3/15/2017 Disclosures I have no disclosures. Herpesviruses 38 th - PDF document

3/15/2017 Disclosures  I have no disclosures. Herpesviruses 38 th Annual Advances in Infectious Diseases March 2017 Jennifer Babik, MD, PhD Assistant Clinical Professor Division of Infectious Diseases, UCSF Learning Objectives Common Herpesviruses in Clinical Practice 1. To recognize the key clinical features of the most common herpes virus infections seen in the inpatient and outpatient setting. 1. To develop a framework for diagnosis and HSV ‐ 1, HSV ‐ 2 management of common herpes virus infections VZV EBV CMV 1

3/15/2017 Case #1 The next best test is: A 28 year old man presents 1. Throat swab for VZV DFA with fever and severe sore throat after returning from 1. Throat swab for HSV culture his honeymoon. He has mild anterior cervical LAN and the oral exam shown. The 2. Throat swab for CMV PCR rest of his exam is normal. Tests for Group A Strep, 3. Tonsillar biopsy to r/o lymphoma acute HIV, and EBV are negative. Photo courtesy of Matt Russell. Oral HSV: Primary Infection Case #2  Children/young adults, HSV ‐ 1 A 30 year old man presents to clinic complaining of “fever  Symptomatic in 10 ‐ 30%: blisters” for the past 24 hours.  Gingivostomatitis He has moderate pain but  Pharyngitis/tonsillitis ‐ may not have vesicles! mostly feels a great degree of  Systemic sx (can look like mono) stress and embarrassment  Duration of symptoms 10 ‐ 14d about the lesions. This is his 5 th  Oral antivirals  duration of symptoms episode in the last year.  Acyclovir 200mg PO 5x/day (7 days)  Famciclovir 500mg PO bid (7 days)  Valacyclovir 1gm PO bid (7 days) Ardino and Porter, J Oral Pathol Med 2008; 37:107. McMillan et al, Pediatr Infect Dis J 1993; 12:280. Ireland, Oxford Dictionary of Dentisty 2010. Cernik et al, Arch Intern Med 2008; 168:1137. Photo courtesy of Laura Pincus. 2

3/15/2017 Oral antivirals Recurrent Oral HSV: Herpes Labialis  Almost always HSV ‐ 1 1. Shorten the time for lesions to heal  Recurrences in 20 ‐ 40% of HSV ‐ 1 (+) 2. Are effective as suppressive therapy  1.5 recurrences/year  Triggers: 3. Both #1 and #2  Fever, URI  UV light exposure (sun)  Emotional stress, fatigue 4. Have no treatment effect  Immunosuppression  Oral/facial surgery or trauma  Menstruation Cernik et al, Arch Intern Med 2008; 1168:1137. Ardino and Porter, J Oral Pathol Med 2008; 37:107. Oral HSV Reactivation in Immunocompromised Oral HSV: Treatment Episodic therapy   time to heal by 0.5 ‐ 2.5 days (does not abort lesions)  Antivirals:  Acyclovir 200mg PO 5x/day x 5 days  Famciclvoir 1500mg PO x 1  Valacyclovir 2gm PO bid x 1 day Suppressive therapy   recurrences by 40 ‐ 50% (if ≥ 4 ‐ 6 recurrences/year)  Not known if can  oral HSV ‐ 1 shedding or transmission  Antivirals:  Acyclovir 400mg PO bid  Famciclovir 500mg PO bid  Valacyclovir 500 ‐ 1000mg PO daily Cernik et al, Arch Intern Med 2008; 168:1137. 3

3/15/2017 Oral HSV: Take Home Points Case #3  Primary HSV ‐ 1 can be a cause of pharyngitis in young A 22 year old man has fever, adults (and may not present with vesicles) lymphadenopathy, and painful blisters at the base of his penis.  HSV PCR of a lesion is the most sensitive diagnostic He is diagnosed with primary test for mucocutaneous herpes infections genital herpes. HSV ‐ 2 is detected  Oral antivirals have a modest treatment effect: they on culture of one of the lesions. can shorten healing time and be used as suppressive He wants to know how likely this is therapy to prevent recurrences to recur in the next 12 months. Photo courtesy of Laura Pincus. The likelihood of recurrence in the next 12 mo: Genital Herpes: Epidemiology and Transmission  HSV ‐ 1 versus HSV ‐ 2: 1. 10%  HSV ‐ 1 now accounts for >50% of 1 ˚ GH  HSV ‐ 1 = HSV ‐ 2 clinically 2. 30%  But HSV ‐ 2 recurrence rate is  3. 50%  Most transmission occurs from:  People unaware they have GH (<25% know they have it) 4. >70%  Asymptomatic shedding (25% of days) Bernstein et al, Clin Infect Dis 2013;56:344. Gupta et al, Lancet 2007; 370:2127. Horowitz et al, J Amer Coll Health 2010; 59:69. Mark et al, J Infect Dis 2008; 198:1. Sacks et al, Antiviral Res 2004; 63S1:S19.. 4

