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Latest Research on Herpes
     
Sex Transm Dis. 2008 Apr;35(4):383-386.
One-Day Regimen of Valacyclovir for Treatment of Recurrent Genital Herpes Simplex Virus 2 Infection.
Bavaro JB, Drolette L, Koelle DM, Almekinder J, Warren T, Tyring S, Wald A.
From the Departments of Medicine, Laboratory Medicine, and Epidemiology, University of Washington, Seattle, Washington; §GlaxoSmithKline, Research Triangle Park, North Carolina; Westover Heights Clinic, Portland, Oregon; Departments of Dermatology, Microbiology and Molecular Genetics, and Internal Medicine, University of Texas Health Science Center, Houston, Texas.

OBJECTIVES:: To evaluate the efficacy of a 1-day course of valacyclovir in reducing the duration and severity of genital herpes recurrences and to measure the frequency of viral shedding episodes subsequent to antiviral therapy. STUDY DESIGN:: In an open-label pilot study, patients with recurrent genital herpes simplex virus 2 (HSV-2) infection were given a 1-day course of valacyclovir (2000 mg given by mouth twice daily) to be taken at the first sign of recurrence or prodrome. Participants maintained diaries of signs and symptoms and collected genital swabs for viral culture while lesions persisted and HSV DNA PCR for 14 days after initiating treatment. RESULTS:: Ninety (78%; 41 men, 49 women) of the 115 enrolled persons experienced either a lesional recurrence or prodrome. Seventy- seven (86%) participants developed lesions; 4 (5%) participants experienced a second lesional recurrence during the 14-day study period. The median lesion duration was 5 days, episode duration was 5 days, and pain duration was 3 days. Viral shedding was detected in 60 persons by PCR and 31 persons by culture. Shedding detected by culture lasted for a median of 2 days, and shedding detected by PCR lasted for a median of 3 days. Of 60 participants with viral shedding, 14 (23%) had an additional shedding episode after their initial lesion healed, lasting for a median of 2 days. CONCLUSIONS:: A 1-day course of valacyclovir may be a convenient treatment for recurrent genital herpes and comparative trials are warranted.

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Sex Health. 2008 Mar;5(1):1-8.
Condoms for sexually transmissible infection prevention: politics versus science.
Mindel A, Sawleshwarkar S.
Sexually Transmitted Infections Research Centre, Marian Villa, Westmead Hospital and University of Sydney, Westmead, NSW 2145, Australia.

The present review assesses the protection that condoms offer against sexually transmissible infections (STI) and the impact that social, political and religious opinion in the USA has had in the past 8 years on promoting condoms for safer sex. Condoms offer protection against most STI. However, the degree of protection depends on correct and consistent use, the type of sexual activity and the biological characteristics of different infections. Cross-sectional and case-control studies and other observational data provide the majority of evidence for STI prevention. Condoms provide a high level of protection against those infections that are transmitted mainly via infected secretions, including HIV, gonorrhoea, chlamydia and trichomoniasis. Protection against those infections transmitted via skin and mucous membrane contact, including Herpes simplex virus infection and human papilloma virus, appears to be less. The Bush administration, driven by conservative political, social and religious elements in the USA, has mounted a concerted campaign to undermine the role of the condom in health-promotion activities in the USA and overseas by undervaluing and misrepresenting scientific data, and through a sustained and well-funded promotion of abstinence-only education. However, this has lead to considerable controversy and disillusionment with abstinence-only education, both at home and abroad, and there is now incontrovertible evidence that abstinence-only programs are ineffectual.

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Pediatr Infect Dis J. 2008 Mar 20 [Epub ahead of print]
Clinical and Laboratory Features of Neonatal Herpes Simplex Virus Infection: A Case-Control Study.
Caviness AC, Demmler GJ, Selwyn BJ.
From the Sections of *Pediatric Emergency Medicine and †Infectious Diseases, Department of Pediatrics, Baylor College of Medicine; ‡Diagnostic Virology Laboratory, Texas Children's Hospital; and §University of Texas School of Public Health, Houston, TX.

BACKGROUND:: Neonatal herpes simplex virus (HSV) infection can cause significant morbidity and mortality but can be difficult to identify, particularly in neonates without vesicular rash. OBJECTIVE:: 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. METHODS:: 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. RESULTS:: 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. CONCLUSIONS:: 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.

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Can Fam Physician. 2008 Mar;54(3):373-7.
Treatment of herpes zoster.
Opstelten W, Eekhof J, Neven AK, Verheij T.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. W.Opstelten@umcutrecht.nl

OBJECTIVE: To review the evidence regarding treatment of herpes zoster (HZ) in the short-term, focusing on the prevention of postherpetic neuralgia (PHN). QUALITY OF EVIDENCE: The evidence relating to treatment of HZ is derived mainly from randomized controlled trials (level I evidence). MAIN MESSAGE: Antiviral drugs might have some effect on the severity of acute pain and on the duration of skin lesions. Corticosteroids also alleviate acute pain. Oral antiviral medication reduces the risk of eye complications in patients with ophthalmic HZ. There is no convincing evidence that antiviral medication reduces the risk of PHN. Some studies, however, have shown that famciclovir and valacyclovir shorten the duration of PHN. The effectiveness of amitriptyline or cutaneous and percutaneous interventions in preventing PHN has not been proven. CONCLUSION: Oral antiviral drugs should be prescribed to elderly HZ patients with high risk of PHN. Moreover, these drugs should be prescribed to all patients at the first signs of ophthalmic HZ, irrespective of age or severity of symptoms.

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Ophthalmology. 2008 Feb;115(2 Suppl):S35-8.
Preventing herpes zoster through vaccination.
Gelb LD.
Division of Infectious Disease, Washington University School of Medicine, Department of Internal Medicine, Barnes-Jewish Medical Center, St. Louis, Missouri 63110, USA. ldgelb@swbell.net

TOPIC: The role of the zoster vaccine in the prevention of herpes zoster and its sequelae, including postherpetic neuralgia (PHN) and herpes zoster ophthalmicus. CLINICAL RELEVANCE: Wide administration of the herpes zoster vaccine in accordance with the recommendations of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) will lead to a decline in the incidence and morbidity of herpes zoster and its complications, including PHN. METHODS: The key study leading to the approval of the zoster vaccine for use, the Centers for Disease Control and Prevention ACIP's recommendations for appropriate use of the zoster vaccine, and predictions regarding the cost efficacy of a zoster vaccination program are reviewed. RESULTS: The Shingles Prevention Study established that the zoster vaccine was safe, well tolerated, and effective in reducing the burden of illness due to herpes zoster and the incidence of PHN. The ACIP recommended that the zoster vaccine be given to adults 60 and older for the prevention of herpes zoster. Cost-efficacy analyses suggest that the greatest gain in quality-adjusted life-years can be gained by vaccinating individuals at the younger end of the ACIP-recommended age range. CONCLUSION: The zoster vaccine promises to reduce the morbidity and mortality of herpes zoster. Administering the vaccine at the younger end of the age range may offer a greater cost benefit.

