Recurrent Genital Herpes Simplex Infections Research Articles

The Scarlet H

The Scarlet H

Herpes Simplex and HIV Infections and Preterm PROM

Maternal human immunodeficiency virus (HIV) and genital herpes simplex virus (HSV) infection in pregnancy have potential for vertical transmission that may result in death or morbidity. The risk increases with preterm delivery and prolonged ruptured membranes. When managing preterm premature rupture of membranes, the risk of transmission must be weighed against the risk of prematurity. Before 32 to 34 weeks, expectant management is preferred for patients with well controlled HIV or recurrent active genital HSV infection. For patients with advanced HIV disease or primary genital HSV infection, the risk of vertical transmission is higher and many clinical factors need to be considered.

Chronic urticaria associated with recurrent genital herpes simplex infection and success of antiviral therapy — a report of two cases

The role of infectious agents as a cause of chronic idiopathic urticaria (CIU) is uncertain. The objective of this study was to investigate whether genital herpes simplex infection is causally related to CIU. We identified two patients with recurrent genital herpes simplex infections associated with CIU. Episodes of genital herpes were especially associated with acute exacerbation of urticaria. Anti-herpes simplex 2 antibodies and Tzanck smears were done in both patients, along with other relevant investigations for CIU. Acyclovir was added to antihistamine therapy. Both patients were apparently in good health and appeared clinically immunologically stable, though one of them was found to be diabetic. Clinical and laboratory investigations for genital lesions supported a diagnosis of herpes simplex. Anti-herpes simplex 2 antibodies were markedly raised in both patients. The Tzanck smear was positive in one case and negative in the other, despite a definitive clinical diagnosis of herpes progenitalis. CIU, which was inadequately controlled with antihistamines alone, responded dramatically to the addition of acyclovir therapy. Our results may not be applicable to other patients with CIU, especially when there is inadequate evidence of an association with genital herpes. CIU may be associated with recurrent genital herpes simplex infection. In such situations, the addition of acyclovir to therapy may be beneficial.

Guidelines for the Management of Herpes Simplex Virus in Pregnancy

ObjectiveTo provide recommendations for the management of genital herpes infection in women who want to get pregnant or are pregnant and for the management of genital herpes in pregnancy and strategies to prevent transmission to the infant. OutcomesMore effective management of complications of genital herpes in pregnancy and prevention of transmission of genital herpes from mother to infant. EvidenceMedline was searched for articles published in French or English related to genital herpes and pregnancy. Additional articles were identified through the references of these articles. All study types and recommendation reports were reviewed. ValuesRecommendations were made according to the guidelines developed by the Canadian Task Force on Preventive Health Care. Recommendations1.Women’s history of genital herpes should be evaluated early in pregnancy. (III-A)2.Women with known recurrent genital herpes simplex virus (HSV) should be counselled about the risks of transmission of HSV to their neonates at delivery. (III-A)3.At delivery, women with recurrent HSV should be offered a Caesarean section if there are prodromal symptoms or in the presence of a lesion suggestive of HSV. (II-2A)4.Women with known recurrent genital HSV infection should be offered acyclovir or valacyclovir suppression at 36weeks’ gestation to decrease the risk of clinical lesions and viral shedding at the time of delivery and therefore decrease the need for Caesarean section. (I-A)5.Women with primary genital herpes in the third trimester of pregnancy have a high risk of transmitting HSV to their neonates and should be counselled accordingly and should be offered a Caesarean section to decrease this risk. (II-3B)6.A pregnant woman who does not have a history of HSV but who has had a partner with genital HSV should have type-specific serology testing to determine her risk of acquiring genital HSV in pregnancy before pregnancy or as early in pregnancy as possible. Testing should be repeated at 32 to 34weeks’ gestation. (III-B) ValidationThese guidelines have been reviewed and approved by the Infectious Diseases Committee of the SOGC. SponsorThe Society of Obstetricians and Gynaecologists of Canada

