Neonatal HSV SARA SAPORTA-KEATING 3/1/17

Transcription

1 Neonatal HSV SARA SAPORTA-KEATING 3/1/17

2 Pt Sx onset Presentation Clinical Presentation HSV risk factor(s) HSV results CSF WBC 1 DOL 7 DOL 8 Vesicular rash FOC with active cold sore (DOL2), C/S 2 DOL 7 DOL 68 Recurring scalp vesicles Maternal primary genital outbreak around delivery; Vacuum delivery +DFA vesicle, +blood, - CSF (HSV-1) +DFA vesicle, +blood, - CSF (HSV-2) 3 DOL 14 DOL 16 Seizure, fever, sleepy None determined +CSF, +blood (HSV- 2) 4 DOL 3 DOL 3 Fever (101.1), fussy, respiratory distress 5 DOL 6 DOL 6/ DOL 14 Fever, hypoxia/ Fever, fussy, sleepy MGF with active cold sore (DOL5), FOC with h/o HSV FOC with h/o HSV, maternal fever at delivery 7 SEM HSV Diagnosis 12 SEM and CNS (mild pleocytosis) 6 CNS +CSF, +blood (HSV-1) 48 Disseminated and CNS (liver, resp failure) +blood (HSV-2) N/A Disseminated and CNS (liver, resp failure; encephalopathy) Death

3 Classification Classification Proportion Common presentation(s) HSV evaluation SEM 45% 9-11 days after birth Vesicular or ulcerative skin lesions If no lesions: poor PO, temperature instability, irritability CNS 30% days after birth Lethargy, irritability, poor PO Temperature instability Seizure, bulging fontanelle High morbidity Disseminated 25% 9-11 days after birth Septic appearance Liver, respiratory failure, DIC High mortality/morbidity + vesicle DFA, PCR, cx + SEM culture + blood PCR + CSF PCR + blood PCR + blood PCR +/- SEM culture +/- CSF PCR (~50%) + Evidence of organ failure (e.g., liver, respiratory, GI, adrenal)

4 Timing of exposures Maternal to child transmission: Peripartum (85%) Symptomatic or asymptomatic viral shedding from genital tract around time of delivery Of women with recurrent genital herpes, 1.4% can have asymptomatic shedding at delivery Infants can have transplacental HSV Ab Up to 80% of women who transmitted HSV to their infants have no known history of HSV Postpartum (10%) Direct contact with HSV (usually from oral or cutaneous lesions) In utero (5%) Presents with: Active lesions, aplasia cutis, microcephaly, intracranial calcifications, optic atrophy, microphthalmia, chorioretinitis

5 Epidemiology Seroprevalence >90% of adults have acquired HSV-1 by 5 th decade of life Incidence of neonatal HSV infection in the US estimated at 1:3200 deliveries in 2012 Difficult to quantify, not reportable in many areas Red Book cites incidence at 1:3000 to 1:20,000 live births

6 Diagnosis of neonatal HSV

7 Diagnostics Special instructions How it is helpful SEM HSV culture Eyes, mouth, rectum Coupled with DFA to detect HSV Vesicle HSV culture Unroof vesicle, swab base Coupled with DFA to detect HSV CSF HSV PCR Repeat towards end of treatment for CNS disease; must be negative prior to stopping therapy Blood HSV PCR Qualitative; not enough data to support use of quantitative Do not repeat to monitor response to treatment LFTs Coag studies Diagnose CNS disease Document clearance of virus prior to stopping treatment Positive in many patients with neonatal HSV regardless of classification Diagnosing disseminated disease Diagnosing disseminated disease

8 Seattle Children s has performed CSF PCR since 1999 and quantitative PCR from blood and CSF since 2001 Retrospective review of confirmed HSV cases Classified as SEM, CNS, or disseminated Reviewed quantitative PCRs from blood and CSF for each patient (done real-time) Total 63 cases (41% SEM, 29% CNS, 30% disseminated)

9 Use of all three diagnostic tests beneficial for diagnosis CSF contaminated with blood

10 HSV PCR copies in blood (not CSF) associated with severity of disease and outcome Blood HSV PCR CSF HSV PCR

11 Repeating blood HSV PCR to follow disease? Median viral half-life ~1.26 days Each patient had severe DIC 5 patients had severe hepatitis Patient 6 with clinical worsening and increase in viral load after ACV stopped

12 Possibilities for additional uses of HSV PCR in the future? Need more data!!! Interesting correlations made with this study Plasma viral load corresponded with clinical outcome CNS viral load did not correlate with neurologic outcomes at 2mo following treatment Can follow the progression of viremia, but not cleared until end of treatment, or even after

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14 References Long SS, et al. Herpes Simplex virus infection in young infants during 2 decades of empiric acyclovir therapy. PIDJ (2011); 30(7): Curfman AL, et al. Initial presentation of neonatal herpes simplex virus infection. JPeds (2016); 172: Wolfert SIM, et al. Diagnostic and therapeutic management for suspected neonatal herpes simplex virus infection. JClinVirol (2011); 51:8-11. James SH and DW Kimberlin. Neonatal Herpes Simplex virus infection: Epidemiology and treatment. ClinPerinatol (2015); 42: Looker KJ, et al. First estimates of the global and regional incidence of neonatal herpes infection. Lancet Glob Health (2017); 5:e James SH and DW Kimberlin. Neonatal Herpes Simplex virus infection. InfectDisClinNAm (2015); 29: James SH and DW Kimberlin. Quantitative Herpes Simplex virus concentrations in neonatal infection. Editorial, JPeds (2015); 166(4): Gottlieb SL and C Johnston. Future prospects for new vaccines against sexually transmitted infections. CurrOpin InfDis (2017); 30: Melvin AJ, et al. Plasma and cerebrospinal fluid Herpes Simplex virus levels and outcome of neonatal infection. JPeds (2015); 166: Wilson P, et al. Persistent gaps in appropriate use of empiric acyclovir in neonates. ClinPeds (2016); p1-8 Kotzbauer D, Frank G, Dong W, S Shore. Clinical and laboratory characteristics of disseminated Herpes Simplex virus infection in neonates. HospPeds (2014); 4(3):