# Presentation: 863370

## Current Issues in STD Management Implications for Improving Women’s Reproductive Health Outcomes

- Gail Bolan MD
- Chief, STD Control Branch
- CA Department of Public Health
- August 16, 2007

## Overview of Presentation

- Diagnosis and Treatment options:
- Prevention and Screening
- Chlamydia, Gonorrhea, and PID
- Cervicitis
- Vaginitis:  Trich, BV
- Genital ulcers:  Syphilis, HSV
- HPV
- Clinical Management Strategies
- Screening Strategies
- Partner Services

## Prevention & Screening Issues

- Sexual history taking and risk reduction client centered counseling  including the 5 P’s
- Partners
- Practices
- Past History of STDs
- Protection for STDs
- Pregnancy prevention
- Patents should be informed about which STDs they are tested for (and which not) and if positive which must be reported to the HD

## Key Elements of Client Centered Counseling

-  establish rapport/maintain non-judgmental attitude
-  ask open-ended questions to gain understanding of client’s risk
-  facilitate risk reduction on client terms (i.e.: what they can realistically do)
-  limit information giving to essential facts in order to  reduce misinformation
-  encourage client to actively participate in session

**Notes:**
This step demands a developmental perspective, as the 14 yo with Chlamydia will need a different level of support in planning for behavior change than the 30 yo will need

## Steps in Counseling: A client centered approach

-   Conduct a personalized risk assessment (open ended questions)
- “Actual” (provider assessed) risk
-  Self perceived (client assessed) risk
-  Support client-initiated behavior change
*Listen *with an open mind, in a non-  judgmental manner

**Notes:**
What a clients thinks they can do and wants to do , is what they are most likely to be successful in doing. Behavior change is incremental , and success builds upon success

## Steps in Counseling: A client centered approach

-  Help the client to recognize barriers to risk reduction (active listening)
-  Negotiate an acceptable and achievable risk reduction plan (contract)
-  Refer client to other specialized services, if needed (e.g. partner services, couples counseling, substance abuse treatment, etc.)

## STD Screening for Women

- Adolescents & up to age 25
- Annual chlamydia and gonorrhea screening
- Others STDs/HIV based on risk
- Women over 25 years of age
- Based on risk factors
- Pregnant women (first trimester)
- HIV, Syphilis serology, Hep B sAg, and CT
- Gonorrhea based on age and risk
- Hep C based on risk
- BV if high risk pregnancy

## Chlamydia Summary

- Screen, screen, screen!  (women 25 and under)
- NAATs recommended
- Treatment issues
- Expedited partner treatment
- Re-testing after treatment

## Current Chlamydia/Gonorrhea Diagnostic Tests

- Gram stain only for men
- Culture
- Antigen Detection Tests: EIA, DFA
- Nucleic Acid Non-amplified Detection Tests
- GenProbe PACE 2
- Nucleic Acid Amplification Tests (NAATs)
- Roche *Amplicor** *(PCR)
- GenProbe *Aptima** (*TMA)
- B-D *ProbeTec** *(SDA)
- What is the current test you used to screen your female clients?

## Nucleic Acid Amplification Tests Recommended

- Noninvasive
- Urine and self-collected vaginal swabs
- Non-clinical exam settings
- Pelvic and genital exams not necessary
- Clinic intake areas and pregnancy only tests
- Home testing

- Highest sensitivity
- Able to detect up to 40% more Chlamydia infections
- Less dependent on specimen collection and handling

## Estimated Chlamydia Screening Coverage (HEDIS) for Females Age 16-26 USA and California, 1999-2004

- *Family PACT program paid claims data

## Are we screening the wrong women?

- The many women in the target age range (25 and younger) are NOT being screened
*Meanwhile*
- A large proportion of current testing is being done for women over age 25
- Guidelines for screening women over 25 are not specific
- Other women “at risk” such as prior history of STD, new or multiple partners, or inconsistent use of barrier contraception

## Chlamydia Test Volume and Prevalence by Age among Female Patients in Public and Private Clinics

**Source:  ****	****PUBLIC: Family PACT, January-June 2001 & Infertility Prevention Project 2003****	****PRIVATE:  PHIP - Kaiser Permanente, managed care organization, 1999-2002**

