Kidz Medical Services Infant Exposed to Genital Herpes Simplex Virus

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1 Kidz Medical Services Infant Exposed to Genital Herpes Simplex Virus Guideline: HSV Guideline: I. Herpes Simplex Virus (HSV): A. HSV is an enveloped, double-stranded DNA virus that enters the body via mucosal surfaces or abraded skin. B. The strains of HSV are grouped into two serologic subtypes: HSV-1 and HSV-2. C. Managing infants potentially exposed to HSV at the time of delivery is not uncommon, and prevention of the devastating outcomes of neonatal HSV disease is paramount. II. Perinatal Transmission: A. Maternal Genital Herpes is classified as: 1. Primary infection first episode - A woman with no HSV-1 or HSV-2 antibody acquires either virus in the genital tract, a first-episode primary infection results. 2. Nonprimary infection first episode- A woman with preexisting HSV-1 antibody acquires HSV-2 genital infection (or vice versa), a first episode nonprimary infection ensues. 3. Recurrent- A woman with clinical or serologic evidence of prior genital herpes. B. Five factors known to influence transmission of HSV from mother to neonate are: 1. Type of maternal infection (primary versus recurrent) 2. Maternal HSV antibody status 3. Duration of rupture of membranes- greater than 6 hours increases risk 4. Integrity of mucocutaneous barriers (eg, use of fetal scalp electrodes) 5. Mode of delivery (cesarean versus vaginal delivery) C. Women with primary genital HSV infections who are shedding HSV at delivery are 10 to 30 times more likely to transmit the virus to their newborn infants than are women with recurrent HSV infection who are shedding virus at delivery. D. Risk of transmission during vaginal delivery with recurrent infection is low (< 2-5%) E. Differentiating primary, nonprimary and recurrent HSV infection in the mother is helpful for assessing the risk of HSV infection for the exposed infant, but the distinction may be difficult and antibody Screening is needed: III. Obstetrical Management: A. Women with history of genital HSV should be questioned about recent symptoms and perineum examined before delivery. If no lesions, babies may be delivered vaginally. B. Suspicious lesions should be sampled for culture and PCR to assist in subsequent management of the newborn. If positive further analysis to determine if the virus is HSV-1 or HSV-2. C. Cesarean delivery is indicated for all women with active genital HSV lesions or with typical herpetic prodrome at time of delivery. D. In patients with active genital HSV and ruptured membranes at or near term, a cesarean section should be done ASAP. E. In patients with active genital HSV and ruptured membranes preterm, the risk of potential infection versus those of prematurity must be individualized. F. Neonatal HSV infection has occurred despite cesarean delivery performed before the rupture of membranes. G. In women with a previous diagnosis of genital herpes, cesarean delivery to prevent neonatal HSV infection is not indicated if there are no genital lesions at the time of labor.

2 H. In an effort to reduce cesarean deliveries performed for the indication of genital herpes, the use of oral acyclovir or valacyclovir near the end of pregnancy to suppress genital HSV recurrences has become increasingly common in obstetric practice. I. Fetal scalp monitors should be avoided, when possible, in infants of women suspected of having active genital herpes infection during labor. IV. Neonatal HSV Disease Clinical manifestations: A. Distinction between neonatal HSV infection and HSV disease: 1. HSV infection occurs when viral replication has been established, but the virus is not causing illness. 2. HSV disease occurs when viral replication produces clinical signs of illness (eg, skin lesions, encephalitis, and hepatitis). 3. Once an infant is infected with HSV, progression to neonatal HSV disease is virtually certain. 4. In an effort to prevent this progression from neonatal infection to neonatal disease, parenteral acyclovir be administered preemptively to HSV-infected neonates B. Neonatal HSV Disease symptoms can occur anytime from birth to 6 weeks of age. C. Neonatal HSV Disease is classified in three Categories: 1. SEM- Localized to the skin, eyes and mouth disease: a) Clinical findings include vesicles (80%) often develop on presenting part of body, mouth lesions with or without cutaneous involvement, keratoconjunctivitis, and chorioretinitis. 2. Disease with central nervous system (CNS) involvement with or without SEM: a) 40-60% do not have vesicles. b) Clinical findings include lethargy, tremors, poor feeding, bulging fontanelle, seizures, temperature instability and hypotonia. 3. Disseminated disease involving multiple organs mostly liver and lungs: a) Earliest age of onset, often during 1-2 week of life. b) Clinical findings include vomiting, apnea, jaundice, seizures, shock, respiratory distress, disseminated intravascular coagulation (DIC) and pneumonitis. c) Vesicular rash absent in up to 20% of infants. D. Any neonate with HSV manifestations (fever, irritability, abnormal CSF findings, vesicular lesions of skin, respiratory distress, seizures, shock, DIC, severe liver dysfunction and signs of sepsis) should be evaluated immediately for HSV infection. V. Testing to assist with early diagnosis of infant exposed to genital HSV: A. Herpes viral cultures are the testing modalities recommended for the diagnosis of genital HSV lesions. 1. Herpes viral cultures: a) If skin lesions are present, a scraping of the vesicles should be transferred in appropriate viral transport media on ice to a diagnostic virology laboratory. b) Other sites from which specimens should be obtained for culture of HSV ( surface cultures ): (1) The conjunctivae (2) Mouth (3) Nasopharynx (4) Rectum

