Understanding Congenital Infections: TORCH Complex and Their Impact on Neonatal Health

1. CONGENITAL INFECTIONS Dr. Mohammad A. Khan, MD PhD Consultant Microbiologist Prince Mohammad Bin Abdul Aziz Hospital Riyadh April 24, 2017

2. Congenital Infections: Objectives • Complications of infection • Route of infection • TORCH infections • Congenital Parvovirus • Congenital Varicella • Neonatal Sepsis (GBS)

3. Complications of Congenital Infections • Intrauterine growth retardation • Microcephaly and hydrocephalus • Intracranial calcifications • Blueberry muffin skin rash • Jaundice • Cataracts • Chorioretinitis • Deafness LONG-TERM COMPLICATIONS WITH INCREASED PERINATAL MORTALITY AND PUBLIC HEALTH BURDEN

5. Route of Infection

6. Screening in Pregnancy (Antenatal Care) -Routine examination -Ultrasound -TORCH Screen

7. Congenital Infections • Toxoplasmosis T • Syphilis Other • Rubella R • Cytomegalovirus C • Herpes simplex H • Parvovirus B19 • Varicella • Group B Strep

8. Toxoplasmosis (Toxo) • Toxoplasma gondiicauses zoonotic parasitic infection • Definitive host is the domestic cat • Contact with oocysts in feces • Ingestion of cysts (meats, garden products) • Transmitted from the mother to the baby

9. Toxoplasmosis in KSA Dhahran: IgG 28% among 400 pregnant women US seroprevalence: 14% (1990s) to 9% (2010)

10. Toxoplasmosis

11. Toxo: Clinical Presentation • Mostly asymptomatic • Classic triad of symptoms: • Chorioretinitis • Hydrocephalus • Intracranial calcifications • Other symptoms include fever, rash, HSM, microcephaly, seizures, jaundice, thrombocytopenia, lymphadenopathy

12. Toxo: Diagnosis and Management • Diagnosis 1. Maternal serology IgM, IgG 2. Fetal ultrasound and PCR 3. Newborn IgM, IgA ELISA PCR • Treatment Spiramycin Pyrimethamine and Sulfadiazine • Prevention Avoid exposure to contaminated food, water, undercooked meat Hand washing

13. Congenital Syphilis • Treponema pallidum (spirochete)-STD • Mother with primary or secondary syphilis • Typically acquired in second half of pregnancy • May cause: miscarriage, stillbirth, prematurity low birth weight and increased perinatal mortality

14. Intrauterine death in 25% 3 major classification Congenital Syphilis Frontal bossing, Short maxilla, High palatal arch, Saddle nose, Perioral fissures

15. Diagnosis and Treatment Treatment • Penicillin G Prevention • EIA/RPR/VDRL screen in ALL pregnant women early in pregnancy and at time of birth Diagnosis • Specific Treponemal EIA test • Non-treponemal test RPR/VDRL • T. pallidum in skin lesions, placenta, umbilical cord, or at autopsy by PCR

16. Syphilis testing algorithm Michael J. Loeffelholz, and Matthew J. Binnicker J. Clin. Microbiol. 2012;50:2-6

17. Rubella • RNA enveloped virus, Togaviridae family, German measles, 3 day measles  • Spread: respiratory droplets and trans-placental • Mild infection in women with fever, sore throat and rash (face body) lasts about 3 days • Non-immune pregnant women • do not immunize during pregnancy • avoid exposure to rubella • post-partum vaccine

18. Rubella • Vaccine-preventable (MMR), self-limiting disease • No longer considered endemic, eliminated in some countries • Infection earlier in pregnancy has a higher probability of transmission: - first 12 weeks 70% - 13-16 weeks 20% - rare after 16 weeks of pregnancy

19. Public Health Efforts Can Eliminate Disease

20. Congenital Rubella: Clinical Findings • Asymptomatic: 50% at birth • Sensorineural hearing loss • Mental retardation • PDA, peripheral pulmonary stenosis • Ocular: cataracts, chorioretinitis, glaucoma • Microcephaly • Blueberry muffin rash

21. Congenital Rubella: skin Lesions

22. Congenital Rubella Syndrome

23. Congenital Rubella Syndrome: Diagnosis • Diagnosis: • Rubella specific IgM positive > 5 days after rash < 5 days after rash may need multiple samples • IgM false +ve due to Parvo, Entero & HHV-6 (Roseola) • Rising IgG titres • Rubella RT-PCR (newborn): Pharyngeal and Urine sample • Viral culture: nasopharynx, blood, urine, CSF

24. Rubella: Treatment & Prevention • Supportive care with parent education • Prevention by immunization-Rubella MMR Vaccine • Maternal screening in pregnancy • Vaccinate if not immune (avoid pregnancy for three months)

