Herpes virus infection, treatment

Neonatal herpes simplex virus infection Treatment of neonatal herpes infections. Parenteral Treatment of initial and recurrent mucosal and cutaneous herpes simplex virus (HSV)-I and -2 and varicella-zoster virus (VZV/shingles) infections in immunocompromised patients. 

Antiviral activity. Water extract of the dried fruit, in cell culture at a concentration of 10%, was inactive on herpes virus-type 2, influenza, poliovirus, and vaccina . Tincture of the dried fruit, administered orally to adults of both sexes at a dose of 60 mL/person, was active on herpes virus. PCT patent number W096/14064 reported treatment of six subjects with herpes virus infections. The activity was highly dose... 

Interferons (IFN) are glycoproteins that, among other products, are released from virus-infected cells. In neighboring cells, interferon stimulates the production of antiviral proteins. These inhibit the synthesis of viral proteins by (preferential) destruction of viral DNA or by suppressing its translation. Interferons are not directed against a specific virus, but have a broad spectrum of antiviral action that is, however, species-specific. Thus, interferon for use in humans must be obtained from cells of human origin, such as leukocytes (IFN-a), fibroblasts (IFN-p), or lymphocytes (IFN-y). Interferons are used in the treatment of certain viral diseases, as well as malignant neoplasias and autoimmune diseases e.g., IFN-a for the treatment of chronic hepatitis C and hairy cell leukemia and IFN-p in severe herpes virus infections and multiple sclerosis. 

This chapter is a review of the antimicrobial susceptibilities of the causative organisms and the treatment of the sexually transmitted infections most prevalent in North America and Western Europe, gonorrhea, nongonococcal urethritis, genital herpes virus infections, and trichomoniasis. Because of their relative rarity or because no important advances in therapy have been made in the past decade, syphilis, lymphogranuloma venereum, chancroid, and granuloma inguinale are not considered. 

Its principal use is against superficial herpes virus infections of humans in which it produces a moderate cure rate without harming the tissue to which the drug is applied. Since dermal herpes simplex is usually self-limiting and of short duration, the assessment of clinical effect is not easy when double-blind trials are carried out. Some authors claim that a statistically positive result is obtained and an almost equal number conclude that the difference between drug and placebo treated patients is not significant. Some patients, however, consider the treatment to be beneficial [190]. 

Acyclovir (Zovirax) and penciclovir (Denavir) are the only topical antiviral dragp currently available These dragp inhibit viral replication. Acyclovir is used in the treatment of initial episodes of genital herpes, as well as heqies simplex virus infections in immunocompromised patients (patients with an immune system incapable of fighting infection). Penciclovir is used for the treatment of recurrent herpes labialis (cold sores) in adults. 

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] (ACV) is clinically useful in the treatment of infections caused by several members of the herpes virus (e.g., herpes simplex, varicella zoster and Epstein-Barr virus [2,38,39]). An enzyme coded for by the virus phosphorylates ACV to a monophosphate intermediate. This species in turn undergoes further phosphorylation to a triphosphate with the aid of normal cell enzymes. Then, ACV triphosphate inhibits the herpes virus DNA... 

YT Bryson, M Dillon, G Acuna, S Taylor, JD Cherry, BL Johnson, E Wiesmeier, W Growden, T Greagh-Kirk, R Keeney. Treatment of first episodes of genital herpes simplex virus infection with oral acyclovir. A randomized double-blind controlled trial in normal subjects. N Engl J Med 308 916-921, 1983. 

Aciclovir (acyclovir) was one of the first effective selective antiviral agents. It is a guanine derivative of value in treating herpes viruses, though it does not eradicate them, and is only useful if drug treatment is started at the onset of infection. 

WraZ/nfecf/on. Treatment with tacrolimus ointment may be associated with an increased risk of varicella zoster virus infection (chicken pox or shingles), herpes simplex virus infection, or eczema herpeticum. 

Antibodies against the virus but also amantadine and derivatives, interfere with host cell penetration. There are nucleoside analogues such as aciclovir and ganciclovir, which interfere with DNA synthesis, especially of herpes viruses. Others like zidovudine and didanosine, inhibit reverse transcriptase of retroviruses. Recently a number of non-nucleoside reverse transcriptase inhibitors was developed for the treatment of HIV infections. Foscarnet, a pyrophosphate analogue, inhibits both reverse transcriptase and DNA synthesis. Protease inhibitors, also developed for the treatment of HIV infections, are active during the fifth step of virus replication. They prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new vi-rons. 

