Prevention and management of neonatal herpes simplex virus infections

Question 1

Worldwide what percentage of HSV infections are caused by HSV-1 and HSV-2 infections?

Answer 1

HSV-1: 25%
HSV-2: 75%

Although one study found up to 63% of cases were HSV-1 in Canada

Question 2

What factors affect transmission of HSV?

Answer 2

Nature of maternal infection
Mode of delivery
Duration of ROM
Use of Intrapartum instrumentation

Question 3

What two ways can you classify maternal HSV?

Answer 3

Newly acquired:

• First episode of primary infection (no serum antibodies to HSV-1 or 2)
• First-episode non-primary infection (mother has new infection with one HSV type in the presence of the other type)

OR:

Recurrent:
Mother has pre-existing antibodies to the HSV type that is isolated from the genital tract.

Question 4

What are the ways in which neonates may acquire Neonatal HSV infection? Which is most common?

Answer 4

• During Delivery (75%) - often from newly acquired and asymptomatic mothers (75-90% of HSV seropositive mothers are unaware of their status)
• In utero (< 5% of cases)
• Postnatal transmission (maternal or non-maternal sources)

Question 5

What percentage of HSV positive women shed HSV in their genital tracts on a given day?

Answer 5

10-20%

Question 6

What are the transmission rates for the different types of infection (Ie First episode primary, first episode non-primary, recurrent)?

Answer 6

Up to 60%. Infants born to mothers who have first episode primary infection are at the highest risk for acquiring HSV.

Transmission risk is < 30% for first episode non-primary infections because of transmission of cross-reactive antibodies.

Transmission risk is < 2% for recurrent infection because type-specific antibodies are present

Question 7

Why is instrumentation a risk factor?

Answer 7

May cause scalp abrasions. If possible forceps, vacuum assistance and other scalp sampling and monitoring should be avoided if possible.

Question 8

How can you classify perinatal and post-natal neonatal HSV infection?

Answer 8

Disseminated HSV - Involves multiple systems, notably liver and lungs. Does not need to involve skin (39% don’t)

Localized CNS HSV (Does not need to involve skin (32% don’t)

Skin, Eye and Mucous Membrane (SEM) infection (Does not need to involve skin (17% don’t)

Question 9

When does Neonatal HSV infection present?

Answer 9

Within first 4 weeks of life (rarely up to 6 weeks).
Can present in a variety of ways, be suspicious if appearing septic with liver dysfunction (even if no known history of HSV). Be especially concerned if abnormal CSF and seizures.

Consider investigations and treatment if not improving after 24 hours of antibiotics in children admitted with R/O sepsis, especially if blood cultures negative at 24 hours (and not improving), if a child is admitted with pneumonia and not improving on antibiotics (and not improving, cxr appears viral)

Also consider investigating if unexplained bleeding or hepatitis.

Question 10

How has antivirals helped with mortality in neonatal HSV?

Answer 10

Reduced mortality from 85% in disseminated to 29% in disseminated disease and from 50% to 14% in CNS disease. (Disseminated has higher mortality)

Question 11

What percentage of children have neurologic complications?

Answer 11

Based on type of infection!

Disseminated - 25% have neurologic complications
CNS infection alone - 70% have neurologic complications
SEM infection - Low likelihood of neurologic complications

Question 12

What methods CAN be used to diagnose HSV?

Answer 12

Viral cultures (oropharynx, nasopharynx, skin lesions, eye and mouth mucous membranes, rectal swabs, blood buffy coat, CSF)
    - Recognized as definitive diagnosis

PCR tests (CSF, skin lesions, mucous membranes, blood)
- Believed to be most senstitive (especially with CSF, even more sensitive than culture)
- Can get false positive and negative
- PCR on serum is less well studied
Direct immunoflourescent antibody staining (skin lesions)

Enzyme immunoassays for HSV antigens (skin lesions)

Question 13

Why can serology not be used in neonatal HSV infection?

Answer 13

1) Transplacental IgG can’t be differentiated from infantile IgG
2) Severely affected neonates have impairment in making antibodies
3) commercially available assays for HSV IgM antibodies have variable reliability

Question 14

How do you treat neonatal HSV? (Drug, dose, route, interval, length of treatment)

Answer 14

Acyclovir 60mg/kg/day divided q8 hrs, IV.

SEM: 14 days –> also give topical agent
CNS or Disseminated: Minimum 21 days (Sample CSF again at end of 21 day treatment course)

PO route has variable bioavailability and results in inadequate levels. However should be given to infants as suppresive therapy (after 21 days of acyclovir) for 6 months.

Question 15

What are the side effects of acyclovir?

Answer 15

Can affect renal function. Can cause neutropenia.

Question 16

What tests SHOULD be done when considering a diagnosis of HSV?

Answer 16

CSF PCR
Swabs of lesions and mucous membranes for culture
Serum hepatic transaminase levels

Question 17

How long do HSV-1 or HSV 2 antibodies take to develop?

Answer 17

~ 3 weeks. Should test for them if available.

Question 18

What is the risk for transmission of HSV in a presumed first episode primary or first episode non-primary infection when an infant is delivered by C-section prior to ROM?

Answer 18

Very low! Obtain mucous membrane and nasopharyngeal swabs at 24 hours of life, and once results obtained, child can be D/C’d

Question 19

What should you do in a presumed first episode primary or first episode non-primary infection when an infant is delivered vaginally or by C-section after ROM?

Answer 19

Obtain testing in mom to confirm whether it is primary, non-primary or recurrent HSV.

Swab mucous membranes (controversial whether to do this at birth or at 24 hours) and start acyclovir. If available get serum PCR.

If any swabs are positive then must obtain CSF sample for PCR to determine length of treatment.

If swabs are negative, stop acyclovir if type specific serology shows that mother has recurrent HSV. If you can’t do type specific testing or shows first episode HSV, then acyclovir is given for 10 days.

Question 20

How do you manage an infant of a mother with history of HSV but no active lesions?

Answer 20

Observe infant, but don’t start Acyclovir. Generally, because risk of transmission is low you don’t even need to do mucous membrane swabs, unless clinically the child shows signs of HSV infection

Question 21

What kind of bloodwork do kids with CSF HSV infection on suppresive acyclovir need for follow up?

Answer 21

CBC, Urea, Cr –> Monthly for adverse effects

Also want to assess neurodevelopment.

Question 22

What kind of isolation is required for mothers or infants with HSV? Is breastfeeding contraindicated?

Answer 22

Neonates and mothers should be treated with contact precautions. If a neonates mother has active HSV, contact precautions are in place until the end of incubation period (14 days) or skin samples are negative.

If mom has active oral HSV she should wear a mask around the hospital and avoid kissing her infant.

Breastfeeding is not contraindicated unless lesions are present on the breast.