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Ophthalmology. 2008 Feb;115(2 Suppl):S3-12.
Herpes zoster ophthalmicus natural history, risk factors, clinical presentation, and morbidity.
Liesegang TJ.
Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA. tliesegang@mayo.edu

TOPIC: The incidence and morbidity of herpes zoster (HZ) and HZ ophthalmicus (HZO), and the potential impact of varicella vaccine on their epidemiology. CLINICAL RELEVANCE: Herpes zoster affects 20% to 30% of the population at some point in their lifetime; approximately 10% to 20% of these individuals will have HZO. METHODS: The peer-reviewed literature published from 1865 to the present was reviewed. RESULTS: Herpes zoster is the second clinical manifestation of varicella-zoster virus (VZV). The incidence and severity of HZ increase with advancing age. Varicella-zoster virus-specific cell-mediated immunity, which keeps latent VZV in check and is boosted by periodic reexposure to VZV, is an important mechanism in preventing VZV reactivation as zoster. Thus, widespread varicella vaccination may change the epidemiology of HZ. Herpes zoster ophthalmicus occurs when HZ presents in the ophthalmic division of the fifth cranial nerve. Ocular involvement occurs in approximately 50% of HZ patients without the use of antiviral therapy. There is a long list of complications from HZ, including those that involve the optic nerve and retina in HZO, but the most frequent and debilitating complication of HZ regardless of dermatomal distribution is postherpetic neuralgia (PHN), a neuropathic pain syndrome that persists or develops after the zoster rash has resolved. The main risk factor for PHN is advancing age; other risk factors include severe acute zoster pain and rash, a painful prodrome, and ocular involvement. Many cases of HZ, HZO, and PHN can be prevented with the zoster vaccine. CONCLUSION: Vaccination is key to preventing HZ, HZO, and PHN, but strategies for both varicella and HZ vaccines will need to be evaluated and adjusted periodically as changes in the epidemiology of these VZV diseases become more evident.

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Ophthalmology. 2008 Feb;115(2 Suppl):S13-20.
Herpes zoster antivirals and pain management.
Pavan-Langston D.
Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA. deborah.langston@meei.harvard.edu

TOPIC: Evaluation of evidence-based strategies for managing herpes zoster (HZ) and the pain of postherpetic neuralgia (PHN). CLINICAL RELEVANCE: Approximately 20% of the world's population suffers from herpes zoster at least once in a lifetime, with 10% to 20% having ophthalmic involvement. Treatment of the acute disease with oral antivirals may reduce the incidence and severity of complications but does not reliably prevent PHN or postherpetic itch (PHI). The acute pain abates as the acute phase resolves; the long-term pain of PHN or PHI may be severe and difficult to manage. Although many therapeutic agents have efficacy in the management of these complications, relief is frequently partial for months to the remainder of the lifetime. METHODS: Literature review was performed using the resources of the Harvard Medical School/Massachusetts Eye and Ear Infirmary Ophthalmic library as well as the National Library of Medicine and the National Institutes of Health PubMed service searching by pertinent topics, authors, and journals. RESULTS: If started within 72 hours of the onset of the acute HZ rash, the oral antiviral agents acyclovir, valacyclovir, and famciclovir significantly shorten the periods of acute pain, virus shedding, rash, acute and late-onset anterior segment complications, and, in the case of valacyclovir and famciclovir, the incidence and severity of PHN. However, these medications do not prevent PHN, which remains a common and debilitating complication of HZ in older patients, requiring assiduous pain management. Tricyclic antidepressants, antiseizure drugs, opioids, and topical analgesics all offer some pain relief, and may be combined. CONCLUSION: Options are available to manage HZ and reduce the pain of PHN. However, prevention, now possible with the HZ vaccine, is preferable to treatment.

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Nat Clin Pract Neurol. 2008 Feb;4(2):97-104.
Drug Insight: steroids in CNS infectious diseases—new indications for an old therapy.
Fitch MT, van de Beek D.
Department of Neurology, Center of Infection and Immunity Amsterdam, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.

Infectious diseases of the CNS lead to overwhelming inflammatory processes within the brain and spinal cord that contribute substantially to patient morbidity and mortality. Pharmacological strategies to modulate inflammation have been investigated, although the resulting guidelines have sometimes been contradictory. Steroids have been proposed as adjunctive treatments for bacterial meningitis, tuberculous meningitis and herpes simplex virus encephalitis. Well-designed randomized controlled trials have established dexamethasone as an adjunctive therapy for adult patients receiving antibiotics for bacterial meningitis, and physicians prescribing the initial antibiotics need to be aware of current guidelines. Morbidity and mortality in patients with tuberculous meningitis exceeds 50%. Steroid treatments reduce mortality through an as yet unknown mechanism, although their effects on morbidity are less clear. Herpes simplex virus encephalitis is also associated with considerable morbidity and mortality. Despite a lack of randomized trials, there is some evidence that steroids used alongside antiviral therapy might be beneficial in this condition. As we discuss in this Review, systemic steroid treatment is an important aspect of treatment regimens for CNS infectious diseases, and the recent literature provides guidelines for the use of steroids in combination with appropriate antimicrobial therapy.

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Pediatrics. 2008 Jan;121(1):e150-e156. Epub 2007 Dec 17.
Primary Varicella and Herpes Zoster Among HIV-Infected Children From 1989 to 2006.
Wood SM, Shah SS, Steenhoff AP, Rutstein RM.
Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Room 2419, Philadelphia, PA 19104. rutstein@email.chop.edu.

