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PubMed2003

Herpes zoster guideline of the German Dermatology Society (DDG).

Varicella zoster virus (VZV) causes varicella (chickenpox), remains dormant in dorsal root and cranial nerve ganglia and can be reactivated as a consequence of declining VZV-specific cellular immunity leading to herpes zoster (shingles). Patients older than 50 years of age affected by herpes zoster may suffer a significant decrease of quality of life. These patients and immunocompromised individuals are at increased risks for severe complications, involving the eye, the peripheral and the central nervous system (prolonged pain, postherpetic neuralgia). Such complications occur with and without cutaneous symptoms. The German Dermatology Society (DDG) has released guidelines in order to guarantee updated management to anyone affected by herpes zoster. Diagnosis is primarily clinical. The gold standard of laboratory diagnosis comprises PCR and direct identification of VZV in cell cultures. Detection of IgM- and IgA-anti VZV antibodies may be helpful in immunocompromised patients. Therapy has become very effective in the last years. Systemic antiviral therapy is able to shorten the healing process of acute herpes zoster, to prevent or to alleviate pain and other acute and chronic complications, particularly, when given within 48 h to a maximum of 72 h after onset of the rash. Systemic antiviral therapy is urgently indicated in patients beyond the age of 50 years and in patients at any age with herpes zoster in the head and neck area, especially in patients with zoster ophthalmicus. Further urgent indications are severe herpes zoster on the trunk and on the extremities, herpes zoster in immunosuppressed patients and in patients with severe atopic dermatitis and severe ekzema. Only relative indications for antiviral therapy exist in patients younger than 50 years with zoster on the trunk and on the extremities. In Germany acyclovir, valacyclovir, famciclovir and brivudin are approved for the systemic antiviral treatment of herpes zoster. These compounds are all well tolerated by the patients and do not differ with regard to efficacy and safety. Brivudin has a markedly higher anti-VZV potency than oral acyclovir, valacyclovir and famciclovir and thus offers a simpler dosing regimen. It must be given only once daily during 7 days in comparison to three and five times dosing per day of valacyclovir, famciclovir and acyclovir, respectively. Brivudin is an antiviral agent with no nephrotoxic properties, which is an advantage when compared to acyclovir. The most important aim of therapy of herpes zoster is to achieve painlessness. Appropriately dosed analgesics in combination with a neuroactive agent (i.e. amitriptylin) are very helpful when given together with antiviral therapy. The additive therapy with corticosteroids may shorten the degree and duration of acute zoster pain, but has no essential effect on the development of postherpetic neuralgia, which is a very difficult condition to treat. Thus early presentation to a pain therapist is recommended in specific cases.

Adolescent↗
PubMedDate not supplied

Inhibition of sickling in vitro by three purine-based antiviral agents: an approach to the treatment of sickle cell disease.

As a result of an in vitro screening effort the antiviral agent acyclovir was found to inhibit aggregation of hemoglobin S and the sickling of erythrocytes from individuals with sickle cell disease. Sickling of the erythrocytes was significantly inhibited at 200 microg/ml under essentially anaerobic conditions, considerably more hypoxic than the conditions in which sickling occurs in sickle cell patients. The structurally related guanine-based antiviral agents ganciclovir, valacyclovir, and penciclovir were also tested. Valacyclovir and ganciclovir showed comparable anti-sickling activity at concentrations similar to that of acyclovir. An examination of the shared structural characteristics of the four guanine derivatives linked anti-sickling activity to the presence of an oxygen atom alpha to the N9 of the guanine moiety. These findings suggest a new approach in the search for new agents for the treatment of patients with sickle cell disease.

Acyclovir↗
PubMed1999

Prevention of perinatal herpes: prophylactic antiviral therapy?

