Maternity Care Calendar and Guidelines: Screening for herpes simplex

Literature Search:

Medline was searched using the MeSH exp HERPES SIMPLEX/ or exp HERPES GENITALIS AND pregnancy.mp or exp PREGNANCY (MeSH or keyword), limited to English and human from 1998-2003. Primarily clinical practice guidelines and review articles were selected. EBM reviews including the Cochrane Database of Systematic Reviews (CDSR), ACP Journal Club, Database of Abstracts and Reviews of Effectiveness (DARE) and Cochrane Central Register of Controlled Trials (CCTR) were searched using the MeSH exp HERPES SIMPLEX/ or exp HERPES GENITALIS AND pregnancy.mp or exp PREGNANCY (MeSH or keyword). The Canadian Task Force on Preventive Health Care, the US Preventive Services Task Force and the US National Guideline Clearinghouse were also reviewed for guidelines on herpes simplex and pregnancy.

Summary of Evidence:

Background

The 2 herpes simplex virus types; type 1 (HSV-1) and type 2 (HSV-2) share enough antigenic determinants that antibodies to one are capable of neutralizing the other.[1] Initial contact with HSV generally occurs in childhood, is often asymptomatic and usually involves HSV type 1.[1] HSV-1 is responsible for most herpes labialis, gingivostomatitis and keratoconjunctivitis. Approximately 90% of adults have antibody to HSV-1.[2] Although most genital infection is from HSV-2, either type can result in genital herpes infection. Approximately 30% of women in the US have antibodies to HSV-2.[1] The first population estimates of HSV-2 seroprevalence in Canada were determined through an anonymous unlinked seroprevalence study of stored sera of pregnant women in British Columbia in 1999. [3] The overall age-adjusted prevalence for HSV-2 was 17.3%, ranging from 7.1% in women 15-19 years to 28.1% in women age 40-44.

There are 3 stages of HSV clinical infection, determined by clinical presentation and serology:[1]

Primary genital HSV - no antibodies to HSV-1 or HSV-2 are present when patient is infected with HSV-1 or HSV-2. Nonprimary first-episode genital HSV -acquisition of genital HSV-1 or HSV-2 with preexisting antibodies to the other type. Recurrent genital herpes - reactivation of genital HSV when there are preexisting antibodies to the type involved.

In practice it can be difficult to differentiate between primary disease and a non-primary first episode without serologic testing.

HSV is transmitted through direct contact. One study showed that that annual rate of transmission of HSV between partners who were discordant for HSV infection was 31.9% for women with no antibodies to HSV-1 or HSV-2 and 9.1% for women with HSV-1 antibodies. [1] More than 50% of the cases of transmission were the result of asymptomatic shedding, making this virus particularly difficult to control and prevent.

Rates of vertical transmission at the time of delivery are 50% for primary HSV, 33% for non-primary first episode and 0-3% for recurrent HSV. [1] [2]Genital herpes that is acquired during pregnancy is not generally thought to be associated with an increase in neonatal illness or congenital HSV infection as long as HSV seroconversion has completed by the time of labour. [2, 4]There have been case reports of hematogenous spread of HSV to the fetus in early pregnancy resulting in fetal anomalies similar to the other TORCH infections.

Neonatal HSV, acquired in the birth canal can cause localized disease in the skin, eye or mouth (no associated mortality), CNS disease (15% mortality) or disseminated disease (57% mortality).[1]

Serologic Testing:
Traditional HSV antigen enzyme immunoassays (EIAs) do not distinguish between HSV-1 and HSV-2.[2] In recent years, type-specific serologic tests have become available. Assays such as the western blot are 98% sensitive and 100% specific for detecting HSV -2. [4] However, the western blot is not widely available.[2, 5, 6] Gull Laboratories in the US is marketing a HSV type-specific serology kit that is less expensive and labour intensive. [4]

