Herpes Simplex Virus Infection in Labor Case File

Herpes Simplex Virus Infection in Labor Case File

Eugene C. Toy, MD, Patti Jayne Ross, MD, Benton Baker III, MD, John C. Jennings, MD

CASE 9

A 31-year-old G3P2 woman at 39 weeks’ gestation arrives at the labor and delivery area complaining of strong uterine contractions of 4-hour duration; her membranes ruptured 2 hours ago. She has a history of herpes simplex virus (HSV) infections. She denies any blisters, and her last herpetic outbreak was 4 months ago. She is taking oral acyclovir. She notes a 1-day history of tingling in the perineal area. On examination, her blood pressure (BP) is 110/60 mm Hg, temperature is 99°F (37.2°C), and heart rate (HR) is 80 beats per minute (bpm). Her lungs are clear to auscultation. Her abdomen reveals a fundal height of 40 cm. The fetal heart rate is 140 bpm, reactive, and without decelerations. The uterine contractions are every 3 minutes. The external genitalia are normal without evidence of lesions. The vagina, cervix, and perianal region are normal in appearance. The vaginal fluid is consistent with rupture of membranes, showing ferning and an alkalotic pH.

» What is your next step?

» What is the most likely diagnosis?

ANSWER TO CASE 9:

Herpes Simplex Virus Infection in Labor                                          

Summary: A 31-year-old G3P2 woman at 39 weeks’ gestation is in labor and her membranes ruptured 2 hours ago. She has a history of herpes simplex virus (HSV) infections and is taking oral acyclovir suppressive therapy. She has a 1-day history of tingling in the perineal area.

• Next step: Counsel patient about risks of neonatal HSV infection and offer a cesarean delivery.
• Most likely diagnosis: Herpes simplex virus recurrence with prodromal symptoms.

ANALYSIS

Objectives

1. Understand the indications for cesarean delivery due to HSV infection in pregnancy.
2. Know that HSV may cause neonatal encephalitis.
3. Understand that symptoms of prodromal infection may indicate viral shedding.

Considerations

The patient is in labor and has experienced rupture of membranes. She has a history of HSV infections. Although she has no lesions visible and is taking acyclovir suppressive therapy, she complains of tingling of the perineal region. These symptoms are sufficient to suggest an HSV outbreak. With HSV shedding of the genital tract, there is risk of neonatal infection, especially encephalitis, which can lead to severe permanent CNS compromise. The patient should be counseled about the neonatal risks, and offered cesarean delivery to decrease the risk of neonatal exposure to the HSV.

APPROACH TO:

Herpes Simplex Virus in Pregnancy                                                   

DEFINITIONS

HERPES SIMPLEX VIRUS PRODROMAL SYMPTOMS: Prior to the outbreak of the classic vesicles, the patient may complain of burning, itching, or tingling.

NEONATAL HERPES INFECTION: H SV can cause disseminated infection with major organ involvement; be confined to encephalitis, eyes, skin, or mucosa; or be asymptomatic. The vast majority of neonatal herpes infections occur via exposure to virus in fluids and secretions of the genital tract, although 5% to 10% may occur in the antepartum period transplacentally. Infants born to women who acquire a new HSV infection near delivery have a 30% to 50% risk of infection, due mostly to increased viral load in the mother.

CLINICAL APPROACH

Herpes cultures or polymerase chain reaction (PCR) are not useful in the acute management of pregnant women who present in labor or with rupture of membranes. They are helpful in making the diagnosis during the prenatal course, when the patient may develop lesions and the diagnosis is in question. Once a woman has been diagnosed with HSV, the practitioner uses his or her best clinical judgment to assess for the presence of HSV in the genital tract during the time of labor. A meticulous inspection of the external genitalia, vagina, cervix (including by speculum examination), and perianal area should be undertaken for the typical herpetic lesions, such as vesicles or ulcers (Figure 9– 1). Additionally, the patient

should be queried thoroughly about the presence of prodromal symptoms. When there are no lesions or prodromal symptoms, the patient should be counseled that she is at low risk for viral shedding and likely has a small but possible risk of neonatal herpes infection. Usually the patient will opt for vaginal delivery under these circumstances. In contrast, the presence of prodromal symptoms or genital lesions suspicious for HSV is sufficient to warrant a recommendation for cesarean delivery to prevent neonatal infection.

