1. South Dakota STD Update Webinar – August 15, 2012 Kees Rietmeijer, MD, PhD Medical Director, Denver STD/HIV Prevention Training Center

2. A Man with a Faint Rash The 5-Minute STI Clinical Case Study

3. Case History 30 year-old gay man complaining of a faint, non- itching rash for >4 weeks Took left-over amoxicillin for sore throat about 1 month ago – however, pt. does not have a prior history of penicillin allergy No neurological symptoms or other physical complaints

4. Case History -Continued Sexual and STI History –2 partners in past 6 months: One steady partner One occasional partner (about 3 months ago) –Protected receptive and insertive anal sex with steady partner only –Unprotected oral sex with steady and occasional partners –No history of genital/rectal sores –Rectal gonorrhea and chlamydia > 1 year ago –History of primary syphilis – treated 4 years ago with 2.4 MU LAB –Most recent RPR: NR (14 months ago; this clinic –HIV: negative (14 months ago; this clinic)

5. Physical Exam Faint erythematous macular rash trunk and extremities Soles of feet involved, but palms of hands are not No excoriations or scratch marks noted No penile or anal lesions observed Neurological exam: normal

11. Question 1 What laboratory test would be the least useful in this case? a)Qualitative (stat) RPR b)Quantitative RPR c)Treponemal test (TPPA or FTA-abs) d)HIV rapid test e)HIV viral load

12. Stat Lab Results Qualitative RPR reactive: ++++ HIV Rapid Test: Positive

13. Question 2 Based on our knowledge so far, what is the most likely diagnosis? a)Acute HIV Infection b)Drug rash c)Secondary syphilis d)Scabies

14. Question 3 You decide to treat the patient for secondary syphilis – what do the CDC treatment guidelines recommend: a)LAB 2.4 MU i.m. now and refer to HIV care b)LAB 2.4 MU i.m. now and once a week for 2 subsequent weeks + refer to HIV care c)Patient should undergo LP before treatment is initiated d)Refer to HIV care as treatment will depend on HIV viral load and CD4 count

15. Question 4 Regarding the patient’s follow up – which is a CDC recommendation? a)Patient should return for follow-up at 1 and 2 weeks for additional treatment b)Serological follow-up should be more frequent than in HIV negative patients c)Follow-up should include a neurological work-up and LP to exclude neurosyphilis

17. Gonorrhea The Continuing Saga

18. Gonorrhea—Rates, United States, 1941–2010

19. Gonorrhea—Rates by State, United States and Outlying Areas, 2010 NOTE: The total rate of gonorrhea for the United States and outlying areas (Guam, Puerto Rico, and Virgin Islands) was 99.6 per 100,000 population.

22. Gonorrhea—Percentage of Reported Cases by Sex and Selected Reporting Sources, United States, 2010 * HMO = health maintenance organization; HD = health department. NOTE: These categories represent 69.5% of cases with known reporting source. Of all cases, 13.2% had a missing or unknown reporting source. Percentage MenWomen 0 5 10 15 20 25 30 35 STD Clinic Private Physician/HMO* Other HD* Clinic Family Planning Clinic Emergency Room

23. Gonococcal Isolate Surveillance Project (GISP)— Penicillin, Tetracycline, and Ciprofloxacin Resistance Among GISP Isolates, 2010 NOTE: PenR = penicillinase producing Neisseria gonorrhoeae and chromosomally mediated penicillin- resistant N. gonorrhoeae; TetR = chromosomally and plasmid mediated tetracycline-resistant N. gonorrhoeae; and QRNG = quinolone-resistant N. gonorrhoeae. PenR/QRNG PenR TetR/QRNG PenR/TetR QRNG PenR/TetR/QRNG TetR Susceptible 72.8% 1.8% 6.9% 2.0% 2.9% 9.4% 3.5% 0.6%

24. Uncomplicated Gonococcal Infections of the Cervix, Urethra, and Rectum Ceftriaxone 250 mg IM in a single dose OR, IF NOT AN OPTION Cefixime 400 mg orally in a single dose or 400 mg by suspension (200 mg/5ml) PLUS Azithromycin 1g orally in a single dose Or Doxycycline 100 mg twice a day for 7 days CDC 2010 STD Treatment Guidelines

25. Uncomplicated Gonococcal Infections of the Pharynx Recommended Regimens Ceftriaxone 250 mg IM in a single dose PLUS Azithromycin 1g orally in a single dose Or Doxycycline 100 mg twice a day for 7 days CDC 2010 STD Treatment Guidelines

26. Alternative Regimens Alternative regimens for uncomplicated gonorrhea –Cefpodoxime 400 mg – poor cure rates for pharyngeal infections –Cefuroxime 1 g orally – poor cure rates for pharyngeal infections –Spectinomycin: no longer available in U.S. –Azithromycin 2 g orally – concerns about macrolide resistance CDC 2010 STD Treatment Guidelines

27. Gonococcal Isolate Surveillance Project (GISP)—Drugs Used to Treat Gonorrhea Among GISP Participants, 1988–2010 NOTE: For 2010, “Other” includes no therapy (1.2%), azithromycin 2 g (1.7%), and other less frequently used drugs.