- Family PACT

- HMO

- AGE

## What about chlamydia screening among men?

- Obvious source of transmission
- Urine-based testing advantage
- Unpublished cost effectiveness analysis demonstrate community and future partner benefits; need > 5% prevalence
- Limited data on prevalence & outcomes in women
- No guidelines available

## Chlamydia TreatmentAdolescents and Adults

- _Recommended regimens:_
-  Azithromycin 1 g PO x 1
-  Doxycycline 100 mg PO BID x 7 d
- _Alternative regimens:_
-  Erythromycin base 500 mg PO QID x 7 d
-  Erythro ethylsuccinate 800 mg PO QID x 7 d
-  Ofloxacin 300 mg PO BID x 7 d
-  Levofloxacin 500 mg PO QD x 7 d

**** NO CHANGES FOR 2006 GUIDELINES ****

##  for patients with gonorrhea in California...

**CIPRO**

## Gonorrhea Treatment 

- _Recommended regimens:_
- Ceftriaxone 125 mg IM x 1*
- Cefixime 400 mg PO x 1
- _Alternative oral regimen:_
- Cefpodoxime 400 mg po x 1
- _Alternatives for Cephalosporin allergic:_
- Spectinomycin 2 g IM x 1
- Azithromycin 2 gm x 1
- Co-treat for chlamydia unless ruled out by NAAT* *

- *Preferred and only recommended regimen for pharyngeal infection

## Partner Treatment Options

- Patient referral
- Provider or clinic referral
- Health department referral
- Expedited Partner Treatment (EPT)
- Patient-delivered partner therapy (PDPT)
- Health department-delivered therapy
- Pharmacy-delivered therapy

## Infection During Follow-up Among Patients Completing the EPT Trial

- P=.02

- P=.17

- P=.04

**Percent**

- N=358

- N=1595

- N=1860

*Golden et al., NEJM 2005; 352:676-85*

## Chlamydia and Gonorrhea Expedited Partner Treatment

- Expedited Partner Treatment (EPT) or Patient-Delivered Partner Treatment (PDPT)
- Option for partner management for heterosexual men and women
- Written materials should accompany medication and specially mention concern about PID in female partners
- First line management is clinical evaluation
- CDC has developed separate guidance on EPT/PDPT

## Recommendations for Chlamydia and Gonorrhea Re-Testing after Treatment

- Prefer “re-testing” to “re-screening”
- High rates of re-infection after treatment
- Recommend re-testing of females with CT; some experts suggest re-testing of males
- Consider re-testing of females with GC; some experts suggest re-testing of males
- Time frame: 3 months after treatment or whenever seek care within 12 months if did not return at 3 months
- TOC not recommend unless treated initially with a fluoroquinolone and symptoms persist or recur after treatment or a pregnant women with CT

## Chlamydia and Gonorrhea Repeat Infection1-6 months after infectionby Data Source, 2004

- CHLAMYDIA

- GONORRHEA

**Notes:**
This is the epi curve for years 2001-2003 of gonorrhea cases by month in Butte County. These are all the cases. The aqua green represents Oroville cases, the light blue is Chico and the top grey is Other area.  

Oroville cases, represented in green, represent the majority of gonorrhea cases.  For this reason we focused our investigation on Oroville case-patients.

## Pelvic Inflammatory Disease Issues

- Newest etiologic agent:  *Mycoplasma genitalium*
- Pathogenesis unclear
- No recommendation for Mg testing
- If no evidence of cervicitis and no WBCs on wet mount the diagnosis of PID is unlikely
- Modify minimal criteria for presumptive treatment:
- CMT OR uterine tenderness OR adnexal tenderness
- Clarify use of metronidazole*:
- Treatment to cover anaerobes should be considered
- If BV is present or cannot be ruled out, add metronidazole*
- Azithromycin treatment mentioned “outside the box”
- Not recommended

## PID Oral Treatment Regimens Discussed *

- _Recommended Regimens __*__:_
- Ofloxacin 400 mg PO BID x 14 d
- Levofloxacin 500 mg PO QD x 14 d
- Ceftriaxone 250 mg IM (or other parenteral  3rd generation cephalosporin) x 1
*	**	**	**	**plus *
- 	Doxycycline 100 mg PO BID x 14 d
- Cefoxitin 2 g IM *and* probenecid 1 g PO x 1
- 				*plus *
- 	Doxycycline 100 mg PO BID x 14 d*	**	**	*

