Study Evaluates Use Of Corticosteroids And Antiviral Agents For Treatment Of Bell Palsy

ScienceDaily (Sep. 3, 2009) — Among patients with Bell Palsy, a facial paralysis with unknown cause, treatment with corticosteroids is associated with a reduced risk of an unsatisfactory recovery, and treatment with a combination of corticosteroids and antiviral agents may be associated with additional benefit, according to a systematic review and meta-analysis of previously published studies, reported in the September 2 issue of JAMA.

In background information provided by the authors, they note that Bell Palsy "is an acute weakness or paralysis of the facial nerve," and has an annual incidence of 20 to 30 per 100,000 population. "While 71 percent of untreated patients will completely recover and 84 percent will have complete or near normal recovery, the remainder will have persistent to moderate to severe weakness, facial contracture, or synkinesis [involuntary movement]." The authors explain that a herpes infection likely causes the disorder. DNA samples from patients have yielded herpes simplex virus type 1 (HSV-1). Varicella zoster virus (VZV) reactivation is also associated with Bell Palsy.

John R. de Almeida, M.D., from Sunnybrook Hospital and the University of Toronto, Canada, and colleagues conducted a search of the medical literature for randomized controlled trials comparing treatment with either corticosteroids or antiviral agents with a control measuring unsatisfactory facial recovery (four months or more), unsatisfactory short-term recovery (six weeks to less than four months), synkinesis and autonomic dysfunction, or adverse effects. The authors identified 854 studies, of which 18 were eligible for inclusion for evaluation. The 18 studies included 2,786 patients and were conducted in 12 countries and five continents.

"… high-quality evidence suggests that corticosteroids alone reduce the risk of unsatisfactory recovery by 9 percent in absolute terms, with a NNTB (number of patients needed to treat for one patient to experience benefit) of 11," the authors report. "Corticosteroid therapy combined with antiviral agents reduced the risk of unsatisfactory recovery compared with antiviral agents alone. Corticosteroids were also associated with a 14 percent absolute risk reduction of synkinesis and autonomic dysfunction (NNTB, 7; moderate quality of evidence). Corticosteroids were not associated with an increased risk of adverse effects."

"Our results suggest a possible incremental benefit of antiviral agents in addition to corticosteroids, with an absolute risk reduction of 5 percent compared with corticosteroids alone. This effect, however, is not definitive and did not quite reach statistical significance," the authors write. "Further primary studies are needed to definitively establish – or refute – an incremental benefit of combined therapy compared with corticosteroid mono therapy," the authors conclude.

Editorial: Treatment of Bell Palsy – Translating Uncertainty Into Practice

"The systematic review by de Almeida et al of medications for treatment of Bell palsy helps resolve lingering doubt about the benefits of corticosteroids, but raises questions about the adjunctive role of antiviral medications," John F. Steiner, M.D., M.P.H., of Kaiser Permanente Colorado, Denver, writes in an accompanying editorial.

"Until the next generation of clinical trials is completed, clinicians and patients will have to deal with substantial uncertainty in deciding whether to add antiviral drugs to corticosteroids for Bell palsy. By assessing how clinicians alter their prescribing patterns and how treatment guidelines are revised in response to this new evidence, it will be possible to learn more about how clinical uncertainty is translated into practice."

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by JAMA and Archives Journals.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

John R. de Almeida; Murtadha Al Khabori; Gordon H. Guyatt; Ian J. Witterick; Vincent Y. W. Lin; Julian M. Nedzelski; Joseph M. Chen. Combined Corticosteroid and Antiviral Treatment for Bell Palsy: A Systematic Review and Meta-analysis. JAMA, 2009; 302 (9): 985-993 [link]

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Antiviral therapy associated with fewer recurring eye problems from herpes simplex virus

ScienceDaily (Sep. 14, 2010) — Taking oral antiviral medications following infection with the herpes simplex virus may be associated with a reduced risk of recurring eye-related manifestations of the disease, according to a report in the September issue of Archives of Ophthalmology, one of the JAMA/Archives journals.

"Herpes simplex virus (HSV) is a common cause of corneal disease and is the leading infectious cause of corneal blindness among developed nations," the authors write as background information in the article. After the initial exposure to the virus and the resulting systemic infection, herpes simplex establishes a latent infection in sensory nerve structures. Reactivation of this latent infection could lead to initial or recurrent disease in one or both eyes, including inflammation or infection of the cornea, eyelid, membrane inside the eye (conjunctivitis, or pink eye) or middle layer of the eye (uveitis).

