Genital Herpes. Assoc Professor Catherine O Connor & Ms. Barbara Hatten. RPA Sexual Health. RPA Sexual Health

Transcription

1 Genital Herpes Assoc Professor Catherine O Connor & Ms. Barbara Hatten Presentation developed: A/Prof David Templeton, A/Prof Catherine O Connor & Ms. Loretta Healey

2 Program outline Overview of genital herpes (Genital Herpes) Epidemiology Clinical presentation Viral shedding & transmission Diagnosis Treatment approaches Case studies

3 Genital Herpes Overview

4 Genital herpes Genital Herpes can result from infection with either HSV-1 or HSV-2 HSV-1 and HSV-2 lesions are clinically indistinguishable There has been an increase in genital HSV % in 1980 to 34.9% in > 50% of first episodes in young heterosexual women and men who have sex with men (MSM) 2 HSV-2 continues to be the most common cause of recurrent Genital Herpes

5 Prevalence of HSV-2 in Australia Prisons (Men) Prisons (Women) 21% 58% HIV- (MSM) HIV+ (MSM) 20% 61% Non Indigenous Indigenous Rural Metropolitan 9% 18% 9% 13% 1. Cunningham AL et al. Sex TransmInfect 2006; 82: CunninGenitalHerpesamAL et al. Med J Aust1993;158 (8): Bassett I et al. Med J Aust1994; 160(11): Russell DB et al. J ClinVirol2001;22(3): Butler T et al. IntJ STD AIDS2000; 11(11); Men Women 8% 16% 0% 20% 40% 60% 80%

6 Under-diagnosis of Genital Herpes Asymptomatic 20% Diagnosed 20% Symptoms, but not diagnosed 60% Adapted from Corey L, Simmons A. The medical importance of genital herpes simplex virus infection. International Herpes Management Forum, C O Connor & B Hatten May IWSML 2015

7 Symptoms of Genital Herpes Classical signs of blisters or ulcers are uncommon Atypical manifestations are more common and include 1 4 fissures localised erythema Irritation / itch / tingling / soreness of skin

8 Severe Primary HSV

9 Severe Primary HSV

10 Severe Primary Perianal HSV

11 Penile HSV

12 Primary versus recurrent disease Primary 1st episode Lesions appear 2-14 days after exposure and without therapy can last 20+ days Manifestations typically include bilaterallesions, itching, dysuria, vaginal or urethral discharge, fever, headache, or fatigue regional symptoms include parasthesiaeand paresis Recurrent episode Usually unilateral lesions Fewer and shorter symptoms (<7 days)

13 HSV-2 recurrence 89% of individuals with symptomatic HSV-2 will experience recurrences 1 Median of 4-6 recurrences in the first year following newly acquired HSV-2 1,2 Patients who experience a severe primary HSV-2 infection may have twice as many recurrences in the first year 1 HSV-2 several times more recurrent than HSV Benedetti J et al. Ann Intern Med 1994; 121: Benedetti J et al. C Intern O Connor Med & B HattenMay 1999; 131: IWSML

14 Virological& clinical course of HSV infection in a subject taking a placebo Adapted from Wald A et al. J ClinInvest 1997; 99: The graph above shows the virological and clinical course of HSV infection of subject 14 All subjects obtained daily swabs of genital secretions for viral isolation and PCR

15 Genital Herpes Transmission

16 Transmission of HSV-2 Risk factors for transmission include: gender: M F higher than F M shorter duration of infection longer length of relationship higher number of recurrences more sex lack of condom use sex whilst symptoms present 1. AHMF Guidelines for Clinicians, Reducing Sexual Transmission of Genital Herpes, Revised February AHMF Genital Herpes: Essential Facts

17 Who transmits genital herpes Most HSV-2 infections are acquired from a person with no history of Genital Herpes 1 In HSV-2-positive individuals who have a history of recurrent Genital Herpes, most transmissions occur when lesions are not present 2 Transmission during asymptomatic viral shedding 70% Transmission during prodrome or just before lesions 30% 1. Mertz et C al. O Connor Sex Transm & B HattenMay Dis 1985;12: IWSML Mertz et al. Ann Intern Med1992; 116:

