • Sexual partners and sexual orientation • Information about mother’s travels • Blood transfusions.

6. Cytomegalo Virus • Herpes virus – Family • Largest DNA genome of any known virus • Commonest congenital viral infections

7. Incidence • 50% – 90% • Old age, low socio economic and low educational status. • Viral excretions in the cervix or urine rises during pregnancy from 3% in the first trimester to 50% during term. • Estimated sero conversion rate during pregnancy – 0.7% - 4.1%.

8. Mode of Spread • Fetus infected primary maternal infection and reactivated maternal infections. • Infants exposed to virus - shed from cervix. • Excreted in Breast milk. • Excrete atleast one year. • Transfusion related infections

9. Maternal Exposure and History • Child care providers • 90% of pregnant women – asymptomatic • Symptomatic - Flu like illness • Fever fatigue , Headache, Myalgia, Lymphadenitis, Pharyngitis

10. Etiopathogenesis • Infections occurs throughout gestations • Higher incidence during first trimester

11. Virus ↓ Placenta ↓ Placental Fibroblast ↓ Umblical Cord ↓ Kidneys ↓ Fetal Urine ↓ Amniotic Fluid ↓ Oropharynx ↓ Fetal Circulation ↓ Target Organs

12. Laboratory Evaluations • No universal prenatal screening • Use of IgM antibody testing in mothers and infant – Limitations • Mother with reactivation as well as infection may have positive CMV IgM • IgM testing has vide variability in accuracy and reproductability • Only 10% of pregnant women transmit infection to their fetus • CMV specific IgG. - Discriminate primary from and recurrent infection

13. Lab Evaluation • Detection of virus in organs or culture specimens at birth (or) within first 2 to 3 weeks of life. • Sensitive detection is from urine. • Rapid method of isolation - Shell viral assay. • Elevation of liver transaminases and thrombocytopenia • Urine usually contains bile but not urobilin • Peripheral Smear – red cell, inclusion bodies owl eye cells

14. Lab Evaluation – Contd.. CT Brain • Periventricular calcification • Ventriculomegaly • Cerebellar hypoplasia • Neural migration disorders HPE • Intranuclear inclusion bodies in brain • Mono nuclear cell infiltration and diffuse fibrosis • Sub ependymal and peri ventricular necrosis and contains, heavy growth calcium

15. Prenatal Diagnosis • Isolation of virus by amniocentesis. • A specific nucleic acid test for CMV in amniotic fluid (or) CVS via PCR.

16. Treatment • CMV lacks enzyme thymidine kinase. This feature renders its resistanceto antiviral agents like acyclovir. • Ganciclovir – IV for 6 weeks showed a decreased in viral urine titre. Side affects : Neutropenia, Thrombocytopenia.

18. MRI Brain

19. Prognosis • Risk of deafness • Reduction of IQ scores • Infected infants - Asymptomatic at birth have minimal to no sequale other than potential hearing loss. • Symptomatic at birth – mortality varies from 4 – 30%. • 90% of symptomatic neonate late complications - Intellectual and developmental impairment • Small percentage chorioretinitis. • Minimal abnormalities at birth – normal at long term follow up.

20. Preventions • No role for antiviral therapy during pregnancy • Vaccines - Progress • Basic hygiene, Hand washing for pregnant women after contact with urine, diapers, oral secretions and other body fluids

21. Rubella RNA Virus Toga viridae family German measles

22. Incidence • Dropped from 58 per 100,000 population in 1969 to less than 0.5 per 100,000 population in 1997 – 1998. • Maternal infection occurs from one month before conception to the second trimester and may be associated with disease in infants. • Classical findings of congenital rubella predominates with onset of maternal infection during first 8 weeks of gestation and is low after 17 weeks of gestation.

23. Etiopathogenesis • Transmitted from person to person via respiratory droplet. • Once the oral (or) nasopharyngeal mucosa are infected, viral replication occurs in both upper respiratory tract and nasopharyngeal lymphoid tissue. • Virus spread contiguously to regional nodes, and haematogenously to distant sites. • Fetal infection is presumed to occur during maternal viraemia.

24. Etiopathogenesis – Contd.. • Virus induced apoptosis of cells leading to cytopathic effects and virus induced inhibition of cell division. • Foetus infected with rubella demonstrate cellular damage in multiple sites and a non inflammatory necrosis in target organs including eyes, heart, brain and ears.

