Genital Tract Infections in Women. Michael S. Policar, MD, MPH UCSF School of Medicine

Transcription

1 Genital Tract Infections in Women Michael S. Policar, MD, MPH UCSF School of Medicine

2 Value of STI Screening and Testing Benefits Detect infection Patient treatment Partner treatment Behavior change PH Surveillance Absence of infection Behavior change Reassurance Hazards False positives Unnecessary W/Us Emotional impact Economic costs, esp if high NNT Goals of STI Testing Test the right patients For the right organisms With the right test Interpret result correctly

3 Pretest Question In the lab most commonly used in your practice, which Chlamydia test is used? 1. Nucleic acid amplification test 2. DNA hybridization test 3. Chlamydia culture 4. Enzyme immunoassay 5. Don t t know

4 Pretest Question 2 To make a diagnosis of vaginitis (BV, trich,, Candida) in patients seen in my practice 1. I use a microscope in my office 2. I use point of care tests in my office 3. I send a sample of vaginal discharge to the lab 4. I make a presumptive diagnosis based on symptoms 5. I refer my patients to a specialist

5 Understanding Predictive Value Important for policy makers Sensitivity: : ability to detect condition if present Specificity: : ability to identify those without the condition Important for clinical decisions Positive Predictive Value: : likelihood that someone with a positive test result has the condition Negative Predictive Value: : likelihood that someone with a negative result does not have the condition

6 Understanding Predictive Value PPV and NPV are dependent upon the prevalence of the condition in the population being tested Example: Test has a specificity of 97% (3 FPs/ 100 tested) Prevalence =30%, 30 TP + 3 FP: PPV= 93% Prevalence = 3%, 3 TP + 3 FP: PPV= 50% Message: when used in low prevalence settings, even excellent tests have poor positive predictive values Grimes DA, Lancet 2002; 359:881

7 Genital Herpes HSV serotypes in genital infections Majority of genital infections caused by HSV % of genital infections caused by HSV % new cases of genital HSV due to HSV-1 Herpes seroprevelence HSV-1 1 antibody: 60-95% (mean: 80%) HSV-2 2 antibody: 20-25% 25% 90% of prior HSV infections unrecognized

8 Genital Herpes Recurrence risk after primary infection HSV-2: 50%; HSV-1: 10% 95% of people with genital HSV-2 2 have intermittent subclinical shedding Highest in 1 st year after infection (25% of days), then declines; 4-6% 4 of days for many years Similar frequency in persons with and without recognized symptoms Cause of most new cases of HSV-2 2 genital herpes Uncommon in new cases of HSV-1 1 genital herpes

9 Source: SFCC Genital Herpes

10 Source: SFCC Genital Herpes

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12 HSV: Organism Tests Sensit Specif Cost Comment PCR $$$$ Not in most labs HSV culture ELVIS rapid $$$ 1 day; no typing ELVIS std $$$ 5 days; typing* Cytopathic $$ Phasing out Herpes DFA $$ Scrape; plate Cytology $$ Scrape; plate * HSV typing is helpful for counseling regarding recurrence risk, but not for clinical management decisions

13 HSV-2 2 Serologic Diagnostic Testing Used mainly to exclude genital herpes diagnosis History suggestive of HSV but no lesions to test, OR Culture negative recurrent lesion Seronegative: : not due to genital herpes Seropositive: : HSV lesion or prior infection Suspected 1 o herpes more than 6 weeks ago with initial testing negative; serology repeated Seronegative: : not due to genital herpes Seropositive: : HSV infection confirmed

14 HSV-2 2 Serology: Screening Screen general population Universal screening in pregnancy Screening in HIV-positive patients Screening in patients in partnerships with HSV-2 infected people Screening in patients at risk for STD/HIV Should not be offered Should not be offered Should generally be offered Should generally be offered Should be offered to select patients Guidelines for the Use of HSV-2 2 Type-Specific Serologies,, CA DHS 2003

15 Prevention of Genital Herpes partner HSV-2 serostatus; ; susceptible if negative Avoid intercourse/touch of lesions during outbreak Condoms will provide some degree of protection Patient treatment of during outbreak (or long term suppression) reduces shedding Daily prophylactic treatment reduces shedding Incident HSV infection reduced by 1.7% over 1 year» 96.4% don t t seroconvert in absence of treatment» 1.9% seroconvert with treatment NNT: 59 people to prevent one case/ year

