DISCLOSURES 9/25/2018. Sexually Transmitted Infections: New and Not so New Bugs. Center for Community Practice. Designated by AIDS Institute

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1 Sexually Transmitted Infections: New and Not so New Bugs Melinda S Godfrey MBA, MS, NP University of Rochester Infectious Disease Division Monroe County STD Clinic New York State, STD Center of Excellence Center for Community Practice Designated by AIDS Institute NYSDoH as the New York State STD Center of Excellence STD/HIV/VH Training Center Monroe County STD/HIV Program Provided integrated STD/HIV prevention services since 1988 Designated by CDC Capacity Building Center for health departments in the U.S. DISCLOSURES I have no disclosures to report. I will mention some testing methodologies and treatments that are not FDA approved but are CDC recommended 1

2 LEARNING OBJECTIVES 1. Describe current epidemiology of common & new Sexually Transmitted Infections. 2. Identify the clinical manifestations and diagnosis of STIs 3. List the current treatment recommendations of common STIs STDs Organisms and Syndromes N. gonorrheae HBV Epididymitis Vulvitis C. trachomatis HSV Molluscum contagiosum Vaginitis M. genitalium HPV Viral Hepatitis Vaginosis U. urealyticum CMV Proctitis Cervicitis T. pallidum HTLV-I & - II AIDS PID G. lambria HTLV-11 Urethritis Neoplasia H. ducreyi HHV-8 Arthritis Infertility C. granulomatis HIV Conjunctivitis Iritis T. vaginalis S. scabiei Neonatal Diseases Warts E. histolytica P. pubis Adverse Pregnancy Outcomes Recent - Ebola virus, Zika virus, meningococcus 2

3 CDC Estimates of the STD Burden in the US Now > 20 million (10/13/16) STIs and STDs - in general: 1/3 of those infected with an STI: have no clinical signs and no symptoms 1/3 have no symptoms: but have clinical signs on examination 1/3 of those infected with an STI: have clinical signs on exam and complaints of symptoms Syphilis 3

4 2015 April, 2017 STD Awareness Month

5 Syphilis: What s new New cases still on the rise Newer testing algorithms widely utilized Health alert for eye diseases "New rapid CLIA waived test Congenital syphilis (NYS Alert 7/2018) Primary and Secondary Syphilis Rates of Reported Cases by State, United States and Outlying Areas 2016 STD Surveillance Report 2016 Primary and Secondary Syphilis Rates of Reported Cases by County, United States and Outlying Areas, 2016 STD Surveillance Report 2016 NOTE: In 2016, 1,699 (54.1%) of 3,140 counties in the United States reported no cases of primary and secondary syphilis 5

6 Primary and Secondary Syphilis Reported Cases by Sex and Sexual Behavior, 36 States*, STD Surveillance Report 2016 Primary and Secondary Syphilis Rates of Reported Cases by Sex and Male-to-Female Rate Ratios, United States, STD Surveillance Report 2016 Primary and Secondary Syphilis Reported Cases by Sex, Sexual Behavior, and HIV Status, 31 States*, 2016 STD Surveillance Report

7 Congenital Syphilis Reported Cases by Year of Birth and Rates of Reported Cases of Primary and Secondary Syphilis Among Women, United States, STD Surveillance Report 2016 Primary and Secondary Syphilis Distribution of Cases by Sex and Sexual Behavior, United States,

8 Syphilis Primary (10-90 days) chancre (painless ulcer) with non-tender adenopathy resolves spontaneously Secondary (6-9 weeks later; may recur if untreated) chancre still present ~15%; classic rash (palms and soles), condylomata lata, patchy alopecia, mucus patches, hepatitis Tertiary (years later) end organ damage, cardiovascular (thoracic aneurysm), gumma, CNS (meningitis, eye dx, CN defects, paresis, tabes dorsalis) Signs & Communicability Vary by Stage No Signs or Symptoms Incubating 0-90 days Early Latent Late Latent Primary Secondary 2 weeks 6 months 12 months.years Chancre Rash, Nodes, lesions Sexual Transmission Tertiary Cartilaginous, heart & central nervous system Perinatal Transmission Primary syphilis-chancre 8

9 Primary Syphilis Develops ~ 3 weeks after infection (10-90 days) Lesion begins with painless erythema that subsequently ulcerates Ulcer (chancre) has clean base and clear exudate Indurated (can t press the edges together) May have painless unilateral inguinal lymphadenopathy RPR may be negative when chancre develops. Specific tests positive earlier. Secondary Syphilis Secondary Syphilis 9

