“ update and new perspectives on hsv infections ” paulo r. cunha, md, phd. professor of...
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““Update and new Update and new perspectives on HSV perspectives on HSV
infectionsinfections””
Paulo R. Cunha, MD, PhD.Professor of Dermatology
Jundiaí Medical SchoolSão Paulo, Brazil
21st World Congress of Dermatology
Oct/2007
Introduction
Over 70% of the population has been infected by either HSV-1 or HSV-2
Produce: primary, latent and recurrent infections.
Clinical manifestation: “benign and malign”
Extragenital Herpes: 80-90%: HSV-1
Genital Herpes: (normally sexual transmission)
80-90%: HSV-2
DNA Virus
Serological techniques:
HSV-1: glycoprotein gC1 HSV-2: glycoprotein gC2
Capsid
Capsomers
Cell membrane
Cytoplasm Herpes virus
Virus new particle
Keratinocyte
DNA HSV
Cytoplasmic Membrane
Acyclovir
Timidina Kinase (TK)
AcyclovirMonophosphate
AcyclovirTriphosphate
Genital Herpes: CDC Treatment Recommendations
Valacyclovir 1000 bid 500 bid (3†-5 d) 500 qd‡
1000 qd (5 d) 1000 qd
Acyclovir 400 tid 400 tid (5 d) 400 bid 200 5/day800 bid (5 d)
200 5/day (5 d)
Famcyclovir 250 tid* 125 bid (5 d) 250 bid up to 1 year
genital herpesepisode episodic
suppressive(mg for 7–10 days) (mg days) (mg, daily)
*Not FDA approved†New FDA-approved dosing‡May be less effective in patients who have very frequent recurrences (10 episodes/year)
First clinical Recurrent genital
herpes
Centers for Disease Control and Prevention. MMWR. 2002;51(RR-6)12-17.
Issues to be considered in Suppressive Therapy
Not necessary to wait 6 outbreaks in 12 months
Define impact of genital herpes
Gravity and duration of the outbreak
New Therapeutic Options 1) Analog of nucleoside
Cidofovir (gel 0.3 or 1%) Single-dose confers a significant antiviral effect on lesions of recurrent genital herpes.
Antimicrob Agents Chemother 1998 Nov;42(11):2996-9
New Therapeutic Options 2) Immunomodulator
Resiquimod (gel 0.05%) Significant reduction in number of recurrences
J Infect Dis 2001 Jul 15;184(2):196-200
New Therapeutic Options 3) Fusion Inhibitor
Docosanol (Abreva®) (cream 10%) interferes with the process of viral fusion with the host cell.
Effective treatment for recurrent HSL.
J Am Acad Dermatol 2001 Aug; 45 (2): 222-30)
Foscarnet is the choice in pts with HSV resistant to acyclovir. It is effective in destroying the virus timidina kinase lacking (nephrotoxicity).
Rio Dermatológico 2001 July/August/September
Foscarnet (cream 2%) is an effective and safe medication in the treatment of HSL.
Hautarzt. 2006 Jan;57(1):40-6
New Therapeutic Options 4) Direct action in DNA polimerase of
HSV
New Therapeutic Options 5) Helicase inhbitors
Nature Med. 8,392-398, 2002). (Phase III)
(Phase III)
Could increase the intervals between the
crises and it is more effective then acyclovir
Avoid: Arginine, “Herpetogenic” foods like chocolate, peas, cola drinks, grain cereals, peanuts, gelatin, cashews, beer.
Encourage: Lysine, Foods like dairy products, milk, potatoes, brewer’s yeast.
Treatment of Recurrent Herpes Simplex with L-Lysine
Decreases recurrence and severity
Long-term: L-Lysine 1 g/day
New Antiherpes Vaccines by Genetic Engineering
An ideal vaccine should induce Cellular and Humoral Immune Response adequate to prevent infection.
Vaccines by genetic engineering
Plasmid insertion Plasmid transference
Chromosome
transformed bacteria
PCMV T7His6EK BGH f1 SV40 N SV40 ColE1 Amp pA ori ori pA
Vaccines with DNA of plasmid that contains the codes of viral glycoproteins (pcDNA3.1/His A,B,C
5.5 kb )
Cellular and Humoral Immune Response
Herpes Virus Vaccine: News and Perspectives
The most hopeful result was obtained with HSV-2 gD2 and alum/MPL vaccine (Glaxo SmithKline) in clinical studies. -74% effective in preventing genital disease -Only in women who had never been exposed to HSV previously. -Not effective in men
DISC (Disabled Infectious Single Cycle) virus HSV vaccine contains a virus with deletion of an essential gene (gH gene), so the replication has been limited to a single cycle only. Guinea pigs were protected from a primary infection. Significant protection from recurrent disease was also observed.
Herpes Virus Vaccine: News and Perspectives
Herpes Virus Vaccine Studies
Prophylactic Vaccines for HSV-2Genetically engineered HSV to produce a vaccine that is protective without causing human disease is in development. Using a vaccine with live attenuated HSV from which neurovirulence gene (gamma 1 34.5) has been removed, has debilitated HSV in its ability to establish latency and be reactivated.Animals vaccinated are able to elicit protective immune responses
Mikrobiyol Bul. 2006 Oct;40(4):413-33
ConclusionsHSV Vaccine is still a challenge.
Seronegative individuals at high risk for infection represent ideal candidates for vaccine trials.
Individuals with frequent recurrences are not significantly responsive to vaccines so far.
Promising approaches to engineered HSV vaccines should be possible within the next several years.
We are in the right road but we have to keep walking.
Sexual education, campaigns of information and the use of preservative continues to be essential.
Thank [email protected]