Figure 9–1. First episode of primary genital herpes simplex virus infection. (Reproduced with permission from Wendel GD, Cunningham FG. Sexually transmitted diseases in pregnancy. In: Williams Obstetrics. 18th ed. (Suppl. 13). Norwalk, CT: Appleton & Lange.)

The highest risk factor for neonatal infection is acquisition of new HSV infection near the time of delivery, anywhere from a 30% to 50% risk. For this reason, the Centers for Disease Control and Prevention (CDC) recommends that women who have not been infected with HSV abstain from sex with partners with known HSV infection in the third trimester.

Two subtypes of HSV have been identified: HSV-1 and HSV-2. HSV-1 is responsible for most nongenital disease; however, HSV-1 has been increasingly implicated in up to 50% of new onset genital infections in adolescents and young adults. HSV-2 is found almost exclusively in the genital region, and the vast majority of recurrences are due to HSV-2. Although there is cross-reactivity between HSV-1 and HSV-2 proteins, prior HSV-1 exposure often fails to prevent infection with HSV-2, though it may reduce severity of symptoms (see Table 9– 1). Acyclovir has activity against both HSV-1 and HSV-2. In a primary herpes outbreak, oral acyclovir reduces viral shedding, pain symptoms, and is associated with faster healing of the lesions. Newer medications such as valacyclovir or famciclovir require less frequent dosing due to their increased bioavailability, but are more expensive.

Table 9–1 • CATEGORIES OF GENITAL HSV INFECTIONS
Terminology	Definition	Clinical Manifestation	Transmission Rate
Primary infection	HSV infection in an individual who has no HSV IgG antibodies (no prior exposure to HSV; HSV-1 and HSV-2 negative)	Systemic symptoms include fever, malaise, fever, nausea Local symptoms: burning, itching, lesions (last about 21 days) NOTE: Up to 75% of women have asymptomatic primary HSV infections	50%
Nonprimary first episode infection	A first HSV infection in a woman who has the heterologous IgG antibody (Example: The first HSV-2 outbreak in a woman with HSV-1 IgG antibody, but no HSV-2 antibody)	Systemic symptoms and local symptoms usually milder and less duration that primary infection (lesions last about 14 days)	33%
Recurrent infection	A genital HSV infection in a woman who has homologous IgG antibody (Example: HSV-2 outbreak in a woman who has HSV-2 IgG)	No systemic symptoms; local symptoms (lesions last about 9 days, and viral shedding about 4 days and lower viral load than primary or nonprimary first episode)	0%-4%
Asymptomatic viral shedding	Presence of HSV virus in the genital region in the absence of symptoms	Usually brief periods (24-48 hours) of viral shedding, affecting about 1%-2% of pregnant women	0%-4%

The use of oral suppressive antiviral therapy at 36 weeks for women who have had a recurrence or first episode during pregnancy has been shown to decrease viral shedding and the frequency of outbreaks at term, and decrease the need for cesarean delivery. It is unclear whether this prophylaxis is useful for those without a recurrence during pregnancy, yet many practitioners will recommend prophylaxis. If there is no HSV involvement of the breast, the patient may breastfeed. Use of acyclovir for suppression has also been found to be safe in breastfeeding mothers.

Controversies

Some experts recommend serologic screening for HSV-2 antibodies for couples so that antiviral suppression and safer sex practices as well as counseling of women can be performed. For instance, in the circumstance where the pregnant woman is HSV-2 antibody negative, and the partner is HSV-2 antibody positive, safer sex practices may be adopted. However, there is no evidence that this practice is costeffective or would reduce neonatal HSV infection. At this time, routine screening for antibodies and suppressive therapy for seropositive partners is not recommended.