Ryan C. Young, B.A., of Mayo Clinic, Rochester, Minn., and colleagues estimated the incidence of HSV eye disease in a community-based cohort, in Olmstead County, Minnesota, from 1976 through 2007. During this time period, 394 patients with ocular HSV were identified, for an annual incidence of 11.8 per 100,000 individuals.

Oral antiviral therapy was prescribed in 175 (44 percent) of these patients, who underwent therapy for an average of 2.8 years (36 percent of the average 7.7 years of follow-up). Patients not taking this prophylactic therapy were 9.4 times more likely to have a recurrence of epithelial keratitis (infection of the top layer of the cornea), 8.4 times more likely to have a recurrence of stromal keratitis (infection of deeper layers of the cornea) and 34.5 times more likely to have a recurrence of blepharitis (eyelid infection) or conjunctivitis than those taking antiviral medications.

A total of 20 patients experienced adverse outcomes, including visual loss and perforation of the cornea; of these, 17 (85 percent) were not taking oral antiviral prophylaxis.

"Overall, this community-based retrospective study demonstrated a stable incidence of HSV eye disease during a recent 32-year period," the authors write. "We found a more dramatic protective effect of oral antiviral prophylaxis on recurrences of ocular HSV than had been described previously."

"The results of this study suggest that oral antiviral prophylaxis should be considered for patients with frequent recurrences of corneal disease," they conclude. "Additionally, we recommend an evaluation of the possible barriers preventing compliance with antiviral prophylaxis and a reassessment of the cost-effectiveness of long-term oral antiviral therapy."

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by JAMA and Archives Journals.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Ryan C. Young; David O. Hodge; Thomas J. Liesegang; Keith H. Baratz. Incidence, Recurrence, and Outcomes of Herpes Simplex Virus Eye Disease in Olmsted County, Minnesota, 1976-2007: The Effect of Oral Antiviral Prophylaxis. Arch Ophthalmol, 2010; 128 (9): 1178-1183 [link]

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

New way to target viruses could make antiviral drugs more effective

ScienceDaily (July 21, 2010) — Scientists have developed a new way to target viruses which could increase the effectiveness of antiviral drugs.

Instead of attacking the virus itself, the method developed at the University of Edinburgh alters the conditions which viruses need to survive and multiply.

By making the site of infection less hospitable for the virus, the virus becomes less able to mutate and build up resistance to drugs. The researchers were also able to target more than one virus at the same time.

Viruses take up residence in host cells within our body, which produce proteins that enable the virus to multiply and survive.

The study, published in the journal Proceedings of the National Academy of Sciences (PNAS), analysed molecules known as microRNAs, which regulate how much of these proteins are made.

The scientists were able to manipulate the microRNA levels, which enabled them to control a network of proteins and stop viruses from growing.

Most existing antiviral therapies only work against one virus. However, by adapting the virus host environment the researchers were able to target different types of viruses.

It is hoped that the research could lead to new treatments for patients suffering from a range of infections.

Dr Amy Buck, of the University's Centre for Immunity, Infection & Evolution, said: "A problem with current antiviral therapies, which generally target the virus, is that viruses can mutate to become resistant. Since new viral strains emerge frequently, and many infections are difficult to diagnose and treat, it is important to find new ways of targeting infection. Our hope is that we will be able to use host-directed therapies to supplement the natural immune response and disable viruses by taking away what they need to survive."

Scientists studied the herpes family of viruses, which can also cause cancer with the Epstein-Barr virus, and the Semliki Forest virus, which is mainly spread by mosquitoes.

Both viruses have different characteristics. Viruses from the herpes family replicate inside the nuclei of cells, while the Semliki Forest multiplies outside the nucleus of a cell.

Further research has begun to look at how this method could be used to target influenza.

