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Important Note: The following information
is provided for your education. It should not be relied upon for
personal diagnosis or treatment. If you believe that a
particular therapy applies to you or someone you care about, be
sure to consult a doctor before trying it.
Herpes
Research: 2002-2006
Herpes. 2006 Aug;13(2):53-5.
New Approaches to the Therapy of HSV Infections.
Whitley R.
University of Alabama at Birmingham, Birmingham, AL, USA.
Free full text at: http://www.ihmf.org/journal/download/132Whitley(53)vol1353.pdf
Two recent studies have demonstrated single-day regimens of high-dose antiviral
therapy (famciclovir 1000 mg twice daily for genital herpes, and famciclovir
1500 mg single dose for herpes labialis) to be effective episodic treatment
strategies. Both have the potential to improve patient compliance and
therapeutic satisfaction. Patient-initiated episodic therapy (PIE) regimens such
as these may improve the time to treatment initiation, which can halt lesion
development: PIE allows antiviral drugs to be administered in the narrow
therapeutic window that occurs early in the course of a herpes simplex virus (HSV)
infection episode. This review article discusses short-course antiviral therapy,
which may offer an effective alternative to traditional episodic or suppressive
antiviral regimens for HSV-related disease outbreaks.
-----
Clin Infect Dis. 2006 Aug 15;43(4):460-7. Epub 2006 Jul 3.
Topical iontophoretic administration of acyclovir for the
episodic treatment of herpes labialis: a randomized, double-blind,
placebo-controlled, clinic-initiated trial.
Morrel EM, Spruance SL, Goldberg DI; Iontophoretic Acyclovir Cold Sore Study
Group.
Transport Pharmaceuticals, Framingham, Massachusetts 01701, USA.
BACKGROUND: Multiple studies of the use of acyclovir for the treatment of herpes
labialis have suggested that the nominal efficacy of the topical formulation is
the result of inadequate penetration of the drug into the target site of
infection, the basal epidermis. METHODS: We developed a low-voltage, wireless,
hand-held, computer-controlled, iontophoretic applicator to enhance the skin
penetration of topical acyclovir in the treatment of herpes labialis. We
performed a multicenter, placebo-controlled, clinic-initiated, pilot trial of a
single, topical, iontophoretic application of 5% acyclovir cream for the
episodic treatment of herpes labialis among 200 patients with an incipient cold
sore outbreak at the erythema or papular/edema lesion stage. RESULTS: The median
classic lesion healing time (aborted lesions were assigned a value of 0 h) was
1.5 days shorter for the active treatment group than for the vehicle group (113
h vs. 148 h; P = .02). In the subgroup of patients who presented with lesions in
the erythema stage, the median classic lesion healing time was 3 days shorter
for the acyclovir group, compared with the control group (49 h vs. 120 h; P <
.03), and the acyclovir group tended to have more aborted lesions than did the
control group (46% vs. 24%; P = .10). CONCLUSIONS: Single-dose topical
iontophoresis of acyclovir appears to be a convenient and effective treatment
for cold sores and merits further clinical investigation.
-----
Clin Infect Dis. 2006 Aug 1;43(3):347-56. Epub 2006 Jun 15.
Management of herpes simplex virus type 2 infection in HIV type
1-infected persons.
Strick LB, Wald A, Celum C.
Department of Medicine, Division of Allergy and Infectious Diseases, University
of Washington, Seattle, WA 98104, USA. strick@u.washington.edu
Human immunodeficiency virus type 1 (HIV-1)-infected persons have high rates of
herpes simplex virus type 2 (HSV-2) infection, ranging from 50% to 90% in
studies of HIV-infected populations from different parts of the world. Genital
herpes in persons with HIV type 1 (HIV-1) infection is associated with
more-severe and chronic lesions, as well as increased rates of asymptomatic
genital shedding of HSV-2. Nucleoside analogues (acyclovir, valacyclovir, and
famciclovir) decrease the frequency and severity of HSV-2 recurrences and
asymptomatic HSV-2 reactivation and are effective, safe, well-tolerated drugs in
patients with HIV-1 infection. These anti-HSV drugs may result in additional
clinical and public health benefits for persons with HIV-1 and HSV-2 coinfection
by decreasing HIV-1 levels in the blood and genital tract. Given these benefits,
HIV-1-infected persons should be routinely tested for HSV-2 infection using
type-specific serologic tests. Persons with HSV-2 infection should be offered
HSV-2 education and treatment options. Studies to quantify the potential
clinical and public health benefits of treating individuals who have HIV-1 and
HSV-2 coinfection with anti-HSV therapy are underway.
-----
Curr Med Res Opin. 2006 Jul;22(7):1307-10.
Single-day famciclovir therapy for recurrent genital herpes.
Whitley R, Diaz-Mitoma F, Hamed K.
Department of Pediatrics, Division of Infectious Disease, University of Alabama
at Birmingham, Birmingham, AL 35233, USA. RWhitley@Peds.uab.edu
BACKGROUND: Genital herpes is a lifelong incurable viral infection that can have
a significant psychological and emotional impact on patients. A common therapy
for treating recurrent outbreaks is the episodic use of nucleoside analogues for
3-5 days. However, since maximum viral replication occurs within 24 h after
symptoms first appear, the best option may be short-term, patient-initiated
episodic therapy, administered during the onset of prodromal symptoms. This
commentary will examine the results of a recent clinical trial of
patient-initiated episodic famciclovir therapy that is administered for a single
day and compare efficacy data from that trial with data from trials of currently
prescribed antiviral therapies. FINDINGS: This recent trial that evaluated the
efficacy of single-day famciclovir compared to placebo in the treatment of
recurrent genital herpes found that famciclovir decreased time to lesion healing
and duration of symptoms, and increased the proportion of patients who did not
progress to a full outbreak. Although no head-to-head studies have been
completed, single-day famciclovir therapy seems to provide improvement that is
similar to or better than that associated with traditional longer-term
treatments. CONCLUSION: The increased convenience for the patient of single-day
therapy may lead to improved patient compliance and better overall management of
recurrent genital herpes outbreaks.
-----
J Am Acad Dermatol. 2006 Jul;55(1):47-53.
Single-dose, patient-initiated famciclovir: a randomized,
double-blind, placebo-controlled trial for episodic treatment of herpes labialis.
Spruance SL, Bodsworth N, Resnick H, Conant M, Oeuvray C, Gao J, Hamed K.
Division of Infectious Diseases, University of Utah School of Medicine, Salt
Lake City, UT 84132-2405, USA.
BACKGROUND: The brief period of viral replication in recurrent herpes labialis
lesions suggests shorter therapeutic regimens are a logical episodic treatment
strategy. OBJECTIVE: We sought to assess the efficacy and safety of single-dose
and single-day famciclovir treatments. METHODS: In all, 701 randomly assigned
patients self-initiated therapy with famciclovir (1500 mg once [single dose] or
750 mg twice a day for 1 day [single day]) or placebo within 1 hour of onset of
the prodromal symptoms of an episode of herpes labialis. Lesion healing was
monitored by diaries and frequent clinic visits. RESULTS: Median healing times
of primary (first to appear) vesicular lesions in the famciclovir single-dose,
famciclovir single-day, and placebo groups were 4.4, 4.0, and 6.2 days,
respectively. There was no significant difference between the famciclovir
regimens. Adverse events in the famciclovir groups were similar to placebo.
LIMITATIONS: The active arms of this trial were not directly compared to other
antiviral regimens. CONCLUSION: Single-dose famciclovir reduced time to healing
of herpes labialis lesions by approximately 2 days compared with placebo.
-----
Obstet Gynecol. 2006 Jul;108(1):141-7.
Valacyclovir prophylaxis to prevent recurrent herpes at delivery:
a randomized clinical trial.
Sheffield JS, Hill JB, Hollier LM, Laibl VR, Roberts SW, Sanchez PJ,
Wendel GD Jr.
Department of Obstetrics & Gynecology, University of Texas Southwestern Medical
Center at Dallas, Dallas, Texas 75390-9032, USA. Jeanne.Sheffield@utsouthwestern.edu
OBJECTIVE: To measure the efficacy of valacyclovir suppression in late pregnancy
to reduce the incidence of recurrent genital herpes in labor and subsequent
cesarean delivery. METHODS: A total of 350 pregnant women with a history of
genital herpes were assigned randomly to oral valacyclovir 500 mg twice a day or
an identical placebo from 36 weeks of gestation until delivery. In labor,
vulvovaginal herpes simplex virus (HSV) culture and polymerase chain reaction (PCR)
specimens were collected. Vaginal delivery was permitted if no clinical
recurrence or prodromal symptoms were present. Neonatal HSV cultures and
laboratory tests were obtained, and infants were followed up for 1 month after
delivery. Data were analyzed using chi2 and Student t tests. RESULTS: One
hundred seventy women treated with valacyclovir and 168 women treated with
placebo were evaluated. Eighty-two percent of the women had recurrent genital
herpes; 12% had first episode, nonprimary genital herpes; and 6% had first
episode, primary genital herpes. At delivery, 28 women (8%) had recurrent
genital herpes requiring cesarean delivery: 4% in the valacyclovir group and 13%
in the placebo group (P = .009). Herpes simplex virus was detected by culture in
2% of the valacyclovir group and 24% of the placebo group (P =.02). No infants
were diagnosed with neonatal HSV, and there were no significant differences in
neonatal complications. There were no significant differences in maternal or
obstetric complications in either group. CONCLUSION: Valacyclovir suppression
after 36 weeks of gestation significantly reduces HSV shedding and recurrent
genital herpes requiring cesarean delivery. LEVEL OF EVIDENCE: I.
-----
Hautarzt. 2006 Jul;57(7):586-591.
[Eczema herpeticum : Pathogenesis and therapy.]
[Article in German]
Rerinck HC, Kamann S, Wollenberg A.
Klinik und Poliklinik fur Dermatologie und Allergologie, Ludwig-Maximilians-Universitat
Munchen, Frauenlobstrasse 9-11, 80337 , Munchen, wollenberg@lrz.uni-muenchen.de.
Eczema herpeticum is an acute, disseminated herpes simplex virus infection which
remains a feared complication of eczematous skin diseases, especially atopic
dermatitis. The vesicular and erosive clinical picture is often accompanied by
systemic signs and symptoms. Why some atopic patients experience multiple
attacks of eczema herpeticum and others never have the disorder remains a
mystery. Patients with severe or untreated atopic dermatitis are more likely to
be affected. The pathogenesis appears to involve a complex interplay of factors,
including demasking of binding sites for the virus through the dermatitis,
failure to up-regulate antiviral proteins and a lack of plasmacytoid dendritic
cells. Treatment of choice is systemic acyclovir therapy.
-----
Expert Rev Anti Infect Ther. 2006 Jun;4(3):367-76.
Valacyclovir for the treatment of genital herpes.
Brantley JS, Hicks L, Sra K, Tyring SK.
The University of Texas Medical Branch, Department of Dermatology, 301
University Boulevard, Galveston, TX 77555-0783, USA. jsbrantl@utmb.edu
Genital herpes is the most prevalent sexually transmitted infection in the USA.
While sometimes mild in severity, it can be a distressing and painful chronic
condition. Likewise, herpes labialis and herpes zoster can be both physically
and psychologically painful. While there is no cure for these conditions,
treatment to alleviate symptoms, suppress recurrences and reduce transmission
has been drastically improved over the past 20 years with the use of guanine
nucleoside antivirals, such as valacyclovir hydrochloride (Valtrex),
GlaxoSmithKline) the highly bioavailable prodrug of acyclovir (Zovirax((R)),
GlaxoSmithKline), and famciclovir (Famvir, Novartis), a highly bioavailable
prodrug of penciclovir (Denavir, Novartis). Clinical trials involving
approximately 10,000 patients (including patients from nongenital herpes
studies, such as herpes zoster) have assessed the safety and efficacy of
valacyclovir in the treatment of initial genital herpes outbreaks, episodic
treatment of recurrent episodes and daily suppressive therapy. It was shown that
valacyclovir has similar efficacy to acyclovir in the episodic and suppressive
treatment of genital herpes. Valacyclovir is the only antiviral drug approved
for a once-daily dose of suppressive therapy for genital herpes, as well as the
only antiviral drug US FDA approved for a 3-day regimen of episodic treatment of
recurrent genital herpes. In addition, valacyclovir is also indicated in the
reduction of the sexual transmission of herpes simplex virus infection and for
the treatment of herpes labialis. In herpes zoster, valacyclovir is more
effective than acyclovir or placebo (and as equally effective as famciclovir) in
shortening the length and severity of herpes zoster-associated pain and
postherpetic neuralgia. Valacyclovir has an acceptable safety profile in
patients with herpes simplex and herpes zoster. The less frequent dosing regimen
makes it an attractive option in the treatment of genital herpes and other viral
infections, and may contribute to increased patient adherence to therapy.
-----
Rev Med Liege. 2006 May-Jun;61(5-6):442-7.
[Recurrent labial herpes. How to treat and prevent it best]
[Article in French]
Nikkels AF, Pierard GE.
Service de Dermatopathologie, CHU Sart Tilman, Liege.
Labial herpes is a recurrent muco-cutaneous disorder caused by the herpes
simplex virus (HSV), particularly the HSV type I. It affects 10 to 30% of the
adult population. The recurrence rate varies from episodic events to monthly
recurrences. Several triggering factors have been identified. They include
physical factors such as ultraviolet radiations and any local traumatism such as
dental and neurosurgical interventions, and dermo-cosmetic procedures of the
face. Hormonal factors are also involved including those related to menses and
pregnancy. Psychogenic factors, particularly severe stress are also involved.
Any other intercurrent infection may also be complicated by recurrent labial
herpes. The management of recurrent labial herpes currently relies on the
identification and possible avoidance of triggering factors, and on the use of
antiviral agents. There is no curative treatment available so far.
-----
Indian J Pediatr. 2006 Apr;73(4):313-21.
New antiviral agents.
Abdel-Haq N, Chearskul P, Al-Tatari H, Asmar B.
Division of Infectious Diseases, Children's Hospital of Michigan, Carman and Ann
Adams, Department of Pediatrics, Wayne State University, School of Medicine,
Detroit 48201, USA. nabdel@dmc.org
Free full text at: http://www.ijppediatricsindia.org/article.asp?issn=0019-5456;year=2006;volume=73;issue=4;spage=313;epage=321;aulast=Abdel-Haq
During the last three decades, a better understanding of viral replication and
disease states caused by viral infections have led to the development of newer
antiviral agents with enhanced activity and better tolerability. This review
focuses on newer systemic and topical antiviral agents that are used in
treatment of herpes viruses including herpes simplex type-1 (HSV-1) and type-2
(HSV-2), varicella-zoster virus (VZV) and cytomegalovirus CMV) as well as the
human papilloma virus (HPV). Included in this article are the agents famciclovir,
penciclovir, valganciclovir, imiquimod, docosanole and brivudin.
-----
Am J Ophthalmol. 2006 Apr;141(4):771-2.
Treatment of herpes simplex virus stromal keratitis unresponsive
to topical prednisolone 1% with topical cyclosporine 0.05%.
Rao SN.
University of Chicago, Chicago, Illinois 60605, USA. sanjayrao@pol.net
PURPOSE: To assess the efficacy of topical cyclosporine 0.05% (Restasis) in
patients with herpes simplex virus nonnecrotizing stromal keratitis unresponsive
to topical prednisolone. DESIGN: Prospective case series. METHODS: Patients with
herpes simplex virus stromal keratitis (n = 12) that was unresponsive to topical
prednisolone acetate 1% for at least four weeks were evaluated at a single site.
Eyes were treated with topical cyclosporine twice a day and begun on a rapid
prednisolone taper. Visual acuity, slit-lamp appearance, intraocular pressure,
and corneal sensitivity were evaluated every two weeks for at least three
months. RESULTS: Stromal keratitis resolved with cyclosporine in 10 of 12
patients after one month. The mean lesion area decreased more with cyclosporine
than with prednisolone (2.0 mm with cyclosporine compared with 0.25 mm with
prednisolone). After stopping cyclosporine therapy, four patients had recurrence
of stromal keratitis. CONCLUSION: This series suggests that herpes simplex virus
stromal keratitis can be treated effectively with topical cyclosporine,
particularly in cases that are not responsive to topical prednisolone.
-----
Expert Opin Pharmacother. 2006 Apr;7(6):665-75.
Genital herpes: antiviral therapy for symptom relief and
prevention of transmission.
Gupta R, Wald A.
Department of Medicine, University of Washington, Virology Research Clinic,
Seattle, WA 98122, USA. rachnabanner@aol.com
The episodic and daily suppressive treatment of genital herpes is safe and
effective with the currently available antiviral agents: acyclovir, valacyclovir
and famciclovir. Clinical strategies for the comprehensive management of genital
herpes simplex virus infections are recommended. Data from recent clinical
trials demonstrating the efficacy of shorter duration of therapy for recurrences
and the use of antivirals for the prevention of transmission are reviewed in
this article. The factors influencing the choice of therapy, such as cost, ease
of dosing and acyclovir resistance are also discussed.
-----
Sex Transm Dis. 2006 Mar 8;Publish Ahead of Print [Epub ahead of print]
Comparative Efficacy of Famciclovir and Valacyclovir for
Suppression of Recurrent Genital Herpes and Viral Shedding.
Wald A, Selke S, Warren T, Aoki FY, Sacks S, Diaz-Mitoma F, Corey L.
>From the *Departments of Medicine, daggerEpidemiology, and double
daggerLaboratory Medicine, School of Medicine and School of Public Health and
Community Medicine, University of Washington, Seattle, Washington; section
signWestover Heights Clinic, Portland, Oregon; parallelViridae Clinical Sciences
Inc., Vancouver, BC, Canada; paragraph signDepartment of Pharmacology and
Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada; #Department of
Pathology and Laboratory Medicine, University of Ottawa, Ontario, Canada; and
the **Fred Hutchinson Cancer Research Center, Seattle, Washington.
