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PubMed2004

Clinical trials of prophylactic and therapeutic herpes simplex virus vaccines.

Herpes simplex virus type 2 (HSV-2) is a suitable target for a vaccine, despite available antiviral therapies, because the virus causes lifelong infection and significant medical and psychosocial morbidity. A vaccine has the potential to reduce HSV acquisition, disease severity and the number of cases of neonatal herpes. It could also reduce transmission of HIV, which is epidemiologically linked to HSV. Prophylactic vaccines for HSV-2 must give broad and durable immunity across all mucosal surfaces to be effective. This is a significant challenge, as the major determinants of effective immunity have not yet been identified. Even if full protection cannot be achieved, vaccines would still be useful if they could increase the threshold of infection, or prevent clinical disease. However, it is possible that a vaccine could reduce symptomatic disease, but not eliminate asymptomatic shedding, which could inadvertently increase transmission from individuals who believe they are not infectious. Investigated prophylactic vaccines for HSV-2, including subunit vaccines encoding HSV glycoproteins packaged with adjuvants, have shown some benefits. The Chiron gD2gB2-MF59 vaccine gave transient protection of less than 6 months. The GlaxoSmithKline gD2-alum MPL vaccine conferred a 73-74% reduction in acquisition of symptomatic HSV-2 disease and a 38-42% reduction in the acquisition of HSV-2 infection in HSV-seronegative women, but gave no protection in men or HSV-1 seropositive women. Therapeutic vaccines aim to prevent HSV recurrences or minimise disease severity and duration, thereby reducing transmission. Research indicates that to be effective, therapeutic vaccines need to stimulate strong cell-mediated immune responses. Vaccines have induced HSV-specific antibody responses alone but have failed to protect recipients from recurrences. Further research is needed to define determinants of immunity to HSV-2, including identifying HSV-2 antigens, in order to design more effective vaccines.

Clinical Trials as Topic↗

PubMedDate not supplied

[Perinatal herpes simplex infection].

Neonatal herpes is a rare disease which has to be distinguished from herpes simplex virus infection later on in life. Most neonates in whom HSV infection develops have acquired the virus from the maternal genital tract during delivery. Clinical symptoms and prophylactic measures are discussed. Antiviral therapy with acyclovir is the treatment of choice and appears to improve outcome of neonatal herpes. The prognosis depends on early therapy, but the available diagnostic techniques not always allow early detection of the disease. Therefore treatment should be initiated in relation to clinical findings.

Antiviral Agents↗

PubMed2003

Intrauterine herpes simplex infection.

Neonatal herpes simplex virus (HSV) infection is usually acquired at birth. We present an infant with intrauterine HSV infection acquired after rupture of membranes. The infant was born prematurely to a woman with a first episode of genital herpetic infection in early pregnancy and rupture of membranes 11 days prior to delivery. The infant, at delivery had extensive brain damage, hemorrhage, and cystic encephalomalacia due to herpes infection. On 2nd day of life, Magnetic Resonance Imaging, suggested that the hemorrhage had occurred 7 to 14 days before the scan and the placental pathology was supportive of an ascending infection. The case of an ascending herpetic intrauterine infection after rupture of the membranes raises the question of prevention and suppressive antiviral therapy.

Abnormalities, Multiple↗

PubMed1987

Treatment of herpes simplex virus infections.

Herpes simplex virus infections cause considerable morbidity in immunocompromised and immunocompetent individuals. The development of immunomodulatory agents and nucleoside analog drugs has been responsible for important advances in the treatment of HSV infections. Acyclovir, an acyclic guanosine derivative, has played a major role in the treatment and suppression of HSV episodes in immunocompromised and immunocompetent patients.

Acyclovir↗

PubMed1992

Concomitant oculoglandular and ulceroglandular fever due to herpes simplex virus type I.

Herpes simplex virus is a commonly encountered infectious agent in clinical practice. The syndromes with which it is usually associated are well described and generally easily recognized. This report documents that two uncommon clinical syndromes, ulceroglandular fever and oculoglandular fever, may be caused by this virus. Our patient's case was even more unusual in that both conditions occurred simultaneously.

Adolescent↗

PubMed1991

Acute confusion--an unusual form of cerebral herpes simplex virus infection?

Herpes simplex virus (HSV) infections are common and, if afflicting the central nervous system, may cause death or severe sequelae. Since specific therapy is now available there is an increasing demand for the recognition of the various ways in which cerebral HSV-infections may be manifested. This report describes a 15-year-old boy who presented acutely with mental symptoms of confusion, hallucinations and sleep disturbance. Simultaneously, but without any increase in cerebrospinal fluid cell or protein content, an intrathecal production of HSV-antibodies of transient nature was detected. These findings suggest that the patient may have suffered from an unusual form of herpes infection in the central nervous system. We suggest that similar cases should be thoroughly explored for possible herpes etiology as early as possible during the acute phase of the disease.

