Primary Herpes Simplex Virus Infection Research Articles

Is Prophylactic Acyclovir Treatment Warranted for Prevention of Herpes Simplex Virus Infections in Facial Burns? A Review of the Literature

Both cosmetic facial resurfacing and facial burns cause an injury to the dermal layer of the skin. This injury renders the patient susceptible to primary herpes simplex virus (HSV) infection or, more commonly, to HSV reactivation. This in turn can lead to bacterial superinfection, possibly resulting in scarring and systemic dissemination in the immunosuppressed burn patient. HSV reactivation rates have been reported to be up to 50% in cosmetic procedures without acyclovir prophylaxis and up to 25% in patients with burn injury. Currently, acyclovir prophylaxis is a common practice in facial resurfacing, but no such recommendations have been issued for patients with burn injury. HSV usually presents in a febrile burn patient between the first and third postburn weeks as a cluster of small, umbilicated vesicles or vesicopustules on an erythematous base found within or around the margins of healing partial-thickness wounds. Diagnosis is confirmed through viral culture from the base of an unroofed vesicle, and treatment is begun with intravenous acyclovir. Antiviral prophylaxis should be strongly considered for HSV infection prevention in patients with major burn injury, particularly with burns involving the face. Acyclovir is the primary drug of choice, and contact precautions should be practiced. High suspicion levels and alertness to this entity can help prompt diagnosis and timely treatment while alleviating late complications.

Development of a Glycoprotein D-Expressing Dominant-Negative and Replication-Defective Herpes Simplex Virus 2 (HSV-2) Recombinant Viral Vaccine against HSV-2 Infection in Mice

Using the T-REx (Invitrogen, California) gene switch technology and a dominant-negative mutant polypeptide of herpes simplex virus 1 (HSV-1)-origin binding protein UL9, we previously constructed a glycoprotein D-expressing replication-defective and dominant-negative HSV-1 recombinant viral vaccine, CJ9-gD, for protection against HSV infection and disease. It was demonstrated that CJ9-gD is avirulent following intracerebral inoculation in mice, cannot establish detectable latent infection following different routes of infection, and offers highly effective protective immunity against primary HSV-1 and HSV-2 infection and disease in mouse and guinea pig models of HSV infections. Given these favorable safety and immunological profiles of CJ9-gD, aiming to maximize levels of HSV-2 glycoprotein D (gD2) expression, we have constructed an ICP0 null mutant-based dominant-negative and replication-defective HSV-2 recombinant, CJ2-gD2, that contains 2 copies of the gD2 gene driven by the tetracycline operator (tetO)-bearing HSV-1 major immediate-early ICP4 promoter. CJ2-gD2 expresses gD2 as efficiently as wild-type HSV-2 infection and can lead to a 150-fold reduction in wild-type HSV-2 viral replication in cells coinfected with CJ2-gD2 and wild-type HSV-2 at the same multiplicity of infection. CJ2-gD2 is avirulent following intracerebral injection and cannot establish a detectable latent infection following subcutaneous (s.c.) immunization. CJ2-gD2 is a more effective vaccine than HSV-1 CJ9-gD and a non-gD2-expressing dominant-negative and replication-defective HSV-2 recombinant in protection against wild-type HSV-2 genital disease. Using recall response, we showed that immunization with CJ2-gD2 elicited strong HSV-2-specific memory CD4(+) and CD8(+) T-cell responses. Collectively, given the demonstrated preclinical immunogenicity and its unique safety profiles, CJ2-gD2 represents a new class of HSV-2 replication-defective recombinant viral vaccines in protection against HSV-2 genital infection and disease.

Herpes simplex ulcerative esophagitis in healthy children

Herpes simplex virus is a common cause of ulcerative esophagitis in the immunocompromised or debilitated host. Despite a high prevalence of primary and recurrent Herpes simplex virus infection in the general population, Herpes simplex virus esophagitis (HSVE) appears to be rare in the immunocompetent host. We report three cases of endoscopically-diagnosed HSVE in apparently immunocompetent children; the presentation was characterized by acute onset of fever, odynophagia, and dysphagia. In two cases, the diagnosis was confirmed histologically by identification of herpes viral inclusions and culture of the virus in the presence of inflammation. The third case was considered to have probable HSVE based on the presence of typical cold sore on his lip, typical endoscopic finding, histopathological evidence of inflammation in esophageal biopsies and positive serologic evidence of acute Herpes simplex virus infection. Two cases received an intravenous course of acyclovir and one had self-limited recovery. All three cases had normal immunological workup and excellent health on long-term follow-up.