10 PE no ulcer no rash RPR 1: 256 HIV negative Syphilis - Diagnosis Clinical Diagnosis poor Direct visualization of organism (very specialized) Culture - not available Serology cornerstone of diagnosis Non-Treponemal (non-specific tests) e.g. RPR Treponemal Tests (specific confirmatory tests) e.g. FTAab, ELISA need both specific and non-specific tests to accurately diagnose and stage syphilis Decline in RPR in follow up used to assess response to treatment 10

11 Traditional Syphilis Screening Algorithm NT: RPR, etc Nonreactive Reactive No Syphilis or Early primary syphilis Order FTA if syphilis suspected) Nonreactive T: FTA, etc Reactive No Syphilis False positive RPR or early primary - repeat testing if syphilis suspected Syphilis Evaluate for Need for treatment 32 Reverse Syphilis Screening Algorithm T: EIA, etc Nonreactive Reactive No syphilis or Early primary syphilis (Order FTA if syphilis suspected) Nonreactive T: FTA or TPPA Nonreactive Reactive NT: RPR Reactive Syphilis Evaluate need for treatment 33 Syphilis Treatment by Stage Primary, Secondary, Early Latent Syphilis* LA Benzathine Penicillin 2.4 million units IM x 1 Doxycycline 100 mg po bid x 14 days * sexual partners need treatment as well!! Late Latent Syphilis LA Benzathine PCN 2.4 million units x 3 weekly Doxycycline 100 mg po bid x 14 days *Diagnosis of syphilis should prompt test for HIV 11

12 CDC Alert Ocular Syphilis Issued 2015 after increased cases reports from LA, San Francisco, and Seattle 24 cases reported in WA and CA in first quarter MSM/HIV+ Some Heterosexuals Few with sequelae of blindness Several probable/possible cases in addition Report suspected cases: 11/4/16 MMWR update 377 cases in past 2 years in 20 states. Primarily HIV/MSM Syphilis Rapid Test Now CLIA-waived 12/2014, the FDA issued a CLIA waiver for a rapid syphilis screening antibody test (whole blood, serum, or plasma) This waiver allows the test to be performed by nonlaboratory staff in a variety of settings, e.g., Medical offices, emergency departments/urgent care centers, outreach sites, community-based organizations Studies leading to FDA approval reported 95-99% sensitivity & 91-98% specificity respectively Recent reports at NCSD conference 45% false positive Negative predictive value high 12

13 Gonorrhea Gonorrhea - What s new Resistance Worries - Cephalosporin resistance coming (soon?) single case in North America so far (Quebec) - Azithromycin resistance reported in US NAATs for Extra-genital testing Gonorrhea Rates of Reported Cases, United States, STD Surveillance Report

14 Gonorrhea Rates of Reported Cases by State, United States and Outlying Areas 2016 STD Surveillance Report Gonorrhea Rates of Reported Cases by County, United States and Outlying Areas, 2016 STD Surveillance Report Gonorrhea Rates of Reported Cases by Sex, United States, STD Surveillance Report 2016 NOTE: In 2016, 1,699 (54.1%) of 3,140 counties in the United States reported no cases of primary and secondary syphilis 44 14

15 GC Urethritis Males Incubation Typically 3-7 days asymptomatic infection may occur (10%) Symptoms Dysuria, purulent or mucopurulent discharge Signs Yellow purulent discharge may be mucoid or mucopurulent (10%) Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides GC Cervicitis Incubation Unknown but S/S generally develop by 10 days Symptoms Present in 50% of cases and are non-specific vaginal discharge, dysuria, cervical bleeding Signs Exam is highly variable- normal to frank purulent discharge Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides 15

16 Antimicrobial Susceptibility of N. gonorrhoeae Quinolone resistance: widespread in US/worldwide (~ 1/3) PCN/TCN resistance: widespread (~1/4) Azithro: emerging - ~ 0.5% of isolates with decreased susceptibility Cephalosporins. Sporadic cases of decreased susceptibility to ceftriaxone & cefixime reported internationally Clinical failures with cephalosporins have occurred in Japan, Western Europe. Cefixime failure more widely reported than ceftriaxone failures Most patients have been MSM Updates: CDC STD Prevention Conference /1/16 5/10/16 Hawaii DOH identified 8 GC isolates with Azithromycin resistance (MIC >1:16) All also resistant to PCN, TCN, Cipro 5/8 with elevated increased CTX MIC -.125ug/ml Likely clonal expansion from single clade Isolates from 7 patients 6M, 1F All heterosexual and with typical symptoms All successfully treated - CTXone 250 mg IM plus Azithro 1 gm 8 partners identified 1 male with GC dx by NAAT and successfully treated before investigation. Remainder tested negative for GC 16