Adolescent↗

PubMed2003

Herpes simplex virus latency.

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are ubiquitous human pathogens. They share with other herpesviruses the ability to establish lifelong latent infection of the host. Periodic reactivation from latency is responsible for most of the clinical disease burden of HSV infection. This review focuses on what we have learned from molecular studies in model systems of HSV latency, and the implications these findings have for treating recurrent HSV disease.

Antiviral Agents↗

PubMed1991

Reversible decrease of fluoride resistant acid phosphatase-positive neurons after herpes simplex virus infection.

Herpes simplex virus (HSV) frequently infects human sensory ganglion neurons, and similar infections have been reported in experimental animals. Reported here is an investigation of in vivo neuronal function after HSV infection. It was observed that the proportion of fluoride resistant acid phosphatase (FRAP)-positive trigeminal ganglion neurons was decreased for several months after experimental infection of mice, and it is suggested that other neuronal functions may also be altered by HSV.

Acid Phosphatase↗

PubMed2004

Treatment of herpes simplex virus infections.

Herpes simplex virus (HSV) types 1 and 2 are ubiquitous organisms that cause infections in human populations throughout the world. The clinical manifestations of HSV infections are varied, ranging from asymptomatic disease to life-threatening illness in neonates and immunocompromised hosts. This article will review the common presentations for HSV disease and the current recommendations for the treatment of these infections. A detailed summary of the antiviral drugs used to treat HSV infections is also presented.

Antiviral Agents↗

PubMed1985

Cultured human neural cells accumulate a heat-shock protein during acute herpes simplex virus infection.

Herpes simplex virus-1 (HSV-1) infection of cultured human neural cells causes the accumulation of a host cell-encoded nuclear protein identified as a 57,000 mol.wt. stress protein by monoclonal antibody TI56. This protein is cell cycle-related in fibroblast, may mediate host cell control during HSV infection and could play a role in the regulation of HSV latency.

Antibodies, Monoclonal↗

PubMed2001

Herpes simplex virus infections.

Herpes simplex virus (HSV) is a member of the herpesviridae family. Recognised since ancient Greek times, the virus frequently infects human beings, causing a range of diseases from mild uncomplicated mucocutaneous infection to those that are life threatening. In the past 50 years, substantial advances in our knowledge of the molecular biology of HSV have led to insights into disease pathogenesis and management. This review provides a contemporary interpretation of the biological properties, function, epidemiology, and treatment of HSV diseases.

Antiviral Agents↗

PubMed2001

Optimisation of DNA vaccines for the prophylaxis and modulation of herpes simplex virus infections.

Herpes simplex virus (HSV) lacks an effective vaccine. Despite its prevalence and importance HSV infection is not controlled with an acceptable vaccine. Perhaps the best candidate and so far untested approach is the use of plasmid DNA encoding viral proteins. Immunomodulators are also holding some hope as a potential therapeutic. In this review various DNA vaccine approaches used in animal model systems to prevent HSV infections are discussed. Judgements are made as to which of these may prove effective for prophylactic or therapeutic vaccines in humans.

Adjuvants, Immunologic↗

PubMed1998

Epstein-Barr virus DNA in cerebrospinal fluid from an immunocompetent man with herpes simplex virus encephalitis.

Herpes simplex virus 1 meningo-encephalitis was ascertained in a 63-year-old immunocompetent man. To determine the duration of the persistence of herpesvirus DNA in the central nervous system, the cerebrospinal fluid was periodically monitored by polymerase chain reaction for 53 days. In addition to HSV-1, Epstein-Barr virus DNA was detected in the cerebrospinal fluid 9 days after disease onset. The possible meaning of the Epstein-Barr virus DNA finding is discussed.

DNA, Viral↗

PubMed2001

Management of neonatal herpes simplex virus infection.