Acyclovir Exposure and Birth Defects

Acyclovir Exposure and Birth Defects

Disseminated primary herpes simplex virus infection in a newborn

Disseminated primary herpes simplex virus infection in a newborn

Disseminated Herpes Simplex Virus Type 1 Primary Infection in a Healthy Individual

Primary herpes simplex virus (HSV) infection usually involves one mucosal region. To describe an unusual disseminated HSV-1 infection involving two mucosal sites in a healthy man. Primary HSV infection involved oral and genital mucosa and was associated with viremia, hepatitis and rash. Phylogenetic analysis of genital and oral viruses revealed that the patient was infected by a single HSV-1 strain. Use of polymerase chain reaction detection techniques for HSV may identify viremic patients in the absence of obvious immunosuppression.

Herpes Simplex Virus Viremia during Primary Genital Infection

Primary genital herpes simplex virus (HSV) infection is commonly associated with systemic symptoms. A systematic evaluation of HSV viremia during primary genital infection has not been performed previously. Plasma samples from adults with a first clinical episode of genital HSV infection were assayed for HSV DNA by polymerase chain reaction. One hundred sixty-four adults had confirmed primary genital HSV infection. Of these, 40 (24%) had HSV DNA detected in plasma. Thirty-seven (93%) of 40 were infected with HSV-2. Viremic participants were more likely to be women, compared with aviremic participants (83% vs. 61%; P=.01). Viremia was detected more frequently and at a higher number of copies per milliliter early in infection. We conclude that HSV viremia during primary genital HSV infection is common, especially among women.

Clinical and Laboratory Features of Neonatal Herpes Simplex Virus Infection

Neonatal herpes simplex virus (HSV) infection can cause significant morbidity and mortality but can be difficult to identify, particularly in neonates without vesicular rash. To determine the unique clinical and laboratory features of neonates with and without HSV infection admitted to Texas Children's Hospital during a 14-year period. An historic case-control study of all hospitalized neonates with laboratory-confirmed HSV infection and a restricted sample (ratio 1:4) of HSV test-negative hospitalized neonates. Univariate and multivariate analyses were performed to identify clinical and laboratory factors associated with neonatal HSV infection. Forty cases and 160 comparison subjects were identified. The following factors were associated with neonatal HSV infection by univariate analysis: maternal primary HSV infection, maternal fever, vaginal delivery, prematurity, postnatal HSV contact, vesicular rash, hypothermia, lethargy, seizures, severe respiratory distress, hepatosplenomegaly, thrombocytopenia, elevated hepatic enzymes, and cerebrospinal fluid (CSF) pleocyosis and proteinosis. Factors not associated with neonatal HSV infection were fever, total peripheral white blood cell count, and red blood cells in the CSF. For neonates presenting without vesicular rash, maternal fever, respiratory distress requiring mechanical ventilation, and CSF pleocytosis were independently associated with HSV infection. Inclusion of the newly appreciated features of maternal fever, respiratory distress, and thrombocytopenia might improve the detection of neonatal HSV infection. Clinical and laboratory factors typically associated with neonatal HSV infection were confirmed to be maternal primary HSV infection, vaginal delivery, prematurity, neonatal seizures, vesicular rash, elevated hepatic enzymes, and CSF pleocytosis.

Low-level-laser Therapy as an Alternative Treatment for Primary Herpes Simplex Infection: A Case Report

Gingivostomatitis is the most common primary and symptomatic clinical manifestation of HSV-1 infection. Painful oral lesions appear as ulcerative erosions on the gingiva, palate, buccal mucosa, and tongue, leading to eating and drinking difficulties with an evolution between 10-14 days. This paper describes a case of a 19-month-old boy with severe painful Gingivostomatitis lesions. Low level laser therapy (LLLT) was used with an immediate outcome.