3/15/2017 Recurrent Genital Herpes Genital HSV: Diagnostics HSV primary % with a recurrence # recurrences Test Sensitivity Specifcity Important points in 1 st year infection within 1 year Culture Vesicle 70 ‐ 90% 100% Moderate sensitivity Ulcer 30 ‐ 40% Takes 1 ‐ 2 days HSV ‐ 1 20 ‐ 50% 1 Crusted 20 ‐ 30% HSV ‐ 2 70 ‐ 90% 4 ‐ 5 DFA Vesicle 70 ‐ 90% 99% Rapid (hours) Slight  sensitivity c/w culture Ulcer 30% *Another strong predictor of recurrence risk is Crusted 10% severity of primary infection PCR ~90% overall 99% Most sensitive test if available Classic “scalloped” border Mosely et al, J Clin Microbiol 1981; 13:913. Wald et al, J Infect Dis 2003; 188:1345. Van Wagoner and Hook, Curr Infect Dis Rep 2012; Benedetti et al, Annals Int Med 1994; 121:847. Benedetti et al, Annals Int Med 1999; 131:14. Photo courtesy of Laura Pincus 14:175. Lafferty et al, J Clin Microbiol 1987; 25:323. Screening for HSV ‐ 2 By Serology? Treatment Regimens: First episode  New 2016 US Preventative Task Force Recs  No!  Efficacy   duration of symptoms by 2 ‐ 4 days  Why not?  No impact on recurrence rate  Sensitivity 99% but specificity only 83%  As many false positives as true positives  Regimens  Acyclovir 400mg PO tid or 200mg PO 5x/day (7 ‐ 10 days)  When might serology be useful?  Valacyclovir 1gm PO bid (7 ‐ 10 days)  Recurrent genital symptoms and ( ‐ ) HSV cultures/PCR  Famciclovir 250mg PO tid (7 ‐ 10 days) USPSTF, JAMA 2016, 316:2525. CDC, STD Treatment Guidelines 2015. Mertz et al, JAMA 1984; 252:1147. 5

3/15/2017 Episodic Therapy: Recurrent Episodes Suppressive Therapy for Genital Herpes Efficacy :  Efficacy:  Start in prodrome or <1 day of symptoms   recurrences by 70 ‐ 80% and  shedding   transmission to negative partner by ~50% (but absolute RR of ~2%)  Can abort lesions in 20 ‐ 30% or  symptoms by 1 ‐ 2 days  Does not reduce rate of transmission to uninfected partners  When to use?  CDC: consider if “frequent” episodes (? ≥ 6) or discordant couples Regimens  SF City Clinic: offers to most with a new diagnosis of HSV ‐ 2  Acyclovir 400mg PO tid or 800mg PO bid (5 days)  Acyclovir 800mg PO tid (2 days)  Antivirals:  Valacyclovir 500mg PO bid (3 days)  Acyclovir 400mg bid, famciclovir 250mg bid, valacyclovir 500 ‐ 1000mg daily  Valacyclovir 1gm PO daily (5 days)  Discuss a trial off therapy qyear  Famciclovir (options for 1, 2, 5 days) CDC, STD Treatment Guidelines 2015. Strand et al, Sex Transm Infect 2002; 78:435. CDC, STD Treatment Guidelines 2015. Corey et al, N Engl J Med 2004; 350:11. Genital Herpes: Take Home Points Case #4  HSV ‐ 1 and HSV ‐ 2 are clinically identical, but HSV ‐ 2 is 55 year old man is brought in by his neighbor for bizarre behavior for 12 much more likely to recur hours. He is found to be febrile and has a witnessed seizure in the ED.  Most transmission occurs in patients who are MRI is shown. He is started on asymptomatic or are unaware they have genital herpes vancomycin, ceftriaxone, and acyclovir and is tapped 24 h later.  HSV culture and DFA are the diagnostic methods of choice Lumbar puncture:  Oral antivirals can shorten symptom duration, abort  50 WBC (89% lymphs), 50 RBC, protein 80, glucose 78 lesions entirely, and can be used as suppressive therapy  CSF culture is NGTD to decrease the number of recurrences as well as  PCR is negative for HSV and VZV transmission 6

3/15/2017 What Would You Do With His Antibiotics? The HSV PCR May Be Negative Because: 1. Stop acyclovir 1. He got 24 hours of acyclovir 2. Change acyclovir to ganciclovir 2. It’s not a sensitive test 3. Continue acyclovir 3. It’s early in the disease course HSV Encephalitis HSV Encephalitis: Diagnosis and Rx  Epidemiology/Clinical:  CSF PCR:  96% sensitive, 99% specific  Accounts for 10 ‐ 20% of encephalitis  May have false ( ‐ ) in the first 3d  if suspicion is high re ‐ tap  >90% due to HSV ‐ 1, most reactivation (HSV2 rare, in ICH)  ACV has little effect on PCR (+) within the first 5 days of therapy  Fever, personality change, seizures, focal neuro findings  MRI: temporal/frontal lobe involvement in 90%  CSF studies:  WBCs: lymphocytic pleocytosis (median 130 cells) Can be normal in  RBCs: elevated <500  Treatment: up to 15%  Mildly  protein (median 80 mg/dl), normal glucose  ACV 10mg/kg IV q8h x 14 ‐ 21 days  Can check HSV PCR at d14 to define duration Whitley et al, JAMA 1982, 247:312. Whitley et al, JAMA 1989, 262:234. Tang et al, Clin Infect Dis 1999, 29:803. Domingues et al, DeBiasi and Tyler, Clin Microbiol Rev 2004, 17:903. Tyler, Herpes 2004, 11 Suppl 2: 57A Clin Infect Dis 1997, 25:86. 7