COMPREHENSION QUESTIONS

9.1 A 32-year-old G1P0 woman at 24 weeks’ gestation is seen by her obstetrician for painful vesicles on the vulva. PCR is performed and returns as HSV-2. The obstetrician counsels the patient about the possibility of needing cesarean when she goes into labor. Which of the following is an indication for cesarean section due to maternal HSV?

A. Vesicular lesions noted on the cervix

B. History of lesions noted on the vagina 1 month previously, now not visible

C. Lesions noted on the posterior thigh

D. Tingling of the chest wall with lesions consistent with herpes zoster

9.2 A 29-year-old G2P1 woman is seen in the office for her pregnancy at 16 weeks’ gestation. She complains of some burning of the vulvar area. Two blisters are noted on the labia majora. PCR is performed on the lesions, which returns as HSV-1. Which of the following statements is most accurate in the counseling of this patient?

A. Because this result is HSV-1, the finding is likely a false-positive result and the patient does not likely have a herpes infection.

B. Because of the finding of HSV-1, the neonate is not at risk for herpes encephalitis.

C. The patient should be treated the same whether the infection is HSV-1 or HSV-2.

D. The patient likely has an HIV infection since HSV-1 was isolated in the vulvar area.

9.3 A 35-year-old healthy G2P1 woman at 20 weeks’ gestation presents with primary episode of herpes simplex virus, confirmed by PCR. Oral acyclovir is given for a 10-day course. Which of the following is the rationale for the acyclovir therapy?

A. Decrease the likelihood of recurrence and need for cesarean

B. Decrease the likelihood of transplacental transmission to the fetus

C. Decrease the duration of viral shedding and duration of the current infection

D. Increase the patient’s immunity and IgG levels to HSV

9.4 A 34-year-old woman is seen at her internist’s office complaining of vulvar pain. On examination, three ulcers are noted on the right labia majora. The lesions have ragged edges, a necrotic base, and there is adenopathy noted on the right inguinal region. Which of the following is the most likely diagnosis?

A. Syphilis

B. Herpes simplex virus

C. Chancroid

D. Squamous cell carcinoma

E. Bartholin gland abscess

9.5 A 3-day-old 3500-g neonate is seen in the neonatal intensive care unit with suspected congenital herpes simplex virus infection. The infant has had several seizures and is on antiviral therapy. Which of the following is the most likely scenario of infection to this infant?

A. Primary infection during the time of labor

B. Nonprimary first episode infection at the time of labor

C. Recurrent infection at the time of labor

D. Asymptomatic shedding in a patient with a history of HSV

E. Asymptomatic shedding in a patient without a history of HSV

ANSWERS

9.1 A. The presence of prodromal symptoms or lesions along the genital tract (ie, cervix) suspicious for HSV is sufficient to warrant a cesarean delivery to prevent neonatal infection. When there are no lesions or prodromal symptoms, the patient should be counseled that she is at low risk for viral shedding and has an unknown risk of neonatal herpes infection; typically, the patient will opt for vaginal delivery. The posterior thigh is unlikely to inoculate the baby during delivery, and is not an indication for cesarean delivery. Lesions on the chest wall consistent with herpes zoster would not necessitate cesarean delivery; however, the baby should still not come in contact with these lesions, and breast feeding should be avoided. Herpes zoster infection in a neonate can have fatal consequences.

9.2 C. Although HSV-1 is usually found above the waist and HSV-2 below the waist, there are often exceptions. PCR is highly sensitive and specific, and it is unlikely that the viral subtype is erroneous. HSV-1 can also cause neonatal encephalitis, and the patient should be counseled and treated the same as if HSV-2 were isolated. A finding of HSV-1 in the vulvar region does not suggest HIV infection; nevertheless, the patient should have screening for sexually transmitted infections.

