Rises in STI Rates: Who, What, Why, and What Public Health Can Do

Transcription

1 Number of Cases 5/24/2018 Rises in STI Rates: Who, What, Why, and What Public Health Can Do Katherine Hsu, MD, MPH, FAAP* Medical Director, Div. of STD Prev., Mass. Dept. of Pub. Health Associate Professor of Pediatrics, Boston Univ. Med. Ctr. June 2018 Disclosures In the past 12 months, Dr. Hsu has had the following 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: GSK Neisseria Vaccines Consultation, Sept 2017 Reimbursed travel only 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 Goals Review STI epidemiologic trends Explain why expanded STI screening in high-risk populations, and rapid STI treatment can decrease population STI burden Discuss newer STI diagnosis and prevention technologies Hint at the future of STD prevention STIS HAVE RETURNED TO 1990S LEVELS Syphilis and Gonorrhea Over Time Gonorrhea Trends by Gender Identity 4000 Reported Gonorrhea Cases by Gender Identity*: Massachusetts ( ) Co-infections: Gonorrhea-HIV ~8% Syphilis-HIV ~40% Decreases in syphilis cases were due to BOTH behavior change AND to deaths occurring in HIV-syphilis co-infected individuals Male Female 500 Infectious syphilis is defined as primary, secondary and early latent stages of syphilis within one year of infection. Data Source: Massachusetts Department of Public Health/Bureau of Infectious Disease and Laboratory Sciences/ Division STD Prevention Interpret 2014 STI data with caution due to a mid-year conversion to a new surveillance system Year N=40,929 Data are current as of 6/16/2017 and are subject to change. Data Source: Massachusetts Department of Public Health/Bureau of Infectious Disease and Laboratory Sciences/ Division STD Prevention *There were several cases reported as transgendered in 2014 through Transgender identity was not documented prior to the MAVEN transition in 2014 and transgendered individual are included in the specified gender categories. 1

2 N = 498 N = 26,448 STI COMPLICATIONS ARE THEREFORE MORE COMMON Epi Take Home Points STI case reports are at record highs Reflective of national and regional trends Increases in male cases dominating reporting trends for bacterial STIs Increases not limited to those 25 years of age We are seeing more STI complications Fiumara Collection, MDPH Are these increases reflective of Increased screening and reporting? More people acquiring STIs? The same people acquiring more STIs? All of the above? Graciaa et al., OFID 2017 Massachusetts Department of Public Health Bureau of Infectious Disease and Laboratory Sciences Division of STD Prevention Individuals with Repeated Sexually Transmitted Infections Massachusetts, WHAT IS PUBLIC HEALTH DOING ABOUT THIS? Katherine Hsu, Lauren Molotnikov, Kathleen Roosevelt, Heather Elder, R. Monina Klevens, Alfred DeMaria, Jr., Sevgi Aral Clin Infect Dis,

