HSV Seroprevalence and Diagnosis of Genital Herpes in Pregnant Women
Condition: Pregnancy
MeSH terms: Herpes Genitalis
Study type: Observational

Summary: 
      Brief summary: The current management guidelines recommended by ACOG rely on history as a
      screening method to determine pregnant women who are at risk for transmitting herpes to their
      newborn. History fails completely in identifying the women most at risk of transmitting
      herpes to their newborn - the seronegative woman who acquires a primary infection from her
      partner during pregnancy. Despite recent advances, both pregnant women and newborns continue
      to be at risk of acquiring herpes infection. Genital herpes infections are epidemic in the
      United States. In the early 1990's, 25% of women in the US were seropositive for the HSV-2
      antibody. These numbers are likely higher now. The incidence of neonatal herpes in the US
      cannot be accurately estimated since it is not a reportable disease. However, in some areas
      of the US, the incidence is 1 in 3,200 live births which would translate to an incidence of
      approximately three infants a day in the US . In other areas of the US, the incidence is even
      higher, approaching 1 in 1,500 liveborns. This protocol examines patient acceptance of HSV-1
      and HSV-2 type specific serologic testing and assesses patient counseling tools. In addition,
      seroprevalence of HSV-2 in pregnant patients will be collected and evaluated.
    

Detailed description: 
      Detailed Description: Despite recent advances, both pregnant women and newborns continue to
      be at risk of acquiring herpes infection. Genital herpes infections are epidemic in the
      United States. In the early 1990's, 25% of women in the US were seropositive for the HSV-2
      antibody (Fleming, 1997). These numbers are likely higher now. The incidence of neonatal
      herpes in the US cannot be accurately estimated since it is not a reportable disease.
      However, in some areas of the US, the incidence is 1 in 3,200 live births which would
      translate to an incidence of approximately three infants a day in the US (Brown, 2003). In
      other areas of the US, the incidence is even higher, approaching 1 in 1,500 liveborns
      (Whitley, personal communication, December 2002).

      The current management guidelines recommended by ACOG (Guidelines for Perinatal Care, 2002)
      rely on history as a screening method to determine pregnant women who are at risk for
      transmitting herpes to their newborn. Based on data reported in NHANES III, history is an
      unreliable method of determining those who are infected with genital herpes (Fleming, 1997).
      Most importantly, history fails completely in identifying the women most at risk of
      transmitting herpes to their newborn - the seronegative woman who acquires a primary
      infection from her partner during pregnancy.

      Since at-risk women can now be accurately identified by new and more accurate type-specific
      serologic tests, effective prevention strategies should be instituted to minimize risk of
      transmission to the neonate. The first obligation is to diagnose who is at risk. The highest
      risk is that of neonatal transmission from a mother experiencing a primary genital HSV-1 or
      HSV-2 infection in late pregnancy. Studies indicate that approximately 1.3% of women
      seroconvert during pregnancy and, among those who do, the risk of neonatal transmission is as
      high as 30 - 50% (Brown 1991). Conversely, the rate of neonatal transmission from women with
      recurrent genital herpes infection is low (<1%) (Brown, 1991, 1997; Smith, 1998; Arvin, 1986;
      Fonnest, 1997). However, since genital herpes is so common, the total number of cases of
      neonatal herpes from women with recurrent disease remains high (Fleming, 1997; STD
      Guidelines, 2002). Once a mother is identified as being infected with HSV-2, the health care
      providers - both pediatrician and obstetrician - can be alerted to the potential risk of
      neonatal herpes.

      Management of pregnant women with or without herpes infections should include steps designed
      to minimize the risk of herpes transmission to neonates. This protocol examines patient
      acceptance of HSV-1 and HSV-2 type specific serologic testing and assesses patient counseling
      tools. In addition, seroprevalence of HSV-2 in pregnant patients will be collected and
      evaluated.

      STUDY DESIGN

      This is a non-treatment study of acceptance rates of HSV-1 and HSV-2 type specific serologic
      testing by pregnant women and their partners. This study will also evaluate Health Care
      Provider time spent in counseling, effectiveness of counseling tools/sessions, and acceptance
      of antiviral suppression by pregnant women and/or their partners. In addition, HSV-2
      seroprevalence will be assessed. This study will be conducted at a single center (Obstetrics
      and Gynecology Office) and is not designed to yield nationally representative estimates of
      HSV-2 seroprevalence rates.