Foscarnet is an inorganic pyrophosphate analogue which causes selective inhibition of viral DNA polymerase and reverse transcriptase. Topical foscarnet cream has appeared to be a safe and effective treatment for aciclovir-unresponsive mucocutaneous herpes simplex virus infection in AIDS patients. 

Trifluoromethyl-2 -deoxyuridine, trifluridine (Viroptic ), is an anti-viral drug acting on TS via another mechanism. It is a mechanism-based inactivator of thy-midylate synthase (Figs. 27 and 28). Trifluridine is marketed for the topical treatment of Herpes simplex virus infection in eyes. 

Trifluridine (5-trifluoromethyl-2 -deoxyuridine) (Viroptic ) is marketed for the topical treatment of herpes simplex virus infection in the eyes. This antiviral drug is a mechanism-based inactivator of thymidylate synthase. The mechanism of inhibition and synthesis of trifluoridine are reported in Chapter 7. 

Treatment of herpes simplex virus infection of the skin and mucous membrane, including initial and recurrent genital herpes. 

IgG receptors on cultured, human lymphocytes.526 Sialidase treatment of lymphocytes from sensitized subjects increased the responsiveness to viral, bacterial, and fungal antigens.527 The same treatment of human, Herpes simplex virus-infected cells was found to enhance the sensitivity of the cells to lysis mediated by antibody and complement.528... 

Inhibition of glycosylation in virus-infected cells usually has dramatic effects on virus multiplication. This discovery prompted promulgation of a new concept in the experimental therapy of virus-induced diseases. Local treatment of the affected regions with 2-deoxy-D-arabtno-hexose led50n s02 to significant improvements in human-genital herpes infections, or Herpes simplex virus infection of the eye. 

Topical acyclovir (Zovirax) is available as a 5% ointment topical penciclovir (Denavir), as a 1% cream for the treatment of recurrent orolabial herpes simplex virus infection in immunocompetent adults. Adverse local reactions to acyclovir and penciclovir may include pruritus and mild pain with transient stinging or burning. 

Acyclovir is useful in the treatment of herpes. Oral herpes is caused by the herpes simplex virus 1 (HSV-1), and genital herpes is caused by the herpes simplex virus 2 (HSV-2). More than 90 percent of the world s population is infected with the oral herpes virus, though there are many infected people who do not exhibit symptoms. Genital herpes is the most prevalent nondurable sexually transmitted disease. In the United States, there are about 30 million people infected with HSV-2 and an estimated 200,000 to 500,000 new cases each year. 

Acyclovir (ACV) is not a true nucleoside, because the guanine residue is attached to an open-chain structure, but it mimics deoxyribose well enough for the compound to be accepted as a substrate by a thymidine kinase specified by certain herpes-type viruses. The normal thymidine kinase in mammalian cells does not recognize ACV as a substrate, however, so only virus-infected cells convert ACV to its monophosphate. Once the first phosphate has been added, the second phosphate is added by cellular guanylate kinase several other cellular kinases can add the third phosphate. The triphosphate is a more potent inhibitor of the viral DNA polymerases than of cellular DNA polymerases and also inactivates the former but not the latter. The net result is that ACV has been an effective treatment of, and prophylaxis for, genital herpes. Also it can result in dramatic relief of pain associated with shingles caused by reactivation of latent varicella-zoster virus, and has been successful in many patients with herpes encephalitis. 

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... 

Phosphorylated aciclovir inhibits DNA polymerase and so prevents viral DNA being formed. It effectively treats susceptible herpes viruses if started early in the course of infection, but it does not eradicate persistent infection. Taken orally about 20% is absorbed from the gut, but this is sufficient for the systemic treatment of some infections. It distributes widely in the body the concentration in CSF is approximately half that of plasma, and the brain concentration may be even less. These differences are taken into account in dosing for viral encephalitis (for which aciclovir must be given i.v.). The drug is excreted in the urine (t, 3 h). For oral and topical use the drug is given x 5/d. 

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