OBJECTIVES. The primary objective of this study was to determine the incidence of herpes zoster in perinatally HIV-infected children. Secondary objectives included assessing the impact of highly active antiretroviral therapy and varicella zoster virus immunization on primary varicella and herpes zoster incidence and identifying risk factors for herpes zoster. We hypothesized that the incidence of herpes zoster has decreased in this population as a result of highly active antiretroviral therapy and routine varicella zoster virus immunization. PATIENTS AND METHODS. This retrospective cohort study included HIV-infected children at a pediatric HIV clinic from 1989 to 2006. Incidence rates for 3 intervals (1989-1996, 1997-1999, and 2000-2006) were compared on the basis of introduction of highly active antiretroviral therapy (1996) and varicella zoster virus vaccination (1999). A Cox proportional-hazards regression model was developed for the time to herpes zoster among the subset of patients with primary varicella infection. RESULTS. In 356 patients followed for 1721 person-years, the incidence of herpes zoster according to period was 30.0 per 1000 person-years in 1989-1996, 31.9 per 1000 person-years in 1997-1999, and 6.5 per 1000 person-years in 2000-2006. There was no difference in incidence-rate ratio between 1989-1996 and 1997-1999. However, there was a significant difference in herpes zoster incidence when comparing 1989-1999 with 2000-2006. The incidence of primary varicella zoster virus infection and herpes zoster in the 57 patients who received the varicella zoster virus vaccine was 22.3 per 1000 and 4.5 per 1000 person-years, respectively. Highly active antiretroviral therapy at the time of primary varicella zoster virus infection was protective against herpes zoster and increased herpes zoster-free survival. CONCLUSIONS. The incidence of herpes zoster has decreased since 1989. The decline occurred after 2000, likely representing the combined effect of immunization and highly active antiretroviral therapy. The use of highly active antiretroviral therapy at the time of primary varicella zoster virus infection decreased the risk of herpes zoster and increased herpes zoster-free survival. Varicella zoster virus immunization was effective in preventing both primary varicella zoster virus and herpes zoster in this cohort.

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Sex Transm Dis. 2007 Dec 20 [Epub ahead of print]
The Effect of Daily Valacyclovir Suppression on Herpes Simplex Virus Type 2 Viral Shedding in HSV-2 Seropositive Subjects Without a History of Genital Herpes.
Sperling RS, Fife KH, Warren TJ, Dix LP, Brennan CA.
From the *Mount Sinai Medical Center, New York City, New York; †Indiana University, School of Medicine, Indianapolis, Indiana; ‡Westover Heights Clinic, Portland, Oregon; and §GlaxoSmithKline, Research Triangle Park, North Carolina.

BACKGROUND:: A substantial number of HSV-2 seropositive individuals lack a history of clinically recognized genital herpes. These individuals can transmit disease during periods of asymptomatic viral shedding. The frequency of asymptomatic shedding and the efficacy of antiviral therapy in reducing shedding has not been assessed in this population. OBJECTIVE:: To compare the effect of valacyclovir 1 g once daily for 60 days versus placebo on asymptomatic viral shedding in immunocompetent, HSV-2 seropositive subjects without a history of symptomatic genital herpes infection. STUDY DESIGN:: Seventy-three subjects were randomized to receive valacyclovir 1 g daily or placebo for 60 days each in a 2-way crossover design. A daily swab of the genital area was self-collected for HSV-2 detection by polymerase chain reaction. RESULTS:: Fifty-six subjects with at least 1 polymerase chain reaction measurement in both treatment periods comprised the primary efficacy population. Valacyclovir significantly reduced shedding during subclinical days compared to placebo [mean, 1.5% vs. 5.1% of subclinical days (P <0.001), a 71% reduction]. Eighty-four percent of subjects had no shedding while receiving valacyclovir versus 54% of subjects on placebo (P <0.001). Eighty-eight percent of patients receiving valacyclovir had no recognized signs or symptoms versus 77% for placebo (P = 0.033). Valacyclovir was not associated with any safety risk compared with placebo. CONCLUSIONS:: In this study, asymptomatic viral shedding occurred in a substantial number of HSV-2 seropositive subjects without a history of genital herpes. Valacyclovir 1 g daily significantly reduced asymptomatic shedding compared with placebo in this population.

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J Am Acad Dermatol. 2007 Dec;57(6 Suppl):S143-7.
Vaccination strategies for the prevention of herpes zoster and postherpetic neuralgia.
Betts RF.
Infectious Diseases Unit, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA. robert_betts@urmc.rochester.edu

Herpes zoster disease and its most common complication, postherpetic neuralgia, are associated with significant morbidity in the elderly. The zoster vaccine boosts cell-mediated immunity to varicella-zoster virus, the virus that causes both varicella and herpes zoster. This vaccine has demonstrated the ability to reduce the zoster-related burden of illness and the incidence of both zoster and postherpetic neuralgia in a randomized, controlled trial conducted in individuals aged 60 years and older, an age group at increased risk of herpes zoster. Widespread use of this vaccine could prevent as many as a quarter of a million cases of zoster disease each year. The design and outcomes of the Shingles Prevention Study, which examined the efficacy and safety of the vaccine, and the rationale for widespread immunization against varicella-zoster virus, are presented here.

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J Am Acad Dermatol. 2007 Dec;57(6 Suppl):S136-42.
Management of herpes zoster and postherpetic neuralgia.
Tyring SK.
Department of Dermatology, The University of Texas, Houston, Texas, USA. styring@ccstexas.com

Patients with herpes zoster experience severe pain and potential lasting complications such as postherpetic neuralgia, ophthalmic disease/damage, and, rarely, skin complications (eg, infection of rash area). Treatment for acute zoster aims to accelerate healing, control pain, and, when possible, reduce the risk of complications. Early intervention with antivirals can accelerate rash healing, reduce rash severity, and reduce the risk of some complications. The addition of corticosteroids to antiviral medication may further alleviate short-term zoster pain, but is associated with an increased risk of serious adverse effects, especially among older adults. If a patient does develop postherpetic neuralgia, gabapentin, pregabalin, opioids, tricyclic antidepressants, lidocaine patch 5%, and capsaicin may all be considered as palliative treatments. For individuals with treatment-refractory postherpetic neuralgia, nonpharmacologic approaches may be considered and a pain-management specialist should be consulted. There is a need for more effective agents to treat herpes zoster and postherpetic neuralgia.

