Genital Herpes Lesions Research Articles

2-day versus 5-day famciclovir as treatment of recurrences of genital herpes: results of the FaST study

The brief period of viral replication in recurrent genital herpes lesions suggests shorter therapeutic regimens may be as effective as standard 5-day courses. To demonstrate that a 2-day course of famciclovir 500 mg statim, then 250 mg twice daily was non-inferior to the standard 5-day course of 125 mg twice daily. Patients were randomly assigned either the 2-day or 5-day famciclovir course and initiated therapy within 12 h of onset of prodromal symptoms. They were instructed to complete daily questionnaires on herpes-related symptoms and functioning and to attend the clinic for assessment of healing 5.5 days after initiating therapy. A total of 873 patients were randomised at least once and 1038 recurrences were treated. The proportion of evaluable recurrences with lesions present at 5.5 days was less in the 2-day arm (24%) than in the 5-day (28%) arm. The upper 97.5% confidence limit (CL) for this difference in favour of the 2-day arm was 2% in favour of the 5-day arm, well within the 10% predefined for non-inferiority. The upper 97.5% CL was similar in the intent-to-treat, evaluable and per-protocol recurrence populations and when adjusted for baseline differences (in gender, age, herpes history and HIV infection) or for clustering of recurrences within patients. Both treatments had similar side-effects; proportion of lesions aborted; time to next recurrence; patient-reported symptoms; and impact on daily functioning. The 2-day course was as safe and effective as the standard 5-day course and can only enhance patient convenience and compliance.

Corrigendum to: 2-day versus 5-day famciclovir as treatment of recurrences of genital herpes: results of the FaST study

Background: The brief period of viral replication in recurrent genital herpes lesions suggests shorter therapeutic regimens may be as effective as standard 5-day courses. Objective: To demonstrate that a 2-day course of famciclovir 500 mg statim, then 250 mg twice daily was non-inferior to the standard 5-day course of 125 mg twice daily. Methods: Patients were randomly assigned either the 2-day or 5-day famciclovir course and initiated therapy within 12 h of onset of prodromal symptoms. They were instructed to complete daily questionnaires on herpes-related symptoms and functioning and to attend the clinic for assessment of healing 5.5 days after initiating therapy. Results: A total of 873 patients were randomised at least once and 1038 recurrences were treated. The proportion of evaluable recurrences with lesions present at 5.5 days was less in the 2-day arm (24%) than in the 5-day (28%) arm. The upper 97.5% confidence limit (CL) for this difference in favour of the 2-day arm was 2% in favour of the 5-day arm, well within the 10% predefined for non-inferiority. The upper 97.5% CL was similar in the intent-to-treat, evaluable and per-protocol recurrence populations and when adjusted for baseline differences (in gender, age, herpes history and HIV infection) or for clustering of recurrences within patients. Both treatments had similar side-effects; proportion of lesions aborted; time to next recurrence; patient-reported symptoms; and impact on daily functioning. Conclusions: The 2-day course was as safe and effective as the standard 5-day course and can only enhance patient convenience and compliance.

Effect of Resiquimod 0.01% Gel on Lesion Healing and Viral Shedding When Applied to Genital Herpes Lesions

Resiquimod, a Toll-like receptor 7/8 agonist developed as a topical treatment to decrease recurrences of anogenital herpes, induces proinflammatory cytokines that may delay lesion healing. Adults with frequently recurring anogenital herpes were randomized within 24 h of onset of a recurrence to vehicle or resiquimod 0.01% gel two times per week for 3 weeks. Subjects underwent daily lesion assessments and sampling for herpes simplex virus DNA PCR for 21 days or until investigator-determined healing of lesion(s). Eighty-two subjects with a mean age of 39 +/- 10.5 years and a median of seven recurrences per year were enrolled in the study. The qualifying recurrence was positive by PCR for herpes simplex virus in 68% of subjects. No difference was observed between the vehicle (39 subjects) and resiquimod (43 subjects) groups with respect to time to healing (median of 7.0 days versus median of 6.5 days, respectively; Cox proportional hazard model ratio of 1.229; 95% confidence interval, 0.778 to 1.942; P = 0.376). The distributions of maximum severity scores for any investigator-assessed local skin signs and for subject-assessed local symptoms were similar between treatment groups (P = 0.807 and P = 0.103, respectively). For subjects with at least one positive PCR result, no difference was observed for time to cessation of viral shedding (median of 7 days versus median of 5 days for vehicle and resiquimod groups, respectively; Cox proportional hazard model ratio of 1.471; 95% confidence interval, 0.786 to 2.754; P = 0.227). Application of resiquimod 0.01% two times per week for 3 weeks did not delay the healing of genital herpes lesions or reduce acute viral shedding.

