Infectious Genital Lesions (The Sores and More)

Transcription

1 Infectious Genital Lesions (The Sores and More) Nicholas Van Wagoner, MD PhD, FACP Associate Professor of Medicine Disclosures Research Funding Genocea Biosciences Vical, Inc Consulting Genocea Biosciences Will not discuss off-label use of commercial products and/or services Accurately identify patients at risk for Genital Herpes, Syphilis and Human Papillomavirus and then test, diagnose, and treat according to CDC STD Treatment Guidelines

2 Case 1: 27 year old male graduate student Colleague asks you to see him Patient has a rash on his genitals for 2 days. Has had some muscle aches and fevers over the last week Married 6 months ago Wife had no sex partners prior to him Reports casual female partners in the past, intermittent condom use Our patient: Cluster of vesicles at the base of the penis You re pretty sure it s genital herpes He asks you what it is. What do you do? A. Tell him you re not sure. You will run some tests and get back to him. B. Tell him you re not sure. Go find your colleague and make him tell the patient. C. Tell him you suspect that it is genital herpes and that he must have been infected by his wife. D. Tell him that you suspect that it is genital herpes and that you would like to run some tests to confirm the diagnosis.

3 He asks you how long you think he s had it. You say A. I have no idea. B. The tests that I send may help us understand if you were recently infected or if you have had it for a while. C. You must have just been infected because this is the first time that you ve had symptoms. What else do you do at this visit? A. What tests do you run? B. How do you counsel the patient? A. If my wife isn t infected, how do I protect her from getting it? B. I can only give it to her when I have lesions, right? C. What do you prescribe for his outbreak? Seroprevalence of HSV-2, NHANES, Overall Seroprevalence of HSV-2 (Ages 14-49): 12.1% Women: 15.9% Men: 8.2% SEROPREVALENCE OF HSV-2 BY AGE McQuillian et al. NCHS Data Brief

4 Seroprevalence of HSV-2, NHANES, Overall Seroprevalence of HSV-2 (Ages 14-49): 12.1% Women: 15.9% Men: 8.2% Trends in HSV-2 among persons by race and Hispanic Origin McQuillian et al. NCHS Data Brief HSV-2 Trends By Race Disparities Are Increasing Women Men Fanfair, R, et al. STD : HSV Risk Biology Gender Race Male Circumcision Age Sociodemographics Income Living conditions Sexual Networks Race Behavior No. of Partners Early Sexual Debut Condom Use Xu et al., JAMA : Newman, STD :S4-S12.

5 Causes of Genital Herpes Herpes Simplex Virus 2 Herpes Simplex Virus 1 Anogenital Herpes Caused by HSV-1 Anogenital herpes caused by HSV-1 is common Younger MSM Younger heterosexual women Why the shift toward more HSV-1 anogenital herpes? Reduced childhood acquisition Increase in oral sex Clinical manifestations of HSV-2 and HSV-1 genital herpes are the same Ryder et al. Sex Transm Infect : Bernstein et al. CID : Looker et al. Lancet Glob Health (epub). Asymptomatic Infection Gupta et al. Lancet :

6 Asymptomatic Infection Sexual Transmission Exposure Vaginal Penile Anal Oral (HSV-1) Efficiency of transmission: greater from men to women Gupta et al. Lancet : Asymptomatic Infection When symptomatic at time of initial infection Local 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 Systemic Symptoms Last 2-4 weeks Fever, headache, malaise, myalgias Gupta et al. Lancet : Asymptomatic Infection Gupta et al. Lancet :

7 Asymptomatic Infection Symptomatic Recurrence Disease is milder and shorter in duration Antibody to HSV-2 present Prodrome Lesions last 5-10 days No systemic symptoms HSV-2 is more prone to recur than HSV-1 Gupta et al. Lancet : Genital Herpes: Primary Outbreak, Ulcerative Phase Gnann and Whitley. NEJM : Genital Herpes: Recurrences Source: Cincinnati STD/HIV Prevention Training Center

8 Other presentations Linear Fissures Excoriation-like lesions Urethritis Proctitis Cervicitis Atypical Presentations Viral shedding occurs in the absence of symptoms Transmission occurs in the absence of symptoms Mark et al, JID 198: Detect the virus Viral culture HSV Tests Most sensitive when lesions are in the vesicular-pustular stage Nucleic Acid Amplification User Friendly More Sensitive Detect Antibodies to the virus Type specific IgG tests should be used Presence of HSV-2 antibody indicates anogenital infection Presence of HSV-1 does not distinguish anogenital from orolabial infection.