Perineal Herpes Simplex Infection in Bedridden Geriatric Patients

Herpes simplex virus (HSV) lesions are prone to reactivation and recurrence in response to various local or systemic triggering factors. To study the characteristics of five bedridden geriatric patients who presented with herpetic recurrences on the buttocks, gluteal cleft, and perianal region during hospitalization. Data were gathered regarding age, gender, reason for hospitalization, localization of lesions, clinical presentation, previous clinical diagnosis and topical treatments, immune status and immunosuppressant drug intake, as well as prior history of labial or genital herpes. A skin biopsy was taken for histologic examination and immunohistochemical viral identification. Viral culture and viral serology were performed and data regarding antiviral therapy were recorded. The five patients (three women, two men) were aged >80 years and hospitalized for either severe drug-induced renal insufficiency (one case), severe pneumonia (two cases), or stroke causing restricted mobility (two cases). Numerous well demarcated, painful ulcerations developed in the perianal region of these patients, and one patient also presented with some vesicular lesions. The lesions had been confused with mycotic and/or bacterial infections for 10-14 days. No inguinal lymphadenopathies were present and there was no fever. None of the patients had a previous history of recurrent labial or genital HSV infections or HIV infection. Histology was suggestive of HSV infection in two of five patients. Immunohistochemistry identified HSV type I (three patients) and HSV type II (two patients) infections. Viral culture with immunofluorescence viral identification revealed HSV type I in one of the four patients in whom a swab for viral culture was taken. Serology revealed past HSV infection. All lesions cured gradually after 10-14 days of intravenous acyclovir (aciclovir) treatment. Herpetic lesions of the perineal region represent a rare complication in bedridden geriatric patients in the absence of a previous history of HSV infections at the same site. Common traits of patients with this condition were the presence of numerous ulcerated lesions, prolonged time course, and confinement to bed. The latter probably modifies the skin condition, which triggers viral reactivation and favors cutaneous extension of the infection. Complementary diagnostic methods for viral detection and identification are mandatory.

Anogenital lesions (viral diseases and ectoparasitic infestations): unapproved treatments

In terms of improving the quality of life of patients with recurrent genital herpes simplex infection, suppressive antiviral therapy is an effective strategy. Acyclovir is the treatment of choice for herpes simplex virus (HSV) infections. In an Indian study it was stated that acyclovir was not being prescribed because of the high price of the drug. Continuous-dose therapy is more effective than episodic therapy in suppressing recurrences. Although there were not any records to show acyclovir is either teratogenic or mutagenic in humanbeings, it should be known that any agent interferes with DNA syntesis must be used with caution during pregnancy. Transplacental passage of acyclovir has been documented. Recently there are several reports on successful therapy of acyclovir-resistant HSV with oral zidovudine and IV trisodium phosphonoformate (foscarnet) which is a drug under research and active against human immunodeficiency virus (HIV) and cytomegalovirus. Bid valacyclovir is as effective and well tolerated in the treatment of recurrent genital herpes infection as 5-times-daily acyclovir. Therefore, valacyclovir could be an useful alternative to acyclovir. Valacyclovir twice-daily was found as effective and safe as acyclovir five-times-daily in the treatment of recurrent genital herpes infection. In the treatment of the first clinical episode of genital herpes infection, recommendations of the Center for Disease Control and Prevention (CDC) are as follows: oral acyclovir 400 mg, 3 times a day or oral acyclovir 200 mg, 5 times a day; or oral famciclovir 250 mg, 3 times a day; or oral valacyclovir 1 g, bid, each for a duration of 7–10 days. Currently, antiviral therapy including acyclovir and more recently famciclovir and valacyclovir are the mainstays of the treatment of HSV disease in humans. A group of physicians has used cimetidine to prevent recurrent HSV infections. Since the 1930s a research was underwent to find out a form primary prevention of herpes genitalis or an immunotherapy for the established disease. The vaccines first preparated as inactivated whole virus preperations, by the time they became advanced technologically to include virion components or subunits, replication impaired HSV mutants, nonpathogenic replicating vectors, and plasmids expressing one or more HSV genes. Recombinant DNA vaccine and mutant HSV type 2 vaccine researchs were performed. DNA vaccine was proved to be immunogenic in mice, rats, guinea pigs and baboons. The vaccine has prevented recurrences in animals infected with HSV type 2. On the other hand the vaccine has provided prophylaxis in uninfected animals when challenged with HSV. Human testing of the vaccine is underway. Imiquimod (R-837), an immune response modifier, can be effectively used to treat primary genital HSV disease and can suppress HSV infection recurrences in the guinea-pig. Some similar immune response modifiers may play role in the treatment of genital warts but just imiquimod was currently approved by Food and Drug Administration (FDA). For the entire 15 weeks of observation period, imiquimod alone reduced recurrence rate by 62.6%, while addition of HSV vaccine to imiquimod reduced recurrence rate by 80.6% compared to placebo/placebo. Resiquimod, also known as R-848 or S-28,463, is a member of the imidazoquinoline that is a family of immune response modifiers. Resiquimod is a more potent analogue of imiquimod. Imiquimod was approved in the United States as a 5% cream formulation (Aldera) for the treatment of external genital warts. In animal From the Department of Dermatology, Trakya University, Medicla Faculty, Edirne, Turkey; Dermatology Unit, Kaplan Medical Center, Rechovot, Israel; and the Department of Dermatology, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey. Address correspondence to Binnur Tuzun, MD, Trakya University, Medical Faculty, 22030, Edirne, Turkey. E-mail address: yalcintuzun@superonline.com