      Pregnant women who present for their first prenatal visit will be invited to enroll. A total
      of 300 patients will be enrolled.

      The clinician or staff will describe the study to the patient based on the provided
      description.

      If the patient is interested in participating in the study, she will be given an informed
      consent to sign, told that the blood test is to determine whether she is seropositive or
      seronegative for genital herpes (HSV-2) and the virus that causes cold sores (HSV-1), and
      given a demographic form to complete. If the patient is willing to be tested for HSV-1 and
      HSV-2, she will continue with counseling and completion of questionnaires. For those patients
      willing to be tested, counseling and questionnaires will be completed during visit 1 and
      visit 2. For those patients who are unwilling to be tested, counseling and questionnaires
      will be administered during this first visit.

      The investigator and office staff will monitor time spent in each counseling session, and
      also provide assessment of effectiveness and satisfaction with counseling tools.

      STUDY ASSESSMENTS AND PROCEDURES

      Screening and Assessments

      Prior to inviting the patient to take part in the clinical trial, each patient's chart should
      be reviewed to be certain that the patient does not have a known history of genital herpes or
      prior knowledge of HSV-2 seropositivity.

      Prior to enrollment of patients in the study, the investigator and appropriate study
      personnel will be provided with training on HSV serologic testing and provided with the
      counseling tools. This will ensure that all patients receive standardized HSV counseling at
      the initial visit and during the follow-up visit when test results are discussed.

      It is important to note that ideally, the same person on staff should administer the
      Counseling Scripts using verbiage consistent with the provided scripts This should be
      administered with care and concern in a private setting. The counselor then should give the
      patient sufficient time to ask questions.

      Following is an outline of study assessments and procedures Visit #1

        -  The clinician or staff will describe the study to the patient by the following script:

      This study involves your willingness to have a blood test to determine if you are infected
      with the virus that causes genital herpes or the virus that causes cold sores. If you decide
      to participate in this study and decide to have the blood test or even if you decide NOT to
      have the blood test, you will be asked to complete questionnaires and counseling sessions
      given by the office staff. This will be a time commitment of about 1 hour and may include an
      additional 20 minute office visit next week.

        -  All patients willing to be a part of the study will sign an informed consent

        -  Patients will complete a Demographics Questionnaire

      Patients willing to be tested will:

        -  Sign informed consent for blood test

        -  Have blood drawn for serological assessment via the FOCUS HerpeSelect 1 and 2 ELISA
           assay.

        -  Receive counseling

        -  Complete Questionnaire on Understanding Counseling

        -  Age, race and infection history will be documented on the CRF based on information from
           the patient's chart and the medical history sheet routinely used by the clinic
           (completed by the patient)

        -  Be given brochure and one-page information sheet

        -  Instruct the patient to read the entire brochure but to also focus on Page 4, the
           section related to pregnancy

        -  Schedule visit in one week (Visit 2)

      Patients unwilling to be tested will:

        -  Complete Questionnaire about Barriers to Testing

        -  Receive counseling

        -  After receipt of counseling the patient will be asked again if willing to be tested

        -  If willing to be tested o Go to list of "patients willing to be tested, sign the
           informed consent for the blood test and draw the blood test without further counseling
           at this visit.

        -  If not willing to be tested

           o Complete Understanding of Counseling and Survey on Satisfaction with Counseling

           o Be given brochure and one-page information sheet

           o Instruct the patient to read the entire brochure but to also focus on Page 4, the
           section related to pregnancy

           o Repeat barriers questionnaire

           o Schedule next visit (continue with prenatal visits consistent with standard of care)

             -  At next visit, ask again if willing to be tested (if yes, clinic staff will proceed
                with assessments and procedures under patients willing to be tested [above] except
                third bullet point, Receive Counseling and sixth bullet point Complete
                questionnaire Understanding Counseling. Offer the patient the brochure and
                information sheet again.

             -  If at any point during the study the patient changes her mind and becomes willing
                to be tested, document the reason for this change in the CRF.