Single-Day, Patient-Initiated Famciclovir Therapy for Recurrent Genital Herpes: A Randomized, Double-Blind, Placebo-Controlled Trial

Orally administered antiviral therapy for genital herpes improves the time to lesion healing and resolves symptoms during an outbreak. Although traditional therapy for a recurrent episode for healthy adults has consisted of twice-daily dosing for 5 days, recent studies have indicated that shorter courses of antiviral therapy are effective. This study was conducted to assess the efficacy and safety of a patient-initiated, single-day regimen of famciclovir therapy, compared with placebo, in immunocompetent adult patients with recurrent genital herpes. This multicenter, multinational, randomized, double-blind, parallel-group, placebo-controlled study compared single-day, patient-initiated oral famciclovir (1000 mg given twice daily) with placebo for the treatment of recurrent genital herpes. Patients were instructed to initiate therapy within 6 h after onset of prodromal symptoms or genital herpes lesions. Famciclovir reduced (P < .001) the time to healing of nonaborted lesions (i.e., those that progressed [corrected] beyond the papule stage) (median time, 4.3 vs. 6.1 days) and all nonaborted and aborted lesions (median time, 3.5 vs. 5.0 days), compared with placebo. The proportion of patients with aborted lesions was larger in the famciclovir group than in the placebo group (23.3% vs. 12.7%; P = .003). Adverse events in the famciclovir group were infrequent overall; most were of mild-to-moderate severity and were similar to adverse events in the placebo group. A single-day regimen of patient-initiated famciclovir treatment was well tolerated and safe, and the healing of recurrent genital herpes lesions occurred approximately 2 days faster than with placebo. Moreover, single-day famciclovir treatment stopped the development or progression of lesions beyond the papule stage. This convenient single-day regimen has the potential for improving patient compliance and satisfaction with therapy.

The novel synthetic immune response modifier R-848 (Resiquimod) shifts human allergen-specific CD4+ TH2 lymphocytes into IFN-γ–producing cells

Background: In experimental models, imidazoquinolines exhibit several immunomodulatory activities via Toll-like receptor signaling on cells of the innate immunity. Objective: The aim of our study was to investigate whether R-848 (Resiquimod), a small-molecular-weight synthetic compound belonging to the imidazoquinoline family and known for its ability to substantially delay the onset of recurrent genital herpes lesions in both animals and human beings, could influence, at least in vitro, the cytokine production profile of human hapten- or allergen-specific T cells. Methods: Ampicillin- and Der p 1–specific T-cell lines were derived from peripheral blood of allergic donors in the absence or presence of R-848 and assessed by flow cytometry at the single-cell level for their ability to produce IL-4 and/or IFN-γ. Results: R-848 induced both hapten- and allergen-specific circulating T cells, including TH2 effectors, to produce IFN-γ and even to lose the ability to produce IL-4, thus shifting their phenotype of cytokine production to a type 0 (TH0) or even TH1 profile. This effect was associated with an increase in the production of IL-12, IFN-α, IL-18, TNF-α, IL-10, and IL-15 by CD14+ cells, as well as an increase in the proportions of IFN-γ–producing CD3–CD16+ (natural killer) cells. Conclusions: These results suggest that R-848, and probably other imidazoquinolines, might be used as adjuvants in view of novel allergen-specific immunotherapeutic regimens for the treatment of allergic disorders. (J Allergy Clin Immunol 2003;111:380-8.)

Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant.