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J Am Acad Dermatol. 2007 Dec;57(6 Suppl):S130-5.
Herpes zoster: epidemiology, natural history, and common complications.
Weinberg JM.
Clinical Research Center, Department of Dermatology, St. Luke's-Roosevelt Hospital Center, and Columbia University College of Physicians and Surgeons, New York, New York 10025, USA. jmw27@columbia.edu

Herpes zoster is a disease associated with aging that can significantly impair quality of life for affected individuals. Anyone infected with varicella (chickenpox) virus in childhood is at risk for reactivation of dormant virus and the onset of zoster disease, although it occurs with increasing frequency in the elderly as a result of waning of cell-mediated immunity. The most common complication of herpes zoster is postherpetic neuralgia, which can cause chronic and debilitating pain. Current treatments can decrease the severity of zoster rash and pain but cannot prevent disease onset or completely eliminate the most frequent symptoms. The zoster vaccine may help prevent the onset of herpes zoster in the target population of those age 60 years and older. This summary reviews the epidemiology, pathogenesis, natural history, and common symptoms of zoster disease.

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Ann Otolaryngol Chir Cervicofac. 2007 Oct;124 Suppl 1:S74-83.
[Pain associated with craniofacial and cervical herpes zoster]
[Article in French]
George B, Lory C.
Service d'anesthésie-réanimation chirurgicale, unité d'évaluation et de traitement de la douleur, hôpital Saint-Louis, 75010 Paris, France.

Ophthalmological and cervical involvement of herpes zoster virus ranks second and third, respectively, in terms of localization frequency. Involvement of the cranial nerves is a particular sign of complications, notably ocular complications, possibly compromising the visual or facial prognosis through involvement of the VIIth nerve, which is responsible for facial paralysis. These types of involvement should be rapidly diagnosed and treated so as to limit these complications. The pain associated with herpes zoster remains frequent and difficult to treat, even if today the criteria for defining postzoster pain is increasingly refined. Antalgic and antiviral treatment should be initiated early, from the very first signs, to attempt to reduce the incidence of this postzoster pain. The risk factors, associated with the development of postzoster pain are age over 50 years, the severity of the skin rash and the intensity of the acute pain, and the existence of a prodromic pain phase before onset. The European Federation of Neurological Societies has recently published guidelines on the pharmacological treatments for postzoster pain. Nerve block treatments remain at a limited evidence level. Patients with postzoster pain should be managed by teams specializing in pain management as soon as conventional treatments fail.

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Herpes. 2007 Sep;14 Suppl 2:45-7.
Prevention strategies: herpes zoster, post-herpetic neuralgia and immunogenicity.
Levin MJ, Schmader K.
Section of Pediatric Infectious Diseases, Department of Pediatrics, University of Colorado School of Medicine, Denver, CO 80262, USA. myron.levin@uchsc.edu

Herpes zoster is a common condition that can have a significant impact on quality of life among older adults. A significant proportion of older subjects with herpes zoster develop post-herpetic neuralgia (PHN), a chronic condition that is difficult to treat. The Shingles Prevention Study was a large-scale clinical trial to determine the efficacy of a live, attenuated varicella zoster virus (VZV) vaccine ('zoster vaccine') for preventing or attenuating herpes zoster in subjects aged > or =60 years. A total of 38 546 subjects were given either zoster vaccine or placebo. The burden of illness (pain severity-by-duration), incidence of herpes zoster, and PHN decreased by 61.1%, 51.3% and 66.5% (all P<0.001), respectively, following vaccination. Vaccine efficacy was maintained for a 4-year follow-up period. A sub-study of the vaccine trial evaluated VZV-specific immunity in approximately 1200 vaccine or placebo recipients prior to vaccination, at 3 months and annually for 3 years. VZV-specific cell-mediated immunity (CMI) was boosted significantly by the zoster vaccine. This boost remained substantially intact for the 3 years of follow-up. It is likely that the vaccine-induced boost in VZV-specific CMI reversed the natural decline in these responses that occurs as part of the ageing process, thereby protecting vaccine recipients against herpes zoster and its complications.

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Liver Transpl. 2007 Sep 27;13(10):1428-1434 [Epub ahead of print]
Herpes simplex virus hepatitis: An analysis of the published literature and institutional cases.
Norvell JP, Blei AT, Jovanovic BD, Levitsky J.
Department of Internal Medicine, Division of Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL.

Hepatitis is a rare complication of herpes simplex virus (HSV), often leading to acute liver failure (ALF), liver transplantation (LT), and/or death. Our aim was to identify variables associated with either survival or progression (death/LT), based on an analysis of cases in the literature and our institution. A total of 137 cases (132 literature, 5 institutional) of HSV hepatitis were identified. The main features at clinical presentation were fever (98%), coagulopathy (84%), and encephalopathy (80%). Rash was seen in less than half of patients. Most cases (58%) were first diagnosed at autopsy and the diagnosis was suspected clinically prior to tissue confirmation in only 23%. Overall, 74% of cases progressed to death or LT, with 51% in acyclovir-treated patients as compared to 88% in the untreated subjects (P = 0.03). Variables on presentation associated with death or need for LT compared to spontaneous survival: male gender, age >40 yr, immunocompromised state, ALT >5,000 U/L, platelet count <75 x 10(3)/L, coagulopathy, encephalopathy, and absence of antiviral therapy. In conclusion, HSV hepatitis has a high mortality and is often clinically unsuspected. Patients who are male, older, immunocompromised, and/or presenting with significant liver dysfunction are more likely to progress to death and should thus be evaluated for LT early. Based on the frequent delay in HSV diagnosis, low risk-benefit ratio, and significantly improved outcomes, empiric acyclovir therapy for patients presenting with ALF of unknown etiology is recommended until HSV hepatitis is excluded. Liver Transpl 13:1428-1434, 2007. (c) 2007 AASLD.

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Cornea. 2007 Sep;26(8):930-4.
Effect of prophylactic oral acyclovir after penetrating keratoplasty for herpes simplex keratitis.
Garcia DD, Farjo Q, Musch DC, Sugar A.
Henry Ford Health System, Livonia, MI, USA.

PURPOSE: To determine the effect of routine use of prophylactic oral acyclovir after penetrating keratoplasty (PK) for herpes simplex virus (HSV) keratitis on recurrence, rejection, and graft failure rates. METHODS: Records from 70 consecutive patients who underwent PK for HSV keratitis at the W.K. Kellogg Eye Center between August 1, 1990, and December 31, 2000, were reviewed. Data collected included preoperative disease activity, duration, host vascularity, pre- and postoperative vision, and antiviral use. Particular attention was given to all episodes of HSV recurrence, graft rejection, and failure. RESULTS: Fifty-six patients (80%) were treated with prophylactic oral acyclovir after surgery. This cohort experienced fewer episodes of rejection (P = 0.006) and better overall graft survival (P = 0.04) than those who were not treated with prophylactic oral antivirals. There was no statistically significant difference in recurrence-free survival between the 2 groups (P = 0.22). Cox regression analysis failed to identify any single variable as a statistically significant predictor of recurrence, rejection, or graft failure. CONCLUSIONS: Prophylactic oral acyclovir use after PK for HSV keratitis is associated with decreased episodes of rejection and improved graft survival.

