Barbara A Majeroni, Sreelatha Ukkadam
Screening and treatment for sexually transmitted infections in pregnancy.
Am Fam Physician. 2007 Jul 15;76(2):265-70.
Abstract/Text
Many sexually transmitted infections are associated with adverse pregnancy outcomes. The Centers for Disease Control and Prevention recommends screening all pregnant women for human immunodeficiency virus infection as early as possible. Treatment with highly active antiretroviral therapy can reduce transmission to the fetus. Chlamydia screening is recommended for all women at the onset of prenatal care, and again in the third trimester for women who are younger than 25 years or at increased risk. Azithromycin has been shown to be safe in pregnant women and is recommended as the treatment of choice for chlamydia during pregnancy. Screening for gonorrhea is recommended in early pregnancy for those who are at risk or who live in a high-prevalence area, and again in the third trimester for patients who continue to be at risk. The recommended treatment for gonorrhea is ceftriaxone 125 mg intramuscularly or cefixime 400 mg orally. Hepatitis B surface antigen and serology for syphilis should be checked at the first prenatal visit. Benzathine penicillin G remains the treatment for syphilis. Screening for genital herpes simplex virus infection is by history and examination for lesions, with diagnosis of new cases by culture or polymerase chain reaction assay from active lesions. Routine serology is not recommended for screening. The oral antivirals acyclovir and valacyclovir can be used in pregnancy. Suppressive therapy from 36 weeks' gestation reduces viral shedding at the time of delivery in patients at risk of active lesions. Screening for trichomoniasis or bacterial vaginosis is not recommended for asymptomatic women because current evidence indicates that treatment does not improve pregnancy outcomes.
L Corey, H G Adams, Z A Brown, K K Holmes
Genital herpes simplex virus infections: clinical manifestations, course, and complications.
Ann Intern Med. 1983 Jun;98(6):958-72.
Abstract/Text
The clinical course and complications of 268 patients with first episodes and 362 with recurrent episodes of genital herpes infection were reviewed. Symptoms of genital herpes were more severe in women than in men. Primary first-episode genital herpes was accompanied by systemic symptoms (67%), local pain and itching (98%), dysuria (63%), and tender adenopathy (80%). Patients presented with several bilaterally distributed postular ulcerative lesions that lasted a mean of 19.0 days. Herpes simplex virus was isolated from the urethra, cervix, and pharynx of 82%, 88%, and 13% of women with first-episode primary genital herpes, and the urethra and pharynx of 28% and 7% of men. Complications included aseptic meningitis (8%), sacral autonomic nervous system dysfunction (2%), development of extragenital lesions (20%), and secondary yeast infections (11%). Recurrent episodes were characterized by small vesicular or ulcerative unilaterally distributed lesions that lasted a mean of 10.1 days. Systemic symptoms were uncommon and 25% of recurrent episodes were asymptomatic. The major concerns of patients were the frequency of recurrences and fear of transmitting infection to partners or infants.
Kimberly A Workowski, Gail A Bolan, Centers for Disease Control and Prevention
Sexually transmitted diseases treatment guidelines, 2015.
MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137.
Abstract/Text
These guidelines for the treatment of persons who have or are at risk for sexually transmitted diseases (STDs) were updated by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta on April 30-May 2, 2013. The information in this report updates the Sexually Transmitted Diseases Treatment Guidelines, 2010 (MMWR Recomm Rep 2010;59 [No. RR-12]). These updated guidelines discuss 1) alternative treatment regimens for Neisseria gonorrhoeae; 2) the use of nucleic acid amplification tests for the diagnosis of trichomoniasis; 3) alternative treatment options for genital warts; 4) the role of Mycoplasma genitalium in urethritis/cervicitis and treatment-related implications; 5) updated HPV vaccine recommendations and counseling messages; 6) the management of persons who are transgender; 7) annual testing for hepatitis C in persons with HIV infection; 8) updated recommendations for diagnostic evaluation of urethritis; and 9) retesting to detect repeat infection. Physicians and other health-care providers can use these guidelines to assist in the prevention and treatment of STDs.
L A Koutsky, C E Stevens, K K Holmes, R L Ashley, N B Kiviat, C W Critchlow, L Corey
Underdiagnosis of genital herpes by current clinical and viral-isolation procedures.