So what is the take-home message from these studies? The first question, about fetal and neonatal safety, appears to be answered positively. With more than 1,812 infants reported to have been exposed to varying amounts and duration of maternal acyclovir suppression, there has not been any apparent, short-term adverse fetal or neonatal effect. Use of acyclovir in infants, even in those that are premature, is very well tolerated, with a wide margin of safety. In addition, the pharmacokinetics studies by Frenkel et al and Kimberlin et al, as well as the animal studies, suggest that maternal use of acyclovir may actually provide a prophylactic and therapeutic benefit to an infant who is exposed to HSV. The second question, as to whether acyclovir suppression would simply change symptomatic outbreaks into asymptomatic ones, also appears to have some answers. The information provided by Wald et al indicated that acyclovir suppression actually decreases asymptomatic shedding, along with decreasing clinical recurrences. Because asymptomatic shedding seems to be similar in pregnant and nonpregnant patients, it would be reasonable to assume that asymptomatic shedding also would be decreased at delivery in pregnant women with HSV infection. This supposition is supported by the data from the randomized trials and cohort studies that demonstrated a lower than expected asymptomatic shedding rate. As yet, however, there has been no randomized trial in pregnant women that has had an adequate sample size to confirm this on a statistically significant basis. The third question, whether acyclovir suppression would lower the frequency of symptomatic recurrences at parturition, reducing the need for cesarean in these patients, has answers as well, although they may not be as clear cut as one would like. Women who experience their first genital herpes outbreak while they are pregnant seem to benefit from acyclovir suppression, with both a decrease in the risk of clinical recurrences at delivery and a decreased need for cesarean delivery. This is well documented by a randomized trial and other cohort studies. Acyclovir's efficacy in patients who have a history of genital herpes infections antedating their pregnancy is less clear. The data appear to indicate a clinically important decrease in the likelihood of symptomatic reactivations at the time of delivery, although the sample sizes in the randomized studies have been too small to draw a statistically significant conclusion one way or the other. Unfortunately, a definitive trial for this group of women may never be done. Assuming a 13% recurrence risk at the time of delivery and a 50% decrease in recurrences with the use of acyclovir, 652 women would have to complete the study to achieve a power of 80%. Conducting the study at the largest, single institution, prenatal center in the United States, Scott et al were only able to enroll 222 women during a period of 6 years. Likewise, Brocklehurst et al terminated their trial early because of recruitment difficulties. They enrolled only 63 women during a period of 4 years using two different sites in the United Kingdom. Unless a multicenter trial is conducted or a meta-analysis performed on the available data, we will probably have to be content with the data as it now stands. With valacyclovir and famciclovir now available, it is unlikely that any further work will be done with acyclovir. Information from the valacyclovir trials, however, may reach statistical significance because of changes in the study design that will allow smaller sample sizes to reach adequate power. Famciclovir treatment holds promise because of its longer intracellular half-life, but until concerns about potential mutagenicity are resolved and more information on its efficacy for suppressive therapy becomes available, it should not be considered for maternal suppressive therapy. Acyclovir appears to be effective, at least in some cohorts, and is probably safe for the fetus. (AB

Acyclovir↗
PubMed2003

Axonal transport and sorting of herpes simplex virus components in a mature mouse visual system.

The time course for delivery and transport of two major proteins of herpes simplex virus (HSV) has been determined for mature mouse retinal ganglion cell axons in vivo. Twenty-four hours after intravitreal injection of HSV, valacyclovir was introduced into the drinking water of the mice to inhibit subsequent viral replication. Without treatment, viral spread and replication in periaxonal glial cells confound study of axonal transport. At 2 to 5 days after infection, the animals were sacrificed and contiguous segments of the optic pathway were removed. Immunofluorescence microscopy indicated that the number of infected astrocytes was reduced in the proximal optic nerve and eliminated in the optic tract. Western blots of the retina with antibodies for envelope and capsid components, glycoprotein D (gD) and VP5, respectively, revealed that both components were expressed in retinal homogenates by 2 days. Results of reverse transcription-PCR indicated that there was no gD mRNA present in the treated optic tract 5 days after infection. Therefore, we conclude that gD is transcribed from viral mRNA in the retinal ganglion cell bodies. The gD accumulated in the proximal ganglion cell axon by 2 days and reached the most distal segment after 3 days. The VP5 first appeared in the proximal axons at 4 days, about 48 h after the appearance of gD. Thus, gD entered the axon earlier and independent of VP5. These finding confirm the subassembly model of viral transport in neurons and suggest that there is a 4- to 5-day window for initiation of effective antiviral treatment with valacyclovir.

