Presentation is loading. Please wait.

Presentation is loading. Please wait.

U PDATE : G ENITAL H ERPES S IMPLEX V IRUS I NFECTION Nick Van Wagoner, MD, PhD University of Alabama at Birmingham Webinar.

Similar presentations


Presentation on theme: "U PDATE : G ENITAL H ERPES S IMPLEX V IRUS I NFECTION Nick Van Wagoner, MD, PhD University of Alabama at Birmingham Webinar."— Presentation transcript:

1 U PDATE : G ENITAL H ERPES S IMPLEX V IRUS I NFECTION Nick Van Wagoner, MD, PhD University of Alabama at Birmingham Webinar

2 N ICK V AN W AGONER : D ISCLOSURES Will not discuss off-label use of commercial products and/or services No commercial interest or affiliations

3 L EARNING O BJECTIVES B Y THE END OF THE L ECTURE : 1. Reviewed HSV-2 epidemiology in the U.S. 2. Understand the pathogenesis of HSV-2 3. Identify the clinical manifestations of HSV-2 4. Choose appropriate test(s) for HSV-2 diagnosis 5. Discuss the management of HSV-2 6. Introduce new research in HSV-2 prevention and treatment

4 1. Genital Herpes is the most prevalent STD in the U.S. 2. Life-long infection 3. Sexually transmitted 4. Most people don’t know their infected 5. Viral shedding occurs in the absence of symptoms 6. Transmission usually occurs when symptoms are absent

5 E PIDEMIOLOGY G ENITAL HSV IN THE U.S.

6 Centers for Disease Control and Prevention: available at Xu et al. JAMA. 2006: 296: Leone, Update on Epidemiology and Treatment Strategies for Genital Herpes HSV IS THE M OST P REVALENT STD IN THE US Over 1 million new genital herpes infections occur each year.

7 S EROPREVALENCE OF HSV-2, NHANES, Overall Seroprevalence: 16.2% Women: 20.9% Men: 11.9% MMWR (15):456

8 HSV R ISK F ACTORS XU et al., JAMA : Newman, STD : S4-S12 Behavior No. of Partners Early Sexual Debut Drug Use Behavior No. of Partners Early Sexual Debut Drug Use Biology Gender Race Male Circumcision Age Sociodemographics Income Living conditions Sexual Networks Sociodemographics Income Living conditions Sexual Networks

9 U NKNOWN HSV-2 I NFECTION Men Attending the JCHD HSV-2 Negative HSV-2 Positive Don’t know it HSV-2 Positive Know it ~80-90% of people that test positive for HSV-2 in the U.S are unaware that they are infected Xu et al. JAMA. 2006: 296: , MMWR (15):456

10 P ATHOGENESIS

11 V IROLOGY : HSV-1 AND HSV-2 Members of the human herpes virus family (herpetoviridae). Genome: ~154,000 bp DS DNA HSV-1 and HSV-2 50% Identical HSV-2 causes about ½ of genital ulcers The other ½ are caused by HSV-1 Dwyer and Cunningham. MJA (5): Todar. Ken Todar’s Microbial World. U of Wisconsin. 2006

12 Gupta et al., Lancet 2007 Asymptomatic Infection

13 HSV G ENITAL /A NOGENITAL T RANSMISSION Sexual Receptive Vaginal--Insertive Vaginal Receptive Anal--Insertive Anal Receptive Oral (HSV-1) Efficiency of sexual transmission: greater from men to women Likelihood of transmission declines with duration of infection

14 D EFINITIONS OF F IRST C LINICAL E PISODES Primary infection First infection ever (HSV-1 or HSV-2) More severe No antibody present when symptoms appear Non-primary infection New HSV-1 or HSV-2 in an individual previously seropositive to the other virus Will have antibody to the other HSV virus when symptoms appear Symptoms usually milder than primary infection

15 F IRST E PISODE P RIMARY I NFECTION  Characteristics of Lesions: Usually multiple and bilateral More severe than recurrences Contain higher virus titers than in recurrence Last days and shed virus for ~12 days Local symptoms include pain, itching, dysuria, vaginal or urethral discharge, and tender inguinal adenopathy ○ Cervicitis is common  Systemic Symptoms Last 2-4 weeks Fever, headache, malaise, myalgias

16 R ECURRENT S YMPTOMATIC I NFECTION Disease is milder and shorter in duration Antibody to HSV-2 present Prodromal Lesions last 5-10 days No systemic symptoms HSV-2 is more prone to recur than HSV-1