3 2. PCR testing: a) Send PCR assay of blood specimens from infants with suspected HSV disease b) PCR assay of the CSF is the method of choice for documenting CNS involvement in an infant suspected of having HSV disease. c) However, PCR assay of CSF should only be performed in conjunction with HSV surface cultures, given that up to 40% of infants with disseminated disease will not have CNS involvement, and, by definition, no infants with SEM disease will have CNS involvement. d) The sensitivity of CSF PCR testing in neonatal HSV disease is 75% to 100%. e) PCR analysis of CSF also should play a role in determining the duration of antiviral therapy, because available data suggest that having HSV DNA detected in CSF at or after completion of intravenous therapy is associated with poor outcomes see management. VI. Early Diagnosis and Management of Neonate with HSV: A. Asymptomatic neonates after vaginal delivery or Cesarean Section with maternal history of HSV disease or antibodies but no maternal genital herpetic lesions: 1. Close Observation. 2. Educate parents on signs and symptoms of neonatal HSV infection; vesicular lesions of skin, respiratory distress, seizures, and signs of sepsis. 3. Educate mother on contact precautions; good hand washing, barrier between baby and lesions. 4. Breast feeding is permissible as long as no vesicular herpetic lesions in breast area. 5. No specific isolation precautions needed. B. Asymptomatic neonates after vaginal or cesarean delivery to women with genital HSV lesions at deliver and history of genital HSV preceding pregnancy; 1. See Algorithm on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions 2. Obtain surface cultures at 24 hours after delivery 3. Send blood for HSV DNA PCR assay 4. The importance of waiting until ~24 hours to obtain viral studies is based on the fact that a positive virological test result at that point represents actively replicating virus on the infant s mucosa, whereas as positive test result shortly after birth could reflect only transient maternal contamination that may not lead to replication with resulting neonatal HSV disease. 5. Acyclovir need not be started as long as infant stays asymptomatic 6. If at any time during the evaluation an infant develops symptoms that could possibly indicate neonatal HSV disease (fever, hypothermia, lethargy, irritability, vesicular rash, seizures) a full diagnostic evaluation should be undertaken and IV acyclovir therapy initiated. 7. It is permissible to discharge an asymptomatic infant after 48 hours of negative HSV cultures (and negative PCR assay results) if other discharge criteria have been met, there is ready access to medical care, and a person who is able to comply fully with instructions for home observation will be present. a) If any of the conditions is not met the infant should be observed in the hospital until HSV cultures are finalized as negative or are negative for 96 hours after being set up in cell culture

4 8. If the surface and blood virological study results are negative at 5 days, the infant should be evaluated if signs or symptoms of neonatal HSV disease develop during the first 6 weeks of life. 9. If the surface and blood virological study results become positive, the infant should undergo a complete evaluation (LP with CSF sent for indices and HSV DNA PCR assay and serum alanine transaminase) to determine the extent of the disease and IV acyclovir should be initiated ASAP. 10. If the evaluation findings are normal, indicating that the neonate has HSV infection but not HSV disease, the infant should be treated empirically with IV acyclovir for 10 days to prevent progression from infection to disease. 11. If the evaluation findings are abnormal indicating the neonate already has neonatal HSV disease, the infant should be treated days with IV acyclovir on the basis of the extent of the disease. See treatment. C. Asymptomatic Neonates after vaginal or cesarean delivery to women with genital HSV lesions at deliver and no history of genital HSV preceding pregnancy: 1. For women without history of genital herpes preceding pregnancy, the presence of lesions at delivery could represent: a) First episode primary infection (risk of transmission to newborn 57%) b) First episode nonprimary (risk of transmission to newborn 25%) c) Recurrent infection (risk of transmission to newborn 2%) 2. Thus, with the availability of type specific serological testing, the practitioner can determine which type of infection the outbreak represents, given the risks to the infant are so disparate. 3. Accordingly, serological testing should be performed to determine the type of HSV infection in the mother to delineate between the three. 4. Obtain surface cultures at 24 hours after delivery 5. Send blood for HSV DNA PCR assay 6. The infant should undergo a complete evaluation a) LP with CSF sent for indices and HSV DNA PCR assay b) Serum alanine transaminase 7. IV acyclovir therapy should be initiated pending the evaluation results 8. It is acceptable to wait to initiate therapy until ~24 hours after delivery in an asymptomatic full term neonate because the average age at onset of neonatal HSV is 1-3 weeks. 9. Start evaluation and treatment immediately after delivery if the infant is preterm or Rom >4 hours. 10. If the mother has a documented or assumed first episode primary or first episode nonprimary infection and the neonates evaluation results: a) Normal: Infant should be treated empirically with IV acyclovir for 10 day - preemptive therapy b) Abnormal: Continue acyclovir- treat accordingly see management of disease 11. If the mother has recurrent genital HSV infection (that is she has type specific antibodies to the HSV serotype detected by her genital swab) and the neonatal HSV study results: a) Negative: (1) Stop acyclovir

