Prophylaxis Of Herpesvirus Infections Research Articles

Latent viral infections in critically ill patients

A key message of Osawa and Singh's review of cytomegalovirus infection in critically ill patients is that the infection occurred in 25% of patients and was associated with worse outcome [1]. Emphasis was placed on the lack of proof of causality between infection and outcome, and reactivation may reflect illness severity. The herpesvirus family all cause latent infections in humans, and similar rates of infection, morbidity and mortality have also been reported in comparable patients with herpes simplex virus [2,3]. Nevertheless, although infection rates with latent herpesviruses appear high, the majority of seropositive patients do not suffer reactivation. Acquisition of herpesviruses in infancy results in trivial clinical illness, suggesting we have co-evolved effectively with these pathogens. Indeed a recent report highlighted how herpesviruses offer protection from bacterial infections [4]. Latent, but not acute, infection conferred a 100-fold to 1,000-fold reduction in bacterial burden due to IFNγ-dependent macrophage activation. Latency with all herpesviruses in humans is probably associated with frequent subclinical reactivation, which may lead to reticuloendothelial cell priming [5]. We suggest that the sequelae of latent infection may not be universally adverse in all patients, some of whom may be protected from developing septic shock and never enter the intensive care unit. Osawa and Singh suggested a study to determine the role of antiviral agents; until the mechanisms and significance of reactivation in different patient groups are elucidated, however, such studies will prove difficult to interpret. A pilot study of acyclovir in the prophylaxis of herpesvirus infections in critical care is already underway in the United Kingdom (ISRCTN29934637).

Prophylaxis of herpesvirus infections in the elderly

Prophylaxis of herpesvirus infections in the elderly

Prophylaxis of herpesvirus infections in immunocompetent and immunocompromised older patients.

In older patients, prophylaxis of herpesvirus infections mainly involves preventing the recurrence of herpes simplex virus (HSV) and complications of herpes zoster in immunocompetent patients, while in immunocompromised patients it is more concerned with the prevention of opportunistic virus reactivation. HSV ocular infection is the most frequent cause of corneal blindness in the US. The effectiveness of aciclovir 400mg twice daily in preventing the recurrence of HSV eye disease in immunocompetent patients has been well demonstrated. The issue of treatment duration for patients with highly recurrent ocular herpes remains unresolved. Post-herpetic neuralgia (PHN) is one of the most common neuralgic illnesses worldwide. Some progress in prevention of PHN has been made with a combination of antiviral therapy (famciclovir or valaciclovir), started within 72 hours of onset of the rash, and analgesic treatment. However, the best prevention of PHN is the prevention of herpes zoster disease, and the varicella vaccine is an option which over the next few years will be tested in clinical trials. For immunocompromised patients of any age, restoring immunity prevents herpesvirus disease, as demonstrated for cytomegalovirus (CMV) in AIDS patients receiving highly active antiretroviral therapy. Specific antiviral therapy during the initial period after transplantation could prevent reactivation of HSV or CMV in seropositive recipients. Whether pre-emptive therapy or prophylaxis with ganciclovir is the optimal approach against CMV remains controversial, and the relative merits and limitations of each approach may guide the choice. In stem cell transplantation, pre-emptive therapy with foscarnet avoids the neutropenia and related complications associated with ganciclovir. In renal transplant recipients, universal prophylaxis of CMV infection with valaciclovir has the same efficacy as ganciclovir. Although it is relatively toxic, cidofovir should be further evaluated because of its in vitro activity against most DNA viruses.

Advances in Antiviral Therapy

Recent developments have increased the options for treatment of viral infections. Vidarabine, an agent originally released for herpes simplex encephalitis, has more recently been shown to be of benefit in neonatal herpes simplex infection and in varicella-zoster infections in immunocompromised hosts. The introduction of acyclovir represents a major advance in antiviral therapy because of its low host toxicity and marked selectivity for herpes simplex and varicella-zoster viruses. Extensive controlled clinical trials demonstrate efficacy in the treatment of infections caused by these viruses in the immunocompromised host and in genital herpes simplex infections in normal hosts. The use of recombinant DNA technology has increased the purity, variety, and availability of interferons for clinical trial. Earlier experience with natural buffy coat-derived alpha interferon showed efficacy in the treatment of varicella-zoster infections in the immunocompromised host, as well as prophylaxis of herpes virus infections in high-risk populations. These results have to be confirmed using the newer interferon preparations. Under development are a variety of new drugs with broadened viral spectrum and improved pharmacokinetic properties. These include nucleoside analogues and novel interferons with modified amino acid sequences. One or more of these agents, used singly or in combination, may prove useful in the more difficult therapeutic problems, such as cytomegalovirus and hepatitis B infections.

Advances in antiviral therapy.

Recent developments have increased the options for treatment of viral infections. Vidarabine, an agent originally released for herpes simplex encephalitis, has more recently been shown to be of benefit in neonatal herpes simplex infection and in varicella-zoster infections in immunocompromised hosts. The introduction of acyclovir represents a major advance in antiviral therapy because of its low host toxicity and marked selectivity for herpes simplex and varicella-zoster viruses. Extensive controlled clinical trials demonstrate efficacy in the treatment of infections caused by these viruses in the immunocompromised host and in genital herpes simplex infections in normal hosts. The use of recombinant DNA technology has increased the purity, variety, and availability of interferons for clinical trial. Earlier experience with natural buffy coat-derived alpha interferon showed efficacy in the treatment of varicella-zoster infections in the immunocompromised host, as well as prophylaxis of herpes virus infections in high-risk populations. These results have to be confirmed using the newer interferon preparations. Under development are a variety of new drugs with broadened viral spectrum and improved pharmacokinetic properties. These include nucleoside analogues and novel interferons with modified amino acid sequences. One or more of these agents, used singly or in combination, may prove useful in the more difficult therapeutic problems, such as cytomegalovirus and hepatitis B infections.

Antiherpes drugs: promises and pitfalls.

In recent years several selective antiherpes drugs have been developed which all show great promise for the systemic and topical treatment of herpes simplex virus and varicella-zoster virus infections. These new antiherpes agents include acyclovir, bromovinyldeoxyuridine, fluoroiodoaracytosine and phosphonoformate. Acyclovir has already been licensed for both topical and systemic use, and it is expected that other compounds will follow soon. Although this new generation of antiherpes drugs suffer from some drawbacks, i.e. narrow spectrum of activity, inefficacy during virus latency, and the possible emergence of drug-resistant virus strains, these limitations by no means outweigh the potentials of these drugs in the therapy and prophylaxis of herpesvirus infections in humans.