N Engl J Med. 1992 Jun 4;326(23):1533-9. doi: 10.1056/NEJM199206043262305.
Abstract/Text
BACKGROUND: The current clinical strategy for diagnosing genital herpes simplex virus (HSV) infection in women relies on clinical findings plus the selective use of viral culture. The effectiveness of this approach for identifying women with genital herpes is unknown.
METHODS: We performed physical examinations, colposcopy, Pap smears, viral cultures, and HSV type-specific serologic assays of 779 randomly selected women attending a sexually transmitted disease clinic.
RESULTS: Evidence of HSV type 2 infection was detected in 363 women (47 percent), and 9 others (1 percent) had positive cultures indicative of urogenital or anal infection with HSV type 1. Of these 372 women, only 82 (22 percent) had symptoms. Fourteen women (4 percent) had viral shedding without symptoms, 60 (16 percent) had formerly had symptomatic episodes, and 216 (58 percent) had antibodies to HSV-2 with neither viral shedding nor a history of clinical episodes. Characteristic ulcerations of the external genitalia were present in only two thirds of the 66 women with positive HSV cultures; the others had atypical genital lesions or asymptomatic viral shedding. Isolation of HSV from a genitourinary tract specimen was the most sensitive (77 percent) test for confirming a first episode of infection. The detection of HSV-2-specific antibodies was the most sensitive (97 percent) way to confirm symptomatic reactivations of HSV-2 infection. HSV-2 serologic testing also identified the 290 women with asymptomatic HSV-2 infections (37 percent), including 14 (5 percent) who were shedding virus asymptomatically on the day of the examination.
CONCLUSIONS: The current strategy for diagnosing genital HSV infection in women misses many cases. Newly developed type-specific serologic methods can identify women with recurrent genital HSV-2 infection, as well as those with unrecognized or subclinical infection.
A Scoular
Using the evidence base on genital herpes: optimising the use of diagnostic tests and information provision.
Sex Transm Infect. 2002 Jun;78(3):160-5.
Abstract/Text
There have been several important advances in the range of available diagnostic tests for genital herpes simplex virus (HSV) infection in recent years; polymerase chain reaction (PCR) is emerging in routine clinical use and the potential role of type specific serological tests is currently under debate. Several large trials of prophylactic vaccines, subsequently proved to be ineffective, have expanded knowledge of the transmission and epidemiology of HSV infection. This article discusses optimal application of recent research evidence to clinical care, structured around the key issues for patients and their partners. These include acquisition and transmission of genital HSV-1 and HSV-2 infection, the natural history of genital herpes, and the role of partner notification.
E L Chan, K Brandt, G B Horsman
Comparison of Chemicon SimulFluor direct fluorescent antibody staining with cell culture and shell vial direct immunoperoxidase staining for detection of herpes simplex virus and with cytospin direct immunofluorescence staining for detection of varicella-zoster virus.
Clin Diagn Lab Immunol. 2001 Sep;8(5):909-12. doi: 10.1128/CDLI.8.5.909-912.2001.
Abstract/Text
A new rapid direct immunofluorescence assay, the SimulFluor direct fluorescent-antibody (DFA) assay, which can simultaneously detect herpes simplex virus types 1 and 2 (HSV-1 and -2) and varicella-zoster virus (VZV), was evaluated in comparison with our current standard procedures of (i) shell vial direct immunoperoxidase (shell vial IP) staining and cell culture for detection of HSV and (ii) cytospin DFA staining for VZV detection. A total of 517 vesicular, oral, genital, and skin lesion specimens were tested by all three procedures. For HSV detection, the SimulFluor DFA assay had an overall sensitivity, specificity, positive predictive value, and negative predictive value of 80.0, 98.3, 92.3, and 95.1%, respectively, when compared to culture. Shell vial IP staining had a sensitivity, specificity, positive predictive value, and negative predictive value of 87.6, 100, 100, and 96.9%, respectively, when compared with cell culture. The SimulFluor DFA assay, however, offers same-day, 1.5-hours results versus a 1- to 2-day wait for shell vial IP staining results and a 1- to 6-day wait for culture results for HSV. For VZV detection SimulFluor DFA staining detected 27 positive specimens as compared to 31 by our standard cytospin DFA technique--a correlation of 87.1%. A positive SimulFluor reaction for VZV is indicated by yellow-gold fluorescence compared to the bright apple-green fluorescence observed by cytospin DFA staining. There is no difference in turnaround time between the two assays. The SimulFluor DFA assay is a rapid immunofluorescence assay that can detect 80% of the HSV-positive specimens and 87% of the VZV-positive specimens with a 1.5-h turnaround time.