Neonatal herpes most commonly results from fetal exposure to infected maternal genital secretions at the time of delivery. The risk of transmission from mother to infant as it relates to maternal herpes simplex virus (HSV) serologic status and exposure to HSV in the maternal genital tract at the time of labor has not been quantified. Furthermore, no data exist on whether cesarean delivery, the standard of care for women with genital herpes lesions at the time of delivery, reduces HSV transmission. To determine the effects of viral shedding, maternal HSV serologic status, and delivery route on the risk of transmission of HSV from mother to infant. Prospective cohort of pregnant women enrolled between January 1982 and December 1999. A university medical center, a US Army medical center, and 5 community hospitals in Washington State. A total of 58 362 pregnant women, of whom 40 023 had HSV cultures obtained from the cervix and external genitalia and 31 663 had serum samples tested for HSV. Rates of neonatal HSV infection. Among the 202 women from whom HSV was isolated at the time of labor, 10 (5%) had neonates with HSV infection (odds ratio [OR], 346; 95% confidence interval [CI], 125-956 for neonatal herpes when HSV was isolated vs not isolated). Cesarean delivery significantly reduced the HSV transmission rate among women from whom HSV was isolated (1 [1.2%] of 85 cesarean vs 9 [7.7%] of 117 vaginal; OR, 0.14; 95% CI, 0.02-1.08; P =.047). Other risk factors for neonatal HSV included first-episode infection (OR, 33.1; 95% CI, 6.5-168), HSV isolation from the cervix (OR, 32.6; 95% CI, 4.1-260), HSV-1 vs HSV-2 isolation at the time of labor (OR, 16.5; 95% CI, 4.1-65), invasive monitoring (OR, 6.8; 95% CI, 1.4-32), delivery before 38 weeks (OR, 4.4; 95% CI, 1.2-16), and maternal age less than 21 years (OR, 4.1; 95% CI, 1.1-15). Neonatal HSV infection rates per 100 000 live births were 54 (95% CI, 19.8-118) among HSV-seronegative women, 26 (95% CI, 9.3-56) among women who were HSV-1-seropositive only, and 22 (95% CI, 4.4-64) among all HSV-2-seropositive women. Neonatal HSV infection rates can be reduced by preventing maternal acquisition of genital HSV-1 and HSV-2 infection near term. It can also be reduced by cesarean delivery and limiting the use of invasive monitors among women shedding HSV at the time of labor.

Virus de l'immunodéficience humaine: actualités en maternité

Identify measures to diagnose, prevent, and treat genital herpes infection during pregnancy and childbirth as well as neonatal herpes infection.Bibliographic search from the Medline and Cochrane Library databases and review of international clinical practice guidelines.Genital herpes lesions are most often due to HSV-2 (LE2). The risk of HSV seroconversion during pregnancy is 1–5% (LE2). Genital herpes lesions during pregnancy in a woman with a history of genital herpes is a recurrence. In this situation, there is no need for virologic confirmation (Grade B). In pregnant women with genital lesions who report they have not previously had genital herpes, virological confirmation by PCR and identifying the specific IgG type is necessary (professional consensus). A first episode of genital herpes during pregnancy should be treated with aciclovir (200 mg 5 times daily) or valaciclovir (1000 mg twice daily) for 5–10 days (Grade C), and recurrent herpes during pregnancy with aciclovir (200 mg 5 times daily) or valaciclovir (500 mg twice daily) (Grade C). The risk of neonatal herpes is estimated at between 25% and 44% if a non primary and primary first genital herpes episode is ongoing at delivery (LE2) and 1% for a recurrence (LE3). Antiviral prophylaxis should be offered to women with either a first or recurrent episode of genital herpes during pregnancy from 36 weeks of gestation until delivery (Grade B). Routine prophylaxis is not recommended for women with a history of genital herpes but no recurrence during pregnancy (professional consensus). A cesarean delivery is recommended if a first episode of genital herpes is suspected (or confirmed) at the onset of labor (Grade B) or if it occured less than 6 weeks before delivery (professional consensus) or in the event of premature rupture of the membranes at term. When a recurrence of genital herpes is underway at the onset of labor, cesarean delivery is most likely to be considered when the membranes are intact and vaginal delivery in cases of prolonged rupture of membranes (professional consensus). Neonatal herpes is rare and mainly due to HSV-1 (LE3). In most cases of neonatal herpes, mothers have no history of genital herpes (LE3). When neonatal herpes is suspected, various samples (blood and cerebrospinal fluid) for HSV PCR must be taken to confirm the diagnosis (professional consensus). Any newborn with suspected neonatal herpes should be treated with intravenous acyclovir (20 mg/kg 3 times daily) (grade A) before the PCR results are available (professional consensus). The duration of the treatment depends on the clinical form (professional consensus)There is no formal evidence that it is possible to reduce the risk of neonatal herpes in genital herpes during pregnancy. However, appropriate care can reduce the symptoms associated with herpes and the risk of recurrence at term, as well as cesarean rate because of herpes lesions.