5 VII. Guideline: HSV (2) Educate parents regarding signs and symptoms of HSV (3) Discharge infant (4) Reevaluate with any of signs or symptoms of illness in first 6 weeks b) Positive: Confirming HSV infection (1) Continue acyclovir- treat accordingly see management of disease Management of infant with HSV infection: A. If cultures of samples obtained from the neonate 24 hours following delivery subsequently grow HSV, HSV infection is confirmed and the infant then should be evaluated for HSV disease. B. Complete evaluation should include: 1. Lumbar puncture for CSF indices and HSV DNA PCR a) Increased protein and WBC count found with CNS involvement may not be found for 7 days, so normal values do not rule out CNS involvement 2. Whole blood for HSV PCR 3. Determination of serum hepatic transaminases. C. Start or continue IV Acyclovir 1. Acyclovir inhibits viral DNA synthesis 2. Dose 20mg/kg IV every 8 hours 3. Infuse via syringe pump over 1 hour. (Decreases risk of transient renal dysfunction and crystalluria). 4. Consider increasing dosing interval in premature infants <34 weeks or patients with significant renal impairment or hepatic failure. 5. Monitor periodic CBC because neutropenia occurs in approximately 20% of patients.(decrease dose or treat with GCSF if ANC less than 500) 6. Prepared by dissolving contents of 500mg vial in 10 ml of sterile water. Infusion solution concentration should be no greater than 7mg/ml. A 5mg/ml dilution may be made by adding 1 ml of 50mg/ml concentration to 9 ml of normal saline. 7. Incompatible with dextrose and amino acids solution and fat emulsion, caffeine, dopamine and dobutamine D. Length of treatment: 1. Neonatal HSV infection - no signs or symptoms of HSV disease and normal HSV evaluation - should be treated empirically with intravenous acyclovir for 10 days to prevent HSV infection from progressing to HSV disease. This includes: a) Positive surface cultures b) An infant born to a mother with documented or assumed HSV first episode primary or first episode nonprimary infection 2. HSV Disease - An infant with HSV disease should be treated with intravenous acyclovir for days depending on the extent of the neonatal HSV disease. a) An infant with HSV disease and initial CSF PCR assay is positive for HSV DNA treat for 21 days. b) A repeat lumbar puncture should be obtained near the end of therapy (day 17 or 18 of an anticipated 21 day course of therapy) and IV acyclovir should be discontinued at 21 days if the repeat HSV PCR assay result is negative. c) If at the end of therapy CSF PCR assay result is positive, IV acyclovir should be continued for another 7 days with another repeat LP near the end-of-therapy,