16 CDC 2006: Treatment of Genital Herpes Primary (7-10 days) Recurrent Suppression Prophylaxis Acyclovir (generic) Famciclovir (Famvir) Valacyclovir (Valtrex) 400 mg TID 250 mg TID 1 gram BID 200 mg 5 times/d 800 mg TID x2d 1 gm BID x1d 500mg BID x3d 800 mg BID x5d 125mg BID x5d 1 gm QD x5d 400 mg TID x5d 400 mg BID 250 mg BID gm QD 400 mg BID** 500 mg QD ** Drug class extrapolation, based upon suppressive regimen

17 Vaginitis Tests: Trichomoniasis Lobo, Sex Transm Dis 2003;20:694 Sensit Specif Cost Comment PCR $$$$ Not in most labs Diamonds culture $$$ Not in most labs Point of care tests Affirm VP III $$$ DNA probe OSOM Rapid $$ CLIA waived Saline suspension st line Pap smear n/a Confirm if low prevalence

18 CDC 2006: Vaginal Trichomoniasis Recommended regimen Metronidazole 2 grams PO single dose Tinidazole (Tindamax)) 2 grams x1 Alternative regimen: Metronidazole 500 mg PO BID x7d Cost per dose AWP Generic MTZ 2 gm $ 1.25 Flagyl 2 gm Tindamax 2 gm 12.00

19 Trich Tips : Advice to Clinicians Advise client that Trich could have been transmitted by any partner since sexual debut Evaluate NaCl suspensions pronto (< 5 minutes) Use fresh NaCl solutions ( < 1 month old) Question the existence of dead Trich on micro Single dose MTZ still is the treatment of choice Tinidazole worth the investment if prior failure or adverse effects (but not urticaria or anaphylaxis) Women who are or who may be pregnant can be treated with MTZ

20 Model of BV Pathogenesis Douching Antibiotics loss of competitive inhibition WSW Viral phage Adhesion to Sperm Decreased Lactobacillus Increased ph suppression by amines Increased Anaerobes BVAB Atopobium Mobiluncus

21 Sexual Transmission of BV? Sexually associated in heterosexuals Rare in virginal women Greater risk of BV with multiple male partners Condom use decreases risk But No BV carrier state identified in men Treatment of partner does not affect recurrences Women having sex with women (WSW) Infected vaginal fluid transmits BV Studies of concurrence in lesbian couples suggest horizontal transmission

22 BV: Diagnostic Criteria Amsel Criteria: : 3 or more of Homogenous white discharge Amine odor ( whiff( whiff test) ph > 4.5 (most sensitive) Clue cells > 20% (most specific) Spiegel criteria, Nugent score: Gram stain with Few or no gram positive Lactobacillus spp. Excess of other gram negative morphotypes

23 Point of Care BV Tests Gardnerella PIP Affirm VP III ph and Amines OSOM BV Blue

24 Vaginitis Tests: Bacterial Vaginosis Sensit Specif Cost Comment Nugent score Labor intensive Point of care tests Affirm VP III $$$ DNA probe OSOM BV Blue $$ CLIA moderate G vag PIP $$$ CLIA moderate ph + amines $ CLIA waived Amsel criteria line Pap smear n/a Coccobacilli

25 Who Should Be Tested for BV? Routine screening (asymptomatic): not indicated Diagnostic testing Check discharge, amines, vaginal ph, clue cells Microscopy not available or inconclusive Affirm VP III OSOM BV Blue G vaginalis PIP, ph+amine test cards Shift in vaginal flora on Pap No consensus, but poor correlation with BV most experts recommend no further f/u

26 CDC 2006: Bacterial Vaginosis Recommended regimens Metronidazole 500 mg PO BID x 7 days Metronidazole gel 0.75% vaginaally QD x 5 days Clindamycin 2% cream vaginally QHS x 7 days Clindamycin SR 2% cream* as single dose Alternative regimens Metronidazole 2 g PO x 1 Clindamycin 300 mg PO BID x 7 days Clindamycin ovules 100 mg vaginally QHS x 3 days * Not listed in CDC guidelines, but cure rate equivalent to Cleocin vag

27 Counseling Women with Recurrent BV Suppression with MTZ vaginal gel twice weekly Abstain form vaginal sex during treatment Don t t douche with anything! Use of condoms (especially in 1 st month after treatment) may reduce recurrences Clean sex toys (or use condoms) between use by one woman then another Avoid vaginal insertion following anal insertion of fingers or penises

28 Audience Question Which is the best strategy to prevent re-infection with gonorrhea or chlamydia? 1. Test of cure 2. Partner notification 3. Patient delivered partner therapy 4. Retesting 3 months after treatment