Herpes simplex viruses (HSV) are ubiquitous pathogens which can be transmitted vertically causing significant morbidity and mortality in neonates. Neonatal HSV infection is infrequent with an incidence ranging from 1 in 3,500 to 1 in 20,000, depending on the population. Neonatal HSV infection is much more frequent in infants born to mothers experiencing a primary HSV infection with an incidence approaching 50%, while infants born to mothers experiencing recurrent HSV infection have an incidence of less than 3%. Neonatal infections are clinically categorised according to the extent of the disease. They are: (i) skin, eye and mouth (SEM) infections; (ii) central nervous system infection (encephalitis)--neonatal encephalitis can include SEM infections; and (iii) disseminated infection involving several organs, including the liver, lung, skin and/or adrenals. The central nervous system may also be involved in disseminated infections. Caesarean section, where the amniotic membranes are intact or have been ruptured for less than 4 hours, is recommended for those women who have clinical evidence of active herpes lesions on the cervix or vulva at the time of labour. This procedure significantly decreases the risk of transmission to the infant. Diagnosis of neonatal infection requires a very high level of clinical awareness as only a minority of mothers will have a history of genital HSV infection even though they are infected. Careful physical examination and appropriate investigations of the infant should accurately identify the infection in the majority of cases. Treatment is recommended where diagnosis is confirmed or there is a high level of suspicion. The current recommendation for treatment is aciclovir 20 mg/kg 3 times daily by intravenous infusion. Careful monitoring of hydration and renal function as well as meticulous supportive care of a very sick infant is also required. The newer anti-herpes agents, valaciclovir and famciclovir, offer no advantage over aciclovir and are not recommended for neonatal HSV infection. Prognosis is dependent upon the extent of disease and the efficacy of treatment, with highest rates of morbidity and mortality in disseminated infections, followed by central nervous system infection and the least in SEM infection. However, SEM infection is associated with poor developmental outcome even in infants who do not have encephalitis. Studies to improve the outcome of SEM infection are in progress. Neonatal HSV infections, although being relatively uncommon, are associated with significant morbidity and mortality if unrecognised and specific treatment is delayed. Diagnosis relies on a high level of clinical suspicion and appropriate investigation. With early therapy, the prognosis for this infection is considerably improved.

Acyclovir↗

PubMed2004

The Toll of herpes simplex virus infection.

Herpes simplex virus (HSV) infections provoke an inflammatory cytokine response, but the innate pathogen-sensing mechanisms that transduce the signal for this response are poorly understood. Recent findings have revealed that Toll-like receptor (TLR) 2 initiates the inflammatory process, and surprisingly that the response the TLR triggers might be overzealous in its attempt to counter the attack by the virus. Other recent findings suggest complexity in the array of TLRs that are triggered by HSV and the cell types they activate. Here we discuss the new revelations about these guardians against HSV infection and the consequences of the alarms raised in the host that they are assigned to protect.

Animals↗

PubMed1999

[Recurrence of herpes simplex encephalitis].

UNLABELLED: Herpes simplex encephalitis (HSE) rarely occurs in children, is not easily diagnosed, and has a poor prognosis. CASE REPORT: We report a pediatric case with a relapse on the 29th day despite conventional acyclovir therapy. As the relapse mechanism is not clearly understood, antiviral and immunosuppressive therapy was administered. CONCLUSION: This case underlines the importance of clinical examination and the necessity of accurate testing prior stopping antiviral treatment. A better understanding of the relapse mechanism is required in order to propose more efficient treatment.

Acyclovir↗

PubMed1988

Antiviral treatment of a serious herpes simplex infection: encephalitis.

Herpes simplex encephalitis is the most common cause of sporadic encephalitis in the western world. Patients usually have altered levels of consciousness, altered levels of mentation, fever, headache, and personality changes. These may progress to hemiparesis and seizures. Exact diagnosis must be established by brain biopsy and identification of the virus in biopsy material. There is a great need for a noninvasive test that is positive early in the disease. Without antiviral treatment the mortality rate is greater than 70%, and many survivors have serious disabilities. Both adenine arabinoside and acyclovir decrease death and morbidity, but acyclovir is the preferred drug. With acyclovir about 40% of patients will survive with normal development or minor levels of impairment but more than half of the patients will die or suffer significant impairment. It is essential to treat early; patients who are young and have not reached coma or impaired consciousness may show 65% recovery and return to normal function. Development of new antiviral drugs or other types of therapies is desirable. Herpetic skin lesions are likely to be more confusing than diagnostic because other types of encephalitis with fever often precipitate recurrent herpes that is unrelated to the encephalitis.

Acyclovir↗

PubMed2002

Clinical manifestations and treatment considerations of herpes simplex virus infection.

Herpes simplex viruses (HSV) types 1 and 2 cause infections manifesting as dermatologic, immunologic, and neurologic disorders. Some of the most important manifestations and complications of HSV infection are considered here in a neuroanatomic context. This discussion should aid in understanding the pathogenesis and, in some cases, diagnosis and management of associated HSV-related diseases. The sensory nervous system, rather than skin and mucous membranes, is the primary target of HSV infection. With the intention of extending the benefits of acyclovir, valacyclovir is now being explored in a number of HSV-related conditions. This review extends contemporary thinking about how new antiherpetic drugs might be put to greater therapeutic use in the future.

Antiviral Agents↗