BACKGROUND:: Daily antiviral therapy with famciclovir and valacyclovir has been
shown to be effective in reducing both symptomatic and asymptomatic reactivation
of herpes simplex virus type 2 HSV-2 when compared to placebo. However, few
comparative studies between the 2 antivirals have been performed. OBJECTIVES::
To compare the clinical and virologic effects of famciclovir and valacyclovir
administered as daily suppressive therapy for persons with genital herpes. STUDY
DESIGN:: Two randomized, double-blind, placebo-controlled studies comparing
daily famciclovir 250 mg bid with valacyclovir 500 mg qd were performed. Study 1
randomized 320 participants and compared the clinical effect of the drugs given
for 16 weeks, and study 2 enrolled 70 HSV-2 seropositive subjects and compared
the virologic effect of the drugs given for 10 weeks. RESULTS:: In study 1, the
time to first recurrence was similar in famciclovir and valacyclovir recipients,
hazard ratio (HR) 1.17 (95% CI, 0.78-1.76), but time to first virologically
confirmed recurrence was shorter among famciclovir recipients, HR = 2.15 (95%
CI, 1.00-4.60). In study 2, HSV was detected on 3.2% of days among famciclovir
recipients and 1.3% of days among valacyclovir recipients, relative risk 2.33
(95% CI, 1.18-4.89). CONCLUSION:: Valacyclovir appear to be somewhat better than
famciclovir for suppression of genital herpes and associated shedding. Further
comparative trials of antiviral drugs for various indications should be
performed as acyclovir and penciclovir appear to have different ability to
abrogate HSV reactivation.
-----
Am J Ophthalmol. 2006 Mar;141(3):547-557.
Ocular herpes simplex: changing epidemiology, emerging disease
patterns, and the potential of vaccine prevention and therapy.
Pepose JS, Keadle TL, Morrison LA.
Pepose Vision Institute, 16216 Baxter Road, Ste. 205, Chesterfield, MO 63107,
USA. jpepose@peposevision.com
PURPOSE: To review the changing epidemiology of herpes simplex virus infection,
emerging patterns of herpetic ocular disease, and the challenges and promise of
herpes simplex virus vaccine therapy. DESIGN: Perspective. METHODS: Literature
review. RESULTS: An epidemic increase in genital herpes simplex type 2 infection
is reflected in a 30% increase in HSV-2 antibodies in the United States since
1976. Approximately one in four people in the United States over age 30 is
infected with HSV-2. Primary acquisition of herpes simplex type 1 is becoming
progressively delayed in many industrialized countries, in contrast to
developing nations where the virus is acquired early in life and is ubiquitous.
Changes in sexual behavior among young adults have been associated with a recent
increase in genital HSV-1 infection, resulting from oral-genital rather than
genital-genital contact. Clinical trials of HSV vaccines using selected herpes
simplex virus type 2 proteins mixed in adjuvant have shown limited efficacy in
seronegative women, but not in men. CONCLUSIONS: The recent epidemic of genital
herpes simplex type 2 infection is likely to result in an increase in neonatal
ocular herpes and in delayed cases of acute retinal necrosis syndrome. The
increase in genital HSV-1 may lead to industry production of vaccines that
contain components of both HSV-1 and HSV-2 targeted toward limiting genital
disease and transmission. As newer herpes simplex vaccines become available,
ophthalmologists must be vigilant that a boost in immunity against HSV does not
have a paradoxical effect in exacerbating break-through cases that develop
immune-mediated herpes simplex stromal keratitis.
-----
Am J Obstet Gynecol. 2006 Mar;194(3):774-81.
Valacyclovir therapy to reduce recurrent genital herpes in
pregnant women.
Andrews WW, Kimberlin DF, Whitley R, Cliver S, Ramsey PS, Deeter R.
Department of Obstetrics and Gynecology, Center for Research in Women's Health,
University of Alabama, Birmingham, AL, USA.
OBJECTIVE: The purpose of this study was to estimate the efficacy of
valacyclovir suppressive therapy in pregnant women with recurrent genital
herpes. STUDY DESIGN: At 36 weeks' gestation, herpes simplex virus (HSV)-2
seropositive women were randomized to receive oral valacyclovir 500 mg or
placebo twice daily until delivery. Genital tract and neonatal specimens were
collected weekly for HSV culture and qualitative polymerase chain reaction (PCR)
assay to detect viral DNA from the time of randomization to delivery. Both
maternal and neonatal toxicity measures were obtained. RESULTS: The 112 enrolled
women (57 valacyclovir, 55 placebo) had similar HSV recurrence risks, including
mean number of active HSV recurrences before randomization during the index
pregnancy (1.1 +/- 1.9 vs 1.5 +/- 2.1, P = .308) and days between randomization
and delivery (20.3 +/- 10.2 vs 22.0 +/- 8.9, P = .344). The number of women with
clinical HSV recurrences between the time of randomization and delivery was
significantly lower in the valacyclovir versus placebo group (10.5% vs 27.3%; P
= .023, RR 0.4, 95% CI 0.2-0.9). Shedding of HSV within 7 days of delivery was
similar in the valacyclovir and placebo group (10.4% vs 12.0%, P = .804; RR 0.9,
95% CI 0.3-2.7), as was the number of women with clinical HSV lesions at
delivery (5.3% vs 14.6%, P = .121; RR 0.4, 95% CI 0.1-1.3). No neonates had
symptomatic congenital HSV infection before discharge or up to 2 weeks'
postpartum, and no clinical or laboratory safety concerns were identified.
CONCLUSION: Administration of valacyclovir beginning at 36 weeks' gestation to
women with a history of recurrent genital HSV reduced the number of women with
subsequent clinical HSV recurrences.
-----
Hautarzt. 2006 Mar;57(3):207-16.
[Infections with herpes simplex and varicella-zoster viruses
during pregnancy.]
[Article in German]
Marculescu R, Richter L, Rappersberger K.
Abteilung fur Dermatologie, Krankenanstalt Rudolfstiftung, Wien.
Primary infections with herpes simplex virus (HSV) and varicella-zoster virus (VZV)
may lead to severe illness in pregnancy. Both diseases may be associated with
transplacental virus transmission and fetal infection. Such infections can lead
to intrauterine death, severe malformations and premature birth; the
fetal/congenital varicella syndrome is well-defined. Herpes genitalis and
varicella at the time of labor may lead to life threatening neonatal-herpes or
varicella of the newborn. Currently neither active immunization nor neutralizing
immunoglobulin is available for HSV infections. VZV-seronegative women in
child-bearing age can be vaccinated and pregnant women exposed to VZV can be
given specific immunoglobulins. While an infection is rarely blocked, the
severity is generally reduced. For severe disease antiviral treatment is
necessary, with valacyclovir and acyclovir represents the drugs of choice.
Primary or recurrent overt disease of the genital tract at the time of delivery
an indication for caesarean section. Suppression of recurrent genital herpes
during the last weeks of pregnancy with valacyclovir and acyclovir reduces the
need for surgical intervention. Neonates exposed to VZV should receive specific
immunoglobulin. If neonates show signs of either infection, immediate treatment
with acyclovir must be initiated.
-----
Curr Opin Investig Drugs. 2006 Feb;7(2):136-41.
Vaccines for herpes simplex virus infections.
Koelle DM.
University of Washington, Harborview Medical Center, Seattle 98104, USA.
viralimm@u.washington.edu
Infections with herpes simplex virus (HSV) type 1 (HSV-1) and type 2 (HSV-2) can
have serious medical consequences. Although antiviral medications can suppress
symptomatic disease, asymptomatic shedding and transmission, they neither cure
nor alter the natural history of HSV infections. Manipulation of the immune
response is one potential method to decrease disease burden. Current research on
prophylactic and therapeutic vaccination approaches is discussed in this review,
with a focus on compounds that have entered clinical trials or that display
novel compositions or proposed mechanisms of action. One such vaccine is an alum
and monophosphoryl lipid A-adjuvanted subunit glycoprotein D2 vaccine that has
demonstrated activity in the prevention of HSV-2 infection and disease in HSV-uninfected
women in a phase III clinical trial. Further confirmatory clinical trials of
this vaccine are currently underway. Other vaccine formats also in development
include attenuated live or replication-incompetent HSV-2 strains and
technologies that target virus-specific CD8 T-cell responses.
-----
Am J Clin Dermatol. 2006;7(1):13-29.
Viral infections affecting the skin in organ transplant
recipients : epidemiology and current management strategies.
Tan HH, Goh CL.
National Skin Centre, Singapore.
Viral skin infections are common findings in organ transplant recipients. The
most important etiological agents are the group of human herpesviruses (HHV),
human papillomaviruses (HPV), and molluscum contagiosum virus. HHV that are
important in this group of patients are herpes simplex virus (HSV) types 1 and
2, varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV),
HHV-6 and -7, and HHV-8, which causes Kaposi sarcoma (KS). HSV infections are
characterized by their ability to establish latency and then reactivate at a
later date. The most common manifestations of HSV infection in organ transplant
recipients are mucocutaneous lesions of the oropharynx or genital regions.
Treatment is usually with acyclovir, valaciclovir, or famciclovir. Acyclovir
resistance may arise although the majority of acyclovir-resistant strains have
been isolated from AIDS patients and not organ transplant recipients. In such
cases, alternatives such as foscarnet, cidofovir, or trifluridine may have to be
considered. VZV causes chickenpox as well as herpes zoster. In organ transplant
recipients, recurrent herpes zoster can occur. Acute chickenpox in organ
transplant patients should be treated with intravenous acyclovir. CMV infection
occurs in 20-60% of all transplant recipients. Cutaneous manifestations, which
include nonspecific macular rashes, ulcers, purpuric eruptions, and
vesiculobullous lesions, are seen in 10-20% of patients with systemic infection
and signify a poor prognosis. The present gold standard for treatment is
ganciclovir, but newer drugs such as valganciclovir appear promising. EBV is
responsible for some cases of post-transplant lymphoproliferative disorder,
which represents the greatest risk of serious EBV disease in transplant
recipients. HHV-6 and HHV-7 are two relatively newly discovered viruses and, at
present, the body of information concerning these two agents is still fairly
limited. KS is caused by HHV-8, which is the most recently discovered
lymphotrophic HHV. Iatrogenic KS is seen in solid-organ transplant recipients,
with a prevalence of 0.5-5% depending on the patient's country of origin. HPV is
ubiquitous, and organ transplant recipients may never totally clear HPV
infections, which are the most frequently recurring infections in renal
transplant recipients. HPV infection in transplant recipients is important
because of its link to the development of certain skin cancers, in particular,
squamous cell carcinoma. Regular surveillance, sun avoidance, and patient
education are important aspects of the management strategy.
-----
J Neurol Neurosurg Psychiatry. 2005 Nov;76(11):1544-9.
Evaluation of combination therapy using aciclovir and
corticosteroid in adult patients with herpes simplex virus encephalitis.
Kamei S, Sekizawa T, Shiota H, Mizutani T, Itoyama Y, Takasu T, Morishima T,
Hirayanagi K.
Division of Neurology, Department of Medicine, Nihon University School of
Medicine, Itabashi-ku, Tokyo 173-8610, Japan. skamei@med.nihon-u.ac.jp
OBJECTIVE: Herpes simplex virus encephalitis (HSVE) is associated with
significant morbidity and mortality, even with appropriate antiviral therapy. In
the present investigation, the first to assess efficacy of corticosteroid
treatment with aciclovir therapy in HSVE, multiple logistic regression analysis
was performed of predictors of outcome in adult patients with HSVE. METHODS: A
non-randomised retrospective study of 45 patients with HSVE treated with
aciclovir was conducted. The patients were divided into poor and good groups
based on outcome at three months after completion of aciclovir treatment. The
variables evaluated were: clinical variables (sex, age, days after onset at
initiation of aciclovir, Glasgow Coma Scale (GCS) at initiation of aciclovir,
initial and maximum values for the cell numbers and protein concentration in the
cerebrospinal fluid, and corticosteroid administration); neuroradiological
variables (detection of lesions by initial cranial computed tomography and by
initial magnetic resonance imaging); and one neurophysiological variable
(detection of periodic lateralised epileptiform discharges on the initial
electroencephalogram). Single variable logistic regression analysis was
performed followed by multiple logistic regression analysis. The best set of
predictors for the outcome of HSVE was estimated by stepwise logistic regression
analysis. RESULTS: A poor outcome was evident with older age, lower GCS score at
initiation of aciclovir, and no administration of corticosteroid. Patient age,
GCS at initiation of aciclovir, and corticosteroid administration were found to
be significant independent predictors of outcome on multiple logistic regression
analysis, and these three variables also formed the best set of predictors (R(2)
= 0.594, p<0.0001). CONCLUSION: Combination therapy using both aciclovir and
corticosteroid represents one of the predictors of outcome in HSVE.
-----
Curr Med Res Opin. 2005 Oct;21(10):1577-82.
Reducing the risk of transmitting genital herpes: advances in
understanding and therapy.
Leone P.
Department of Infectious Diseases, University of North Carolina, Chapel Hill,
NC, USA.
BACKGROUND: This review considers the epidemiology and impact of genital herpes,
discusses how herpes simplex virus-2 (HSV-2) is transmitted, and reviews data on
methods of reducing the risk of HSV transmission.Scope: Information for the
paper was identified through multiple PubMed searches. Information in the
section on interventions was identified through PubMed searches using several
pairs of key words (herpes and transmission, herpes and treatment, herpes and
antiviral, herpes and valacyclovir, herpes and famciclovir, herpes and
acyclovir, herpes and condom, herpes and clinical trial). The searches,
conducted in January 2005, did not have date limits. Papers were selected for
inclusion based on the author's judgment of their relevance to the topic of the
review.FINDINGS: An estimated 45 million persons in the United States have
genital herpes infection, and new infections occur at a rate of approximately
one million per year. Approximately 85% to 90% of infections are unrecognized
and therefore undiagnosed. Individuals with genital HSV-2 infection shed virus
during asymptomatic periods as well as symptomatic periods. In fact,
transmission frequently occurs during periods of asymptomatic viral shedding.
Asymptomatic viral shedding (1) occurs in the majority of patients with genital
HSV-2 infection; (2) accounts for approximately one third of the days of viral
shedding; (3) occurs regardless of duration of infection but is most frequent
during the first year after infection; (4) occurs more than 7 days before or
after a symptomatic recurrence 50% of the time; and (5) does not differ
significantly when comparing patients with 1 to 12 annual recurrences to those
with no recurrences. A recently published study of discordant couples counseled
on safe sex practices found that once daily suppressive therapy with
valacyclovir reduced the risk of transmission of HSV-2 in heterosexual
immunocompetent adult couples discordant for HSV-2 infection. In an 8-month
study, daily valacyclovir compared with placebo reduced the risk of acquisition
of symptomatic genital HSV-2 infection by 75% (2.2% placebo vs. 0.5%
valacyclovir; hazard ratio = 0.25; p = 0.008). The overall risk of acquisition
of HSV-2 infection (defined via laboratory-confirmed symptoms or seroconversion)
was reduced by 48% (3.6% placebo vs. 1.9% valacyclovir hazard ratio = 0.52; p =
0.04). The most common adverse events in the study were headache,
nasopharyngitis, and upper respiratory infection.CONCLUSION: Daily suppressive
therapy is recommended as a therapeutic option for HSV-2seropositive individuals
at risk of transmitting HSV-2. Because no intervention completely protects
against transmission of HSV, infected individuals and their partners should be
counseled to use safer sex practices, including the use of condoms.
-----
Am J Clin Dermatol. 2005;6(5):317-25.
Current management of herpes zoster : the European view.
Volpi A, Gross G, Hercogova J, Johnson RW.
Department of Public Health, University of Rome, Rome, Italy.
The overall incidence of herpes zoster in Europe is approximately 3 per 1000
people per year and more than 10 per 1000 people per year in those aged >80
years. Post herpetic neuralgia (PHN) is a common debilitating complication of
herpes zoster, particularly in patients aged >50 years, in persons with severe
pain or rash at presentation, and in those with significant prodromal
symptoms.Antiviral drugs can effectively control acute symptoms and, if used
early enough in the course of the illness, can help prevent the development of
PHN and other complications. However, despite this, many patients do not receive
such treatment. The economic impact of zoster and PHN is largely underestimated
in Europe. Furthermore, there is considerable variation throughout Europe in the
management of herpes zoster. Use of antiviral therapy including the newer potent
antiviral agents such as brivudin, which requires less frequent administration
than acyclovir, is improving patient outcomes in some European countries.
However, in many countries, patient awareness of herpes zoster and, as a result,
overall antiviral use is low.Guidelines recommending the use of antiviral
agents, particularly in patients at risk of developing PHN, are available but
are not widely used. More needs to be done to educate the general public and
increase awareness among primary healthcare providers of the benefits of timely
and appropriate pharmacological therapy in patients with herpes zoster.
-----
Curr Pharm Biotechnol. 2005 Oct;6(5):373-9.
Nutritional and therapeutic potential of spirulina.
Khan Z, Bhadouria P, Bisen PS.
Department of Biotechnology, J.C. Bose Institute of Life Sciences, Bundelkhand
University, Jhansi 284128, U.P., India. psbisen@gmail.com.
Spirulina, a filamentous cyanobacterium, possesses diverse biological activities
and nutritional significance due to high concentration of natural nutrients,
having bio-modulatory and immuno-modulatory functions. Different Spirulina
preparations influence immune system viz. increase phagocytic activity of
macrophages, stimulating the production of antibodies and cytokines, increase
accumulation of NK cells into tissue and activation and mobilization of T and B
cells. Spirulina have also shown to perform regulatory role on lipid and
carbohydrate metabolism by exhibiting glucose and lipid profile correcting
activity in experimental animals and in diabetic patients. Preparations have
been found to be active against several enveloped viruses including herpes
virus, cytomegalovirus, influenza virus and HIV. They are capable to inhibit
carcinogenesis due to anti-oxidant properties that protect tissues and also
reduce toxicity of liver, kidney and testes.
-----
Expert Rev Vaccines. 2005 Oct;4(5):615-27.
Glycoprotein D adjuvant herpes simplex virus vaccine.
Bernstein D.
Cincinnati Children's Hospital Medical Center, Division of Infectious Diseases,
University of Cincinnati, Cincinnati, OH 45229, USA. david.bernstein@cchmc.org
Herpes simplex virus (HSV) Type-1 and -2 are common infections that can cause
primary and recurrent herpes labialis and genitalis, as well as
gingivostomatitis, keratoconjunctivitis, encephalitis, disseminated infections
in immunocompromised persons and neonatal infections. Despite several decades of
HSV vaccine development, no effective vaccine has been developed until recently.
