Current management of herpes simplex virus infection in pregnant women and their newborn infants

Infectious Diseases and Immunization Committee, Canadian Paediatric Society (CPS)

Abstract published in Paediatrics & Child Health 2006;11:363-5
Reference No. ID06-03

Revision in progress February 2011

Summary

Index of position statements from the Infectious Diseases and Immunization Committee

Contents

• Statement of the problem
• Herpes simplex viruses
• Epidemiology
• Characteristics and outcomes of neonatal infection
• Laboratory diagnostic issues
• Treatment of neonatal HSV infection
• Recommendations
  • Prevention of neonatal HSV infections
    • Pregnant women
    • Women in labor
    • Newborn Infants
    • Infection control measures
  • Diagnostic tests for neonatal HSV infection
  • Treatment and follow-up of neonates with HSV infection
• Future research issues
• References
• Table 1
• Table 2
• Table 3
• Table 4

STATEMENT OF THE PROBLEM
Herpes simplex virus (HSV) has been associated with neonatal disease for more than 6 decades (1). Over the past 20 years, there have been major advances in our knowledge of the epidemiology, pathogenesis and natural history of this disease. In addition, the availability of effective antiviral therapy has resulted in major advances in the management of neonatal HSV infections. Despite these advances, HSV remains a major cause of morbidity and mortality among neonates. This statement will address current issues relating to the prevention, diagnosis and treatment of neonatal HSV infection. It replaces a previous statement on this subject (ID92-03).

BACKGROUND  

HERPES SIMPLEX VIRUSES
Herpes simplex viruses types 1 and 2 are members of the herpesvirus family (2). Like the other herpesviruses, HSV exhibits latency by remaining inactive within the host. Reactivation of infectious virus is not usually associated with clinical signs of recurrent HSV lesions. Clinically silent reactivations are more frequent than recurrent lesions. Reactivations are often spontaneous with no obvious precipitating factors, although symptomatic recurrences may be associated with physical or emotional stress, exposure to ultraviolet light, tissue damage and immune suppression. In the case of genital HSV, many recurrences are not truly silent but are clinically unrecognized or undiagnosed.

EPIDEMIOLOGY
Incidence of Neonatal Infection: Data from the Canadian Paediatric Surveillance Program (CPSP) indicate that, between 2000-2003, there were 43 cases of neonatal HSV (5.9 per 100,000 live births in Canada ) and a case fatality rate of 15.5%. (3). While the incidence varies across regions in the USA, a rate of 1 in 3200 deliveries was recently documented (4) Only approximately 70% of neonatal disease is caused by HSV type 2 and 30% by HSV type 1 (5).  

Maternal Infection and Factors Influencing Transmission to the Newborn: Maternal genital HSV infection may be classified into the following categories: (1)

• Newly acquired
  First episode primary (mother is seronegative for HSV types 1 and 2 at the onset of infection). 
  First episode nonprimary (mother has a new infection with one virus type, in the presence of antibodies to the other virus type)

• Recurrent (mother has pre-existing antibodies to the virus type that has been isolated from the genital tract). 

Genital HSV infection is a common occurrence among pregnant women (6-12). However, most are clinically silent during pregnancy. Maternal disseminated disease rarely occurs; however, the mortality is high (13-15). When maternal HSV lesions are present, they are most often localized (1).  

Transmission of infection to the newborn infant is most often related to viral shedding at the time of delivery. The incidence of viral shedding at delivery is reported to be 0.01-0.39% for all pregnant women, regardless of past history of genital herpes (6, 11).In one study, symptomatic recurrent infections occurred during pregnancy in 84% of pregnant women who had a history of symptomatic disease (16). However, viral shedding at delivery occurred in only 0.56% of symptomatic infections and 0.66% of asymptomatic infections. Similar data have been obtained in other studies (17). The frequency of shedding does not appear to vary by trimester. The data suggest that the frequency of shedding is low, which reduces the risk of neonatal infection when a pregnant woman has recurrent infections.                       