9 Back to our case NAAT from a swab of the ulcer is positive for HSV-2 Type specific antibody tests for HSV-1 and HSV-2 are negative. A. This was his primary outbreak. He was most likely infected recently B. This was a recurrence. He has likely been infected for a long time Diagnosing Genital Herpes Infection Type First episode, Primary (Type 1 or 2) First episode, Nonprimary Type 2 First episode, Recurrence Type 2 Symptomatic, Recurrence Type 2 Asymptomatic, Infection Type 2 Lesions/ Symptoms +/Severe, bilateral Viral Culture or NAAT Type-specific antibody at time of presentation HSV-1 HSV /Moderate /Mild + +/- + +/Mild, unilateral + +/ /- + How we use genital herpes therapy Symptoms Suppression

10 Initial How we use genital herpes therapy Gnann and Whitley. NEJM : Acyclovir: 400 mg 3 times a day for 7-10 days or 200 mg 5 times a day for 7-10 days Valacyclovir: 1 g twice a day for 7-10 days Famciclovir: 250 mg 3 times a day for 7-10 days Symptoms Episodic Acyclovir: 400 mg 3 times a day for 5 days or 800 mg twice a day for 5 days or 800 mg 3 times a day for 2 days Valacyclovir: 500 mg twice a day for 3 days or 1 g once a day for 5 days Famciclovir: 125 mg twice a day for 5 days or 1 g every 12 hr for 2 doses or 500 mg for 1 dose followed by 250 mg twice a day for 2 days. How we use genital herpes therapy Gnann and Whitley. NEJM : Recurrences Acyclovir: 400 mg twice a day Valacyclovir: 500 mg once a day or 1 g once a day Famciclovir: 250 mg twice a day Suppression In pregnancy Beginning at 36 weeks gestation Acyclovir: 400 mg 3 times a day Valacyclovir: 500 mg twice a day State of the Art in Genital Herpes Prevention Condoms reduce transmission from men to women (96%). Condomless sex is associated with increased acquisition of genital herpes. Consistent condom use lowers risk for HSV-2 acquisition by 30%. Wald et al. JAMA : Stanaway et al. STD : Maragaret. CID :

11 Back to The Case Presented with new HSV-2 infection and his initial outbreak Severity of symptoms Presence of HSV-2 in lesion and absence of antibody to HSV-2 Prescribed Valacyclovir 1 gm bid for 10 days at initial visit Placed on suppressive therapy (given prescription for recurrence treatment) Ongoing counseling Case #2 A 33 y.o. AAM with well-controlled HIV presents with right upper quadrant abdominal pain, jaundice and skin rash. He denies alcohol, acetaminophen use. He and his ex-girlfriend reunited and started having sex 4 weeks ago. His labs show abnormal liver function tests (elevated alkaline phosphatase (727 IU/ml) and a bilirubin of 7.2. Hepatitis A, B, and C serologies are negative. The patient was hospitalized for further evaluation of his liver. Which of the following tests will provide the diagnosis? a. Abdominal Ultrasound b. RPR c. Tylenol Level d. TP-PA e. Alcohol Level

12 Which of the following tests will provide the diagnosis? a. Abdominal Ultrasound b. RPR c. Tylenol Level d. TP-PA e. Alcohol Level 1:512 Treated with PCN and symptoms resolved. Treponema pallidum Morphology Spiral, 8-13x0.15 µm Motility Corkscrew, Flexing Electron Micrograph Dark Field Microscopy Dark Field Microscopy

13 Syphilis Reported Cases by Stage of Infection, United States, Primary and Secondary Syphilis by State, United States and Outlying Areas, Primary and Secondary Syphilis by County, 2017 Syphilis rates are increasing in Florida 16.2/100,000 in /100,000 in

14 Primary and Secondary Syphilis, Reported Cases by Sex and Sexual Behavior Cases are increasing over time Majority of cases are in MSM, Rates of Congenital Syphilis are Increasing Pathology Penetration Enters via skin and mucous membranes through abrasions during sexual contact Transplacentally from mother to fetus Dissemination Via the lymphatics to regional lymph nodes and then hematogenously Can invade the CNS at any stage.

