Novos desafios para controlar as infecções sexualmente transmissíveis [New Challenges in Managing Sexually Transmitted Infections]

Transcription

1 Novos desafios para controlar as infecções sexualmente transmissíveis [New Challenges in Managing Sexually Transmitted Infections] Khalil Ghanem, MD, PhD Associate Professor of Medicine Directors, STD/HIV/TB Clinical Services Baltimore City Health Department

2 Overview Screening for STDs 5 Clinical Cases that cover: Neisseria gonorrhoeae Chlamydia trachomatis Serotypes D-K Serotypes L1-L3 Mycoplasma genitalium Trichomonas vaginalis Treponema pallidum

3 I. STD SCREENING

4 The Percent of AsymptomaticSTDs

5 Screening for STDs in HIV+ Persons Syphilis: at least annually for all sexually active HIV-infected persons, with more frequent screening (every 3 6 months) in those with multiple partners, a history of unprotected intercourse, a history of sex in conjunction withillicit drug use, methamphetamine use, or sexual partners who participate in such activities Chlamydia: all sexually active women 25y and men and women >25y at increased risk(new or multiple partners; previous CT history; area of high prevalence; CSW, drug use, inconsistent condom use) Repeat testing of all CT+ women and men is recommended 3-6 months after treatment Gonorrhea: Annual screening for gonorrhea is recommended for all sexually active MSM, and targeted screening is recommended for high-risk women (e.g., women with previous gonorrhea infection, other STDs, new or multiple sex partners, and inconsistent condom use; CSW and drug use; area of high prevalence) Repeat testing of GC+ patients recommended 3 months after treatment Trichomonas: All HIV+ women should be screened for trichomoniasis on a yearly basis Repeat testing of all trichomonas+ women recommended 3 months after treatment

6 Prevalence of Extragenital Sexual Behaviors ORAL SEX Oral Sex Males Females Active Oral Passive Oral Active Oral Passive Oral Lifetime 77% 79% 68% 73% ANAL SEX Young MSM: 50% Young heterosexual men and women: 14-49% Last sex 27% 28% 19% 28% Michael RT, et al. Sex in America: A Definitive Survey. Little, Brown and Co. UK Ekstrand M, et al. AIDS 1999; 13 (12): Halperin D, et al. AIDS Patient Care STDs 1999; 13(12);

7 Extragenital STIs Studies suggest that up to 65% of cases of gonorrhea and 50% of cases of chlamydia among MSM may be missed if genital-only testing were performed. Sex Transm Dis. 2008;35(10):845 Clin Infect Dis. 2005;41(1):67 In women, 10% of CT and 31% of GC infections would have been missed if extragenital testing were not done Sex Transm Dis. 2011;38(9):783 The majority of rectal and pharyngeal GC & CT infections are ASYMPTOMATIC Rectal and pharyngeal infections are of public health significance Clin Infect Dis. 2009;49(12):1793

8 Extragenital STI Diagnostics All HIV+ persons should be tested for rectal and pharyngeal gonorrhea and rectal chlamydia if they report pharyngeal or rectal exposures Sensitivity of culture <50% to detect rectal and pharyngeal GC vs. >90% sensitivity for Nucleic Acid Amplification Tests (NAATs) Sex Transm Infect Jun;85(3):182-6 The CDC recommends that NAATs be used to detect these infections MMWR Recomm Rep ;60(1):18

9 II. CLINICAL CASES

10 Case 1 Sandra, a 22 year old HIV+ commercial sex worker presents 1 week after treatment of gonococcal cervicitis diagnosed by NAAT. She states her symptoms did not get better after a single dose of cefixime. She has had 7 sex partners since her last visit but she usually uses a condom. On examination, she has a purulent discharge exuding from the cervical os. Now what?

11 Gonorrhea Therapy: A Historical Perspective Pre-1937 Antiseptic Irrigation With Potassium Permanganate, Silver Salts, Mercurochrome 1937 Sulfonamide Therapy 1943 Penicillin Therapy % Treatment Failure With Sulfonamides 1972 Penicillin Regimen Increased to 4.8 Million Units Plus Probenecid 1976 Recognition of PPNG 1984 High Level Chromosomal Penicillin Resistance, 1985 Recognition of Plasmid Mediated Tetracycline Resistance 1987 High Level Spectinomycin Resistance 1989 Penicillin No Longer Drug of Choice for GC 2001 High level azithromicin resistance detected 2001 Cephalosporin resistance detected Concern Regarding Rising Quinolone MICs Fluoroquinolones no longer drugs of choice for GC

12 Drug Resistant Gonorrhea Azithromycin Drug resistant strains (MIC >1024) described in San Diego and Hawaii (MSM) Cephalosporins Drug resistant strains described in Japan (ceftriaxone MIC >2) and Norway (cefixime>2) In US: MMWR 2011; 60(26): 873