Approximately 60-80% of women, whose infants are infected, are asymptomatic during pregnancy and delivery and have no history of genital herpes in themselves or their partners  (5, 18-19).  The category of maternal infection at the time of delivery influences the likelihood of neonatal acquisition of HSV. Infants born to mothers who have true primary infections at the time of delivery are at the highest risk of acquiring HSV, with transmission rates of 50% or greater (5, 20). For infants born to mothers who have new infections that are nonprimary, the transmission rates are in the order of 30%. The lowest risk of neonatal transmission occurs in maternal recurrent infection. The attack rate for neonatal HSV in these infants is less than 2% (1).  

Women with primary infections have large quantities of replicating virus shed in their genital tracts (21). Women with new non-primary infections also shed virus in high titres (1). Many of the latter women are asymptomatic. Thus, an important lesson is that new infections often occur without the classic clinical features originally believed to be  associated with primary and recurrent genital herpes.  

Transplacental neutralizing antibody may have a beneficial effect on neonatal infection (22). If maternal primary infection occurs late in gestation, significant amounts of neutralizing antibodies may not be transferred to the newborn infant. The highest risk of transmission is from mothers with newly acquired genital herpes that develops when the infant is born before the transfer of passive antibodies and exposed at delivery or within the first few days of life (19, 20, 23).  

Another factor is the duration of ruptured membranes. Data from the early 1970s showed that prolonged rupture of membranes (> 6 hours) increased the risk of acquisition of HSV (24). Cesarean sections are recommended if active lesions are present at the time of the onset of labour (25). However, the benefit of cesarean section has not been determined, if the membranes have been ruptured for more than 6 hours. Cesarean section reduces, but does not eliminate the risk of newborn infection (5, 26). In a large prospective cohort study cesarean section significantly reduced the rate HSV transmission by 86% relative to vaginal delivery among women from whom HSV was isolated prior to delivery (4).

The effect of suppressive therapy with oral acyclovir has been shown to compare favorably with cesarean section when initiated at 36 weeks for pregnant women with genital herpes in pregnancy  (27-31). This was first demonstrated in women diagnosed with HSV for the first time in pregnancy (27).  

In a meta-analysis of randomized clinical trials of acyclovir to prevent herpes simplex recurrence at delivery, acyclovir prophylaxis was effective in reducing clinical HSV recurrences at the time of delivery (OR 0.25 [95% CI 0.15-0.40]), caesarian deliveries for herpes (OR 0.30 [95% CI 0.13-0.67]), total HSV detection at delivery (OR 0.11 [95% CI 0.04-0.31]), and asymptomatic HSV shedding at delivery (OR 0.09 [95% CI 0.02-0.39]). These data support the use of acyclovir therapy for women with recurrent genital herpes during pregnancy to reduce the risk of cesarean delivery for herpes and the risk of HSV being present in the genital tract at delivery (32).   

It has also been suggested that oral acyclovir prophylaxis in late pregnancy for women with recurrent genital herpes is more cost-effective than cesarean delivery (33).  

The use of acyclovir in the settings abouve has given rise to several questions. First, there have been no significant short-term fetal and maternal adverse effects resulting from the ue of acyclovir in late pregnancy (34-35). However, additional data are required before definitive conclusions can be made. Acyclovir-induced neutropenia in newborns whose mothers received acyclovir is possible (36). Second, acyclovir use may merely change the clinical scenario at delivery from one of symptomatic shedding to asymptomatic shedding (29). Third, is development of acyclovir resistance which is unlikely given the expected short duration of acyclovir prophylaxis if the drug is started at 36 weeks. However, this is an area in need of further study, as illustrated by a recent report indicating that an acyclovir-resistant mutant was observed in a neonate after only 7 days of acyclovir in a setting where there was no maternal use of the drug (37).

Besides acyclovir, other agents that may be considered include famciclovir and valacyclovir because of better bioavailability and less frequent administration.  

Finally, certain types of procedures during labor and delivery may influence the likelihood of transmission of HSV to the newborn infant. These include early rupture of membranes (resulting in prolonged rupture of membranes), fetal scalp sampling and monitoring, forceps and vacuum-assisted deliveries. (24, 38-40).