18 Reducing transmission risk Disclosure to partners Abstaining when symptoms are present Use of condoms Use of antiviral therapy

19 HSV transmission and condoms Condoms have been shown to reduce the transmission of Genital Herpes 1,2 More effective in prevention of transmission from male to female 1 BUT Viral shedding occurs from areas not covered by condoms Consistent use Condom breakage/ slippage can still occur 1.Wald A et al. JAMA 2001; 285: Wald et al. Ann Intern Med 2005;143: Lytle CD et al. Sex TransmDis 1997; 24:

20 Genital Herpes Diagnosis

21 Diagnostic tests PCR* More rapid than other tests More sensitive than other detection methods late in infection when lesions have begun to crust Controls for cross contamination important * PCR is now considered the diagnostic gold standard ahmf.com.au

22 Type-specific serology Circumstances where type-specific serology useful: Relationships where one partner has genital herpes and the other is asymptomatic 1 Pregnancy Male partner has Genital Herpes, female pregnant & no Hx Genital Herpes First episode genital herpes during pregnancy 2 To determine if new infection positive serology only indicates a person has been infected do not identify site of infection The place for serology in diagnosis cannot prove that a genital lesion is due to HSV cannot distinguish genital from oro-labial HSV infection Current ELISAs may fail to detect HSV-2 antibodies in patients who have longstanding infection 1. The Use of Type-Specific Serlogy for the Diagnosis of genital Herpes, AHMF Guidelines for Clinicians, Revised February 2008

23 Genital Herpes Treatment Strategies

24 Initial Episode Episodic Therapy Standard course Short course Suppressive Therapy Continuous Pre-emptive Treatment strategies 1. AHMF Guidelines for Clinicians, Managing Genital Herpes, Revised February IHMF Guidelines

25 Management of an initial episode Take a complete sexual history, perform genital examination and STI screen as indicated Swab lesion(s) for HSV PCR (not serology) Best chance of confirming and typing lesions is at initial episode Results more accurate when lesions are fresh Accuracy drops as lesions crust, so a repeat test may be required Don t delay start treatment on clinical suspicion 1,2,3 Treatment offers real benefit in reducing severity and pain of attack Most effective the earlier commenced Averts serious sequelae such as meningitis and urinary retention 1. Pharmaceutical Benefits Schedule, effective 1 May, AHMF Guidelines for Clinicians, Managing Genital Herpes, Revised February AHMF Guidelines for Clinicians, The Diagnosis of Herpes Simplex Viruses, Updated February 2008

26 Episodic therapy Aim = reduce the duration and severity of a recurrence 5 days of antivirals effective at reducing episode duration, pain & formation of new lesions 1-3 wiceas likely to abort episode if therapy is started 6 hrs of symptoms/signs 4 : Advise patient to carry medications with them Short course regimens Rationale: recurrent HSV viral replication reaches peak within hours of the onset of symptoms 5 & viral replication is usually terminated within 2 days of commencing anti-viral therapy 5 Impact on healing, viral shedding and lesion abortion of short course therapy equivalent to standard 5 day therapy 6-11 Famciclovir(Famvir) only antiviral approved for 2-day episodic Rx of Genital Herpes (3-day Valtrex also useful, but not approved)

27 Episodic therapy Who would benefit? Episodic therapy could be considered when: Transmission not a major concern Patient not overly concerned about recurrences Recurrences infrequent & well defined Patient gets clear prodromal symptoms Patient doesn t want to take daily, ongoing medication

