TORCH INFECTION

Pediatric Resident
MGMCRI
Pondicherry

1. TORCH INFECTION IN NEONATES DR. RAVI KUMAR S PEDIATRIC RESIDENT MGMCRI 1

2. DISCUSSION Introduction Perinatal Infections Clinical features Diagnosis Treatment Prevention 2

3. INTRODUCTION CONGENITAL INFECTIONS “Infections acquired in utero or during the birth process” The infected newborn may show abnormal growth, developmental anomalies, or multiple clinical and laboratory abnormalities Severity depends on the gestational age of fetus at the time of infection & virulence of the organism Timely diagnosis of perinatally acquired infections is crucial to the initiation of appropriate therapy. 3

4. PERINATAL INFECTIONS T = Toxoplasmosis O = Others R = Rubella C = Cytomegalovirus H = Herpes Simplex virus The TORCH acronym has now become Obsolete , due to a large basket of infections in “Others” 4

5. TOXOPLASMOSIS Causative Organism: Toxoplasma gondii Oocyst excreted in cats feces is the source of infection to humans  Contaminates in soil, water & raw meat Transmission : Vertical transmission can occur in utero or during vaginal delivery & r isk of fetal transmission is 25 % in 1 st Trimester 75 % in 3 rd Trimester 90 % during last few weeks prior delivery. 5

6. CLINICAL FEATURES Most infected newborns are asymptomatic at birth Few develop IUGR Fever Maculopapular rash Anemia 6 J aundice Seizure Hepatospleenomegaly Thrombocytopenic purpura

7. Contd., Classical Triad Chorioretinitis Diffuse Nodular Intracranial calcifications Hydrocephalus 7

8. DIAGNOSIS Maternal history & Serology Clinical Examination Laboratory Evaluation - Serology/ CBC / LFT Fundus Examination - Chorioretinitis Neuroimaging – Intracranial Calcifications/ Hydrocephalus Lumbar Puncture – Elevated CSF Protein/ Mononuclear Pleocytosis Prenatal Diagnosis- PCR by Amniocentesis is the best method for prenatal diagnosis of fetal infection. 8

9. CONFIRMED CONGENITAL TOXOPLASMA INFECTION Any of the following: Detection of toxoplasma specific IgM (after 5 days of life) or IgA titres (after 10 days of life) is considered diagnostic of congenital toxoplasmosis in infants with a positive Toxoplasma IgG titre Positive for Toxoplasma IgG beyond 12months of age Positive CSF PCR Increase in anti-Toxoplasma IgG titer during the first year of life or increasing IgG titer compared with the mother's 9

10. MANAGEMENT WHO & CDC Recommends Combination Therapy for standard treatment of congenital toxoplasmosis Pyrimethamine (1mg/kg/day daily for first 6months & 1mg/kg/day thrice a week for second 6 months) Sulfadiazine (100mg/kg/day in 2 divided doses for 1 year) Leucovorin ( Folinic Acid; 5-10mg thrice a week) Prevention Avoidance of Exposure- Food hygiene Materna l Screening Prenatal Treatment - Spiramycin 10

11. RUBELLA Also known as German Measles Organism: RNA virus, a member of the Togavirus family Transmission: Direct droplet contact from nasopharyngeal secretions  virus replicates in the lymph tissue of the upper respiratory tract  spreads hematogenously across the placenta  CRI Maternal infection rate is high, especially at the time of 1st trimester & last 1 month Malformation occurs in 90% of infection during 2-10 weeks of gestation. 11

12. CLINICAL FEATURES General: IUGR, Prematurity, Stillbirth, Abortion CVS: PDA, PAS, CoA Eye: Cataracts, Microphthalmia , Pigmentary Retinopathy Ear: Sensory Neural Deafness GIT: HepatoSpleenomegaly CNS: Meningoencephalitis, Microcephaly, Hypotonia , MR Skin: Blueberry Muffin Rash, Dermatoglyphic abnormalities Blood : Thrombocytopenia Skeletal: Radio- lucencies of long bones 12