Timing of Transmission of Infection: Newborns may acquire HSV infection as a result of in utero, intrapartum or postnatal infection. While, the most common and important route of infection is intrapartum, postnatal infection is also of concern. Recent data from the National Institute of Allergy and Infectious Diseases (NIAID) Antiviral Study Group indicate that the frequency HSV type 1 infections are approximately 30 % (5). However, since HSV type 1 accounts for 5-20% of all genital HSV infections this would suggest that some cases of neonatal HSV type 1 infections are acquired from non-maternal sources during the postnatal period.

Postnatal acquisition of HSV may occur from relatives and hospital personnel with orolabial herpes (38-39, 41-45). In addition, nosocomial transmission of HSV infection has been documented by the use of special laboratory techniques, such as restriction endonuclease analysis (1).  

CHARACTERISTICS AND OUTCOMES OF NEONATAL INFECTION
A classification scheme for neonatal HSV infection is essential for purposes of arousing the clinical suspicion of HSV disease and in assigning prognosis and therapy (46-47). The current scheme is shown in table 1. There may be overlap between the different syndromes. Disseminated disease involves multiple organs, notably the liver and lungs. Neonates with localized CNS or disseminated disease do not necessarily have skin lesions (48). In the NIAID Collaborative Antiviral Study, 39% of infants with disseminated disease did not have skin lesions at any time during their illness, while 32% with CNS disease and 17% with disease localized to the skin, eyes and mouth (SEM), did not develop skin lesions (49). Thus, neonatal HSV infection should be considered in neonates with sepsis syndrome, particularly when this is accompanied by liver dysfunction. In addition, HSV should be considered in neonates with fever and irritability with abnormal CSF findings particularly when accompanied by seizures.  

In most cases, the initial symptoms of HSV infection present within the first 4 weeks of life. However, occasionally disease may present for the first time between 4-6 weeks of age (50-51). Newborns with intrauterine infection may present at birth or shortly thereafter with symptoms of HSV disease.  

Infants who present with disseminated disease have the worse prognosis overall. In some situations, these infants are born to mothers who are experiencing a new infection and they may lack passively transferred maternal antibody (52-53). In the preantiviral era 85% of infants with disseminated HSV disease and 50% with CNS disease died (54). Vidarabine and lower dose acyclovir (30 mg/kg/day) were both shown to reduce mortality at 1 year from disseminated disease and CNS disease of 54% and 14%, respectively (55). The use of higher dose acyclovir (60 mg/kg/day) resulted in a further reduction in 1-year mortality rates from disseminated and CNS disease (29% and 14%, respectively) (56).  

Among survivors enrolled in 2 studies of parenteral acyclovir for which follow-up data were available at 12 months of age, 25% of those with disseminated disease had neurologic sequelae, compared with 70% of those with CNS disease and 2% with SEM disease (49). Among neonates with SEM disease, long-term neurologic sequelae have been documented in those infants whose disease appeared to be confined to the SEM. Despite normal examinations initially, neurologic impairment became apparent between 6 months and 1 year of life (5, 47, 54-55). Infants with skin lesions often develop recurrences. While mortality does not usually result from these recurrences, up to 30% of these children have had documented evidence of neurologic impairment  (5)  

LABORATORY DIAGNOSTIC ISSUES
HSV may be detected by viral cultures of the oropharynx, nasopharynx, stool, blood buffy coat, CSF and urine, polymerase chain reaction (PCR) testing of CSF and blood, direct immunofluorescent antibody staining of skin lesions and enzyme immunoassays for HSV antigens. The utility of these testing modalities varies according to the type of sample that is being tested. It is important for the clinician to speak with the virologist when cases of neonatal HSV are suspected.

Virus isolation remains the definitive diagnostic method for neonatal HSV (1-2). However, if skin lesions are present, rapid diagnostic techniques are of value, such as direct immunofluorescence for virus-infected cells and enzyme immunoassays for the presence of HSV antigens. Direct immunofluorescence staining is not reliable unless the sample was obtained from a skin lesion. Cells from oropharyngeal samples are not adequate for testing by direct immunofluorescence (1).