- * Plus metronidazole if BV or BV cannot be ruled out

*** ******* Discussed at the ***
***2006 Guidelines Meeting***

## PID:  Oral Treatment Regimens

- _Oral regimen A:_
**Ofloxacin* ****400 mg PO BID****** x 14 d *****or***
**Levofloxacin* 500 mg PO QD x 14 d **
***	******	******	******plus***** (**_**with**_** or without)**
**Metronidazole 500 mg PO BID x 14 d**

- *Contraindicated pregnant or nursing women

**** typographical error in CDC guidelines- not once daily**

## PID:  Oral Treatment Regimens Continued

- _Oral regimen B:_
**Ceftriaxone 250 mg IM (or other parenteral  3rd generation cephalosporin) x 1 *****or*****  **
**Cefoxitin 2 g IM *****and***** probenecid 1 g PO x 1 **
**	****	****	****	*****plus ***
**Doxycycline* 100 mg PO BID x 14 d**
**	****	****	****with or **_**without**_** **
**Metronidazole 500 mg PO BID x 14 d**

- *Contraindicated pregnant or nursing women

## Cervicitis Diagnostic Evaluation 

- Clinical criteria for the diagnosis of cervicitis
- easily induced endocervical bleeding
- mucopurulent discharge: swab test
- CT/GC NAAT
- Evaluated for BV and trichomoniasis
- Point-of-care Ag-based detection assay (OSOM rapid test, Genzyme;), sens 83.3%, spec 98.8%
- Affirm test
- Quantifying WBCs in vaginal fluid
- >10 WBC/HPF in vaginal fluid strongly associated with cervical CT/GC, high PPN (particularly in BV)

## Empiric Therapy of Cervicitis

- Age- and risk-based empiric therapy:
- Age < 25, treat for Ct and (usually) GC
- Age > 25, treat for Ct based on risk factors and likelihood of follow-up, otherwise await Ct/GC test result
- GC treatment should be based on risk, likelihood of follow-up, local (patient group/clinic/neighborhood) prevalence
- Evaluate for BV and trichomoniasis; treat if present
- If treatment is deferred, use NAAT results to direct future treatment for CT/GC

## Chronic or Persistent Cervicitis

- Prevalence, incidence, etiology, natural history and clinical significance are unknown
- Re-evaluate for all potentially associated organisms at least once
- The patient should be treated with azithromycin at least once
- Be sure partner was treated
- Ablative treatment (laser or cryotherapy) is often used, and is anecdotally successful; no data in literature
- No data on prolonged antibiotic use (2+ weeks) but some experts provide it

## BV Treatment

- _Recommended regimens:_
- Metronidazole 500 mg PO BID x 7 d
- Metronidazole gel 0.75% 5 g per vagina QD/BID x 5 d
- Clindamycin cream 2% 5 g per vagina QHS x 7 d
- _Alternative regimens:_
- Clindamycin 300 mg PO BID x 7 d
- Clindamycin ovules 100 mg per vagina QHS x 3 d
- _Recommended regimens in pregnancy:__ _
- Metronidazole 500 mg PO BID x 7 days
- Metronidazole 250 mg PO TID x 7 days
- Clindamycin 300 mg PO BID x 7 days
- _Suppressive treatment:_
**Metronidazole gel 0.75% twice weekly for 6 months**

## Trichomoniasis Issues

- Diagnosis on Pap test lacks specificity; recommended confirm with culture if patient is at low risk
- New point of care tests have better sensitivity but FP in lower prevalence population
- OSOM Trichomonas Rapid Test and Affirm TM VP III
- Culture is the most sensitive and specific and should be done if wet mount is negative and Trichomoniasis is suspected
- New treatment:
- ADD tinidazole 2 g po x 1
- Higher cost but better tolerated
- New management of treatment failure (after metro 2 g po x 1) and Metronidazole-resistant trichomonas

## Trichomoniasis Treatment

- _Recommended regimen:_
-  Metronidazole 2 g PO x 1
-  **Tinidazole 2 g po x 1**
- _Alternative regimen:_
-  Metronidazole 500 mg PO BID x 7d
- _Recommended regimen in pregnancy:_
-  Metronidazole 2 g PO x 1
- Pregnancy category B and Tinidazole is category C