A number of authors have proposed that HSV type-specific serologic testing should be carried out routinely in pregnancy.[7, 8] Women who were found to be HSV-2 seropositive could be counseled to recognize the symptoms of their reactivations and about the option of aciclovir (acyclovir) at term to decrease the risk of Caesarian section. Also, invasive procedures such as the use of fetal scalp clips, artificial rupture of membranes, forceps and vacuum extractors should be avoided if possible. [9]The partners of seronegative women, could also be tested and discordant couples could be counseled about the risk of neonatal HSV if herpes is acquired at term as well as how to decrease this risk (abstinence/condoms/suppression of the seropositive partner with acyclovir during the pregnancy). HSV negative women with HSV-1 seropositive partners should be counselled to avoid oral genital contact in the second half of pregnancy. [9] As one author advocating routine type-specific serology for all pregnant women explains, caesarian section of all women with recurrent genital herpes is not an efficient strategy for preventing neonatal HSV, because most symptomatic lesions are caused by recurrent HSV-2, while most neonatal herpes is caused by asymptomatic first episodes. [4, 9] Because of the relatively low risk of vertical transmission, he states that HSV-2 seropositive women with genital lesions in labour could be considered for vaginal delivery. Women with recurrent genital HSV-1, those who are seroconverting to HSV-1 or HSV-2 or those whose serostatus is unclear should undergo caesarian section. The Canadian STD Guidelines state that type-specific serology should be considered to identify when pregnant women with no history of herpes are at risk of primary herpes infection from a partner.[10]

However, others have argued against type-specific serologic screening, particularly in the UK where the prevalence is lower than the US.[6, 11-13] One British study found that the intervention would not be cost-effective, costing between £100, 000 to £4 million per case of severe neonatal herpes prevented. [11] An American cost-effectiveness analysis similarly found that it would cost hundred of thousands - 4 million dollars per case of neonatal HSV prevented.[14] Also, concerns have been raised about the potential emotional impact of the test results on couples and the lack of evidence demonstrating that counselling interventions are effective in preventing the spread of STDs.[14] One author points out that most neonatal HSV would not be prevented by screening.[14]

Most authors advocate questioning all pregnant women and their partners about a history of herpes. [5, 15-19]. Women whose partners have genital herpes should be counselled regarding how to avoid sexual transmission. Individuals with orolabial herpes should be counselled about avoid transmission through oral genital contact and avoiding transmission to the newborn through kissing.

Recommendations of Others:

Canadian Task Force on Preventive Health Care (CTFPHC)

The CTFPHC has a review on The "Prevention of Neonatal Herpes Simplex" on their website written in 1989, updated in 1994 (http://www.ctfphc.org/). They make the following recommendations: The review on herpes has not been updated since 1989 and does not address the issues of screening women routinely by history and counselling those at risk or screening serologically.

U.S. Preventive Services Task Force (USPSTF):

The USPSTF most recently reviewed screening for genital herpes simplex in 1996. The make the following recommendations: [16] Recommendations from the Centers for Disease Control and Prevention: [15]

The recently released sexually transmitted disease treatment guidelines from CDC state that prevention of neonatal HSV depends on both preventing acquisition of HSV during late pregnancy and avoiding exposure of the infant to HSV during delivery. They note that although the risk of vertical transmission is much lower in women with recurrent herpes (<1%) vs. women with newly acquired herpes (30-50%), because recurrent herpes is much more common than new infections, the proportion of cases of vertical transmission due to recurrent HSV remains high. The CDC recommends: American College of Obstetricians and Gynecologists (ACOG):[1]

A practice bulletin, published in 1999, makes the following recommendations about universal screening for HSV in pregnancy or at delivery: In the ACOG, guidelines for Perinatal Care, the following recommendations are made:[19] Society of Obstetricians and Gynaecologists of Canada (SOGC):[17]
http://www.sogc.org/sogcnet/sogc%5Fdocs/common/guide/pdfs/co2.pdf

The most recent SOGC guidelines for herpes in pregnancy were published in 1992. They state that Royal College of Obstetricians and Gynaecologists (RCOG):[18]
(http://www.rcog.org.uk/guidelines.asp?PageID=106&GuidelineID=39)