        -  Investigator/staff will document time spent for counseling in the case report form

      Follow Up Assessment

      Visit #2

      Patients willing to be tested will:

        -  Be given results of the HSV-1 and HSV-2 serologic test

        -  Receive Counseling

             1. Patients with negative HSV-2 serologic test If the woman is HSV-1 seronegative,
                counsel her with the section of the Script: For patients who are HSV-1 seronegative

        -  Encourage the patient to discuss her test results and its meaning with her partner

        -  Ask the following question (answer will be documented in the case report form by Yes/No
           response):

             -  Do you know if your partner is positive for HSV-1 or HSV-2 . If NO to either HSV-1
                and HSV-2, follow up as described below.

      Follow-up visit

      • During normally scheduled pre-natal visits (up to week 28), ask the patient if her partner
      had been tested. Document answer in the case report form.

      OR

      2. Patients with positive HSV-2 serologic test If the woman is HSV-1 seronegative, counsel
      her with the section of the Script: For patients who are HSV-1 seronegative

        -  Encourage the patient to discuss her test results and its meaning with her partner

           o Give the patient the brochure (Taking Charge of your Life and instruct the patient to
           read the entire brochure but to also focus on the section related to pregnancy

        -  Ask the following questions (answer will be documented in the case report form by Yes/No
           response):

             -  Are you willing to take medicine to treat your herpes during your pregnancy?

             -  Do you know if your partner is positive for HSV-1 or HSV-2 . If NO to either HSV-1
                or HSV-2, follow up as described below.

      Follow-up visit

        -  During normally scheduled prenatal visits (up to week 28), ask the patient if her
           partner had been tested. Document answer in the case report form.

        -  Complete Understanding Counseling Questionnaire [appropriate questionnaire for
           seronegative or seropositive patients, respectively] and Survey of Satisfaction with
           Counseling,

      Investigator/counseling staff will:

      • Document time spent for counseling and for ordering HSV-1 and HSV-2 blood tests for each
      patient in the case report form Upon completion of study, complete Satisfaction with
      Counseling Tools Questionnaire

      HEALTH OUTCOMES

      At the first visit a self administered questionnaire regarding barriers to testing will be
      given to each eligible patient refusing to be tested. After counseling, this questionnaire
      will be repeated for those patients who still refuse testing. All patients will be counseled
      and will be given two self administered questionnaires. One questionnaire will assess the
      patient's understanding of the counseling and the other will assess the patient's
      satisfaction with the counseling session. At the second visit, those patients who were tested
      will receive their test results and will be counseled on their status (positive or negative).
      These patients will receive two self administered questionnaires. One questionnaire will
      assess the patient's understanding of counseling (specific to their status), and the other
      will assess the patient's satisfaction with the counseling session. A separate self
      administered questionnaire will be given to the investigator and/or appropriate office
      personnel to assess their satisfaction with the counseling tools and sessions.

      DATA ANALYSIS AND STATISTICAL CONSIDERATIONS

      Hypotheses

      This is a non-treatment study in pregnant women to assess the acceptances of HSV serologic
      testing and their understanding and satisfaction with counseling tools.

      Interim Analysis

      An interim analysis is not planned.

      Primary Analysis

      • The percentage of pregnant patients who accept HSV-1 and HSV-2 type specific testing

      Secondary Analyzes

        -  The mean (SD) percent and frequencies (n, %) of questions answered correctly by all
           subjects in the "Understanding Counseling" questionnaire

        -  The mean (SD) percent and frequencies (n, %) of questions answered correctly by
           seronegative subjects in the "Understanding Counseling" questionnaire

        -  The frequencies (n, %) and mean (SD) percent of questions answered correctly by
           seropositive subjects in the "Understanding Counseling" questionnaire

        -  The frequencies (n, %) and mean (SD) scores for each item in the "Satisfaction with
           Counseling" (for the patient) scale

        -  The frequencies (n, %) and mean (SD) scores for each item in the "Satisfaction with
           Counseling Tools" ( for the counselor) scale

        -  The percentage of partners of pregnant women who were tested

        -  The percentage of pregnant women (who are HSV-2 positive) who would accept antiviral
           suppressive therapy during pregnancy

        -  The frequencies (n, %) and mean (SD) scores for each reason/item in the "Reason For
           Choosing Not To Be Tested" scale

        -  The mean (SD) total time (in minutes) spent by the investigator and clinic staff in
           obtaining the both the HSV-2 type specific serologic test and counseling
    

Intervention name(s): testing for HSV 1 and 2 IgG type specific antibosy
Intervention type(s): Other
Observational model: Ecologic or Community
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        pregnant subjects
      
Keywords: pregnancy, genital herpes