17 Heterosexual male female partner in SE Asia, UK +GC with R to Azithromycin, CTXone (urethral and pharyngeal) Failed 1 gm IV Ceftriaxone/ Spectinomycin (throat still +) Now being treated with Ertapenem 2015 Alternative Rx for Uncomplicated GC Infections of Cervix, Urethra, Rectum Cefixime 400 mg po x 1 dose plus Azithromycin 1 gram po X 1 dose Ideally dispensed at the same time Doxycycline 100 mg po bid x 7 days acceptable in place of azithro in allergic patients 17

18 Chlamydia Chlamydia: What s new Rates remain very high NAATS are gold standard Extragenital testing for MSM population Chlamydia Rates of Reported Cases by State, United States and Outlying Areas 2016 STD Surveillance Report

19 Chlamydia Rates of Reported Cases by County, United States and Outlying Areas, 2016 STD Surveillance Report Chlamydia Rates of Reported Cases by Age and Sex, United States, 2016 STD Surveillance Report Chlamydia Proportion of STD Clinic Patients Testing Positive by Age Group, Sex, and Sexual Behavior, STD Surveillance Network (SSuN), STD Surveillance Report Results are based on data obtained from patients with known sexual behavior (n=75,114) attending SSuN STD clinics in 2016 in all SSuN jurisdictions, excluding Florida. MSM = Gay, bisexual, and other men who have sex with men (collectively referred to as MSM); MSW = Men who have sex with women only 62 19

20 CT Urethritis Incubation Unknown 5-10 days in symptomatic > 50% asymptomatic Symptoms Urethral discharge, dysuria Signs None or Clear, mucoid, or mucopurulent discharge Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides CT Cervicitis Incubation Unknown; > 80% asymptomatic Symptoms Non-specific, including vaginal discharge or spotting, dyspareunia Signs Variable from normal to 30-50% with cervicitis endocervical discharge, edematous cervical ectopy, cervical friability* Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides 20

21 Rx for Uncomplicated Infection Medication Dose Route Frequency Azithromycin 1000 mg PO Single Dose or Doxycycline 100 mg PO BID x 7 days Alternative Agents Erythromycin 500 mg PO QID x 7 days or Ofloxacin 300 mg PO BID x 7 days or Levofloxacin 500 mg PO QD x 7 days Urethritis New Diagnostic Criteria Diagnostic Considerations: Discharge on examination (mucoid, mucopurulent, or purulent) Gram stain > 2 WBCs/oil immersion, methylene blue or gentian violet on urethral secretions + leukocyte esterase on first void urine If Gram stain not available: IF least one diagnostic criteria: Test and treat for gonorrhea AND chlamydia IF Symptoms without signs Chlamydia/gonorrhea testing Empiric treatment for high risk or unlikely follow-up 3/14/14 MMWR Updated Recommendations for Laboratory Based Detection of Chlamydia trachomatis and Neisseria gonorrhoeae The performance of NAATs with respect to overall sensitivity, specificity and ease of specimen transport is better than any other tests available for the diagnosis of chlamydial and gonococcal infections. Preferred specimens (FDA approved): Males urine (equivalent to urethra) Females vaginal (equivalent to cervical; superior to urine) Laboratories should use NAATs to detect chlamydia and gonorrhea except in cases of: Child sexual assault involving boys Rectal and oropharyngeal infections in prepubescent girls Potential gonnorhea treatment failure ( need culture for antibiotic susceptibility testing) 21

22 Extragenital Testing Proportion of extragenital gonorrhea and chlamydia infections associated with concurrent negative urethral tests. Monica E. Patton et al. Clin Infect Dis. 2014;cid.ciu184 Published by Oxford University Press on behalf of the Infectious Diseases Society of America This work is written by (a) US Government employee(s) and is in the public domain in the US. Figure 1 Figure 1. Genital and extragenital GC (top) and CT (bottom) in women. Neisseria gonorrhoeae and Chlamydia trachomatis Among Women Reporting Extragenital Exposures. Trebach, Joshua; Chaulk, C; Page, Kathleen; Tuddenham, Susan; MD, MPH; Ghanem, Khalil; MD, PhD Sexually Transmitted Diseases. 42(5): , May DOI: /OLQ % GC cases missed if extragenital tests not done 13.8% CT cases missed if extragenital tests not done Copyright 2015 American Sexually Transmitted Diseases Association. Published by Lippincott Williams & Wilkins, Inc. 22