The following review of the genital HSV-2 glycoprotein D (gD2t, t is for
truncated) subunit vaccine formulated with a new adjuvant (AS04) containing alum
and 3-O deacylated monophosphoryl lipid A (MPL) provides a background in which
to evaluate the vaccine as well as a brief review of other approaches to herpes
vaccines. The gD2t-AS04 vaccine has been demonstrated to be safe in several
large clinical trials. In two trials, the vaccine reduced genital herpes disease
by 73 and 74%, but only in females with no previous HSV infection. A large
ongoing trial in HSV seronegative females will provide additional data on
protection from HSV disease and infection.
-----
Obstet Gynecol. 2005 Oct;106(4):845-56.
Genital herpes complicating pregnancy.
Brown ZA, Gardella C, Wald A, Morrow RA, Corey L.
Departments of Obstetrics and Gynecology, Laboratory Medicine, Medicine and
Epidemiology, University of Washington; and the Program in Infectious Disease,
Fred Hutchinson Cancer Research Center, University of Washington, Seattle,
Washington.
Approximately 22% of pregnant women are infected with herpes simplex virus (HSV)-2,
and 2% of women will acquire HSV during pregnancy. Remarkably, up to 90% of
these women are undiagnosed because they are asymptomatic or have subtle
symptoms attributed to other vulvovaginal disorders. Diagnosis of genital herpes
relies on laboratory confirmation with culture or polymerase chain reaction
assay of genital lesions and type-specific glycoprotein G-based serologic
testing. Neonatal herpes is the most severe complication of genital HSV
infection and is caused by contact with infected genital secretions at the time
of labor. Maternal acquisition of HSV in the third trimester of pregnancy
carries the highest risk of neonatal transmission. Despite advances in the
diagnosis and treatment of neonatal herpes, little change in the incidence or
serious sequelae from this infection has occurred. As such, prevention of the
initial neonatal infection is critically important. Obstetricians are in a
unique position to prevent vertical HSV transmission by identifying women with
genital lesions at the time of labor for cesarean delivery, prescribing
antiviral suppressive therapy as appropriate, and avoiding unnecessary invasive
intrapartum procedures in women with genital herpes. Enhanced prevention
strategies include identification of women at risk for HSV acquisition during
pregnancy by testing women and possibly their partners for HSV antibodies and
providing counseling to prevent transmission to women in late pregnancy.
-----
Rev Med Brux. 2005 Sep;26(4):S360-3.
[Genital herpes]
[Article in French]
Parent D.
Clinique de Pathologie des Muqueuses, Hopital Erasme, Bruxelles.
In developed countries, genital herpes is, together with papillomavirus
infections, among the most common sexually transmitted diseases. HSV is a
dormant virus causing lifelong infection and recurring with or without clinical
symptoms. Exposure to lesions and to asymptomatic viral shedding result in
transmission. Thus, in most cases, finding the exact path of viral transmission
is impossible. The diagnosis is often clinical: classic lesion presentation and
typical localised recurrences. The confirmation of the diagnosis is obtained by
virus isolation, the most sensitive method is PCR but viral culture techniques
are the most widely used. Today, the nucleoside analog antivirals (aciclovir,
valacicovir, famciclovir, penciclovir), are the only efficient and well
tolerated treatments for genital herpes. The virus resistance to these molecules
in immunocompetent patients is very low and has not increased since their
introduction. Thus, for these patients, treatment failure is generally due to
low bioavailability which is resolved by increasing doses. Ideally a vaccine
against herpes should be prophylactic (preventing primary infection) and
therapeutic (preventing recurrences). None is available today despite intensive
research for the past two decades.
-----
Herpes. 2005 Sep;12(2):38-41.
Use of complementary and alternative medicine for the treatment
of genital herpes.
Perfect MM, Bourne N, Ebel C, Rosenthal SL.
Department of Pediatrics and Sealy Center for Vaccine Development, University of
Texas Medical Branch, Galveston, TX, USA and American Social Health Association,
Research Triangle Park, NC, USA.
Conventional antiviral drugs have proven effectiveness for genital herpes;
however, patients continue to use a variety of complementary and alternative
medicine (CAM) treatments. Given that patients may be using these products, it
is important that healthcare providers become familiar with the data regarding
safety and efficacy. We have reviewed available scientific data on six commonly
used treatments (echinacea, eleuthero, L-lysine, zinc, bee products and aloe).
In addition, information about a number of other products is presented in
tabular form. Currently, there are insufficient clinical data to be confident of
the efficacy and safety of any of these products for the treatment of genital
herpes. It is hoped that future clinical trials will be conducted with
sufficient rigour to provide guidance to the patients using these products.
-----
South Med J. 2005 Sep;98(9):914-20.
Current and potential uses of imiquimod.
Chang YC, Madkan V, Cook-Norris R, Sra K, Tyring S.
Department of Intemal Medicine, University of Texas Health Science Center at
Houston, Houston, TX 77030, USA.
Imiquimod, an imidazoquinoline amine, is an immune response modifier first
FDA-approved for the treatment of external genital and perianal warts in 1997.
Since its appearance on the market, its antiviral and antitumor properties have
been used in the treatment of a variety of dermatologic conditions. In this
review article, the basic mechanism of action of imiquimod, current FDA-approved
and non-FDA-approved uses of imiquimod, and key points of medication application
frequency, possible adverse effects, and use in combination therapy are
discussed. Common skin conditions that may be eradicated with imiquimod are
emphasized.
-----
Vaccine. 2005 Sep 21; [Epub ahead of print]
A randomized controlled trial of a replication defective (gH
deletion) herpes simplex virus vaccine for the treatment of recurrent genital
herpes among immunocompetent subjects.
de Bruyn G, Vargas-Cortez M, Warren T, Tyring SK, Fife KH, Lalezari J, Brady RC,
Shahmanesh M, Kinghorn G, Beutner KR, Patel R, Drehobl MA, Horner P, Kurtz TO,
McDermott S, Wald A, Corey L.
Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle,
WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA.
BACKGROUND:: A replication incompetent herpes virus lacking the glycoprotein H
gene has been developed as a potential therapeutic vaccine for genital herpes.
GOAL:: To determine vaccine efficacy on reducing HSV reactivation and clinical
disease among immunocompetent persons with recurrent genital HSV-2 infection.
STUDY DESIGN:: Randomized multicenter placebo-controlled trial. Healthy
volunteers who had six or more recurrences of genital herpes per year were
randomized to receive injections of vaccine at 0 and 8 or 0, 4, and 8 or 0, 2,
4, and 8 weeks or placebo and were followed for subsequent recurrences for 1
year. RESULTS:: The median times to first recurrence of genital herpes (40 days
versus 30 days versus 37 days versus 42 days, respectively), mean number of
recurrences (3 versus 3 versus 2.4 versus 1.9, respectively), and time to lesion
healing of the first recurrence (8 days versus 7.8 days versus 7.4 days versus
7.5 days, respectively), were similar for all treatment groups. Asymptomatic
viral shedding was detected by PCR in 61/74 (82%) persons performing daily
sample collection following completion of the vaccination series. No differences
were noted in the proportion of days with shedding between treatment groups
(11.9% versus 17.2% versus 13.1% versus 16.4%, respectively). CONCLUSION:: This
replication incompetent HSV-2 vaccine lacking the glycoprotein H gene was safe
but had no clinical or virologic benefit in the amelioration of genital HSV-2
disease among immunocompetent men and women.
-----
Am Fam Physician. 2005 Sep 15;72(6):1075-80.
Herpes zoster and postherpetic neuralgia: prevention and
management.
Mounsey AL, Matthew LG, Slawson DC.
Department of Family Medicine, University of Virginia, Charlottesville, Virginia
22908, USA.
The recognizable appearance and the dermatomal distribution of herpes zoster
lesions usually enable a clinical diagnosis to be made easily. Herpes zoster and
postherpetic neuralgia occur mainly in older patients. The role of the varicella
vaccine in preventing herpes zoster is uncertain, but is being studied. There is
evidence to support using antiviral therapy and possibly low-dose tricyclic
antidepressants to prevent postherpetic neuralgia. There is good evidence that
treating herpes zoster with antiviral medication is beneficial, particularly in
patients older than 50 years with severe outbreaks. The use of steroids has an
unfavorable risk-benefit ratio. In patients who develop postherpetic neuralgia,
there is good evidence to support treatment with gabapentin and tricyclic
antidepressants. More evidence for treatment with capsaicin cream, lidocaine
patch, and opioids is needed. Intrathecal methylprednisolone is an option for
patients with persistent pain.
-----
J Oral Pathol Med. 2005 Aug;34(7):423-5.
Recurrent herpes labialis: a pilot study of the efficacy of zinc
therapy.
Femiano F, Gombos F, Scully C.
Stomatology Clinic, II University of Medicines and Surgery, Naples, Italy.
femiano@libero.it
BACKGROUND: The objective of this study was to investigate the effect of zinc on
recurrent herpes labialis. MATERIALS/METHODS: Twenty patients (12 females;
median age 26.6 years) with a history of recurrent herpes labialis >6 episodes
each year were treated with systemic zinc sulphate 22.5 mg twice daily for the
months of February, March, September and October. All patients were followed for
12 months. Results: Herpetic lesions reduced to <4 episodes (average 3) for the
12 months and the duration was <7 days for each episode (average 5.7).
CONCLUSIONS: Systemic zinc sulphate appeared to reduce both the number of
episodes and the time to recovery of herpes labialis.
-----
J Infect Dis. 2005 Jul 1;192(1):156-61. Epub 2005 May 27.
Recurrent antiviral-resistant genital herpes in an
immunocompetent patient.
Kriesel JD, Spruance SL, Prichard M, Parker JN, Kern ER.
Department of Medicine, University of Utah, Salt Lake City, Utah 84132, USA.
jkriesel@hsc.utah.edu
Herpes simplex virus type 2 (HSV-2) resistance to antiviral drugs has been
described primarily in immunocompromised patients. We report an apparently
immunocompetent, human immunodeficiency virus-negative male patient who has
experienced repeated HSV-2 genital outbreaks despite receiving antiviral
prophylaxis with several different drugs. Several of the HSV-2 genital isolates
from this patient have been confirmed as resistant to acyclovir and penciclovir.
Antiviral resistance occurred in the setting of long-term prednisone treatment
and intermittent acyclovir prophylaxis at suboptimal doses and persisted despite
the cessation of oral steroid treatment. The patient's genital herpes outbreaks
were not controlled by high-dose prophylaxis with acyclovir, valacyclovir, and
famciclovir. Cessation of antiviral prophylaxis resulted in reversion of this
patient's HSV-2 isolates to acyclovir and penciclovir sensitivity, although
resistant virus reappeared when antiviral prophylaxis was resumed. Transmission
of a sensitive HSV-2 strain from this patient to a female sex partner was
observed. These observations confirm previous reports that resistance to
acyclovir may develop during prophylactic therapy in an otherwise well,
immunocompetent patient. These findings support the conclusion that both
drug-sensitive and drug-resistant HSV-2 strains established latency in this
patient and that both strains are capable of frequent reactivation.
-----
Herpes. 2005 Jun;12(1):10-4.
Genital herpes in young adults: changing sexual behaviours,
epidemiology and management.
Roberts C.
University Health Services, Madison, WI 53726, USA. cmrober1@wisc.edu
Genital herpes is a common sexually transmitted infection throughout the world.
The majority of new infections occur in adolescents and young adults, although
prevalence rates generally increase with age and cumulative sexual experience.
In young adults, herpes simplex virus 1 (HSV-1) infection is becoming a more
common cause of genital herpes. Reasons for this trend include changing sexual
practices, notably oral-genital exposure and the use of condoms for intercourse.
Important implications of having genital herpes include the risk of transmission
to sexual partners and the increased risk of acquiring and transmitting HIV.
Genital herpes infections are often unrecognized, and transmission to uninfected
partners is likely to occur during asymptomatic shedding. A diagnosis of herpes
may also affect psychosexual development, particularly in adolescents. Such
factors contribute to the growing global HSV prevalence and suggest a need to
implement better screening programmes in young adults. Recognizing and treating
HSV early offers benefits to patients and their sexual partners by reducing the
frequency and severity of outbreaks, limiting the likelihood of disease
transmission, and preventing new infections.
-----
Altern Med Rev. 2005 Jun;10(2):123-7.
Safety and effectiveness of an L-lysine, zinc, and herbal-based
product on the treatment of facial and circumoral herpes.
Singh BB, Udani J, Vinjamury SP, Der-Martirosian C, Gandhi S, Khorsan R,
Nanjegowda D, Singh V.
Southern California University of Health Sciences, SCU Research Division, 16200
E. Amber Valley Drive, Whittier, California 90604, USA. drbetsysingh@verizon.net
CONTEXT: L-lysine, an essential amino acid, inhibits normal replication of
Herpes simplex virus (HSV), shortening the normal course and duration of the
disease. This study was conducted to determine the effectiveness of a
combination of L-lysine with botanicals and other nutrients in relieving the
symptoms of facial and circumoral herpes. METHODS: This small pilot study was
conducted using an outcome (open-label) model. Thirty male and female
participants (15 in each group) meeting the inclusion/exclusion criteria were
admitted to the study. The 10 outcome measures used to monitor the sores were
tingling, itching, burning, tenderness, prickling, soreness, bump/swelling,
small blister(s), oozing blister(s), and crusting, as well as before-and-after
photographs of the lesion, and a daily diary. RESULTS: At the end of treatment
the ointment produced full resolution in 40 percent of the participants by the
third day and in 87 percent by the end of the sixth day. A cold sore episode may
last up to 21 days without treatment. CONCLUSIONS: Overall data indicated
significant improvement in participants by the sixth day of treatment for all
but two participants. There were no adverse effects reported during this study.
-----
N Engl J Med. 2005 Jun 2;352(22):2271-84.
A vaccine to prevent herpes zoster and postherpetic neuralgia in
older adults.
Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, Arbeit RD,
Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman KD, Williams HM, Zhang
JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli JC, Brooks PA, Kauffman CA,
Pachucki CT, Neuzil KM, Betts RF, Wright PF, Griffin MR, Brunell P, Soto NE,
Marques AR, Keay SK, Goodman RP, Cotton DJ, Gnann JW Jr, Loutit J, Holodniy M,
Keitel WA, Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM,
Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS, Wang WW,
Annunziato PW, Silber JL; Shingles Prevention Study Group.
Shingles Prevention Study (Mail code 111F-1), VA San Diego Healthcare System,
3350 La Jolla Village Dr., San Diego, CA 92161,USA. mnoxman@ucsd.edu
BACKGROUND: The incidence and severity of herpes zoster and postherpetic
neuralgia increase with age in association with a progressive decline in
cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis
that vaccination against VZV would decrease the incidence, severity, or both of
herpes zoster and postherpetic neuralgia among older adults. METHODS: We
enrolled 38,546 adults 60 years of age or older in a randomized, double-blind,
placebo-controlled trial of an investigational live attenuated Oka/Merck VZV
vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical
and laboratory criteria. The pain and discomfort associated with herpes zoster
were measured repeatedly for six months. The primary end point was the burden of
illness due to herpes zoster, a measure affected by the incidence, severity, and
duration of the associated pain and discomfort. The secondary end point was the
incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the
subjects continued in the study to its completion, with a median of 3.12 years
of surveillance for herpes zoster. A total of 957 confirmed cases of herpes
zoster (315 among vaccine recipients and 642 among placebo recipients) and 107
cases of postherpetic neuralgia (27 among vaccine recipients and 80 among
placebo recipients) were included in the efficacy analysis. The use of the
zoster vaccine reduced the burden of illness due to herpes zoster by 61.1
percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5
percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent
(P<0.001). Reactions at the injection site were more frequent among vaccine
recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly
reduced morbidity from herpes zoster and postherpetic neuralgia among older
adults. Copyright 2005 Massachusetts Medical Society
-----
Expert Rev Anti Infect Ther. 2005 Jun;3(3):385-92.
Antiviral therapy for genital herpes infections in pregnancy.
Baker DA.
Department of Obstetrics, Gynecology and Reproductive Medicine, Stony Brook, NY
11794-8091, USA. dbaker@notes.cc.sunysb.edu
One of the most deleterious consequences of maternal infection with herpes
simplex virus is neonatal herpes, which results in death or significant
neurodevelopmental impairment in the majority of infected babies. Herpes simplex
virus infection during pregnancy can also impact the psychologic health of the
mother. The ability to minimize the risk of herpes simplex virus transmission
has improved in tandem with advances in understanding of the mechanisms and
epidemiology of acquisition of neonatal herpes simplex virus. In particular,
antiviral pharmacotherapy is now recognized as an important option both for
reducing the risk of transmission of herpes simplex virus from a seropositive to
a seronegative partner and, potentially, for modifying several risk factors for
transmission of the virus from a herpes simplex virus-infected mother to the
neonate. This review discusses the consequences and management of herpes simplex
virus infection during pregnancy, with a focus on the evolving role of antiviral
therapy.
-----
Clin Infect Dis. 2005 May 1;40(9):1271-81. Epub 2005 Mar 24.
Safety and immunogenicity of glycoprotein D-adjuvant genital
herpes vaccine.
Bernstein DI, Aoki FY, Tyring SK, Stanberry LR, St-Pierre C, Shafran SD,
Leroux-Roels G, Van Herck K, Bollaerts A, Dubin G; GlaxoSmithKline Herpes
Vaccine Study Group.
Cincinnati Children's Hospital Medical Center, University of Cincinnati,
Cincinnati, Ohio, USA. david.bernstein@cchmc.org
BACKGROUND: Two previous trials have suggested that a herpes simplex virus (HSV)
type 2 glycoprotein D (gD) vaccine combined with the adjuvants alum and
3'-O-deacylated-monophosphoryl lipid A (MPL) is well tolerated and provides
protection against genital herpes disease in women with no preexisting HSV
antibody. METHODS: The safety and immunogenicity of this vaccine were evaluated
in a large, multicenter, double-blind, randomized, placebo-controlled trial. The
effects of sex and preexisting HSV immunity were sought. RESULTS: When solicited
symptoms that continued after the initial 4 days of observation were excluded,
the incidence of unsolicited symptoms occurring during the 7 months after
vaccination (the primary analysis period) was 22.1% in vaccine recipients and
21.9% in placebo recipients. Significant increases in the number of local and
systemic symptoms were found in vaccine recipients within 4 days after
vaccination. However, most symptoms were mild to moderate in severity and were
short lived. Women reported symptoms more frequently than did men, but
preexisting immunity had little effect. The vaccine induced higher titers of HSV
gD antibody on enzyme-linked immunosorbent assays than did natural infection
with HSV. CONCLUSION: The vaccine was generally safe, well tolerated, and
immunogenic.