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Cutis. 2007 Jul;80(1):77-81.
Famciclovir for cutaneous herpesvirus infections: an update and review of new single-day dosing indications.
Chacko M, Weinberg JM.
Department of Dermatology, St. Luke's-Roosevelt Hospital Center, 1090 Amsterdam Ave, New York, NY 10025, USA.

Infections with herpes simplex virus (HSV) types 1 and 2 and herpes zoster are common and a substantial public health issue. Famciclovir is an effective treatment for herpes simplex and herpes zoster. We review studies evaluating the efficacy of single-day doses of famciclovir for the treatment of recurrent herpes labialis (cold sores) and genital herpes. Famciclovir has received single-day dosing indications for both of these entities. The studies leading to these new indications are reviewed.

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Am Fam Physician. 2007 Jul 15;76(2):265-70. Summary for patients in:
Am Fam Physician. 2007 Jul 15;76(2):272.
Screening and treatment for sexually transmitted infections in pregnancy.
Majeroni BA, Ukkadam S.
School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA. bamajeroni@aol.com

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.

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Herpes. 2007 Jun;14 Suppl 1:13A-18A.
An update on short-course intermittent and prevention therapies for herpes labialis.
Gilbert S, Corey L, Cunningham A, Malkin JE, Stanberry L, Whitley R, Spruance S.
Dermatology and Laser Center Northwest, Bellingham, WA 98225, USA. scgilbert@hinet.org

Infection with herpes simplex virus (HSV) has increased in prevalence worldwide over the past two decades, making it a major public health concern. Approximately 90% of recurrent HSV type 1 (HSV-1) infections manifest as non-genital disease, primarily as orofacial lesions known as herpes labialis. Improvements in our understanding of the natural history of herpes labialis support the rationale for early treatment (during the prodrome or erythema stages) with high doses of antiviral agents in order to maximize drug benefit. When evaluating the efficacy of different antiviral and anti-inflammatory agents in clinical trials, episode duration, lesion healing time, reduction in maximum lesion size and the proportion of aborted lesions should be used as the most reliable measures of therapeutic efficacy. There has also been considerable research into the most beneficial treatment for recurrent episodes of herpes labialis in immunocompetent individuals. Data from clinical studies confirm that short-course, high-dose oral antiviral therapy should be offered to patients with recurrent herpes labialis to accelerate healing, reduce pain and most likely increase treatment adherence. Optimal benefits may be obtained when these oral antiviral agents are combined with topical corticosteroids, but more research is needed with this combination. Patients undergoing facial cosmetic procedures (i.e.facial resurfacing) are at risk of HSV reactivation, but further data are required on the actual risk according to the specific procedure. Aciclovir, valaciclovir and famciclovir all provide effective prophylaxis against HSV-1 reactivation following ablative facial resurfacing. However, no definitive recommendations can be made regarding prophylactic therapy for minimally invasive procedures at present.

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Herpes. 2007 Jun;14 Suppl 1:5A-11A.
An update on short-course episodic and prevention therapies for herpes genitalis.
Corey L, Bodsworth N, Mindel A, Patel R, Schacker T, Stanberry L.
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

The prevalence of herpes genitalis (genital herpes) has increased markedly over the past three decades. The most common cause is infection with the herpes simplex virus type 2 (HSV-2), but it can also occur as a result of HSV-1 infection. Herpes genitalis can cause substantial psychosexual as well as physical morbidity and, in immunocompromised individuals, such as those who are HIV-positive, HSV infection can result in severe disease with progressive and extensive lesions. The natural history of herpes genitalis and the pathways of infection are now well known; however, the factors associated with reactivation have yet to be fully defined. A number of management approaches with antiviral medications are commonly used, including episodic and suppressive treatments. For episodic therapy, the duration of both lesions and symptoms, as well as the proportion of aborted episodes, are the most important measures of efficacy. For suppressive therapy, the time to first recurrence and frequency of recurrences over time are the most important clinical measures of antiviral benefit. Regarding the duration of episodic regimens, comparisons of 1-, 2- and 3-day antiviral courses with standard 5-day regimens show similar benefits on healing and relief of symptoms, with the obvious improvement in convenience, economy and compliance. In HIV-positive patients, antiherpes therapy has proved effective in speeding healing of lesions and reducing subclinical shedding, and can be used to treat genital HSV-2 infections in this group. Suppressive antiviral therapy has been shown to decrease the risk of HSV transmission in heterosexual couples. New approaches to the prevention of HSV infection, including vaccines and topical microbicides, are under investigation.

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Herpes. 2007 Jun;14(1):23-6.
Review of recent HSV recurrent-infection treatment studies.
Patel R, Stanberry L, Whitley RJ.
Southampton University Hospitals, University of Southampton, UK. Rajul.Patel@suht.swest.nhs.uk

Antiviral management options for recurrent herpes simplex virus (HSV) infection include daily suppressive and episodic therapy. New data on patient-initiated, short-course, high-dose antiviral therapy provide a new, more convenient option for patients who choose episodic therapy. A head-to-head comparison of suppressive valaciclovir versus famciclovir treatment indicates that both drugs have comparable clinical benefits, but that valaciclovir may have a greater impact on virological end-points. However, a more recent study shows that famciclovir effectively reduces the frequency of total and subclinical HSV shedding compared with placebo, as well as the percentage of days with genital lesions for subjects with or without a history of genital herpes. This article reports on presentations given at the IHMF Annual Meeting and International Congress of Antimicrobial Agents and Chemotherapy, both of which took place in late 2006.

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Herpes. 2007 Jun;14(1):11-6.
Management of HSV encephalitis in adults and neonates: diagnosis, prognosis and treatment.
Kimberlin DW.
Division of Pediatric Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL 35233, USA. dkimberlin@peds.uab.edu

Herpes simplex virus (HSV) infections of the central nervous system (CNS) are infrequent in occurrence, but potentially devastating in outcome. Tremendous advances in the ability to diagnose HSV CNS disease without the need for invasive procedures such as brain biopsy, coupled with the establishment of safe and effective antiviral therapies, have improved overall outcomes. However, the seriousness of HSV CNS infections requires that clinicians maintain a high index of suspicion to initiate evaluation under suitable circumstances. In addition, clinicians need an understanding of the clinical disease course in order to interpret the diagnostic tests appropriately. Intravenous aciclovir remains the mainstay of antiviral management. Even with recent treatment advances and enhanced awareness, potentially devastating outcomes remain possible.