29 Case Study 27 year old woman requests STI screening In a monogamous relationship until 6 months ago 4 weeks ago, had unprotected sex with new partner Because she is concerned that she may have acquired an infection, wants to be screened for everything

30 Which STD screening test is considered to be unnecessary in this case? 1. Gonorrhea + chlamydia 2. Hepatitis B serology 3. Syphilis serology 4. HIV serology 5. All are considered to be necessary

31 Routine STI Screening Cervical Chlamydia (in women) Annually in sexually active women thru 25 years old Cervical gonorrhea (in women) Annually in sexually active women thru 25 years old Only if practice-site prevalence is at least 1% HIV serology (CDC 2006) ; USPSTF (2007): [C] recomm dn Screen once 13-64; repeat < annually if known risk Only if practice site prevalence is at least 0.1% Pregnant women Syphilis, HIV, Chlamydia (under 26 years old) Hepatitis B antigen (newborn treatment)

32 Are the Wrong Women Screened for Ct? Many women in the target age range (25 and younger) are not being screened Yet, in many systems, screening rates for women over age 25 are equal to women 25 and younger So what?? Rates of chlamydia in women over age 25 are <1% and decline with age Chlamydia infects the columnar epithelium of the cervical ectropion; recedes with aging As prevalence decreases, positive predictive value declines, making incorrect diagnoses more likely

33 2.8% 2.6% yo: 0.15% 1.0% CDC,2005

34 Targeted Screening: Risk Factors Syphilis, HIV screening Sexual history, partner behaviors, local prevalence GC + Ct screening History of GC, chlamydia, or PID in the past 2 years More than 1 sexual partner in the past year New sexual partner within 90 days Reason to believe that a sex partner has had other partners in the past year

35 GC+Ct Screening Recommendations Nucleic acid amplification tests (NAAT) are preferred Urine and (self-administered) vaginal swab samples are highly accurate Sample endocervix only if client is having a speculum exam for another reason DNA probe test (e.g., Genprobe PACE 2) is less accurate and cervical or urethral samples required In asymptomatic heterosexual women and men who engage in oral or anal sex, CDC does not recommend pharyngeal or anal GC or Ct tests

36 Contact Testing for STI Exposure Test asymptomatic persons with high risk sexual exposure (new or multiple sexual partners) for Gonorrhea Chlamydia Syphilis HIV Maybe: HSV-2 2 serology No contact testing for HSV (culture), HPV (DNA) HBV, HBC (strategy for HBV is vaccination)

37 CDC 2006: Screening for Hepatitis B Prevaccination Hepatitis B antibody screening is not cost effective in low prevalence populations Not recommended in adolescents Prevaccination Hepatitis B antibody screening is cost effective in high prevalence adult populations IDU, MSM, sexual contacts of chronic carriers, persons from endemic countries If screening is done, the first dose of vaccine should be given at the same time

38 CDC 2006: Screening for Hepatitis C Sexual transmission is very uncommon Candidates for targeted screening Blood transfusion from a donor who later tested positive for hepatitis C Injected illegal drugs, even if experimented a few times many years ago Transfusion or organ transplant before 7/1992 Recipient of clotting factor(s) made before 1987 Ever been on long-term kidney dialysis Evidence of liver disease (e.g., abnormal LFTs)

39 Testing for STI Co-Infection If positive for Test for Chlamydia GC, syphilis, HIV GC Chlamydia, syphilis, HIV Syphilis Chlamydia, GC, HIV Primary herpes Chlamydia, GC, syphilis, HIV Recurrent herpes (?) may be long standing Trichomoniasis (?) may be long standing Ext genital warts (?) may be long standing BV, candida Not STIs, therefore don t t screen

40 Diagnostic Testing for GC and Ct Women Abnormal vaginal discharge Abnormal vaginal bleeding Dyspareunia, chronic pelvic pain, PID Mucopurulent cervicitis Cervical friability Unexplained infertility Men Dysuria Urethral discharge Testicular pain

41 Post-Treatment Screening and Testing Test of Cure Not after high efficacy, single dose treatment» Only long-regimen antibiotics with high failure rate Risk false positive NAAT if <6 weeks from treatment Re-testing Women treated for chlamydia or GC should be re- tested in 3-12 months» High likelihood of repeat infection» Short time to repeat positive test» Re-testing identifies highest risk patients