Acyclovir↗
PubMed2000

Treatment of common cutaneous herpes simplex virus infections.

Herpes simplex virus infection is increasingly common in the United States. New antiviral medications have expanded treatment options for the two most common cutaneous manifestations, orolabial and genital herpes. Acyclovir therapy remains an effective and often less expensive option. Famciclovir and valacyclovir offer improved oral bioavailability and convenient oral dosing schedules but are more expensive than acyclovir. Patients who have six or more recurrences of genital herpes per year can be treated with one of the following regimens: acyclovir, 400 mg twice daily; valacyclovir, 1 g daily; or famciclovir, 250 mg twice daily. These regimens are effective in suppressing 70 to 80 percent of symptomatic recurrences. Episodic treatment of recurrent genital herpes is of questionable benefit, but it may be helpful in appropriately selected patients. There is little evidence indicating benefit from treatment of recurrent orolabial herpes, which tends to be mild and infrequent.

2-Aminopurine↗
PubMed2001

Recognition and transport characteristics of nonpeptidic compounds by basolateral peptide transporter in Caco-2 cells.

Recent studies have revealed that diverse compounds lacking peptide bonds, such as valacyclovir and delta-aminolevulinic acid (delta-ALA), can be recognized by H+-coupled peptide transporters (PEPT1 and PEPT2). In the present study, recognition and transport characteristics of nonpeptidic compounds by the basolateral peptide transporter, which is distinct from PEPTs, were compared with those by PEPT1 using the human intestinal Caco-2 cells. [14C]Glycylsarcosine uptake via PEPT1 was inhibited by all nonpeptidic compounds tested. Similarly, most nonpeptidic compounds showed an inhibitory effect on [14C]glycylsarcosine uptake by the basolateral peptide transporter, although some kinds of nonpeptidic compounds, such as valine methyl ester, did not. Direct measurements of valacyclovir and delta-ALA transport revealed that both compounds were able to be transported by the basolateral peptide transporter. Because delta-ALA has been used recently in vitro and in clinical studies as an endogenous photosensitizer for photodynamic therapy, the intestinal transport characteristics of delta-ALA were further examined. Inhibition studies and Eadie-Hofstee plot analysis suggested that delta-ALA transport across the brush-border and basolateral membranes of the intestine was mainly mediated by peptide transporters. In addition, the apical-to-basolateral transport of delta-ALA was greater than that of the opposite direction. These findings provide the first evidence that the intestinal basolateral peptide transporter can recognize and transport nonpeptidic compounds, and play a definitive role in the absorption of delta-ALA.

ATP-Binding Cassette Transporters↗
PubMed1997

Management of herpes simplex and varicella-zoster virus infections.

Herpes simplex virus and varicella-zoster virus are common infections and are seen frequently in clinical practice. Infection with these viruses results in cutaneous lesions that may be diagnosed clinically, but widely available laboratory testing is useful for confirmation. Asymptomatic herpes simplex virus shedding, or "subclinical reactivation," likely occurs in all persons infected with herpes simplex virus and results in the transmission of virus despite the absence of signs or symptoms that suggest active infection. Oral and intravenous acyclovir are effective in treating initial and recurrent herpes simplex and varicella-zoster virus infections. The daily administration of oral acyclovir as suppressive therapy is effective in patients with frequently recurring genital infection with herpes simplex virus by reducing the number of symptomatic recurrences and the frequency of asymptomatic virus shedding. Two new antiviral agents, famciclovir and valacyclovir hydrochloride, have been approved for the short-term treatment of recurrent genital herpes simplex virus and recurrent zoster in nonimmunocompromised hosts. Famciclovir and valacyclovir demonstrate superior pharmacokinetics compared with acyclovir and allow for less frequent daily dosing with higher achievable serum drug concentrations. The attenuated live varicella virus vaccine is now available in the United States and prevents primary varicella-zoster virus infection in susceptible children and adults.