## Tinidazole (Tindamax)

- Second-generation nitroimidazole recently approved for
- Trichomoniasis
- Giardiasis: probably drug of choice
- Amebiasis
- Highly active against anaerobic bacteria, some protozoa
- Lower MIC’s to trichomonas
- Recent efficacy study in MTZ-R trich: 92% cure
- Elimination 1⁄2 life twice that of MTZ (12-14 h vs. 6-7 h)
- Excellent tissue penetration
- Better safety and tolerance profile relative to MTZ
- Less nausea/vomiting
- No alcohol during and 3 days after treatment, Category C in pregnancy, don’t use

## Management of Trichomoniasis Treatment Failures

- Re-treat with:  Metronidazole 500 mg po BID x 7 d  or Tinidazole 2 g po x 1
- If repeat failure, treat with:  Metronidazole or Tinidazole 2 g po x 5 d
- Some experts treat with:  Tinidazole 2-3 g po x 14 d*
- Susceptibility testing: Send isolate to CDC
- 707-488-4115 or _[www.cdc.gov/std](http://www.cdc.gov/std)__ for instructions _

*** ******* Discussed at the ***
***2006 Guidelines Meeting***

## Genital Herpes

- 50 million in U.S. likely have genital HSV
- 90% of infections unrecognized
- 95% of people with genital HSV-2 have intermittent subclinical shedding
- Present 5-30% of days in persons with genital HSV-2
- Frequency highest in first year after infection (20 - 30% of days), then declines; ~ 4 - 6% of days for many years
- Accounts for most HSV-2 transmission
- Uncommon if genital herpes due to HSV-1
- Similar frequency in persons with and without recognized symptoms

## Genital Herpes

- What’s New:
- Overall declines in HSV-2 seroprevalence in U.S.
- Availability of affordable type-specific serology
- Glycoprotein G type-specific HSV-2 serology tests:
- HerpeSelect- 1 or 2 ELISA, HerpeSelect- 1 and 2 Immunoblot and HSV-2 ELISA, Biokit HSV-2, and SureVue HSV-2
- Role in enhancing HIV transmission
- Prevention of transmission with antiviral therapy and condoms
-  Proportion of genital herpes due to HSV-1
- Trends toward shorter courses of treatment

## First Episode 
Acyclovir 400 mg TID x 7-10 d
Acyclovir 200 mg 5x/d x 7-10 d
Famciclovir 250 mg TID x 7-10 d
Valacyclovir 1.0 g BID x 7-10 d
Suppressive Treatment
Acyclovir 400 mg bid
Famciclovir 250 mg bid
Valacyclovir 500 mg or 1000 mg once daily

- Acyclovir 400 mg TID x 7-10 d
- Acyclovir 200 mg 5x/d x 7-10 d
- Famciclovir 250 mg TID x 7-10 d
- Valacyclovir 1.0 g BID x 7-10 d
- Suppressive Treatment
- Acyclovir 400 mg bid
- Famciclovir 250 mg bid
- Valacyclovir 500 mg or 1000 mg once daily

**Genital Herpes Treatment**

- Episodic Treatment
- Acyclovir 400 mg TID x 5 d
- Acyclovir 800 mg BID x 5 d
- Acyclovir 800 mg TID x 2 d
- Famciclovir 125 mg bid x 5 d
- Famciclovir 1 g BID x 1 d
- Valacyclovir 500 mg BID x 3 d
- Valacyclovir 1 gm q D x 5 d

## Uses of Herpes Serology

- Definite indications:
- Diagnosis of genital ulcers or lesions, especially when lesions cannot be sampled or are unlikely to yield virus
- Management of sex partners of persons w/ herpes
- Implications for counseling, antiviral therapy in infected partner
- Screen persons at risk for HIV transmission (HIV+)
- Other uses under discussion:
- Pregnant women and partners (select vs. all)
- Patient request
- Not clear whether all sexually active persons should be screened (cost vs. benefit) but currently not recommended

**Notes:**
Role of Serology
Type-specific serology is the final diagnostic test in the testing algorithm.  Remember that patients who are experiencing true first-episode genital herpes will not have seroconverted 
In addition to the reasons shown in the algorithm (slide 26), serology should be undertaken to establish a genital herpes diagnosis for the additional reasons noted above, either for patients presenting with symptoms or for certain subclinical, high-risk patients

Reference:
Ashley R. Diagnostic technologies. Slides presented at: VALTREX Speakers Education Program;
March 18-19, 2000; Charleston, SC.