28 Suppressive therapy Benefits of daily antiviral suppressive therapy recurrences 1-3 viral shedding 3-5 transmission (shown for valaciclovironly) 6 quality of life 7-9 Patient preference 7* * In an open-label, randomised, cross-over 48-week study comparing Valtrex OD suppressive therapy versus Valtrex BD episodic therapy, n=202; p< Patel R et al. GenitourinMed 1997;73: Diaz-MitomaF et al. JAMA 1998; 280(10): Wald A et al. Sex TransmDis2006 Sep; 33(9): Wald A et al. J ClinInvest 1997; 99: SperlingRS et al. Sex TransmDis2008; 35(3): Corey L et al. N EnglJ Med Jan 1;350(1): RomanowskiB et al. Sex TransmDis 2003; 30(3): HandsfieldHH et al. Sex TransmDis2007; 34(6): Patel R et al. Sex TransmInf1999; 75(6): AHMF Guidelines for Clinicians, Suppressive Therapy for Genital Herpes, First Edition April 2008

29 Suppressive therapy Recurrence reduction Suppressive therapy significantly increases time to first genital HSV recurrence and allows more patients to be recurrence free 1,2 Suppressive Valtrex vs. Suppressive Famvir 3 : No difference in proportion of persons with a clinically confirmed recurrence BUTFamvirgroup More commonly had virological recurrence Shorter time to virological recurrence 1. Patel R et al. Genitourin Med 1997;73: Diaz-Mitoma F et al. JAMA 1998; 280(10): Wald A et al. Sex Transm Dis 2006 Sep; 33(9):

30 Suppressive therapy (aciclovir) Viral shedding reduction C O Connor & B HattenIWSML 2015 Wald A et al. J Clin Invest 1997; 99:

31 Suppressive therapy (valaciclovir) Viral shedding reduction Percent of subclinical days with HSV-2 shedding 6.0% 5.0% 5.1% 4.0% 3.0% 2.0% 1.0% 71% risk reduction p< % 0.0% Placebo Valaciclovir C O Connor & B HattenMay IWSML Sperling 2015 RS et al. Sex Transm Dis 2008; 35(3):

32 Rates of viral shedding Valaciclovir vs. Famciclovir Suppressive Therapy Valaciclovir Famciclovir 1.3% 3.2% 0.0% 1.0% 2.0% 3.0% 4.0% Percentage of total days* Adapted from Wald et al. Sex TransmDis2006; 33(9): A randomised, double-blind 10 week study comparing oral famciclovir 250mg bd and oral valaciclovir 500mg OD on genital HSV shedding, n=320 *Mean number of days with swabs for viral shedding was 66.4 days Reduced viral shedding does not necessarily directly relate to clinical outcome

33 Rates of viral shedding Valaciclovir vs. Famciclovir Respondents (%) % of famciclovir recipients (vs. none of the valaciclovir recipients) experienced > 6% of days of shedding >0 to<=2 >2 to <=4 >4 to <=6 >6 Percent of days with viral shedding 1. Wald et al. Sex TransmDis 2006; 33(9): A randomised, double-blind 10 week study comparing oral famciclovir 25mg bd and oral valaciclovir 500mg OD on genital HSV shedding, n=320 Famciclovir Valaciclovir *Mean number of days with swabs for viral shedding was 66.4 days Reduced viral shedding does not necessarily directly relate to clinical outcome

34 Pre-emptive suppressive therapy Pre-emptive suppressive therapy Tactical use of suppressive therapy over short period of time Helpful during periods when patients wish to reduce the risk of an outbreak Social examples that may warrant pre-emptive suppressive therapy: To prevent a recurrence leading up to a special occasion To decrease viral load and reduce transmission risk when entering into a new relationship Pre-emptive suppressive therapy is a common patient choice IHMF guidelines

35 Reducing transmission

36 Proportion of susceptible partners with HSV-2 infection Primary endpoint Percentage of Patients with HSV-2 4.0% 3.5% 3.0% 2.5% 2.0% 1.5% 1.0% 0.5% 0.0% 3.6% (27 / 741) Placebo 48% risk reduction p = % (14 / 743) Valaciclovir Corey L et al. N Engl J Med Jan 1;350(1):11-20.