3 Objectives Methods To characterize the proportion of reported STIs in individuals with repeated infections To describe patterns among individuals with the greatest number of repeated infections Retrospective, population-based study Laboratory-confirmed chlamydia, gonorrhea, or infectious syphilis cases (STIs) Time period: July 28, July 27, 2016 Selected population : 13 to 65 year olds Sub-group of interest: cases with 5 STIs during 2 years (highvolume repeaters) Analysis performed using SAS 9.3 Results: Cases of Confirmed Chlamydia, Gonorrhea, and Infectious Syphilis, Massachusetts High-Volume Repeaters ( 5 STIs) Overall Sample Male Female P value[1] N = 160 (%) N = 118 (74%) N = 42 (26%) Age at Last STI Diagnosis (years)[2] <0.001 Of year olds in Massachusetts (N = 4,847,510): 1% (49,142) were reported with bacterial STI 0.1% (6,999) accounted for 28% of all reported bacterial STIs (25) 11 (9) 29 (69) (45) 60 (51) 12 (29) (19) 29 (25) 1 (2) (9) 14 (12) 0 (0) (3) 4 (3) 0 (0) Race/Ethnicity[3] Non-Hispanic White 59 (37) 51 (43) 8 (19) Non-Hispanic Black 49 (31) 35 (30) 14 (33) Hispanic 30 (19) 15 (13) 15 (36) Non-Hispanic Other 17 (11) 14 (12) 3 (7) Unknown 5 (3) 3 (3) 2 (5) [1] P values were calculated using Fisher s exact test. [2] No high-volume repeaters were over age 59 years. [3] White, Black, and Other Non-Hispanic include those with unknown or unreported ethnicity. Other race category may include Asian/Pacific Islander, American Indian/Alaskan Native, Multi-Racial, and those reported as Other. Hispanics can be of any race. [4] No high-volume repeaters were gonorrhea or syphilis-infected only. [5] Clinical system defined as a network with shared access to clinical and laboratory information. High-Volume Repeaters: Sexual Risk and Type of Infection Overall Sample Male Female P value[1] N = 160 (%) N = 118 (74%) N = 42 (26%) Gender of Sexual Partners <0.001 Male 120 (75) 93 (79) 27 (64) Female 6 (4) 6 (5) 0 (0) Both 10 (6) 10 (8) 0 (0) Unknown 24 (15) 9 (8) 15 (36) STI[4] <0.001 Syphilis, gonorrhea, and chlamydia 30 (19) 30 (25) 0 (0) Gonorrhea and chlamydia 103 (64) 84 (71) 19 (45) Syphilis and gonorrhea 2 (1) 2 (2) 0 (0) Syphilis and chlamydia 1 (1) 1 (1) 0 (0) Chlamydia only 24 (15) 1 (1) 23 (55) [1] P values were calculated using Fisher s exact test. [2] No high-volume repeaters were over age 59 years. [3] White, Black, and Other Non-Hispanic include those with unknown or unreported ethnicity. Other race category may include Asian/Pacific Islander, American Indian/Alaskan Native, Multi-Racial, and those reported as Other. Hispanics can be of any race. [4] No high-volume repeaters were gonorrhea or syphilis-infected only. [5] Clinical system defined as a network with shared access to clinical and laboratory information. High-Volume Repeaters: HIV Status, Field and Clinical Follow-up Overall Sample Male Female P value[1] N = 160 (%) N = 118 (74%) N = 42 (26%) HIV Status <0.001 Prior infection 31 (19) 31 (26) 0 (0) Infected in this time period or after 10 (6) 10 (9) 0 (0) Not known to be HIV-infected 119 (74) 77 (65) 42 (100) Field Epidemiologist Contact <0.001 Yes (ever interviewed) 15 (9) 15 (13) 0 (0) No (declined, unable to locate) 25 (16) 25 (21) 0 (0) No (not offered) 120 (75) 78 (66) 42 (100) Diagnosing Clinical System[5] 0.37 One system 71 (44) 58 (49) 13 (31) Multiple systems 89 (56) 60 (51) 29 (69) [1] P values were calculated using Fisher s exact test. [2] No high-volume repeaters were over age 59 years. [3] White, Black, and Other Non-Hispanic include those with unknown or unreported ethnicity. Other race category may include Asian/Pacific Islander, American Indian/Alaskan Native, Multi-Racial, and those reported as Other. Hispanics can be of any race. [4] No high-volume repeaters were gonorrhea or syphilis-infected only. [5] Clinical system defined as a network with shared access to clinical and laboratory information. 3