13 Reduced Susceptibility to Cephalosporins

14 Updated CDC Treatment Recommendations for Gonorrhea Ceftriaxone 250 mg IM X1 +Azithromycin 1gPO X 1 Even if C. trachomatis is ruled out! If a patient experiences cefixime treatment failure: Re-treat with 250 mg ceftriaxone intramuscularly and 2gazithromycin orally Return for tests-of-cure within 2 weeks, preferably with culture, or, if culture is not available, with NAAT. If the follow-up NAAT result is positive, a specimen for culture should be obtained MMWR Recomm Rep ;60(1):18

15 Case 1 Sandra, a 22 year old HIV+ commercial sex worker presents 1 week after treatment of gonococcal cervicitis diagnosed by NAAT. She states her symptoms did not get better after a single dose of cefixime. She has had 7 sex partners since her last visit but she usually uses a condom. On examination, she has a purulent discharge exuding from the cervical os. Send a GC cultureto potentially detect antimicrobial resistance Treat her with ceftriaxone 250mg IM X1 + azithromycin 1g PO X1 Now what?

16 Case 2 Jon, a 23 year old HIV+ gay man complains of rectal pain with defecation. He admits to receptive anal sex and oral sex. On physical examination, he has no oral lesions, and he experiences exquisite tenderness on digital rectal examination What is the most appropriate management approach?

17 Causes of Proctitis Neisseria gonorrhoeae Chlamydia trachomatis D-K Chlamydia trachomatis L1-L3 Treponema pallidum HSV 1 and HSV-2 Workup Rectal NAAT for GC Rectal NAAT for CT* Rectal culture for HSV RPR serology

18 LGV: Chlamydia trachomatis Serological Classification A,B, Ba, C (Trachoma) D-K (Genitourinary and ocular infections) L1-L3 (Lymphogranuloma venereum)

19 LGV Unilateral painful inguinal lymphadenopathy; groove sign ; initial ulcer is short-lived ***Rectal exposure leads to proctocolitis (serovar L2b) Dx: culture, immunofluorescence, or nucleic acid detection Rx: Doxycycline 100mg po BID X 21d (at least)

20 Histology is misleading in LGV Clin Infect Dis 2004 ;39(7):996 MMWR 2004;53(42):985 Euro Surveill. 2005;10(3):E J Clin Gastroenterol. 2006;40(5):385 PROCTITIS Histology: Mucosal ulcers, cryptitis, crypt abscesses and granulomas

21 LGV Diagnostics Cell culture X Limited availability Limited sensitivity Serology X (complement fixation titer 1:64 or microimmunofluorescence 1:128) Lack of standardization for rectal infections Indirect measure of infection Sensitivity/Specificity issues NAATs Lack of FDA clearance for rectal specimens New multiplex tests that detect LGV strains not widely available clinically

22 Empiric Treatment of Proctitis Ceftriaxone 250mg IM Covers GC Doxycycline 100 mg PO BID X 3 weeks Will (over)treat C. trachomatis D-K and will adequately treat C. trachomatis L1-L3 Will (over)treat early syphilis Alternate is azithromycin 1g PO q week X 3 weeks (will NOT adequately treat syphilis) +/- acyclovir or valacyclovir Modify duration once lab results are back

23 Case 2 Sean, a 23 year old HIV+ gay man complains of rectal pain with defecation. He admits to receptive anal sex and oral sex. On physical examination, he has no oral lesions, and he experiences exquisite tenderness on digital rectal examination What is the most appropriate management approach? Send oral, rectal, and genital specimens for GC and CT NAATs testing Perform syphilis serological testing Send rectal specimen for HSV PCR/or culture Treat with Ceftriaxone 250mg IM X1 and doxycycline 100mg po BID X1-3 weeks depending on testing results +/- acyclovir

24 Case 3 Steve, a 20 year-old HIV+ man was seen 2 weeks earlier and treated for NGU with 7 days of doxycycline. A week later, he noted no improvement in symptoms and was given 1g of azithromycin. At that visit, urine was sent for GC and CT NAATs testing. He presents today without improvement yet again. His CT and GC NAATs were negative. On examination, he has a thin urethral discharge. He denies any sexual encounters in the last 3 weeks What next?

25 Non-Gonococcal Urethritis (NGU) Urethritis caused by organisms other than N. gonorrhoeae More common etiologies: Chlamydia trachomatis (25% cases) Mycoplasma genitalium (30% of cases) Trichomonas vaginalis (10-25% of cases) Ureaplasma urealyticum (controversial) HSV Less common etiologies: anaeobes; enterobacteriaceae, Haemophilus, Staphylococcus saprophyticus, adenovirus NGU treatment: Azithromycin 1g PO x1 OR doxycycline 100mg PO BID X 7 days If a person with NGU fails to respond to therapy, think of 2 possibilities: (1) T. vaginalis (treat with metronidazole) or (2) M. genitalium that did not respond to above therapy (see next slide)

26 Mycoplasma genitalium May be associated with up to 30% of cases of non-gonococcal urethritis (NGU) & cases of PID Treatment with Azithromycin 1g PO X1 (success rate ~85%) superior to doxycycline 100mg PO BID X 7days(success rate <50%) Clin Infect Dis Jun 15;48(12): Limited data on efficacy of moxifloxacin 400mg POX 10 days if azithromycin fails PLoS One. 2008;3(11):e3618