-----
Dermatol Clin. 2005 Apr;23(2):313-22.
Advances in antiviral therapy.
Wu JJ, Pang KR, Huang DB, Tyring SK.
Department of Dermatology, University of California at Irvine, C340, Medical
Science I, Irvine, CA 92697-2400, USA.
Infections with five of the herpesviruses (herpes simplex virus 1 [HSV-1],
HSV-2, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus) are
treated with topical or systemic antiviral therapies. There are more than 100
genotypes of human papillomaviruses (HPVs), which may manifest as warts, skin
cancers, cervical cancer, anogenital cancers, and upper digestive tract cancers.
Molluscum contagiosum (MC) is a common, benign viral infection of the skin.
Immunomodulating agents, such as imiquimod, act on HPV and MC indirectly by
inducing host immune responses, such as cytokines and cell-mediated immunity,
and thereby reduce recurrences. There are multiple vaccines available for
certain viral diseases and others in development for HSV-2 and HPV.
-----
J Clin Periodontol. 2005 Apr;32(4):341-6.
Efficacy of Listerine Antiseptic in reducing viral contamination
of saliva.
Meiller TF, Silva A, Ferreira SM, Jabra-Rizk MA, Kelley JI, Depaola LG.
Department of Diagnostic Sciences and Pathology, Dental School, University of
Maryland, Baltimore, MD, USA.
Meiller TF, Silva A, Ferreira SM, Jabra-Rizk MA, Kelley JI, DePaola LG. Efficacy
of Listerine((R)) Antiseptic in reducing viral contamination of saliva. J Clin
Periodontol 2005; 32: 341-346. doi: 10.1111/j.1600-051X.2005.00673.x. (c)
Blackwell Munksgaard, 2005. Abstract Aim: The anti-viral efficacy of oral
antimicrobial rinses has not been adequately studied in terms of potential
clinical significance. As a follow-up to an in vitro study on the effect of oral
antiseptics on Herpes simplex virus, Type 1, this study was undertaken to
evaluate the in vivo effect of an essential oil containing oral antiseptic on
the reduction of viral titer in saliva during active viral infection. Method:
Patients were recruited and evaluated in a single visit protocol at the onset of
a perioral outbreak, consistent historically and clinically with recurrent
Herpes labialis. Direct immunofluorescence of cytological smears of the
lesions/oral fluids was used to confirm Herpes simplex virus types I or II.
Patients were randomly assigned to one of two treatment groups: (1) active
ingredient and (2) sterile water control. The viral lesion was evaluated as to
clinical stage according to standard protocol. Salivary fluid samples were
taken: (1) at baseline; (2) immediately following a 30 s rinse; (3) 30 min.
after the 30 s rinse; and (4) on the repeat trial, also at 60 min. after the 30
s rinse. All samples were evaluated for viral titer and results compared.
Results: In Trial 1, the sample population consisted of 19 males and 21 females
with an average age of 29.2 and in Trial 2, 21 males, 19 females with an average
age of 28. In both Trials 1 and 2, recoverable infectious virions were reduced
to zero after a 30 s experimental rinse; whereas, the control rinse resulted in
a non-significant (p>0.05) reduction. The experimental group also demonstrated a
continued significant (p<0.05) reduction 30 min. post rinse when compared with
baseline while the control group returned to baseline levels. In Trial 2, the 60
min. post rinse follow-up demonstrated a 1-2 log residual reduction from
baseline in the experimental group; however, this was not significant.
Conclusions: There is clinical efficacy in utilizing an oral rinse with the
antimicrobial agent Listerine((R)) Antiseptic in reducing the presence of viral
contamination in oral fluids for at least 30 min. after oral rinse. The risk of
viral cross contamination generated from these oral fluids in person to person
contact or during dental treatment may be reduced.
-----
J Neurol. 2005 Mar;252(3):268-72. Epub 2005 Mar 11.
Viral encephalitis.
Kennedy PG.
Department of Neurology, Division of Clinical Neurosciences, Southern General
Hospital, Institute of Neurological Sciences, Glasgow G51 4TF, Scotland, UK,
P.G.Kennedy@clinmed.gla.ac.uk.
Acute viral encephalitis may be caused by a wide range of viruses but the most
important is herpes simplex encephalitis (HSE) because of its severity,
especially if untreated, and its good response to specific treatment with
acyclovir. The outcome of any CNS viral infection is dependent on both the
immune status of the host and the virulence of the infecting virus. In
evaluating a patient with suspected viral encephalitis there are 3 essential
steps, namely the identification of a true parenchymal virus infection of the
brain rather than a non-infective encephalopathy, the distinction of an
infectious viral encephalitis from an acute disseminated encephalomyelitis (ADEM),
and then the determination, where possible, of the specific virus involved. In
practice, the precise viral cause of the encephalitis may never be established.
Analysis of the CSF for herpes simplex virus (HSV) DNA using the Polymerase
Chain Reaction (PCR) has been a significant advance in the diagnosis of HSE as
this test has a very high sensitivity and specificity especially with
appropriate sample timing. It is essential to commence early treatment with
intravenous acyclovir in patients suspected of having HSE because of the
remarkable safety and efficacy of this drug and the dangers of delaying
potentially effective treatment of life threatening disease. This review
outlines the general management approach in patients suspected of having viral
encephalitis.
-----
Expert Opin Investig Drugs. 2005 Feb;14(2):135-61.
Agents and strategies in development for improved management of
herpes simplex virus infection and disease.
Kleymann G.
Gerald.Kleymann@freenet.de
The quiet pandemic of herpes simplex virus (HSV) infections has plagued humanity
since ancient times, causing mucocutaneous infection such as herpes labialis and
herpes genitalis. Disease symptoms often interfere with every-day activities and
occasionally HSV infections are the cause of life-threatening or sight-impairing
disease, especially in neonates and the immuno-compromised patient population.
After infection the virus persists for life in neurons of the host in a latent
form, periodically reactivating and often resulting in significant psychosocial
distress for the patient. Currently no cure is available. So far, vaccines, ILs,
IFNs, therapeutic proteins, antibodies, immunomodulators and small-molecule
drugs with specific or non-specific modes of action lacked either efficacy or
the required safety profile to replace the nucleosidic drugs acyclovir,
valacyclovir, penciclovir and famciclovir as the first choice of treatment. The
recently discovered inhibitors of the HSV helicase-primase are the most potent
development candidates today. These antiviral agents act by a novel mechanism of
action and display low resistance rates in vitro and superior efficacy in animal
models. This review summarises the current therapeutic options, discusses the
potential of preclinical or investigational drugs and provides an up-to-date
interpretation of the challenge to establish novel treatments for herpes simplex
disease.
-----
Semin Pediatr Infect Dis. 2005 Jan;16(1):31-7.
Pediatrics and herpes simplex virus vaccines.
Rupp R, Rosenthal SL, Stanberry LR.
Department of Pediatrics and Sealy Center for Vaccine Development, University of
Texas Medical Branch, Galveston, TX 77555-1119, USA. rrupp@utmb.edu
This review explores the development of prophylactic genital herpes vaccines and
their potential impact on perinatal and oral-facial disease. Vaccine strategies
have included the use of whole killed virus, viral subunits, attenuated live
virus, viral vectors, and bare DNA. To date, the recombinant subunit vaccine,
truncated HSV-2 gD and alum/MPL, has been the most efficacious. The vaccine is
73 to 74 percent effective in preventing genital disease in herpes simplex virus
seronegative women but is not effective in men or seropositive women. Models
predict a significant impact on genital herpes if it limits viral shedding.
Reductions in perinatal and oral-facial disease are likely to occur as well.
Once an efficacious herpes vaccine is available, its effectiveness will depend
ultimately on vaccine acceptance by professional organizations, healthcare
professionals, and parents. Further research is required to improve on and fully
understand the implications of prophylactic herpes simplex vaccines.
-----
Semin Pediatr Infect Dis. 2005 Jan;16(1):7-16.
Neonatal herpes: what have we learned.
Kimberlin DW, Whitley RJ.
Department of Pediatrics, The University of Alabama Birmingham, AL 35233, USA.
dkimberlin@peds.uab.edu
Neonatal herpes simplex virus (HSV) infection usually is acquired during the
birth process, as the neonate comes in contact with the virus during passage
through an infected birth canal. After an incubation period which can last as
long as 2 to 4 weeks, neonatal HSV disease then manifests in 1 of 3 ways: (1)
disseminated disease, with visceral organ involvement (including infection of
the brain in two-thirds to three-quarters of patients); (2) central nervous
system disease (with no other visceral organ involvement, but with skin lesions
in two-thirds of patients); or (3) disease limited to the skin, eyes, and/or
mouth (ie, SEM disease). Diagnostic advances in recent years have focused
primarily on applying polymerase chain reaction technology to babies suspected
of having neonatal HSV disease. Treatment of neonatal HSV disease with
intravenous acyclovir has improved the likelihood of survival substantially,
although neurologic morbidity remains a common sequelae, especially among
survivors of central nervous system disease. Despite these advances, the
duration of time from onset of symptoms and initiation of antiviral therapy has
remained unchanged for the past 20 years. The surest way to improve outcomes
rapidly at this point is to raise awareness of neonatal HSV disease, resulting
in the establishment of earlier diagnoses and more rapid institution of
antiviral therapy. In the longer term, development of a bedside nucleic acid
detection kit for real-time detection of HSV DNA in the maternal genital tract
at the time of delivery could identify which babies are at risk of developing
neonatal HSV disease.
-----
J Infect Dis. 2005 Feb 1;191(Suppl 1):S97-S106.
Role of Herd Immunity in Determining the Effect of Vaccines
against Sexually Transmitted Disease.
Garnett GP.
Department of Infectious Disease Epidemiology, Imperial College London, St.
Mary's Campus, London, United Kingdom. g.garnett@imperial.ac.uk.
Background. Vaccination programs provide both direct protection to those
immunized and herd immunity, which is indirect protection of those who remain
susceptible, owing to a reduced prevalence of infections.Methods. The
well-understood impact of vaccination against ubiquitous childhood infections is
compared with that of vaccination against sexually transmitted infections (STIs),
and theoretical insights are derived from a review of mathematical modeling
studies.Results. Typically, a large fraction of cases of STIs are acquired by
those with modest risk, and these cases could be prevented by low-efficacy
vaccines. If coverage is good, vaccination of only one sex can protect the other
sex. Candidate vaccines against human papillomavirus (HPV) and genital herpes
are in the final stages of testing. The former is likely to be highly
efficacious for a limited number of disease-causing HPV types, and the latter
has provided protection against disease in women who initially were seronegative
for both herpes simplex virus (HSV) type 1 and HSV-2, with 73% efficacy. In
models, this vaccine had a substantial impact when infectiousness was assumed to
be reduced along with incidence of disease.Conclusion. With such vaccines on the
horizon, the requirements for vaccine delivery need to be considered,
particularly who should be vaccinated and at what age.
-----
J Perinatol. 2004 Dec 16; [Epub ahead of print]
Improved Neurodevelopmental Outcomes following Long-Term
High-Dose Oral Acyclovir Therapy in Infants with Central Nervous System and
Disseminated Herpes Simplex Disease.
Tiffany KF, Benjamin DK, Palasanthiran P, O'donnell K, Gutman LT.
1Department of Pediatrics (K.F.T., D.K.B., K.O'.D., L.T.G.), Duke University,
Durham, NC, USA.
OBJECTIVE:: Infants with neonatal herpes, classified as central nervous system
or disseminated disease, have a high incidence of moderate and severe neurologic
deficits despite standard acute therapy. STUDY DESIGN:: Following completion of
parenteral therapy, infants with central nervous system and/or disseminated
disease received 2 years of continuous oral acyclovir therapy. Target minimum
peak serum acyclovir concentrations were >2 mug/ml for the first three patients,
and >3 mug/ml for the subsequent 13 patients. Safety assessments were made every
3 months. We evaluated neurodevelopmental outcomes with Bayley Scales of Infant
Development. RESULTS:: A total of 16 consecutive herpes simplex virus-infected
infants born during 1990 to 2003 received the treatment plan; 13/16 infants had
central nervous system disease; 3 had disseminated disease without central
nervous system involvement. A total of 69% (11/16) had Bayley scores in the
normal range for mental development and 79% (11/14) had motor scores in the
normal range. At the final assessment, five children had developmental delays.
One child had severe mental delay with normal motor development. Four children
had mild mental delays, with severe motor delays in three. All children were
independently mobile, without seizure disorder, had normal vision, and had
speech development. During the 2-year course of treatment, five children had
brief recurrences of dermal lesions, and none had evidence of neurologic
deterioration. There were no serious or sustained adverse drug reactions.
CONCLUSION:: This pilot study reports improved outcomes in a small cohort of
infants with a prolonged course of oral acyclovir. A minority of these children
exhibited mild or significant developmental delays. Further investigation of
this approach to treatment is warranted.Journal of Perinatology advance online
publication, 16 December 2004; doi:10.1038/sj.jp.7211247.
-----
Expert Opin Pharmacother. 2004 Dec;5(12):2567-71.
Docosanol: a topical antiviral for herpes labialis.
Leung DT, Sacks SL.
Wake Forest University School of Medicine, Box 2642, Medical Center Blvd,
Winston Salem, NC 27157, USA. dleung@wfubmc.edu
Recurrent herpes labialis is a painful and potentially disfiguring infection
affecting an estimated 40 million people in the US alone. The majority of
recurrences are caused by herpes simplex virus type 1. Various oral and topical
formulations of nucleoside analogues have demonstrated efficacy for this
indication. Over-the-counter treatments are palliative in nature and do not
reduce time to healing. Docosanol is a compound with a unique mechanism of
action involving viral fusion inhibition. In randomised, clinical trials, a 10%
docosanol cream formulation, initiated within 12 h of symptoms onset,
demonstrated efficacy in reduction of time-to-healing compared with a
polyethylene glycol control. Despite its potential to be a mild irritant, this
novel antiviral was well-tolerated in clinical trials. Docosanol is the first
topical antiviral approved for over-the-counter use in recurrent herpes labialis.
-----
Curr Opin Ophthalmol. 2004 Dec;15(6):531-6.
Herpes zoster virus infection.
Liesegang TJ.
Mayo Clinic Medical School, Jacksonville, Florida, USA. tliesegang@mayo.edu
PURPOSE OF REVIEW: The virology, pathophysiology, and treatment of the varicella
zoster virus (VZV) have been investigated for many years now. Infection with VZV
has different ramifications for people of different ages and immune status. The
various aspects of VZV disease make it difficult to treat. Selected aspects of
VZV disease that pertain to ocular disease are presented. RECENT FINDINGS: The
risk factors for VZV disease in the different age spectrums and with concomitant
immunodeficiencies have been further clarified. Studies suggest that the VZV may
persist for prolonged periods on the cornea after herpes zoster ophthalmicus (HZO).
Herpes Simplex Virus (HSV) or VZV may cause many cases of idiopathic uveitis
with sectoral iris atrophy. The different patterns of retinal disease caused by
VZV may relate to the immune status. Systemic antiviral medications for herpes
zoster should be instituted within 72 hours of the rash but could be used later.
Systemic antivirals combined with systemic corticosteroids improve the early
quality of life in HZ patients. Postherpetic neuralgia is not prevented by early
systemic antivirals or corticosteroids. Present systemic antivirals are all
effective, but Famvir offers the best dosing schedule. The VZV vaccine is
effective but there are some issues that suggest the need for a different
vaccination regimen. SUMMARY: Further research must be performed on the clinical
and therapeutic aspects of the VZV disease. Although both the vaccine and
systemic antivirals have brought tremendous improvements, the disease persists.
Therapy lessens but does not eliminate many of the complications. The disease
may manifest in unpredictable patterns in this era of vaccination.
-----
Leuk Lymphoma. 2004 Nov;45(11):2215-9.
Oral valacyclovir as prophylaxis against herpes simplex virus
reactivation during high dose chemotherapy for leukemia.
Orlowski RZ, Mills SR, Hartley EE, Ye X, Piantadosi S, Ambinder RF, Gore SD,
Miller CB.
The Sidney Kimmel Comprehensive Cancer Center, Divisions of Hematological
Malignancies, Baltimore, Maryland 21287-8985, USA. R_Orlowski@med.unc.edu
Reactivation of herpes simplex virus is a common event in patients undergoing
dose-intensive remission induction or consolidation chemotherapy of acute
leukemia, for which either intravenous or oral acyclovir provides effective
prophylaxis. This drug's short serum half-life and low oral bioavailability make
frequent dosing necessary, however, and we therefore sought to determine if the
pro-drug valacyclovir, which has improved bioavailability, could be successfully
substituted for this indication. Eighty-one patients with leukemia were
randomized to receive either 500 mg or 1,000 mg of valacyclovir orally every 8 h
and followed clinically, as well as with serial surveillance cultures. Over a
total of 1,979 days on study between the groups, and 380 throat cultures, no
documented episodes of herpes simplex reactivation were noted. Valacyclovir was
tolerated well with no evident drug-related toxicities. We conclude that
valacyclovir at either of the two doses studied can be safely substituted for
oral or intravenous acyclovir, and that it provides effective prophylaxis
against reactivation of herpes simplex virus in this patient population.
-----
J Pediatr Gastroenterol Nutr. 2004 Nov;39(5):560-3
Herpes simplex virus esophagitis in immunocompetent children.
Rodrigues F, Brandao N, Duque V, Ribeiro C, Antonio AM.
Hospital Pediatrico de Coimbra, Portugal. fmprodrigues@hotmail.com
OBJECTIVES: To review clinical, laboratory, endoscopic and histologic features,
treatment and outcome of immunocompetent children with Herpes simplex virus
esophagitis. METHODS: Retrospective analysis of the medical records of six
children (five males) referred to our unit between 1997-2001. RESULTS: The
median age at presentation was 4 years. Fever was present in all, odynophagia/dysphagia
in five, retrosternal pain in four, vomiting in three, drooling in two and
irritability and drowsiness in one. The median time between the onset of
symptoms and the diagnosis was 6.5 days. Endoscopy, performed in all, showed
friable mucosa and erosive-ulcerative involvement, with histology showing
inflammation and ulcerated esophagitis. Tissue viral culture was performed in
five patients and was positive in three, and polymerase chain reaction was
positive in two of four tested. Serology was consistent with primary Herpes
simplex virus infection in all. All received nasogastric feeding and acyclovir.