The Pattern of Skin Diseases in Hail Region, Saudi Arabia

The Pattern of Skin Diseases in Hail Region, Saudi Arabia

Recognition of Herpes Simplex Virus Type 2 Tegument Proteins by CD4 T Cells Infiltrating Human Genital Herpes Lesions

The local cellular immune response to herpes simplex virus (HSV) is important in the control of recurrent HSV infection. The antiviral functions of infiltrating CD4-bearing T cells may include cytotoxicity, inhibition of viral growth, lymphokine secretion, and support of humoral and CD8 responses. The antigens recognized by many HSV-specific CD4 T cells localizing to genital HSV-2 lesions are unknown. T cells recognizing antigens encoded within map units 0. 67 to 0.73 of HSV DNA are frequently recovered from herpetic lesions. Expression cloning with this region of DNA now shows that tegument protein VP22 and the viral dUTPase, encoded by genes UL49 and UL50, respectively, are T-cell antigens. Separate epitopes in VP22 were defined for T-cell clones from each of three patients. Reactivity with the tegument protein encoded by UL21 was identified for an additional patient. Three new epitopes were identified in VP16, a tegument protein associated with VP22. Some tegument-specific CD4 T-cell clones exhibited cytotoxic activity against HSV-infected cells. These results suggest that herpes simplex tegument proteins are processed for antigen presentation in vivo and are possible candidate compounds for herpes simplex vaccines.

Genital herpes infection in pregnancy

Genital herpes infection remains a difficult problem to manage during pregnancy. The natural history of the infection during pregnancy is not well understood and potential management strategies remain unevaluated. For example the risk of mother-to-child transmission in women with recurrent genital herpes lesions at the time of vaginal delivery is still unknown. We do not know whether delivery by caesarean section decreases this risk and yet it is the most widely used intervention in this situation. We are only just beginning to understand the epidemiology of asymptomatic infection and the risk that asymptomatic viral shedding may pose to the newborn. In addition, new methods of diagnosis and new strategies for management are regularly being proposed with little formal evaluation of their effectiveness in the clinical setting.This article aims to review current knowledge applicable to the clinical situation and suggest how our knowledge and management of this problem may be improved in the future.

Safety and efficacy of Virend ® for topical treatment of genital and anal herpes simplex lesions in patients with AIDS

Virend ® (SP-303), a new topical antiviral agent with activity against herpesvirus, was evaluated in a multicenter, double-blind, placebo-controlled Phase II study for safety and effectiveness against recurrent genital herpes lesions in patients with AIDS. The primary endpoints of this study were complete healing of lesions and time to healing. Patients had a history of recurrent genital or anogenital herpes with at least one lesion and positive HSV culture at enrollment. Participants received Virend ® (15% ointment; 24 patients) or matching placebo (21 patients) three times a day for 21 days. Excluding two patients in the Virend ® group who received an initial treatment but were lost to follow-up, 9 of 22 (41%) patients treated with Virend ® experienced complete healing of their lesions compared with three (14%) patients in the placebo group ( P = 0.053). Viral culture revealed that 50% of Virend ®-treated patients and 19% of placebo-treated patients became culture-negative during treatment ( P = 0.06). Based on these preliminary clinical findings, further evaluation of Virend ® for topical treatment of genital herpes in patients with AIDS is planned.