13. Blueberry Muffin Rash 13

14. DIAGNOSIS HISTORY OF MATERNAL INFECTION Symptoms - Low-grade fever/Headache/mild coryza and conjunctivitis occurring 1 to 5 days before the onset of rash. M aculopapular exanthem that begins on the face and behind the ears and spreads downward over 1 to 2 days. The rash disappears in 5 to 7 days from onset, Posterior cervical lymphadenopathy is common. 14

15. DIAGNOSIS ANTENATAL DETECTION Specific IgM in Fetal blood obtained by percutaneous umbilical cord blood sampling. Rubella antigen and RNA in a Chorionic villous biopsy specimen. POSTNATAL DETECTION OF CONFIRMED CRI Serology: Detection of Rubella Specific IgM below 3months (or) IgG between 6months to 12 months . Virus Isolation: pharyngeal secretions/urine sample upto 1 yr 15

16. MANAGEMENT Supportive care Multi disciplinary approach Hearing loss - hearing aids and referral to an early intervention program Structural cardiac defects – Surgical correction Ocular abnormalities – Referral to Ophthalmology expert CNS abnormalities - special education services, speech, language, occupational, and/or physical therapy . Endocrine abnormalities – Expert Followup for Diabetes/ Hypothyroidism 16

17. PREVENTION Girls should be vaccinated against rubella before entering the childbearing years . Rubella vaccine is a live attenuated vaccine which is available separately or as triple vaccine (MMR) that contain measles, mumps and rubella . Principal goal of Rubella vaccination is P revention of CRS . As per IAP recommendation – two doses of MMR vaccines - 1st at 15 months and t he 2nd at 4–6 years Special care should be taken in reproductive females to avoid pregnancy for 3 months after MMR vaccination . Avoidance of Exposure 17

18. CMV Causative Organism: Cytomegalovirus - member of herpes virus family It is the most common cause for Non-Hereditary cause of SNHL worldwide. Transmission: Close contact – young children attending daycare center Saliva / Urine/ Blood & Breastmilk * Route – Transplacental / Intrapartam / Postnatal 18

19. CLINICAL FEATURES 19 At birth, most infants with congenital CMV are asymptomatic. Few Develop: SGA /Prematurity Hepatospleenomegaly Microcephaly/ Periventricular Calcifications / SNHL /Seizures Petechiae & Jaundice at Birth Thrombocytopenia Pneumonia

20. DIAGNOSIS Diagnostic Testing of Urine/Saliva for CMV by PCR Viral Culture(Shell vial assay) Detection of CMV IgG antibodies in blood Post Natal Evaluation Include Physical & Neurological Examination Laboratory testing (CBC/Coagulation/LFT) Hearing assessment (ABR) Opthal assessment ( C horioretinitis ) Neuroimaging ( USG Cranium/CT Brain) 20

21. MANAGEMENT For symptomatic congenital CMV Ganciclovir* (12mg/kg/day iv infusion 2 div doses for 6 weeks) Valganciclovir Close monitoring & Followup of infected infants Prevention Personal protective measures/ Avoidance of unnecessary blood transfusion & use of leukocyte depleted blood. Prenatal diagnosis- B y viral culture or CMV DNA detection in amniotic fluid, or by CMV IgM antibody measurement in fetal blood of the symptomatic fetus 21

22. HSV Organism: Herpes Simplex Virus(HSV) - DNA virus with two virologically distinct types : 1 and 2 The virus can cause localized disease of the infant's skin , eye, or mouth ( SEM ) or may be Disseminated disease or CNS disease . Transmission: Contact with genital lesions during delivery: Common Transplacental : Rare . 22