17 HSV L ESION P ROGRESSION Images /Definitions from: missinglink.ucsf.edu/ (2009) living with herpes.net (2009) Cincinnati STD/HIV Prevention Training Center A circumscribed elevated, sollid lesion, less than 1 cm PapuleVesicle A circumscribed, serous,fluid filled elevation of the skin, less than 0.5 cm Pustule A small (< 1 cm in diameter), circumscribed superficial elevation of the skin that is filled with purulent material. Ulcer A localized defect in the skin of irregular size and shape where epidermis and some dermis have been lost. V arying colors of liquid debris (serum or pus) that has dried on the surface of the skin Crust

18 HSV L ESION P ROGRESSION Images /Definitions from: missinglink.ucsf.edu/ (2009) living with herpes.net (2009) Cincinnati STD/HIV Prevention Training Center A circumscribed elevated, sollid lesion, less than 1 cm PapuleVesicle A circumscribed, serous,fluid filled elevation of the skin, less than 0.5 cm Pustule A small (< 1 cm in diameter), circumscribed superficial elevation of the skin that is filled with purulent material. Ulcer A localized defect in the skin of irregular size and shape where epidermis and some dermis have been lost. V arying colors of liquid debris (serum or pus) that has dried on the surface of the skin Crust Herpes Doesn’t Read Textbooks Lesions Can Have Many Appearances

19 Gupta et al., Lancet 2007 Asymptomatic Infection Asymptomatic But Shedding HSV-2 Gupta et al., Lancet 2007

20 A SYMPTOMATIC V IRAL S HEDDING No genital lesions present Between clinical outbreaks No history of clinical outbreaks Antibody present Common sites Women: vulva and perianal region Men: penile skin and perianal region Greatest in the first 3 months but continues Asymptomatic shedding is of briefer than during clinical recurrences

21 V IRAL S HEDDING OCCURS IN THE ABSENCE OF SYMPTOMS Mark et al, JID 198:

22 T RANSMISSION USUALLY OCCURS WHEN SYMPTOMS ARE ABSENT Median 334 Days 14 of 144 partners were infected (9.7%) 144 discordant couples followed over time 70% of transmission occurred when the index case was asymptomatic Mertz et al Risk Factors for the Sexual Transmission of Genital Herpes. Ann Intern Med. 116(3)

23 C LINICAL M ANIFESTATIONS

24 H ERPES : P RIMARY C OMPLEX Source: Cincinnati STD/HIV Prevention Training Center Clinical Manifestations papules  vesicles  pustules  ulcers  crusts  healed

25 H ERPES : G ENITALIS M ULTIPLE U LCER Source: Cincinnati STD/HIV Prevention Training Center Clinical Manifestations papules  vesicles  pustules  ulcers  crusts  healed

26 H ERPES : G ENITALIS E XTERNAL - L ABIA M INOR Source: Cincinnati STD/HIV Prevention Training Center Clinical Manifestations papules  vesicles  pustules  ulcers  crusts  healed

27 H ERPES : G ENITALIS C LINICAL P ERIURETHAL L ESIONS ON V ESTIBULE Source: Cincinnati STD/HIV Prevention Training Center Clinical Manifestations papules  vesicles  pustules  ulcers  crusts  healed

28 H ERPES : C ERVICITIS Source: Cincinnati STD/HIV Prevention Training Center Clinical Manifestations papules  vesicles  pustules  ulcers  crusts  healed

29 H ERPES ON THE B UTTOCK Source: Cincinnati STD/HIV Prevention Training Center Clinical Manifestations papules  vesicles  pustules  ulcers  crusts  healed

30 HSV D IAGNOSIS

31 Clinical diagnosis is insensitive and nonspecific Clinical diagnosis should be confirmed by lab testing Two types Virologic Serologic

32 V IROLOGIC T ESTS  Viral culture (gold standard) Preferred test for patients with genital ulcers or other mucocutaneous lesions ○ Most sensitive when lesions are in the vesicular-pustular stage ○ Sensitivity rapidly declines as lesions ulcerate and crust  Nucleic Acid Amplification User Friendly More Sensitive

33 T YPE -S PECIFIC S EROLOGIC T ESTS Type-specific and nonspecific antibodies to HSV develop during the first several weeks following infection and persist indefinitely Presence of HSV-2 antibody indicates anogenital infection Presence of HSV-1 does not distinguish anogenital from orolabial infection.