Acyclovir prophylaxis in late pregnancy to prevent neonatal herpes: A cost-effectiveness analysis

To compare the cost-effectiveness of oral acyclovir prophylaxis in late pregnancy to the current strategy of cesarean delivery for genital herpes lesions in the prevention of neonatal herpes transmission from mothers with recurrent genital infections. Decision analysis was used to evaluate the clinical outcomes and direct costs of a prevention program from the health care payer's perspective. Probabilities were obtained from the literature and experts. Cost data were based on hospital costs and a cohort of herpes-infected neonates. Acyclovir prophylaxis during late pregnancy followed by cesarean delivery for genital lesions at delivery in women with recurrent genital herpes requires 1818 women to follow this strategy to prevent one neonatal infection and 7.4 women to take acyclovir to prevent one outbreak of genital herpes at delivery, at a cost (above no intervention) of over $493,000 per neonatal infection prevented, $1.1 million per neonatal death or disability prevented, and $1444 per maternal outbreak prevented. Cesarean delivery for genital herpes lesions requires 386 women with recurrent herpes to undergo cesareans to prevent one neonatal infection, at a cost of more than $1.3 million per neonatal infection prevented and more than $3 million per neonatal death or disability prevented. If acyclovir is given and herpes lesions still occur, the incremental cost of requiring cesarean delivery for these women over vaginal delivery with culture and follow-up of exposed infants is more than $1.4 million per neonatal infection prevented. Oral acyclovir prophylaxis in late pregnancy for women with recurrent genital herpes is more cost-effective than the current strategy of cesarean delivery for all women presenting with genital herpes lesions.

Famciclovir

Famciclovir, a synthetic acyclic guanine derivative, is a prodrug which, after oral administration, is rapidly metabolised to the highly bioavailable antiviral compound penciclovir. Penciclovir is active in vitro against the herpesviruses herpes simplex virus (HSV)-1, HSV-2 and varicella zoster virus (VZV). Famciclovir is an effective treatment of immunocompetent patients with acute herpes zoster (shingles) caused by VZV. Comparative studies have demonstrated that famciclovir has therapeutic efficacy similar to that of oral aciclovir (acyclovir) in attenuating the acute signs and symptoms of infection (including pain during the acute phase of infection). In a placebo-controlled study, famciclovir significantly reduced the duration of postherpetic neuralgia; this effect was more pronounced (almost a 3-fold reduction) in patients aged > or = 50 years. In immunocompetent patients with recurrent genital herpes infection, suppressive treatment with oral famciclovir effectively prolonged the time to recurrence of symptomatic episodes of infection compared with placebo. In addition, famciclovir significantly reduced the duration of viral shedding, accelerated healing of genital herpes lesions and reduced the duration of symptoms. Famciclovir is reported to be the first antiviral agent to significantly reduce symptoms associated with multiple genital herpes lesions. Famciclovir is a well-tolerated drug with a tolerability profile similar to that of placebo and aciclovir. Thus, famciclovir is now established as an effective treatment of immunocompetent patients with herpes zoster or genital herpes infection, particularly as famciclovir is administered in a convenient dosage regimen that may improve compliance compared with aciclovir.

Cesarean Delivery for Women Presenting With Genital Herpes Lesions

To assess the effect of cesarean delivery on neonatal and maternal morbidity and mortality and their associated costs for two populations of women presenting with genital herpes lesions at delivery: those with and those without a history of genital herpes. MEDLINE (search for herpes simplex virus and neonatal, cesarean, and mortality) and recognized experts. The quality of the overall data used for baseline values was graded using a predetermined scale. The practice of cesarean delivery for women with a history of genital herpes lesions that recur at delivery results in more than 1580 excess cesarean deliveries performed for every poor neonatal outcome prevented, a cost per neonatal herpes case averted of $2.5 million and a cost per quality-adjusted life-year gained of $203,000. For these women, lowering the efficacy of cesarean delivery or the herpes simplex virus vertical transmission rate could result in maternal deaths outnumbering neonatal deaths prevented. In contrast, cesarean delivery for women with no history of genital herpes simplex virus who have lesions at delivery has low maternal costs per neonatal benefit and saves money. Women who present with their first clinical episode of genital herpes at delivery should have a cesarean section performed. However, the current practice of cesarean delivery for women with a history of genital herpes lesions that recur at delivery results in high maternal morbidity and mortality at substantial financial expense, underscoring the urgency of examining alternative management strategies.

