Screening, Vaccinations, and Expedited Partner Therapy

Transcription

1 Screening, Vaccinations, and Expedited Partner Therapy Will Make a Difference on HIV/STIs Katherine Hsu, MD, MPH, FAAP* Director, Ratelle STD/HIV Prevention Training Center of New England Massachusetts Department of Public Health Associate Professor of Pediatrics, Boston Univ. Med. Ctr. Waltham, MA June 2013 *No commercial disclosures or conflicts of interest Disclosures Dr. Hsu has NOT had significant financial interests or other relationships with manufacturer(s) of product(s) or provider(s) of service(s) that will be discussed in this presentation. This presentation will include discussion of pharmaceuticals or devices that have not been approved by the FDA. Off-label use of extra-genital (rectal and pharyngeal) nucleic acid amplification tests (NAATs) for gonorrhea and chlamydia 1

2 Before we begin Goals Review screening, vaccination, and expedited partner therapy recommendations for STI/HIV Highlight resources to support these activities Accomplish this in an interactive fashion Screening 2

3 Jeremy 24 year-old web designer presents for STD and HIV testing He reports exclusively male partners, 5 in past 6 months, insertive and receptive oral sex, occasionally anal sex (condoms) Good health, no complaints, GC ~3 years ago, last tested for HIV/STD 8 months ago Do you screen MSM differently than MSW for STI/HIV? 1. Yes 2. No 3. Sometimes 66% 23% 11%

4 HIV and Syphilis Rates in MSM Numerator based upon national 2008 surveillance data on new HIV and syphilis diagnoses Denominator based upon estimated proportion of men who engaged in same-sex behavior in past 5 years (3.9%) HIV diagnosis rate = 672/100,000 MSM 67x rate of other men 58x rate for women 1 o and 2 o syphilis diagnosis rate = 154/100,000 MSM 71x rate of other men 96x rate for women Purcell et al., Open AIDS J, 2012 People Living with HIV/AIDS, Diagnosed HIV Infection Cases, and Deaths among People with HIV/AIDS Massachusetts, People Living with HIV/AIDS Newly Diagnosed HIV Cases and Deaths among People with HIV/AIDS People Living with HIV/AIDS Diagnosed HIV Cases* Deaths among People with HIV/AIDS *Includes people concurrently or subsequently diagnosed with AIDS Data Source: MDPH, Bureau of Infectious Disease 4

5 Infectious Syphilis Cases by Gender Massachusetts, Male Massachusetts is no exception to the epidemic of syphilis occurring in MSM in the United States Female Data Source: MDPH, Bureau of Infectious Disease How common are CT and GC infections among MSM seeking STD testing? Urethral Rectal Pharyngeal Chlamydia Gonorrhea Kent CK et al, Clin Infect Dis 2005;41:

6 Majority of Rectal Infections in MSM are Asymptomatic Rectal Infections 86% 84% Urethral Infections Chlamydia n=316 Gonorrhea n=264 10% Asymptomatic Symptomatic 42% Chlamydia n=315 Gonorrhea n=364 Kent CK et al, Clin Infect Dis July 2005 STD Screening for MSM HIV Syphilis Urethral GC and CT Rectal GC and CT (if RAI) Pharyngeal GC (if oral sex) HSV-2 serology (consider) Hepatitis B (HBsAg, unless vaccinated) Anal Pap (consider for HIV+) * At least annually, more frequent (3-6 months) if at high risk (multiple/anonymous partners, drug use, high risk partners) CDC 2010 STD Tx Guidelines 6

7 What proportion of CT/GC infections may be missed if extragenital sites in MSM are not screened? 1. 10% 2. 25% 3. 50% 4. Over 50% 20% 29% 46% 6% Proportion of CT and GC infections among MSM not identified if screening only urine/urethral sites: Chlamydia Gonorrhea Identified Not Identified Kent, CK et al, Clin Infect Dis July