Rhoda Ashley-Morrow, Elizabeth Krantz, Anna Wald
Time course of seroconversion by HerpeSelect ELISA after acquisition of genital herpes simplex virus type 1 (HSV-1) or HSV-2.
Sex Transm Dis. 2003 Apr;30(4):310-4.
Abstract/Text
BACKGROUND: HerpeSelect HSV-1 and HSV-2 ELISAs are glycoprotein G-based, type-specific antibody detection tests that are approved by the US Food and Drug Administration for diagnosis of genital herpes.
GOAL: The goal was to determine seroconversion times by means of HerpeSelect ELISAs.
STUDY DESIGN: Four-hundred thirteen sera from 113 patients with recently acquired genital herpes were tested by HerpeSelect ELISAs and Western blot (WB). Thirty-one patients had primary genital HSV-1 (group 1), 56 had primary HSV-2 (group 2), and 26 had prior HSV-1 antibodies and newly acquired HSV-2 (group 3).
RESULTS: Median interval from onset of symptoms to seroconversion was 25 days, as determined by HerpeSelect HSV-1, versus 33 days by WB for group 1; 21 days by HerpeSelect HSV-2 versus 40 days by WB (group 2; P = 0.0005); and 23 days by HerpeSelect HSV-2 ELISA versus 47 days by WB (group 3; P = 0.02). In long-term follow-up, transient reversion to HerpeSelect negativity occurred in 3 of 31 HSV-1-infected subjects (10%) and in 2 of 82 HSV-2-infected subjects (2%).
CONCLUSION: Seroconversion to HSV-2 was determined faster by HerpeSelect than by WB.
Y J Bryson, M Dillon, M Lovett, G Acuna, S Taylor, J D Cherry, B L Johnson, E Wiesmeier, W Growdon, T Creagh-Kirk, R Keeney
Treatment of first episodes of genital herpes simplex virus infection with oral acyclovir. A randomized double-blind controlled trial in normal subjects.
N Engl J Med. 1983 Apr 21;308(16):916-21. doi: 10.1056/NEJM198304213081602.
Abstract/Text
We performed a double-blind placebo-controlled trial of oral acyclovir in the treatment of first episodes of genital herpes simplex virus infections in 48 young adults (31 women and 17 men). Subjects were randomized to receive either placebo or acyclovir (200 mg per dose) five times daily for 10 days; they were examined on at least eight visits until healed and at monthly visits thereafter. Acyclovir treatment, as compared with placebo, significantly reduced virus shedding, new lesion formation after 48 hours, and the duration of genital lesions in both men and women. The total duration and severity of clinical symptoms (such as pain, adenopathy, dysuria, and malaise) were significantly reduced by acyclovir in both men and women by the third and fourth day, respectively (P less than or equal to 0.025), as compared with placebo. No toxicity was observed. Recurrence rates have so far been similar in placebo and acyclovir recipients. Oral acyclovir treatment of first-episode genital herpes simplex virus infections is clinically effective, but it does not seem to prevent virus latency or associated recurrent disease.
K H Fife, R A Barbarash, T Rudolph, B Degregorio, R Roth
Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection. Results of an international, multicenter, double-blind, randomized clinical trial. The Valaciclovir International Herpes Simplex Virus Study Group.
Sex Transm Dis. 1997 Sep;24(8):481-6.
Abstract/Text
BACKGROUND AND OBJECTIVES: Valaciclovir, the L-valine ester prodrug of acyclovir, is much better absorbed than acyclovir and produces acyclovir exposures three to five times those attainable with the parent drug.
GOALS: To determine whether the improved bioavailability of valaciclovir and a more convenient, less frequent dose regimen can maintain the clinical efficacy previously demonstrated for acyclovir.