The study was funded by the Wellcome Trust and the Biotechnology and Biological Sciences Research Council.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by University of Edinburgh.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Diwakar Santhakumar, Thorsten Forster, Nouf N. Laqtom, Rennos Fragkoudis, Paul Dickinson, Cei Abreu-Goodger, Sergei A. Manakov, Nila Roy Choudhury, Samantha J. Griffiths, Annaleen Vermeulen, Anton J. Enright, Bernadette Dutia, Alain Kohl, Peter Ghazal, and Amy H. Buck. Combined agonist-antagonist genome-wide functional screening identifies broadly active antiviral microRNAs. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.1008861107

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Use of certain antiviral drugs during pregnancy not linked with higher risk of major birth defects, study suggests

ScienceDaily (Aug. 31, 2010) — An analysis of data from Denmark finds no associated increased risk of major birth defects for mothers who were exposed during the first trimester of pregnancy to the antiviral drugs acyclovir, valacyclovir, and famciclovir, often used to treat herpes simplex and herpes zoster infections, according to a study in the August 25 issue of JAMA.

The prevalence of herpes simplex is high, and more than 1 percent of susceptible women acquire herpes simplex during the first trimester of pregnancy, with antiviral treatment indicated for a significant number of women in pregnancy. "Although the safety of acyclovir, valacyclovir, and famciclovir in general has been well established, data on the use of these antivirals in early pregnancy are limited," the authors write.

Bjorn Pasternak, M.D., Ph.D., and Anders Hviid, M.Sc., Dr.Med.Sci., of Statens Serum Institut, Copenhagen, Denmark, conducted a registry-based study to assess associations between acyclovir, valacyclovir, and famciclovir use in the first trimester of pregnancy and major birth defects. The study included 837,795 live-born infants in Denmark from January 1996 to September 2008. Participants had no diagnoses of chromosomal aberrations, genetic syndromes, birth defect syndromes with known causes, or congenital viral infections. Nationwide registries were used to ascertain individual-level information on dispensed antiviral drugs, birth defect diagnoses and potential confounders (factors that can influence outcomes).

Among 1,804 pregnancies exposed to acyclovir, valacyclovir, or famciclovir at any time in the first trimester, 40 infants (2.2 percent) had a diagnosis of a major birth defect, compared with 19,920 of 835,991 infants (2.4 percent) among the unexposed pregnancies. Adjusting for several variables, acyclovir, valacyclovir, or famciclovir exposure at any time in the first trimester was not associated with increased risk of major birth defects. First-trimester use of acyclovir, the most commonly prescribed antiviral, was not associated with major birth defects (32 cases among 1,561 exposed [2.0 percent] vs. 2.4 percent in the unexposed). Neither valacyclovir (7 of 229 infants [3.1 percent]) nor famciclovir (1 of 26 infants [3.8 percent]) were associated with major birth defects, although use of famciclovir was uncommon.

Additional analyses revealed no associations between antiviral drug exposure and 13 different subgroups of birth defects, but the number of exposed cases in each subgroup was small.

"Our study, to our knowledge the largest of its kind, found no significant association between first-trimester exposure to antiherpetic antiviral drugs and major birth defects. Consequently, it has immediate clinical implications and may support informed decisions on safety when prescribing antivirals for herpes infections in early pregnancy. Acyclovir is the most extensively documented antiviral and should therefore be the drug of choice in early pregnancy, while data on valacyclovir and famciclovir are still insufficient. Future research on antiherpetic antivirals and mother-child health should include safety studies with regard to spontaneous abortion and preterm birth, and during breastfeeding," the authors conclude.

Editorial: Acyclovir Exposure and Birth Defects -- An Important Advance, But More Are Needed

In an accompanying editorial, James L. Mills, M.D., M.S., and Tonia C. Carter, Ph.D., of the National Institutes of Health, Bethesda, Md., comment on the findings of this study.

"The study by Pasternak and Hviid is helpful in demonstrating the safety of acyclovir in pregnancy, but additional strategies must be developed to resolve the remaining issues. At a time when the health care system in the United States is facing enormous financial challenges, it is important not to ignore any sources of data that could answer critical medical questions."

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by JAMA and Archives Journals.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Björn Pasternak, MD, PhD; Anders Hviid, MSc, DrMedSci. Use of Acyclovir, Valacyclovir, and Famciclovir in the First Trimester of Pregnancy and the Risk of Birth Defects. JAMA, 2010;304(8):859-866 DOI: 10.1001/jama.2010.1206

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Antiviral drugs may slow Alzheimer's progression

ScienceDaily (Oct. 20, 2011) — Antiviral drugs used to target the herpes virus could be effective at slowing the progression of Alzheimer's disease (AD), a new study shows.