The isolation of virus from superficial cultures may represent colonization if such samples are obtained with the first 24 hours after birth (1). If such cultures are positive at > 48 hours after birth, they are likely to represent active viral replication and not colonization. Among infants exposed to active genital lesions, data from prospective studies are lacking regarding the utility of regular surveillance cultures in the early diagnosis of neonatal HSV infection. A suggested approach that is favored by some experts is weekly cultures for the first 4-6 weeks of life as a guide to the need for acyclovir therapy (25).

While HSV cultures may be positive in infants with disseminated disease, in patients with localized CNS disease, CSF cultures are usually negative. For the above patients, polymerase chain reaction (PCR) is an important diagnostic test as it is more sensitive than culture. CSF DNA HSV PCR has obviated the need for brain biopsies in infants with presumed HSV CNS disease. However, since there is no commercially available HSV DNA PCR assay, the results of this test varies across laboratories. Due to the variability, caution should be exercised when using a negative CSF HSV PCR to rule out HSV encephalitis, particularly if this decision is based on the results of a single lumbar puncture done in the early stages of the illness.

False-positive DNA PCR results due to contamination are difficult to control. PCR sensitivity rates vary from 75% to 100% (57-58). In one study, HSV was detected by PCR in the CSF of 71% of infants before initiation of antiviral therapy (59). The PCR was positive in 24% of infants whose disease was clinically defined as mucocutaneous (59). Additional data are required regarding the clinical importance of these observations.

Patients without obvious clinical evidence of CNS disease should also have a lumbar puncture performed for CSF DNA PCR because some of these infants may have unrecognized CNS HSV infection. It has been determined that neonatal HSV infection may occur despite the finding of ‘normal’ CSF cell counts and biochemical features, particularly during the early stages of infection. The CSF DNA PCR testing should still be performed even if the above parameters are normal.

The evaluation of HSV viremia using DNA PCR is less well established compared with CSF DNA PCR (60-62). One study evaluated HSV viral load in serum and CSF using a real-time PCR assay (60). Patients with disseminated disease had higher viral loads in their sera, while those with CNS infection had higher viral loads in the CSF. Viral loads were higher in patients who succumb to HSV disease, suggesting that HSV viral load may be useful in assessing the prognosis of neonatal HSV disease. A poorer prognosis has also been associated with persistence of HSV DNA in the CSF while on therapy (60).

The use of serology in the diagnosis of neonatal HSV infection is hampered by several factors. First, transplacental IgG antibodies cannot be differentiated from IgG produced by the infant. Second, the ability of some severely affected infants to make antibody is impaired. Third, the commercially available assays for HSV IgM antibodies have variable and limited reliability.

Overall, each of the specific laboratory tests for HSV has important limitations. Thus, the results of these tests should be interpreted with careful consideration of the clinical picture and the results of general laboratory tests that may be consistent with HSV infection. These tests include EEG, computerized tomography or magnetic resonance imaging, liver transaminases and complete blood count.  

TREATMENT OF NEONATAL HSV INFECTION
Among the agents that have been evaluated for the treatment of neonatal HSV infection, acyclovir has emerged as the agent of choice (63-64).  

Recent data support the use of high-dose acyclovir (60 mg/kg/day in 3 divided doses) for the treatment of neonatal HSV.  Data from the NIAID Collaborative Study suggest that mortality and morbidity were lower in infants who were treated with higher doses of acyclovir (56); data support the use of 21 days duration of therapy for CNS and disseminated disease. Oral acyclovir has limited bioavailability in neonates resulting in inadequate drug levels (65). Consequently, parenteral therapy is required.  

The use of higher doses of acyclovir is associated with an increased frequency of neutropenia (56). In addition, adequate hydration is necessary to reduce the risk of nephrotoxicity.  

Topical agents (e.g., trifluridine) are recommended for use along with parenteral acyclovir in neonates with ocular disease (66).  