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Herpes. 2007 Jun;14(1):4-10.
Herpetic retinitis.
Cordero-Coma M, Anzaar F, Yilmaz T, Foster CS.
Massachusetts Eye Research and Surgery Institute, Cambridge, MA 02142, USA.

This paper provides an appreciation of the various forms and consequences of retinal inflammation caused by human herpesviruses. Herpes simplex virus types 1 and 2, varicella zoster virus, cytomegalovirus and Epstein-Barr virus are known to cause retinitis. The prognosis of herpetic retinitis remains poor because it is associated with a high incidence of complications, both during and after the acute disease phase. On diagnosis of retinal necrosis, antiviral treatment must be started promptly to limit disease progression; following this, prophylactic maintenance therapy may be required.

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Clin Infect Dis. 2007 Jun 1;44(11):e96-9. Epub 2007 Apr 18.
Thalidomide therapy for the treatment of hypertrophic herpes simplex virus-related genitalis in HIV-infected individuals.
Holmes A, McMenamin M, Mulcahy F, Bergin C.
Department of Infectious Diseases, University of Texas Health Sciences Center at Houston, Houston, TX 77030, USA. andrea.m.e.holmes@uth.tmc.edu

Hypertrophic genital herpes is a disfiguring manifestation of a common infection seen in immunocompromised hosts that can be clinically mistaken for malignancy. We review the literature and describe hypertrophic genital herpes in a human immunodeficiency virus-positive patient receiving antiretroviral therapy. Treatment with valacyclovir, cidofovir, and foscarnet failed, but thalidomide treatment was successful.

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Am J Clin Dermatol. 2007;8(2):79-83.
Perineal herpes simplex infection in bedridden geriatric patients.
Nikkels AF, Pierard GE.
Department of Dermatopathology, University Hospital of Liege, Liege, Belgium.

BACKGROUND: Herpes simplex virus (HSV) lesions are prone to reactivation and recurrence in response to various local or systemic triggering factors. OBJECTIVE: To study the characteristics of five bedridden geriatric patients who presented with herpetic recurrences on the buttocks, gluteal cleft, and perianal region during hospitalization. METHODS: Data were gathered regarding age, gender, reason for hospitalization, localization of lesions, clinical presentation, previous clinical diagnosis and topical treatments, immune status and immunosuppressant drug intake, as well as prior history of labial or genital herpes. A skin biopsy was taken for histologic examination and immunohistochemical viral identification. Viral culture and viral serology were performed and data regarding antiviral therapy were recorded. RESULTS: The five patients (three women, two men) were aged >80 years and hospitalized for either severe drug-induced renal insufficiency (one case), severe pneumonia (two cases), or stroke causing restricted mobility (two cases). Numerous well demarcated, painful ulcerations developed in the perianal region of these patients, and one patient also presented with some vesicular lesions. The lesions had been confused with mycotic and/or bacterial infections for 10-14 days. No inguinal lymphadenopathies were present and there was no fever. None of the patients had a previous history of recurrent labial or genital HSV infections or HIV infection. Histology was suggestive of HSV infection in two of five patients. Immunohistochemistry identified HSV type I (three patients) and HSV type II (two patients) infections. Viral culture with immunofluorescence viral identification revealed HSV type I in one of the four patients in whom a swab for viral culture was taken. Serology revealed past HSV infection. All lesions cured gradually after 10-14 days of intravenous acyclovir (aciclovir) treatment. CONCLUSION: Herpetic lesions of the perineal region represent a rare complication in bedridden geriatric patients in the absence of a previous history of HSV infections at the same site. Common traits of patients with this condition were the presence of numerous ulcerated lesions, prolonged time course, and confinement to bed. The latter probably modifies the skin condition, which triggers viral reactivation and favors cutaneous extension of the infection. Complementary diagnostic methods for viral detection and identification are mandatory.

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Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007 Mar;103 Suppl:S50.e1-23.
Management of oral lesions in HIV-positive patients.
Baccaglini L, Atkinson JC, Patton LL, Glick M, Ficarra G, Peterson DE.
Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, Gainesville, FL 32610-3628, USA. lbaccaglini@dental.ufl.edu

HIV/AIDS is currently the leading cause of death in Africa and the fourth leading cause of death worldwide. This systematic review of the literature was conducted to evaluate the evidence for treatment of the most common oral lesions associated with HIV: oral candidiasis with or without oropharyngeal involvement (OPC), oral hairy leukoplakia (OHL), recurrent aphthous-like ulcerations (RAU), oral Kaposi's sarcoma (OKS), orolabial herpes simplex infection (HSV), oral herpes zoster infection (VZV), intraoral or perioral warts (HPV), and HIV-associated periodontal diseases. Treatment of HIV-associated salivary gland disease is addressed in a different section of this World Workshop. We found the largest body of evidence for treatment of OPC in HIV patients. Future trials will be needed to test drugs currently in development for treatment of Candida strains that are resistant to existing therapies. There were no double blind, placebo-controlled randomized clinical trials (RCT) for topical treatment of OHL, and only one RCT for systemic treatment of the lesion with desciclovir. Systemic thalidomide was the only drug tested in RCT for treatment or prevention of RAU. Only 1 double-blind RCT comparing vinblastine and sodium tetradecyl sulfate was identified for localized treatment of OKS. Three drugs (famciclovir, acyclovir, and valaciclovir) were shown to be effective in randomized, double-blind trials for treatment or suppression of mucocutaneous HSV lesions in HIV patients. In all 3 trials, the effects of these medications on orolabial HSV lesions were not reported separately. There were no double-blind, placebo-controlled RCT testing topical treatments for orolabial HSV lesions in HIV patients. No trials testing treatments of oral VZV were identified. There were no double-blind, placebo-controlled RCT for treatment of HIV-associated intraoral or perioral warts or periodontal diseases. In conclusion, there is a need for well-designed RCTs to assess the safety and efficacy of topical and systemic treatments of most oral mucosal and perioral lesions in HIV patients. There is also a need to develop newer drugs for treatment of resistant fungal and viral microorganisms. Finally, standardized outcome measures should be developed for future clinical trials to allow comparisons of studies using different populations.