28. WestMidwest Northeast/Sout hTotal No.% # TestedNo.% # TestedNo.% # TestedNo.% # Tested 2000001,91030.21,56570.41,986100.25,461 2001402,06610.21,56170.41,845120.25,472 200200.22,16310.11,27380.41,93190.25,367 2003102,55800.11,62830.12,36640.16,552 2004202,540201,67320.12,10960.16,322 200550.22,55100.11,409102,23960.16,199 200640.22,489001,420102,18050.16,089 2007 2008 2009371.91,92470.51,398102,308450.85,630 2010683.32,07260.51,14630.12,475771.45,693 20113.20.60.3 1 Gonorrhea Isolates with Cefixime MICS >0.25μg/mL MMWR 2011;60:873-877 and MMWR 2012;61:590-594

29. Percentage of urethral Neisseria gonorrhoeae isolates with elevated cefixime MICs (≥0.25 µg/mL), by U.S. Census region and gender of sex partner — Gonococcal Isolate Surveillance Project, United States, 2006–August 2011 Region 2006200920102011* %(95% CI)% % % West (total)0.2(0.1–0.4)1.9(1.4–2.6)3.3(2.6–4.0)3.2(2.3–4.2) MSM0.1(0.0–0.6)2.6(1.7–3.8)5.0(3.8–6.5)4.5(3.1–6.3) MSW0.2(0.0–0.6)1.4(0.7–2.3)1.3(0.7–2.2)1.8(0.9–3.1) Midwest (total)0.0(0.0–0.3)0.5(0.2–1.0)0.5(0.2–1.1)0.6(0.2–1.5) MSM0.0(0.0–2.8)2.3(0.6–5.7)3.4(1.1–7.7)4.9(1.4–12.2) MSW0.0(0.0–0.3)0.3(0.1–0.7)0.1(0.0–0.6)0.0(0.0–0.6) Northeast and South (total) 0.1(0.0–0.3)0.0(0.0–0.2)0.1(0.0–0.4)0.3(0.1–0.8) MSM0.6(0.0–3.0)0.3(0.0–1.9)0.9(0.2–2.5)1.5(0.4–3.9) MSW0.0(0.0–0.2)0.0(0.0–0.2)0.0(0.0–0.2)0.1(0.0–0.4) MMWR 2012;61:590-594

30. CDC Recommendations for Gonorrhea Treatment - February 2012 Treat with most effective regimen –Ceftriaxone 250 mg + Azithromycin 1 g Closely monitor treatment failure –Persistent symptoms: Test by culture Submit isolate for resistance testing –MSM: Consider test of cure after 1 week (by culture or NAAT) especially if treated with cefixime Report suspected treatment failure Dear Colleague Letter, Dr. Gail Bolan, February 12, 2012

31. MMWR August 10, 212 “CDC no longer recommends cefixime at any dose as a first-line regimen for treatment of gonococcal infections.” “If Cefixime is used as an alternative agent, then the patient should return in 1 week for a test-of-cure at the site of infection.”

32. MMWR August 10, 2012 Recommended regimen –Ceftriaxone 250 mg in a single i.m. dose PLUS –Azithromycin 1 g orally in a single dose or –Doxycycline 100 mg orally twice a day for 7 days

33. MMWR August 10, 2012 Alternative regimen (if ceftriaxone is not available) –Cefixime 400 mg in a single dose PLUS –Azithromycin 1 g orally in a single dose or –Doxycycline 100 mg orally twice a day for 7 days Alternative regimen (severe cephalosporin allergy) –Azithromycin 2 g in a single oral dose PLUS with both of the above: Test-of-cure in 1 week –NAAT –Culture ( preferred if failure is suspected)

34. Expedited Partner Therapy

35. Approach whereby partners are treated without an intervening clinical assessment – Patients delivering medications to partners – Patients delivering prescriptions to partners – Field treatment by DIS or outreach workers (with or without testing)

36. EPT Studies Schillinger et al. Sex Transm Dis 2003;30:49-56 – 20% reduction in CT re-infection of 20% among women (P = 0.102) Golden et al. New Engl J Med 2005;352:676-85 – 73% reduction in GC re-infection among men and women (P < 0.01) – 17% reduction in CT re-infection (P = 0.17) Kissinger et al. Clin Infect Dis 2005; 41:623-9 – 46% reduction in GC and/or CT infection among men with urethritis (P<0.001)

37. EPT and the STD Treatment Guidelines “….patient delivered therapy (i.e., via medications or prescriptions) can prevent re-infection of index case and has been associated with a higher likelihood of partner notification, compared with unassisted patient referral of partners” EPT recommendations are limited to GC and CT contacts only EPT is not recommended for MSM CDC 2010 STD Treatment Guidelines

38. EPT Medications Contact to gonorrhea – Cefixime 400 mg PO x 1 – Azithromycin 1 g PO x 1 Contact to chlamydia – Azithromycin 1 g PO x 1

39. Partner Pack Chlamydia

40. Legal Status of EPT

42. EPT Acceptance DMHC 2006 - 2009 Mickiewicz et al. Sex Transm Dis 2012; In Press

43. In the context of decreasing cefixime susceptibility, is it still safe to provide EPT for gonorrhea?

44. What is the Future for EPT for Gonorrhea? No recommendations have been made thus far (August 2012 MMWR does not address EPT) While cefixime susceptibility appears to be decreasing, frank resistance has not (yet) been reported in the U.S. There are important differences in cefixime susceptibility by region and by sexual preference Probably safe to continue EPT for gonorrhea among heterosexuals while monitoring susceptibility and resistance regionally Convey message to patients with gonorrhea that the best option for their partners is to see a health care provider

45. Gonorrhea The Continuing Saga is….. …well…. Continuing…… Stay Tuned!!!