STUDY DESIGN: This was an international, multicenter, randomized, double-blind clinical trial comparing 10-day regimens of valaciclovir (1000 mg, twice daily) and acyclovir (200 mg, 5 times daily) in the treatment of 643 otherwise healthy adults (> or = 18 years of age) with first-episode genital herpes. Patients were evaluated clinically and lesions were staged and cultured on days 1, 2, 3, 5, 7, 10, 14, and then twice weekly until healed. Blood for herpes serology tests was obtained on days 1 and 14; hematology and chemistry toxicity screening was done on days 1 and 7.
RESULTS: Valaciclovir and acyclovir did not differ significantly in efficacy with respect to duration of viral shedding (hazard ratio, 1.00; 95% confidence interval [CI], 0.84-1.18), time to healing (hazard ratio, 1.08; 95% CI, 0.92-1.27), duration of pain (hazard ratio, 1.0; 95% CI, 0.85-1.18), and time to loss of all symptoms (hazard ratio, 1.02; 95% CI, 0.85-1.22). Patients with primary genital herpes (no preexisting antibody to either herpes simplex virus type at enrollment with seroconversion at day 14) had longer times to healing and longer duration of viral shedding and pain than patients with nonprimary first genital episodes. Adverse experiences were generally infrequent and mild and were comparable in the two treatment groups.
CONCLUSIONS: Twice-daily valaciclovir proved as effective and well tolerated in the treatment of first-episode genital herpes as five-times-daily acyclovir. Valaciclovir provides a useful alternative to acyclovir with the advantage of a more convenient dosing regimen and the potential for improved compliance.
M Reitano, S Tyring, W Lang, C Thoming, A M Worm, S Borelli, L O Chambers, J M Robinson, L Corey
Valaciclovir for the suppression of recurrent genital herpes simplex virus infection: a large-scale dose range-finding study. International Valaciclovir HSV Study Group.
J Infect Dis. 1998 Sep;178(3):603-10.
Abstract/Text
A randomized, double-blind study of valaciclovir for suppression of recurrent genital herpes was conducted among 1479 immunocompetent patients. Patients were randomized to receive valaciclovir (250 mg, 500 mg, or 1 g once daily, or 250 mg twice daily), acyclovir (400 mg twice daily), or placebo, for 1 year. All valaciclovir dosages were significantly more effective than placebo at preventing or delaying recurrences (P < .0001). There was a dose-response relationship (P < .0001) across the once-daily valaciclovir regimens. Twice-daily valaciclovir and acyclovir were similar in effectiveness. Subgroup analysis showed that patients with a history of < 10 recurrences per year were effectively managed with 500 mg of valaciclovir once daily. One gram of valaciclovir once daily, 250 mg of valaciclovir twice daily, or 400 mg of acyclovir twice daily were more effective in patients with > or = 10 recurrences per year. Safety profiles of all treatments were comparable. Thus, valaciclovir is highly effective and well tolerated for suppression of recurrent genital herpes. Once-daily regimens offer a useful option for patients who require suppressive therapy for management of genital herpes.
J K Benedetti, J Zeh, L Corey
Clinical reactivation of genital herpes simplex virus infection decreases in frequency over time.
Ann Intern Med. 1999 Jul 6;131(1):14-20.
Abstract/Text
BACKGROUND: Visits to physicians for genital herpes simplex virus (HSV) infection continue to increase. Most patients with symptomatic infections have recurrences, but no studies of the long-term clinical course of genital herpes are available.
OBJECTIVE: To determine whether the frequency of HSV recurrences decreases over time.
DESIGN: Observational cohort study.
SETTING: University-based research clinic.
PATIENTS: 664 persons with genital herpes followed for at least 14 months.
MEASUREMENTS: Patients were classified as having initial or recurrent HSV-1 or HSV-2 infection. Patient-reported recurrences and observed recurrences were recorded in a database; more than 12,000 recurrences were analyzed.
RESULTS: Median recurrence rates in the first year of follow-up were one and five per year in patients with newly acquired HSV-1 and HSV-2 infection, respectively; second-year rates were significantly lower in both groups. Patients presenting with recurrent HSV-2 infection had higher rates of recurrence in the first and second years and no significant decrease; significant decreases were detected with longer follow-up. One third of all patients experienced a decrease of two or more recurrences per year between years 1 and 2. Patients infected with HSV-2 who were followed for more than 4 years had a median decrease of two recurrences between years 1 and 5. However, 25% of these patients had an increase of at least one recurrence in year 5, illustrating the variability among HSV-infected persons. Decreases over time among patients who never received suppressive therapy were similar to decreases during untreated periods in patients who received suppressive therapy.