The outcome was very good. CONCLUSIONS: This is an uncommon and under-recognized
condition in the immunocompetent child. The most common symptoms are sometimes
not diagnostic, particularly in very young children. The presence of unusual
clinical signs may lead to a difficult and delayed diagnosis. Treatment with
acyclovir may have hastened the resolution of symptoms, but a controlled
clinical study was not performed.
-----
Drugs. 2004;64(24):2763-92.
Viral prophylaxis in organ transplant patients.
Slifkin M, Doron S, Snydman DR.
Division of Infectious Diseases, Tufts-New England Medical Center, Boston,
Massachusetts, USA.
Viral pathogens have emerged as the most important microbial agents having
deleterious effects on solid organ transplant (SOT) recipients. Antiviral
chemoprophylaxis involves the administration of medications to abort
transmission of, avoid reactivation of, or prevent progression to disease from,
active viral infection. Cytomegalovirus (CMV) is the major microbial pathogen
having a negative effect on SOT recipients. CMV causes infectious disease
syndromes, augments iatrogenic immunosuppression and is commonly associated with
opportunistic superinfection. CMV has also been implicated in the pathogenesis
of rejection. Chemoprophylactic regimens for CMV have included oral aciclovir
(acyclovir) at medium and high doses, intravenous and oral ganciclovir, and the
prodrugs valaciclovir (valacyclovir) and valganciclovir. CMV prophylactic
strategies should be stratified, with the highest-risk patients receiving the
most 'potent' prophylactic regimens. Herpes simplex virus (HSV) reactivation in
SOT recipients is more frequent, may become more invasive, takes longer to heal,
and has greater potential for dissemination to visceral organs than it does in
the immunocompetent host. Prophylactic regimens for CMV are also effective
chemoprophylaxis against HSV; in the absence of CMV prophylaxis, aciclovir,
valaciclovir or famciclovir should be used as HSV prophylaxis in seropositive
recipients. Primary varicella-zoster virus (VZV) after SOT is rare and most
commonly seen in the paediatric transplant population because of VZV
epidemiology. Zoster occurs in 5-15% of patients, usually after the sixth
post-transplant month. Prophylactic regimens for zoster are neither practical
nor cost effective after SOT because of the late onset of disease and low
proportion of affected individuals. All SOT recipients should receive VZV immune
globulin after contact with either varicella or zoster. Epstein-Barr virus has
its most significant effect in SOT as the precipitating factor in the
development of post-transplant lymphoproliferative disorders. Antiviral agents
that could be effective are the same as those used for CMV, but indications for
and effectiveness of prophylaxis are poorly established. Hepatitis B virus (HBV)
and hepatitis C virus (HCV) are important pathogens in the SOT population as
indications for transplantation. So-called 'prophylaxis' for recurrent HBV and
HCV after liver transplantation is controversial, suppressive rather than
preventive, and potentially lifelong. Influenza infection after SOT is acquired
by person-to-person contact. During epidemic periods of influenza, transplant
populations experience a relatively high frequency of infection, and influenza
may affect immunosuppressed SOT recipients more adversely than immunocompetent
individuals. Antiviral medications for prevention of influenza are administered
as post-exposure prophylaxis to SOT recipients, in addition to yearly vaccine,
in circumstances such as influenza epidemics and nosocomial outbreaks, and after
exposure to a symptomatic individual during 'flu season'.
-----
Indian J Pediatr. 2004 Oct;71(10):921-6.
Management of neonatal herpes simplex virus infections.
Freij BJ.
Division of Infectious Diseases, Department of Pediatrics, William Beaumont
Hospital, 3535 West Thirteen Mile Road, Royal Oak, MI 48073, USA. bfreij@beaumont.edu
As many as 2,500 infants develop neonatal herpes each year, most of whom are
born to women with no history or physical findings suggestive of genital herpes.
Infection usually takes one of three forms: 1) disease localized to skin, eyes,
and mucous membranes, 2) localized central nervous system infection, or 3)
disseminated infection. Exposure to the virus occurs during passage through an
infected birth canal, but 5% of infants acquire the infection in utero. The
mortality rate is 31% for disseminated infection and 6% for localized central
nervous system disease; long-term neurologic sequelae are seen in 17% and 70% of
survivors, respectively. Diagnosis is made by isolating of the virus from skin
lesions or other involved sites. The polymerase chain reaction for the detection
of viral DNA in cerebrospinal fluid or serum is now the diagnostic test of
choice for central nervous system or disseminated neonatal herpes because it has
higher sensitivity than traditional culture methods. Treatment is with high-dose
intravenous acyclovir (60 mg/kg per day in three divided doses), with
adjustments made for infants with renal or hepatic insufficiency. Supportive
measures and neuroimaging studies are often required. Acyclovir is administered
for three weeks, but infants with disease localized to the skin, eyes, and
mucous membranes can be treated for two weeks if the cerebrospinal fluid
polymerase chain reaction assay is negative for herpes simplex virus DNA.
Prevention of infection in infants can be accomplished by cesarean delivery when
women have active lesions at the onset of labor. Neonates delivered through an
infected birth canal should be screened between 24 and 48 hours of age with
viral cultures of eyes, nasopharynx, mouth, and rectum. If positive, they should
be treated with acyclovir even if asymptomatic. Suppressive acyclovir therapy
beginning at 36 weeks gestation is often prescribed for women with frequent
recurrences of genital herpes.
-----
Leuk Lymphoma. 2004 Nov;45(11):2215-9.
Oral Valacyclovir as Prophylaxis against Herpes Simplex Virus
Reactivation During High Dose Chemotherapy for Leukemia.
Orlowski R, Mills S, Hartley E, Ye X, Piantadosi S, Ambinder R, Gore S, Miller
C.
The Sidney Kimmel Comprehensive Cancer Center Divisions of Hematological
Malignancies Baltimore Maryland 21287-8985 USA.
Reactivation of herpes simplex virus is a common event in patients undergoing
dose-intensive remission induction or consolidation chemotherapy of acute
leukemia, for which either intravenous or oral acyclovir provides effective
prophylaxis. This drug's short serum half-life and low oral bioavailability make
frequent dosing necessary, however, and we therefore sought to determine if the
pro-drug valacyclovir, which has improved bioavailability, could be successfully
substituted for this indication. Eighty-one patients with leukemia were
randomized to receive either 500 mg or 1,000 mg of valacyclovir orally every 8 h
and followed clinically, as well as with serial surveillance cultures. Over a
total of 1,979 days on study between the groups, and 380 throat cultures, no
documented episodes of herpes simplex reactivation were noted. Valacyclovir was
tolerated well with no evident drug-related toxicities. We conclude that
valacyclovir at either of the two doses studied can be safely substituted for
oral or intravenous acyclovir, and that it provides effective prophylaxis
against reactivation of herpes simplex virus in this patient population.
-----
Clin Infect Dis. 2004 Nov 1;39 Suppl 5:S258-66.
Efficacy and safety of valacyclovir for the suppression and
episodic treatment of herpes simplex virus in patients with HIV.
Warren T, Harris J, Brennan CA.
Westover Heights Clinic, 2330 NW Flanders, Ste. 207, Portland, OR 97210, USA.
TWESTOVER@aol.com
Three randomized controlled trials of valacyclovir for the management of
recurrences of genital herpes in HIV-infected persons were conducted between
1991 and 2002. One study evaluated episodic therapy for the treatment of genital
herpes, and 2 studies evaluated continuous suppressive therapy. Valacyclovir at
1000 mg twice daily for 5 days was comparable to acyclovir at 200 mg 5 times
daily in accelerating healing of a single episode of genital herpes (hazard
ratio, 1.0; 95% confidence interval [CI], 0.8-1.2; P=.89). Valacyclovir at 500
mg twice daily was effective in preventing or delaying recurrences of genital
herpes compared with placebo (hazard ratio, 0.20; 95% CI, 0.13-0.30; P<.001) and
with valacyclovir at 1000 mg once daily (hazard ratio, 0.56; 95% CI, 0.40-0.80;
P=.001), in 6-month and 48-week studies, respectively. The safety profile of
valacyclovir was similar to that of acyclovir. Valacyclovir is well tolerated,
safe, and effective for the treatment and suppression of recurrent genital
herpes in human immunodeficiency virus-infected persons.
-----
Skin Pharmacol Physiol. 2004 Sep-Oct;17(5):214-8.
Penciclovir cream--improved topical treatment for Herpes simplex
infections.
Schmid-Wendtner MH, Korting HC.
Department of Dermatology and Allergology, Rheinische Friedrich Wilhelm
University, Bonn, Germany. Monika-Hildegard.Schmid-Wendtner@ukb.uni-bonn.de
Human herpesviruses can be found worldwide and cause many viral infections in
immunocompetent as well as in immunocompromised patients. Herpes simplex virus (HSV)
diseases can be the cause of life-threatening disease, especially in neonates.
After initial infection, HSV persists latently in host neurons with the risk of
periodical reactivation over a lifetime. The development of acyclovir, a potent
and specific nucleoside inhibitor of the herpes DNA polymerase, was a milestone
in the history of antiviral drugs in the late 1970s. During the last decades a
better understanding of the replication and disease-causing state of HSV types 1
and 2 has been achieved enabling the development of new and potent antiviral
compounds. In the mid-1990s, for example, valacyclovir and famciclovir were
launched as prodrugs of acyclovir with improved bioavailability. Despite the
numerous drugs available for the systemic treatment of HSV infections, the
topical application of a cream containing an antiviral agent is still the most
convenient method of treating herpes simplex labialis/facialis in the general
population. For some time, the topical standard treatment for recurrent HSV
infections has been acyclovir cream, despite the fact that the evidence for
efficacy in recurrent episodes has been equivocal. Penciclovir, a novel acyclic
nucleoside analogue, has demonstrated efficacy against HSV types 1 and 2 and
seems to have a pharmacological advantage due to a prolonged half-life of its
active form in HSV-infected cells. This review discusses and compares the
topical treatment modalities available for HSV infections. As a conclusion,
different studies are available that have shown that it is possible to reduce
viral replication and hasten lesion resolution with 1% penciclovir treatment
beyond the prodromal phase of the HSV infection. Comparing data of topical
treatment with acyclovir and penciclovir revealed a superiority for penciclovir
cream showing a significant decrease in time to lesion healing, lesion area and
pain. While systemic acyclovir or valacyclovir may be valid drugs especially for
HSV prophylaxis, 1% penciclovir cream should be preferred as topical treatment
since there are good therapeutic results independent of the phase of development
of herpetic eruptions. 2004 S. Karger AG, Basel
-----
Drugs. 2004;64(18):2091-7; discussion 2098-9.
Brivudin (bromovinyl deoxyuridine).
Keam SJ, Chapman TM, Figgitt DP.
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Brivudin is an oral thymidine analogue indicated for the early treatment of
acute herpes zoster in immunocompetent adults. It has high, selective activity
against varicella zoster virus (VZV), inhibiting VZV replication, possibly
through competitive inhibition of viral DNA polymerase, or by acting as an
alternative substrate to deoxythymidine triphosphate, causing viral DNA strand
breakage. In a large, 7-day, phase III trial in immunocompetent patients with
herpes zoster, once-daily brivudin 125mg was significantly more effective than
oral acyclovir 800mg five times daily in reducing the mean time from start of
treatment to last vesicular eruption, and was as effective as acyclovir at
healing lesions and alleviating acute zoster-related pain. The likelihood of
developing post-herpetic neuralgia (PHN) in immunocompetent patients aged > or
=50 years was significantly lower with brivudin than with acyclovir. Brivudin
was as effective as oral famciclovir 250mg three times daily in terms of the
prevalence of PHN, the time to last vesicular eruption and lesion healing in
another large, 7-day, phase III study in immunocompetent patients with herpes
zoster. Oral brivudin is generally well tolerated, with a similar tolerability
profile to those of oral acyclovir or famciclovir. Nausea was the most commonly
reported adverse event.
-----
J Am Dent Assoc. 2004 Sep;135(9):1311-8.
The efficacy of valacyclovir in preventing recurrent herpes
simplex virus infections associated with dental procedures.
Miller CS, Cunningham LL, Lindroth JE, Avdiushko SA.
Department of Oral Health Practice, University of Kentucky College of Dentistry
and College of Medicine, Lexington 40536-0297, USA. cmiller@uky.edu
BACKGROUND: Oral herpes simplex virus, or HSV, infections recur after trauma and
stress. The prevalence of these infections after dental procedures is not known.
Also, it is unclear whether antiviral agents are effective in preventing dental
procedure-induced HSV recurrences. This study determined the efficacy and safety
of oral valacyclovir in suppressing dentally related cold sore outbreak and HSV
shedding. METHODS: The authors enrolled 125 otherwise healthy HSV-seropositive
adults who reported having recurrent herpes labialis (more than one episode per
year and at least one episode in the previous year) in a randomized,
double-blind, placebo-controlled study and gave them valacyclovir
prophylactically (2 grams taken twice on the day of dental treatment and 1 g
taken twice the next day) or a matching placebo. To detect the presence of the
virus, the authors used clinical examinations, viral cultures and real-time
polymerase chain reaction analysis of saliva. RESULTS: During the one-week
observation period after treatment, there were more clinical lesions (20.6
percent versus 11.3 percent), more HSV-1-positive culture specimens (7.9 percent
versus 1.6 percent) and more HSV-1-positive saliva specimens (7.9 percent versus
4.0 percent) in placebo than in valacyclovir-treated patients, respectively. The
percentage of patients who developed recurrences and shed HSV-1 in saliva 72
hours after dental procedures was significantly smaller in the valacyclovir
group than in the placebo group (11.3 percent versus 27 percent; P = .026). The
mean time to pain cessation was significantly less in the valacyclovir group
(3.2 days) than in the placebo group (6.2 days) (P = .006). CONCLUSION: HSV
recrudescence after routine dental treatment is suppressed by valacyclovir
prophylaxis. CLINICAL IMPLICATIONS: HSV recrudescence is common after routine
dental treatment. Clinicians should consider antiviral therapy for patients at
risk of experiencing a recurrence, as well as to minimize transmission of the
disease.
-----
J Perinat Neonatal Nurs. 2004 Jul-Sep;18(3):206-15.
Living with genital herpes: how effective is antiviral therapy?
Roe VA.
Midwifery Education Program, State University of New York Downstate Medical
Center, 450 Clarksen Ave, Box 1227, Brooklyn, NY 11203, USA. valerie.roe@downstate.edu
Twenty-five percent of American women and 20% of American men have genital
herpes. Most of these individuals have never been diagnosed because of the
prevalence of atypical clinical presentation and subclinical infection. This
chronic, recurrent infection poses a significant public health challenge,
particularly in women of childbearing age, who are at risk of transmitting the
virus to their infants during pregnancy and birth, as well as to their
discordant sexual partners. Antiviral therapy decreases the rate of recurrent
episodes, decreases asymptomatic shedding of the virus, reduces the risk of
transmission to sexual partners, and reduces the rate of operative delivery in
women with a history of genital herpes. This article reviews the literature to
explore evidence-based strategies for addressing the physical and psychological
sequelae of herpes simplex virus infection and for accurately diagnosing and
managing neonates who acquire this infection perinatally.
-----
Expert Rev Anti Infect Ther. 2003 Aug;1(2):283-95.
Review of antiviral therapy for herpes labialis, genital herpes
and herpes zoster.
Moomaw MD, Cornea P, Rathbun RC, Wendel KA.
Oklahoma University Health Science Center Department of Internal Medicine,
Section Infectious Diseases, Oklahoma City, OK, USA.
Acyclovir (Zovirax) was approved for the treatment of herpesvirus infections
almost two decades ago. It was the first agent in a novel group of antiviral
medications that now include valacyclovir (Valtrex), penciclovir (Denavir and
famciclovir (Famvir). These agents have made a dramatic impact on the morbidity
associated with herpes simplex virus infections and herpes zoster. Topical and
oral antiviral use have shown modest but statistically significant efficacy in
treating herpes labialis with most studies demonstrating a significant reduction
in episode length and/or healing time. Oral acyclovir, valacyclovir and
famciclovir are efficacious and safe for the treatment of the first episode and
recurrent genital herpes and are useful as suppressive therapy for individuals
with frequent genital herpes recurrences. In addition, high doses of oral
acyclovir, valacyclovir and famciclovir have been shown to speed the healing of
herpes zoster, and data suggests that these agents also decrease associated
acute and chronic pain in people of 50 years of age or older. Further research
is required to clarify the safety of these agents in pregnant women with genital
herpes, the role of antiviral therapy in decreasing the sexual transmission of
genital herpes, and the efficacy and cost-effectiveness of these agents in
treating herpes zoster in people below the age of 50 years.
-----
Curr Opin Infect Dis. 2004 Aug;17(4):357-361.
Prevention and treatment of cytomegalovirus infection in solid
organ transplant recipients.
Pereyra F, Rubin RH.
Division of Infectious Disease, Brigham and Women's Hospital and Harvard Medical
School, Boston. Massachusetts, USA.
PURPOSE OF REVIEW: Cytomegalovirus remains the single most important pathogen
affecting solid organ transplant recipients. Its importance lies both in its
effects and as a model for deciphering the clinical impact and management of
other agents such as hepatitis C virus and other herpes viruses such as human
herpes virus-6 and 7. The effects of cytomegalovirus infection in these patients
can be divided into two categories: the direct causation of a wide variety of
infectious disease syndromes; and the indirect effects, which include
contributing to the net state of immunosuppression, allograft injury, and
potentiating posttransplant lymphoproliferative disease. RECENT FINDINGS: The
advent of valganciclovir, with its excellent oral bioavailability, combined with
intravenous ganciclovir have provided powerful tools for controlling the direct
effects of cytomegalovirus, particularly with the recognition that the intensity
of the antiviral therapy has to be linked to the intensity of the
immunosuppression required.Unfortunately, far less is known about the efficacy
of antiviral therapy in managing the indirect effects of cytomegalovirus.
Preliminary data suggest antiviral prophylaxis protects against acute allograft
injury, as well as decreasing the incidence of some opportunistic infection.
SUMMARY: A great deal of progress has been made in the prevention and treatment
of the infectious disease syndromes caused by cytomegalovirus, with the
development of the concept of the therapeutic prescription. This has two
components: an immunosuppressive component to prevent and treat rejection and an
antimicrobial component to make it safe. Much more information, however, is
required.