9.3 C. The rationale for oral acyclovir therapy at the primary outbreak is to decrease viral shedding and the duration of infection. The acyclovir does not affect the likelihood of future recurrence and does not change the patient’s immune response. Oral suppressive antiviral therapy beginning at 36 weeks should also be considered in this patient to reduce the chance of viral shedding and recurrence near the time of delivery. There is no evidence that oral acyclovir alters transplacental transmission to the fetus, although reducing the viremia may help.

9.4 C. Chancroid is a rare cause of infectious vulvar ulcers in the United States, although worldwide it is quite common; thus, cases occurring in the United States are related to ports of entry. Chancroid is a sexually transmitted disease (STD) caused by the gram-negative bacterium Haemophilusducreyi and, like HSV, is characterized by painful genital lesions. HSV is the most common cause of infectious vulvar ulcers in the United States, and individuals are typically infected with the HSV-2 virus that is sexually transmitted. Genital herpes can cause recurrent painful genital sores, and herpes infection can become severe in people who are immunosuppressed. Syphilis typically presents during the first stage of the disease as a small, round, and painless chancre in the area of the body exposed to the spirochete. The Bartholin glands, responsible for vaginal secretions, are located at the entrance of the vagina; they may enlarge into painless abscesses when they become clogged and infected. Vulvar carcinoma typically is nontender, ulcerative, and is more common in postmenopausal women.

9.5 E. Currently in the United States, the vast majority of neonatal H SV infections occur due to asymptomatic viral shedding during a primary infection or nonprimary first episode at term. In 75% to 90% of situations involving neonatal HSV infection, the women have had no history of an HSV infection. Thus, strategies for prevention are challenging. Some investigators have advocated for serologic screening of all pregnant women, and advising those who are seronegative for one or both HSV subtypes to refrain from genital/ genital or oral/ genital exposure in the third trimester.

    CLINICAL PEARLS    

» Cesarean delivery should be offered to a woman with a history of HSV who has prodromal symptoms or suspicious lesions of the genital tract. » Herpes simplex virus is the most common cause of infectious vulvar ulcers in the United States. » Most neonatal herpes infections occur from HSV from genital tract secretions and fluids, although 5% of neonatal infections are acquired in utero. These are usually due to primary or nonprimary first episode infections. » The cervix, vagina, and vulva must be inspected carefully for lesions in a patient in labor with a history of herpes simplex virus. » Acyclovir and analogous agents given in pregnancy during primary episodes mcan decrease the duration of viral shedding and duration of lesions. » Acyclovir suppression, when a primary HSV infection or recurrence occurs in pregnancy, can decrease the likelihood of recurrence and need for cesarean.

REFERENCES

American College of Obstetricians and Gynecologists. Gynecologic herpes simplex virus infections. ACOG Practice Bulletin 57. Washington, DC; 2004. (Reaffirmed 2014.) 

American College of Obstetricians and Gynecologists. Management of herpes in pregnancy. ACOG Practice Bulletin 82. Washington, DC; 2007. (Reaffirmed 2014.) 

Castro LC, Ognyemi D. Common medical and surgical conditions complicating pregnancy. In: H acker NF, Gambone JC, Hobel CJ, eds. Essentials of Obstetrics and Gynecology. 5th ed. Philadelphia, PA: Saunders; 2009:191-218 [no updated reference]. 

Centers for Disease Control and Prevention (CDC). Sexually-Transmitted Diseases Treatment Guidelines; 2015. http:/ / www.cdc.gov/ std/ tg2015/ herpes.htm; Accessed 30.06.15. 

Cunningham F, Leveno KJ, Bloom SL, et al. Sexually transmitted infections. In: Williams Obstetrics. 24th ed. New York, NY: McGraw-Hill; 2013:1271-1274.

HomeObstetrics and Gynecology Case FileHerpes Simplex Virus Infection in Labor Case File