23. CLINICAL FEATURES Inutero Infection: Skin: Scarring, vesicles, hypo/ hyperpigmenation Eyes: Microphthalmia , retinal dysplasia CNS: Microcephaly, encephalomalacia , hydranencephaly Intrapartam / Postpartam Infection: SEM disease : Vesicular lesions, Conjunctivitis, excessive tearing, Ulcerative lesions of the mouth , palate & tongue Disseminated disease : Sepsis, Fever, Respiratory distress, DIC, Skin lesions, CNS involvement(60 to 75%) CNS disease +/ − Skin : Seizures, Lethargy, Irritability, Tremors, Poor feeding, Skin lesions(60 to 70 %) 23

24. LESIONS OF NEONATE WITH SEM DISEASE 24 NECK VESICLES SCALP LESIONS

25. LESIONS OF NEONATE WITH SEM DISEASE 25 EYE VESICLES HYPOPIGMENTED, SCALING, AND CRUSTED EROSIONS OF THE TRUNK AND EXTREMITIES

26. DIAGNOSIS For SEM disease - Viral Culture by Isolation – Newer vesicular fluid , Urine & conjunctival smears. For Non SEM disease– PCR of CSF EEG and I maging studies of brain also aids in the diagnosis of HSV encephalitis Cytology of vesicular fluid – Presence of Tzanck cells 26

27. MANAGEMENT Acyclovir Therapy - 60 mg/kg/day 3 div doses SEM disease : Duration for 14 days CNS / Disseminated disease : Duration f or at least 21 days, or longer if the CSF PCR remains positive. Infants with ocular involvement : Ophthalmologic evaluation / Topical ophthalmic antiviral agents in addition to parenteral therapy . 27

28. Contd., Recent evidence : Suggests to start on suppressive therapy following parenteral treatment with oral acyclovir 300 mg/m2 per dose three times per day for six months as it reduces cutaneous recurrences and is associated with improved neurologic outcomes in infants with CNS disease. Prevention : C-Section for mothers with genital lesions Acyclovir for pregnant mothers with primary HSV 28

29. PERINATAL HIV INFECTION Organism: Retrovirus 80% of HIV Infections in children occur during perinatal period Transmission: 35% Risk of Mother to child transmission(MTCT) of HIV during perinatal period 30% Vertical 6 0% During labor & delivery 10% Breastmilk 29

30. RISK FACTORS Maternal: High viral load/ Low CD4 count Primary infection during pregnancy/Vaginal delivery Pronlonged ROM Fetoplacental : Chorioamnionitis Prematurity Postnatal: Breastfeeding (viral load)/Cracked nipples/Mastitis EBF Infant having oral thrush at less than 6 months 30

31. PREVENTION OF PERINATAL HIV Risk of MTCT can be reduced by ARV Prophylaxis to the mother during pregnancy/ labor & to the infant after birth. Elective C-Section( prior to onset of labor & ROM) & Complete avoidance of breastfeeding Membranes should not be artificially ruptured unless there is fetal distress/delay in progress of labor Repeated vaginal examinations/instrumental delivery/ invasive procedure on fetus / routine episiotomy must be avoided 31

32. ARV REGIME – PREGNANT WOMEN R ecent WHO guidelines recommends an simplified, optimized & fixed dose combination of ART HIV detected Pregnant women during antenatal period must be initiated on ART regimen as below throughout the pregnancy (regardless of clinical stage/CD4 count) Tenofovir (TDF) 300mg Lamivudine(3TC) 300mg Efavirez (EFV) 600mg Initiation shouldn’t be delayed for C4 count Lifelong ART is initiated as soon as possible 32 Alternate Regimen AZT+3TC+EFV AZT+3TC+NVP TDF+3TC+NVP