Ultraviolet Light Induces Reactivation in a Murine Model of Cutaneous Herpes Simplex Virus-1 Infection¶

We have developed a model of cutaneous herpes simplex virus-1 (HSV-1) reactivation in SKH-1 hairless mice which closely mimics the condition in humans. Sixty plaque-forming units of HSV-1 strain 17 syn+ were applied to a superficially abraded area on the lateral body wall. More than 85% of mice developed primary HSV-1 infection characterized by a zosteriform pattern of cutaneous vesiculation and ulceration. Approximately one-third of mice with primary skin lesions succumbed to neurologic disease and in the remaining mice cutaneous lesions healed completely. Subsequent exposure of healed areas to two minimal inflammatory doses of UV resulted in recrudescence of skin lesions in the irradiated areas in almost 60% of mice. Lesions appeared approximately 4 days after irradiation, persisted for 3–5 days and then resolved completely. Reactivation rarely resulted in death due to neurologic disease. Primary lesions had a histologic appearance typical of cutaneous HSV-1 infection with vesicles and focal epithelial necrosis accompanied by the formation of epithelial syncytial cells and the presence of herpetic intranuclear inclusion bodies. In primary lesions HSV-1 was demonstrated by immunohistochemistry, polymerase chain reaction and culture. In reactivated lesions epithelial syncytia and inclusion bodies were not seen; however, virus was demonstrable by polymerase chain reaction and culture. Exposure of the uninfected side to UV did not stimulate disease recurrence suggesting that local effects of UV rather than systemic immunosuppression were responsible for reactivation. Reactivation could also be obtained with two minimal inflammatory doses of UV from a UV-340 light source which emits light approximating the solar spectrum.

Condoms do not cover everything: an unusual presentation of herpes simplex virus-2 infection

We report on a patient who presented with an unusual manifestation of primary herpes simplex virus (HSV) infection. Furthermore, this case again shows that even the correct use of a condom has limited protecting value. We emphasize the usefulness of informing patients carefully about transmission risks of HSV.

Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 1: Herpes simplex virus infections

Primary herpes simplex virus (HSV) infection may lead to severe illness in pregnancy and may be associated with transplacental virus transmission and fetal infection. The consequences may be abortion, stillbirth and congenital malformations. In neonates, the clinical findings after intrauterine HSV infection are characterized by skin lesions, diseases of the eye and neurologic damage. Herpes genitalis of pregnant women at the time of labor may result in life-threatening neonatal herpes. Currently, neither active nor passive immunization is available to prevent HSV infections during pregnancy and in the newborn infant. Therefore, antiviral treatment using aciclovir and/or valaciclovir must be considered in all primary episodes of genital herpes as well as in neonates who show signs of either infection. Clinical herpes lesions of the genitalia and/or positive test for virus detection at the time of delivery are an indication for cesarean section. However, this surgical intervention may be reduced by suppressive treatment of recurrent genital herpes with aciclovir or valaciclovir.

Major brain lesions by intrauterine herpes simplex virus infection: MRI contribution

The majority of neonatal Herpes Simplex Virus (HSV) infections are acquired at birth as a consequence of direct fetal contact with the infected birth canal or through an ascending infection after premature rupture of the amniotic membranes. Intrauterine transmission of HSV infection from mother to the fetus is rare; in only 5% of the cases it occurs from haematogenous transplacental dissemination. We present a case of transplacental intrauterine HSV infection after a primary maternal HSV infection in the first trimester of pregnancy. The diagnosis was assessed by viral culture and serologic tests. Ultrasound imaging revealed fetal brain damage in the third trimester. Finally, the MRI showed the devastating extensiveness of the HSV infection, which was beyond the expectation based on the ultrasound images.

O.044 Hepatitis B epidemiology and prevention: where are we in Europe in 2006

Keratin is a strong, fibrous protein that coats the skin, male genitalia and some tissues in the mouth and female genitalia. Keratin protects the host by providing a barrier against primary herpes simplex virus infection. We postulate that keratin may also hinder the host by protecting the virus from effective immune responses such as those present on mucosal surfaces, enabling recurrent lesions to preferentially develop within keratinized tissues at mucocutaneous junctions. The natural history of infection supports the importance of preventing infection in keratinized tissues for developing an effective herpes simplex virus vaccine, since potent immunity on mucosal surfaces may be inadequate to protect keratinized tissues.

