Nothing to disclose.

Transcription

1 Update on Diagnosis and Treatment Lisa Winston, MD University of California, San Francisco/ Zuckerberg San Francisco General Nothing to disclose. 1

2 This talk will be a little depressing Rising incidence of many STDs Increasing antibiotic resistance gonorrhea Clusters of complications syphilis Success of PrEP and advances in HIV treatment are positives! CDC 2015 STD surveillance report Total combined cases of chlamydia, gonorrhea, and syphilis reached the highest number ever reported in the U.S. Yet, not that long ago, gonorrhea rates were at historic lows, syphilis was close to elimination, and we were able to point to advances in STD prevention, such as better chlamydia diagnostic tests and more screening, contributing to increases in detection and treatment of chlamydial infections. That progress has since unraveled. Gail Bolan, MD, Director, Division of STD Prevention, CDC, published October 19, 2016 Situation worse in

3 Outline organisms and syndromes Gonorrhea Chlamydia Trichomonas Urethritis Syphilis Genital HSV Emerging STDs Gonorrhea CDC 2016 STD Surveillance Report 3

4 Gonorrhea CDC 2016 STD Surveillance Report Gonorrhea CDC 2016 STD Surveillance Report 4

5 Gonorrhea Second most commonly reported communicable diseases Chief complication in women tubal scarring Infertility and ectopic pregnancy Screening Sexually active women < 25 years annually Women 25 years and older with New sex partner, more than one partner, partner with concurrent partners, partner with STI Sexually active MSM at least annually Urethral, rectal, oropharyngeal depending on sex practices Gonorrhea diagnostic testing Culture and nucleic acid amplification testing (NAAT) NAAT FDA approved for women Endocervical swab Vaginal swab self or clinician collected First catch urine NAAT FDA approved for men Urethral swab First catch urine 5

6 Gonorrhea Culture provides susceptibility information Endocervical (women) Urethral (men) Rectal Oropharyngeal Conjunctival Many laboratories have met CLIA requirements to perform NAAT on rectal and oropharyngeal specimens Gonorrhea newly scary 6

7 Failure of dual antibiotic therapy in the treatment of gonorrhea June 23, 2016 Correspondence from UK regarding gonorrhea in a MSW infected in Japan Treatment failure after ceftriaxone 500 mg IM plus azithromycin 1 g PO Isolate resistant to ceftriaxone, azithromycin, cefixime, cefotaxime, penicillin, tetracycline, ciprofloxacin Susceptible to spectinomycin Gonorrhea resistance to azithromycin Gonococcal isolates collected at Public Health Seattle & King County STD Clinic : no azithromycin resistance in 292 isolates collected from 263 patients From : 5% of isolates from MSM with reduced susceptibility to azithromycin Clin Infect Dis 2017; 7

8 Gonorrhea preferred treatment Cervix, urethra, rectum, pharynx: Ceftriaxone 250 mg IM in a single dose Plus Azithromycin 1 g orally in a single dose Gonorrhea alternative regimens Preferred (not pharyngeal): Cefixime 400 mg orally in a single dose Plus Azithromycin 1 g orally in a single dose Other possible regimens Gemifloxacin 32o mg PO + Azithromycin 2 g PO Gentamicin 240 mg IM + Azithromycin 2 g PO * National shortage of gemifloxacin continues 8

9 Expedited partner therapy (EPT) As permitted by law EPT gonorrhea CDC recommends for heterosexual partners if inperson treatment impractical Cefixime 400 mg PO + Azithromycin 1 g PO Educational materials Not currently recommended for MSM due to high risk co existing infections (especially HIV) and lack of data 9

10 Chlamydia CDC 2016 STD Surveillance Report Chlamydia Most frequently reported communicable disease Highest rates in those < 25 years Chief complications in women infertility and ectopic pregnancy Screening similar to GC Sexually active women < 25 years annually Women 25 years and older with New sex partner, more than one partner, partner with concurrent partners, partner with STI Sexually active MSM at least annually Urethral, rectal (but not oropharyngeal) depending on sex practices 10

11 Chlamydia Mostly diagnosed by NAAT most sensitive, recommended FDA approved for women Endocervical swab Vaginal swab self or clinician collected, optimal urogenital specimen First catch urine FDA approved for men Urethral swab Urine, optimal urogenital specimen Some laboratories have met CLIA requirements to perform NAAT on rectal and oropharyngeal specimens Some NAATs detect both GC and chlamydia from the same specimen Self collected rectal swabs are acceptable Some NAATs are FDA approved for liquid cytology Chlamydia treatment Recommended regimens Azithromycin 1 g orally as a single dose Doxycycline 100 mg orally twice a day for 7 days Equally efficacious, except azithromycin may be less efficacious for rectal infections Alternative agents include erythromycin, levofloxacin, and ofloxacin EPT same considerations as for GC; use recommended oral regimen 11