The 2002 Guidelines "Genital Herpes in Pregnancy-Management" gave the following recommendations: Association for Genitourinary Medicine and the Medical Society for the Study of Venereal Disease:
In the 2001 National Guideline for the Management of Genital Herpes are the following recommendations:
http://www.guideline.gov/summary/summary.aspx?doc_id=3035

Conclusions:
The new guideline on the MCC will be as follows:
Reviewer: Colleen Kirkham,MD,CCFP,FCFP February 2003

3/30/2005 11:29:00 PM


1. Anonymous, ACOG practice bulletin. Management of herpes in pregnancy. Number 8 October 1999. Clinical management guidelines for obstetrician-gynecologists. International Journal of Gynaecology & Obstetrics., 2000. 68(2): p. 165-73.
2. Desselberger, U., Herpes simplex virus infection in pregnancy: diagnosis and significance. Intervirology., 1998. 41(4-5): p. 185-90.
3. Patrick, D.M., et al., Antenatal seroprevalence of herpes simplex virus type 2 (HSV-2) in Canadian women: HSV-2 prevalence increases throughout the reproductive years. Sexually Transmitted Diseases., 2001. 28(7): p. 424-8.
4. Brown, Z.A., Genital herpes complicating pregnancy. Dermatol Clin, 1998. 16(4): p. 805-10, xiv.
5. Smith, J.R., F.M. Cowan, and P. Munday, The management of herpes simplex virus infection in pregnancy. British Journal of Obstetrics & Gynaecology., 1998. 105(3): p. 255-60.
6. Wilkinson, D., S. Barton, and F. Cowan, HSV-2 specific serology should not be offered routinely to antenatal patients.[comment]. Reviews in Medical Virology., 2000. 10(3): p. 145-53.
7. Brown, Z.A., et al., The acquisition of herpes simplex virus during pregnancy. N Engl J Med, 1997. 337(8): p. 509-15.
8. Kinghorn, G.R., Debate: the argument for. Should all pregnant women be offered type-specific serological screening for HSV infection?[comment]. Herpes., 2002. 9(2): p. 46-7.
9. Brown, Z.A., HSV-2 specific serology should be offered routinely to antenatal patients. Rev Med Virol, 2000. 10(3): p. 141-4.
10. Canadian STD Guidelines, ed. H. Canada. 1998. http://www.hc-sc.gc.ca/pphb-dgspsp/publicat/std-mts98/.
11. Qutub, M., et al., Genital herpes in pregnancy: is screening cost-effective? International Journal of STD & AIDS., 2001. 12(1): p. 14-6.
12. Arvin, A.M., Debate: the argument against. Should all pregnant women be offered type-specific serological screening for HSV infection?[comment]. Herpes., 2002. 9(2): p. 48-50.
13. Munday, P.E. and H.M. Mullan, Clinical uses of herpes simplex virus type-specific serology. Int J STD AIDS, 2001. 12(12): p. 784-8.
14. Rouse, D.J. and J.S. Stringer, An appraisal of screening for maternal type-specific herpes simplex virus antibodies to prevent neonatal herpes. American Journal of Obstetrics & Gynecology., 2000. 183(2): p. 400-6.
15. Centers for Disease Control and Prevention Sexually transmitted disease treatment guidelines. MMWR, 2002. 51 (no. RR-6): p. 1-80.
16. U.S. Preventive Services Task Force Guide to Clinical Preventive Services: report of the U.S. Preventive Services Task Force. 2nd ed. 1996, Baltimore: Williams & Wilkins. 953.
17. SOGC Committee Opinion: toward the rational management of herpes infection in pregnant women and their newborn infants. 1992.
18. Royal College of Obstetricians and Gynaecologists Clinical Green Top Guidelines No. 30: Genital Herpes in pregnancy - Management. 2002.
19. Guidelines for Perinatal Care 5th ed. Fifth ed. 2002, Elk Grove Village, Il.: American Academy of Pediatrics, and Washington, D.C.: American college of Obstetricians and Gynecologists: American Academy of Pediatrics, The American College of Obstetricians and Gynecologists.