The effects of aminoguanidine on primary and recurrent ocular herpes simplex virus infection

In primary ocular herpes simplex virus (HSV) infection, nitric oxide may function to control viral replication and herpetic stromal keratitis (HSK) lesions. Recurrent HSK, manifested as corneal opacity and neovascularization, is the potentially blinding sequel to primary infection. Here, we assess the effects of nitric oxide synthase inhibition on a mouse model of recurrent HSK. In preliminary primary infection experiments, NIH inbred mice treated with aminoguanidine, an inhibitor of inducible nitric oxide synthase (iNOS), experienced no changes in post-infection tear, brain, or ganglia virus titers, but encephalitis-related mortality was elevated. After UV-B stimulated viral reactivation, iNOS inhibition did not affect virus shedding or clinical disease. In contrast to primary HSK, there was no exacerbation of mortality in recurrent disease. Our findings indicate that nitric oxide can be neuroprotective without antiviral effects in primary HSK, and does not play a significant role in the pathogenesis of recurrent HSK. Compared with data from other mouse strains, this work suggests that there may be a genetic component to the importance of NO in controlling ocular HSV infection.

Herpes simplex esophagitis in the immunocompetent host

We report here a case of herpes esophagitis with Mallory-Weiss syndrome in an immunocompetent host. A 26-year-old man was admitted to our hospital because of common cold symptoms and eruptions on the body. On day 2 after hospitalization, the patient showed high-grade fever, odynophagia and hematemesis. Upper gastrointestinal endoscopic examination showed multiple ulcerations throughout the mid- and distal esophagus. Bleeding from a Mallory-Weiss tear was also seen. Follow-up endoscopic examinations showed whitish exudates on day 5. Histological examination of biopsy specimens showed Cowdry type A intranuclear inclusion bodies in epithelial cells. Positive staining of a specific antibody against herpes simplex virus-1 (HSV-1) was seen in the nuclei of esophageal epithelial cells. Primary HSV-1 infection was suspected because ELISA titers of serum IgM antibody against HSV-1 were high and titers of serum IgG antibody against HSV-1 increased from an almost cut-off ratio. A diagnosis of herpes esophagitis in an immunocompetent host was made. Our case is the first report of herpes esophagitis with Mallory-Weiss syndrome in the immunocompetent host. It is important to remind herpes esophagitis in cases of severe odynophagia even in immunocompetent hosts.

Macrophages and cytokines in the early defence against herpes simplex virus.

Herpes simplex virus (HSV) type 1 and 2 are old viruses, with a history of evolution shared with humans. Thus, it is generally well-adapted viruses, infecting many of us without doing much harm, and with the capacity to hide in our neurons for life. In rare situations, however, the primary infection becomes generalized or involves the brain.Normally, the primary HSV infection is asymptomatic, and a crucial element in the early restriction of virus replication and thus avoidance of symptoms from the infection is the concerted action of different arms of the innate immune response. An early and light struggle inhibiting some HSV replication will spare the host from the real war against huge amounts of virus later in infection. As far as such a war will jeopardize the life of the host, it will be in both interests, including the virus, to settle the conflict amicably. Some important weapons of the unspecific defence and the early strikes and beginning battle during the first days of a HSV infection are discussed in this review.Generally, macrophages are orchestrating a multitude of anti-herpetic actions during the first hours of the attack. In a first wave of responses, cytokines, primarily type I interferons (IFN) and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. In the next wave, interleukin (IL)-12 together with the above and other cytokines induce production of IFN-γ in mainly NK cells. Many positive feed-back mechanisms and synergistic interactions intensify these systems and give rise to heavy antiviral weapons such as reactive oxygen species and nitric oxide. This results in the generation of an alliance against the viral enemy.However, these heavy weapons have to be controlled to avoid too much harm to the host. By IL-4 and others, these reactions are hampered, but they are still allowed in foci of HSV replication, thus focusing the activity to only relevant sites. So, no hero does it alone. Rather, an alliance of cytokines, macrophages and other cells seems to play a central role. Implications of this for future treatment modalities are shortly considered.

Keratin, a dual role in herpes simplex virus pathogenesis

Keratin is a strong, fibrous protein that coats the skin, male genitalia and some tissues in the mouth and female genitalia. Keratin protects the host by providing a barrier against primary herpes simplex virus infection. We postulate that keratin may also hinder the host by protecting the virus from effective immune responses such as those present on mucosal surfaces, enabling recurrent lesions to preferentially develop within keratinized tissues at mucocutaneous junctions. The natural history of infection supports the importance of preventing infection in keratinized tissues for developing an effective herpes simplex virus vaccine, since potent immunity on mucosal surfaces may be inadequate to protect keratinized tissues.