Valaciclovir for the suppression of recurrent genital HSV infection: a placebo controlled study of once daily therapy. International Valaciclovir HSV Study Group.

OBJECTIVE: To determine the efficacy and safety of once daily valaciclovir for the suppression of recurrent genital herpes simplex virus (HSV) infection in immunocompetent patients. METHODS: 382 otherwise healthy patients...

Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: a randomised, double blind clinical trial. International Valaciclovir HSV Study Group.

OBJECTIVE: To compare the efficacy and safety of twice daily valaciclovir with five times daily aciclovir in the treatment of an episode of recurrent genital herpes simplex virus (HSV) infection...

Valacyclovir

Valacyclovir is the l-valyl ester prodrug of acyclovir and exhibits similar potency, but has more favorable pharmacokinetic characteristics, requiring a less frequent dosing schedule and achieving higher blood plasma levels than acyclovir. With the acyclovir prodrugs, the physical properties such as water or lipid solubilities (log P) are not major determinants of the most effective bioavailability. The structure-activity relationship of the amino acid esters suggests the involvement of a stereospecific transport process. The common branched chain amino acids, l-valine and l-isoleucine, are favored by this proposed transporter. 2 Acyclovir is a derivative of guanosine. A critical step in its activation is phosphorylation by viral thymidine kinase. The affinity of acyclovir for herpes virus-encoded thymidine kinase is approximately 200 times greater than for human thymidine kinase, and phosphorylation of acyclovir by the human enzyme occurs at a negligible rate. This selective affinity results in the activation and concentration of acyclovir in virus-infected cells. After phosphorylation to acyclovir monophosphate (acyclo-GMP), normal cellular enzymes catalyze the sequential phosphorylation to acyclovir diphosphate (acyclo-GDP) and acyclovir triphosphate (acyclo-GTP). Acyclovir triphosphate terminates the production of viral DNA by inhibiting DNA polymerase via competition with deoxyguanosine triphosphate; it has selective affinity for viral DNA polymerase. In addition, acyclo-GTP is incorporated into the elongating viral DNA, where it causes termination of the viral DNA strand. 3,4,5 After oral administration, valacyclovir is rapidly absorbed and extensively converted to acyclovir via first-pass metabolism. Acyclovir has been detected in plasma as early as 15 min after the valacyclovir administration. Oral administration results in plasma acyclovir concentrations approximately 3- to 5-fold greater than those achievable with comparable oral doses of acyclovir. 6,7,8 The elimination half-life of acyclovir is approximately 3 h; acyclovir is primarily excreted unchanged in the urine. Valacyclovir appears to be a significant development in antiviral therapy. Its significantly greater oral bioavailability results in plasma acyclovir levels comparable to those seen with intravenous acyclovir. Although acyclovir has been effective in immunocompetent patients with mucocutaneous herpes simplex virus (HSV) infection, the need for multiple daily dosing has been problematic. With a higher C max after valacyclovir administration, less frequent dosing may be equally effective, both for acute treatment and for suppression. In the treatment of recurrent genital herpes simplex infections, valacyclovir 1,000 mg orally twice a day for 5 days has been effective. In patients receiving the drug within 24 h of initiation of signs and symptoms, valacyclovir was as effective as acyclovir in reducing time to lesion healing and length of episode. 9 Herpes zoster (shingles) patients treated with oral valacycyclovir report complete cessation of postherpetic pain in a statistically shorter time than patients treated with oral acyclovir; the two drugs have a similar time to rash healing. Valacyclovir has been approved for marketing in the U.S.A. as a treatment for shingles in immunocompetent patients. Valacyclovir was first launched in the U.K. and Ireland in January 1995, and has since been launched in Sweden.