42 Gonorrhea (GC) + Chlamydia (Ct) Indications for Treatment Positive GC or Ct screening test Sexual partner with known GC or Ct Presumptive therapy of mucopurulent cervicitis or urethritis (treat both) Pelvic inflammatory disease (treat both)

43 CDC 2006: LGT Chlamydia Preferred treatment Azithromycin 1 gm orally»dispensed as sachet (powder) or capsules»2006: first line treatment in pregnancy Doxycycline 100 mg PO BID for 7 days»avoid prolonged sun exposure (photosensitivity) Alternative treatment Ofloxacin 300 mg PO BID for 7 days Levofloxacin 500 mg PO QD for 7 days Erythromycin base or EES QID for 7 days

44 CDC: QRNG 2006 GISP findings of QRNG isolates (5% threshold) Overall population MSM: Heterosexual men: Philadelphia 26.6%; Miami 15.3% 13.3% (8.6% no CA, HI) 38.3% (30.7% no CA, HI) 6.7% (5.1% no CA, HI)

45 CDC 2007: : LGT Gonorrhea Adv Eff AWP Ceftriaxone 125 mg IM + 2 (IM) Cefixime 400 mg PO + 1 $ 6.76 Quinolones Ciprofloxacin 500 mg PO Ofloxacin 400 mg PO Levofloxacin 250 mg PO Co-treat Chlamydia, unless ruled out by NAAT No longer recommended by CDC

46 CDC 2006: LGT Gonorrhea Alternative Regimens Antibiotic Trade name Dose Adv Eff Cefpodoxime Vantin (b) 400 mg PO + 1 Cefuroxime Ceftin (g) 1 gm PO + 1 Azithromycin Zithromax (g) 2 gms PO + 2 Spectinomycin Trobicin (b) 2 gms IM + 3 Single dose IM cephalosporins Ceftizoxime Cefizox (b) 500 mg IM + 2 Cefotaxime Claforan (b) 500 mg IM + 2 Cefoxitin Mefoxin (b) 2 gm IM + 2 g: generic b: brand name

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48 Types of Expedited Partner Therapy Patient-delivered partner therapy (PDPT) Provide patients with drugs intended for the partners Write prescriptions in the partners names Prescribe extra doses of medication in the index patients name Arrangements with cooperating pharmacies Retrieval of medication by partners at public health clinics or other venues Delivery of medication to partners in non-clinical settings by public health workers

49 Expedited Partner Treatment Commonly applied to GC and Ct; EPT has limited role in partner management of trichomoniasis EPT studies show that partners are more likely both to be notified and treated for their presumed infections Studies included only heterosexual men and women No data regarding syphilis or GC/Ct among MSM Written materials should accompany medication and specially mention concern about PID in female partners First line management is clinical evaluation

50 CDC 2006: PID Treatment Principles Better to over-diagnose and treat, rather than to under-diagnose diagnose Early, aggressive therapy helps to avoid hospitalization, infertility Treatment must address N. gonorrhoeae Chlamydia trachomatis Anaerobic bacteria (Concomitant) Bacterial vaginosis

51 CDC 2006: Outpatient PID Treatment Regimen A Levofloxacin 500 mg QD for 14 days OR Ofloxacin 400 mg PO BID for 14 days Regimen B Ceftriaxone 250 mg IM then doxycycline 100 mg PO BID for 14 days OR Cefoxitin 2 grams IM plus probenecid 1 gram PO, then doxycycline 100 mg PO BID for 14 days If BV is diagnosed or to improve anaerobe coverage Add: Metronidazole 500 mg BID for 14 days

52 CDC 2006: Outpatient PID Treatment AWP Comment Ceftriaxone IM + $ 31 Good for mild PID Doxycycline + MTZ Cefoxitin IM Doxycycline + MTZ $ 37 Cefoxitin usually not stocked in offices Levofloxacin + MTZ $ 164 Good for moderate PID Ofloxacin + MTZ $ 174 More daily doses; no advantage

53 QRNG and Treatment of PID CDC, 2006 CA STD Treatment Guidelines, 2007 Quinolones may be used for PID if the risk of GC is low, a NAAT test for GC is performed, and follow-up is likely If GC is documented, change to a medication regimen that does not include a quinolone or obtain a test of cure to ensure that the patient does not have a resistant GC infection

54 Take Home Messages Understand the 7 categories of STI screening and testing and stick with established indications Screening without a clear indication may do more harm than good Make clinical decisions on the basis of predictive value, not test sensitivity and specificity Single sample multiple pathogen tests are preferred when testing all pathogens is intended Avoid multiple pathogen test panels which include pathogens that do not need to be found