8 Chlamydia and Gonorrhea Nucleic Acid Amplification Testing still not FDA-cleared for rectal or pharyngeal specimens but now the preferred testing method over culture But Validation procedures can be done by labs to allow use of a non-fda-cleared test or application Test panel of known positive & negative samples against the cleared test t technology to demonstrate t good performance Many public health laboratories and at least two national commercial labs currently provide gc/chl NAAT for rectal/pharyngeal specimens Quest and LabCorp are two national commercial labs List of labs offering this type of testing is on the NNPTC website MDPH Hinton State Lab Institute offers gc/chl rectal NAAT on the Becton-Dickinson Qx platform, and gc culture for screening the pharynx This NAAT assay platform has not been validated for use on gc pharyngeal specimens because of lack of specificity (crossreactivity with other Neisseria species in the oropharynx) 8

9 Marrazzo, CDC-NNPTC Webinar: Sexual Health in MSM, June 7, 2012 Jeremy Comprehensive sexual health care: HIV Syphilis Urethral GC/CT Rectal GC/CT Pharyngeal GC HSV-2 serology Hep B (HBsAg) Hep C (HCV) HPV (DNA test) Anal Pap Vaccinations Counseling 9

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11 Chlamydia & Gonorrhea Screening: Preferred Genitourinary Specimens Females: Vaginal swab Vaginal swab samples are as sensitive as endocervical swab specimens, with no difference in specificity Self-collected vaginal swab versus cliniciancollected vaginal swab?! Endocervical swab and urine samples are acceptable, but urine may have performance when compared to genital swab samples Males: First catch urine In some studies, urethral swab samples sensitive than urine, though equivalently specific CDC Chlamydia & Gonorrhea Re-Screening Recommendations Increased emphasis on repeat screening of all infected with chlamydia and gonorrhea Recommended at 3 months after treatment Test of re-infection, not test of cure 11

12 Effective Practice Changes to Increase Uptake of Re-Screening Implementation of pop-up reminders at six large family planning clinics in California retesting rates for chlamydia and gonorrhea among those patients who returned to the clinic increased by 23% (from 70 to 86%) Western New York, University at Buffalo student health clinic implemented a three-step Treatment-Letter-Reminder ( , phone calls) in those with chlamydia infection re-testing rates went from 16 to 89% Howard et al., Burstein et al., 2012 National STD Prevention Conference Abstracts What is your usual first-line screening test for syphilis? 1. RPR 2. Syphilis EIA 3. Not sure 69% 26% 4%

13 Marrazzo, CDC-NNPTC Webinar: Sexual Health in MSM, June 7, 2012 Newer Treponemal Screening Tests Enzyme immunoassays (EIA) Trep-Sure IgM/IgG, CAPTIA Syphilis G (Trinity Biotech) wild type treponemal antigens Chemiluminescence immunoassays (CIA) LIAISON IgM/IgG (Diasorin) recombinant TpN17 Microbead immunoassays (MBIA) BioPlex 2200 Syphilis IgM and IgG (BioRad) recombinant TpN15, TpN17, TpN47 AtheNA Multi-Lyte T. pallidum IgG (Zeus Scientific) recombinant T. pallidum antigen p17kda Sena at al., CID

14 Syphilis Screening Paradigm EMERGING TRADITIONAL / NEW Treponemal Non-treponemal tests (e.g., EIA, tests CIA, (e.g., MBIA) RPR, VDRL) NON-SPECIFIC TO TP ANTIBODY QUALITATIVE TO LIPOIDAL ANTIGENS REACTIVITY PERSISTS OVER QUANTITATIVE LIFETIME REACTIVITY DECLINES WITH TIME reflex to Treponemal Non-treponemal tests (e.g., TPPA, tests FTA-Abs (e.g., RPR, VDRL) NON-SPECIFIC TO TP ANTIBODY QUALITATIVE TO LIPOIDAL ANTIGENS REACTIVITY PERSISTS OVER QUANTITATIVE LIFETIME REACTIVITY DECLINES WITH TIME Why switch to EIA/CIA? 180 tests per hour, no manual pipetting 14

15 CDC-Recommended Algorithm for Reverse Sequence Syphilis Screening 3% Radolf JD et al. MMWR, 2011 Probable false positive EIA If high risk: repeat RPR in several weeks 57% Assess for hx of treated syphilis, sx/signs If treated, no further action If untreated, consider tx for latent syphilis 32% 15

