VZV infection

VZV radiculopathy or myeloradiculopathy AIDS Acute Lumbosacral pain saddle anesthesia rapidly progressive flaccid paraparesis VZV infection Schwann ceU-endothelial cells infection... 

Patients who are HSV- or VZV-seronegative prior to HCT rarely develop primary HSV or VZV infection therefore, prophylactic antivirals are not warranted. Patients who are HSV-antibody-seropositive before HCT are at high risk for reactivation of their... 

In those with a history of VZV infection, VZV disease occurs in 30% of allogeneic HCT recipients.91 The appropriate duration of VZV prophylaxis is controversial.8 Although VZV infections are reduced by prophylactic acyclovir (800 mg twice daily), administered from 1 to 2 months until 1 year after HCT, the risk of VZV persists in those on continued immune suppression.91... 

AGENTS TO TREAT HERPES SIMPLEX VIRUS (HSV) VARICELLA-ZOSTER VIRUS (VZV) INFECTIONS... 

Three oral nucleoside analogs are licensed for the treatment of HSV and VZV infections acyclovir, valacyclovir, and famciclovir. They have similar mechanisms of action and similar indications for clinical use all are well tolerated. Acyclovir has been the most extensively studied it was licensed first and is the only one of the three that is available for intravenous use in the United States. Comparative trials have demonstrated similar efficacies of these three agents for the treatment of HSV but modest superiority of famciclovir and valacyclovir for the treatment of herpes zoster. Neither valacyclovir nor famciclovir has been fully evaluated in pediatric patients thus, neither is indicated for the treatment of varicella infection. 

Table 49-1 Agents to Treat or Prevent Herpes Simplex Virus (HSV) and Varicella-Zoster Virus (VZV) Infections. ...

Foscarnet1 Intravenous Acyclovir-resistant HSV and VZV infections 40 mg/kg q8h until healed... 

Intravenous acyclovir is the treatment of choice for herpes simplex encephalitis, neonatal HSV infection, and serious HSV or VZV infections (Table 49-1). In immunocompromised patients with VZV infection, intravenous acyclovir reduces the incidence of cutaneous and visceral dissemination. 

The bioavailability of penciclovir from orally administered famciclovir is 70% less than 20% is plasma protein-bound. A peak serum concentration of 2 vgJmL is achieved following a 250 mg oral dose. Penciclovir triphosphate has an intracellular half-life of 10 hours in HSV-1-infected cells, 20 hours in HSV-2-infected cells, and 7 hours in VZV-infected cells in vitro. Penciclovir is excreted primarily in the urine. 

Vidarabine [vye DARE a been] arabinofuranosyl adenine, ara-A, adenine arabinoside) is one of the most effective of the nucleoside analogs and is also the least toxic. However, it has been supplanted clinically by acyclovir, which is more efficacious and safe. Although vidarabine is active against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), its use is limited to treatment of immunocompromised patients with herpes simplex keratitis or encephalitis, or VZV infections. Vidarabine, an adenosine analog, is converted in the cell to its 5 -triphosphate analog (ara-ATP), which is postulated to inhibit viral DNA synthesis. Some resistant herpes virus... 

Acute VZV infection leads to chickenpox, which is characterized by malaise, fever, and an extensive vesicular rash (Abendorth and Arvin, 2000). Chickenpox in the immunocompetent child is mostly benign and associated with lassitude and a temperature of 100-103 °F for 1-2 days. Other symptoms include malaise, itching, anorexia, weakness, and exhaustion, and these gradually resolve as the illness improves. The hallmark of chickenpox is the skin manifesta-... 

Aciclovir After oral application, only about 20% of the applied dose of this guanosine derivative is absorbed. Aciclovir is mainly eliminated via the kidneys (ca. 85% of the dose within 48 hours). Its half-life, which is approx. 3 hours, depends on renal function. The substance is employed especially in HSV and VZV infections. This agent inhibits DNA polymerase (i.e. replication) and effects a chain break. As a monotherapy in HBV infection, aciclovir only shows moderate efficacy. Side effects are rare. 

J.) Ganciclovir This is a guanosine derivative exhibiting a good action profile in HBV, EBV, CMV and VZV infection. Ganciclovir triphosphate inhibits virus replication. The half-life is about 4 hours. Elimination is via the kidneys. Only a minor fraction of this substance is absorbed after oral administration application (e.g. in CMV infection) is usually intravenous (10 mg/kg BW/ day). It has severe toxic side effects. Ganciclovir was... 