Due to the association between late sequelae and recurrent HSV skin lesions, questions have arisen regarding the role of long-term suppressive therapy with oral acyclovir. Administration of oral acyclovir as suppressive therapy can prevent recurrences of HSV after SEM disease (67). However, data are lacking regarding whether the suppression of cutaneous recurrences with oral acyclovir will result in a reduction of the incidence of late neurologic sequelae (66).  

There are no data to suggest that intravenous immune globulin is of value in the treatment of neonatal HSV  (68-69).  

Given the potential for significant neurological sequelae among survivors of neonatal HSV infection, affected infants should be followed carefully. They should have a structured follow-up program that allows for neurodevelopmental, ophthalmologic and hearing assessments.

RECOMMENDATIONS

PREVENTION OF NEONATAL HSV INFECTIONS
Pregnant women

• All pregnant women should be asked about any past history of genital HSV infection in themselves or their sexual partner(s). Signs and symptoms of current genital HSV infection should be checked in all patients during their prenatal evaluations (B-II-3).

• Primary or First Episode Infections: These women are known to be at high risk of transmitting HSV to their newborns. Such women may experience benefit from antiviral treatment of primary or first episode infections and suppressive acyclovir therapy starting at 36 weeks’ gestation at a dose of 400 mg tid (B-ll-3). 

• Primary HSV in third trimester: Cesarean delivery should be offered to women who develop primary HSV in the third trimester (after 28 weeks), notably in the setting where lesions occur within 6 weeks of anticipated delivery and adequate maternal seroconversion has not yet occurred (B-ll-3). Consultation with experts in infectious diseases is recommended, particularly if there are questions regarding the woman’s serologic status. 

• Recurrent genital HSV during pregnancy. There is increasing evidence and consensus to suggest that acyclovir suppressive therapy (400 mg tid starting at 36 weeks gestation) should be offered to pregnant women who experience recurrent genital herpes during pregnancy (B-I).

Women in labor

•  During labour all women should be asked about recent symptoms and carefully examined for evidence of genital HSV infection (A-II-3).

• In the presence of HSV lesions in the perineal region, cesarean section is recommended. This mode of delivery may reduce the risk of neonatal HSV infection if performed within 4-6 hours of membrane rupture (B-II-3). However, many experts recommend cesarean delivery even if the membranes have been ruptured for longer than 6 hours (B-III).

• Cesarean section should be performed immediately on a woman who presents with ruptured membranes and active genital lesions at term (B-II-3). However, the appropriate management of delivery is not established if the membranes are ruptured at a gestational age when the fetal lung is very immature. In such situations, some experts recommend that intravenous acyclovir (15 mg/kg per day in 3 divided doses, maximum 1200 mg/day) be given to the mother if labor and delivery are delayed (F-III).

• In the absence of genital lesions, a maternal history of genital HSV is not an indication for cesarean delivery (D-III).

• Procedures that potentially increase the risk of infection should be avoided when possible in women with active genital herpes infection (D-II-3). Such procedures included early rupture of membranes, fetal scalp monitors and scalp sampling. 

Newborn Infants (Table 3)
The approach to the management of asymptomatic infants who were exposed to HSV at the time of delivery takes into account whether the mother has proven or presumed primary infection, known recurrent lesions or unknown current status. Women in the latter category may be regarded as having presumed primary infection.  

Infants Born by Vaginal Delivery

• All asymptomatic infants who were exposed to HSV at the time of delivery should have HSV cultures performed at 48 hours after birth (B-III). In addition, cultures are recommended if the mother had HSV during pregnancy, but with no visible lesions at delivery. Samples for HSV cultures should be taken from urine, stool or rectum, mouth, eyes and nasopharynx. One option is to perform weekly surveillance cultures for 4-6 weeks in an effort to detect evidence of active viral replication prior to the frank manifestations of disease (B-III).