37 Suppressive therapy Consider in: Patient groups at higenital Herpes risk of HSV transmission Patients in new relationships Newly-diagnosed patients (recurrence rate higenitalherpesestin first year) Patients with frequent recurrences Patients with more severe symptoms Patients not coping well psychologically with the diagnosis Partners of seronegativepregnant women (or those contemplating pregnancy) 1. AHMF Guidelines for Clinicians, Managing Genital Herpes, Revised February AHMF Guidelines for Clinicians, Suppressive Therapy for Genital Herpes, First Edition April AHMF Guidelines for Clinicians, Herpes Simplex in Pregnancy, Revised & Updated July AHMF Herpes In Pregnancy: Esential Facts

38 Use of suppressive therapy in newly HSV-2- diagnosed women 4 women, symptomatic HSV-2, daily swabs for 30 days from multiple sites HSV detected on 37% days by PCR labia 23% days perianal 21% days cervix 14% days urethra 12% days BUTclinical lesions absent 40% days Patient info: can t predict when or where HSV shedding will occur shedding may not be at areas where lesions are or have been present Suppressive therapy for prevention of transmission may be most important in newly-hsv-2-diagnosed individuals Tata et al. J Infect Dis 2010;201:

39 Suppressive therapy Summary Transmission Reduction Valaciclovir transmission study shows that once daily valaciclovir reduces risk of transmission by 48% 1* Safety Data from long-term use of ciclovir s 2 Resistance Viral resistance to ciclovir srare 3,4 Patient Attitude to Suppressive Therapy 72% of patients prefer suppressive to episodic therapy 5^ 1. Corey N EnglJ Med Jan 1;350(1): Tyring SK et al. J Infect Dis 2002; 186 (Suppl1): S40 6; 3. Bacon TH et al. ClinMicrobiolRev 2003; 16: ; 54 BodsworthN et al. Curr Med Res Opin2009; 25(2): Romanowskiet al. Sex TransmDis 2003; 30: *in heterosexual, monogamous, HSV-2-discordant couples when taken by the HSV-2 seropositive immunocompetent partner with < 10 recurrences ^Valtrex OD suppressive therapy versus Valtrex BD episodic therapy

40 Primary episode Episodic therapy Suppressive therapy Prevention of Recurrence Suppressive therapy Transmission Antiviral therapies Aciclovir 1 Valaciclovir 2 Famciclovir 3 200mg 5X daily 10 days 200mg 5X daily 5 days 500mg BD 5 10 days 500 mg BD 5 days *Immunocompetent: < 10 recurrences 500 mg once daily; 10 or more recurrences 1000 mg once daily; Reduction Immunocompromised: 500 mg twice daily **Adjust dosage in immunocompromised (see full Prescribing Information) *** Immunocompetent heterosexual adults with < 10 recurrences per year and with a susceptible partner No Indication 125 mg BD 5 days OR 500mg statim followed by 250mg BD for 2 days 200mg 2-3X daily 500 mg D* 250 mg BD** No Indication 500 mg D*** No Indication 1. Zovirax (aciclovir) Product Information. 2. Valtrex (valaciclovir) C O Connor & B HattenMay Product IWSML Information Famvir (famciclovir) Product Information

41 PBS authority restrictions PBS requirement for authority script: Microbiological confirmation of diagnosis (viral culture, antigen detection or nucleic acid amplification by PCR) is required but need not delay treatment. Aciclovir Valaciclovir Famciclovir Primary episode 200mg tablets (50 x0 repeats) 500mg tablets (20 x0 repeats) No Indication Episodic therapy 200mg tablets (90 x5 repeats) 500mg tablets (30 x5 repeats) 125mg tabs (40 x5 repeats) 250mg tabs (20 x5 repeats) 500mg tabs (56 x5 repeats)* Suppressive therapy Prevention of Recurrence 200mg tablets (90 x5 repeats) 500mg tablets (30 x5 repeats) 250mg tabs (20 x5 repeats) * Immunocompromised patients Pharmaceutical Benefits Schedule, effective 1 May (accessed online at pbs.gov.au)

42 Useful clinician resources New Zealand Herpes Foundation: Sexual health info line Provides advice for patients and clinicians, or for contacts to a local sexual health clinic

43 HSV Counselling Barbara Hatten Social Worker SLHD

44 Psychological responses to diagnosis High levels of distress Shame Fear that partner has been unfaithful Belief that life is ruined Belief that sex life is over Guilt Regard it as punishment Anger

