Prevention and management of neonatal herpes simplex virus infections

Question 1

What is the incidence of neonatal HSV in Canada?

Answer 1

1 per 16 500

6 per 100 000 live births

Question 2

What is a maternal first episode primary infection?

Answer 2

Newly acquired maternal genital HSV in which the mother has no serum antibodies to HSV-1 or -2 at onset.

Question 3

What is a maternal first episode non-primary infection?

Answer 3

Newly acquired maternal genital HSV in which the mother has new infection with one HSV type in the presence of antibodies to the other type

Question 4

What is recurrent maternal genital HSV?

Answer 4

Maternal genital HSV in which the mother has pre-existing antibodies to the HSV type that is isolated from the genital tract

Question 5

What percentage of individuals who are seropositive for HSV-2 were unaware of their infection?

Answer 5

75-90%

Question 6

What percentage of individuals with HSV-2 shed on any given day?

Answer 6

10-20%

Question 7

What is the rate of transmission for infants born to mother who have their first episode primary infection at time of delivery?

Answer 7

60%

No maternal antibodies to transmit

Question 8

What is the rate of transmission for infants born to mother who have their first episode non-primary infection at time of delivery?

Answer 8

<30%

Cross reactive maternal antibodies are present

Question 9

What is the rate of transmission for infants born to mother who have recurrent infection at time of delivery?

Answer 9

<2%

Type-specific antibodies are present

Question 10

What steps can be taken perinatally to reduce risk of transmission?

Answer 10

1. Elective cesarean section

2. Maternal prophylaxis with acyclovir or valacyclovir from 36wks GA until delivery

Question 11

What obstetrical procedures/events can increase risk of transmission?

Answer 11

1. Fetal scalp sampling and monitoring
2. Forceps assisted delivery
3. Vacuum assisted delivery
4. Early or prolonged rupture of membranes

Question 12

What are the classification of HSV infection acquired in the perinatal, natal, and postnatal periods?

Answer 12

1. Disseminated HSV
2. Localized CNS HSV
3. Skin, eye, and mucous membrane (SEM) infection

Question 13

When do the initial symptoms of HSV infection typically present?

Answer 13

Within 4-6 weeks (fully investigate up to 42d if suspect NHSV)

Question 14

What percentage of infants with NHSV do not have skin lesions during their illness?

Answer 14

39% Disseminated disease
32% CNS disease
17% SEM

Question 15

What is the mortality rate for NHSV with treatment with acyclovir?

Answer 15

29% Disseminated disease

14% CNS disease

Question 16

What is the mortality rate for NHSV without treatment with antivirals?

Answer 16

85% Disseminated disease

50% CNS disease

Question 17

What is the rate of neurological complications in survivors of NHSV who received treatment with acyclovir?

Answer 17

25% Disseminated disease

70% CNS infection alone

Question 18

What tests can detect HSV?

Answer 18

1. Viral cultures from the oropharynx, nasopharynx, skin lesions, mucous membrane (eye and mouth) swabs, rectal swabs, blood buffy coat and CSF;
2. PCR testing of CSF, skin lesions, mucous membranes and blood;
3. Direct immunofluorescent antibody staining of skin lesions;
4. Enzyme immunoassays for HSV antigens in skin lesions.

Question 19

What are the risk of skin samples taken before 24h after birth?

Answer 19

May represent skin contamination by intrapartum exposure as opposed to active viral replication

Question 20

Which is more sensitive for CSF HSV - PCR or viral culture?

Answer 20

PCR

Question 21

Why is infant serology not useful for diagnosing NHSV?

Answer 21

1. Transplacental IgG Ab cannot be differentiated from IgG produced by neonate
2. Severely affected infants have impaired ability to make antibodies
3. Commercial available assays for HSV IgM Ab have only limited and variable reliability

Question 22

What is the recommended treatment for NHSV?

Answer 22

Acyclovir 60mg/kg/day IV q8h

Question 23

What is the duration of treatment for NHSV?

Answer 23

Disseminated and CNS minimum 21d

SEM 14d

Question 24

What risks are associated with higher doses of acyclovir?

Answer 24

1. Neutropenia

2. Nephrotoxicity

Question 25

What are the recommended laboratory diagnostics for NHSV infection?

Answer 25

1. Whenever a diagnosis of NHSV is being considered, it is essential to order laboratory testing for HSV in addition to performing skin and mucous membrane examinations:
   a) The standard tests for HSV include CSF PCR and swabs of vesicular lesions and mucous membranes (tested by the method recommended by the local laboratory). Also, blood for HSV PCR may be tested, if available.
   b) Serum hepatic transaminase levels should be measured to provide supporting evidence for disseminated HSV infection.
2. When evaluating NHSV infection in exposed asymptomatic infants, mucous membrane swabs should be obtained from the mouth, nasopharynx and conjunctivae at least 24 h after delivery. Additional swabs may be obtained (eg, from sites of scalp electrodes, if present).
3. PCR testing for CSF HSV DNA is the diagnostic method of choice for CNS HSV.
4. For all the above tests, clinicians and laboratory staff should work together to minimize the turn-around time for test results.

Question 26

What is the management of asymptomatic term infant with a mother with first episode genital HSV at delivery with either membrane rupture pre-delivery for cesarian section OR vaginal delivery?

Answer 26

1. Mucous membrane swabs taken before ACV administered
2. IV ACV treatment for 10d, unless HSV detected then full treatment course
3. Some experts recommend performing CSF cell count, chemistries, and PCR when mucous membrane swabs are taken

Question 27

What is the management of asymptomatic term infant with a mother with first episode genital HSV at delivery with infant delivered via cesarean section with no membrane rupture prior to delivery?