4 Summary: Patterns Among Individuals with Greatest Number of Repeated Infections The majority of high-volume repeaters sought care in more than one clinical system (56%) Few had interaction with our field epidemiologists (9%) No interviewed high-volume repeaters named each other as sexual contacts Only males were co-infected with HIV (35%) Majority of males reported same-sex contacts (87%) Conclusions Repeaters are a small portion of the overall population, but contribute a large volume of STIs Disproportionately high impact on the circulating of STI and HIV infection in the population Infections among high volume repeaters may be hidden from clinicians and clinical systems due to fragmented care Public health can play a crucial role in identifying and reaching these individuals State and local jurisdictions have sufficient identifying information to act Next Steps New Model for Public Health Follow-up? Need greater understanding of the underlying sexual network In order to intervene in the spread of STIs and HIV Provide Pre-Exposure Prophylaxis (PrEP) referrals and other services to repeatedly infected HIV-negative cases Help reduce risk to reproductive-aged females Infertility prevention Contact tracing, treatment, and prevention during pregnancy results in double benefit (mother and infant) WHAT COULD COLLABORATING WITH CLINICAL MEDICINE ACCOMPLISH? Population-level Control of STIs 1. ENCOURAGE GENERAL STI SCREENING, THEN FOCUS SCREENING AND PREVENTION ON HIGH- RISK POPULATIONS FOR HIGHEST YIELD R o = T C D Basic Reproductive Rate Screening decreases D (duration) of carriage and therefore transmission Anderson & May, 1980s 4

5 Proportion of CT and GC infections MISSED among 3398 asymptomatic MSM if screening only urine/urethral sites, San Francisco, A. MSM STI SCREENING IS IMPORTANT FOR MAINTAINING SEXUAL HEALTH Chlamydia Gonorrhea Marcus et al, STD Oct 2011; 38: The q3mth Triple Dip for at-risk MSM Screen more or screen more often? Agent-based model of syphilis transmission representing 2,000 high-risk MSM from Toronto, Canada data HIV/Syphilis/ HepC* Serologies Pharyngeal GC NAAT** Urine GC/CT NAAT Rectal GC/CT NAAT** How do we scale up screening frequency in high-risk MSM? *In HIV-coinfected individuals, screen hep C at least annually **Off-label use - not FDA-approved for testing at extragenital sites, but many reference labs have validated the assay for use Slide courtesy of Brad Stoner Figure 2. Model-projected annual rates of reported infectious syphilis. Results are based on 1000 realizations of each intervention scenario and are presented as mean values with corresponding 95% uncertainty bounds. Prior to 2011, all scenarios included annual screening only, with the specified interventions implemented at the start of 2011 (indicated by a dashed line). Tuite et al. BMC Pub Health, 2013 Self-collected STI Testing but concerns about sensitivity & specificity abound Fakile Y, STD Prevention Conference, Acceptable to many patient populations FDA-approved for certain GC/CT/trich NAAT testing platforms and sample types Equivalent or greater sensitivity than clinician-collected samples Improved uptake of STI screening Gaydos. Sex Trans Dis,

6 Dean St Express Clinic, Soho, London Walk-ins Treatment for positive gonorrhoea and chlamydia tests If you ve had sex with a person who tells you they had gonorrhoea or chlamydia HIV PrEP three monthly monitoring Follow up for people who started emergency HIV PEP at 56 Dean Street Vaccines Appointments Sexual health screening for people without symptoms (STI/STD and HIV tests) with results in 6 hours 1B. RE-SCREENING FOR STIS IN THOSE PREVIOUSLY INFECTED, REACHES THOSE AT HIGHEST STD RISK Repeat Screening after STI Current CDC STI screening guidelines for GC and CT recommend screening persons at-risk, including those with a prior STI Among sex workers with baseline GC, CT or trichomonas infection, the adjusted HR for any of these at follow up was 2.6 (95% CI ) (Turner 2010) Project RESPECT in US STD clinic patients: 25.8% of women had 1 or more new infections with CT, GC, or Trich at one year of follow up. 14.7% of men had a new GC or CT infection. Conclusion: patients with GC/CT or trich infections should return at 3 months because they are at high risk for new infections (Peterman 2006) One in four women with chlamydia infection at baseline retested positive, supporting recent recommendations to routinely retest chlamydia positives. Sexually active female students years old, enrolled in the British Prevention of Pelvic Infection (POPI) trial between , who self-collected 2 vaginal swab specimens Aghaizu A et al. STI 2014 Recommendations: Repeat Screening After STI Women with CT, GC or trich should be rescreened at 3 months after treatment. Men with CT or GC should be rescreened at 3 months after treatment. Patients diagnosed with syphilis should undergo follow up serologic serology per current recommendations. One Massachusetts ACO: Percent of Chlamydia trachomatis cases retested within recommended time period Among cases with repeat tests, 17.3% of pregnant females, 16.2% of non-pregnant females, and 18.1% of males had positive results. Dee et al., manuscript submitted. We are underutilizing repeat testing as a tool for identifying higher risk patients 2015 CDC STD Treatment Guidelines 6