45 Perceived Trauma of Contracting Genital Herpes I m going to read you a list of items that people may or may not consider traumatic. For each one I read, please tell me how traumatic it would be for you personally: very traumatic, somewhat traumatic, not very traumatic, or not traumatic at all. Percent Saying Very Traumatic Acquiring AIDS 96% Having genital herpes 68% Breaking up with a significant other Getting fired from a job 54% 51% Failing a course in school 28%

46 Emotional Response to Diagnosis Respondents (%) Depression Fear of rejection Primary Feelings of Isolation Fear of discovery Recurrent Selfdestructive feelings

47 Stigma In 1980s made cover of Time Magazine Not openly discussed among friends Isolation Blisters, pain feeling dirty Feelings of shame Identity formed around diagnosis More recent positive coverage in US publications: Women s Health & The Washington Post (April 2015)

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49 Ella Dawson I didn t see you as Ella with herpes. I just saw you as Ella. C O Connor & B HattenIWSML 2015

50 Partner issues Concern re possible infidelity of partner Fear of disclosure Fear of rejection Fear of infecting partner Fear that they will never be able to form new relationships Concern over need to use condoms long-term

51 Common Questions How did I get it; has my partner been unfaithful? Should I tell all my future partners and when? Will it affect my fertility? What if I (my partner) get pregnant? How many recurrences will I get? What can I do to stop recurrences?

52 Common Questions Can I catch it from toilet seats/ towels etc? Does the medication have long term side effects? Can it spread from my genitals to other parts of my body? What can I expect in the future? Can I have a blood test for Genital Herpes?

53 Strategies Having counselling and information session at time of diagnosis helpful Reassurance re future adjustment Use of written resources, New Zealand website Discuss prevalence Cognitive strategies

54 Strategies Discuss ways of discussing HSV with partner Offer to see partner Establish trust before sex May need to change ways of forming relationships Discuss concept of good relationship versus avoidance of virus

55 Lifestyle issues Long term high levels of stress predict reoccurrences Management of chronic anxiety Short term stress does not predict reoccurrences Sleep, food and exercise

56 Take home message Refer distressed patients to for counselling and Information session

57 Case Studies

58 Case study 1 -Jemima Jemima is a 29-year-old woman who presents with vulvalsoreness and pain when urinating Physical examination Vulva unusually red and tender A few small ulcers on the right labia majora No vaginal discharge Bilateral tender and mildly swollen inguinal nodes Oral temperature 37.5 o C History Was treated 5 months ago for a UTI (MSU -ve) She recalls having associated genital soreness, and also having a few sores on her inner thighs She remembers a similar episode almost a year ago C O Connor & B HattenIWSML 2015

59 Further information / history Jemima has had three short-term sexual relationships in the past 8 months, and separated from her latest partner 1 week ago She says her partners always used condoms, but not with oral sex Her first boyfriend, Harry, is returning next week after 2 years working on an isolated cattle station in North Queensland. She hopes to resume their former (sexual) relationship Jemima has not previously been screened She does not think any of her previous partners have had Genital Herpes or any other STI She is currently not taking any medication What are some provisional diagnoses? C O Connor & B HattenIWSML 2015

60 What tests would you perform? Swab of lesion for HSV-PCR HSV type-specific serology Cervical or vaginal swab for Neisseria culture and Chlamydia PCR Serology for HIV, HBV, syphilis MSU Pap smear High vaginal swab Gram stain C O Connor & B HattenIWSML 2015

61 How would you treat Jemima s symptoms? Antiviral therapy? Topical antiviral? Oral analgesic? Oral antibiotic? Vaginal antifungal? Lesion management? Recommend urinating in tepid saline bath to ease dysuria? HiGenital Herpes fluid intake? Nothing? C O Connor & B HattenIWSML 2015

62 Viral swab PCR HSV-1 negative HSV-2 positive Serology - HSV IgG HSV-1 negative HSV-2 positive Results - Scenario 1 Diagnosis and patient concerns Recurrent episode of Genital Herpes caused by HSV-2 Jemima is distressed by the diagnosis She wants to know where she got it from? She is particularly concerned about the possibility of transmission to Harry Should therapy with valaciclovirbe suggested to Jemima both for symptom control and to reduce the risk of transmission?