The University of Manchester scientists have previously shown that the herpes simplex virus type 1 (HSV1) is a risk factor for Alzheimer's when it is present in the brains of people who have a specific genetic risk to the disease.

AD is an incurable neurodegenerative condition affecting about 18 million people worldwide. The causes of the disease or of the abnormal protein structures seen in AD brains -- amyloid plaques and neurofibrillary tangles -- are completely unknown.

The Manchester team has established that the herpes virus causes accumulation of two key AD proteins -- ß-amyloid (Aß) and abnormally phosphorylated tau (P-tau) -- known to be the main components of plaques and tangles respectively. Both proteins are thought by many scientists to be involved in the development of the disease.

"We have found that the viral DNA in AD brains is very specifically located within amyloid plaques," said Professor Ruth Itzhaki, who led the team in the University's Faculty of Life Sciences. "This, together with the production of amyloid that the virus induces, suggests that HSV1 is a cause of toxic amyloid products and of plaques.

"Our results suggest that HSV1, together with the host genetic factor, is a major risk for AD, and that antiviral agents might be used for treating patients to slow disease progression."

Currently available antiviral agents act by targeting replication of HSV1 DNA, and so the researchers considered that they might be successful in treating AD only if the accumulation of ß-amyloid and P-tau accumulation caused by the virus occurs at or after the stage at which viral DNA replication occurs.

"If these proteins are produced independently of HSV1 replication, antivirals might not be effective," said Professor Itzhaki. "We investigated this and found that treatment of HSV1-infected cells with acyclovir, the most commonly used antiviral agent, and also with two other antivirals, did indeed decrease the accumulation of ß-amyloid and P-tau, as well as decreasing HSV1 replication as we would expect.

"This is the first study investigating antiviral effects on AD-like changes and we conclude that since antiviral agents reduce greatly ß-amyloid and P-tau levels in HSV1-infected cells, they would be suitable for treating Alzheimer's disease. The great advantage over current AD therapies is that acyclovir would target only the virus, not the host cell or normal uninfected cells. Further, these agents are very safe and are relatively inexpensive.

"Also, by targeting a cause of Alzheimer's disease, other viral damage, besides ß-amyloid and P-tau, which might be involved in the disease's pathogenesis, would also be inhibited.

"The next stage of our research -- subject to funding -- will focus on finding the most suitable antiviral agent -- or combination of two agents that operate via different mechanisms -- for use as treatment. We then need to investigate the way in which the virus and the genetic risk factor interact to cause the disease, as that might lead to further novel treatments.

"Eventually, we hope to begin clinical trials in humans but this is still some way off yet and again will require new funding."

The study, carried out with Dr Matthew Wozniak and other colleagues in the Faculty of Life Sciences, is published in the Public Library of Science (PLoS) One journal.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by University of Manchester.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Matthew A. Wozniak, Alison L. Frost, Chris M. Preston, Ruth F. Itzhaki. Antivirals Reduce the Formation of Key Alzheimer's Disease Molecules in Cell Cultures Acutely Infected with Herpes Simplex Virus Type 1. PLoS ONE, 2011; 6 (10): e25152 DOI: 10.1371/journal.pone.0025152

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Study Evaluates Use Of Corticosteroids And Antiviral Agents For Treatment Of Bell Palsy

ScienceDaily (Sep. 1, 2009) — Among patients with Bell Palsy, a facial paralysis with unknown cause, treatment with corticosteroids is associated with a reduced risk of an unsatisfactory recovery, and treatment with a combination of corticosteroids and antiviral agents may be associated with additional benefit, according to a systematic review and meta-analysis of previously published studies, reported in the September 2 issue of JAMA.

In background information provided by the authors, they note that Bell Palsy "is an acute weakness or paralysis of the facial nerve," and has an annual incidence of 20 to 30 per 100,000 population. "While 71 percent of untreated patients will completely recover and 84 percent will have complete or near normal recovery, the remainder will have persistent to moderate to severe weakness, facial contracture, or synkinesis [involuntary movement]." The authors explain that a herpes infection likely causes the disorder. DNA samples from patients have yielded herpes simplex virus type 1 (HSV-1). Varicella zoster virus (VZV) reactivation is also associated with Bell Palsy.