16 CDC Recommendations All reactive EIA/CIAs should be reflexed to a quantitative non-treponemal test (e.g. RPR, VDRL) Confirm reactive EIA/CIA Detect active infection Discordant specimens (e.g. EIA+/RPR-) should be confirmed with a 2nd treponemal test Confirmatory treponemal test should ideally be similarly sensitive and more specific than EIA/CIA TP-PA recommended FTA-ABS ABS test not recommended (lower specificity than other treponemal tests and probably lower sensitivity; also requires trained personnel and a dedicated fluorescence microscope) Results of all 3 tests (EIA, RPR, TP-PA) should be reported simultaneously to provider MMWR / February 11, 2011 / Vol. 60 / No. 5 Screening for STI/HIV in WSW WSW at risk for acquiring STIs from current and prior partners, both male and female Most self-identified WSW (53-99%) report having had sex with men and indicate they might continue Routine STI/HIV screening should be offerred to all women, regardless of sexual preference or practices CDC, 2010 STD Treatment Guidelines, MMWR 59(RR-12),

17 Screening Guideline Sources American Cancer Society (ACS) American College of Obstetrics and Gynecology (ACOG) American Society for Colposcopy and Cervical Pathology (ASCCP) HIV Medicine Association (HIVMA) American College of Physicians (ACP) American Academy of Pediatrics (AAP) American Academy of Family Physicians (AAFP) Centers for Disease Control and Prevention (CDC) United States Preventive Services Task Force (USPSTF) MSM in SF City Clinic Diagnosed with Rectal Chlamydia or Gonorrhea Rectal Chl or GC Annual HIV Incidence Adjusted HR Still HIV Uninfected None 2.25% % 2 or more episodes 15.00% % Bernstein et al. JAIDS,

18 Screening: This form of secondary prevention can be one pathway to sexual health! (But do we always remember to do it when appropriate? Can we build systems to remind us at appropriate intervals?) Vaccinations 18

19 Sexually Transmitted Infections Vaccine development Lab Testing Clinical Trials Marketed Neisseria gonorrhoeae Chlamydia trachomatis Treponema pallidum Haemophilus ducreyi HSV type 2 HPV types 6/11/16/18 Hepatitis A and B virus Trichomonas vaginalis HIV Slide courtesy of Peter Rice (updated) HPV Vaccines: Background, Safety, Efficacy, Recommendations 19

20 Epithelial HPV Infection Galloway DA. Lancet Infectious Diseases 2003; 3:469 Major Structural Viral Protein L1 Most abundant structural protein (each viral particle has 360 copies), highly immunogenic Can induce neutralizing i antibodies (>40-fold higher h than after natural HPV infection) which are thought to block viral entry into basal cells Self-assemble to form Virus-Like Particles (VLPs) Infectious Viral Particles (contain viral DNA) VLPs made in Insect Cells (no viral DNA) 20

21 Summary of HPV4 Vaccine Efficacy Data Population Endpoint Efficacy* % (CI) Females years HPV 16/18 CIN2 98% (93, 100) VIN/VaIN 2/3 100% (83, 100) Genital Warts 99% (96, 100) Males years AIN 2/3 75% (9, 96) Genital Warts 89% (65, 98)? Penile Cancer??? Oropharyngeal Cancer?? *Per protocol populations Pre-licensure Safety Data Summary* MCV4 Tdap HPV4 HPV years years 9-26 years years Injection-site pain 59% 75-78% 84% 92% Erythema 11% 21%** 25% 48% Swelling 11% 21-23%** 23% 25% 44% Fever 5% 5%** NS NS *Package insert data **Tdap non-inferior to Td 21

22 Bottom Line on HPV Vaccine Safety No live virus, no mercury, no thimerosal Widespread distribution; most common events consistent with trial data Post-licensure safety surveillance expected rate of adverse events CDC and FDA: Gardasil safe to use Recent Kaiser study ~190,000 females followed 2 years no evidence of autoimmune problems but for the faint of heart Slade et al. JAMA, August 19, 2009; 302 (7):750-7 Chao et al. J Internal Medicine. Feb 2012; 271(2): Is it the better part of valor to wait 15 minutes?! Syncopal events post-vaccination 63% occur <=5 min 89% occur within 15 min Although syncopal episodes are uncommon [~1%] and severe allergic reactions are rare, vaccine providers should strongly consider observing patients for 15 minutes after they are vaccinated. ACIP. MMWR 2006; 55(RR-15):19 Klein Arch Pedi Adol Med