25. Cytomegalovirus • Cytomegalovirus: DNA virus, Herpesviridae, latency and reactivation (transplants, neutropenic) • Most common congenital viral infection~0.5-2.5% of all live births per year • Primary infection in women: Inf. mononucleosis (Mono) and hepatitis • Rule out EBV and Hep A, B & C

26. Cytomegalovirus: Transmission • Vertical transmission • Transplacental • perinatal acquisition: contact, birth canal, breastfeeding • maternal primary and reactivated CMV • Incidence: • 2.5% • most are asymptomatic - 95%

27. Congenital Cytomegalovirus Infection • Intracranial calcifications, hydrocephalus • Thrombocytopenia, petechiae, purpura • Hepatitis • Pneumonia • Hearing loss-most common complication • Mental retardation • Neurologic impairment, cerebral palsy • Chorioretinitis • Intestinal obstruction

28. CMV: Hydrocephalus & Calcifications BPD

29. Cytomegalovirus: Diagnosis • CMV titers in mothers: • IgM, IgG avidity tests • Acute and convalescent • Ultrasound in pregnancy (BPD and CNS comp.) • Newborns-CMV PCR of Saliva & Urine • Children > 1 year: Serology, CNS & Eye exam

30. Cytomegalovirus: Prevention & Treatment • Antenatal screening • Anti-viral treatment • Ganciclovir (inhibits viral DNA polymerase) • limited efficacy • Hearing and Visual tests • Infectious disease consultation

31. Herpes Simplex Virus (HSV) • HSV 1 and 2 enveloped DNA virus cause neonatal infections • Vertical transmission most common • perinatal exposure with ROM and delivery • 50% risk if infant exposed to primary maternal HSV • increased risk in premature infants (reduced IgG) • Horizontal transmission in nursery outbreaks • Time of onset: 2 days - several weeks

32. Herpes Simplex: Clinical Presentation • Fever • skin vesicles • encephalitis • seizures • respiratory distress, pneumonia • hepatitis

33. Herpes Simplex Skin Lesions

34. Herpes Simplex Skin Lesions

35. Herpes Simplex Conjunctivitis

36. Herpes Simplex Oral Lesions

37. Herpes Simplex: Encephalitis

38. Neonatal Herpes Simplex: Treatment • Acyclovir (viral DNA polymerase inhibitor) • Supportive: control seizures, respiratory and cardiovascular support • Reduce cutaneous or ocular spread • High mortality rate for CNS or systemic HSV, even with treatment

39. Parvovirus B19 • Single stranded non-enveloped DNA Virus • Respiratory droplet spread, blood & transplacental • Associated with multiple disorders: • Erythema infectiosum (fifth disease), slapped cheek • Aplastic crisis (hemolytic disorders, sickle cell) • Acute arthritis • Congenital: Fetal death (hydrops) due to anemia

40. Parvovirus B19

41. Diagnosis and Treatment • Treatment • intrauterine transfusion • Supportive tmt. • Diagnosis • Ultrasound • Serology IgM, persistant IgG • PCR Prevention • Washing hands with soap and water • Covering mouth and nose when coughing/sneezing • Not touching your eyes, nose, or mouth • Avoiding close contact with people who are sick • Staying home when you are sick

42. Congenital Varicella • Varicella: DNA enveloped Herpes virus • 90% of pregnant women already immune • Primary infection during pregnancy carries a greater risk of severe disease • Disease dependent on timing of exposure to Varicella

43. Varicella • Maternal varicella before 20 weeks: congenital anomalies reported to be 1-2% • Skin lesions • Limb hypoplasia • CNS, ocular, neurologic • Maternal varicella in last 5 days of pregnancy to 2 days post partum: • Skin lesions, pneumonitis, disseminated disease • Varicella Zoster Immunoglobulin (VZIG) • Acyclovir

44. Varicella: Skin lesions

45. Congenital varicella: Limb hypoplasia

46. Varicella Pneumonia

47. Varicella Diagnosis

48. Varicella: Treatment and Prevention • Acyclovir for Varicella pneumonia in new born • Pre-exposure: live-attenuated vaccines before or after pregnancy but NOT during pregnancy. • Post-exposure:Zoster immunoglobulin (VZIG) for: -susceptible pregnant women -infants whose mothers develop Varicella during the last 5 days of pregnancy or the first 2 days after delivery -premature babies born <28 wks of gestation

49. Group B Streptococcus (GBS) & Neonatal Sepsis • Gram positive, beta hemolytic bacteria • Common colonizer of human gastrointestinal and genitourinary tracts • Causes serious disease in newborns • Common cause of sepsis and meningitis in infants

50. GBS Disease in Infants Early-onset: 0-6 days of life Late onset: 7-89 days of life A Schuchat. Clin Micro Rev 1998;11:497-513.