John R. de Almeida, M.D., from Sunnybrook Hospital and the University of Toronto, Canada, and colleagues conducted a search of the medical literature for randomized controlled trials comparing treatment with either corticosteroids or antiviral agents with a control measuring unsatisfactory facial recovery (four months or more), unsatisfactory short-term recovery (six weeks to less than four months), synkinesis and autonomic dysfunction, or adverse effects. The authors identified 854 studies, of which 18 were eligible for inclusion for evaluation. The 18 studies included 2,786 patients and were conducted in 12 countries and five continents.

"… high-quality evidence suggests that corticosteroids alone reduce the risk of unsatisfactory recovery by 9 percent in absolute terms, with a NNTB (number of patients needed to treat for one patient to experience benefit) of 11," the authors report. "Corticosteroid therapy combined with antiviral agents reduced the risk of unsatisfactory recovery compared with antiviral agents alone. Corticosteroids were also associated with a 14 percent absolute risk reduction of synkinesis and autonomic dysfunction (NNTB, 7; moderate quality of evidence). Corticosteroids were not associated with an increased risk of adverse effects."

"Our results suggest a possible incremental benefit of antiviral agents in addition to corticosteroids, with an absolute risk reduction of 5 percent compared with corticosteroids alone. This effect, however, is not definitive and did not quite reach statistical significance," the authors write. "Further primary studies are needed to definitively establish – or refute – an incremental benefit of combined therapy compared with corticosteroid mono therapy," the authors conclude.

Editorial: Treatment of Bell Palsy – Translating Uncertainty Into Practice

"The systematic review by de Almeida et al of medications for treatment of Bell palsy helps resolve lingering doubt about the benefits of corticosteroids, but raises questions about the adjunctive role of antiviral medications," John F. Steiner, M.D., M.P.H., of Kaiser Permanente Colorado, Denver, writes in an accompanying editorial.

"Until the next generation of clinical trials is completed, clinicians and patients will have to deal with substantial uncertainty in deciding whether to add antiviral drugs to corticosteroids for Bell palsy. By assessing how clinicians alter their prescribing patterns and how treatment guidelines are revised in response to this new evidence, it will be possible to learn more about how clinical uncertainty is translated into practice."

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by JAMA and Archives Journals.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

John R. de Almeida; Murtadha Al Khabori; Gordon H. Guyatt; Ian J. Witterick; Vincent Y. W. Lin; Julian M. Nedzelski; Joseph M. Chen. Combined Corticosteroid and Antiviral Treatment for Bell Palsy: A Systematic Review and Meta-analysis. JAMA, 2009; 302 (9): 985-993 [link]

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Transcriptional Coactivators Not Useful As Herpes Antiviral Drug Targets

ScienceDaily (Mar. 25, 2009) — Researchers at Van Andel Research Institute (VARI) have determined that the herpes simplex virus type 1 (HSV-1) does not require transcriptional coactivators for viral gene expression early in the infection process. The finding is significant in determining that, in contradiction to earlier models, chemical inhibitors of these cellular proteins are not likely to serve as useful antiviral drugs.

Researchers sought to determine how herpes simplex virus “turns on” its viral genes during the first stages of infection. Specifically, they tested whether the expression of the viral genes would be similar to how cellular genes are turned on, and specifically whether the viral genes would depend on a set of cellular proteins called “coactivators.”

“Based on an earlier model we expected that expression of the viral genes would depend on a set of transcriptional coactivators,” said Scientific Investigator Steve Triezenberg, Ph.D., head of the VARI Laboratory of Transcriptional Regulation and co-author of the study published in a recent issue of the Journal of Virology. “As it turns out, we got an unexpected answer.  Using several different approaches, we consistently saw that the coactivator proteins are not required for viral gene expression.”

Researchers have understood that virion protein 16 (VP16) of herpes simplex virus type 1 is a potent transcriptional activator of viral immediate early (IE) genes. However, the role of transcriptional coactivators had not been fully understood.

“This is a significant finding because it tells us that chemical inhibitors of these coactivators are not likely to be good antiviral drugs, despite our earlier model,” said Triezenberg.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by Van Andel Research Institute.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Use of certain antiviral drugs during pregnancy not linked with higher risk of major birth defects, study suggests

ScienceDaily (Aug. 24, 2010) — An analysis of data from Denmark finds no associated increased risk of major birth defects for mothers who were exposed during the first trimester of pregnancy to the antiviral drugs acyclovir, valacyclovir, and famciclovir, often used to treat herpes simplex and herpes zoster infections, according to a study in the August 25 issue of JAMA.