Answer 27

1. Discharge infant to reliable caregiver who is aware of NHSV symptoms while mucous membrane swab or blood PCR results are pending
2. If HSV not detected in swabs then caregiver continues to observe infant
3. If HSV detected in swabs readmit for CSF and blood PCR and transaminases
4. If HSV detected on swabs and PCR on blood and CSF are negative give 14d IV ACV
5. If HSV detected on swabs and PCR on blood or CSF are positive then give minimum 21d IV ACV
6. Some experts recommend performing CSF cell count, chemistries, and PCR when mucous membrane swabs are taken

Question 28

What is the management of asymptomatic term infants born to mother with recurrent genital HSV born via either vaginal or cesarean delivery?

Answer 28

1. Infants have mucous membrane swabs at 24h
2. Discharge infant while mucous membrane swab results are pending
3. If HSV not detected on swabs and no signs of NHSV develop caregiver continues to observe infant
4. If HSV detected in swabs or signs of NHSV develop readmit for CSF and blood PCR and transaminsases
5. If CSF and blood HSV PCR negative and swabs positive or signs of NHSV give 14d IV ACV
6. If CSF or blood HSV PCR positive and swabs positive or signs of NHSV give minimum 21d IV ACV

Question 29

What is the management of asymptomatic term infants whose mothers have no active lesions at delivery (including women on ACV prophylaxis)?

Answer 29

1. Observe for signs of NHSV by caregiver
2. Mucous membrane swabs not routinely recommended for this infant
3. Does not require ACV

Question 30

What is the management of the neonate with symptoms compatibly with NHSV?

Answer 30

Consider investigations (mucous membrane swabs, blood and CSF PCR, and transaminases) and treatment (IV ACV) in unwell infants <6 weeks with following at risk criteria:

1. Infants started on IV antibiotics for suspected sepsis (especially infants presenting with seizure or yielding abnormal CSF) who do not improve rapidly and have negative bacterial cultures at 24 h incubation.
2. Infants admitted with pneumonia of uncertain etiology who do not improve after 24 h on antibiotics, especially if the radiographic picture is consistent with viral pneumonia.
3. Infants with unexplained bleeding from venipuncture sites or an unexplained, documented coagulopathy.
4. Infants started on IV antibiotics for suspected sepsis who are found to have unexplained hepatitis.

Question 31

What is the treatment and follow-up of infants with NHSV infections?

Answer 31

1. Early therapy with IV ACV improves the prognosis for all three presentations of NHSV. Therefore, infants should be started on IV ACV before laboratory confirmation of NHSV, as soon as the infection is suspected clinically.
2. The dose is 60 mg/kg/day IV q8h, assuming that renal function is normal. Treatment duration should be 14 days if the disease is limited to the skin, eyes or mouth, and a minimum of 21 days if the infection involves the CNS or is disseminated.
3. For infants with CNS disease, CSF should be sampled near the end of a 21-day course of therapy. If the PCR remains positive, treatment should be extended with weekly CSF sampling and ACV stopped when a negative result is obtained.
4. In combination with parenteral ACV, neonates with ocular involvement should receive a topical ophthalmic agent such as trifluridine. An ophthalmology consultation is essential.
5. Oral ACV is contraindicated for the acute treatment of NHSV because drugs levels are too low. Levels from oral ACV are only high enough for suppressive therapy.
6. Suppressive therapy with oral ACV (300 mg/m2 per dose PO TID) should be given for six months to infants with CNS disease. A tool for calculating body surface area can be found at: http://www.csgnetwork.com/bsacalc.html. Data are less convincing for SEM or disseminated disease, but suppressive therapy may still be offered.
7. Follow-up is necessary to detect and manage adverse effects related to suppressive ACV treatment as well as for the neurodevelomental sequelae of NHSV. Complete blood count, and urea and creatinine levels should be checked monthly for adverse effects, and the dose of ACV adjusted for growth. Infants should be followed in a program that enables their evaluation for the neurodevelopmental, ophthalmological and aural consequences of NHSV infection.

Question 32

What are the infection control guidelines for neonates with HSV infection and exposed neonates?

Answer 32

1. Neonates with HSV infection should be managed using contact precautions when mucocutaneous lesions are present and until lesions have crusted.
2. Asymptomatic neonates whose mothers have active HSV lesions should be managed using contact precautions until the end of the incubation period (day 14) or until samples from the infant taken after the first 24 h of life are negative. Some experts do not recommend contact precautions if an infected infant is born by Cesarean section and membranes are ruptured <4-6h

Question 33

What are the infection control guidelines for mothers with active HSV?

Answer 33

1. Mothers who are in hospital should be on contact precautions until their lesions have crusted.
2. Mothers with herpes labialis should wear a disposable mask when caring for their infant <6 weeks of age, until lesions are crusted. Advise these mothers not to kiss their infant. There is no contraindication to breastfeeding unless there are herpetic lesions on the breast.
3. Mothers with skin lesions should keep them covered whenever their newborn is present.

Question 34

What are the infection control guidelines for staff with orofacial or skin lesions?

Answer 34

1. Staff with skin lesions due to HSV must practice meticulous hand hygiene. Individuals who have contact with infants should keep their lesions covered. If this is not possible, direct care of neonates should be avoided.
2. Some experts recommend wearing a surgical mask to cover orolabial lesions because these cannot be covered by dressings.
3. Staff with active herpetic whitlow should avoid contact with neonates.