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Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007 Mar;103 Suppl:S12.e1-18.
Management of recurrent oral herpes simplex infections.
Woo SB, Challacombe SJ.
Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA. swoo@rics.bwh.harvard.edu

The literature has been reviewed for evidence of the efficacy of antiviral agents in both the prophylaxis and treatment of recurrent oral herpes simplex virus (HSV) infections and discussed by a panel of experts. Emphasis was given to randomized controlled trials. Management of herpes-associated erythema multiforme and Bell palsy were also considered. The evidence suggests that 5% acyclovir (ACV) in the cream base may reduce the duration of lesions if applied early. Recurrent herpes labialis (RHL) and recurrent intraoral HSV infections can be effectively treated with systemic ACV 400 mg 3 times a day or systemic valacyclovir 500 to 1000 mg twice a day for 3 to 5 days (longer in the immunocompromised). RHL in the immunocompetent can be effectively prevented with (1) sunscreen alone (SPF 15 or above), (2) systemic ACV 400 mg 2 to 3 times a day, or (3) systemic valacyclovir 500 to 2000 mg twice a day. Valacyclovir 500 mg twice a day is also effective in suppressing erythema multiforme triggered by HSV. Further studies are needed to compare treatment efficacy between topical penciclovir, docosanol, and ACV cream for RHL.

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Semin Perinatol. 2007 Feb;31(1):19-25.
Herpes simplex virus infections of the newborn.
Kimberlin DW.
Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL 35233, USA. dkimberlin@peds.uab.edu

Herpes simplex virus (HSV) infections are fortunately quite rare in the neonatal population. Nevertheless, due to their life-threatening nature and the tremendous damage that surviving infants can incur, neonatal HSV is actually considered in a differential diagnosis relatively commonly. The availability of safe and effective antiviral therapy for the management of neonatal HSV also can accelerate a clinician's decision to consider HSV as the cause of a neonate's disease presentation, and then to obtain appropriate diagnostic studies and empirically institute antiviral treatment. Decisions on whether to continue antiviral therapy for a full course are predicated on the appropriate interpretation of these diagnostic studies as they subsequently are reported to the treating physician. For HSV-infected neonates, the duration of parenteral acyclovir therapy ranges from 14 to 21 days, depending on the extent of disease. Use of subsequent oral suppressive antiviral therapy is under investigation in randomized controlled trials, and at this time cannot be routinely recommended. This article will summarize the current state of neonatal HSV disease presentation, diagnosis, and management.

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Curr Opin Infect Dis. 2007 Feb;20(1):73-6.
Consequences of herpes simplex virus in pregnancy and their prevention.
Baker DA.
Stony Brook University Medical Center, Stony Brook, New York, USA.

PURPOSE OF REVIEW: New findings reveal that first-time infection of the mother is the most important factor for the transmission of genital herpes from mother to fetus/newborn. Interventions based on these findings will lead to new management of the pregnant patient with genital herpes prior to pregnancy and measures to prevent the acquisition of herpes during pregnancy. RECENT FINDINGS: Risk factors for the transmission of herpes from mother to newborn have been detailed. It is the pregnant woman who acquires genital herpes as a primary infection in the latter half of pregnancy, rather than prior to pregnancy, who is at greatest risk of transmitting this virus to her newborn. This is true for both herpes simplex virus type-1 and herpes simplex virus type-2. Additional risk factors for neonatal herpes simplex virus infection include the use of a fetal-scalp electrode and maternal age of less than 21 years. SUMMARY: Risk factors for the transmission of herpes from mother to newborn are detailed. Antiviral suppressive therapy initiated in the late third trimester has been shown to decrease viral shedding and the need for cesarean section.

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Cochrane Database Syst Rev. 2007 Jan 24;(1):CD002898.
Therapeutic interventions for herpes simplex virus epithelial keratitis.
Wilhelmus K.

BACKGROUND: Many clinical trials have been performed on the acute treatment of dendritic epithelial keratitis. Surveys of ocular antiviral pharmacology and of herpes simplex virus (HSV) eye disease have evaluated different interventions, but a systematic review of all comparative clinical studies has not previously been undertaken. OBJECTIVES: The objective of this review was to compare the effects of various therapeutic interventions for dendritic or geographic HSV epithelial keratitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) in The Cochrane Library (Issue 3, 2006), MEDLINE (1966 to July 2006, week 3), EMBASE (1980 to 2006, week 30), LILACS (up to August 2006), SIGLE (1980 to March 2005), ZETOC (1 August 2006), BIOSIS (up to 2005), JICT-EPlus (up to 2005), Index Medicus (1960 to 1965), Excerpta Medica Ophthalmology (1960 to 1973), reference lists of primary reports and review articles, and conference proceedings pertaining to ocular virology. SELECTION CRITERIA: This review included comparative clinical trials that assessed one-week or two-week healing rates of topical ophthalmic or oral antiviral agents and or physical or chemical debridement in people with active epithelial keratitis. DATA COLLECTION AND ANALYSIS: The review author extracted data and assessed trial quality. Interventions were compared by the proportions of participants healed at seven days and at fourteen days after trial enrolment. MAIN RESULTS: This review included data from 98 trials that randomised a total of 5211 participants. Compared to idoxuridine, the topical application of vidarabine, trifluridine, or acyclovir resulted in a significantly greater proportion of participants healing within one week of treatment. Among these latter three antiviral agents, no treatment emerged as significantly better for the therapy of dendritic epithelial keratitis. Insufficient placebo-controlled studies were available to assess debridement and other physical or physicochemical methods of treatment. Interferon monotherapy had a slight beneficial effect on dendritic epithelial keratitis but was not better than other antiviral agents. Interferon was very effective when combined with another antiviral agent such as trifluridine. AUTHORS' CONCLUSIONS: Currently available antiviral agents are effective and nearly equivalent. The combination of a nucleoside antiviral with either debridement or with interferon seems to speed healing. Future trials of the acute treatment of HSV epithelial keratitis must aim to achieve adequate statistical power for assessing the primary outcome of epithelial healing and should consider the effect of lesion size and other characteristics on treatment response.

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Rev Med Interne. 2007 Jan;28(1):16-21. Epub 2006 Oct 12.
[Herpes simplex virus vaccines: perspectives.]
[Article in French]
Deback C, Huraux JM.
Service de virologie du groupe hospitalier de la Pitie-Salpetriere, 83, boulevard de l'Hopital, 75651 Paris cedex 13, France.