6 again with decisions regarding cessation of therapy predicated on the repeat CSF PCR assay result. E. Infants with ocular involvement attributable to HSV infection should receive a topical ophthalmic drug (1% trifluridine, 0.1% iododeoxyuridine, or 3% vidarabine) as well as parenteral antiviral therapy. F. After completion of parenteral acyclovir for treatment of neonatal HSV disease, infants should receive oral acyclovir suppression therapy for 6 months. 1. To prevent skin lesion recurrences (~ 50% of infants surviving neonatal HSV experience cutaneous recurrences). 2. Improves neurodevelopmental outcomes in infants with HSV CNS disease 3. The dose is 300 mg/m 2 /dose, administered 3 times daily for 6 months 4. Absolute neutrophil counts should be assessed at 2 and 4 weeks after initiating suppressive therapy and then monthly during the treatment period G. MRI of head and electroencephalogram (multiple independent foci of periodic slow and sharp wave discharge) are better than CT at detecting earlier disease. L. Consult and follow up with infectious disease, neurology and ophthalmology important with all types of HSV infection. M. All cases of Herpes Simplex Virus (HSV) in neonates and infants up to 6 months of age with disseminated infection with involvement of liver, encephalitis and infections limited to skin, eyes, mouth and anogenital in children 12 years must be reported to local public health officials. VIII. Infection Control measures A. Neonates with HSV disease should be managed with contact precautions if mucocutaneous lesions are present. B. Infants born to women with active HSV lesions should be managed with contact precautions during the incubation period. 1. Some experts believe that contact precautions are unnecessary if exposed infants were born by cesarean delivery, provided membranes were ruptured for less than 4 hours. 2. The risk of HSV infection in infants born to mothers with a history of recurrent genital herpes who have no genital lesions at delivery is low, and special precautions are not necessary. C. One method of infection control for neonates with documented perinatal exposure to HSV is continuous rooming-in with the mother in a private room. D. Mothers with herpes labialis or stomatitis should wear disposable surgical mask when touching newborn until lesion dry and crusted, should not kiss or nuzzle newborn until the lesions have cleared and use good hand washing, E. Direct contact with other family members who have active HSV should be avoided. F. Women with active HSV lesions should be managed with contact precautions during labor, delivery, and the postpartum period. 1. These women should be instructed about the importance of careful hand hygiene before and after caring for their infants. 2. The mother may wear a clean covering gown to help avoid contact of the infant with lesions or infectious secretions. 3. Herpetic lesions on other skin sites should be covered.

7 G. Breastfeeding is acceptable if no lesions are present on the breasts and if active lesions elsewhere on the mother are covered H. Transmission of HSV in hospital nurseries from infected health care professionals to newborn infants rarely has been documented. I. The risk of transmission to infants by health care professionals who have herpes labialis or who are asymptomatic oral shedders of virus is low. Compromising patient care by excluding health care professionals with cold sores who are essential for the operation of the hospital nursery must be weighed against the potential risk of newborn infants becoming infected. J. Health care professionals with cold sores who have contact with infants should cover and not touch their lesions and should comply with hand hygiene policies. K. Health care professionals with an active herpetic whitlow (Herpetic whitlow consists of single or multiple vesicular lesions on the distal parts of fingers) should not have responsibility for direct care of neonates or immunocompromised patients and should wear gloves and use hand hygiene during direct care of other patients. L. Intrafamilial transmission of HSV to newborn infants has been described but is rare. Household members with herpetic skin lesions should be counseled about the risk and should avoid contact of their lesions with newborn infants by taking the same measures as recommended for infected health care professionals as well as avoiding kissing and nuzzling the infant while they have active lip lesions or touching the infant while they have a herpetic whitlow. References: 1. American Academy of Pediatrics and the American College of Obstetricians and Gynecologists. Herpes Simplex Virus. In: Lockwood, C, Lemons, J, eds. Guidelines for Perinatal Care. 6 th ed. Elk Grove Village, IL.American Academy of Pediatrics; 2007:pp Avery, G etal. Neonatology Pathophysiology and Management of the Newborn, ed. 4. Philadelphia: J.B. Lippincott Company, USA, 1994, pp Cloherty, J. and Stark, A.. Manual of Neonatal Care. 6 th ed. Philadelphia, PA: Lippincott-Raven Publishers, Gomella, T. Neonatalogy. 6 th ed. Stanford, Connecticut: Appleton & Lange, Kimberlin, D. Neonatal herpes simplex infection. Clinical Microbiology Reviews Vol. 17, (January 2004): pp Feb 25, < 6. Kimberlin, D. Safety and Efficacy of High-Dose Intravenous Acyclovir in the Management of Neonatal Herpes Simplex Virus Infections. PEDIATRICS Vol. 108 No. 2,( August 2001): pp.

8 Feb 25, Kimberlin, D., Baily, J., COMMITTEE ON INFECTIOUS DISEASES and COMMITTEE ON FETUS AND NEWBORN, Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions. Pediatrics 2013;131;e635; originally published online January 28, 2013 DOI: /peds Knezevic A, Martic J, Stanojevic M, Jankovic S, Nedeljkovic J, Nikolic L, et al. Disseminated neonatal herpes caused by herpes simplex virus types 1 and 2. Emerg Infect Dis [serial on the Internet]. Feb 25, < > 9. Red Book Online: Report of the Committee on Infectious Disease. American Academy of Pediatrics; Sexually Transmitted Diseases Treatment Guidelines, MMWR recommendations and reports. August 4, 2006 / 55(RR11); /10/2008. < 11. Young, TE, Mangum, B: Neofax: A Manual of Drugs Used in Neonatal Care. Raleigh, North Carolina: Acorn Publishing, USA, 2011