-----
Int J STD AIDS. 2004 Jul;15(7):429-33.
Antiviral treatment of genital herpes.
Apoola A, Radcliffe K.
Whittall Street Clinic, Whittall Street, Birmingham B4 6DH, UK.
A review of the randomized, controlled trials in the literature on the treatment
of genital herpes infection with aciclovir, famciclovir and valaciclovir. Common
clinical questions encountered by physicians, such as the effect of antivirals
on symptoms, healing, aborting attacks and subsequent recurrences, are
addressed. There is very little comparative data between the three licensed
drugs but the little data that there is shows no difference in efficacy,
tolerability and toxicity between aciclovir, valaciclovir or famciclovir when
taken orally. Choice of therapy would then depend on convenience of dosing and
cost.
-----
Hautarzt. 2004 Jul;55(7):646-52.
[Eczema herpeticatum]
[Article in German]
Wetzel S, Wollenberg A.
Klinik und Poliklinik fur Dermatologie und Allergologie der Ludwig-Maximilians-Universitat
Munchen, Munchen.
Patients affected by atopic dermatitis tend to develop viral infections.
Probably the most feared complication of atopic dermatitis is eczema herpeticum,
a disseminated infection with herpes simplex virus. A monomorphic eruption of
dome-shaped blisters, pustules and erosions in the eczematous skin lesions along
with severe systemic illness leads to the diagnosis. The clinical diagnosis may
be confirmed by polymerase chain reaction, viral culture, electron microscopy
with negative staining, Tzanck test, immunofluorescence tests or serology. While
intravenous acyclovir is still regarded as standard treatment of eczema
herpeticum, several recently-developed antiviral drugs provide therapeutic
options.
-----
Curr Opin Infect Dis. 2004 Jun;17(3):243-6.
Neonatal herpes simplex virus infection.
Whitley R.
University of Alabama at Birmingham, Birmingham, Alabama 35233, USA. rwhitley@peds.uab.edu
PURPOSE OF REVIEW: In spite of the availability of antiviral therapy for the
treatment of neonatal herpes simplex virus infections, the outcome remains poor,
particularly for babies with disseminated multi-organ infection or central
nervous system disease. This review considers recent advances that impact on
disease management. RECENT FINDINGS: Two areas of investigation have impacted on
our understanding of neonatal herpes simplex virus infection. First, the
transmission of infection from mother to baby has been clarified by extensive
epidemiological investigations of genital herpes in pregnant women at term. Risk
factors for neonatal herpes simplex virus disease include first-episode maternal
infection in the third trimester, invasive monitoring, delivery before 38 weeks,
and maternal age of less than 21 years. Regarding the management of neonatal
herpes simplex virus disease, the utilization of high-dose acyclovir (20 mg/kg
every 8 h) for 21 days significantly reduces mortality for babies with either
encephalitis or disseminated disease. SUMMARY: Recent findings from
epidemiological studies have identified women at risk of delivering a child who
develops neonatal herpes simplex virus infection, and suggest methods to
decrease maternal-fetal transmission. If infection is identified in the pregnant
woman, cesarean delivery decreases the frequency of neonatal disease. With
neonatal disease, acyclovir should be administered promptly at higher dosages
and for longer periods than previously reported.
-----
J Clin Virol. 2004 Jun;30(2):115-33.
Antiviral drugs in current clinical use.
De Clercq E.
Rega Institute for Medical Research, Katholieke Universiteit Leuven,
Minderbroedersstraat 10, B-3000 Leuven, Belgium. erik.declercq@rega.kuleuven.ac.be
The current armamentarium for the chemotherapy of viral infections consists of
37 licensed antiviral drugs. For the treatment of human immunodeficiency virus
(HIV) infections, 19 compounds have been formally approved: (i) the nucleoside
reverse transcriptase inhibitors (NRTIs) zidovudine, didanosine, zalcitabine,
stavudine, lamivudine, abacavir and emtricitabine; (ii) the nucleotide reverse
transcriptase inhibitor (NtRTI) tenofovir disoproxil fumarate; (iii) the
non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine, delavirdine
and efavirenz; (iv) the protease inhibitors saquinavir, ritonavir, indinavir,
nelfinavir, amprenavir, lopinavir (combined with ritonavir at a 4/1 ratio) and
atazanavir; and the viral entry inhibitor enfuvirtide. For the treatment of
chronic hepatitis B virus (HBV) infections, lamivudine as well as adefovir
dipivoxil have been approved. Among the anti-herpesvirus agents, acyclovir,
valaciclovir, penciclovir (when applied topically), famciclovir, idoxuridine and
trifluridine (both applied topically) as well as brivudin are used in the
treatment of herpes simplex virus (HSV) and/or varicella-zoster virus (VZV)
infections; and ganciclovir, valganciclovir, foscarnet, cidofovir and fomivirsen
(the latter upon intravitreal injection) have proven useful in the treatment of
cytomegalovirus (CMV) infections in immunosuppressed patients (i.e. AIDS
patients with CMV retinitis). Following amantadine and rimantadine, the
neuraminidase inhibitors zanamivir and oseltamivir have recently become
available for the therapy (and prophylaxis) of influenza virus infections.
Ribavirin has been used (topically, as aerosol) in the treatment of respiratory
syncytial virus (RSV) infections, and the combination of ribavirin with (pegylated)
interferon-alpha has received increased acceptance for the treatment of
hepatitis C virus (HCV) infections.
-----
J Antimicrob Chemother. 2004 May;53(5):703-7. Epub 2004 Mar 24.
Clinical significance of antiviral therapy for episodic treatment
of herpes labialis: exploratory analyses of the combined data from two
valaciclovir trials.
Spruance SL, Hill J.
Division of Infectious Diseases, RM 4B319, University of Utah School of
Medicine, 50 North Medical Drive, Salt Lake City, UT 84132, USA. woody.spruance@hsc.utah.edu
Valaciclovir (Valtrex) 2 g twice daily for 1 day was recently approved in the
United States for treatment of cold sores. In order to apply more clinically
relevant assumptions to the analysis, we examined the effect of different
missing data and endpoint assumptions on apparent valaciclovir efficacy. Results
of each analysis demonstrate statistically significant increases in the
proportion of subjects whose cold sores were aborted with valaciclovir compared
with placebo, and significant decreases in healing times for subjects with cold
sore lesions who were treated with valaciclovir compared with placebo. These
exploratory analyses provide evidence of the robustness of the results to
differing missing data assumptions and show that use of more clinically relevant
endpoint assumptions increases the magnitude of some therapeutic responses. We
also introduce a new measure that combines the two observed drug effects
(reduced lesion duration, increased aborted lesions) into a single endpoint that
captures the global benefit of the drug to the patient.
-----
Photochem Photobiol Sci. 2004 May;3(5):406-11. Epub 2004 Feb 17.
Photoinactivation of viruses.
Wainwright M.
Centre for Photobiology and Photodynamic Therapy, Department of Colour
Chemistry, University of Leeds, Leeds, UKLS2 9JT.
Although the photodynamic effect was demonstrated against viral targets more
than seventy years ago, the use of photosensitisers as antivirals in vivo has
been slow in gaining acceptance. From a clinical viewpoint, this may be due to
the pronounced side effects produced in several cases of the phototreatment of
herpes genitalis in the early 1970s, the unfortunate patients presenting with
post-treatment Bowen's disease. Currently, the clinical use of photosensitisers
in this field is limited to the treatment of laryngeal papillomata. However,
considerable progress has been made in the photodynamic disinfection of blood
products. Photoantivirals have traditionally been targeted at viral nucleic
acid, in many cases via an intercalative mechanism. However, given the potential
for deleterious sequelae associated with this route, the design of new
photosensitisers should encourage alternative targets, such as viral enzymes or
the cell envelope (where this exists). Targeting is obviously determined by the
chemistry of the photosensitiser employed and there are many different
structural types available. The chemistry, photochemistry and cellular effects
of the various agents are discussed, along with future prospects for this
exciting area of medicine.
-----
J Fr Ophtalmol. 2004 May;27(5):547-57.
[The latest in herpes simplex keratitis therapy]
[Article in French]
Labetoulle M.
Service d'Ophtalmologie, Centre Hospitalier Universitaire de Bicetre, Assistance
Publique-Hopitaux de Paris, Laboratoire de Virologie moleculaire et structurale,
CNRS, Gif sur Yvette. marc.labetoulle@bct.ap-hop-paris.fr
Herpetic keratitis is characterized by spontaneous recurrences and a risk of
vision loss, the latter being more serious when relapses are frequent and
severe. Two clinical forms are commonly distinguished: epithelial keratitis,
usually quickly resolved with topical antivirals, and stromal keratitis, which
has a slower progression, even when both steroids and antivirals are used. Great
strides have been made during the last 20 Years in the therapy of herpes
keratitis, which is now considered and treated as a chronic disease. Randomized
controlled studies definitively showed the decrease in spontaneous herpetic
ocular events in patients treated with long-term oral acyclovir. The
effectiveness of preventive treatment has also been shown during high-risk
periods, especially ocular surgery, in patients with a history of herpes
keratitis. However, the optimal duration and dosage of antiviral prevention have
yet to be defined. We can also hope that in the future novel antiviral
strategies such as vaccination will reduce the place of herpes keratitis as an
indication for corneal graft.
-----
Pediatr Infect Dis J. 2004 May;23(5):451-7; quiz 458-60.
Herpes zoster in otherwise healthy children.
Feder HM Jr, Hoss DM.
Department of Pediatrics, University of Connecticut Health Center, Farmington,
CT, USA.
In normal infants and children, zoster can occur at any time after varicella or
varicella vaccination. It is usually diagnosed clinically: a unilateral
vesicular eruption following a dermatome or dermatomes. The incidence of zoster
increases with age, although children who have had varicella during the first
year of life (or in utero) are at increased risk of developing zoster. The
incidence of zoster is less after varicella vaccination than after natural
infection. Zoster in children is frequently mild, postzoster neuralgia rarely if
ever occurs, and antiviral therapy is usually not needed. In a previously normal
child with zoster, if the history and physical examination are normal, a
laboratory search for occult immunodeficiency or malignancy is not needed. We
present five cases of zoster in healthy children and review zoster in the
pediatric age group.
-----
J Microbiol Immunol Infect. 2004 Apr;37(2):75-81.
Double-blind, randomized, acyclovir-controlled, parallel-group
trial comparing the safety and efficacy of famciclovir and acyclovir in patients
with uncomplicated herpes zoster.
Shen MC, Lin HH, Lee SS, Chen YS, Chiang PC, Liu YC.
Section of Infectious Diseases, Department of Medicine, Kaohsiung Veterans
General Hospital, 386 Ta-chung 1st Road, Kaohsiung, Taiwan 813, ROC.
This randomized, double-blind, parallel-group study compared the efficacy and
safety of famciclovir administered at 250 mg thrice daily with acyclovir 800 mg
5 times daily for the treatment of acute uncomplicated herpes zoster in
immunocompetent adults. A total of 55 patients participated in this trial.
Twenty seven patients (49.1%) were randomized into the famciclovir plus placebo
treatment group and 28 (50.9%) into the acyclovir plus placebo group. Six of the
55 patients did not complete the study. Two of these patients were in the
famciclovir plus placebo group and dropped out due to deviation from the study
protocol. Four patients in the acyclovir plus placebo group did not complete the
study protocol due to adverse events (n = 2), deviation from the protocol (n =
1), or loss to follow-up (n = 1). Treatment was initiated within 72 h of onset
of the zoster rash and was continued for 7 days. When treatment was initiated
within 72 h, famciclovir was as effective as acyclovir for healing the cutaneous
lesion, as indicated by the time to full crusting, loss of acute phase pain,
loss of vesicles, and loss of crusts. Famciclovir was well tolerated and had a
more favorable adverse event profile compared to acyclovir. Constipation,
hematuria, and glycosuria were the most commonly reported adverse events, but
only constipation was considered to have a possible relationship to the
treatment. In conclusion, famciclovir, administered less frequently and at lower
unit doses than acyclovir, is an effective treatment for uncomplicated herpes
zoster.
-----
Ann Dermatol Venereol. 2004 Mar;131(3):255-61.
[Lithium]
[Article in French]
Sparsa A, Bonnetblanc JM.
Service de Dermatologie, CHRU Dupuytren, 2, avenue Martin Luther King, 87042
Limoges Cedex.
The mode of action of the cation lithium is not well known. It is at present
used as a topical drug in dermatology. Lithium inhibits many enzymes: Na/K
ATPase, adenylcyclase, enzymes of the prostaglandines E1 synthesis,
inositol-1-phosphatase. It is active on neutrophils et T lymphocytes, explaining
in part its anti-inflammatory activity. It has a dose-dependent action on
levures. It has possibly a direct inhibitory activity on DNA synthesis of herpes
viruses. Lithium has a good local safety. Percutaneous penetration is weak and
plasma concentrations are very much lower than that observed after oral intake.
Lithium has been studied in seborrhoeic dermatitis. Its efficacy was primarily
observed in psychotic patients. An assay with oral lithium did not confirmed the
first observations. Topical lithium was found more efficient. Topical lithium
succinate associated with zinc sulfate and lithium gluconate had a greater
efficacy than placebo. Comparison with topical ketoconazole showed a non
inferiority of lithium gluconate. Oral lithium also showed a reduction of
symptoms' duration of herpes simplex. Cutaneous side-effects of oral lithium are
frequent and numerous. Some of them may be explained by a lithium
pharmacological cell activity (such as psoriasis). Teratogenicity is observed in
mice and rats. Drug interactions are not expected after topical application.
Irritants side effects are mainly observed after topical application; they are
moderate and transitory. Lithium gluconate treatment of seborrhoeic dermatitis
is a bid application during at least 8 weeks. It may be used in renal
insufficiency. It is not recommended in the first trimester of pregnancy.
-----
Ann Pharmacother. 2004 Apr;38(4):705-9. Epub 2004 Feb 13.
Oral antivirals for the acute treatment of recurrent
herpes labialis.
Jensen LA, Hoehns JD, Squires CL.
College of Pharmacy, University of Iowa, Iowa City, IA.
OBJECTIVE: To evaluate the use and benefit of oral antivirals
in the acute treatment of episodic, recurrent herpes labialis.
DATA SOURCES: A literature search was performed in MEDLINE (1966-August
2003) using acyclovir, famciclovir, valacyclovir, cold sores,
herpes labialis, and HSV-1 as search terms. DATA SYNTHESIS: We
reviewed 5 placebo-controlled and 2 comparative studies evaluating
oral antivirals for acute treatment of recurrent herpes labialis.
No studies directly compared different antivirals. Studies discussing
the efficacy of antivirals for chronic suppression of herpes simplex
virus-1 infection were not included. CONCLUSIONS: Treatment with
oral antivirals decreases the duration of lesion episodes and
pain by approximately one day; however, the antivirals do not
abort lesions from developing. Clinical implications of these
results appear relatively modest.
-----
J Am Dent Assoc. 2004 Jan;135(1):48-54.
Treatment modalities and medication recommended
by health care professionals for treating
recurrent herpes labialis.
Raborn GW, Chan KS, Grace M.
Department of Dentistry, Faculty of Medicine and Dentistry, University
of Alberta, Edmonton, Canada. wayne.raborn@ualberta.ca
BACKGROUND: The authors conducted a survey to determine how
health care professionals respond to patients' inquiries about
cold sores, also known as recurrent herpes labialis, and their
choices of treatment modalities and medications. METHODS: The
authors mailed a one-page, pretested survey to a random sample
of dentists, pharmacists and family physicians in Alberta, Canada.
After receiving ethics approval from the University of Alberta,
Edmonton, the authors mailed 998 surveys. The response rate was
51 percent. RESULTS: Topical antiviral medication was the most
common treatment recommended (63 percent). Over-the-counter medication
was the first choice for pharmacists (83 percent) as compared
with dentists (15 percent) and physicians (16 percent). Emotional
stress (60 percent) was reported by patients to be the most common
trigger, and pain or discomfort (81 percent) was their primary
concern. Acyclovir ointment was the most common antiviral drug
recommended or prescribed by health care professionals (60 percent),
and cost was the major reason they gave for not recommending or
prescribing antiviral drugs (73 percent). CONCLUSIONS: The authors
found variation in treatment modalities and recommendations by
each health profession, despite the fact that patients reported
similar triggers and concerns. This may be due to individual patient
need and the health care professional's lack of knowledge. PRACTICE
IMPLICATIONS: Survey results may serve as a reference for health
care professionals to use to determine how their choices of medications
and treatment modalities compare with those of other practitioners.
Professionals should know the benefits and limitations of all
therapies, discuss them with the patients and select a treatment.
-----
Med Sci Monit. 2003 Jul;9(7):PI93-8.
Role of acyclovir gel in herpes simplex: clinical
implications.
Seth AK, Misra A, Umrigar D, Vora N.
Pharmacy Department, Faculty of Engineering & Technology,
M.S. University, Vadodara, India.
BACKGROUND: Acyclovir (ACY) is effective in the treatment of
herpes simplex (HSV-1) & (HSV-2) but has systemic toxic effects
if given orally or intravenously. ACY has not been used to treat
the disease topically due to poor drug penetration into skin.
A novel 1% liposomal ACY topical gel in a 5% Hydroxypropylmethyl
cellulose (HPMC) K4M gel base has been developed and clinically
evaluated in HSV-1 and HSV-2 patients. MATERIAL/METHODS: 26 patients
suffering from recurrent mild facial (HSV-1) and genital (HSV-2)
infections (HSV-1: 4F, 6M, age 21-34 years; HSV-2: 16M, age 24-40
years) were subjected to double blind clinical evaluation. Plain
ACY gel (PAG) and Liposomal ACY gel (LAG) were clinically evaluated
by application five times daily on herpetic lesions for up to
eight weeks. RESULTS: A significant increase in the average percent
improvement of lesion healing was observed in HSV-1 and HSV-2
patients after 2-3 weeks treatment with LAG, as well as a significant
decrease in side effects associate with ACY, such as itching and
burning in both HSV-1 and HSV-2, and burning micturation in HSV-2.
CONCLUSIONS: The results demonstrate that a five-fold reduction
in the ACY content in liposomal gel is sufficient for the complete
healing of herpetic lesions in HSV-1 and HSV-2 infection. The
increased duration of topical therapy may be acceptable for patients
suffering from mild herpetic lesions because of the advantage
of avoiding systemic and local side effects.