2-Aminopurine↗
PubMed2001

Shingles (Herpes Zoster) and Post-herpetic Neuralgia.

During childhood chickenpox, varicella-zoster virus becomes latent in neurons of the dorsal root or trigeminal ganglia. Shingles results years to decades later from a breakdown of viral latency within a ganglion and subsequent virus spread to the skin producing a unilateral dermatomal vesicular rash accompanied by segmental pain. Treatment with famciclovir, valacyclovir, and high dose acyclovir is beneficial if started within the first 3 days of the rash. All three drugs can be given orally, are equally effective, shorten the duration of viral shedding and time to healing of the rash by 1 to 2 days, and lessen the intensity and duration of the acute neuritic pain. Famciclovir and valacyclovir have more convenient dosing schedules (three times daily) compared to acyclovir (five times daily). Mild cases of shingles in younger healthy individuals often do not require any antiviral treatment. Pain in shingles may have burning, lancinating, or allodynic qualities, ranges in intensity from mild to unbearable, and lasts 2 to 8 weeks. Pain treatment varies on the type and intensity of pain experienced. In a few patients, post-herpetic neuralgia develops and the dermatomal pain persists for months to years. Effective treatment of post-herpetic pain is often difficult.

Journal Article↗
PubMed2002

European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.6.1. Cancer risk after renal transplantation. Post-transplant lymphoproliferative disease (PTLD): prevention and treatment.

GUIDELINES: A. In the first year after organ transplantation, recipients are at the greatest risk of developing lymphoproliferative diseases (PTLDs), which are induced most often by Epstein-Barr virus (EBV) infection, and patients should therefore be screened prior to or at the time of transplantation for EBV antibodies. B. In the rare cases (<5%) where the recipient is EBV seronegative, he or she has a 95% likelihood of receiving an organ from an EBV-seropositive donor, which translates into a high risk of primary EBV infection with seroconversion soon after transplantation. In such cases, the recipient should receive a prophylactic antiviral treatment with acyclovir, valacyclovir or ganciclovir, starting at the time of transplant and lasting for at least 3 months. The specific recommendations given for CMV prophylaxis could be applicable in this situation. C. The treatment of PTLD should be based on accurate pathology with extensive cell markers and phenotyping. The treatment modalities are as follows. Reduction of basal immunosuppression in all cases (either maintain only steroids, or decrease by at least 50% the anti-calcineurin drugs and stop other immunosuppressive drugs). In the case of EBV-positive B-cell lymphoma, antiviral treatment with acyclovir, valacyclovir or ganciclovir may be initiated for at least 1 month or according to the blood level of EBV replication when available. In the case of rare lymphomas from the mucosal-associated lymphoid tissue (MALT) with positive Helicobacter pylori, full eradication of H. pylori should be carried out with a validated protocol. Subsequent H. pylori prophylaxis should be implemented to avoid relapse. In the case of CD20-positive lymphomas, treatment with rituximab, a chimeric monoclonal antibody directed against CD20, should be carried out with one i.v. injection per week for 4 weeks. In the case of diffuse lymphomas or improper response to previous treatment, CHOP chemotherapy should be used alone or in combination with rituximab. The CHOP regimen is cyclophosphamide, doxorubicine, vincristine and prednisone. Complete cessation of immunosuppression with or without graft nephrectomy should also be considered.

Epstein-Barr Virus Infections↗
PubMed1999

Determination of acyclovir in plasma by solid-phase extraction and column liquid chromatography.