23 Which patients benefit from the HPV vaccine? 1. Females age 11-12, before sexual debut 2. Adolescent males thru age Females Young adult MSM thru age All of the above 0% 0% 0% 0% 0% ACIP HPV Vaccine PopulationRecommendations Gender Age Females Routine vaccination with either (as young as 9) HPV4 or HPV Routine catch-up vaccination either HPV4 or HPV2* Males Routine vaccination w HPV4 (as young as 9) Routine catch-up vaccination HPV4 MSM & HIV+ Males Permissive i recommendation HPV Routine catch-up vaccination HPV 4 * Irrespective of history of abnormal Pap, HPV, genital warts MMWR, May ; 59(20): , MMWR, December ; 60(50);

24 HPV Vaccines: Uptake and implementation Estimated Vaccine Coverage Adolescents Ages National Immunization Survey, * On or after age 10 years Among females Among males MMWR 2012, 61(34):671 24

25 Physician Barriers 32-89% report parents negative beliefs about vaccine as significant barriers worries about promoting sexual activity, vaccine safety 34-67% report issues with insurance coverage and reimbursement as significant barriers Kahn, Ca Epidemiol Biomarkers Prev 2009 Daley, Pediatrics 2010 McCave, J Community Health 2010 Young, J Pedi Adol Gyn 2011 Vaccine Funding Programs Vaccines for Children Program Up to age 18, Medicaid eligible, uninsured or underinsured Receiving immunizations through a Federally Qualified Health Center or Rural Health Clinic, or Native American or Alaska Native Merck Vaccine Assistance Program Age 19, low income, and no health insurance coverage Phone number (8a-8p EST) Merck Dose Replacement Program Vaccine doses provided but not reimbursed GSK Vaccines Access Program Age 19-25, income eligible, and no heath insurance 25

26 Physicians Reported Barriers n (%) Parental concerns about vaccine safety 629 (69.2) Inadequate insurance coverage 610 (67.1) Parental lack of education about HPV 593 (65.2) Parental refusal because of negative media about vaccine 549 (60.4) Parental mistrust of vaccines in general 549 (60.4) Parental concern that consent will condone premarital sex 491 (54.0) Parental concern that vaccination would lead to riskier sexual behaviors 422 (46.4) Parental reluctance for clinician to discuss a STI vaccine 358 (39.4) Parental concerns about vaccine efficacy 208 (22.9) Insufficient vaccine supply 67 (7.4) Kahn, Ca Epidemiol Biomarkers Prev 2009 Parents Attitudes % of parents endorsed acceptance of HPV vaccination 58% in 2007 HINTs data (national survey) 75% in 2006 California survey Inconsistent trends reported for Race/ ethnicity Parent education Knowledge of HPV Socioeconomic status Brewer, Prev Med 2007 Fang, Ca Epidemiol Biomarkers Prev 2010 Chao, Am J Epi 2010 Constantine, J Adol Health

27 Factors Influencing Parental Acceptance Increased acceptance Physician recommendation consistently most important factor 1-5 Other factors: Perceived likelihood of contracting HPV; Perceived effectiveness of vaccine But is physician impact decreasing over time? (Darden, Pediatrics 2013) Do parents share physician concerns? Only 6-12% expressed concerns that vaccination would promote sexual activity 74.5% would vaccinate prior to age 13; only 5.5% preferred to vaccinate older child 1 Brewer Prev Med 2007; 2 Guerry Vaccine 2011; 3 Bednarczyk Vaccine 2011; 4 Bartlett J Sch Nurs 2011; 5 Thompson Ethn Dis 2011; 6 Litton J Ped Adol Gyn 2011; Constantine J Adolesc Health 2007 Barriers to Vaccination N=490 mothers of vaccine eligible girls (age 9-18) in Los Angeles, CA 29% of daughters had initiated vaccination, 11% completed series Barriers reported by mothers Not knowing where to get vaccinated (74%) Insufficient information about vaccine to make an informed decision (68%) Concerns over side effects (15-17%) 17%) Concerns that vaccination may lead to promiscuity (13%) Bastani R, Cancer Epi Biomarkers Prev 2011;20:

