2 What does she have?? Hypothetical case S.A. female neonate Has: JaundiceHSMPtechiaePDALymphadenopathyHearing loss
3 Congenital infections: 3 Routs of infection:Trans placental: TORCHAscending/intrapartum: HSV, CMV, HBV, HIVBreast milk: HBV, CMV, HIV
4 Transplacental infection May occur at any time during gestationSigns and symptoms may be present at birth or be delayed for months of even years.importance of stage of embryonic life in the manifestations of the infection:1st trimester: may alter embryogenesis and result in malformations (rubella)3rd trimester: often results in active infection at the time of delivery (toxoplasmosis, syphilis)
5 ProtectionMaternal antibody is effective for protection of the fetus, in some of the cases (rubella)transplacental transmission of infection to a fetus is variable because the placenta may function as an effective barrier
6 Clinical signs and symptoms Maternal- most are asymptomaticInfant- range from early spontaneous abortion, congenital malformation, intrauterine growth restriction, premature birth, stillbirth, acute or delayed disease in the neonatal period, or asymptomatic persistent infection with sequelae later in life.In some cases, no apparent effects are seen in the newborn infant.
7 What is TORCH? T- Toxoplasmosis O- others R- Rubella C- cytomegalovirus (CMV)H- Herpes
8 ToxoplasmosisCaused by the obligate intra-cellular parasite Toxoplasma GondiiRoute of infection:Fecal-oral: Cat feces uncooked meet, contaminated water and soil, unpasteurized goat milk.Usually, the infection causes a mild flu-like illness, or no illness at all.BUT, in immunocompremised or pregnant women it can be fatal, and cause symtoms such as: encephalitis, myocarditis and pneumonitis.
9 Toxoplasmosis- continue… Fetal transmission:in a primary infection, or chronic disease in immunocopremised mother.The risk of fetal transmission increases with gestational ageThe earlier in pregnancy the transmission occurs- the damage is worse.
10 Toxoplasmosis- continue… Signs and symptoms:1st trimester: death, opthlmologic and CNS sequalea2nd trimester: “classic triad”: hydrocephalus, intracranial calcifications, chorioretinitis. Jaundice, HSM, anemia, lymphadenopathy, microcephaly, developemental delay, visual and hearing problems, and seizures.3rd trimester: usually asymptomatic at birth.תמונה תחתונה- צהבת, הפטוספלנומגליה, פורפורה טרומבוציטופניתתמונה אמצעית- קלציפיקציותתמונה עליונה- כוריורטיניטיס- Severe, active retinochoroiditis.
15 Rubella- continue… Diagnosis: Treatment: Positive infant rubella IgM titer- recent infectionCulture: blood, urine, CSF, oral & nasal secretionspersistently elevated or rising IgG titers over time.Treatment:Supportive care only.
16 Cytomegalovirus Member of the Herpesvirus family Most common congenital infection in the US (0.5-1% of live births in industrialized nations, approximately annualy in the US)Route of infection:TransplacentallyDuring deliveryPostnatally (breastmilk (causes no clinical sequelae), or direct contact with other body fluids)Maternal infection before pregnancy significantly reduces the risk of congenital CMV.
17 CMV- continue… Clinical manifestations: 30% mortality rate Symptoms include:IUGRMicrocephalyPeriventricular calcificationsHSMPetechiaeHearing lossJaundiceThrombocytopeniaretinitisHypotonoiaLethargyIn preterm infants may present as sepsisClinical manifestations:Most babies are asymptomatic at birth (90%)Infants to mothers with primary infection- 5-20%: overtly symptomatic.30% mortality rate80% of survivors: severe neurologic morbidityClassic linear periventricular calcifications and cortical atrophy
18 CMV- continue… Treatment: no approved agent Complications:CNS sequelae: retinitis, sensorineural deafness, developmental delay)Will appear in 20% of asymptomatic neonatesWill appear in 50% (or more!) of symptomatic neonatesDiagnosis:demonstration of the virus in body fluids (e.g. urine or pharyngeal secretions).Serology for CMV IgG antibody determination are not useful in this case.Laboratory abnormalities include: abnormal blood counts (especially thrombocytopenia), hemolytic anemia, elevated transaminases, and elevated direct and indirect serum bilirubin.Treatment: no approved agentGanciclovir- improves hearing loss and neurodevelopmental outcomes In a phase II randomized, controlled multicenter clinical trial evaluating the use of ganciclovir for the treatment of infants with symptomatic congenital CMV infection and evidence of CNS involvement, 47 infants received ganciclovir (8 to 12 mg/kg daily in 2 divided doses for up to 6 weeks) . Ganciclovir was discontinued in eight patients because of side effects but was well tolerated in the other newborns. Decreased excretion of virus was noted during ganciclovir administration, although viruria returned promptly after cessation of therapy. Sixteen percent of the infants had stabilization or improvement in hearing at six months of follow-up. Similar results were observed in a smaller trial .A phase III randomized clinical trial of ganciclovir (6 mg/kg per dose IV every 12 hours) for six weeks in neonates with virologically confirmed congenital CMV disease and neurologic involvement suggested that treatment with ganciclovir prevents hearing deterioration at six months and possibly beyond . The conclusions are limited because only 42 of the 100 enrolled subjects were evaluated for the primary outcome (hearing assessment at six months) . In addition, neutropenia (absolute neutrophil count ≤1250/microL) was more common among ganciclovir recipients than controls (63 versus 21 percent).It remains unknown whether this early and intensive administration of ganciclovir will hasten resolution of disease, beneficially influence growth and development, decrease auditory and visual impairment, or improve intellectual outcome in these infants. Ganciclovir should not be used routinely for fear of unforeseen long-term effects, such as testicular atrophy and bone marrow suppression. However, it may be reasonable to consider in selected cases. However, anecdotal evidence does suggest that critically ill newborns, especially those who are premature and have CMV pneumonia, may benefit acutely from ganciclovir treatment. Compassionate use also may be appropriate for patients with life- or sight-threatening congenital CMV. Thus, we recommend its use only after careful consideration in selected cases.The treatment of newborns with asymptomatic congenital infection is not indicated. Even though these infants are at some risk for hearing loss, the side effects of therapy with currently available antiviral agents and the lack of established benefit argue against routine administration.The use of CMV hyperimmune globulin has not been evaluated extensively for the treatment of congenital CMV disease. However, anecdotal reports suggests some benefit [53,54]. Both CMV immune globulin and alpha interferon are being studied for the treatment of congenital CMV. The development of CMV vaccines also is underwa
19 Herpes simplex virusDouble-stranded DNA virus of the herpesviridae familyRoute of infection:Primarily: during birth or virus ascending after the rupture of membranes.Transplacentally- rarePostnatallyGreatest risk: primery maternal infection during third trimester.