After oral administration, valacyclovir, the L-valyl ester of acyclovir, converts to the antiherpes virus drug, acyclovir. The bioavailability of acyclovir after valacyclovir administration is between 3- to 4.5-fold higher than that achieved after oral acyclovir administration. Therefore, despite the drug's short terminal half-life (3 hours), acyclovir plasma concentrations obtained after oral administration of the prodrug offer a more convenient dosage regimen in patients with herpes zoster than that required after acyclovir administration. Acyclovir is also used for viral infection prophylaxis in patients with hematologic disorders and in those who have undergone solid organ transplantation. We have described a simple and selective liquid chromatographic method for the determination of acyclovir in plasma using a new polymeric reversed-phase sorbent for solid-phase extraction. A mean acyclovir absolute recovery of 90% was found after elution of the drug from the cartridge with the mobile phase. This procedure allowed us to measure 62.5 ng/mL of acyclovir with an acceptable precision using a plasma volume of 250 microL, and no drug was found to interfere with the assay. This method is suitable for the therapeutic monitoring of acyclovir in patients who have been given a wide variety of coadministered drugs.

Acyclovir↗
PubMed1999

Advances in antiviral therapy.

Multiple agents for the treatment and prevention of viral illnesses have been developed during the past few years. While in many cases this has been in direct response to the human immunodeficiency virus type 1 epidemic, a number of new antiviral agents are relevant to the practice of general pediatrics. This article reviews recent advances in the therapy of some common and a few unusual viral illnesses of children. The indication and efficacy of the newly developed agents valacyclovir, famciclovir, cidofovir, oral and intraocular ganciclovir, adefovir, respiratory syncytial virus immune globulin, palivizumab, and imiquimod are discussed, as well new uses of acyclovir, lamivudine, and ribavirin. Many of the antivirals discussed, including valacyclovir and cidofovir, have not yet been studied in children, but they hold promise for improving the treatment of pediatric viral infections.

Antiviral Agents↗
PubMed2003

Novel agents and strategies to treat herpes simplex virus infections.

The quiet pandemic of herpes simplex virus (HSV) infection has plagued humanity since ancient times, causing mucocutaneous infection, such as herpes labialis and herpes genitalis. Disease symptoms often interfere with everyday activities and occasionally HSV infections are the cause of life-threatening or sight-impairing disease, especially in neonates and the immunocompromised patient population. After primary or initial infection the virus persists for life in a latent form in neurons of the host, periodically reactivating and often resulting in significant psychosocial distress for the patient. Currently, no cure is available. In the mid-1950s the first antiviral, idoxuridine, was developed for topical treatment of herpes disease and, in 1978, vidarabine was licensed for systemic use to treat HSV encephalitis. Acyclovir (Zovirax), a potent, specific and tolerable nucleosidic inhibitor of the herpes DNA polymerase, was a milestone in the development of antiviral drugs in the late 1970s. In the mid-1990s, when acyclovir became a generic drug, valacyclovir (Valtrex) and famciclovir (Famvir), prodrugs of the gold standard and penciclovir (Denavir), Vectavir), a close analogue, were launched. Though numerous approaches and strategies were tested and considerable effort was expended in the search of the next generation of an antiherpetic therapy, it proved difficult to outperform acyclovir. Notable in this regard was the award of a Nobel Prize in 1988 for the elucidation of mechanistic principles which resulted in the development of new drugs such as acyclovir. Vaccines, interleukins, interferons, therapeutic proteins, antibodies, immunomodulators and small-molecule drugs with specific or nonspecific modes of action lacked either efficacy or the required safety profile to replace the nucleosidic drugs acyclovir, valacyclovir, penciclovir and famciclovir as the first choice of treatment. Recently though, new inhibitors of the HSV helicase-primase with potent in vitro antiherpes activity, novel mechanisms of action, low resistance rates and superior efficacy against HSV in animal models have been discovered. This review summarises the current therapeutic options, discusses the potential of preclinical or investigational drugs and provides an up-to-date interpretation of the challenge to establish novel treatments for herpes simplex disease.

Animals↗
PubMed2002

Oral antivirals revisited in the treatment of herpes zoster: what do they accomplish?