34 Lab-Based Serology Tests % Sensitivity (95% CI) % Specificity (95% CI) HerpesSelect HSV-1 ELISA 91 (85-95)92 (85-97) HerpeSelect HSV-2 ELISA 96 (89-99)97 (93-99) HerpeSelect HSV-1 Immunoblot IgG 99 (96-100)95 (89-98) HerpeSelect HSV-2 Immunoblot IgG 97 (91-100)98 (95-100) Captia HSV-1 ELISA88 (82-94)100 (96-100) Captia HSV-2 ELISA97 (89-100)90 (84-95) Point-of-Care Serology HerpeSelect Express Rapid HSV-2 IgG 98 (95-99) (Capillary whole blood) 99 (97-100) (Capillary whole blood) Biokit HSV-2 Rapid Test Sure-Vue HSV-2 Rapid Tests 92 (91-94) (Capillary whole blood) 87 (85-89) (Capillary whole blood) From: The HERPES Testing Toolkit: A clinician’s guide to serologic testing for Herpes simlex virus (HSV). ASHA

35 D IAGNOSIS Infection Type Lesions/ Symptoms Type-specific antibody at time of presentation HSV-1HSV-2 First episode, Primary (Type 1 or 2) +/Severe, bilateral -- First episode, Non-primary Type 2 +/Moderate+- First episode, Recurrence Type 2 +/Mild+/-+ Symptomatic, Recurrence Type 2 +/Mild, unilateral +/-+ Asymptomatic, Infection Type 2 -+/-+

36 C ANDIDATE P ATIENTS FOR T YPE -S PECIFIC G ENITAL H ERPES T ESTS Testing RecommendedSwab Test (Viral Culture or PCR) Serological Test (Type Specific Ab) Typical Genital LesionXX Clinical dx with negative or no swab testX Atypical Lesion (e.g, fissure, erythema)XX Recurrent lower genital tract inflammation with no lesions (e.g, dysuria, burning, itching) X STI evaluation, no lesionsX Sexually active patient requests test, no lesion X Sex partner of patient with genital herpesX Experts disagree on whether or not these patients should be tested HIV, no lesionX Sexual assault, no lesionX Pregnancy, no lesionsX High risk populations (e.g. MSM), no lesions X From: The HERPES Testing Toolkit: A clinician’s guide to serologic testing for Herpes simlex virus (HSV). ASHA

37 P ATIENT M ANAGEMENT

38 P RINCIPLES OF M ANAGEMENT OF G ENITAL H ERPES Systemic antiviral chemotherapy Partially controls symptoms and signs of herpes episodes Does not eradicate latent virus Does not affect risk, frequency or severity of recurrences after drug is discontinued  Counseling  Natural history  Sexual transmission  Perinatal transmission  Methods to reduce transmission

39 A NTIVIRAL M EDICATIONS  Systemic antiviral chemotherapy includes 3 oral medications: Acyclovir Valacyclovir Famciclovir  Topical antiviral treatment has minimal clinical benefit and is not recommended. Management

40 F IRST C LINICAL E PISODE S TART E ARLY AND T REAT L ONGER 2010 STD Treatment Guideline 2010

41 E PISODIC T REATMENT FOR R ECURRENT G ENITAL H ERPES Therapy should be initiated within one day of symptoms Patients can be given prescriptions ahead of time

42 S UPPRESSIVE T HERAPY FOR R ECURRENT G ENITAL H ERPES Reduces frequency of recurrences Reduces but does not eliminate subclinical viral shedding Periodically (e.g., once a year), reassess need for continued suppressive therapy.

43 S PECIAL P OPULATIONS

44 HIV AND HSV-2 COINFECTION IS COMMON Percent HVS-2 Positive Modifed from Russel et al. J of Clin Vir : 305; and Wald and Celum. Medscape CE course 2005:

45 HSV AND HIV ARE LINKED Effect of HIV on HSV- 2  Alters the clinical presentation of HSV-2  Increased HSV-2 shedding  Larger, slower- healing lesions in persons with advanced HIV  Increased risk of HSV-2 acquisition HSV HIV Effect of HSV-2 on HIV  Increases risk of HIV acquisition/ transmission  Genital Lesions provide a portal of entry for HIV  Increased number of activated CD4+ and CD8+ T cells in genital mucosa and skin  Increased HIV levels in plasma and genital tract Leone, Update on Epidemiology and Treatment Strategies for Genital Herpes. 2008

46 CDC-R ECOMMENDED R EGIMENS FOR E PISODIC I NFECTION IN HIV-I NFECTED P ERSONS T REAT L ONGER

47 CDC-R ECOMMENDED R EGIMENS FOR D AILY S UPPRESSIVE T HERAPY IN HIV-I NFECTED P ERSONS

48 H ERPES IN P REGNANCY (N EONATAL H ERPES ) Most commonly transmitted during delivery 1 in 3,000-20,000 live births Affects ~1,500-2,000 infants/yr in US Greater risk to infant if mother has primary genital lesions Primary genital lesions = 40-50% of infants affected Recurrent genital lesions = 2-3% Risk of transmission Young maternal age Maternal seronegativity Presence of vaginal lesions during delivery Infant prematurity Manifests during first 4 weeks after birth