25. Clinical Spectrum • LBW , Hearing loss, Heart defects, Cataracts, Hepatosplenomegaly, Microcephaly • Skin rashes – Blueberry muffin • Interstitial pneumonia

29. Investigations • IgM titre • Rise in paired IgG titres • Isolation of rubella virus cultured from nasal, blood, throat, urine or C&F specimen, throat swab. • Detection of virus by reverse transcriptase – PCR in specimens from throat swabs; CSF, cataracts • Viruses are recovered up to 1year in life • Thrombocytopenia, Hyperbilirubinemia, Leukopenia

30. X-ray • Large AF • Linear areas of radiolucency in long bone • Increased densities in the metaphysis • Irregular provisional zones of calcification

31. Treatment • No specific therapy • Anemia – Blood transfusion • Seizure control • Phototherapy

32. Treatment – Contd.. • Long Term Care – Multi disciplinary approval • Physiatrist • O.T. • Neurologic audiology monitoring • Surgical interventions as needed for cardiac malformation and cataract

33. Prognosis • Consequences of fetal rubella infection may not be evident at birth. • Infection in 1st or 2nd trimester may lead to deafness or persistent growth restriction • Infections in 3rd trimester – IUGR • Even in the absence of MR Neuromuscular development is commonly abnormal. • Hearing loss, difficulties with balance and gait. Learning deficits and behavioral disturbances.

34. Preventions • No effective antiviral therapy • Live attenuated rubella virus vaccines safe and effective. • Recommended for women of child bearing age in women results of both hemagglutination inhibition antibody test and a pregnancy test are negative.

35. Viral Hepatitis Hepatitis ‘B’ – Etiopathogenisis • DNA Virus • Localised within hepatic parenchymal cells but circulates in blood stream, along with several subviral antigens from periods ranging from a few days to many years • Transplacental leakage of HBe Ag – positive maternal blood, a potential source of intrauterine infections.

36. Viral Hepatitis – Contd.. • During persistent viremia in mother the virus or viral antigens may rarely cross the placenta to cause intrauterine infection. • Infection can occur perinatally during labour or delivery. • Most infants born to mothers infected with HBV, test negative for HBsAg at birth. • In the absence of HBs Ag positive during the first 3 months of life suggesting transmission is peripartum

37. Clinical Manifestations • Do not show clinical signs of disease at birth. • Without immunoprophyalxis - development of chronic antigenemia. • Less commonly manifest as jaundice, fever, hepatomegaly that either recover or leads to chronic active hepatitis.

38. Investigations • Liver enzymes and bilirubin – reflects the extent of liver damage.

39. Investigations – Contd..

40. Treatment • Infants born to mother known to be HBsAg Positive • First dose Vaccine within 12 hours along with HBIG. • Second dose 1 to 2 months • Third dose within 6 months

41. Herpes Simplex • Two Types - HSV I - HSV II Neonatal herpes caused by HSV II

42. Incidence • 20% - 45% • 1 :3500 – 10,000 • Primary genital herpes infection in a pregnant mother – 33% to 50% • Recurrent maternal infection - 1% to 3%.

43. Etiopathogenisis • Acquire infection from maternal genital tract at the time of delivery • HSV infections acquired even during instrumentations during ophthalmologic examination for premature infants an ritual circumcision performed by Jewish. • Inability of neonatal macrophages and unstimulated neonatal lymphocytes to mediate early viral containment and a profound defect in natural killer cell cytotoxicity.

44. Clinical Spectrum • Multiple system involvements- Liver, Lungs, Adrenalglands, Skin, CNS, Eyes • Three groups Skin – Grouped vesicles around flat irregular ulcers within erythematous base. CNS – Poor feeds, Lethargy convulsions irritability Disseminated - Jaundice, Hypotension, DIC, Shock • Very difficult to differentiate from bacterial sepsis and hence differential diagnosis for any neonate with fever during first 2 weeks of life.

47. Investigations • Virus isolated from • Blood, conjunctiva, respiratory Secretions urine and CNS. • Mothers genital tract • Scraping of skins vesicle may show giant, multinucleated cells • Demonstration of viral antigen in cytologic smears by EIA and DFA staining provide rapid results. • CSF – cell count – Lymphocytosis, RBC, Proteins Sugar – Lower (or) Normal PCR of CSF • In disseminated disease – ALT elevated.

48. Investigations – Contd.. • CT and MRI Brain A loss of gray matter and white matter differentiation and features of encephalitis *Dilated ventricles *Intracranial Calcification * Cystic degeneration * Parenchymal echogenecity • EEG - Abnormal

49. Treatment • Acyclovir 60mg / kg/ day. IV q8th hourly for 2 to 3 weeks. • Herpetic conjunctivitis -Tropical ophthalmic antiviral therapy.

50. Prognosis • Mortality 20% with treatment • Neurological abnormality develops later in 5% group • In CNS disease 4% to 14% with antiviral therapy and survivors have long term neurological sequlae. • In Disseminated Disease 80% dies. • In skin involvement recurrent crops of skin vesicles for several years. • More than 3 episode of recurrent infection in first 6 months of life – Poor neurological outcome.