28 Receiving HPV Vaccine Does Not Increase Promiscuity National Survey of Family Growth n= yo females HPV vaccination NOT associated with: Being sexually active Number of sexual partners HPV vaccination was associated with: More consistent condom use among year olds (AOR=3.0, always wearing condom) Kaiser Permanente Center for Health Research n= yo girls in 2006, 30% of whom were vaccinated, followed thru 2010 No difference in markers of sexual activity including pregnancies, counseling on contraceptives, and testing for or diagnoses of sexually transmitted diseases Liddon NC, Am J Prev Med 2012;42:44 Bednarczyk RA, Pediatrics 2012;130:798 Text message reminders increase HPV vaccination *p=0.001, p=0.003 vs historical control Kharbanda EO et al. Vaccine 2011 Mar 21; 29(14):

29 *New* HEDIS MEASURE HPV Vaccination Healthcare Effectiveness Data and Information Set (HEDIS) Performance measurement tool > 90% of health plans use 75 separate measures HPV vaccination measure added in 2012 Percentage of 13 year old females who had 3 doses of HPV vaccine Australian EGW Impact Study 29

30 JO Kahn study on impact on colpo Vaccination: This form of primary prevention is ANOTHER pathway to sexual health! 30

31 Sexual Exploration We don't teach infants to crawl or walk by moving their limbs for them although they are inefficient at first, this is something they have to do for themselves Of course, we want to minimize risk "if crawling is unsafe because the floor is dirty or littered with broken glass, the appropriate response is not to confine and restrict the child from crawling, but to clean up the mess." Bay-Cheng L et al., "Not Always a Clear Path": Making Space for Peers, Adults, and Complexity in Adolescent Girls' Sexual Development, from Sexualization of Girls and Girlhood, Zurbriggen EL and Roberts T-A, eds., Oxford University Press, Young Adult Brain Development Concepts of early, mid and late adolescence Work-in-progress being replaced by adaptive-adolescence adolescence theories» Love of novelty leads directly to useful experience; hunt for sensation provides the inspiration needed to "get you out of the house" and into new terrain» Risk-taking occurs because more weight is given to payoff, particularly new social rewards and relationships, not because less weight is given to risk (risk-taking is necessary to move out of the home into less secure situations)» Douglas Fields, NIH neuroscientist, This makes the period when a brain area lays down myelin a sort of crucial period of learning the wiring is getting upgraded, but once that's done, it's harder to change." 31

32 Rather than trying to eliminate adolescent risk taking via abstinence programs or training in social skills or social norms strategies that have not proven successful to date a better tactic might be to reduce costs of adolescent risk taking by limiting access to particularly harmful risk-taking situations, while providing opportunities to engage in risky and exciting activities under circumstances designed to lessen changes for harm. Spear LP, Adolescent neurodevelopment, JAdolHealth,

33 Expedited Partner Therapy Have you ever prescribed an antibiotic to a contact of someone with an infectious disease, without examining the contact? 1. Yes 2. No 0% 0%

34 What is Expedited Partner Therapy (EPT)? A partner management strategy to tx sex partners of patients diagnosed with STIs Clinician provides medication or prescription to patient, who brings it to his/her partner(s) Partner tx given without the health care provider first examining the sex partner Infection During Follow-up Among Patients Completing The EPT Trial Percent Standard care Expedited care P=.17 P=.04 P= Gonorrhea Chlamydia Gonorrhea or N=358 N=1595 Chlamydia N=1860 Golden MR, NEJM

35 Clinical Provider Notification CLINICAL ADVISORY: UTILIZING EXPEDITED PARTNER THERAPY (EPT) FOR CHLAMYDIA INFECTION IN MASSACHUSETTS August 2011 Advisory is posted on MDPH website Advisory will be distributed through licensing Boards and Division of STD Prevention provider network Will collaborate to provide link on MMS website bit as well as other professional organizations Partner/Patient Information A Message for Partners about Chlamydia Infection Expedited d Partner Therapy (EPT) August 2011 Information sheet provided by the Massachusetts DPH (or comparable to that provided by the DPH) will be given out whenever possible with each dose of azithromycin and dbe available aaabeonline Question/Answer format easy to read language Encouragement to follow up with clinical provider 35