Cesarean delivery for women presenting with genital herpes lesions. Efficacy, risks, and costs

Cesarean delivery for women presenting with genital herpes lesions. Efficacy, risks, and costs

HSV‐IgA serum antibodies in cervical intraepithelial neoplasia and invasive cancer patients, and in their spouses: a case control study

Class-specific IgG and IgA antibodies to HSV were assayed in women with CIN (76), invasive cancer (52) (histological diagnosis) and age-matched controls (119), employing HSV-2-infected HEp-2 cells as antigen during IFA assay. We observed an elevated geometric mean titre (GMT) of serum antibody (IgG five-to eight-fold and IgA four-to five-fold) for the entire spectrum of cervical lesions, as compared to controls. The odds of finding HSV-IgA antibodies were highest with CIN III (OR = 22.0), followed by invasive carcinoma, and CIN I & II (OR = 9.5 and 5.2), respectively. Furthermore, the investigations with respect to married couples (husbands and wives) who volunteered to participate in this study (33 cases and 47 control group) also indicated relatively high antibody titres and increased frequency of HSV sero positivity amongst husbands of cases as compared to their wives, as well as the control group males and females. The contribution of HSV infection in women and/or their husbands to the risk of developing abnormal cervical lesions was analysed after adjusting for the same in respective counterparts. It was observed that the risk was increased 14-fold with HSV-IgA positivity of women, and that HSV-IgA positivity of husbands (male partners) further increased the risk 16-fold. This preliminary observation shows the importance of serum HSV-IgA antibodies as a risk indicator in cervical precancer and cancer lesions in women without a history of recent genital herpes lesions. The serum HSV-IgA may also be taken as an indicator of "high risk" males.

Psychological investigation of genital herpes recurrence: prospective assessment and cognitive-behavioral intervention for a chronic physical disorder.

Previous studies suggest that anxiety and/or depressed mood are associated with recurrence of genital herpes lesions. The present study sought to extend the assessment of factors associated with genital herpes and to investigate the impact of psychological therapy on features of the disorder. Sixteen genital herpes patients received 5 weeks of either structured discussion or cognitive restructuring (CR) therapy in a group format. Measures of attitude about herpes, global coping, distress, loneliness, health locus of control, and recurrence frequency were administered at pretreatment, posttreatment, and 3 months follow-up. Patients also made daily reports during the 5 weeks of treatment from which information was extracted regarding their herpes symptoms, dysphoria, anxiety, and ongoing coping process. Therapy did not produce the expected reductions in reported distress or loneliness. The CR procedure, however, was associated with reduced frequency of lesion recurrence at follow-up. Avoidant coping was associated with lower recurrence rates, and loneliness scores were associated with higher recurrence rates. Prospective data indicated that recurrences were preceded by elevated anxiety that was independent of prodromal symptoms. These results provide support for the general proposals that psychological factors influence health status and that psychological intervention may reduce disease recurrence.

Management of genital herpes simplex virus infection occurring during pregnancy

Genital herpes simplex virus (HSV) infection during pregnancy has caused considerable concern among lay and professional personnel in the past 10 years. Knowledge concerning the potential hazards of HSV to the newborn infant has increased the use of cesarean section for women who have or are suspected of having genital HSV infection near or at the time of labor. Because of this, a 57-month prospective study was begun at Vanderbilt University Hospital and its affiliate, Nashville General Hospital, January 1, 1976, and involved HSV culturing of all suspected genital herpes lesions during pregnancy. Those patients with positive HSV cultures prior to labor and without a subsequent negative culture underwent cesarean section. Those patients whose cultures reverted to negative were considered candidates for vaginal delivery. During the study period, there were 16,381 deliveries at the two institutions. One hundred twenty pregnant women were cultured, with 80 being HSV culture negative and 40 culture positive. The outcome of these pregnancies as well as a review of the experience with neonatal HSV infection in Middle Tennessee is presented. It is concluded that by utilizing HSV cultures of genital lesions as a guide to determining the route of delivery, the incidence of cesarean sections and neonatal HSV infection can be kept to a minimum.