12 Chlamydia follow up Test of cure not routinely recommended Reinfection is common Retest women and men diagnosed with chlamydia infection approximately 3 months after treatment, irrespective of partner treatment Trichomonas Most prevalent, non viral STD Racial disparities: female NHANES participants ages 14 49, nationally representative sample, self collected vaginal swab Non Hispanic white women 1.3% Mexican American women 1.8% Non Hispanic black women 13.3% Sutton et al, Clin Infect Dis 2007;45(10): Associated with pre term birth, low birth weight, enhanced HIV transmission 12

13 Trichomonas diagnostic testing Testing primarily in women with vaginal discharge Consider screening in high risk settings lack of data Uncommon in MSM NAAT is highly sensitive and specific In women, can be performed on vaginal, endocervical, and urine specimens Antigen detection and DNA hybridization probe tests are also available Wet mount microscopy is inexpensive and may be convenient Low sensitivity Incidental finding on Pap test not considered diagnostic False positives and negatives Trichomonas treatment Recommended regimens Metronidazole 2 g orally as a single dose OR Tinidazole 2 g orally as a single dose Alternate: metronidazole 500 mg twice daily for 7 days Concurrent treatment of all sex partners 13

14 Trichomonas treatment Resistance is an emerging issue Treatment failure If single dose metronidazole used initially, treat with metronidazole 500 mg twice daily for 7 days If above fails, consider metronidazole or tinidazole 2 g daily for 7 days CDC can facilitate resistance testing High dose tinidazole x 14 days with intravaginal tinidazole can be considered Trichomonas follow up High rate of reinfection among treated women Repeat testing within 3 months recommended, regardless of sex partner treatment Insufficient data regarding retesting in men 14

15 Urethritis male Urethral inflammation Dysuria, urethral pruritis, urethral discharge Steps in work up Evaluate for gonorrhea and chlamydia urine NAAT Confirm inflammation Exam for urethral discharge Gram stain, if available, of urethra secretions look for WBC and Gram negative intracellular diplococci (specific for GC) First void urine to evaluate for pyuria Consider trichomonas in MSW; NAAT not FDA approved but validated by many labs Urethritis male Non gonococcal urethritis (NGU) non specific diagnosis when inflammation present Mycoplasma genitalium accounts for a significant proportion of cases About 30% when persistent or recurrent NAAT is preferred test but not FDA approved, limited availability Doxycycline usually not effective Resistance to azithromycin emerging 15

16 NGU therapy Recommended: Azithromycin 1 g orally in a single dose OR Doxycycline 100 mg twice daily for 7 days Alternate: erythromycin, levofloxacin, ofloxacin all for 7 days Moxifloxacin 400 mg daily for 7 14 days may be successful for M. genitalium Syphilis CDC 2016 STD Surveillance Report 16

17 Syphilis CDC 2016 STD Surveillance Report Syphilis CDC 2016 STD Surveillance Report congenital syphilis cases 17

18 Syphilis increased concern Clusters of ocular syphilis in Seattle and San Francisco 12 cases included in report 11/12 male 10/12 with HIV 4 with persistent visual deficits; 2 legally blind Recent U.S. increase in congenital syphilis 2014 rate highest in more than a decade Increase most marked in West Continued to increase in 2015 MMWR 2015;64(40): MMWR 2015;64(44): Syphilis Stages help guide treatment Primary/secondary and early latent Late latent and latent of unknown duration Neurosyphilis Tertiary without neurosyphilis now rare 18

19 Syphilis Primary ulcer or chancre at infection site Secondary skin rash, mucocutaneous lesions, lymphadenopathy Syphilis Latent no clinical manifestations, diagnosed by serology Early acquired within the preceding year Late or unknown all others Neurosyphilis Early cranial nerve abnormalities, meningitis, CVA, ocular, auditory Late tabes dorsalis and general paresis, usually years after infection Tertiary without neurosyphilis gumma, cardiovascular 19

