Disseminated Herpes Zoster in the Immunocompromised Host: A Comparative Trial of Acyclovir and Vidarabine

Whitley, Richard J.; Gnann, John W.; Hinthorn, Daniel R.; Liu, Chein; Pollard, Richard B.; Hayden, Frederick G.; Mertz, Grégory; Oxman, Michael N.; Soong, Seng Jaw

doi:10.1093/infdis/165.3.450

Cited by 89 publications

(28 citation statements)

References 9 publications

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“…Ara-A has been used for the treatment of herpesvirus infections, but it is less efficient and more toxic than acyclovir [129][130][131][132]. However, ara-A is capable of inhibiting acyclovir-resistant HSV and VZV (varicella-zoster virus) [133][134][135].…”

Section: Antiviral Activitymentioning

confidence: 99%

Marine Sponges: Potential Sources of New Antimicrobial Drugs

Laport¹,

Santos²,

Muricy³

2009

CPB

259

191

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Sponges (phylum Porifera) are sessile marine filter feeders that have developed efficient defense mechanisms against foreign attackers such as viruses, bacteria, or eukaryotic organisms. Marine sponges are among the richest sources of pharmacologically-active chemicals from marine organisms. It is suggested that (at least) some of the bioactive secondary metabolites isolated from sponges are produced by functional enzyme clusters, which originated from the sponges and their associated microorganisms. More than 5,300 different products are known from sponges and their associated microorganisms, and more than 200 new metabolites from sponges are reported each year. As infectious microorganisms evolve and develop resistance to existing pharmaceuticals, the marine sponge provides novel leads against bacterial, viral, fungal and parasitic diseases. Many marine natural products have successfully advanced to the late stages of clinical trials, as for example ara-A (vidarabine), an anti-viral drug used against the herpes simplex encephalitis virus. This substance is in clinical use for many years. Moreover, a growing number of candidates have been selected as promising leads for extended preclinical assessment, including manzamine A (activity against malaria, tuberculosis, HIV, and others), lasonolides (antifungal activity) and psammaplin A (antibacterial activity). In this review we have surveyed the discoveries of products derived from marine sponges and associated bacteria that have shown in vivo efficacy or potent in vitro activity against infectious and parasitic diseases, including bacterial, viral, fungal and protozoan infections. Our objective was to highlight the substances that have the greatest potential to lead to clinically useful treatments.

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Section: Antiviral Activitymentioning

confidence: 99%

Marine Sponges: Potential Sources of New Antimicrobial Drugs

Laport¹,

Santos²,

Muricy³

2009

CPB

259

191

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show abstract

“…Morbidity, including pain, scarring, post-herpetic neuralgia, and secondary infection occur in up to one third of patients with VZV infection, and hospitalization may be required with disseminated disease. 1,[7][8][9] VZV disease can occasionally also be fatal after allogeneic HCT, even if treated with acyclovir, with most fatalities occurring during the first year after transplantation. [1][2][3] Furthermore, hepatic or gastrointestinal VZV disease may occur with few or no skin lesions, which often delays the diagnosis and leads to a high mortality.…”

Section: Introductionmentioning

confidence: 99%

Long-term acyclovir for prevention of varicella zoster virus disease after allogeneic hematopoietic cell transplantation—a randomized double-blind placebo-controlled study