7 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% success lay in bringing patients back sooner than 3 mos 2. TREAT STIS WITH THE RIGHT DRUGS QUICKLY Howard et al., Burstein et al., 2012 National STD Prevention Conference Abstracts Population-level Control of STIs R o = T C D Basic Reproductive Rate Screening and RAPID APPROPRIATE treatment decrease D (duration) of carriage and therefore transmission Principles of STI Treatment Symptomatic Test AND treat immediately, based on STI syndrome Reports contact Test AND treat immediately, according to reported exposure Asymptomatic, no specific contact Screen and treat according to results Anderson & May, 1980s Delays in Gonorrhea Treatment Massachusetts /2523 randomized cases agreed to interview Symptomatic/contact cases Median time to treatment = 0 days BUT 42% not treated on day 0 Asymptomatic Median time to treatment = 4 days BUT 51% treated 5 days after sample collection Delays more common in symptomatic women, asymptomatic MSM Symptomatic/contact cases had shorter time to treatment compared to asymptomatic cases, who may contribute more to population transmission of gonorrhea. BUT, in both groups, treatment delays are common. MA unpublished data, 2018 Gonorrhea Treatment Uncomplicated Genital, Rectal, or Pharyngeal Infections Ceftriaxone 250 mg IM in a single dose PLUS* * Regardless of CT test result Doxycycline demoted from recommended to alternative, because of tetracycline resistance in U.S. GISP isolates Azithromycin 1 g orally CDC 2015 STD Treatment Guidelines 7

8 How does gonococcal resistance develop? Microorganisms with the threat level of URGENT: 1. C. difficile 2. Carbapenem-resistant Enterobacteriaciae 3. Drug-resistant N. gonorrhoeae Transformation plays the key role N. gonorrhoeae highly competent for transformation throughout life cycle by its own DNA or via closely related bacteria such as other Neisseria commensals and N. meningitidis Pharyngeal gonorrhea may act as a reservoir where asymptomatic co-colonization with other Neisseria species of this obligate human pathogen can occur Example: Asp345A insertion in PBP2 resulting in decreased penicillin binding affinity, likely originates from commensal Neisseria species Cross-species conjugal plasmid transfer also possible TetM and B-lactamase-encoding plasmids relatively efficiently transferred intercellularly between N. gonorrhoeae strains, as well as N. meningitidis, H. influenzae, and E. coli Unemo & Shafer, Ann NY Academy of Sciences, 2011 First Description of High-Level Cephalosporin Resistance Isolate came from pharynx of female CSW in Kyoto Cftx MIC 2 mcg/ml (R) to cefixime (MIC 8 mcg/ml), -lactams, fluoroquinolones, macrolides, tetracycline, TMP-SMX, chloramphenicol, nitrofurantoin (S) to spectinomycin, rifampin, possibly aminoglycosides and tigecycline, possibly carbapenems Unique pena mosaic allele similar to that found in N. meningitidis and N. flavescens encodes variant of PBP2 mtrb, penb, pona1 mutations also present Subsequent Cephalosporin Treatment Failures Mostly Described in Pharynx Unemo et al. Ceftriaxone treatment failure of pharyngeal gonorrhoea verified by international recommendations, Sweden, July Euro Surv, 2011 Cftx MIC mcg/ml Mosaic pena, mtrb and penb alterations identified 250 mg cftx: median times of free cftx in serum above MIC only 24 and 15 hours for these MICs; pharyngeal accessible cftx is of shorter duration Unemo et al. Treatment failure of pharyngeal gonorrhoea with internationally recommended first-line ceftriaxone verified in Slovenia, September Euro Surv, 2012 Cftx MIC mcg/ml Mosaic pena, mtrb and penb alterations identified Unemo et al. High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel pen A mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemo, 2012 Urethral isolate in MSM, unknown if orally acquired Cftx MIC 1-2 mcg/ml, cefixime MIC 4 mcg/ml Mosaic pena alteration identified Gonorrhea: When/How To Do Test-of-Cure? Pharyngeal gonorrhea treated with an alternative regimen (anything other than combined ceftriaxone + azithromycin) Use either culture or NAAT 14 days posttreatment Cftx MIC 0.5 mcg/ml Azithromycin MIC >256 mcg/ml Pharyngeal carriage finally eradicated by ertapenem IV x 3 days Symptoms that persist after treatment Evaluate using culture and susceptibility testing 8

