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CONGENITAL INFECTIONS. Dr. Mohammad A. Khan, MD PhD Consultant Microbiologist Prince Mohammad Bin Abdul Aziz Hospital Riyadh April 24, 2017. Congenital Infections: Objectives. Complications of infection Route of infection TORCH infections Congenital Parvovirus Congenital Varicella
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CONGENITAL INFECTIONS Dr. Mohammad A. Khan, MD PhD Consultant Microbiologist Prince Mohammad Bin Abdul Aziz Hospital Riyadh April 24, 2017
Congenital Infections: Objectives • Complications of infection • Route of infection • TORCH infections • Congenital Parvovirus • Congenital Varicella • Neonatal Sepsis (GBS)
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
Screening in Pregnancy (Antenatal Care) -Routine examination -Ultrasound -TORCH Screen
Congenital Infections • Toxoplasmosis T • Syphilis Other • Rubella R • Cytomegalovirus C • Herpes simplex H • Parvovirus B19 • Varicella • Group B Strep
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
Toxoplasmosis in KSA Dhahran: IgG 28% among 400 pregnant women US seroprevalence: 14% (1990s) to 9% (2010)
Toxo: Clinical Presentation • Mostly asymptomatic • Classic triad of symptoms: • Chorioretinitis • Hydrocephalus • Intracranial calcifications • Other symptoms include fever, rash, HSM, microcephaly, seizures, jaundice, thrombocytopenia, lymphadenopathy
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
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
Intrauterine death in 25% 3 major classification Congenital Syphilis Frontal bossing, Short maxilla, High palatal arch, Saddle nose, Perioral fissures
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
Syphilis testing algorithm Michael J. Loeffelholz, and Matthew J. Binnicker J. Clin. Microbiol. 2012;50:2-6
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
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
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
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
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)
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
Cytomegalovirus: Transmission • Vertical transmission • Transplacental • perinatal acquisition: contact, birth canal, breastfeeding • maternal primary and reactivated CMV • Incidence: • 2.5% • most are asymptomatic - 95%
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
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
Cytomegalovirus: Prevention & Treatment • Antenatal screening • Anti-viral treatment • Ganciclovir (inhibits viral DNA polymerase) • limited efficacy • Hearing and Visual tests • Infectious disease consultation
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
Herpes Simplex: Clinical Presentation • Fever • skin vesicles • encephalitis • seizures • respiratory distress, pneumonia • hepatitis
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
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
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
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
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
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
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
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.