• There is no firm consensus regarding the antiviral management of asymptomatic infants whose mothers had proven or presumed primary infection. Most experts recommend empiric acyclovir at birth (B-III). Others prefer to wait on the results of HSV cultures or signs or symptoms of infection before initiating therapy. If therapy is being initiated, a CSF sample should be obtained prior to treatment. Once initiated, the duration of therapy may be guided in part by emerging laboratory results. The expected duration of therapy is 14-21 days.

• An infant whose mother has known, recurrent, genital lesions should be observed carefully for evidence of infection. Acyclovir therapy is not recommended for the asymptomatic infant (B-III). 

• All symptomatic infants should be evaluated for possible HSV infection as part of a complete evaluation for sepsis. PCR testing of the CSF is recommended for all such infants.

• In the above symptomatic infants, samples for HSV culture should be taken from skin lesions, conjunctiva, nasopharynx, mouth, stool or rectum, urine, blood buffy coat and CSF. PCR testing of blood should also be considered (B-III).

In these infants, acyclovir treatment should be started if HSV infection is strongly suspected or if any of the above tests reveal the presence of HSV infection (B-III). This index of suspicion should be maintained for 6 weeks.

• The length of observation in hospital for infants at increased risk of HSV infection should be individualized, taking into account local resources, adequacy of observation at home and the nature of follow-up care (B-III).

• Given that neonatal HSV infection may occur as late as 4-6 weeks after delivery, physicians and caregivers should be vigilant and rashes and symptoms should be appropriately evaluated (B-III).

Infants Born by Cesarean Delivery

• Infants born by cesarean delivery with at least 6 hours of membrane rupture, whose mothers had herpetic lesions should be observed carefully and cultured as above. Antiviral therapy is not routinely started for such infants who are asymptomatic, but such therapy should be initiated if culture results from the infants are positive for HSV or if HSV infection is strongly suspected on clinical grounds (B-III). 

Infection Control Measures (Table 4) (66, 70)
Women in Labor and Postpartum Women with HSV

• Women who have HSV lesions should be managed during labor, delivery and the postpartum period with contact precautions (routine practice). Careful hand washing before and after care of the infants is important. (B-III). Mothers with hand lesions should use recommended hand hygiene measures and wear gloves before handling their infants

• Breastfeeding may be allowed if no lesions are present on the breast and if active lesions are covered. A clean gown may be used to avoid contact between the infant and lesions or infected secretions (B-III).

• Mothers with herpes labialis or stomatitis should wear disposable masks when touching their newborn infants until the lesions are crusted or dried. Kissing and nuzzling of the newborn infants should be avoided until the lesions have cleared (B-III).

 Neonates with HSV Infection and Exposed Neonates

• Neonates with HSV infection should be managed with Contact Isolation (in addition to standard precautions) for the duration of their illness (B-III).

• Neonates who were born to women with active HSV lesions should be managed with contact precautions during the hospitalization up to 4 weeks of age. However some experts do not recommended contact precautions if the infants were born by cesarean section and the membranes were ruptured for less than 4-6 hours (B-III). 

DIAGNOSTIC TESTS FOR NEONATAL HSV INFECTION
The Canadian Paediatric Society recommends that;

• In the evaluation of neonatal HSV infection, samples should be obtained for culture from skin lesions, mouth, nasopharynx, conjunctiva, urine, stool/ano-rectum, blood buffy coat and CSF. Positive cultures from any of the above sites at more than 48 hours after delivery are consistent with viral replication as opposed to colonization after intrapartum exposure (Category of recommendation: B-III, table 2).

•  Serologic tests should not be relied on as they are generally not helpful in diagnosing acute neonatal HSV infections (E-II-3). 

• PCR testing for CSF HSV DNA is the recommended diagnostic method of choice for HSV encephalitis (A-II-3).

TREATMENT AND FOLLOW-UP OF NEONATES WITH HSV INFECTION

• Intravenous acyclovir is the drug of choice for the treatment of neonatal HSV infection. The dosage of acyclovir is 60 mg/kg per day in 3 divided doses (B-II-2) with appropriate adjustments for renal impairment as necessary. Adverse events from acyclovir can be decreased by ensuring that the patient is adequately hydrated with appropriate urine output.