63 Results -Scenario 2 Viral swab PCR HSV-1 negative HSV-2 negative Serology - HSV IgG HSV-1 negative HSV-2 negative What would you do now?

64 Case study 2 -Giles Giles is a 34-year-old man, recently divorced after 7 years of marriage Diagnosed with genital HSV-2 approximately 8 years ago His ex-wife was HSV-2 positive He experiences approximately 6 recurrences per year He is currently taking episodic antiviral therapy Giles is hoping to enter a new sexual relationship with Melanie, a 26-year-old woman He is concerned about possible transmission of HSV-2 to her How would you advise him? C O Connor & B Hatten IWSML May 2015

65 Case study 3 -Kieran Kieran is a 36-year-old man whose partner Julie (32yrs), is 10 weeks pregnant They have been in a sexual relationship for 3 years Kieran has few recurrences of Genital Herpes due to HSV-2, and mild symptoms when recurrences occur. He is not taking antiviral therapy HSV Status Kieran: HSV-2 positive, HSV-1 positive (diagnosed 6 yrs ago) Julie: HSV-2 negative, HSV-1 positive Further Information Julie seeks treatment for a UTI Julie and Kieran are not aware that HSV can be transmitted from an infected mother to a baby during the birth process They are also unaware of the possible consequences of neonatal herpes How would you advise them? C O Connor & B HattenIWSML May 2015

66 Case study 4 Gina Gina is a 24-year-old woman who suffers with recurrent thrush, diagnosed by another doctor She has been self treating using OTC anti-fungal products She comes to you complaining that the symptoms keep recurring Physical examination Vulvalskin is reddened Several small fissures on the labia SliGenital Herpest vaginal discharge Oral temperature 37.5 o C Further information Gina has been in a stable, monogamous relationship for the past 2 years and has had no prior sexual relationships Gina has had several episodes of cystitis over the past few years, with a particularly severe episode about 18 months ago What is your provisional diagnosis?

67 What further tests would you perform? Swab from vaginal wall for gram staining and microscopy Vaginal swab for bacterial/fungal culture HSV PCR HSV type-specific serology Mid stream urine for microscopy/dipstick test/bacterial culture First pass urine for gonorrhoea/chlamydia PCR testing Serology for HIV, HBV, syphilis Fasting plasma glucose

68 Positive for Candida glabrata Viral swab PCR HSV-1 negative HSV-2 positive Type-specific serology HSV-1 negative HSV-2 positive All other tests negative Results What treatment would you recommend?

69 Counselling What would you advise Gina? Should she tell her partner she is HSV-2 positive? Should she ask her partner his HSV status? Should she ask her partner to undergo serological testing?

70 Case study 5 Ben Ben is a 32 year old labourerwith a 2 year history of Genital Herpes Ben is seeking your advice regarding how to best manage his Genital Herpes What questions do you ask during the consultation?

71 Initial history Ben has 4-6 episodes per year Symptoms last 4-5 days and are severe Ben is bisexual He does not think he has much risk of getting HIV as he only has oral sex with male partners What else would you ask/ do?

72 Clinical examination Action taken No lesions, erythema, discharge or other abnormalities observed Ben is asymptomatic at the time of consultation Full STI screen undertaken Ben asked to return when symptomatic Ben s original GP confirms diagnosis of HSV-2 by PCR 2 years ago Was treated with valaciclovir

73 HSV management Ben returns 2 weeks later with small ulcers on his thigenital Herpess HSV infection is confirmed by PCR Results of STI screen -All negative apart from HSV What treatment regimen would you recommend? What else would you counsel Ben on?

74 16 Marsden Street, Camperdown Down from RydgesHotel on Missenden Road Core clinical business STI & HIV testing & management Free counselling service No Medicare card required; free & confidential Assistance with contact tracing (especially for HIV) Happy to receive referrals & provide telephone advice Ph