Oral antiviral agents currently represent the most important therapeutic keystone in the treatment of herpes zoster. Three oral antiviral agents are available for the treatment of herpes zoster: acyclovir, its derivative valacyclovir, and famciclovir. Meta-analysis of published data has shown that oral acyclovir significantly reduces various herpes zoster-related symptoms as well as the duration, intensity and prevalence of zoster-associated pain (ZAP). However, this drug does not influence postherpetic neuralgia. The newer agents famciclovir and valacyclovir exhibit a better oral bioavailability than acyclovir. These agents have demonstrated similar efficacy to acyclovir with ZAP and they require less frequent administration. When initiated within 72 hours, oral antiviral therapy of herpes zoster is beneficial in selected, elderly immunocompetent patients, reducing the duration and intensity of ZAP and providing more rapid skin lesion healing. Oral antivirals are also of benefit in immunocompromised patients with uncomplicated herpes zoster. However, signs of cutaneous and visceral dissemination should be monitored; if signs occur, intravenous antiviral therapy is indicated.

Administration, Oral↗
PubMed1999

Drug treatment of common STDs: part I. Herpes, syphilis, urethritis, chlamydia and gonorrhea.

In 1998, the Centers for Disease Control and Prevention released guidelines for the treatment of sexually transmitted diseases. Several treatment advances have been made since the previous guidelines were published. Part I of this two-part article describes current recommendations for the treatment of genital ulcer diseases, urethritis and cervicitis. Treatment advances include effective single-dose regimens for many sexually transmitted diseases and improved therapies for herpes infections. Two single-dose regimens, 1 g of oral azithromycin and 250 mg of intramuscular ceftriaxone, are effective for the treatment of chancroid. A three-day course of 500 mg of oral ciprofloxacin twice daily may be used to treat chancroid in patients who are not pregnant. Parenteral penicillin continues to be the drug of choice for treatment of all stages of syphilis. Three antiviral medications have been shown to provide clinical benefit in the treatment of genital herpes: acyclovir, valacyclovir and famciclovir. Valacyclovir and famciclovir are not yet recommended for use during pregnancy. Azithromycin in a single oral 1-g dose is now a recommended regimen for the treatment of nongonococcal urethritis.

Anti-Infective Agents↗
PubMed2000

Does treatment of acute herpes zoster prevent or shorten postherpetic neuralgia?

OBJECTIVE: Our goal was to determine if any treatment of acute herpes zoster alters the incidence or duration of postherpetic neuralgia (PHN), a common sequela in elderly patients. SEARCH STRATEGY: We systematically searched MEDLINE and The Cochrane Library. We also examined the reference lists of identified trials and reviews. SELECTION CRITERIA: We included all randomized controlled trials of treatments of zoster published in English that included assessment of pain at any time after rash healing. DATA COLLECTION/ANALYSIS: Forty-two trials met inclusion criteria, and 2 reviewers independently evaluated them for methodologic quality and the statistical and clinical significance of results. MAIN RESULTS: Four placebo-controlled trials of oral acyclovir with 692 patients provided marginal evidence for reduction in pain incidence at 1 to 3 months following zoster onset. Famciclovir significantly reduced duration but not incidence of PHN in one placebo-controlled trial of 419 patients. Valacyclovir significantly reduced duration but not incidence of PHN in one acyclovir-controlled trial of 1141 patients. Steroids had no effect on PHN. Amitriptyline for 90 days reduced pain incidence at 6 months in one placebo-controlled trial of 80 patients. A single trial of percutaneous electrical nerve stimulation (PENS) in 50 patients suggested a decrease in pain incidence at 3 and 6 months compared with famciclovir. CONCLUSIONS: There is limited evidence that current interventions prevent or shorten PHN. Famciclovir and valacyclovir have been shown to reduce the duration of PHN in single published trials. Well-designed and larger trials of amitriptyline and PENS should be conducted.

Acute Disease↗
PubMedDate not supplied

[Efficacy of cidofovir in an HIV infected patient with an acyclovir and foscarnet resistant herpes simplex virus infection].