36 Pharmacy Information Utilizing Expedited Partner Therapy (EPT) for Chlamydia Infection September 2011 Information sheet provided by the Massachusetts Board of Registration in Pharmacy Although every prescription in the Commonwealth is normally required to contain name and address of patient, EPT (or E.P.T. PT or Expedited Partner Therapy") may be used in place of the name, and the address may be left blank Massachusetts: How to Provide EPT for Chlamydia Provision of EPT by clinicians is voluntary, not required MDPH recommends three options for clinicians implementing EPT for chlamydia: 1. Written prescription for named sex partner(s) of infected patient 2. Written prescription using, in place of the partner s name and address, Expedited Partner Therapy, E.P.T. or EPT, which partner can have filled at any Massachusetts pharmacy 3. Direct dispensation of medication, one dose to be taken immediately by patient, additional dose or doses to be delivered by patient to the sex partner(s) (separate, properly labeled container(s) should be used for dose(s) for each sex partner) If an EMR or e-prescribing system does not permit prescription for Expedited Partner Therapy, E.P.T. or EPT, an information sheet listing fields required is available online to assist prescribers with generating a written prescription Providers may also wish to consider contacting a prescription form vendor to obtain blank prescription forms 36

37 CDC EPT guidelines PDPT can prevent reinfection of index case and has been associated with a higher likelihood of partner notification Expedited Partner Therapy EPT is supported by the CDC and permissible in over 30 states Standard treatment for chlamydia infection is one oral dose of 1g of the antibiotic azithromycin EPT has been shown to be safe and effective in the treatment of sex partners Most states with long standing EPT programs also have had no reports of adverse events 37

38 Timeline: EPT in Massachusetts July 2010 Chapter 131, Section 62, of the Acts of 2010 required Department to promulgate regulations authorizing certain healthcare providers to prescribe or dispense antibiotics to treat t chlamydia infection in the sex partner(s) of infected patients, without an examination of the partner(s) (EPT) August 2011 Passage of regulation: BORM, BORN, BORP Dissemination of clinical and pharmacy advisories, including translated versions of patient/partner information January 2012 New chlamydia case report form implemented to track EPT usage in Massachusetts EPT for Chlamydia Infection in MA: January-June cases of chlamydia reported between January 1 June 30, % of case report forms reported partner notification, mainly via patient notification of partners 6% of case report forms indicated EPT was used 3% patient delivered medication 3% patient delivered t dli dprescription <1% combined methods (both EPT methods or inoffice treatment combined with EPT) Barker K et al., MDPH Internal Communication 38

39 EPT for Chlamydia Infection in MA: Preliminary Conclusions Regarding Usage Partner notification was reported ~1/4 of cases, mainly via patientnotification notification of partners A minority of reported chlamydia cases receive EPT (6%) School based clinics, private practices/hmos and community health centers reported using EPT in a larger proportion of patients compared to emergency room/urgent care settings Female patients were 2.65 times more likely to have received EPT as compared to male patients (95% CI: , p>0.0001) It may be high yield to target emergency room/urgent care settings given that they see a large proportion of chlamydia cases but relatively under utilize EPT Barker K et al., MDPH Internal Communication Expedited Partner Therapy: It will help reduce reinfection, BUT can we convince ourselves and our patients to use it? 39

40 Thinking Beyond the Latex Barrier Expedited Partner Therapy Social Structure, Policy, and Systems Community STI Screening Guidelines and HPV Vaccination Recommendations Institutional/Organizational Condoms Interpersonal Individual Bolan, National STD Prevention Conference

41 Bolan, National STD Prevention Conference 2012 STI Resources CDC STD Treatment Guidelines Misnomer! Prevention Screening Counseling Management AND Treatment Guidelines National Network of STD/HIV Prevention Training Centers Massachusetts Department of Health 41

42 What is your primary profession or discipline? 1. Nurse 2. Advanced Practice RN (NP, CNM) 3. Physician Assistant (PA) 4. MD/DO 5. Other >20 How many years have you been practicing? 42

43 What setting do you primarily practice in? 1. Community health center 2. Largemulti specialtygroup group practice 3. Private practice 4. Hospital based clinic 5. ED/Urgent Care 6. School health (including college/university) 7. Specialty clinic setting (e.g. STI, HIV, or Family Planning) 8. Other THANK YOU! HPV Syphilis Chlamydia HSV-2 HIV Gonorrhea 43