Adjustment to the psychological and social sequelae of recurrent genital herpes simplex infection.

To investigate whether adverse psychological consequences and impaired sexual and interpersonal functioning are present in individuals suffering from recurrent genital herpes simplex infection (HSV). A questionnaire-based study completed by subjects defined as having more than one episode of HSV infection. Completed questionnaires were returned from 90 subjects; 40 from the department of genitourinary medicine at our hospital and 50 from members of the Herpes Association. Stress and being physically run-down were identified as provoking factors by the majority of individuals (78% and 56% respectively). The frequency of sexual activity was not different when comparing rates before and after infection (p < 0.001) and the majority of subjects had told partners of their infection. Women reported significantly greater disturbances in several psychological variables and reported a greater decrement in their general health. However, overall there were no differences in the psychological sequelae following herpes infection. The study suggests that, given time, most people are able to adjust psychologically to having recurrent herpes infection. However, for a minority of subjects this is not the case and these individuals may require psychotherapeutic intervention.

Epidural Anaesthesia for Caesarean Section in Patients with Active Recurrent Genital Herpes Simplex Infections

Department of Anaesthesia, Women's College Hospital and Mount Sinai Hospital, University of Toronto, Toronto, Ontario

Type Incidence of Herpes Simplex Virus in Clinical Isolates from Patients with Herpes Genitalis

Isolates from a total of 228 patients with clinical herpes simplex were included in this study: 92 were from patients in their first episode and 136 were from patients with recurrent genital herpes...

Epidural anaesthesia for caesarean section in patients with active recurrent genital herpes simplex infections: a retrospective review.

The safety of epidural anaesthesia in patients with active, recurrent genital herpes simplex (HSV) infections is controversial. We reviewed the six-year experience of the use of epidural anaesthesia in this patient population in two institutions. Eighty-nine parturients with active genital HSV were administered epidural anaesthesia for Caesarean section. No patient suffered an adverse outcome related to either the anaesthetic or the virus. The theoretical risks of regional anaesthesia in the parturient with active herpes genitalis are reviewed. We conclude from available data that the risk of an adverse outcome is small and does not contraindicate the use of epidural anaesthesia in patients with recurrent infection.

Characteristics of recurrent genital herpes simplex infections in pregnant women

Longitudinal study of 229 pregnancies in 186 pregnant women with recurrent genital herpes simplex virus (HSV) infections revealed an increased incidence of recurrent episodes in the third trimester compared with the first or second trimesters. The duration of symptomatic recurrences did not change with each trimester. Cervical HSV shedding concomitant with HSV culture-positive vulvar lesions did not change significantly with advancing gestation. The presence of an HSV culture-positive vulvar lesion indicated a significantly (P less than .001) greater risk of concomitant cervical HSV shedding (44 of 333, 13.2%) than in pregnant women with HSV culture-positive remote lesions (zero of 60) or in asymptomatic women (27 of 1460, 1.9%). Comparison of the characteristics among 43 pairs of pregnancies in 34 women revealed no consistent change over time. This study of the natural history of genital HSV recurrences in pregnant women demonstrated no proclivity for an increased rate of preterm delivery (1.3%) or congenital anomalies (2.2%) in a predominantly white, non-Hispanic middle-class population.

Recurrent genital herpes: what helps adjustment?

Psychosocial adjustment to recurrent genital infections with herpes simplex virus (HSV) varies greatly among individuals. To identify the factors predictive of psychosocial adjustment to recurrent genital HSV infections, we analyzed data from interviews and psychological tests conducted with infected individuals. We found that avoidant coping strategies such as denial and social support from a counselor were negatively correlated with adjustment to genital HSV, whereas cognitive coping strategies and social support from one's spouse or lover were positively correlated with adjustment. We conclude that psychosocial adjustment to recurrent genital HSV infections might be facilitated by sharing one's diagnosis with supportive intimate others and avoiding denial as a defense mechanism.

Low Risk of Herpes Simplex Virus Infections in Neonates Exposed to the Virus at the Time of Vaginal Delivery to Mothers with Recurrent Genital Herpes Simplex Virus Infections

Prober, C. G.; Sullender, W. M.; Yasukawa, L. L.; Au, D. S.; Yeager, A. S.; Arvin, A. M.Author Information

Low risk of herpes simplex virus infections in neonates exposed to the virus at the time of vaginal delivery to mothers with recurrent genital herpes simplex virus infections.