-----
Cochrane Database Syst Rev. 2003;(3):CD002898.
Interventions for herpes simplex virus epithelial
keratitis.
Wilhelmus KR.
Department of Ophthalmology, Cullen Eye Institute, Baylor College
of Medicine, 6565 Fannin Street, NC-205, Suite NC-304, Houston,
TX 77030, USA.
BACKGROUND: Many clinical trials have been performed on the
acute treatment of dendritic epithelial keratitis. Surveys of
ocular antiviral pharmacology and of herpes simplex virus eye
disease have evaluated different interventions, but a systematic
review of all comparative clinical studies has not previously
been undertaken. OBJECTIVES: The objective of this review is to
compare the effects of various treatments for dendritic or geographic
herpes simplex virus epithelial keratitis. SEARCH STRATEGY: Sources
searched for relevant studies were the Cochrane Central Register
of Controlled Trials - CENTRAL (which contains the Cochrane Eyes
and Vision Group trials register), (Issue 3 2002), MEDLINE (1966
to August 2002), EMBASE (1980 to August 2002), LILACS (up to 2002),
Index Medicus (1960 to 1965), Excerpta Medica Ophthalmology (1960
to 1973), reference lists of primary reports and review articles,
and conference proceedings pertaining to ocular virology. SELECTION
CRITERIA: This review includes comparative clinical trials that
assessed one-week and/or two-week healing rates of topical ophthalmic
or oral antiviral agents and/or physical or chemical debridement
in people with active epithelial keratitis. DATA COLLECTION AND
ANALYSIS: The reviewer extracted data and assessed trial quality.
Interventions were compared by the proportions of participants
healed at seven days and at fourteen days after trial enrollment.
MAIN RESULTS: This review includes data from 97 trials that randomised
a total of 5102 participants. Compared to idoxuridine, the topical
application of vidarabine, trifluridine, or acyclovir generally
resulted in a significantly greater proportion of participants
healing within one week of treatment. Among these three antiviral
agents, no treatment emerged as significantly better for the therapy
of dendritic epithelial keratitis. Insufficient placebo-controlled
studies were available to assess debridement and other physical
or physicochemical methods of treatment. Interferon monotherapy
had a slight beneficial effect on dendritic epithelial keratitis,
but not better than other antiviral agents, although interferon
was very useful combined with debridement or with another antiviral
agent such as trifluridine. REVIEWER'S CONCLUSIONS: Currently
available antiviral agents are effective and nearly equivalent.
The combination of a nucleoside antiviral with either debridement
or with interferon seems to speed healing. Future trials of the
acute treatment of herpes simplex virus epithelial keratitis must
aim to achieve adequate statistical power for assessing the primary
outcome of epithelial healing and should consider the effect of
lesion size and other characteristics on treatment response.
-----
Drugs Today (Barc). 2003 May;39(5):359-71.
Brivudine: a herpes virostatic with rapid antiviral
activity and once-daily dosing.
Rabasseda X.
Department of Medical Information, Prous Science, S.A., PO Box
540, 08025 Barcelona, Spain. service@prous.com
Brivudine is an analog of thymidine, and is incorporated into
the viral DNA. It blocks the action of DNA polymerases, thus inhibiting
viral replication. It has a stronger antiviral effect against
the varicella-zoster virus compared with reference compounds such
as aciclovir or penciclovir. The efficacy of brivudine has been
documented in a number of clinical trials in patients with herpesvirus-related
infections, particularly in patients with herpes-zoster. At a
dose of 125 mg once daily, brivudine has proved to be superior
to aciclovir with respect to reducing the period of new blister
production in patients with herpes-zoster, and has shortened the
duration of post-herpetic neuralgia. Tolerability was equivalent
to that of aciclovir or placebo, with occasional gastrointestinal
disorders leading to treatment withdrawal in a minority of patients.
(c) 2003 Prous Science. All rights reserved.
-----
Antiviral Res. 2003 Jun;59(1):57-60.
Oral brivudin in comparison with acyclovir for
herpes zoster: a survey study on postherpetic neuralgia.
Wassilew SW, Wutzler P.
Dermatological Department, Klinikum Krefeld, Lutherplatz 40, D-47805,
Krefeld, Germany
This concerns a double-blind survey study on 608 herpes zoster
patients treated with 1x 125mg oral brivudin (n=309) or 5x 800mg
acyclovir (n=299), both for 7 days, during two prospective, randomised
clinical herpes zoster trials. The survey aimed at evaluating
the outcome of the two treatment regimens on postherpetic neuralgia
(PHN). During a follow-up ranging from 8 to 17 months after start
of treatment, former study participants aged >/=50 years were
interviewed for the occurrence of PHN. Neither the investigators
nor the patients were aware of which treatment the patients received
during acute herpes zoster. The incidence of PHN, defined as zoster-associated
pain occurring or persisting after rash healing was significantly
lower in brivudin recipients (32.7%) than in acyclovir recipients
(43.5%, P=0.006). Mean duration of PHN was similar with brivudin
(173 days) and acyclovir (164 days, P=0.270). Despite some methodological
disadvantages common to this type of study, the present survey
provides for the first evidence that brivudin treatment during
acute herpes zoster favourably affects the incidence of PHN in
immunocompetent elderly herpes zoster patients.
-----
Cesk Slov Oftalmol. 2003 Mar;59(2):105-12.
[Phototherapeutic keratectomy in the treatment
of superficial corneal diseases]
[Article in Czech]
Horackova M, Hruba H, Vlkova E, Mica Z.
Oftalmologicka klinika LF MU, Brno-Bohunice.
In the retrospective study the authors evaluate clinical results
of phototherapeutic keratectomy (PTK) that is one of the alternative
methods used in treatment of some of the superficial corneal diseases.
The authors present the group of 89 eyes of 63 patients with diagnose:
dry spot corneae in 69 eyes (77.5%), recurrent corneal erosion
in 13 eyes (14.5%), corneal dystrophy in 2 eyes (1.8%), recurrent
herpes simplex keratitis in 3 eyes (2.7%), recurrent pterygium
in 2 eyes (1.8%), atopic keratoconjunctivitis with mucous plaque
in 1 eye (0.9%). The average age was 45.2 years (14-84 years)
and average follow-up period was 29 months (3-52 months). The
operation was done with the use of device Keracor 117 (ArF excimer
laser) in topical anaesthesia, with the average zone of ablation
4.1 mm and average depth of ablation 24 mu in one go. In ten cases
was the operation carried out repeatedly. We evaluated the postoperative
complications, postoperative changes of refraction and final the
best corrected visual acuity. For low percentage of postoperative
complications, decrease or disappearance of subjective difficulties
and improvement of visual acuity with minimal stress for the patient
we can recommend PTK as save and efficient method in treatment
of corneal diseases mentioned above.
-----
Vestn Ross Akad Med Nauk. 2003;(5):23-8.
[The state-of-the art and prospects for the pharmacological
therapy of infectious and allergic eye diseases]
[Article in Russian]
Maichuk IuF.
The inflammatory, infectious and allergic diseases of the eye
still remain an acute problem in practical ophthalmology due to
their high prevalence, relapsing clinical course, a growing frequency
rate of mycotic and acanthoamebic keratitis and a growing number
of resistant causative agents of bacterial keratitis. 55.3% of
corneal pathologies are related with the herpes simplex virus,
37.3%--with secondary bacterial infection, 33.2%--with primary
bacterial infection, 6.7%--with mycotic infection and 5.6%--with
acathoamebic infection. Algorithms of pharmacological therapy
are suggested for a majority of inflammatory lesions of the eye,
i.e. for herpetic keratitis, ulcerous keratitis caused by blue
pus bacillus, gonococcus, staphylococcus, fungi, acanthomebas,
as well as for adenoviral and Chlamidia conjunctivitis and allergy
of the eye. The author points out that the treatment must be complex,
including specific therapy--antiviral one (zovirax ointment, interferon
locally, and zovirax or valtrex perorally), antibacterial one
(okacin, tobrex, vitabact, fucithamic locally, quinine antibiotics
perorally, aminoglycosides or cephalosporins subconjunctivally
or intramuscularly) and antimycotic one (locally and perorally).
Another part of the complex therapy is equally important--pathogenetic
one (carnosine, taufon, vitacic, corneregel ointment), antiallergic
one (spersallerg, allergophtal, alomide, lecrolin), antinflammatory
one (naclof, maxidex, cyclolip) tears replacing one (natural tears,
ophthagel) and immunomodeling one (affinoleicin, lycopid, tactivin).
-----
Int J Antimicrob Agents. 2003 Jun;21(6):510-20.
Local treatment of viral disease using photodynamic
therapy.
Wainwright M.
Department of Colour Chemistry, Centre for Photobiology and Photodynamic
Therapy, The University, LS2 9JT, Leeds, UK. ccdmw@leeds.ac.uk
Although reports of the photodynamic inactivation of viruses
appeared in 1928, long before chemotherapeutic antiviral drugs,
the first clinical trial in humans-the topical treatment of herpes
genitalis-did not take place until the early 1970s. Trials were
discontinued due to the transformation of healthy cells and concomitant
incidence of Bowen's disease in some patients, probably due to
the migration of infective sections of photodamaged viral nucleic
acid. With the modern development of photodynamic therapy as a
cancer treatment and the use of photosensitisers in the photodecontamination
of blood products, a great deal of experience has been gained,
both in the minimisation of side effects in humans and in the
targeting and eradication of viruses. This suggests that the photodynamic
approach to a range of virus-associated infections, lesions and
cancer might now be revisited with greater success.
-----
Prog Drug Res. 2003;60:263-307.
Current and potential therapies for the treatment
of herpes-virus infections.
Villarreal EC.
Eli Lilly and Company, Lilly Centre for Women's Health, Indianapolis,
IN 46285, USA. villarreal_elcira_c@lilly.com
Human herpesviruses are found worldwide and are among the most
frequent causes of viral infections in immunocompetent as well
as in immunocompromised patients. During the past decade and a
half a better understanding of the replication and disease-causing
state of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2),
varicella zoster virus (VZV), and human cytomegalovirus (HCMV)
has been achieved due in part to the development of potent antiviral
compounds that target these viruses. While some of these antiviral
therapies are considered safe and efficacious (acyclovir, penciclovir),
some have toxicities associated with them (ganciclovir and foscarnet).
In addition, the increased and prolonged use of these compounds
in the clinical setting, especially for the treatment of immunocompromised
patients, has led to the emergence of viral resistance against
most of these drugs. While resistance is not a serious issue for
immunocompetent individuals, it is a real concern for immunocompromised
patients, especially those with AIDS and the ones that have undergone
organ transplantation. All the currently approved treatments target
the viral DNA polymerase. It is clear that new drugs that are
more efficacious than the present ones, are not toxic, and target
a different viral function would be of great use especially for
immunocompromised patients. Here, an overview is provided of the
diseases caused by the herpesviruses as well as the replication
strategy of the better studied members of this family for which
treatments are available. We also discuss the various drugs that
have been approved for the treatment of some herpesviruses in
terms of structure, mechanism of action, and development of resistance.
Finally, we present a discussion of viral targets other than the
DNA polymerase, for which new antiviral compounds are being considered.
-----
Dermatol Clin. 2003 Apr;21(2):311-20.
Management of acyclovir-resistant herpes simplex
virus.
Chilukuri S, Rosen T.
Department of Dermatology, Baylor College of Medicine, One Baylor
Plaza, Houston, Texas 77030, USA.
In immunocompetent patients, HSV is controlled rapidly by the
human host's immune system, and recurrent lesions are small and
short lived. When treated with antiviral agents, these patients
rarely develop resistance to these drugs. In contrast immunocompromised
patients might not be able to control HSV infection. Thus, frequent
and severe reactivations are often seen and might lead to fatal
herpetic encephalitis or disseminated HSV infection. Treatment
in these patients is limited because immunocompromised hosts often
develop severe herpes disease refractory to antiviral drug therapy.
It is therefore imperative that physicians develop regimens to
deal with both receptive and refractory HSV disease. The following
treatment protocol (modified from Balfour and colleagues) might
serve as a guide until further investigation of new drugs is performed.
In all patients standard oral ACV therapy should be initiated
at a dose of 200 mg orally, five times a day for the first 3 to
5 days. Prior to treatment, cultures the lesions should be obtained
to verify HSV etiology. If the response is poor, the dose of oral
ACV should be increased to 800 mg five times a day. If no response
seen after 5 to 7 days, it is unlikely that the lesion will respond
to intravenous ACV (or chemically and structurally related drugs
such as VCV or famciclovir), so an alternative regimen must be
assigned. First, repeat cultures for vital, fungal, and bacterial
pathogens must be performed. In addition, ACV susceptibility studies
should be ordered, if available. If the mucocutaneous lesion is
accessible for topical treatment, TFT (as ophthalmic solution)
should be applied to the area three to four times a day until
the lesion is completely healed. If the lesion is inaccessible
or if the response to TFT is poor, therapy with intravenous foscarnet
should be given for 10 days or until complete resolution of the
lesions. The dosage of foscarnet should be 40 milligrams per kilogram
three times per day or 60 milligrams per kilogram twice daily.
If foscarnet fails to achieve clinical clearing, consideration
should be given to use of intravenous cidofovir (or application
of compounded 1% to 3% topical cidofovir ointment). Vidarabine
is reserved for situations in which all of these therapies fail.
If lesions reoccur in the same location following clearing, the
patient should started on high-dose oral ACV (800 mg, five times
daily) or intravenous foscarnet (40 mg/kg tid or 60 mg/kg bid)
as soon as possible. When lesions occur in a different location,
the patient should be treated initially with standard doses of
oral ACV (200 mg, five times daily) and the above protocol should
be followed should there be clinical failure. In the future, new
treatment options for patients with documented HSV resistance
will be important in reducing the clinical impact of HSV.
-----
Curr Opin Investig Drugs. 2003 Feb;4(2):214-8.
Resiquimod 3M.
Jones T.
ID Biomedical Corp of Quebec, 7150 Frederick Banting, Suite 200,
Ville St-Laurent, Quebec H4S 2A1, Canada. tjones@intellivax.com
3M Pharmaceuticals is developing a topical formulation of resiquimod
as an immunomodulator for the potential treatment of herpes simplex
virus (HSV) infections. As of September 2001, resiquimod was to
be commercialized worldwide in association with Eli Lilly. Phase
III trials for the treatment of HSV infection were initiated in
November 2000 and were ongoing in September 2001. In October 2001,
US and European filings were scheduled for 2004, and by February
2002, Lilly was anticipating launch in either 2004 or 2005. The
compound has also been investigated for the potential treatment
of various other diseases, including other viral infections and
eczema and as a vaccine adjuvant.
-----
Cutis. 2003 Mar;71(3):239-42.
Valacyclovir for prevention of recurrent herpes
labialis: 2 double-blind, placebo-controlled studies.
Baker D, Eisen D.
Division of Infectious Diseases, Department of Obstetrics/Gynecology,
State University of New York at Stony Brook School of Medicine,
11794-8091, USA. david.baker@stonybrook.edu
The oral antiviral valacyclovir, which is 3 to 5 times more
bioavailable than its parent compound acyclovir, is a good candidate
for effective therapy to suppress recurrent herpes labialis lesions.
The efficacy of oral valacyclovir in the suppression of herpes
labialis has not previously been reported. Two identical, randomized,
double-blind, parallel-group studies were conducted to evaluate
the efficacy of oral valacyclovir 500 mg (n=49) versus placebo
(n=49) once daily for 16 weeks in the suppression of herpes labialis
among patients with a history of 4 or more recurrent lesions in
the previous year. Data from the studies were pooled for analysis.
Twenty-eight patients (60%) in the valacyclovir group compared
with only 18 patients (38%) in the placebo group were recurrence-free
throughout the 4-month treatment period (P=.041). The mean time
to first recurrence was significantly longer with valacyclovir
(13.1 weeks) compared with placebo (9.6 weeks) (P=.016). The total
number of recurrences in patients using valacyclovir was 24 compared
with 41 in patients using placebo. The incidence of adverse events
during the 4-month treatment period was slightly lower in the
valacyclovir group (22 events, 33% of patients) compared with
the placebo group (29 events, 39% of patients). The results of
these small double-blind, placebo-controlled studies suggest that
oral valacyclovir 500 mg once daily for 4 months is effective
and well tolerated for the prevention of recurrent herpes labialis.
More research with larger patient numbers is warranted to corroborate
and extend these findings.
-----
Sex Transm Dis. 2003 Mar;30(3):226-31.
Patients' preference of valacyclovir once-daily
suppressive therapy versus twice-daily episodic therapy for recurrent
genital herpes: a randomized study.
Romanowski B, Marina RB, Roberts JN; Valtrex HS230017 Study
Group.
University of Alberta, Edmonton, Alberta, Canada. broman@docromanowski.com
BACKGROUND: Valacyclovir is effective for suppressive and episodic
treatment of recurrent genital herpes. Few data on patients' treatment
strategy preferences are available. GOAL: The goal was to assess
patients' preference, satisfaction, and quality of life with suppressive
versus episodic treatment of recurrent genital herpes. STUDY DESIGN:
This was a multicenter, open-label, randomized, two-arm, crossover
48-week study involving 225 patients with genital herpes. RESULTS:
Suppressive valacyclovir therapy was preferred to episodic valacyclovir
treatment by 72% of patients (P < 0.001). Overall treatment
satisfaction and quality of life were significantly greater during
suppressive therapy (P < 0.001 and P = 0.002, respectively).
The risk of recurrence during the first 24 weeks was reduced by
78% with suppressive therapy (P < 0.001). Significantly fewer
patients experienced recurrences during suppressive treatment
than with episodic treatment (P < 0.001). Valacyclovir was
well tolerated. CONCLUSIONS: Suppressive valacyclovir was preferred
to episodic therapy by most patients. Suppressive therapy was
associated with increased treatment satisfaction, and decreased
risk and lower frequency of recurrences.
-----
Am Fam Physician. 2003 Feb 15;67(4):757-62, 675.
Antiviral drugs in the immunocompetent host: part
I. Treatment of hepatitis, cytomegalovirus,
and herpes infections.
Colgan R, Michocki R, Greisman L, Moore TA.
Department of Family Medicine, University of Maryland School of
Medicine, Baltimore, Maryland 21201, USA. rcolgan@som.umaryland.edu
Since the release of amantadine in 1966, other agents designed
to fight a diverse range of viral infections have been released.