23 Extragenital GC and CT Infections NAATs test of choice. Need laboratory validation given no FDA approval CDC recommends pharyngeal GC and rectal CT & GC screening for MSM and HIV + persons at least annually and Q 3-6 months if risk Untreated pharyngeal GC associated with: transmission to male partners acquisition of resistance (GC more difficult to cure in pharynx) Untreated rectal GC and CT often asymptomatic but less known about transmission? associated with increased HIV transmission/acquisition What about Partners? CT and GC Sex Partner Management Sex partners should be evaluated, tested, & treated if they had sexual contact with the patient during the 60 days preceding the onset of symptoms or diagnosis of GC or Chlamydia The most recent sex partner should be evaluated & treated even if the time of the last sexual contact was > 60 days before symptom onset or diagnosis 23

24 2015 STD Treatment Guidelines: Unless prohibited by law or other regulations, medical providers should routinely offer EPT to heterosexual patients w/ chlamydia or gonorrhea infection when the provider cannot confidently ensure that all of a patient s sex partners from the prior 60 days will be treated. NYS EPT Special populations: Male patients known to have sex with other men (MSM) EPT is not recommended for MSM due to the lack of data to demonstrate the effectiveness of EPT in the MSM population and the risk of missing STD/HIV coinfections. Victims of sexual assault/abuse In instances of suspect or confirmed child abuse, sexual abuse/assault or in cases where the patient's safety may be at risk, EPT should not be offered NYS EPT Recommended treatment for EPT for Ct infection Azithromycin* 1 gram po x 1 dose *If the patient's sex partner is allergic to azithromycin or related drugs, EPT should not be used and the partner should be referred for care. "EPT" must be written in the body of the prescription form EPT law overrides the requirement that prescriptions include a patient s name, address, and age If known, the name, address, and date of birth of the sex partner should be included If unknown, the name, address, and date of birth of the sex partner should be left blank and the EPT designation will be sufficient to fill the prescription 24

25 EPT NYS The medication for EPT may be dispensed or prescribed. The preferred method is dispensing in a pre-packaged "partner pack" that includes medication, informational materials and clinic referral. If a health care provider provides EPT using medication: Prescription medication should be dispensed and labeled in accordance with Federal & NYS rules and regulations. Lymphogranuloma venereum (LGV) The Other Chlamydia: LGV Caused by C. trachomatis L1-L3 serovars Infects monocytes not columnar cells Manifests as transient ulcer, large adenopathy(buboes), proctocolitis Most common in tropical/subtropical climates Africa, SE Asia, Latin America, Caribbean Since 2003, increasing reports in Europe, N. America Outbreaks in MSM communities with high rates of HIV co-infection Clinically presenting as proctitis/proctocolitis Occasional heterosexual cases seen 25

26 Clinical Manifestations Primary Infection: Incubation: 3-30 days Localized inflammation often described as papule that evolves to pustule or small ulcer Self limited 2-3 days usually Often not noticed due to short duration Source: CDC Division of STD Prevention Clinical Slides Clinical Manifestations Regional dissemination 2-6 weeks after primary lesion Manifests with regional LN involvement Inguinal/femoral for genital primary lesions Retroperitoneal/intraabdominal for rectal primary lesions May have systemic symptoms: fevers, malaise, arthralgias Source: CDC Division of STD Prevention Clinical Slides MSM outbreaks present Largely due to serovar L2, L2b, L2c Proctitis/Proctocolitis most common clinical manifestation Anorectal syndrome: rectal pain, tenesmus, mucoid or bloody discharge, abdominal or back pain, fever HIV coinfection common (50%- 87%) Asymptomatic cases reported ~ 40% in some reports, < 1% in others 26

27 Lymphogranuloma Venereum: An Increasingly Common Anorectal Infection Among Men Who Have Sex with Men Attending New York City STD Clinics, Pathella, P, et al CDC STD Prevention Conference, 2016 Screen CT isolates from male rectal specimens for LGV serovar % % Correlation: Black, age > 30, HIV+, partner to HIV, h/o syphilis No correlation: GC, CT, condom use, # partners LGV cases: 86% with rectal symptoms Rectal CT (not LGV): 60% with symptoms Diagnosis of LGV Not easy no FDA approved test Historically diagnosed through serology no longer recommended CT NAATs (most) include LGV & non LGV serovars but don t distinguish the two In house NAAT assays to distinguish specific LGV serovars available in some labs Treatment of LGV Standard recommendation: Doxycycline 100 mg po bid x 21 days?? Azithromycin 1 gm po q week x 3 Cure rates appear superior with Doxycycline Empiric treatment if no diagnostic testing available in setting of CT + rectal specimen from MSM with rectal symptoms 27