CONCLUSIONS: Herpes simplex virus type 2 infection continues to be a chronic remitting illness. Over time, however, clinically significant reductions occur in a majority of patients. Physicians may wish to periodically assess the need for continued treatment with daily suppressive antiviral chemotherapy.
A Wald, J Zeh, S Selke, T Warren, A J Ryncarz, R Ashley, J N Krieger, L Corey
Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons.
N Engl J Med. 2000 Mar 23;342(12):844-50. doi: 10.1056/NEJM200003233421203.
Abstract/Text
BACKGROUND: Most persons who have serologic evidence of infection with herpes simplex virus (HSV) type 2 (HSV-2) are asymptomatic. Historically, it has been assumed that these persons have less frequent viral reactivation than those with symptomatic infection.
METHODS: We conducted a prospective study to investigate genital shedding of HSV among 53 subjects who had antibodies to HSV-2 but who reported having no history of genital herpes, and we compared their patterns of viral shedding with those in a similar cohort of 90 subjects with symptomatic HSV-2 infection. Genital secretions of the subjects in both groups were sampled daily and cultured for HSV for a median of 94 days.
RESULTS: HSV was isolated from the genital mucosa in 38 of the 53 HSV-2-seropositive subjects (72 percent) who reported no history of genital herpes, and HSV DNA was detected by the polymerase-chain-reaction assay in cultures prepared from genital mucosal swabs in 6 additional subjects. The rate of subclinical shedding of HSV in the subjects with no reported history of genital herpes was similar to that in the subjects with such a history (3.0 percent vs. 2.7 percent). Of the 53 subjects who had no reported history of genital herpes, 33 (62 percent) subsequently reported having typical herpetic lesions; the duration of their recurrences in these subjects was shorter (median, three days vs. five days; P<0.001) and the frequency lower (median, 3.0 per year vs. 8.2 per year; P<0.001) than in the 90 subjects with previously diagnosed symptomatic infection. Only 1 of these 53 subjects had no clinical or virologic evidence of HSV infection.
CONCLUSIONS: Seropositivity for HSV-2 is associated with viral shedding in the genital tract, even in subjects with no reported history of genital herpes.
K J Mertz, D Trees, W C Levine, J S Lewis, B Litchfield, K S Pettus, S A Morse, M E St Louis, J B Weiss, J Schwebke, J Dickes, R Kee, J Reynolds, D Hutcheson, D Green, I Dyer, G A Richwald, J Novotny, I Weisfuse, M Goldberg, J A O'Donnell, R Knaup
Etiology of genital ulcers and prevalence of human immunodeficiency virus coinfection in 10 US cities. The Genital Ulcer Disease Surveillance Group.
J Infect Dis. 1998 Dec;178(6):1795-8. doi: 10.1086/314502.
Abstract/Text
To determine the etiology of genital ulcers and to assess the prevalence of human immunodeficiency virus (HIV) infection in ulcer patients in 10 US cities, ulcer and serum specimens were collected from approximately 50 ulcer patients at a sexually transmitted disease clinic in each city. Ulcer specimens were tested using a multiplex polymerase chain reaction assay to detect Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV); sera were tested for antibody to HIV. H. ducreyi was detected in ulcer specimens from patients in Memphis (20% of specimens) and Chicago (12%). T. pallidum was detected in ulcer specimens from every city except Los Angeles (median, 9% of specimens; range, 0%-46%). HSV was detected in >/=50% of specimens from all cities except Memphis (42%). HIV seroprevalence in ulcer patients was 6% (range by city, 0%-18%). These data suggest that chancroid is prevalent in some US cities and that persons with genital ulcers should be a focus of HIV prevention activities.
Anna Wald, Katherine Link
Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis.
J Infect Dis. 2002 Jan 1;185(1):45-52. doi: 10.1086/338231. Epub 2001 Dec 14.
Abstract/Text
To determine the contribution of herpes simplex type 2 (HSV-2) infection to the risk of human immunodeficiency virus (HIV) acquisition, a systematic review of literature and data synthesis were done. Thirty-one studies addressed the risk of HIV infection in HSV-2-seropositive persons. For 9 cohort and nested case-control studies that documented HSV-2 infection before HIV acquisition, the risk estimate was 2.1 (95% confidence interval, 1.4-3.2). Thus, the attributable risk percentage of HIV to HSV-2 was 52%, and the population attributable risk percentage was 19% in populations with 22% HSV-2 prevalence but increased to 47% in populations with 80% HSV-2 prevalence. For 22 case-control and cross-sectional studies, the risk estimate was 3.9 (95% confidence interval, 3.1-5.1), but the temporal sequence of the 2 infections cannot be documented. Control strategies for HSV-2 need to be incorporated into control of sexually transmitted infections as a strategy for HIV prevention.
Esther E Freeman, Helen A Weiss, Judith R Glynn, Pamela L Cross, James A Whitworth, Richard J Hayes
Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies.
AIDS. 2006 Jan 2;20(1):73-83.
Abstract/Text
OBJECTIVE: To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection.
BACKGROUND: The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women.
DESIGN: Systematic review and meta-analysis of longitudinal studies.
METHODS: PubMed, Embase and relevant conference abstracts were systematically searched to identify longitudinal studies in which the relative timing of HSV-2 infection and HIV infection could be established. Where necessary, authors were contacted for separate estimates in men and women, adjusted for age and a measure of sexual behaviour. Summary adjusted RR were calculated using random-effects meta-analyses where appropriate. Studies on recent HSV-2 incidence as a risk factor for HIV acquisition were also collated.
RESULTS: Of 19 eligible studies identified, 18 adjusted for age and at least one measure of sexual behaviour after author contact. Among these, HSV-2 seropositivity was a statistically significant risk factor for HIV acquisition in general population studies of men [summary adjusted RR, 2.7; 95% confidence interval (CI), 1.9-3.9] and women (RR, 3.1; 95% CI, 1.7-5.6), and among men who have sex with men (RR, 1.7; 95% CI, 1.2-2.4). The effect in high-risk women showed significant heterogeneity, with no overall evidence of an association.
CONCLUSIONS: Prevalent HSV-2 infection is associated with a three-fold increased risk of HIV acquisition among both men and women in the general population, suggesting that, in areas of high HSV-2 prevalence, a high proportion of HIV is attributable to HSV-2.
日本性感染症学会：梅毒、日本性感染症学会誌、性感染症 診断・治療 ガイドライン 2016、2016; 27(1)Suppl: 46-50.
日本性感染症学会：A型肝炎、日本性感染症学会誌、性感染症 診断・治療 ガイドライン 2016、2016; 27(1)Suppl: 106-107.
J Benedetti, L Corey, R Ashley
Recurrence rates in genital herpes after symptomatic first-episode infection.
Ann Intern Med. 1994 Dec 1;121(11):847-54.
Abstract/Text
OBJECTIVE: To evaluate the frequency of reactivation of genital herpes infection and to identify predictors for recurrence.
DESIGN: Prospective, observational cohort study.
SETTING: Research clinic.
PATIENTS: 457 consecutive patients who did not have acute-phase serum antibodies to herpes simplex virus type 2 (HSV-2) but who did have herpes simplex virus (HSV) isolated from genital lesions.
RESULTS: Eighty-nine percent of patients with HSV-2 had at least one recurrence during follow-up (median, 391 days); the median monthly recurrence rate was 0.34. Thirty-eight percent had at least 6 recurrences during the first year and 20% had more than 10 recurrences. The median monthly recurrence rate was 0.43 for men and 0.33 for women (difference, 0.10 [95% CI, 0.03 to 0.19]; P < 0.01). Twenty-six percent of women and 8% of men had no or 1 recurrence in year 1 of follow-up, whereas 14% of women and 26% of men had more than 10 recurrences. Patients who had severe primary HSV-2 infection (duration, > or = 35 days) had recurrences nearly twice as often (0.66 compared with 0.36 recurrences per month [95% CI, 0.18 to 0.57]) and had a shorter time to first recurrence when compared with those who had shorter first episodes.