Part I of this two-part article focuses on agents used to manage
hepatitis, cytomegalovirus, and herpes infections. In patients
with chronic hepatitis B, interferon alfa-2b or lamivudine is
the treatment of choice. Pegylated interferon alfa-2a or -2b,
along with ribavirin, is standard treatment for patients with
chronic hepatitis C. Although treatment of cytomegalovirus infections
generally is supportive, there have been reports of severely ill
patients who improved after receiving ganciclovir or foscarnet.
Oral antiviral agents for initial and recurrent herpes simplex
virus infections have been shown to shorten the duration of lesions.
Treatment of herpes zoster infections with antiviral drugs shortens
the course of infection and decreases symptoms. Studies have shown
that antiviral treatment can prevent prolonged post-herpetic neuralgia,
although this use remains controversial.
-----
Antimicrob Agents Chemother. 2003 Mar;47(3):1072-80.
High-dose, short-duration, early valacyclovir
therapy for episodic treatment of cold sores: results of two randomized,
placebo-controlled, multicenter studies.
Spruance SL, Jones TM, Blatter MM, Vargas-Cortes M, Barber
J, Hill J, Goldstein D, Schultz M.
University of Utah, Division of Infectious Diseases, School of
Medicine, Salt Lake City 84132, USA. woody.spruance@hsc.utah.edu
Oral valacyclovir is better absorbed than oral acyclovir, increasing
acyclovir bioavailability three- to fivefold. This provides the
opportunity to explore whether high systemic acyclovir concentrations
are effective in the treatment of cold sores (herpes labialis).
Two randomized, double-blind, placebo-controlled studies were
conducted. Subjects were provided with 2 g of valacyclovir twice
daily for 1 day (1-day treatment), 2 g of valacyclovir twice daily
for 1 day and then 1 g of valacyclovir twice daily for 1 day (2-day
treatment), or a matching placebo and instructed to initiate treatment
upon the first symptoms of a cold sore. In study 1, the median
duration of the episode (primary endpoint) was reduced by 1.0
day (P = 0.001) with 1-day treatment and 0.5 days (P = 0.009)
with 2-day treatment compared to placebo. Similarly, the mean
duration of the episode was statistically significantly reduced
by 1.1 days with 1-day treatment and 0.7 days with 2-day treatment
compared to placebo. The proportion of subjects in whom cold sore
lesion development was prevented and/or blocked was increased
by 6.4% (P = 0.096) with 1-day treatment and 8.5% (P = 0.061)
with 2-day treatment compared to placebo. The time to lesion healing
and time to cessation of pain and/or discomfort were statistically
significantly reduced with valacyclovir compared to placebo. In
study 2, results similar to those in study 1 were obtained. AEs
were similar across treatment groups. These studies provide evidence
supporting a simple, 1-day valacyclovir treatment regimen for
cold sores that is safe and effective. The 1-day valacyclovir
regimen offers patients a unique and convenient dosing alternative
compared to available topical therapies.
-----
Ann Biol Clin (Paris). 2003 Jan-Feb;61(1):33-40.
[Contribution of the laboratory in case of resistance
to acyclovir of herpes simplex and
varicella zoster virus]
[Article in French]
Morfin F, Frobert E, Thouvenot D.
Laboratoire de virologie des Hospices civils de Lyon, Domaine
Rockefeller, 8 avenue Rockefeller, 69373 Lyon cedex 08. fmorfin@rockefeller.univ-lyon1.fr
Herpes simplex virus (HSV) and varicella zoster virus (VZV)
are susceptible to acyclovir which inhibits viral replication
through two viral enzymes, thymidine kinase (TK) and DNA polymerase.
Resistance may occur, it is a rare phenomenon among immunocompetent
patients but resistance is more frequent and may be associated
with serious complications among immunocompromised patients. Virological
survey of these at risk patients is needed to detect resistant
virus as soon as possible through phenotypic tests performed on
virus isolated on cell cultures. Resistant virus may also be genetically
characterised by detection of mutations within TK and DNA polymerase
genes. Pharmacological parameters also have to be taken into consideration
and a determination of acyclovir blood concentration should be
performed in case of unexplained therapeutic failure. Improvement
of immune system, when possible, may resolve these infections.
Alternative treatments using drugs such as foscarnet or cidofovir
which have a different mechanism of action compared to acyclovir,
are recommended but these molecules are often more toxic than
acyclovir.
-----
J Clin Virol. 2003 Jan;26(1):29-37.
Herpes simplex virus resistance to antiviral drugs.
Morfin F, Thouvenot D.
Laboratory of Virology of the Hospices Civils de Lyon, Domaine
Rockefeller, 8 avenue Rockefeller, 69373 Cedex 08, Lyon, France.
fmorfin@rockefeller.univ-lyon1.fr
Herpes simplex virus (HSV) infections are efficiently treated
with antiviral drugs such as acyclovir (ACV). However, resistance
has been reported, mainly among immunocompromised patients (prevalence
around 5%) and particularly allogeneic bone marrow transplant
patients (prevalence reaching 30%). Resistance to ACV is associated
with mutations on one of the two viral enzymes involved in the
ACV mechanism of action: thymidine kinase (TK) and DNA polymerase.
In 95% of the cases, ACV resistance is associated with a mutation
in the TK gene as this enzyme is not essential for viral replication,
unlike viral DNA polymerase, which is rarely involved in resistance.
Strains resistant to ACV are almost always cross-resistant to
other TK-dependent drugs such as penciclovir and famciclovir.
Resistant infections can be managed by foscarnet or cidofovir
but both are more toxic than ACV. These drugs also inhibit viral
DNA polymerase but they are active on most ACV-resistant HSV as
they do not depend on TK; nevertheless virus resistant to ACV
because of a mutation in the DNA polymerase may be cross-resistant
to these molecules. Published data on genetic characterization
of resistant clinical isolates point out hot spots in viral TK
and DNA polymerase genes. TK mutations associated with resistance
are either insertion or deletion (codons 92 and 146 of TK gene)
or substitution (codon 176-177, 336 of TK gene). DNA polymerase
mutations are mainly located in conserved sites of the enzyme.
A high level of gene polymorphism has also been reported for these
genes, especially for TK. These results are useful for the development
of rapid genotypic assays for the detection of mutations associated
with resistance.
-----
Expert Opin Investig Drugs. 2003 Feb;12(2):165-83.
Novel agents and strategies to treat herpes simplex
virus infections.
Kleymann G.
Gerald.Kleymann@freenet.de
The quiet pandemic of herpes simplex virus (HSV) infection
has plagued humanity since ancient times, causing mucocutaneous
infection, such as herpes labialis and herpes genitalis. Disease
symptoms often interfere with everyday activities and occasionally
HSV infections are the cause of life-threatening or sight-impairing
disease, especially in neonates and the immunocompromised patient
population. After primary or initial infection the virus persists
for life in a latent form in neurons of the host, periodically
reactivating and often resulting in significant psychosocial distress
for the patient. Currently, no cure is available. In the mid-1950s
the first antiviral, idoxuridine, was developed for topical treatment
of herpes disease and, in 1978, vidarabine was licensed for systemic
use to treat HSV encephalitis. Acyclovir (Zovirax), a potent,
specific and tolerable nucleosidic inhibitor of the herpes DNA
polymerase, was a milestone in the development of antiviral drugs
in the late 1970s. In the mid-1990s, when acyclovir became a generic
drug, valacyclovir (Valtrex) and famciclovir (Famvir), prodrugs
of the gold standard and penciclovir (Denavir), Vectavir), a close
analogue, were launched. Though numerous approaches and strategies
were tested and considerable effort was expended in the search
of the next generation of an antiherpetic therapy, it proved difficult
to outperform acyclovir. Notable in this regard was the award
of a Nobel Prize in 1988 for the elucidation of mechanistic principles
which resulted in the development of new drugs such as acyclovir.
Vaccines, interleukins, interferons, therapeutic proteins, antibodies,
immunomodulators and small-molecule drugs with specific or nonspecific
modes of action lacked either efficacy or the required safety
profile to replace the nucleosidic drugs acyclovir, valacyclovir,
penciclovir and famciclovir as the first choice of treatment.
Recently though, new inhibitors of the HSV helicase-primase with
potent in vitro antiherpes activity, novel mechanisms of action,
low resistance rates and superior efficacy against HSV in animal
models have been discovered. This review summarises the current
therapeutic options, discusses the potential of preclinical or
investigational drugs and provides an up-to-date interpretation
of the challenge to establish novel treatments for herpes simplex
disease.
-----
Br J Dermatol. 2003 Jan;148(1):142-6.
Valaciclovir as a single dose during prodrome
of herpes facialis: a pilot randomized double-blind
clinical trial.
Chosidow O, Drouault Y, Garraffo R, Veyssier P; Valaciclovir
Herpes Facialis Study Group.
Department of Internal Medicine, Assistance Publique-Hopitaux
de Paris, Groupe Hospitalier Pitie-Salpetriere, Universite Paris
VI, 47-83 boulevard de l'Hopital, France. olivier.chosidow@psl.ap-hop-paris.fr
BACKGROUND: Randomized clinical trials of valaciclovir in recurrent
herpes labialis are lacking. OBJECTIVES: To determine whether
a single course of valaciclovir, i.e. 500, 1000 or 2000 mg, administered
during the prodrome of herpes facialis, could be beneficial. METHODS:
Three hundred and forty-five out-patients with herpes labialis
were screened and randomized for a multicentre, double-blind clinical
trial. Ninety-six patients had no recurrence after 6 months of
follow-up; 249 patients were finally included in the intent-to-treat
(ITT) population. The main outcome measure was the rate of aborted
episodes at day 3. The three treatment groups were similar at
baseline. RESULTS: There was no statistically significant difference
between the groups in rates of aborted lesions at day 3 in the
ITT population, in particular between the 500 mg and 2000 mg treatment
groups. CONCLUSIONS: Although a placebo group was not included
in this pilot study, a single dose of valaciclovir was not considered
beneficial in patients with recurrent herpes facialis.
-----
Clin Microbiol Rev. 2003 Jan;16(1):96-113.
Recent progress in herpes simplex virus immunobiology
and vaccine research.
Koelle DM, Corey L.
Department of Medicine, University of Washington, Seattle, Washington
98195, USA. viralimm@u.washington.edu
Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) cause
prevalent, chronic infections that have serious outcomes in some
individuals. Neonatal herpes may occur when the infant traverses
the cervix during maternal genital herpes. Genital herpes is a
major risk factor for human immunodeficiency virus type 1 transmission.
Considerable efforts have been made to design and test vaccines
for HSV, focusing on genital infection with HSV-2. Several protein
subunit vaccines based on HSV-2 envelope glycoproteins have reached
advanced-phase clinical trials. These antigens were chosen because
they are the targets of neutralizing-antibody responses and because
they elicit cellular immunity. Encouraging results have been reported
in studies of treatment of HSV-seronegative women with a vaccine
consisting of truncated glycoprotein D of HSV-2 and a novel adjuvant.
Because most sexual HSV transmission occurs during asymptomatic
shedding, it is important to evaluate the impact of vaccination
on HSV-2 infection, clinically apparent genital herpes, and HSV
shedding among vaccine recipients who acquire infection. There
are several other attractive formats, including subunit vaccines
that target cellular immune responses, live attenuated virus strains,
and mutant strains that undergo incomplete lytic replication.
HSV vaccines have also been evaluated for the immunotherapy of
established HSV infection.
-----
Compend Contin Educ Dent. 2002 Jul;23(7 Suppl 2):4-8.
Clinical aspects of recurrent oral herpes simplex
virus infection.
Glick M.
Department of Diagnostic Science, University of Medicine and Dentistry
of New Jersey, Newark, New Jersey, USA.
Recurrent oral ulcerations are the most common pathologic condition
seen by general dentists. Because the etiology of oral ulcers
is diverse, it is a continuous challenge for clinicians to reach
a correct diagnosis. Recurrent herpes simplex virus (HSV)-associated
ulcerations mainly affect the lip (herpes labialis). However,
intraoral ulcerations may also be a sign of recurrent disease.
For many patients, these sores are painful and unsightly. Up to
85% to 90% of adults show serologic evidence of exposure to HSV.
HSV infections can cause high morbidity beyond oral and genital
lesions. Furthermore, HSV poses an infectious risk to both patients
and oral health care providers, so it is important that dental
professionals are up-to-date on appropriate therapies and precautions.
This article discusses recurrent oral HSV infection and nonoral
manifestations of HSV infection.
-----
J Can Dent Assoc. 2002 Apr;68(4):247-51.
Acute herpetic gingivostomatitis in adults: a
review of 13 cases, including diagnosis and management.
Chauvin PJ, Ajar AH.
Division of Pathology, Faculty of Dentistry, McGuill University,
Montreal, Quebec. peter.chauvin@muhs.mcgill.ca
OBJECTIVE: To present to general dentists the typical signs
and symptoms associated with adult acute (primary) herpetic gingivostomatitis.
The pertinent laboratory tests, management options and current
pharmacotherapy are also reviewed. REVIEW DESIGN: The clinical
files of 13 adult patients were reviewed. All had no history of
herpes simplex virus infection and presented with oral lesions
suggestive of primary herpetic infection. The subjects were all
patients of one of the investigators, and their workup included
Tzanck testing and viral culture. RESULTS: The patients ranged
in age from 18 to 79 (mean 37.2, standard deviation 19.6) years.
Nine (69%) were men. Viral culture was confirmed as the gold standard
for diagnosis. The sensitivity of Tzanck testing was 77% (10/13),
slightly higher than that reported previously (40% to 50%). In
this patient group the febrile lymphadenopathic profile was typical
of younger patients (18 to 42 years of age), whereas older patients
presented with predominantly oral symptoms. CONCLUSIONS: Primary
herpetic gingivostomatitis is not limited to children but can
affect people of any age. Proper diagnosis and treatment are essential,
particularly in elderly and immunocompromised patients. Tzanck
testing may serve as a useful adjunct in diagnosis. Antiviral
agents such as valacyclovir and famciclovir should be considered
part of early management. Dentists are often the first health
care professionals to be consulted by patients with this condition,
and recognition of the infection is paramount.
-----
Chin Med J (Engl). 2002 Oct;115(10):1569-72.
Acyclovir for the treatment and prevention of
recurrent infectious herpes simplex keratitis.
Wu X, Chen X.
Department of Ophthalmology, Qilu Hospital, Shandong University,
Jinan 250012, China. xywu@public.jn.sd.cn
OBJECTIVE: To evaluate the role of acyclovir in treatment and
prevention of herpes simplex keratitis (HSK). METHODS: A total
of 105 patients with HSK were divided into 4 groups. Group 1 consisted
of 79 patients with HSV epithelial keratitis. Group 2 consisted
of 20 patients with interstitial keratitis. Group 3 consisted
of 6 patients with necrotizing keratitis. Group 4 consisted of
4 necrotizing keratitis patients with corneal perforation treated
with conjunctival flap and corneal transplantation. All patients
were treated with acyclovir systemically and topically. After
full recovery, the patients with epithelial HSK and stromal HSK
were randomly divided into two groups individually. One group
was constantly treated with oral acyclovir at 300 mg/day for 1
year as a prophylaxis group. The other group was designated as
control. RESULTS: During the one-year treatment and follow-up,
5 cases with epithelial HSK recurred in the prophylaxis group
and 14 cases in the control group, showing a statistically significant
difference. One case of stromal HSK recurred in the prophylaxis
group and 4 recurred in the control group. CONCLUSION: Long term
and low dose oral acyclovir for prophylaxis of recurrent epithelial
herpes simplex infection and therapeutic doses of oral acyclovir
reduce both the rate and duration of recurrences of infectious
herpes simplex keratitis.
-----
Clin Lab Med. 2002 Dec;22(4):883-910.
Human herpesvirus 8, Kaposi's sarcoma, and associated
conditions.
Gandhi M, Greenblatt RM.
Infectious Diseases Division, Department of Medicine, University
of California, San Francisco, 405 Irving Street, Second Floor,
San Francisco, CA 94122, USA.
HHV-8 is a recently identified human herpes virus that can
produce tumors, most often in immune compromised hosts. The virus
is most closely associated with Kaposi's sarcoma, but is also
clearly associated with primary effusion lymphomas and multicentric
Castleman's disease. The prevalence of HHV-8 infection varies
considerably, but is highest among men who have sex with men and
others with histories of sexually transmitted diseases and high
numbers of lifetime sexual partners. HHV-8 is shed in saliva,
and less commonly in genital secretions. Treatment of HHV-8 associated
diseases includes reversal of immune compromise either via discontinuation
of immunosuppressives or immune reconstitution via antiretroviral
regimens. Specific antiviral drug inhibit HHV-8 replication, and
can result in responses in certain HHV-8-associated conditions.
-----
Herpes. 2002 Dec;9(3):64-9.
Treatment of herpes simplex labialis.
Spruance SL, Kriesel JD.
Division of Infectious Diseases, University of Utah School of
Medicine, Room 4B319, 30 North 1900 East, Salt Lake City, UT 84132-2405,
USA. woody.spruance@hsc.utah.edu
Recurrent herpes simplex labialis is associated with mild morbidity,
but remains a significant problem for people with frequent and/or
severe recurrences. Both topical and peroral episodic antiviral
treatments of recurrences are modestly effective at reducing the
duration of signs and symptoms. Recent studies with high-dose,
short-course valaciclovir suggest that maximum benefit from antiviral
therapy may be achieved with as little as 1 day of treatment.
Topical steroids may be useful in combination with an antiviral
agent, but more needs to be learnt about the appropriate strength
and duration of steroid therapy before a general recommendation
can be made. Selected subgroups of patients are candidates for
prophylactic treatment with perorally administered nucleoside
antiviral agents. Prophylaxis with topical agents is not effective.
-----
Pathol Biol (Paris). 2002 Oct;50(8):483-92.
[What's new in vaccines against herpes simplex
infections?]
[Article in French]
Bosseray A, Bonadona A, Morand P.
Departement pluridisciplinaire de Medecine, CHU Grenoble, 38043
Grenoble, France.
Herpes simplex viruses (HSV) can cause a variety of infections,
including genital herpes. Despite effective antiviral therapy
HSV infections remain a public health problem. Vaccines offer
the possibility for controlling the spread and limiting HSV disease,
two strategies for herpes vaccination: prophylactic immunization
or therapeutic immunization. The article discusses the results
of different studies, in particular, concerning recombinant vaccines,
DISC vaccines and DNA vaccines.
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