The prevalence of herpes simplex is high, and more than 1 percent of susceptible women acquire herpes simplex during the first trimester of pregnancy, with antiviral treatment indicated for a significant number of women in pregnancy. "Although the safety of acyclovir, valacyclovir, and famciclovir in general has been well established, data on the use of these antivirals in early pregnancy are limited," the authors write.

Bjorn Pasternak, M.D., Ph.D., and Anders Hviid, M.Sc., Dr.Med.Sci., of Statens Serum Institut, Copenhagen, Denmark, conducted a registry-based study to assess associations between acyclovir, valacyclovir, and famciclovir use in the first trimester of pregnancy and major birth defects. The study included 837,795 live-born infants in Denmark from January 1996 to September 2008. Participants had no diagnoses of chromosomal aberrations, genetic syndromes, birth defect syndromes with known causes, or congenital viral infections. Nationwide registries were used to ascertain individual-level information on dispensed antiviral drugs, birth defect diagnoses and potential confounders (factors that can influence outcomes).

Among 1,804 pregnancies exposed to acyclovir, valacyclovir, or famciclovir at any time in the first trimester, 40 infants (2.2 percent) had a diagnosis of a major birth defect, compared with 19,920 of 835,991 infants (2.4 percent) among the unexposed pregnancies. Adjusting for several variables, acyclovir, valacyclovir, or famciclovir exposure at any time in the first trimester was not associated with increased risk of major birth defects. First-trimester use of acyclovir, the most commonly prescribed antiviral, was not associated with major birth defects (32 cases among 1,561 exposed [2.0 percent] vs. 2.4 percent in the unexposed). Neither valacyclovir (7 of 229 infants [3.1 percent]) nor famciclovir (1 of 26 infants [3.8 percent]) were associated with major birth defects, although use of famciclovir was uncommon.

Additional analyses revealed no associations between antiviral drug exposure and 13 different subgroups of birth defects, but the number of exposed cases in each subgroup was small.

"Our study, to our knowledge the largest of its kind, found no significant association between first-trimester exposure to antiherpetic antiviral drugs and major birth defects. Consequently, it has immediate clinical implications and may support informed decisions on safety when prescribing antivirals for herpes infections in early pregnancy. Acyclovir is the most extensively documented antiviral and should therefore be the drug of choice in early pregnancy, while data on valacyclovir and famciclovir are still insufficient. Future research on antiherpetic antivirals and mother-child health should include safety studies with regard to spontaneous abortion and preterm birth, and during breastfeeding," the authors conclude.

Editorial: Acyclovir Exposure and Birth Defects -- An Important Advance, But More Are Needed

In an accompanying editorial, James L. Mills, M.D., M.S., and Tonia C. Carter, Ph.D., of the National Institutes of Health, Bethesda, Md., comment on the findings of this study.

"The study by Pasternak and Hviid is helpful in demonstrating the safety of acyclovir in pregnancy, but additional strategies must be developed to resolve the remaining issues. At a time when the health care system in the United States is facing enormous financial challenges, it is important not to ignore any sources of data that could answer critical medical questions."

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by JAMA and Archives Journals.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Björn Pasternak, MD, PhD; Anders Hviid, MSc, DrMedSci. Use of Acyclovir, Valacyclovir, and Famciclovir in the First Trimester of Pregnancy and the Risk of Birth Defects. JAMA, 2010;304(8):859-866 DOI: 10.1001/jama.2010.1206

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Antiviral drugs may slow Alzheimer's progression

ScienceDaily (Oct. 17, 2011) — Antiviral drugs used to target the herpes virus could be effective at slowing the progression of Alzheimer's disease (AD), a new study shows.

The University of Manchester scientists have previously shown that the herpes simplex virus type 1 (HSV1) is a risk factor for Alzheimer's when it is present in the brains of people who have a specific genetic risk to the disease.

AD is an incurable neurodegenerative condition affecting about 18 million people worldwide. The causes of the disease or of the abnormal protein structures seen in AD brains -- amyloid plaques and neurofibrillary tangles -- are completely unknown.

The Manchester team has established that the herpes virus causes accumulation of two key AD proteins -- ß-amyloid (Aß) and abnormally phosphorylated tau (P-tau) -- known to be the main components of plaques and tangles respectively. Both proteins are thought by many scientists to be involved in the development of the disease.