15 Natural History 20-30% Secondary Syphilis Skin Rash Fever Generalized Lymphadenopathy Inoculation Primary Syphilis (Chancre) Chancre resolves Secondary Syphilis resolves Tertiary Syphilis Gummas Aortitis CNS vasculitis General paresis Tabes Dorsalis 2-6 weeks Yea r 3-5 nth Mo 1+ We ek We ek 0 Da y= ~D a (1 0 y day s) 2-6 weeks Primary Syphilis Chancre Painless ulcer with heaped up borders Regional lymphadenopathy common Occurs at site of primary inoculation Heals in 2-6 weeks CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides, Used with permission from Jeff Hill, DMD Secondary Syphilis Skin Rash (can vary in presentation) Widespread & symmetric Pink, coppery, dusky red Macular or papular Non pruritic Indurated Superficial scale Fever Generalized lymphadenopathy

16 Secondary Syphilis Palmar Rash Nickel/Dime Lesions Plantar Rash Alopecia Secondary Syphilis Mucus Patches Other Manifestations Meningitis Iritis/Anterior Uveitis Condyloma Lata Hepatitis Periostitis Nephropathy/Nephrotic Syndrome Latent Syphilis No lesions present Positive serologic tests May occur Between primary and secondary stages Between secondary relapses After secondary stage Early Latent Infection less than 1 year Late Latent Infection for 1 year or more

17 Diagnosing Syphilis Involves 2 Types of Tests Nontreponemal Antibody Tests Antibody against lipoidal proteins Indicate active treponemal infection Used to evaluate response to therapy Tests Rapid plasma reagin (RPR) test Venereal Disease Research Laboratory (VDRL) test Treponemal Antibody Tests Antibody against T. pallidum May persist for life Cannot be used to evaluate response to therapy Tests T. pallidum particle agglutination (TP-PA) test Fluorescent treponemal antibody absorbed (FTA-ABS) test Traditional Syphilis Screening Algorithm Detects active infection False positives occur Confirm with treponemal test Use of both tests = high PPV Can miss early primary and untreated infection

18 RPR/VDRL in treatment Error of RPR/VDRL Tests dilution Meaningful change is 2 dilution (or 4-fold) change in titer 1:2 à 1:4 or 1:1, no meaningful change 1:2 à 1:8, meaningful change Quantitative RPR or VDRL test results are not interchangeable Two dilution decline in titer indicates response to therapy however, failure to decline > 2 dilutions does not necessarily mean patient has failed treatment Primary and Secondary Syphilis Benzathine penicillin G 2.4 million units IM as a single dose Second Line Agents (Limited data) Doxycycline 100 mg BID for 14 days Tetracycline 500 mg QID for 14 days Ceftriaxone 1 gm daily IM or IV for days Azithromycin 2 gm once Use with caution (may lead to resistances) Do not use in MSM, HIV+, or pregnant women STD Treatment Guidelines Treatment of Latent Syphilis Early Latent Acquired syphilis in the preceding year Documented seroconversion or 4 fold increased in nontreponemal test Unequivocal symptoms of primary or secondary syphilis Sex partner documents having primary, secondary or early latent syphilis Benzathine Penicillin G 2.4 million units IM in a single dose Late Latent Seropositive for syphilis Absence of criteria for early latent disease Benzathine Penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1- week intervals

19 Treatment Follow Up Clinical and serologic evaluation 6 and 12 months after treatment Consider failure (versus reinfection) if: Persistent/Recurrent signs or symptoms Failure to achieve a 4 fold reduction in nontreponemal titer If failure occurs Test for HIV Re-treat if close follow up can t be guaranteed Consider CSF examination Management of Sex Partners Evaluate anyone exposed sexually to the patient (at any stage of disease) Treat presumptively Persons exposed within the preceding 90 days to someone diagnosed with primary, secondary or early latent syphilis. Persons exposed >90 days before the diagnosis of their sex partner if serologic test results are not available immediately/follow up is uncertain. Treat partners based on serological results Long-term sex partners of patients with latent syphilis Case A 23-year-old woman requests HPV vaccination. She reports sex with both men and women with 5 sex partners in the last year. She is tested annually for STI's and HIV. She tested positive for chlamydia 2 years ago and was treated with Azithromycin 1 gm. All STI tests were negative at her last screening 6 months ago. What is the best next step? A. Do not vaccinate. She is too old to receive the vaccine. B. Do not vaccinate. She has likely already been exposed to HPV and vaccination is not indicated. C. Test for presence of HPV using a vaginal swab. If HPV is present, do not vaccinate. D. Vaccinate.

