Genital herpes

doi:10.1016/j.bpobgyn.2014.07.015

Best Practice & Research Clinical Obstetrics & Gynaecology

Volume 28, Issue 7, October 2014, Pages 1098-1110

https://doi.org/10.1016/j.bpobgyn.2014.07.015 Get rights and content

Genital herpes is a relatively common infection caused by herpes simplex virus (HSV) type one or two (HSV-1, HSV-2) respectively. It is acquired most commonly via sexual activity. More recently there has been an increase in infections due to HSV-1. Most new cases of genital HSV are not diagnosed due to HSV infections having short-lived signs and symptoms, or in many instances are asymptomatic. Hence many people infected with HSV are unaware that they have it. The risk of transmission to a partner is highest during outbreak periods, when there are visible lesions, although genital HSV can also be transmitted during asymptomatic periods. Use of condoms and antiviral medications assist in preventing transmission. Antiviral agents are effective in controlling clinical episodes, but do not eradicate infection, which remains latent for the life of a patient. Despite the surge in vaccine research, there is unfortunately no readily available preventative or therapeutic vaccine for HSV to date.

Section snippets

Introduction: HSV virus

Herpes simplex viruses (HSV) are double stranded, enveloped DNA viruses of the Herpesviridae family. There are two distinct serotypes or “types” for short, HSV-1 and HSV-2. These two types share 40% sequence homology of their genome structure, which reaches 83% for their protein-coding regions, which explains antigenic cross-reactivity between them. Typically, due to tropism for specific anatomical sites, HSV-1 predominantly infects the mucus membranes and skin of the orolabial area. However,

HSV infection and clinical presentation

HSV typically infects the epithelial cells of the skin and mucosa through minor breaks and then travels by retrograde transport along sensory nerves to the sensory root ganglia. Here there is viral replication. Establishment of latency occurs for the life of the host. Periodically there is reactivation from the latent state, with anterograde transfer from sensory ganglions to the periphery (skin or mucous membranes), where subclinical shredding as well as overt symptomatic and asymptomatic

Infection terminology

Initial primary genital infection is defined as the acquisition of either HSV-1 or HSV-2 of the genital skin or mucosa in the absence of both HSV-1 and 2 serum antibodies (ie no previous exposure or infection).

Initial non-primary is defined as having pre-existing antibodies to HSV-1 or HSV-2 (IgG), but not necessarily from a previous clinically overt infection. For example, in the setting of someone who has had pre-existing HSV-2 (defined by IgG HSV-2), a new genital infection with HSV-1 can

Sero-epidemiology

There have been changes in the patterns of acquisition of HSV-1 infection in the past few decades in developed populations. Seropositivity for HSV-1 has decreased from near 100% in the past resulting from extended family living. Now, family units are more nuclear and common, especially in higher socio-economic families. This provides less opportunity to acquire HSV-1 in childhood via the oral route [6]. This has resulted in an increase in HSV-1 infections being acquired sexually and presenting

Viral shedding

In recent studies of symptomatic and asymptomatic patients with past infection of HSV-2 (as defined by positive serology for HSV-2 by Western Blot) where data collection included intense daily swabbing (intravaginally, labial, perennial, perianal swabs) and patient diary entries, symptomatic patients were found to shed 20% of the time, whilst asymptomatic patients only shed 10% of the time [4]. Of note the quantity of shedding was not different for either group, despite the different rates.

Viral identification

Viral culture used to be the mainstay of diagnosis, but took over 24 hours to obtain a result [14]. Direct immunofluorescence of infected cells collected from a fresh lesion (by first breaking the vesicle and rubbing the base of the lesion then smearing onto a glass slide) is faster, being performed in a few hours, is inexpensive and has a sensitivity of around 95%. PCR can be used on lesions, CSF, ETA blood, and Guthrie cards (these are filter paper cards for storing infant heel prick

Screening

Type-specific serology is not suggested in patients with no history of genital lesions. If done, it should be accompanied with appropriate counseling. The low positive value of serology are not very specific, thus the positive predictive value in a low prevalence group is low. Moreover, confirmatory testing by a more specific test such as a Western blot is not readily available at most laboratories.

Type specific serology is useful for high risk scenarios such as knowing that a partner is

Treatment

Standard treatment regimens for initial either primary or non-primary HSV include acyclovir 200 mg five times daily, valacyclovir 1 gm bd, and famciclovir 125 mg bd [22], [23]. (See Table1) [24]. Recurrent episodic treatment regimens include shorter course of antivirals commenced at a prodrome or early in lesion development. (See Table 1). Standard treatment regimens of valacyclovir 500 mg bid for suppression of HSV shedding in recurrent infection have been shown to reduce the frequency and

Follow-up cultures

Follow-up cultures are not indicated, except when unusual recurrent symptoms appear or when resistance is suspected as a cause for therapeutic failure and in order to determine in vitro susceptibility. Since resistance to antiviral is rare in immunocompetent patients, careful evaluation should include questions regarding compliance of antiviral therapy and HIV status (offer HIV test if not performed lately). Referral to an experienced colleague for further evaluation is warranted.