Boeckh

Kim

Flowers

et al. 2006

Blood

229

185

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Varicella-zoster virus (VZV) disease occurs in 30% of allogeneic hematopoietic cell transplant recipients who had a history of VZV infection. A safe and effective prevention strategy has not been established. In a double-blind controlled trial, 77 hematopoietic cell transplant recipients at risk for VZV reactivation were randomized to acyclovir 800 mg twice daily or placebo given from 1 to 2 months until 1 year after transplantation. VZV disease at 1 year was the primary end point; VZV disease after discontinuation of prophylaxis, VZV-specific T-cell immunity, herpes simplex virus (HSV) infection, cytomegalovirus (CMV) disease, survival, and safety were secondary end points. Acyclovir significantly reduced VZV infections at 1 year after transplantation (HR, 0.16; 95% CI, 0.035-0.74; P ‫؍‬ .006). In the postintervention observation period, this difference was not statistically significant (2 years: HR, 0.52; 95% CI, 0.21-1.3; 5 years: HR, 0.76; 95% CI, 0.36-1.6). There was no statistically significant difference in reconstitution of VZVspecific T-helper cell responses, HSV infections, CMV disease, chronic graftversus-host disease, and overall survival between the groups. Acyclovir was well tolerated. Post-study VZV disease predominantly occurred in patients with continued need for systemic immunosuppression. In conclusion, acyclovir effectively and safely prevents VZV disease during the first year after hematopoietic cell transplantation. Periods of prophylaxis longer than 12 months may be beneficial for those hematopoietic cell transplant recipients on continued immune suppression.

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“…Early treatment with antiviral agents, such as ACV and vidarabine, needs to shorten the skin lesions and complications related to herpes zoster. 13 In clinical practice, the start of administration of VACV limited within the first 72 h after the onset of symptoms. These results indicated that CP-44161 could be given over 72 h after the onset; that is, the recalcitrant cases against ACV.…”

Section: Discussionmentioning

confidence: 99%

Anti-herpes virus activity of polyether antibiotic CP-44161 in vivo

Yamagishi

Ueno

et al. 2009

J Antibiot

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In the previous study, we discovered a polyether antibiotic CP-44161, which was reported earlier as an anticoccidal agent, as an anti-varicella zoster virus compound. In this study, we demonstrated that CP-44161 had a very strong and broad anti-herpes virus activities against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro. To determine the antiviral activity of CP-44161 in vivo, we examined its effect on the cutaneous HSV-2 infection model in Balb/c mice. CP-44161 showed inhibitory effect on lesion development as well as acyclovir (ACV) when the treatment was started from day 3. Meanwhile, in case the start of treatment was delayed until day 4, when ACV was no longer effective, the effectiveness of CP-44161 still remained. In this model, CP-44161 also showed inhibitory effect on the proliferation of HSV-2 DNA in dorsal root ganglia. This is the first article to report that polyether antibiotics can be effective on viral infection in vivo. INTRODUCTIONThere are eight human herpesvirus that cause various diseases in humans. Herpes simplex virus type 1 (HSV-1), a causative agent of cold sore and corneal herpes, HSV type 2 (HSV-2), a causative agent of genital herpes, and varicella zoster virus (VZV), a causative agent of varicella (chickenpox) and herpes zoster (shingles), belong to alphaherpesvirinae. They usually infect mucosal epithelial cells and travel along the neuron (by a process called retrograde transport) to trigeminal ganglia and then establish latent infection. 1 Most of the problems with herpesvirus infections are due to reactivation that may lead to recurrent infections. The risk of diseases increases with age, and also frequently occurs in immunocompromised hosts, such as cancer patients, transplantation patients or acquired immunodeficiency syndrome patients. 2 Standard antiviral drugs at present used in the treatment of HSV and VZV infections include acyclovir (ACV), valaciclovir (VACV, the oral prodrug of ACV), famciclovir (the oral prodrug of penciclovir) and vidarabine (Ara-A). 3,4 Despite a number of recent therapeutic advancements, there remains an urgent need to develop a new class of therapy, especially novel anti-herpes virus agent with a strong potency against HSV-2 and VZV, because anti-herpes virus agents used at present exhibit lower potency against HSV-2 and VZV. Furthermore, as they had some problems, such as cross-resistance and mutagenicity, the development of new agents with different mechanism of action from nucleoside analogs was required.

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Disseminated Herpes Zoster in the Immunocompromised Host: A Comparative Trial of Acyclovir and Vidarabine

Cited by 89 publications

References 9 publications

Marine Sponges: Potential Sources of New Antimicrobial Drugs

Marine Sponges: Potential Sources of New Antimicrobial Drugs

Long-term acyclovir for prevention of varicella zoster virus disease after allogeneic hematopoietic cell transplantation—a randomized double-blind placebo-controlled study

Anti-herpes virus activity of polyether antibiotic CP-44161 in vivo

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