Enteroviral infection mimicking primary herpetic stomatitis in four children

In autumn 2000 and 2001, four young immunocompetent children were admitted to our paediatric emergency ward for vesicular stomatitis, typical of primary herpes virus infection, and subsequently found to have a coxsackie A16-like virus. None of them had hand-foot-andmouth disease nor herpangina. Primary herpetic gingivostomatitis, herpangina or aphthous stomatitis are difficult to diagnose on the basis of oral lesions alone and virological investigations are important in this clinical context to avoid unnecessary anti-herpes treatment. We describe four herpetiform stomatitis cases due to coxsackie virus A16 (CVA-16). When they are implicated in symptomatic manifestations, enteroviruses, Picornaviridae family, cause a variety of distinctive and difficult to diagnose clinical syndromes. When they are associated with meningoencephalitis, a treatment would be important [1,5]. Virological investigations are not systematically undertaken when the central nervous system is not affected. In enteroviral infections like hand-foot-and-mouth disease, oral lesions are more consistently present than skin lesions [2]. Thus, illnesses may be mistakenly identified as herpes simplex virus (HSV) infection or aphthous stomatitis and treated accordingly (Fig. 1). Two children, aged 2 and 3 years respectively, were admitted to hospital with disseminated lesions of gingivostomatitis, deglutition pain, fever, and cervical adenopathy which led to the clinical diagnosis of primary HSV infection. Because of anorexia, intravenous acyclovir treatment and antiseptic mouth rinse were initiated. After 1 day of treatment, one patient developed some vesicles on the hands and feet, an involvement of a coxsackie virus was then assumed. The two children became apyretic 48 h later and recovered from eating difficulties. Two other patients were not admitted to hospital. They were seen in the emergency ward with fever, deglutition pain concomitant with an erosive and erythemathosous palate, gum and tongue lesions. One patient had cutaneous eruptions on the legs. A herpetic infection was suspected in both patients. A buccal mucosal sample was analysed in all four children. They all gave a cytopathic response in MRC-5 fibroblasts. Immunofluorescence examination of trypsinised cell cultures was negative with an enterovirus monoclonal antibody and with HSV-1 and HSV-2 monoclonal antibodies. All four cell cultures were, however, positive for enterovirus RNA by RT-PCR targeting the 5’ non coding region. The four cultured strains were untypeable by seroneutralisation. They were identified as CVA-16 using sequencing after another RT-PCR targeting a variable VP1–2A capsid region of the enteroviral genome [4]. Viruses are the most common causes of stomatitis, in particular the HSV (herpes gingivostomatitis), coxsackie virus (herpangina, hand-foot-and-mouth disease) and Epstein Barr virus (infectious mononucleosis). The main enteroviral cause of stomatitis and ulcerative lesions in the anterior mouth is the CVA-16, frequently in the context of hand-foot-and-mouth disease [3]. Enteroviruses and HSV are easily isolated from vesicles. For a more rapid diagnosis, molecular amplification or immunofluorescence (HSV only) can be performed. These cases highlight the importance of virological investigations in a clinical context of herpetiform stomatitis. It should help adequate management of this clinical entity avoiding intravenous acyclovir administration in case of enterovirus stomatitis. S. Vallet (&) AE M.-C. Legrand AE B. Picard Virology Laboratory, Department of Microbiology EA 3882 Biodiversity and Microbial Ecology, CHU Morvan, 2 avenue Foch, 29609 Brest Cedex, France E-mail: Sophie.Vallet@univ-brest.fr Tel.: +33-2-98223308 Fax: +33-2-98223987

Herpetic Whitlow as a Harbinger of Pediatric HIV‐1 Infection

Herpetic whitlow applies to a primary or recurrent herpes simplex infection of the fingers. It is a rare condition in immunocompetent patients, and usually has a rapid evolution and prompt response to treatment. We report a 10-year-old girl referred to our department of infectious diseases with recurrent and unresponsive ulcerated and necrotic lesions of the fingers of both hands as a first sign of human immunodeficiency virus infection. Numerous instances of extensive or recurrent herpes lesions of the mouth, lips, and perianal areas have been found in the literature, but we have not found any report of periungual infection as a first manifestation of human immunodeficiency virus infection. Pediatricians and dermatologists need to be aware of this association in order to make an early diagnosis and start treatment of these patients' disease.