9 Other Ways to Stem Tide of MDR GC (1) Rapid POC testing same day diagnosis Almost prime time May include POC testing for resistance too Will eliminate gap time to treatment for asymptomatic patients (therefore less carriage and transmission) May provide information for more targeted antimicrobial treatment Population-level Control of STIs R o = T C D Basic Reproductive Rate What about modifying transmissibility? Anderson & May, 1980s Other Ways to Stem Tide of MDR GC (2) Petousis-Harris et al. Lancet, 2017 Goals for Syphilis Vaccine Development NIAID Workshop on Development of Syphilis Vaccine (2017) Implement modern microbiological, molecular and immunological techniques and technology in syphilis research Develop in vitro culture system for T. pallidum Develop genetic manipulation of T. pallidum Identify human and animal correlates of protection Improved diagnostics, moving towards point-of-care Syphilis vaccine preferred characteristics Ideally vaccine administered before sexual debut to prevent first infections Prevention of mother-to-child transmission Possibly at-risk population targeting MSM At-risk child-bearing aged women Slide courtesy of T. Hiltke and L. Vincent Syphilis Vaccine Candidates T. pallidum repeat protein (Tpr) Tpr Subfamily I (Tpr F/I; Tpr C/D) Β-barrel domain embedded in the outer membrane with surface exposed epitopes Loop 5 in particular is highly conserved amongst T. pallidum strains Reduces ulceration of primary lesions and induces opsonic antibody Tpr K Nearly conserved N-terminal region Induces opsonic antibody and reduces T. pallidum in chancres Tp0751/Pallilysin Vascular adhesin with sequence 100% conserved between strains Shares lipocalin structure with N. meningitidis vaccine component fhbp Inhibits bacterial dissemination TP0326/BamA Loop 4 of B-barrel contains opsonic target and immunodominant epitope TP0435 Slide courtesy of Highly expressed immunogenic lipoprotein adhesin T. Hiltke and L. Vincent Expressed on the surface and in the periplasm of the spirochete Summary STI rates are going up (again) Public health surveillance and contact tracing can provide insight into why Repeatedly infected individuals are a small proportion of the overall population, but contribute a large volume of reported STIs Partnership with clinical medicine can improve screening levels and speed up appropriate treatment Must make better use of systems (reminder/recall) and technology (self-collection) to automate screening STI vaccine development provides hope for the future of prevention Must advocate for investment in STI vaccine research 9

10 RESOURCES Misnomer! Prevention Screening Counseling Management AND Treatment Guidelines Want to know more about STDs? There s an app for that. CDC STD Treatment Guidelines App for Apple and Android Available now, FREE! (accept no competitors) Search STD Treatment in App store STD Clinical Consultation Network STDCCN NEW!!! Provides STD clinical consultation services within 1-5 business days, depending on urgency, to healthcare providers nationally Your consultation request is linked to your regional PTC s STD expert faculty Just a click away! The National STD Curriculum integrates the most recent CDC STD Treatment Guidelines into a free, up-to-date, educational website. The site addresses the epidemiology, pathogenesis, clinical manifestations, diagnosis, management, and prevention of STDs. Seven Self-Study Modules Twelve Question Bank topics with 100+ interactive board-review style questions Modular learning in any order with progress tracker Group registration and tracking for staff, students, and health care organizations FREE CME and CNE credits This curriculum was funded by a grant from the CDC and developed by the National Network of STD Clinical Prevention Training Centers 10