We studied the risk of herpes simplex virus (HSV) infections in neonates exposed to HSV at the time of vaginal delivery to mothers with a history of recurrent genital HSV infections. None of 34 infants exposed to HSV type 2 acquired an HSV infection. On the basis of this sample, the 95 percent confidence limit for the theoretical maximum infection rate is 8 percent. Cord blood or blood obtained during the first two weeks of life was available from 33 of the 34 exposed, uninfected neonates. All 33 of the samples possessed demonstrable neutralizing antibody to HSV type 2, and 79 percent had titers above 1:20. These results were compared with those in a previously studied group of neonates with HSV infections; the latter infants were significantly less likely at the onset of symptoms to have demonstrable neutralizing antibody to HSV type 2 (P = 0.000148) or to have titers above 1:20 (P less than 0.00001). We conclude that given the low attack rate, empirical antiviral therapy is not warranted in all infants of mothers with recurrent genital HSV infection who are exposed to the virus in the birth canal. Our findings suggest that the presence and titer of neutralizing antibody to HSV contribute to the low attack rate.

Failure of antepartum maternal cultures to predict the infant's risk of exposure to herpes simplex virus at delivery.

In 414 pregnant women with a history of recurrent genital herpes simplex infection, we studied the correlation between asymptomatic viral shedding in late pregnancy and at the time of delivery. Antepartum cultures for asymptomatic reactivation of herpes simplex virus were positive in 17 of the 414 women (4.1 percent). None of these women had positive cultures at the time of delivery. Cultures of specimens obtained at delivery from 5 of 354 asymptomatic mother-infant pairs (1.4 percent) were positive for asymptomatic excretion of herpes simplex virus. None of these women had had antepartum cultures that documented asymptomatic excretion of herpes simplex virus, despite the fact that culturing was repeatedly performed during the four weeks before delivery. Asymptomatic shedding of herpes simplex virus occurred with the same frequency at delivery, whether or not any episodes of symptomatic recurrence were noted during the pregnancy (1.4 vs. 1.3 percent). We conclude that antepartum maternal cultures do not predict the infant's risk of exposure to herpes simplex virus at delivery.

Screening to detect asymptomatic shedding of herpes simplex virus (HSV) in women with recurrent genital HSV infection.

To investigate the asymptomatic shedding of herpes simplex virus (HSV) from women with recurrent genital herpes infection, and to assess whether inapparent shedding could occur, eight such women were examined thrice weekly for one month. At each visit colposcopy was performed and multiple sites sampled for HSV. During the study four women had no recurrence of HSV infection, but four had at least one positive viral culture. One of these patients was asymptomatically shedding HSV on nine of her 11 clinic visits. Two episodes of urethral shedding were detected. In this group of patients the presence of inguinal lymphadenopathy was appreciably associated with the isolation of HSV from the urogenital tract.

Suppression of recurrent non-genital herpes simplex infection by prophylactic oral acyclovir

Following a primary infection with herpes simplex virus (HSV) some patients proceed to suffer repeated recurrences of the HSV infection. Whilst it has recently been shown that oral acyclovir taken prophylactically decreases the frequency of recurrent genital HSV infection (Douglas et al., 1984; Mindel et al., 1984; Straus et al., 1984), to date there have been no reports of any form of effective prophylaxis against recurrent HSV infection on non-genital skin in immunocompetent patients. In order to determine if oral acyclovir could afford protection in such patients we have performed a double-blind, placebo-controlled, crossover trial of oral acyclovir in patients experiencing eight or more episodes of recurrent non-genital HSV infection per year. Fourteen patients entered the trial and 11 completed the protocol. Only two patients experienced a recurrence during the 12-week treatment period with acyclovir (200 mg four times daily), compared with nine during placebo treatment (P= 0016, sign test). Although lesion development was effectively suppressed in nine of the patients whilst taking acyclovir, the development of prodromal symptoms and occasionally erythema was reported by five. There was no difference between acyclovir and placebo in the time to first recurrence following completion of treatment. No patient reported any side-effects of either placebo or acyclovir therapy. It is believed that this is the first report of any form of therapy which is effective in the suppression of the frequently recurring non-genital HSV infection in immunocompetent patients.