• The duration of acyclovir treatment for neonatal HSV should be 14 days if disease is limited to the skin, eye and mouth and 21 days if the disease involves the CNS or is disseminated (B-III).

• The use of oral acyclovir is contraindicated for the treatment of HSV infections in neonates (E-III).

• While relapses may occur after cessation of therapy, the optimal management of these recurrences is unclear. The value of long-term suppressive or intermittent acyclovir therapy for infants with skin, eye and mouth disease is being evaluated and a definitive recommendation cannot be made at this time.

• In addition to parenteral acyclovir, neonates with ocular involvement due to HSV infection should receive a topical ophthalmic agent such as trifluridine (B-III). 

• Infants with HSV infection should be followed and evaluated for recurrent disease and neurological sequelae. Such sequelae are most likely to occur among infants who were diagnosed with CNS or disseminated disease. Recurrent skin lesions are frequent in infants with neonatal HSV and may be associated with CNS sequelae if they occur during the first 6 months of life (B-III). Consequently, CSF examination and PCR along with intravenous acyclovir therapy are warranted at the time of recurrence of skin lesions (B-III).

FUTURE RESEARCH ISSUES

Several aspects of the prevention, diagnosis and management of neonatal HSV infection are in need of further research.  The following area should be given priority:

• The optimal management of pregnant women with genital HSV as this relates to the use of acyclovir prior to delivery.

• The management of women with known or presumed primary HSV who present with premature rupture of membranes.

• The pharmacokinetics of acyclovir in very low birth weight infants.

• The magnitude of the problem and the significance of acyclovir-resistant HSV from neonates with prolonged exposure to acyclovir.

• The impact of long-term suppressive therapy on a) infants' neurological outcomes, b). immune responses.

• The role of newer agents such as famciclovir and valacyclovir in situations where oral therapy is desired (long-term suppressive therapy for infants and prophylaxis for women with HSV during pregnancy).

• Further development and standardization of PCR assays with studies on the utility of this test on different body fluids. 

• Future role of combination antiviral therapy with acyclovir plus monoclonal HSV antibodies.

• Development of vaccines against HSV.

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INFECTIOUS DISEASES AND IMMUNIZATION COMMITTEE (2005-06)

Members: Drs Simon Richard Dobson, BC’s Children’s Hospital, Vancouver, British Columbia; Joanne Embree, The University of Manitoba, Winnipeg, Manitoba (chair); Joanne Langley, IWK Health Centre, Halifax, Nova Scotia; Dorothy Moore, The Montreal Children’s Hospital, Montreal, Quebec; Gary Pekeles, The Montreal Children’s Hospital, Montreal, Quebec (board representative); Élisabeth Rousseau-Harsany, Hôpital Sainte-Justine, Montreal, Quebec (board representative); Lindy Samson, Children’s Hospital of Eastern Ontario, Ottawa, Ontario
Consultant: Dr Noni MacDonald, Department of Pediatrics, IWK Health Centre, Halifax, Nova Scotia
Liaisons: Drs Upton Allen, The Hospital for Sick Children, Toronto, Ontario (Canadian Pediatric AIDS Research Group); Scott Halperin, IWK Health Centre, Halifax, Nova Scotia (IMPACT); Monica Naus, BC Centre for Disease Control, Vancouver, British Columbia (Health Canada, National Advisory Committee on Immunization); Larry Pickering, Centers for Disease Control and Prevention, Atlanta, Georgia, USA (American Academy of Pediatrics, Committee on Infectious Diseases)
Principal author: Dr Upton Allen, The Hospital for Sick Children, Toronto, Ontario

TABLE 1
CLASSIFICATION SCHEME FOR NEONATAL HSV DISEASE

TABLE 2
LEVELS OF RECOMMENDATIONS  

TABLE 3  

*Approach recommended by most experts; not an exclusive course of action.

TABLE 4
INFECTION CONTROL MEASURES TO REDUCE
RISK OF TRANSMISSION OF HSV  

Recommendations modified from reference 66.

Posted August 2006