27 Urethritis: Treatment Approach Rule-out reinfection****

28 Case 3 Steve, a 20 year-old HIV+ man was seen 2 weeks earlier and treated for NGU with 7 days of doxycycline. A week later, he noted no improvement in symptoms and was given 1g of azithromycin. At that visit, urine was sent for GC and CT NAATs testing. He presents today without improvement yet again. His CT and GC NAATs were negative. On examination, he has a thin urethral discharge. He denies any sexual encounters in the last 3 weeks What next? Metronidazole 2g PO X1 is the next step. If he fails therapy yet again, consider moxifloxacin

29 Case 4 Sandy is a 23 year old HIV+ woman (CD4 count 560 cells/mm 3, HIV RNA undetectable) on HAART One week earlier, she was treated for a trichomonas infection with 2g of oral metronidazole. She presents today with persistent symptoms; she denies any sexual encounters in the past week What next?

30 Trichomonas vaginalis May be asymptomatic in both men and women; causes vaginitis and NGU Diagnosis: culture and PCR; wet mount is not sensitive (<60%) Vaginal ph usually >4.0 Therapy: metronidazole 2g PO X1 OR tinidazole2g PO X1 OR metronidazole 500mg PO BID X 7 days [do NOT use topical gel formulations] Resistance: ~5% of strains have low-level resistance to metronidazole; <1% have high level resistance (see next slide) Partners in the preceding 60 days must be treated No need to screen asymptomatic pregnant women for Trichomonas

31 Trichomonas & Nitroimidazoles Tinidazole has a longer serum half-life and achieves higher tissue concentrations than metronidazole; MICs to tinidazole lower than to metronidazole If patient fails Rx with metronidazole 2g PO X1 & reinfection is excluded: Option 1: Tinidazole 2 g PO X1 Option 2: Metronidazole 500mg PO BID X 7d If patients fails either option 1 or 2 above: Option 3: Metronidazole 2g PO QD X 5d Option 4: Tinidazole 2g PO QD X 5d

32 Case 4 Sandy is a 23 year old HIV+ woman (CD4 count 560 cells/mm 3, HIV RNA undetectable) on HAART One week earlier, she was treated for a trichomonas infection with 2g of oral metronidazole. She presents today with persistent symptoms; she denies any sexual encounters in the past week What next? Option 1: Tinidazole 2 g PO X1 Option 2: Metronidazole 500mg PO BID X 7d

33 Case 5 A 23 year old HIV+ gay man with a CD4 count of 220 cells/mm 3 and HIV RNA of 35K presents with a non-tender penile ulcer. He has a mild headache, but no photophobia or neck stiffness. Blood tests reveal a positive RPR at 1:256 and a positive FTA-ABS. What is the most appropriate approach to management?

34 Syphilis JAMA. 2003;290(11):1510-4

35 Neurosyphilis There are no established criteria for the diagnosis of neurosyphilis Certain criteria that are used clinically: Serological evidence of syphilis Neurological symptoms A positive CSF VDRL (50% sensitivity; high specificity) Pleocytosis [>5 WBC/ml if HIV-; >20 WBC/ml if HIV+] Elevated protein concentration [>50mg/dl]

36 Current CDC Recommendations for CSF Examination Allneurologically symptomaticpatients All patients with evidence of tertiary syphilis All asymptomaticpatients who don t respond to therapy (i.e. lack of four-fold decline in RPR titers) ConsiderLP in asymptomatic HIV+ patients with a CD4 count 350 cells/ml or RPR titer 1:32

37 CSF EXAMINATION + CSF VDRL NR CSF VDRL CSF WBCs and/or Protein Normal CSF Examination Are the clinical signs and symptoms consistent with NS? Are the clinical signs and symptoms c/w tabes? Yes No Yes No Treat for NS Treat for NS Search for alternate diagnosis Treat for NS Search for alternate diagnosis

38 Syphilis: Rx Early syphilis: Bezathine PCN 2.4 MU IM X1 Late latent: Benzathine PCN 2.4 MU IM q week X3 wks In non-pregnant PCN-allergic pts w/ early and late latent syphilis: doxycycline may be used Azithromycin for early syphilis not recommended if other options are available Pregnant penicillin-allergic women with syphilis need to be desensitized to PCN. There are NO OTHER OPTIONS

39 Case 5 A 23 year old HIV+ gay man with a CD4 count of 220 cells/mm 3 and HIV RNA of 35K presents with a non-tender penile ulcer. He has a mild headache, but no photophobia or neck stiffness. Blood tests reveal a positive RPR at 1:256 and a positive FTA-ABS. What is the most appropriate approach to management? CSF examination is essential because of his headache If CSF exam is negative, treat for early syphilis If CSF exam is positive, treat for neurosyphilis Counseling Partner notification

40 Prevention in HIV Positive Patients MMWR July 18, 2003 / 52(RR12);1-24

41 Thanks Obrigado!