28 Mycoplasma genitalium Mycoplasma genitalium Emerging Issue M. genitalium first identified in the early 1980 s Cause of male urethritis looks like NGU 15 20% of non gonococcal urethritis (NGU) 20 25% of non chlamydial NGU 30% of persistent or recurrent urethritis More common than GC but less than CT NAAT preferred method to detect M. genitalium Research settings/in house PCR assays None FDA approved yet* Mycoplasma genitalium: Treatment 7 day doxycycline regimen - largely ineffective median cure rate of approximately 31% 1 gram single dose azithromycin more effective against M. genitalium than doxycycline in two randomized trials Resistance to azithromycin emerging Median cure rate ~ 85% initially but 39% in the most recent trial (4/15/15) Moxifloxacin 400 q d 7, 14 and 21 day regimens in case reports 28

29 Neisseria meningitidis Case 45 yo AA male with thick purulent green urethral discharge 3 female sexual partners in past month Urethral gram stain: Diagnosis: GC urethritis TX: CTX 250 IM plus Azithromycin 1 gram po Labs: GC/CT NAAT negative Background Neisseria meningitidis (Nm) exclusive human pathogen Gram negative diplococci Serogroups categorized by polysaccharide capsular antigens (13 total) Most disease caused by: A, B, C, Y and W135 NP carriage may result in invasive meningococcal disease usually meningitis, bacteremia Vaccine available for A,C,Y, W 135 and B Some meningococci don t express capsular antigens 29

30 Large Cluster of Neisseria meningitidis Urethritis in Columbus, Ohio, 2015 Bazan, JA, et al CID 2017CID 2017:65 (1 July) 1/1/15-11/18/15: 76 possible cases identified 75/76 confirmed as Nm 1/76 confirmed as GC by culture Hx - 0 cases 1/14-11/14 3 cases from 12/14 not included 297 culture + GC. All also gram stain +/ urine NAAT + 75/373 (20%) gram stain positive for GNID confirmed as Nm Co-infections: not different except pharyngeal GC urethral CT 15% Nm / 24% GC GC pharynx Nm 0 / GC 9% (p =.05) Large Cluster of Neisseria meningitidis Urethritis in Columbus, Ohio, 2015 Bazan, JA, et al CID 2017CID 2017:65 (1 July) Patient Characteristics: similar race, ethnicity, age Median Age: Nm 31 (IQR 24-38) / GC 28 (IQR 23-38) Black: Nm 81% / GC 71% Non Hispanic: Nm 91% / GC 92% Heterosexual - Nm 99% / GC 78% (p <.01) Sexual behavior: no differences in condom use, relationship status, sex w ETOH/drug use, anon partners, exchange sex for $/drugs Oral Sex with female partner total - Nm 99% / GC 73% (p <.01) Oral Sex with female partner of MSW - Nm 99% / GC 80% (p =.02) Symptoms: 99% Nm / 96% GC No of days with symptoms: 4 Nm / 4 GC No partners (90 d): Nm 2 (IQR 1-3) / 2 GC (IQR 2-4) Large Cluster of Neisseria meningitidis Urethritis in Columbus, Ohio, 2015 All treated as if GC, No treatment failures Additional 47 cases identified as of 12/16 Discussion points: Why low MSM (high rates of Nm carriage) No sex partner evaluations done By protocol, only men are tested Reports from Phila, Oakland, MI, Indianapolis Travel reported in 6 of cases but only 1 to affected location (Phila) More research needed Bazan, JA, et al CID 2017CID 2017:65 (1 July) 30

31 Summary: N. meningitidis Urethritis Be aware of classic GC with negative NAAT tests as possible Nm CDC - Treat as usual GC CDC - Treat partners c/w GC partner therapy Not reportable but CDC requesting notification if noticeable increase nmurethritis@cdc.gov Remove from GC surveillance report if your organization reports + GS as diagnostic Further research needed re: women, other sites, effects of vaccination June 5, 2015 October 18, 2016 Other Resources for STD Info CDC STD home page: cdc.gov/std Tremendous amount of info available: webinars, reports, guidelines, news updates

32 Thank You! ANY QUESTIONS? 32