33. ARV REGIME – INFANTS BORN TO HIV MOTHER If mother received ART adequately/regularly in antenatal period: Daily NVP prophylaxis at birth till 6 weeks of life. If Infected Mother did not receive any ART earlier/ directly presents in labor without adequate duration of ART( atleast 24 weeks): Daily NVP prophylaxis at birth till 12 weeks of life. First dose initiated within 6-12 hrs of delivery Dose can be increased to 20mg OD after 6-8 wks of age. 33 B.WT NVP DAILY DOSE DAILY DOSE IN SUSP <2kg 2mg/kg OD 0.2ml/kg 2-2.5kg 10mg OD 1ml OD >2.5kg 15mg OD 1.5ml OD

34. POSTNATAL DIAGNOSIS OF HIV INFECTION 34

35. HEPATITIS B VIRUS Organism: HBV- DNA Virus Most common cause of acute & chronic Hepatitis Transmission: Exposure of Infected maternal blood via percutaneous or permucosal routes during delivery. Amniocentesis Breastfeeding not contraindicated Clinical Features : Affected neonates are mostly asymptomatic. Later Develop chronic antigenemia with mild and often persistent liver enzyme elevations beginning at two to six months of age 35

36. INFANT BORN TO MOTHER WITH HEPATITIS-B INFECTION 36

37. Contd., 37

38. CONGENITAL TUBERCULOSIS Organism: Mycobacterium Tuberculosis Risk factors: Tubercular endometriosis Miliary TB/Genital TB Transmission: Transplacental spread Postnatal exposure from infected mother/healthcare worker Clinical Features: Fever Lymphadenopathy Lethargy Poor feeding 38 HSM Tachypnea Jaundice

39. INFANT BORN TO MOTHER WITH TUBERCULOSIS 39

40. OTHER PERINATAL INFECTIONS DISEASE TRANSMISSION SYMPTOMS DIAGNOSIS TREATMENT Chickenpox VZV 1 st 20wks of Pregnancy Cicatricial lesions L imb hypoplasia Microcephaly Cataract PCR of Vesicular fluid Acyclovir VZIG Syphilis T,Pallidum Between 1 st & 2 nd Trimester of Pregnancy Skeletal abnormalities Pseudoparalysis Persistent rhinitis Maculopapular rash Specific IgM fluorescent antibody Benzathine Penicillin G Malaria P.Vivax & Falciparum Infected blood administration Stillbirth/IUGR Hemolytic Anemia Jaundice Blood Smear Chloroquine Phosphate Parvo Virus B19 Within the first 20 weeks Abortion/ Anemia Hydrops Slapped Cheek rash PCR of Blood Supportive IVIG Coxsackie B Intrauterine exposure Carditis Orofacial clefts Cord serum for specific IgM Supportive care 40

41. DIAGNOSTIC TECHNIQUES FOR DIAGNOSIS OF COMMON PERINATAL INFECTIONS PATHOGEN TEST OF CHOICE RUBELLA Isolation – Viral Culture of Urine/ Throat swab Cord serum for IgM & specific IgM fluorescent antibodies HSV PCR of skin lesion, blood, or CSF CMV PCR urine/saliva Spin-enhanced urine culture (shell vial) HIV DNA PCR – Blood if mother is HIV Infected HBV HBsAg of blood DNA PCR of blood VZV PCR of skin lesion TOXOPLASMA Specific IgM & IgA fluorescent antibody by ELISA/ ISAGA PCR - CSF SYPHILIS Specific IgM fluorescent antibody Paired Maternal & Cord sera for RPR/VDRL 41

42. TAKE HOME MESSAGE CMV, Rubella, Toxoplasma are the most common cause of chronic intrauterine infections in the newborn . Congenital TB should be suspected in newborns who have Non-resolving pneumonia, persistent fever & HSM, in absence of any of the bacterial pathogen isolated on culture. DNA PCR to detect HIV should be conducted in a neonate 6 weeks after cessation of breastfeeding. Timely diagnosis of perinatally acquired infections is crucial to the initiation of appropriate therapy, development of care plan, prognosis, and family counseling . 42

43. T H A N K Y O U 43