49 H ERPES IN P REGNANCY (N EONATAL H ERPES ) Neonatal Herpes Syndromes Skin, eye and mouth (SEM) Typically lesions are on the scalp, mouth, nose, and eye (where the skin comes in contact with the mother’s genital lesions) CNS (Seizures, lethargy, and hypotonia) Accounts for ~60% of cases. May have skin lesions 40% of survivors may have neurological deficits Disseminated (including liver, adrenal glands, lungs) Devastating 50% mortality Present with shock (multi-organ system failure)

50 H ERPES IN P REGNANCY ( CONTINUED )  Prevention of neonatal herpes depends on avoiding acquisition of HSV during late pregnancy and avoiding exposure of the infant to herpetic lesions during delivery.

51 H ERPES IN P REGNANCY ( CONTINUED ) Ask all pregnant women if they have a history of genital herpes. At the onset of labor: Question all women about symptoms of genital herpes, including prodrome. Examine all women for herpetic lesions. Women without symptoms or signs of genital herpes or its prodrome can deliver vaginally.

52 H ERPES IN P REGNANCY ( CONTINUED ) Treatment in Pregnancy Oral Acyclovir may be administered to pregnant women with first-episode genital herpes or recurrent herpes IV Acyclovir may be administered to pregnant women with severe HSV infection No increased risk of birth defects in women treated with acyclovir during 1 st trimester More limited data for valacyclovir and famciclovir

53 L ESSON VI: P REVENTION

54 P ATIENT C OUNSELING AND E DUCATION Goals Help patients cope with the infection Physical and Psychological Aspects Prevent sexual and perinatal transmission Education is an ongoing process Nature of the infection Transmission Treatment Options Risk-reduction Partner Management

55 N ATURE OF THE I NFECTION Sexual transmission of HSV can occur during asymptomatic periods. Stressful events may trigger recurrences. Prodromal symptoms may precede outbreaks.

56 T RANSMISSION Abstain from sexual activity with uninfected partners when lesions or prodromal symptoms are present. Inform current sex partners. Inform future sex partners before initiating sex.

57 T REATMENT O PTIONS Discuss: Effectiveness of suppressive and episodic therapy to prevent or shorten the duration of recurrent episodes When and how to take antiretroviral medications Recognition of prodromal symptoms Treatment is not curative

58 R ISK R EDUCTION Assess client's behavior-change potential. Discuss prevention strategies (abstinence, mutual monogamy with an uninfected partner, condoms, limiting number of sex partners, etc.). Work with patient to develop individualized risk- reduction plans.

59 C OUNSELING FOR A SYMPTOMATIC P ERSONS Asymptomatic HSV-2 infected persons should receive the same counseling messages as symptomatic persons. Teach the common manifestations of genital herpes

60 P ARTNER M ANAGEMENT Symptomatic sex partners Evaluate and treat in the same manner as patients who have genital lesions. Asymptomatic sex partners Ask about history of genital lesions. Educate to recognize symptoms of herpes. Offer type-specific serologic testing.

61 T HE F UTURE OF HSV-2 ( VACCINATION AND MICROBICIDES )

62 H OPE FOR A V ACCINE Johnston et al JCI. 121(12): 4600

63 H OPE FOR A V ACCINE Johnston et al JCI. 121(12): 4600

64 Belshe et al NEJM

65 Johnston et al JCI. 121(12): 4600

66 T HERAPEUTIC V ACCINES FOR HSV-2 Johnston et al JCI. 121(12): 4600

67 T ENOFOVIR M ICROBIDICE : HIV AND HSV-2 P REVENTION HIV 51% Reduction in HSV-2 Acquisition in women using the Tenofovir Gel Karim et al Science. 329:1168

68 N EW T HERAPEUTICS Still Searching…

69 L EARNING O BJECTIVES B Y THE END OF THE L ECTURE : 1. Reviewed HSV-2 epidemiology in the U.S. 2. Understand the pathogenesis of HSV-2 3. Identify the clinical manifestations of HSV-2 4. Choose appropriate test(s) for HSV-2 diagnosis 5. Discuss the management of HSV-2 6. Introduce new research in HSV-2 prevention and treatment


Download ppt "U PDATE : G ENITAL H ERPES S IMPLEX V IRUS I NFECTION Nick Van Wagoner, MD, PhD University of Alabama at Birmingham Webinar."

Similar presentations


Ads by Google