20 Human Papillomavirus >100 types Over 40 anogenital types oncogenic types HPV 16 (54%) and HPV 18 (13%) account for the majority of cervical cancers. 5 Nononcogenic types HPV 6 and 11 are most often associated with external anogenital warts. 3 Nonenveloped double-stranded DNA virus 1 1. Howley PM. In: Fields BN, Knipe DM, Howley PM, eds. Fields Virology. 4 th ed. Philadelphia, Pa: Lippincott-Raven; 2001: Reprinted with the permission of Lippincott-Raven. 2. Schiffman M, Castle PE. Arch Pathol Lab Med. 2003;127: Wiley DJ, Douglas J, Beutner K, et al. Clin Infect Dis. 2002;35(suppl 2):S210 S Muñoz N, Bosch FX, de Sanjosé S, et al. N Engl J Med. 2003;348: Clifford GM, Smith JS, Aguado T, Franceschi S. Br J Cancer. 2003:89; HPV Transmission and Prevalence Sexual contact Genital genital, anal-genital, manual genital, oral genital Nonsexual routes Mother to newborn (vertical transmission; rare) Prevalence of any genital HPV among adults aged NHANES Anogenital Warts and Their Treatment Comparison of Treatments for Genital Warts*,1 Treatment Clearance Rate (%) Risk of Recurrence (%) Cryotherapy Imiquimod Interferon Laser treatment Podofilox Podophyllin resin Images top left and top right: Reprinted with permission from NZ DermNet ( Surgical excision Trichloroacetic acid

21 Incidence of Select HPV-Related Disease Cases of cervical cancer Cases of cervical dysplasia Cases of Genital warts Cases of infection Natural History of High-Risk HPV Infection and Potential Progression to Cervical Cancer 1,2 ~1 Year Transient Infection Cleared HPV Infection HPV Infection Over 2 Years Persistent Infection 2 5 Years Low-Grade Dysplasia CIN Years High-Grade Dysplasia CIN 2/ Years Invasive Cancer Adapted from: 1. Pagliusi SR, Aguado MT. Vaccine. 2004;23: Pinto AP, Crum CP. Clin Obstet Gynecol. 2000;43: HPV Vaccination is highly effective Women should be offered HPV vaccine as per current guidelines. Routine cervical cancer screening should be offered to all women, regardless of sexual orientation or sexual practices. Vaccinate girls year old (may start as early as age 9) Vaccinate girls and women who have not started or completed the vaccine series STD Treatment Guidelines 2015

22 Estimated vaccination coverage with selected vaccines and doses among adolescents aged years, by survey year National Immunization Survey-Teen, United States, Source: MMWR August 25, 2017 *Estimated coverage with 1 dose of human papillomavirus (HPV) vaccine among adolescents aged years, National Immunization Survey Teen (NIS Teen), United States, 2016 Source: MMWR August 25, 2017 Vaccinate boys year old (may start as early as age 9) Vaccinate boys and men who have not started or completed the vaccine series Vaccinate immunocompromised males (including those with HIV) through age 26 Vaccinate MSM through age 26 STD Treatment Guidelines 2015 HPV vaccination is the best way to protect your children from cancers caused by HPV : 2-dose HPV vaccination schedule introduced. Percent Vaccinated : HPV vaccine routinely recommended for boys : HPV vaccine routinely recommended for girls Girls: 1 dose of HPV vaccine Boys: 1 dose of HPV vaccine Girls and boys: 1 dose of HPV vaccine INFECTIONS WITH HPV TYPES THAT CAUSE MOST HPV CANCERS AND GENITAL WARTS HAVE DROPPED 71 PERCENT AMONG TEEN GIRLS 6 OUT OF10 parents are choosing to get the human papillomavirus vaccine for their children CDC RECOMMENDS THE HPV VACCINE AT AGES Talk to your child s doctor about HPV cancer prevention HPV vaccination is the best way to protect your children from cancers caused by HPV Percentage of adolescent boys and girls who have received one or more doses of HPV vaccine * CDC RECOMMENDS THE HPV VACCINE AT AGES Talk to your child s doctor about HPV cancer prevention DC NATIONWIDE 6 OUT OF10 parents are choosing to get the human papillomavirus vaccine for their children. National coverage is 60% Coverage by state: 49% or less 50-59% 60-69% 70% or greater NCIRDig604 August 25, 2017 U.S. Department of Health and Human Services Centers for Disease Control and Prevention

23 Accurately identify patients at risk for Genital Herpes, Syphilis and Human Papillomavirus and then test, diagnose, and treat according to CDC STD Treatment Guidelines Questions: