Primary Genital Herpes Infections Research Articles

Guinea Pig and Mouse Models for Genital Herpes Infection.

This article describes procedures for two preclinical animal models for genital herpes infection. The guinea pig model shares many features of genital herpes in humans, including a natural route of inoculation, self-limiting primary vulvovaginitis, spontaneous recurrences, symptomatic and subclinical shedding of HSV-2, and latent infection of the associated sensory ganglia (lumbosacral dorsal root ganglia, DRG). Many humoral and cytokine responses to HSV-2 infection in the guinea pig have been characterized; however, due to the limited availability of immunological reagents, assessments of cellular immune responses are lacking. In contrast, the mouse model has been important in assessing cellular immune responses to herpes infection. Both the mouse and guinea pig models have been extremely useful for evaluating preventative and immunotherapeutic approaches for controlling HSV infection and recurrent disease. In this article, we describe procedures for infecting guinea pigs and mice with HSV-2, scoring subsequent genital disease, and measuring replicating virus to confirm infection. We also provide detailed protocols for dissecting and isolating DRG (the site of HSV-2 latency), quantifying HSV-2 genomic copies in DRG, and assessing symptomatic and subclinical shedding of HSV-2 in the vagina. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Primary and recurrent genital herpes infection in the guinea pig model Support Protocol 1: Blood collection via lateral saphenous vein or by cardiac puncture after euthanasia Support Protocol 2: Dissection and isolation of dorsal root ganglia from guinea pigs Support Protocol 3: PCR amplification and quantification of HSV-2 genomic DNA from samples Basic Protocol 2: Primary genital herpes infection in the mouse model Alternate Protocol: Flank infection with HSV-2 in the mouse model Support Protocol 4: Dissection and isolation of mouse dorsal root ganglia.

A case of labial adhesions following primary genital herpes infection

Labial adhesions are usually associated with hypo-oestrogenism, but it is also a rare complication of genital herpes infection. We present a case report of a 23-year-old woman presenting with primary genital herpes infection, progressing to labial adhesions.

The Scarlet H

The Scarlet H

O07.3 A Psychological Experiment to Examine the Global Impact of Stigma on Individuals Diagnosed with Type 1 Herpes Simplex Virus (HSV-1)

BackgroundHSV-1 causes at least 50% of primary genital herpes infections in Europe, Canada, Australia and the USA. In the UK, rates may be even higher, as the level 3 STI...

Neonatal herpes simplex virus infection

Herpes simplex virus (HSV) infection in the neonate is a rare event with severe consequences for the child even if adequately treated with antiviral drugs. Mothers with primary genital herpes infections late in pregnancy or at delivery have a high risk of transferring the infection to the child, while the risk of transfer in mothers with recurrent genital infections is only a few percent. Neonatal herpes localized in skin-eye-mouth has no mortality and morbidity after antiviral treatment. In neonatal disseminated and central nervous system disease, early treatment is a predictor for better outcome. The morbidity in survivors is high; after herpes encephalitis, only one-third of children have normal development. While awaiting vaccines or reliable predictors for prevention of neonatal herpes, clinical awareness of primary maternal herpes during pregnancy and recommendations for prophylactic treatment are important tools. For pediatricians the differential diagnosis of a child aged two to four weeks with seizures, neonatal herpes encephalitis must be considered and either excluded or treated. Neurological follow-up and training programs to minimize the consequences of a disability are important clinical aspects.

Is suspicion of genital herpes infection associated with avoiding sex? A clinic-based study

The present study tested the research hypothesis that sexually transmissible disease (STD) clinic patients suspecting genital herpes infection would be more likely than their 'non-suspecting' counterparts to abstain from sex to avoid transmission of a perceived STD. Recruitment (n = 351) occurred in a publicly-funded STD clinic located in a metropolitan area of the southern USA. Participants were tested for herpes simplex virus type 2 (HSV-2) using a rapid test manufactured by Biokit (Lexington, MA, USA) and they completed a self-administered questionnaire (using a 3-month recall period). Well over one-third (38.7%) of those indicating suspicion also indicated avoiding sex with steady partners because of concerns about STDs as compared with 28.0% among those not indicating suspicion (prevalence ratio = 1.38; 95% CI = 1.02-1.87, P = 0.036). The relationship between suspicion and avoiding sex with non-steady partners was not significant (P = 0.720). The relationship with steady partners only applied to people who were female (P = 0.013), single (P = 0.017), reported symptoms of genital herpes (P = 0.003), perceived that genital herpes would have a strong negative influence on their sex life (P = 0.0001), and who subsequently tested positive for HSV-2 (P = 0.012). Among STD clinic attendees, suspicion of genital herpes infection may translate into partner protective behaviour, but only for a minority of people and only with respect to sex with steady partners. Clinic-based and community-based education programs may benefit public health by teaching people (especially single women) how to effectively recognise symptoms of primary genital herpes infections. Reversing the often prevailing ethic of genital herpes as a 'community secret' will clearly be a challenge to these education programs.

CpG oligodeoxynucleotide augments HSV-2 glycoprotein D DNA vaccine efficacy to generate T helper 1 response and subsequent protection against primary genital herpes infection in mice

The present study was undertaken to evaluate the efficacy of a combined use of DNA vaccine of HSV-2 glycoprotein D (gD DNA) and CpG oligodeoxynucleotide (ODN) in comparison to gD DNA vaccine alone in inducing immunity against genital HSV-2 infection. Intramuscular vaccination of C57Bl/6 mice with gD DNA followed 48 h later by CpG ODN administration conferred a strong immunity against genital herpes infection. This was concomitant with development of a robust specific IgG2c (an indicator of Th1-type response in C57Bl/6 mice) antibody response as well as IFN-γ production by genital lymph node and spleen cells in vitro. Administration of CpG ODN prior to gD DNA immunization, on the other hand, was inferior to immunization with gD DNA alone in providing protection against macroscopic signs of the disease. Consistent with the in vivo protection data, mice immunized with CpG ODN followed by gD DNA vaccine showed decreased specific lymphoproliferative and IFN-γ responses compared to gD DNA vaccinated mice. In conclusion, these results indicate that timely administration of CpG ODN augments the immunity elicited by gD DNA vaccine, resulting in augmented Th1-type immunity against genital herpes infection in mice. These findings emphasize the value of using CpG ODN in a DNA vaccination scheme against genital herpes and merit also further evaluation in genetic vaccination approaches against other sexually transmitted infections.

Patterns of Primary Genital Herpes

Our understanding of primary genital herpes infections has been hindered by a dearth of rigorous observational studies. This report from a multicenter

Genital herpes during pregnancy: Inability to distinguish primary and recurrent infections clinically

To determine if the signs and symptoms of genital herpes in pregnancy accurately identify primary genital herpes infections using serologic testing for final classification. Twenty-three women with clinical signs and symptoms suggestive of primary genital herpes infections in the second and third trimesters of pregnancy were subsequently cultured and tested serologically (for herpes simplex virus type 1 and herpes simplex virus type 2 antibodies) and classified as having true primary (no herpes simplex virus type 1 or type 2 antibodies), nonprimary (heterologous herpes simplex virus antibodies present), or recurrent (homologous antibodies present) infections. Only one of 23 women with clinical illnesses consistent with primary genital herpes virus simplex infections had serologically-verified primary infection. This primary infection was caused by herpes simplex virus type 1. Three women had nonprimary type 2 infections, and 19 women had recurrent infections. Among culture-proven recurrent infections, 12 were caused by herpes simplex virus type 2 and three by herpes simplex virus type 1. Only one infant was born preterm, and no clinically significant perinatal morbidity was observed. Correct classification of gestational genital herpes infections can be accomplished only when clinical evaluation is correlated with viral isolation and serologic testing using a type-specific assay. Severe first episodes of genital herpes infections among women in the second and third trimesters of pregnancy are not usually primary infections and are not commonly associated with perinatal morbidity.

Class-specific antibody response in acyclovir-treated and adenine arabinoside-treated patients with primary genital herpes simplex virus infection.

Herpes simplex virus (HSV) class-specific antibody responses after primary genital herpes infection were evaluated with an enzyme-linked immunosorbent assay (ELISA) in 16 patients treated with acyclovir (ACV), given orally, and 17 patients treated with adenine arabinoside (Ara-A), given topically. ACV significantly suppressed the levels of IgM, IgA, and IgG. In the ACV-treated patients, IgM and IgG were not detected in 4 of the 16 and in 1 of the 16 patients, respectively. We must take into account this suppressive effect of ACV on antibody responses, especially on the IgM response, when serodiagnosis of HSV infection is made.

Medical history and clinical presentation does not identify primary genital herpes infections in pregnant women: [formula omitted], W. Andrews, Z. Brown, J.S. Greenspoon, L. Yasukawa x, K. Huerta x, C. Prober. x Stanford Univ/Santa Clara Valley Med. Ctr., San Jose, CA; Univ. of Alabama, Birmingham; U. Wahington, Seattle; Cedars-Sinai Med. Ctr., Los Angeles, CA

Medical history and clinical presentation does not identify primary genital herpes infections in pregnant women: [formula omitted], W. Andrews, Z. Brown, J.S. Greenspoon, L. Yasukawa x, K. Huerta x, C. Prober. x Stanford Univ/Santa Clara Valley Med. Ctr., San Jose, CA; Univ. of Alabama, Birmingham; U. Wahington, Seattle; Cedars-Sinai Med. Ctr., Los Angeles, CA

Cytology of primary versus secondary genital herpesvirus infection

Certain authors state that primary genital herpes infections mainly produce cells with ground-glass nuclei, whereas secondary infections produce a higher percentage of multinucleated or single cells with prominent intranuclear inclusions. The cervicovaginal smears of 11 patients with primary genital herpes infection and 16 patients with secondary infection were studied to determine the validity of this differentiation. The percentage per patient of virally infected cells containing distinct inclusions ranged from 0% to 35% in the primary herpes group and 0% to 100% in the secondary herpes group. In eight additional patients, the initial herpes simplex virus (HSV)-positive smear was compared with recurrent positive smears taken from 2 to 120 mo later. No statistical difference in the incidence of distinct inclusions in the infected cells was detected. Finally, primary rabbit kidney and the heteroploid A549 cell cultures were inoculated with herpes viruses and followed by fixation with several agents at various time intervals. Alcohol and Bouin's fixative favored the recognition of distinct inclusions, as did the duration of the infection.

Painless primary herpes

An adolescent male developed painless but severe genital ulcerations. Evaluation confirmed primary herpes. The medical literature describes the classical presentation of primary genital herpes infection as multiple ulcerations and severe pain, but 5% of male patients present without pain. Consequently, the differential diagnosis of painless genital ulcerations should include Herpes progenitalis.

Update on acyclovir: Oral therapy for herpesvirus infections

The results of the major human clinical trials on oral acyclovir are reviewed, and the pharmacokinetics, adverse effects, and role of oral acyclovir in the management of herpes simplex virus (HSV) infections are discussed. Clinical studies have demonstrated the effectiveness of oral acyclovir in causing significant reductions in the duration of viral shedding, development of new lesions, and time to crusting and healing in several clinical situations. The drug appears to achieve the most dramatic results in the treatment of initial primary genital herpes infections. Oral acyclovir also has a potential role in suppressing reactivations of HSV infections in immunocompromised patients or patients experiencing greater than 10-12 recurrences of genital herpes per year. Most trials have used 200-mg capsules administered five times daily for 5-10 days for treating acute infections. Reduced doses have been successful for suppressive therapy. Acyclovir does not alter the frequency of recurrence once treatment has been discontinued. The absolute bioavailability of oral acyclovir is approximately 20%, and plasma concentrations are about one tenth of those achieved after a typical i.v. infusion. The relationship between plasma concentration and clinical response has not been established. The half-life is 3-4 hours, and the predominant route of elimination is via renal excretion and tubular secretion. Clinical studies have consistently reported minimal adverse effects with oral acyclovir. Conservative use is justified by the potential development of resistant viral strains. The extent and clinical importance of resistant viral selection remain to be determined. Oral acyclovir represents an advance in the development of a nontoxic antiviral agent suitable for both hospitalized and ambulatory patients that should be recommended for formulary inclusion.

Effect of acyclovir treatment of primary genital herpes on the antibody response to herpes simplex virus.

Sera from patients with first episode primary genital herpes infections who were treated with the antiviral drug acyclovir were studied to determine the effect of therapy on the immune response to herpes simplex virus (HSV) glycoproteins and polypeptides. 63 patients were evaluated, 35 patients received acyclovir: 11 intravenously, 12 orally, and 12 topically, while 28 received placebo. Topical application of acyclovir had no effect on the immune response to HSV infection. However, both oral and intravenous acyclovir were associated with later development of antibodies to two glycoproteins (of 80,000 and 60,000 mol wt [IIg80 and gD, respectively]) and one nonglycosylated polypeptide of 66,000 mol wt (vp66). Antibody to IIg80 was present in convalescent phase serum in 13/23 systemic acyclovir recipients vs. 18/19 placebo recipients (P = 0.01) and antibody to gD was detected in 8/23 oral or intravenous acyclovir recipients vs. 11/19 placebo recipients (P = 0.06). The mean time to seroconversion to IIg80 (39.0 d) and gD (55.5 d) was significantly longer for systemic acyclovir recipients than for the placebo controls, 23.4 and 18.5 d, respectively (P less than 0.05 for each comparison). 7 (30%) of 23 systemic acyclovir recipients compared with 100% of the placebo recipients had antibody to vp66 by 30 d after onset of the primary episode (P less than 0.001). Subsequent untreated recurrences of genital herpes were associated with seroconversion to gD, IIg80, and vp66. Patients who lacked antibody to both gD and vp66 in sera taken before their first clinical recurrence of disease experienced a longer duration of the recurrent episode (10.8 d) than those who possessed antibody to both vp66 and gD (6.3 d) (P less than 0.05). In addition, the mean duration of lesions, number of lesions, and mean lesion area were greater in patients who lacked antibody to vp66 but had anti gD, as compared with those who had anti-p66 but lacked anti-gD; suggesting that antibody to vp66 correlated more closely with subsequent disease severity than did antibody to gD. Acyclovir therapy appears to influence the frequency and time of development of antibody to a number of different HSV-specific polypeptides. Further studies of the effects of antiviral therapies on the immune response to these proteins may help clarify the role of these polypeptides in the pathogenesis of disease.

Value of the Erythrocyte Sedimentation Rate in Primary Genital Herpes

An elevated erythrocyte sedimentation rate may be a useful indicator of cervical infection in primary genital herpes infections. Mean ESR in 26 patients with both vulval and cervical herpetic lesions showed a highly significant elevation compared to that obtained from 13 patients with vulval herpetic lesions alone (P < 0.001) and also to that obtained from 527 female control patients with no clinical abnormality (P < 0.001). The ESR should be a routine test in all female patients who are either clinically suspected, or are contacts of genital herpes.

Men and medicine.

A 24 year old woman with Crohn9s disease presented initially with a severe primary genital herpes infection. After the first attack frequent recurrences occurred on the hands, feet, and genitalia. The patient was treated with oral acyclovir for 12 weeks, during which time she had two brief minor recurrences. After treatment was stopped lesions recurred at the same sites.