BACKGROUND: We report the case of an AIDS patient, whose persistant HSV2 ulceration was clinically and phenotypically resistant to acyclovir and foscarnet. Only five clinical isolates of simultaneous acyclovir and foscarnet resistance have been previously described. CASE REPORT: This patient, without history of opportunistic infection, was hospitalized for a recurrent scrotal ulceration resistant to several antiviral treatment such as acyclovir, valacyclovir or foscarnet. The CD4 count was stable at 150/mm(3) and the HIV viral load was below detection level. The last recurrence appeared rapidly under valacyclovir therapy which had been introduced after 65 days of foscarnet therapy. Thus, the patient received a new dose of foscarnet. After initial efficacy, the ulceration increased once again. HSV2 phenotypic determination was done and detected, at that time, a double resistance to acyclovir and foscarnet. Healing was obtained with intravenous cidofovir. DISCUSSION: Foscarnet and acyclovir resistance in an HSV2 isolate is rare. This report presents several particularities. First, whereas the earlier published patients with an acyclovir and foscarnet resistant strain were widely immunocompromised, this was not the case for our patient. Secondly, in contrast with most precedent observations in which acyclovir-resistant strain disappeared after foscarnet therapy, in our case the acyclovir resistant strain remained after foscarnet therapy. Finally, few reports concerned the clinical efficacy of cidofovir in HSV infection. In this case, we proved that intravenously cidofovir was highly and rapidly effective on acyclovir and foscarnet resistant strains.

AIDS-Related Opportunistic Infections↗
PubMed2001

Longitudinal analysis of varicella-zoster virus DNA on the ocular surface associated with herpes zoster ophthalmicus.

PURPOSE: Longitudinal analysis of varicella-zoster virus DNA on the ocular surface of patients with herpes zoster ophthalmicus. METHODS: Clinical specimens were obtained from the bulbar conjunctival surface with a cotton-tipped swab at weekly intervals for 6 consecutive weeks from 21 patients with acute ophthalmic zoster with a skin rash duration of less than 7 days. All patients received oral valacyclovir 1000 mg three times daily for 10 days without additional corticosteroids. The swabs were analyzed by means of polymerase chain reaction for the presence of varicella-zoster virus and herpes simplex virus type 1 DNA. Conjunctival swabs were also obtained from a control group of 20 patients with cataract. RESULTS: On inclusion, varicella-zoster virus DNA was present on the ocular surface of 19 of the 21 patients. Six varicella-zoster virus DNA-positive patients had no signs of ocular inflammation. All control swabs were negative for both varicella-zoster virus and herpes simplex virus DNA. The duration of varicella-zoster virus DNA detection from rash onset varied from 2 to 34 days. The number of days between the onset of herpes zoster skin rash and the latest positive varicella-zoster virus DNA test was significantly longer in patients whose age was equal to or above the median age of 66 years than in the younger patients (Mann-Whitney test: P =.0004). At 6-week follow-up, all conjunctival swabs were negative for varicella-zoster virus DNA. However, at that time, the eyes of seven patients were still inflamed. CONCLUSION: The duration of varicella-zoster virus DNA shedding in herpes zoster ophthalmicus is highly variable and age dependent, and is probably related to the host immune response.

Acyclovir↗
PubMed2001

Infection due to acyclovir resistant herpes simplex virus in patients undergoing allogeneic hematopoietic stem cell transplantation.

Over an eight-month period from October 1997 to May 1998, four patients who had received bone marrow transplant (BMT) from unrelated donor presented with severe mucosal cutaneous infections involving acyclovir resistant herpes simplex virus 1 (HSV-1). The four isolates were acyclovir (ACV) resistant, three of which were also foscarnet resistant as determined by the dye uptake method. The sequencing of the thymidine kinase (TK) gene did not permit to establish a relation between mutations and resistance to ACV. Three patients were considered as clinically cured of their HSV infection by replacement of ACV or foscarnet with either valacyclovir (one case) or cidofovir (two cases) but eventually two of them died of graft vs host disease. One patient died of extensive HSV infection despite administration of cidofovir. This study emphasizes the importance of monitoring the herpes virus resistance to antiviral drugs in bone marrow transplant recipients and the usefulness of the evaluation of novel antiviral drug for treatment of infections due to strains of HSV resistant to ACV and foscarnet that occur in about 5% of immunocompromised patients.

Acute Disease↗