CONCLUSIONS: Almost all persons with initially symptomatic HSV-2 infection have symptomatic recurrences. More than 35% of such patients have frequent recurrences. Recurrence rates are especially high in persons with an extended first episode of infection, regardless of whether they receive antiviral chemotherapy with acyclovir. Men with genital HSV-2 infection have about 20% more recurrences than do women, a factor that may contribute to the higher rate of HSV-2 transmission from men to women than from women to men and to the continuing epidemic of genital herpes in the United States.
S L Spruance, S K Tyring, B DeGregorio, C Miller, K Beutner
A large-scale, placebo-controlled, dose-ranging trial of peroral valaciclovir for episodic treatment of recurrent herpes genitalis. Valaciclovir HSV Study Group.
Arch Intern Med. 1996 Aug 12-26;156(15):1729-35.
Abstract/Text
BACKGROUND: Valaciclovir, the 1-valyl ester of acyclovir, has provided a peroral acyclovir bioavailability 3 to 5 times that of acyclovir itself and is rapidly and completely converted to acyclovir by the liver. Accordingly, valaciclovir has the same antiviral activity as acyclovir, but the potential for enhanced clinical activity and/or less frequent administration because of its superior pharmacokinetics.
METHODS: We conducted a double-blind, placebocontrolled, patient-initiated clinical trial of peroral valaciclovir, 500 or 1000 mg, or matching placebo tablets twice daily for 5 days for the acute treatment of 1 episode of recurrent herpes genitalis among 987 otherwise healthy volunteers.
RESULTS: Both doses of valaciclovir were equally effective. Patients receiving the lower dose of valaciclovir experienced a median episode length of 4.0 days compared with 5.9 days for those receiving placebo treatment (hazard ratio, 1.9; 95% confidence interval [Cl], 1.6-2.3). Valaciclovir therapy increased the proportion of patients in whom the development of vesicular and ulcerative lesions was prevented in comparison with placebo treatment: 31% vs 21% (relative risk, 1.5; 95% CI, 1.1-1.9). Valaciclovir therapy accelerated the resolution of pain (hazard ratio, 1.8; 95% CI, 1.5-2.1) and the time to cessation of viral shedding (hazard ratio, 2.9; 95% CI, 2.1-3.9). Adverse reactions among the valaciclovir groups were comparable with those of the placebo group.
CONCLUSIONS: Valaciclovir therapy provided a clinically significant benefit to patients that included shortening of the duration of lesions, the duration of pain or discomfort, and the duration of virus shedding. In addition, this study, to our knowledge, provides the first convincing demonstration that antiviral therapy can prevent lesion development. These results should prompt a reconsideration of the role that episodic treatment plays in the management of recurrent herpes genitalis.
A Strand, R Patel, H C Wulf, K M Coates, International Valaciclovir HSV Study Group
Aborted genital herpes simplex virus lesions: findings from a randomised controlled trial with valaciclovir.
Sex Transm Infect. 2002 Dec;78(6):435-9.
Abstract/Text
OBJECTIVES: In prospective trials, episodic valaciclovir significantly increased the chance of preventing or aborting the development of painful vesicular genital herpes simplex virus (HSV) lesions compared with placebo. We explored the clinical outcome of aborted lesions and its association with early treatment in a study designed to compare 3 and 5 days' treatment with valaciclovir.
METHODS: In a randomised controlled trial, valaciclovir 500 mg twice daily for 3 or 5 days was initiated at the first symptoms of a genital herpes outbreak. The primary end point was length of episode with pain, HSV shedding, and aborted lesions secondary end points. The effect of time from symptom recognition to treatment initiation on aborted lesions was assessed in a post hoc analysis.
RESULTS: In 531 patients, no differences were observed between 3 and 5 days' treatment in episode duration (median 4.7 v 4.6 days), loss of pain/discomfort (2.8 v 3.0 days), or lesion healing (4.9 v 4.5 days). Vesicular lesions were aborted in 27% of patients treated for 3 days v 21% of patients receiving valaciclovir for 5 days. The odds of achieving an aborted episode were 1.93 (95% CI: 1.28 to 2.90) times higher for those initiating treatment with valaciclovir within 6 hours of first sign or symptom.
CONCLUSIONS: There was no difference between 3 and 5 days' treatment in reducing episode duration or lesion abortion. Prompt treatment with valaciclovir can abort genital HSV reactivation episodes, preventing a vesicular outbreak. Maximum treatment benefit depends on prompt therapy after recognition of symptoms.
日本性感染症学会：性感染症 診断・治療 ガイドライン 2016. 日本性感染症学会誌 2016;27(1)Suppl 64-68.
Marie L Landry, Jennifer Greenwold, Holenarasipur R Vikram
Herpes simplex type-2 meningitis: presentation and lack of standardized therapy.
Am J Med. 2009 Jul;122(7):688-91. doi: 10.1016/j.amjmed.2009.02.017.
Abstract/Text
BACKGROUND: Herpes simplex type-2 (HSV-2) causes both primary and recurrent lymphocytic meningitis, but optimal patient management is not well defined.
METHODS: In this retrospective observational study, we reviewed the medical records of patients with HSV-2-positive cerebrospinal fluid samples in our laboratory between January 2001 and January 2005.
RESULTS: During the study period, 23 patients, aged 16 to 83 years, had HSV-2 detected in spinal fluid. Nineteen (83%) had meningitis and 4 (17%) had evidence of meningoencephalitis. Seventy-four percent were female. Two (8.7%) had a history of prior genital herpes, and one (4.3%) had genital lesions noted at the time of presentation. Genital examinations were performed at presentation in only 3 patients. Seven (30.4%) patients reported previous episodes of meningitis. Two celibate women developed HSV-2 meningitis or meningoencephalitis following lumbar steroid injection for spinal stenosis. One woman developed HSV-2 meningoencephalitis 3 days postpartum following cesarean section. Antiviral treatment for uncomplicated HSV-2 meningitis varied from none (4 patients) to 14-21 days of intravenous (IV) acyclovir therapy (4 patients). The 11 remaining patients with meningitis received 1-7 days of IV therapy, followed by 7-21 days of oral antiviral therapy. Three of 4 patients with meningoencephalitis received 21 days of IV acyclovir, and one received 3 days IV acyclovir followed by 14 days of oral therapy.
CONCLUSIONS: HSV-2 meningitis presents most often without a history of genital herpes, recurrent meningitis, or genital symptoms. Current management practices are highly variable and may lead to unnecessary hospitalization and prolonged intravenous therapy.
Z A Brown, S Selke, J Zeh, J Kopelman, A Maslow, R L Ashley, D H Watts, S Berry, M Herd, L Corey
The acquisition of herpes simplex virus during pregnancy.
N Engl J Med. 1997 Aug 21;337(8):509-15. doi: 10.1056/NEJM199708213370801.
Abstract/Text
BACKGROUND: The acquisition of genital herpes during pregnancy has been associated with spontaneous abortion, prematurity, and congenital and neonatal herpes. The frequency of seroconversion, maternal symptoms of the disease, and the timing of its greatest effect on the outcome of pregnancy have not been systematically studied.
METHODS: We studied 7046 pregnant women whom serologic tests showed to be at risk for herpes simplex virus (HSV) infection. Serum samples obtained at the first prenatal visit, at approximately 16 and 24 weeks, and during labor were tested for antibodies to HSV types 1 and 2 (HSV-1 and HSV-2) by the Western blot assay, and the results were correlated with the occurrence of antenatal genital infections.
RESULTS: Ninety-four of the women became seropositive for HSV; 34 of the 94 women (36 percent) had symptoms consistent with herpes infection. Women who were initially seronegative for both HSV-1 and HSV-2 had an estimated chance of seroconversion for either virus of 3.7 percent; those who were initially seropositive only for HSV-1 had an estimated chance of HSV-2 seroconversion of 1.7 percent; and those who were initially HSV-2-seropositive had an estimated chance of zero for acquiring HSV-1 infection. Among the 60 of the 94 pregnancies for which the time of acquisition of HSV infection was known, 30 percent of the infections occurred in the first trimester, 30 percent in the second, and 40 percent in the third. HSV seroconversion completed by the time of labor was not associated with an increase in neonatal morbidity or with any cases of congenital herpes infection. However, among the infants born to nine women who acquired genital HSV infection shortly before labor, neonatal HSV infection occurred in four infants, of whom one died.
CONCLUSIONS: Two percent or more of susceptible women acquire HSV infection during pregnancy. Acquisition of infection with seroconversion completed before labor does not appear to affect the outcome of pregnancy, but infection acquired near the time of labor is associated with neonatal herpes and perinatal morbidity.