PURPOSE: Despite effective antiviral therapy, infection with herpes simplex virus (HSV) is a critical public health issue, particularly genital herpes by its social and psychological burden and its contribution to the neonatal herpes and possibly to the HIV/AIDS pandemic. CURRENT KNOWLEDGE: Many prophylactic and therapeutic vaccination approaches have been explored but no effective vaccine is presently available. In fact, as members of the Herpesviridae family, both HSV-1 and 2 types have genes involved in immune evasion. FUTURE PROSPECTS: Further research is needed to define determinants of immunity in order to design more effective vaccines.

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Drugs. 2006;66(18):2397-416.
Famciclovir: a review of its use in herpes zoster and genital and orolabial herpes.
Simpson D, Lyseng-Williamson KA.
Wolters Kluwer Health | Adis, Auckland, New Zealand. demail@adis.co.nz

Famciclovir (Famvir) is the oral prodrug of penciclovir, an agent that has demonstrated antiviral activity against herpes simplex viruses, type 1 (HSV-1) and 2 (HSV-2) [which cause orolabial and/or genital herpes simplex], and against varicella zoster virus (VZV) [a reactivation of which leads to herpes zoster]. Famciclovir has efficacy similar to that of aciclovir (in immunocompetent or immunocompromised patients) or valaciclovir (in immunocompetent patients) in the treatment of herpes zoster, and efficacy similar to aciclovir in the treatment of first or recurrent episodes of genital herpes (in immunocompetent or immunocompromised patients). Famciclovir also has efficacy in the suppression of recurrent episodes of genital herpes, and in the treatment of orolabial herpes, in immunocompetent patients. As such, famciclovir is a well tolerated first-line option for the treatment of herpes zoster and the treatment and suppression of genital herpes, and is approved for the treatment of recurrent orolabial herpes. Convenient patient-initiated single-day (for recurrent genital herpes) and single-dose (for orolabial herpes) dosage regimens may contribute to treatment compliance, patient acceptability and subsequent treatment outcomes.

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Pediatrics. 2006 Dec;118(6):e1612-20. Comment in: Pediatrics. 2006 Dec;118(6):2543-4.
Herpes simplex virus infections in preterm infants.
O'Riordan DP, Golden WC, Aucott SW.
Eudowood Neonatal Pulmonary Division, Johns Hopkins University School of Medicine, 600 N Wolfe St, Baltimore, MD 21287, USA.

OBJECTIVE: Neonatal herpes simplex virus infections cause significant neonatal mortality and morbidity, but the course and prognosis in preterm infants is not well documented. We performed a retrospective review of herpes simplex virus infections at out institution within the first 30 days after birth in infants who were born at <37 weeks to help better define the symptoms and signs of herpes simplex virus infections in preterm infants and to assist in prognosis. METHODS: Hospital databases were reviewed to identify culture- or polymerase chain reaction-proven cases of herpes simplex virus-1 or herpes simplex virus-2 infections that occurred in preterm newborns between 1989 and 2003. Maternal and neonatal histories, clinical features, and laboratory results were reviewed systematically. RESULTS: Ten preterm singletons and a set of twins were infected with herpes simplex virus-2 during the first month after birth. No mother had herpes simplex virus lesions at delivery, but a history of genital herpes simplex or other sexually transmitted infections was prevalent among the mothers. Infants presented with either disseminated disease or encephalitis. All infants with disseminated disease (n = 9) died, whereas the 3 infants with encephalitis survived. All infants in the cohort developed respiratory distress, and consistent with the prominence of respiratory symptoms, viral cultures of the respiratory tract were consistently positive. Ten of 12 infants received acyclovir, but despite treatment within 48 hours of symptoms, infants with disseminated disease deteriorated rapidly and died. Two of 3 infants who received high-dosage (60 mg/kg per day) acyclovir survived. CONCLUSIONS: Herpes simplex virus infections in preterm infants usually present during the first 2 weeks of life with respiratory distress and a high incidence of disseminated disease. Viral respiratory cultures have a high yield for documentation of infection. The morbidity of herpes simplex virus in this population may be attributable to a relatively immature immune system in this population. Additional studies are necessary to delineate the evolution of herpes simplex virus disease in preterm infants and the role of antiviral therapy in mitigating the sequelae of herpes simplex virus infections in this population.

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Sex Transm Dis. 2006 Oct 19; [Epub ahead of print]
Suppressive Therapy With Valacyclovir in Early Genital Herpes: A Pilot Study of Clinical Efficacy and Herpes-Related Quality of Life.
Handsfield HH, Warren T, Werner M, Phillips JA.
>From the *Center for AIDS and STD, University of Washington, and Public Health-Seattle & King County, Seattle, Washington; the daggerWestover Heights Clinic, Portland, Oregon; and double daggerSage Statistical Solutions, Inc., Elfand, North Carolina.

BACKGROUND:: Suppressive therapy has not been studied during the first year after acquisition of genital herpes, the time of maximum frequency of reactivation, potential for transmission, and impact on quality of life. OBJECTIVE:: The objective of this study was to evaluate the effectiveness of suppressive therapy with valacyclovir initiated within 3 months of infection. STUDY DESIGN:: The authors conducted a double-blind, randomized, controlled trial of 1.0 g valacyclovir daily versus placebo for 6 months in 119 patients. RESULTS:: Herpes simplex virus (HSV) type 2 and HSV-1 were documented in 75 and 22 patients, respectively. In intention-to-treat analysis, annualized rates of symptomatic recurrences for valacyclovir and placebo, respectively, were 1.7 +/- 2.7 (mean +/- standard deviation) and 3.4 +/- 4.0 outbreaks per year (P = 0.012). Time to first recurrence was 80 +/- 47 days for valacyclovir and 54 +/- 49 days for placebo (P = 0.001). The differences in favor of valacyclovir were greatest in patients with confirmed HSV-2 infection. The Recurrent Genital Herpes Quality of Life score in HSV-2 infected patients rose 11.9 +/- 11.1 points for valacyclovir and 5.9 +/- 9.1 points for placebo (P = 0.040). CONCLUSIONS:: Early suppressive therapy with valacyclovir reduces symptomatic recurrent outbreaks, especially in patients with HSV-2 infection. Valacyclovir therapy was associated with improved herpes-related quality of life.
 

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