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 TRANSMISSION TYPES Intra-uterine Trans-placental
Ascending infection
Intra-partum
Contact with infected materials during delivery, secretion, blood & feces
Post-partum
Breast feeding
Blood transfusion
Nosocomial

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 gondii causes 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
1. Maternal serology
IgM, IgG
2. Fetal ultrasound and
PCR
3. Newborn
IgM, IgA ELISA
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. Congenital Syphilis Intrauterine death in 25% 3 major classification
Frontal bossing, Short maxilla,
High palatal arch, Saddle nose,
Perioral fissures

15. Diagnosis and 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%
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
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. Treatment & Prevention
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~ % 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
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 Test Specimen Mother and Fetus Neonate PCR
Most sensitive
Vesicular fluid +
Fetal blood and amniotic fluid
Serology
(IgM false negatives)
IgM
Rising IgG titres
IgG avidity assay
US and MRI

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. Early-onset: 0-6 days of life Late onset: 7-89 days of life
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:

51. Early-onset GBS Disease (EOGBS)
Leading infectious cause of neonatal sepsis
Annual incidence: 0.28 cases / 1000 live births US 2008,
1.5 cases /1000 live births in KSA 2016
Clinical presentation
Typically symptoms appear on day 0 or day 1 of life
Respiratory distress, apnea, signs of sepsis most common symptoms
Bacteremia most common form of disease (app. 80% of cases)
Pneumonia and meningitis may also occur
Case fatality rate
1970s: As high as 50%
4-6% in recent years

52. Key Prevention Strategies
Universal screening of pregnant women for GBS at weeks gestational age, Vaginal & Rectal Swab
Intrapartum antibiotic prophylaxis for:
GBS positive screening test
GBS colonization status unknown with
Delivery <37 weeks
Temperature during labor >100.4˚ F (>38.0˚ C)
Rupture of membranes >18 hours
Previous infant with GBS disease
GBS in the mother’s urine during current pregnancy
Penicillin for Intra Partum Antibiotic Prophylaxis (IAP)
Ampicillin acceptable alternative
Cefazolin preferred for penicillin-allergic at low risk of anaphylaxis

53. THANK YOU CONCLUSIONS & Take Home Message
Congenital infections cause lifelong debilitating
disease
Comprehensive antenatal screening can identify
diseases early
Treatment with Antimicrobial agents, Vaccines and
Immunoglubulins can be beneficial
Follow up, education and supportive care can improve
clinical outcomes for families
THANK YOU