Acyclovir is useful for treating infections caused by HSV, herpes zoster, and for VZV infections (Whitley and Roizman, 2001). Although HCMV is relatively resistant to acyclovir, some cytomegalovirus infections have responded marginally to large doses of acyclovir, and it seems to be effective for the prophylaxis of cytomegalovirus infections in immunocompromised patients. Epstein-Barr virus is not sensitive to acyclovir, and clinical infections do not respond to the drug. 

Scrape VZV-infected Mewo cells into overlay medium when cytopathic effect is 60-80% (scraping ruptures syncytia and releases virus). 

Remove medium, rinse with PBS, and scrape VZV-infected MRC5 fibroblasts into PSGC (1/10 vol of overlay medium). 

Up to 50% of all patients surviving up to 10 months after transplantation develop an infection caused by VZV. Infection with VZV is most common in patients receiving allogeneic transplants with acute or chronic GVHD. Both primary (varicella) or recurrent disease (herpes zoster) usually present as skin lesions, most of which remain contained to local areas however, 30% to 45% of these infections may disseminate to other cutaneous areas or body organs, causing mortality as high as 50%. " ... 

Although high-dose oral acyclovir given for 6 months after transplantation also significantly reduces reactivation of VZV infections, routine use of long-term acyclovir is controversial and not generally recommended for this indication. Patients who received HSCT within the previous 24 months or those beyond 24 months after HSCT who have chronic GVHD or are on immunosuppressive... 

Zoster usually begins as radicular pain followed by localized erythematous rash and characteristic vesicles. Zoster usually remains confined to a limited number of dermatomes, but complications such as widespread cutaneous involvement and disseminated visceral zoster may occur. As in the treatment of HSV infections, acyclovir is the drug of choice for VZV infections. While an oral acyclovir regimen of 4 g/day is effective for the treatment of zoster in immunocompetent adults, the drug has not been fuUy evaluated in immunocompromised patients such as those with AIDS. For practical reasons, oral acyclovir, famciclovir, or valacyclovir is often used for localized zoster. However, careful monitoring for signs of progression of zoster is essential. AIDS patients with disseminated cutaneous or visceral zoster should receive treatment with intravenous acyclovir in doses of 30 mg/kg per day for at least 7 days or until all lesions are crusted. Acyclovir-resistant VZV infections have been reported in patients with AIDS." ... 

Famciclovir, the oral formulation of penciclovir, is a new antiherpes agent that is well absorbed following oral administration with little intersubject variability, and is rapidly converted to penciclovir with a bioavailability of 77%. Furthermore, although the activities of penciclovir and acyclovir against varicella-zoster virus (VZV) in infected cell lines appear to be comparable, penciclovir-triphosphate persists in virus-infected cells far longer than acyclovir-triphosphate, resulting in more prolonged antiviral activity. The intracellular half-life of penciclovir-triphosphate in VZV-infected cells is reported to be 9 hours, whereas that of... 

The first systemically administered antiherpesvirus agent, vidarabine, was approved by the Food and Drug Administration (FDA) in 1977. However, its toxicities restricted its use to life-threatening infections of HSV and varicella-zoster virus (VZV). The discovery and development of acyclovir, approved in 1982, provided the first effective treatment for less severe HSV and VZV infections in ambulatory patients. Intravenous acyclovir is superior to vidarabine in terms of efficacy and toxicity in HSV encephalitis and in VZV infections of immunocompromised patients. Acyclovir is the prototype of a group of antiviral agents that are phosphorylated intraceUularly by a viral... 

THERAPEUTIC USES In immunocompetent persons, the clinical benefits of acyclovir and valacyclovir are greater in initial HS V infections than in recurrent ones, which typically are milder. These drugs are particularly useful in immunocompromised patients because these individuals experience more frequent and more severe HSV and VZV infections. Since VZV is less susceptible than HSV to acyclovir, higher doses must be used for treating varicella or zoster infections. Oral valacyclovir is as effective as oral acyclovir in HSV infections and more effective for treating herpes zoster. 

Acyclovir-resistant VZV isolates uncommonly have been recovered from HIV-infected children and adults who may manifest chronic hyperkeratotic or verrucous lesions and sometimes meningoradiculitis. Intravenous foscarnet appears to be effective for acyclovir-resistant VZV infections. 

MECHANISMS OF ACTION AND RESISTANCE Penciclovir inhibits viral DNA synthesis. In HSV- or VZV-infected cells, penciclovir is phosphorylated initially by viral TK. Penciclovir triphosphate competitively inhibits viral DNA polymerase (Figure 49-2). Although penciclovir triphosphate is approximately one one-hundredth times as potent as acyclovir triphosphate in inhibiting viral DNA polymerase, it is present in infected cells at much higher concentrations and for more prolonged periods. The prolonged intracellular half-life of penciclovir triphosphate,... 

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