20 Syphilis diagnosis Treponema pallidum cannot be cultured Early syphilis lesions direct tests not widely available Darkfield microscopy PCR Direct fluorescent antibody test Empirical treatment of early disease when suspicion high Most patients have no lesions Diagnosis is usually by serology Syphilis serologies Non treponemal antibodies React against lipoidal antigens such as cardiolipin Rapid plasma reagin (RPR) Venereal Disease Research Laboratory (VDRL) Treponemal antibodies React against specific T. pallidum antigens Fluorescent treponemal antibody absorbed (FTA ABS) Treponema pallidum particle agglutination (TP PA) Enzyme immunoassays (EIAs) Chemiluminescence immunoassays (CIAs) Microbead immunoassays 20

21 This image cannot currently be displayed. This image cannot currently be displayed. 2/7/2018 Syphilis serologies Non treponemal tests Quantitative reported with a titer Decline with treatment and with time Less specific false positives May be negative in early primary disease Treponemal tests Qualitative positive or negative Usually positive lifelong Ideally, more specific Both types of tests usually required Syphilis testing 21

22 This image cannot currently be displayed. 2/7/2018 Syphilis why switch to reverse testing sequence? Faster Lower cost if high volume No manual pipetting Reduce potential false negatives since no prozone phenomenon May be more sensitive for early syphilis; some tests detect IgM 22

23 Syphilis screening Pregnant women All at first visit Early in 3 rd trimester and at delivery if high risk MSM Annually if sexually active Every 3 6 months if increased risk HIV First evaluation Annually if sexually active Consider more frequently if increased risk Syphilis treatment Primary, secondary, and early latent Benzathine penicillin 2.4 million units IM in a single dose Late latent, latent of unknown duration, tertiary syphilis without neurosyphilis Benzathine penicillin 2.4 million units IM x 3 doses at 1 week intervals Neurosyphilis, including ocular Penicillin G million units per day, administered as 3 4 milliion units IV every 4 hours or as a continuous infusion, for days * National shortage of benzathine penicillin 23

24 Syphilis treatment Alternate regimen doxycycline 100 mg twice daily for 14 days can be considered for primary, secondary and latent disease Pregnancy desensitize and treat with penicillin Syphilis follow up Repeat non treponemal testing for up to 24 months to ensure 4 fold decline in titer Recommend testing schedule varies somewhat based on stage of disease More frequent testing with HIV; otherwise, management of persons with HIV is the same 24

25 This image cannot currently be displayed. 2/7/2018 Syphilis treatment of sex partners Prioritize testing and treatment of contacts to persons with primary, secondary, and early latent disease; usually not infectious after 1 year Presumptive treatment if contact within 90 days of diagnosis Genital herpes HSV 2 more common, especially when recurrent Overall, seroprevalence has decreased in those yrs : 21.2% : 15.5% HSV 1 also causes genital lesions, may account for increasing proportion in young people HSV 1 seroprevalence has decreased in adolescents years : 39% : 30.1% CDC 2016 STD Surveillance Report 25

26 This image cannot currently be displayed. 2/7/2018 Genital herpes Updated December 2016 USPSTF continues to recommend against routine serologic screening for genital HSV infection in asymptomatic adolescents and adults, including those who are pregnant Genital herpes diagnosis Direct testing of lesions PCR most sensitive Cell culture Immunofluorescence assay available but less sensitive Tzanck preparation no longer recommended, lacks sensitivity and specificity Serology Use type specific serology, IgG only Consider with diagnostic uncertainty or to assist with management when partner has genital herpes 26

27 Genital herpes treatment First episode Acyclovir 400 mg three times per day x 7 10 days Acyclovir 200 mg five times per day x 7 10 days Valacyclovir 1 g twice per day x 7 10 days Famciclovir 250 mg three times per day x 7 10 days Genital herpes treatment Recurrent episode Acyclovir 400 mg three times per day x 5 days Acyclovir 800 mg twice per day x 5 days Acyclovir 800 mg three times per day x 2 days Valacyclovir 500 mg twice per day x 3 days Valacyclovir 1 g once per day x 5 days Famciclovir 125 mg twice per day x 5 days Famciclovir 1 g twice per day x 1 day Famciclovir 500 mg once, followed by 250 mg twice daily x 2 days 27

28 This image cannot currently be displayed. This image cannot currently be displayed. This image cannot currently be displayed. 2/7/2018 Genital herpes suppression Reduces recurrences by 70 80% Long term safety and efficacy documented Suppressive therapy decreases transmission Condoms, avoidance of sexual activity with active lesions Recurrences usually diminish over time; consider discontinuation after a period of suppressive therapy Regimens Acyclovir 400 mg twice per day Valacyclovir 500 mg once per day Valacyclovir 1 g once per day Famciclovir 250 mg twice twice per day Emerging STDs Hepatitis C Ebola Zika 28