Genital HSV in pregnancy

The greatest risk of transmission to the fetus or neonate is a primary infection in a mother close to labour or within the last trimester. Infection prior to pregnancy or earlier in gestation allows seroconversion and the transmission of neutralizing antibodies to the infant [27]. Without these neutralizing antibodies, the risk of transmission is in the order of 50%. The clinical presentation of neonatal HSV is local skin/mucous membrane disease, central nervous system disease or disseminated

Conclusion

Genital herpes is a relatively common infection with a prevalence rate of 13–25% in western countries. Many infections go unrecognized as they maybe clinically atypical, short lived and the majority is asymptomatic. This largely explains the constant transmission rate from one partner to another. Latency is a feature of infection, thus an outbreak is not predictable and preventable. There has been a change in the epidemiology of this virus, particularly in the higher socio-economic groups, with

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Multiplex PCR can utilize limited clinical material and is more cost-effective and expected to be used for the detection of Treponema pallidum, herpes simplex virus type 1 and 2 (HSV-1,2). We established a multiplex TP-HSV1-HSV2 Polymerase Chain Reaction (multiplex PCR) targeting the conserved regions of the PolA gene of TP and the UL42 gene of HSV1 and HSV2 to test skin lesions of 115 patients suspected of having TP and HSV1/2 infections. The laboratory sensitivities for all 3 pathogens were 300 copies/mL. The overall clinical sensitivity and specificity in secretion samples for TP were 91.7% and 100%, for HSV1 100% and 98%, and for HSV2 89.7% and 100%, respectively. The method appears superior in patients suspected of early TP infection but negative for nontreponemal antibody testing, and the method is also useful for the differential diagnosis of new skin lesions on genital, perianal, and oral sites of patients with a history of previous syphilis.
The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro
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JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.
HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125–50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.
HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).
JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1.
Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277–288.
Layer-by-layer vaginal films for acyclovir controlled release to prevent genital herpes
2022, International Journal of Pharmaceutics
Genital herpes is one of the most common sexually transmitted infections worldwide. It mainly affects women, as the rate of sexual transmission from male-to-female is higher than from female-to-male. The application of vaginal antivirals drugs could reduce the prevalence of genital herpes and prevent future infections. Layer-by-layer vaginal films were prepared by the solvent evaporation method using iota-carrageenan, hydroxypropyl methylcellulose and the polymethacrylates Eudragit® RS PO and Eudragit® S100, for the controlled release of acyclovir. The films were characterized by texture analysis and Raman spectroscopy. Swelling, mucoadhesion, and drug release studies were conducted in simulated vaginal fluid. The results show that Layer-by-Layer films exhibited adequate mechanical properties. The structuring of the layer-by-layer films allowed the controlled release of acyclovir and produced a prolonged mucoadhesion residence time of up to 192 h. The films formed in layer 2 by the combination of Eudragit® RS PO and S100 showed a controlled release of acyclovir for eight days, and adequate mechanical properties. These promising formulations for the prevention of genital herpes deserve further evaluation.
Herpes simplex virus infection in Bulgarian patients with neurological diseases
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Herpes simplex virus (HSV) seroprevalence in Bulgaria is higher than that in other countries but there is no information concerning involvement of these viruses in neuropathology. The aim of the present study was to determine the frequency of HSV DNA detection in cerebrospinal fluid (CSF) of patients with neurological diseases.
This study is a retrospective survey of test results obtained from January 2015 to October 2019. During this period 617 CSF specimens were tested for the presence of HSV-1 and/or HSV-2 DNA by PCR.
Of all 612 CSF samples tested for HSV-1, 16.5% were positive. Of 547 CSF samples tested for HSV-2, 6.2% were positive. Co-infection with HSV-1 and HSV-2 was detected in 1.3% of tested 543 CSF samples. The difference of HSV-1 and/or HSV-2 prevalence in CSF of patients according to the gender and age was not statistically significant. The highest HSV-1 prevalence (25%) was detected in CSF from patients with multiple sclerosis (MS), followed by patients with encephalitis (20.6%). The highest HSV-2 prevalence (22.2%) was detected in CSF from patients with myelitis, followed by patients with encephalopathies (7.5%).
Our results show a considerable prevalence of HSV-1 and HSV-2 in CSF of patients with neurological diseases indicating the important role of these viruses in neuropathology in Bulgaria. HSV-1 is with predominant role in development of both encephalitis and meningitis in different age groups. Testing of CSF for HSV should be indispensable part of diagnostic algoritm of these diseases.
Strong alkaline electrolyzed water efficiently inactivates SARS-CoV-2, other viruses, and Gram-negative bacteria
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A truncated glycoprotein G vaccine formulated with Advax-CpG adjuvant provides protection of mice against genital herpes simplex virus 2 infection
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Herpes simplex virus type 2 (HSV-2) is a common sexually transmitted disease that affects approximately 500 million individuals globally. There is currently no approved vaccine to prevent HSV-2 infection. EXCT4 is a truncated form of the mature glycoprotein G-2 (mgG-2) that unlike full mature form is secreted by expressing cells enabling it to be rapidly scaled up for production. The current study examined whether EXCT4 immunity in mice could be further enhanced through use of adjuvants. EXCT4 formulated with Advax-CpG adjuvant induced a strong Th1-type immune response characterized by interferon gamma (IFN-γ) and protected animals against a lethal genital challenge with HSV-2. This response was associated with reduced viral load in vaginal washes, spinal cord, and dorsal root ganglia. Together the results provide proof of concept that EXCT4 formulated with Advax-CpG adjuvant is a promising HSV-2 vaccine candidate warranting further investigation.

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14Genital herpes

Section snippets

Introduction: HSV virus

HSV infection and clinical presentation

Infection terminology

Sero-epidemiology

Viral shedding

Viral identification

Screening

Treatment

Follow-up cultures

Genital HSV in pregnancy

Conclusion

J Virological Methods

The Lancet

Am J Obstet Gynecol

Genital HSV-1 infections

Sex Transm Infect

A prospective study of new infections with herpes simplex virus type 1 and type 2

NEJM

Sexually transmitted diseases

Genital shedding of herpes simplex virus among symptomatic and asymptomatic persons with HSV-2 infection

JAMA

Genital herpes simplex virus infection

Clin Obstet Gynecol

Prevalence of infection with herpes simplex virus types 1 and 2 in Australia: a nationwide population based survey