20 HSV- continue… Clinical manifestations: Complications: SEM disease: skin, eyes, mucosal involvementCNS disease- temperature instability, respiratory distress, poor feeding, and lethargy (nonspecific)Disseminated disease with multiple organ involvementUsually presents in the first 6 weeks.Most are asymptomatic at birth although many are born prematurelyComplications:Untreated- high morbidity and mortalityTreated: SEM- best prognosis. 50% will suffer from recurrent skin outbreks.CNS- good survival, significant neurologic sequelae
21 HSV- continue… Diagnosis: Treatment: IV acyclovir Serum HSV IgM HSV PCR of CSF- test of choice, may be false negative in the first 5 daysHSV culture of a lesion/mucosal surface- best for SEMTreatment: IV acyclovirimproves mortality in all infantsImproves neurologic development in those with SEM and disseminated disease.
22 And…. Back to Others!HIVHBVParvovirus B19SyphilisHCVVZVTB
23 HIV Member of the retroviridae family. Route of infection to the fetus:TransplacentallyDuring labor and delivery- the highest risk (exposure to maternal blood)Through breastfeedingClinical manifestations:Asymptomatic at birthT-cell count declines and opportunistic infections take hold: Pneumocystis jiroveci, VZV, CMV, HSV….
24 HIV- continue… Diagnosis: The American Academy of Pediatrics and the CDC: HIV screening for all pregnant women in the US.According to viral load:HIV drug prophylaxisC-section before rupture of membranes (viral load greater than copies/mL at full term delivery)avoidance of breastfeedingEarly detection in the infant
25 HIV- continue… Diagnosis: Treatment: In the infant: HIV-1 DNA/RNA pcr at:14-21 days after birth1-2 months4-6 monthsConsidered uninfected if:2 negative tests- one after 1 month, and another at 4 months +2 negative antibody tests from different specimens obtained at 6 months +Treatment:Infants suspected: zidovudine until 6 weeks of ageInfants confirmed: further antiretroviral treatment
26 HBV DNA virus of the hepadnavirus family Route of infection: transplacentally- rareDuring delivery with exposure to maternal blood- most cases.Clinical manifestations:Most asymptomatic at birthRarely- signs of hepatitis: jaundice, thrombocytopenia, elevated transaminase conc. , rash.The risk of morbidity and of progressing to a chronic infection and disease are inversely proportional to gestational age at the initial infection
27 HBV- continue… So… why are we worried? Diagnosis: Because- 25% of children chronically infected with HBV will develop hepatocellular carcinoma or cirrhosis!Diagnosis:In the US- women are screened for HBsAgIf positive- the infant should receive HBV vaccine and Hepatitis B immune globulin within 12 hrs of birth.They should complete the regular program of vaccinations to HBV+two more+ HBsAg and anti-HBs testing at 9 months of age
28 HBV- continue… If the mother’s HBV status is unclear: Treatment: Immediate test for HBsAg:If negative- no further treatmentIf positive- the infant should receive HBV immunoglobin within 7 days of birth.Treatment:There is no treatment for acute HBVFor chronic HBV- Lamivudine- approved for 2 years of age and older.
29 Parvovirus B19 Single-stranded DNA virus Hydrops fetalis: a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments.Very high mortality ratesParvovirus B19Single-stranded DNA virusUsually causes “fifth disease” (“slapped cheek”), and other symptoms.Route of infection:Respiratory tract secretionsContaminated bloodTransplacentallyClinical manifestations:Hydrops fetalis (due to severe fetal anemia)Pleural end pericardial effusionsIUGRdeath
30 Parvovirus B19- continue… Diagnosis:IgM titer from the infant serumPCR of amniotic fluidTreatment:Supportive care
31 Rubella!! What does she have?? Hypothetical case S.A. female neonate Has:JaundiceHSMPtechiaePDALymphadenopathyHearing lossRubella!!
32 SummaryTimely diagnosis of congenital infections is crucial to the initiation of appropiate therapyHigh index of suspicion and awareness is required:Laboratory results obtained from the mother during pregnancyClinical manifestations including:Hydrops fetalisMicrocephalySeizuresCataractHearing lossCongenital heart diseaseHSMJaundiceRashthrombocytopenia