"We have found that the viral DNA in AD brains is very specifically located within amyloid plaques," said Professor Ruth Itzhaki, who led the team in the University's Faculty of Life Sciences. "This, together with the production of amyloid that the virus induces, suggests that HSV1 is a cause of toxic amyloid products and of plaques.

"Our results suggest that HSV1, together with the host genetic factor, is a major risk for AD, and that antiviral agents might be used for treating patients to slow disease progression."

Currently available antiviral agents act by targeting replication of HSV1 DNA, and so the researchers considered that they might be successful in treating AD only if the accumulation of ß-amyloid and P-tau accumulation caused by the virus occurs at or after the stage at which viral DNA replication occurs.

"If these proteins are produced independently of HSV1 replication, antivirals might not be effective," said Professor Itzhaki. "We investigated this and found that treatment of HSV1-infected cells with acyclovir, the most commonly used antiviral agent, and also with two other antivirals, did indeed decrease the accumulation of ß-amyloid and P-tau, as well as decreasing HSV1 replication as we would expect.

"This is the first study investigating antiviral effects on AD-like changes and we conclude that since antiviral agents reduce greatly ß-amyloid and P-tau levels in HSV1-infected cells, they would be suitable for treating Alzheimer's disease. The great advantage over current AD therapies is that acyclovir would target only the virus, not the host cell or normal uninfected cells. Further, these agents are very safe and are relatively inexpensive.

"Also, by targeting a cause of Alzheimer's disease, other viral damage, besides ß-amyloid and P-tau, which might be involved in the disease's pathogenesis, would also be inhibited.

"The next stage of our research -- subject to funding -- will focus on finding the most suitable antiviral agent -- or combination of two agents that operate via different mechanisms -- for use as treatment. We then need to investigate the way in which the virus and the genetic risk factor interact to cause the disease, as that might lead to further novel treatments.

"Eventually, we hope to begin clinical trials in humans but this is still some way off yet and again will require new funding."

The study, carried out with Dr Matthew Wozniak and other colleagues in the Faculty of Life Sciences, is published in the Public Library of Science (PLoS) One journal.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by University of Manchester.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Matthew A. Wozniak, Alison L. Frost, Chris M. Preston, Ruth F. Itzhaki. Antivirals Reduce the Formation of Key Alzheimer's Disease Molecules in Cell Cultures Acutely Infected with Herpes Simplex Virus Type 1. PLoS ONE, 2011; 6 (10): e25152 DOI: 10.1371/journal.pone.0025152

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Antiviral therapy associated with fewer recurring eye problems from herpes simplex virus

ScienceDaily (Sep. 13, 2010) — Taking oral antiviral medications following infection with the herpes simplex virus may be associated with a reduced risk of recurring eye-related manifestations of the disease, according to a report in the September issue of Archives of Ophthalmology, one of the JAMA/Archives journals.

"Herpes simplex virus (HSV) is a common cause of corneal disease and is the leading infectious cause of corneal blindness among developed nations," the authors write as background information in the article. After the initial exposure to the virus and the resulting systemic infection, herpes simplex establishes a latent infection in sensory nerve structures. Reactivation of this latent infection could lead to initial or recurrent disease in one or both eyes, including inflammation or infection of the cornea, eyelid, membrane inside the eye (conjunctivitis, or pink eye) or middle layer of the eye (uveitis).

Ryan C. Young, B.A., of Mayo Clinic, Rochester, Minn., and colleagues estimated the incidence of HSV eye disease in a community-based cohort, in Olmstead County, Minnesota, from 1976 through 2007. During this time period, 394 patients with ocular HSV were identified, for an annual incidence of 11.8 per 100,000 individuals.

Oral antiviral therapy was prescribed in 175 (44 percent) of these patients, who underwent therapy for an average of 2.8 years (36 percent of the average 7.7 years of follow-up). Patients not taking this prophylactic therapy were 9.4 times more likely to have a recurrence of epithelial keratitis (infection of the top layer of the cornea), 8.4 times more likely to have a recurrence of stromal keratitis (infection of deeper layers of the cornea) and 34.5 times more likely to have a recurrence of blepharitis (eyelid infection) or conjunctivitis than those taking antiviral medications.

A total of 20 patients experienced adverse outcomes, including visual loss and perforation of the cornea; of these, 17 (85 percent) were not taking oral antiviral prophylaxis.