## Rates of Transmission of HSV-2 to Susceptible Partners is Reduced with Once-Daily Suppressive Therapy

*Corey et al, NEJM 2004; 350:11-20 *

- Control Group (N=741)

- Valacyclovir Group (N=743)

- 1484 heterosexual couples randomly assigned to take 500 mg of valacyclovir or placebo once daily for 8 months
- Serum samples collected monthly from susceptible partners for HSV analysis
- The valacyclovir group showed
- decreased transmission
- lower frequency of shedding
- fewer copies of HSV-2 DNA when shedding occurred

**Notes:**
NOTE:  Shedding study was a substudy (N=89) of this one... source partners swabbed the genital region daily for 2 months for testing by PCR.
If the source partner had recurrences, they were treated with episodic therapy of 500mg twice daily valacyclovir for 5 days, and then returned to randomly assigned medication.

Corey L, Wald A, Patel R, Sacks SL, Tyring SK, Warren T, Douglas JM Jr, Paavonen J, Morrow RA, Beutner KR, Stratchounsky LS, Mertz G, Keene ON, Watson HA, Tait D, Vargas-Cortes M; Valacyclovir HSV Transmission Study Group. Once-daily valacyclovir to reduce the risk of transmission of genital herpes.  N Engl J Med. 2004 Jan 1;350(1):11-20. 

## Antiviral treatment:  valacyclovir 500 mg PO QD
Indications may include:  
Discordant couples (the only evidence-based indication)
Persons with multiple partners
Men who have sex with men
HIV-infected
Reassess discordant partner annually for seroconversion 
Counsel regarding condoms, disclosure, abstinence

- Indications may include:
- Discordant couples (the only evidence-based indication)
- Persons with multiple partners
- Men who have sex with men
- HIV-infected
- Reassess discordant partner annually for seroconversion
- Counsel regarding condoms, disclosure, abstinence

**HSV Suppressive Therapy to Prevent  Sexual Transmission**

## Syphilis Issues

- Recommend against the use of azithromycin in areas of resistance
- Penicillin usage problems
- BIC shortage
- Specify use of Bicillin L-A (NOT Bicillin C-R)
- Diagnostic issues
- New EIA testing algorithms: reflexive quantitative RPR/VDRL, alternative treponemal test for discrepancies

## Syphilis TreatmentPrimary, Secondary & Early Latent

- _Recommended regimen for adults:_
- Benzathine penicillin G 2.4 million units IM in a single dose
- _Alternatives (non-pregnant PCN-allergic adults):_
- Doxycycline 100 mg po bid x 2 weeks
- Tetracycline 500 mg po qid x 2 weeks
- Ceftriaxone 1 g IV or IM qd x 8-10 d
- DELETED Azithromycin 2 g po in a single dose

## Penicillin G Usage Problems

**Penicillin G Usage Problems**

- Benzathine penicillin G shortage
- Inadvertent use of Bicillin C-R (Bicillin L-A is the appropriate drug)

## HPV Issues

- Clarify uses of HPV DNA test
- No change in diagnosis or treatment of external genital warts
- No discussion of HPV vaccine

## Clinical Indications for HPV DNA Testing

_**Proven to be clinically useful for:**_
- Triage of ASCUS Pap smears
- Adjunct screening in women age 30 and over
- 12-month f/u of LSIL in adolescents
- Post-colposcopy and post-treatment follow-up
_**NO proven benefit for:**_
- Triage of ASC-H, LSIL in adults or higher grade lesions
- STD screening in the general population
- Evaluation of sex partners
- Evaluation of genital warts

## STD Resources

- California STD/HIV Prevention Training Center
- _[www.stdhivtraining.org](http://www.stdhivtraining.org/)_
- National Network of STD/HIV Prevention Training Centers
- _[www.stdhivpreventiontraining.org](http://www.stdhivpreventiontraining.org/)_
- CDC Treatment Guidelines
- _[www.cdc.gov/std/treatment](http://www.cdc.gov/std/treatment)_