"Overall, this community-based retrospective study demonstrated a stable incidence of HSV eye disease during a recent 32-year period," the authors write. "We found a more dramatic protective effect of oral antiviral prophylaxis on recurrences of ocular HSV than had been described previously."

"The results of this study suggest that oral antiviral prophylaxis should be considered for patients with frequent recurrences of corneal disease," they conclude. "Additionally, we recommend an evaluation of the possible barriers preventing compliance with antiviral prophylaxis and a reassessment of the cost-effectiveness of long-term oral antiviral therapy."

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by JAMA and Archives Journals.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Ryan C. Young; David O. Hodge; Thomas J. Liesegang; Keith H. Baratz. Incidence, Recurrence, and Outcomes of Herpes Simplex Virus Eye Disease in Olmsted County, Minnesota, 1976-2007: The Effect of Oral Antiviral Prophylaxis. Arch Ophthalmol, 2010; 128 (9): 1178-1183 [link]

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Herpes Antiviral Drugs Targeted to Delay Progression of Alzheimer Disease: Study

Scientists at the University of Manchester suggest using antiviral drugs to slow the progression of Alzheimer's Disease (AD).  

The results of the study seem to indicate that the herpes simplex virus type 1 (HSV1) is a risk factor for contracting Alzheimer's, when it is present in the brains of people who have a specific genetic risk of the disease. The study states that drugs targeting the herpes virus could slow progression of AD.

The study, published in the Public Library of Science One (PLoS), notes that current treatments for AD are merely palliative and has a calming impact on the individual. However, there is an urgent need for medicines that could delay the progress of the disease.

The new study is based on evidence implicating HSV1 as a causative agent in AD.  The first suggestion that HSV1 might have a role in AD was based on the observation that in herpes simplex encephalitis (HSE), the brain regions damaged are the same ones as those that are affected in AD

Study researchers at Manchester claim that the study is the first to investigate antiviral effects on AD-like changes. They infer that since antiviral agents greatly reduce ß-amyloid and P-tau levels in HSV1-infected cells, they should be suitable for treating AD.

Like us on Facebook

Further, the scientists say that HSV1 theory has an advantage over current AD therapies. This revolves around acyclovir - an antiviral drug - that can be used to target only the virus and not the host or normal and uninfected cells. In addition, these agents are safe and relatively inexpensive.

Researchers have now also established that the herpes virus causes an accumulation of two key AD proteins - ß-amyloid (Aß) that, primarily, causes plaque - and abnormally phosphorylated tau (P-tau), the causative component for tangles. Both proteins are thought by many scientists to be involved in the development of the disease.

"We have found that the viral DNA in AD brains is very specifically located within amyloid plaques," said Professor Ruth Itzhaki, who led the team in the University's Faculty of Life Sciences, "This, together with the production of amyloid that the virus induces, suggests that HSV1 is a cause of toxic amyloid products and of plaques."

"Our results suggest that HSV1, together with the host genetic factor, is a major risk for AD, and that antiviral agents might be used for treating patients to slow disease progression. Also, by targeting a cause of Alzheimer's disease, other viral damage, besides ß-amyloid and P-tau, which might be involved in the disease's pathogenesis, would also be inhibited," Itzhaki adds.

Antiviral drugs currently available act by targeting replications of HSV1 DNA. In the study, researchers considered treating AD once the accumulation of ß-amyloid and P-tau that is caused by the virus occurred. They also tested the drug at the stage at which viral DNA replication occurs.

"If these proteins are produced independently of HSV1 replication, antivirals might not be effective," said Itzhaki, "We investigated this and found that treatment of HSV1-infected cells with acyclovir, the most commonly used antiviral agent, and also with two other antivirals, did indeed decrease the accumulation of ß-amyloid and P-tau, as well as decreasing HSV1 replication as we would expect."

The study underlies the explanation that HSV1 is a neurotropic virus that infects most humans. It is responsible for a number of diseases including herpes labialis (cold sores), herpes simplex encephalitis (HSE) and some cases of genital herpes.

"The next stage of our research -- subject to funding -- will focus on finding the most suitable antiviral agent -- or combination of two agents that operate via different mechanisms -- for use as treatment. We then need to investigate the way in which the virus and the genetic risk factor interact to cause the disease, as that might lead to further novel treatments," noted Itzhaki.

View the original article here