10/1/18

Special thanks to George Walton, MPH, CPH, MLS(ASCP) of the Iowa Department of Health Sexually Transmitted Infections

A (hopefully) practical overview of STIs from a primary care perspective for PAs practicing in Iowa

Erin Hayward, MD

Objectives Reportable STIs

• Epidemiology of STIs in Iowa Disease Causative Agent Type of microbe

• Key elements of a sexual history to determine bacterium

appropriate screening methods bacterium • Complications of common STIs subsp pallidum bacterium • CDC Treatment Guidelines for common STIs HIV Immunodeficiency virus • Accessing Pre-Exposure Prophylaxis for HIV virus prevention Hepatitis C Hepatitis C Virus virus

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CDC Guidance Available for non- reportable STIs • • Conditions Associated – Human Papilloma Virus with vaginal discharge – Virus (1&2) – Vulvovaginal candidiasis* • – Bacterial vaginosis – (Haemophilus – “The good physician treats the disease; the great physician treats the ducreyi) • Dermatologic conditions patient who has the disease” – – - William Osler (Klebsiella granulomatosis) – Pubis (pubic – Mycoplasma genitalium lice) TAKING A SEXUAL HISTORY –

*Associated with STIs but not typically sexually transmitted

The 5 Ps: Risk factors Key elements of a sexual history • New or multiple sex partners • History of STIs or current infection with another • Partners STI • Practices • Lack of barrier contraception or inconsistent use • Protection from STIs • Exchanging sex for drugs or money, drug or • Past history of STIs alcohol use (both associated with higher risk sex) • Adolescents at particular risk due to biological, • Pregnancy/Pregnancy Prevention behavioral reasons, also difficulty accessing healthcare for STIs

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Screening Screening in Special Populations

• CDC recommendations for testing: • Pregnant women – Gonorrhea and chlamydia: annual screening for – Screen for STIs at first prenatal visit women younger than 25 – Screen men who only have sex with women (MSW) – Retest after 3 weeks if positive, again at 3 months men based on risk • Patients on PrEP – Men who have sex with men (MSM) at least annually – Persons with HIV at least annually for other STIs • Iowa Department of Public Health recommends at least annual testing for patients who are sexually active

Chlamydia trachomatis, serovars D-K

• Obligate intracellular bacterium • Infects columnar epithelial cells at mucosal sites • Most common most common nonviral STI

With a few others, • Prevalence in US is estimated at 1.5% CHLAMYDIA AND GONORRHEA • Highest incidence in women aged 15-24 at 4.7%

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Chlamydia in Iowa, 2007-2017 Chlamydia

• Highly transmissible: Number of New Cases Annually – Infection rates approximately 55% between sexual partners, per-act transmission rate of 10% – From mother to infant via genital tract • Symptoms, if they present, at 7-21 days after infection • Infection increases susceptibility to other STIs including HIV

Source: George Walton, IDPH 13

Genital Manifestations of Chlamydia in Men Genital Manifestations of Chlamydia in Women • Asymptomatic infection is the most • Majority are asymptomatic common • : • – Symptoms: Vaginal discomfort, spotting – Signs: Mucopurulent endocervical discharge and/or – Dysuria and spontaneous or endocervical bleeding mucopurulent to clear discharge • Urethritis: – Symptoms: dysuria, frequency • – Mimics acute UTI – Unilateral scrotal pain, • Pelvic Inflammatory Disease

epididymal swelling Source: Mayo Clinic and tenderness • Perihepatitis

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Chlamydial Cervicitis Manifestations in Men or Women

• (in adults, autoinoculation; in neonates, from maternal contact) – Unilateral eye discomfort, hyperemia • Oropharyngeal infection – Typically asymptomatic, but can be dry, itchy throat to exudative tonsillopharyngitis • – Rectal pain, mucoid or hemorrhagic discharge – Rectal infections are typically asymptomatic

Source: St Lousis STD/HIV Prevention Training Center via CDC

Reactive arthritis (aka Reiter’s Chlamydia in Neonates syndrome)

Image Source: National STD Curriculum • Predominantly in • Neonatal conjunctivitis (25% of neonates born males with HLA-B27 to mothers with untreated cervical chlamydial • Syndrome of infection.) conjunctivitis, urethritis, • Neonatal chlamydial pneumonia (10-15% of oligoarthritis, skin untreated cervical chlamydia) lesions (Keratoderma • Urogenital infections acquired perinatally may blennorrhagica) Image Source: BMJ persist 2-3 years • Circinate balanitis is characteristic

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Non-Gonococcal Urethritis Gonorrhea

Mild dysuria, mucoid discharge • Gram negative diplococcus that infects multiple types of mucous- • Most likely chlamydial (40%) secreting epithelial cells • 20-30% genital mycoplasmas • Second most commonly • Occasional Trichomonas reported STD in Iowa and the US vaginalis (trichomoniasis) • Rate of reported cases in men – Urine NAAT for trichomonas (particularly aged 20-29) significantly higher than in women

Gonorrhea in Iowa, 2007-2017 Gonorrhea

• Highly transmissible – Male to female transmission via semen: 50- Number of New 70% per episode of vaginal intercourse Cases Annually – Female to male transmission rate 20% per episode – Transmissible from genitalia to oropharynx and vice versa, also via rectal intercourse – Increased risk of HIV acquisition and transmission as gonococcal urethritis increases HIV shedding in men. – Perinatal spread from untreated mother to neonate

Source: Cincinnati STD/HIV Prevention Training Center via CDC

Source: George Walton, IDPH 24

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Genital Infection in Men Genital Gonorrhea in Women

Purulent urethral discharge associated with gonococcal • Urethritis infection • Cervicitis or urethritis – More commonly symptomatic than chlamydial urethritis, – At least 50% are asymptomatic; if present, symptoms typically presents 2-5 days after exposure within 10 days of exposure – Mucopurulent discharge, dysuria – Symptoms include nonspecific vaginal discharge, • Epididymitis (less common than with chlamydial intermenstrual bleeding, dysuria, lower abdominal infection) pain, dyspareunia • Anorectal infections – Exam may show mucopurulent or purulent discharge, – Typically results from receptive anal intercourse easy bleeding – Symptoms: Anal irritation, painful defecation, tenesmus • Anorectal infections – Signs: purulent discharge, erythema, easy bleeding on • Bartholin’s or Skene’s gland infections anoscopy

Gonococcal syndromes in Gonorrhea impact on neonates and men and women children • Pharyngeal infections • Ophthalmia neonatorum (conjunctivitis) is – Typically asymptomatic preventable with ocular prophylaxis at birth • Ocular infection • All cases of gonorrhea beyond the newborn – Conjunctivitis, starting nonpurulent and progressing period should be considered possible to purulence, corneal perforation, blindness evidence of sexual abuse • Disseminated gonococcal infection • Vulvovaginitis is most common in – More commonly occurs without urogenital infection prepubescent girls than cervicitis in strains that have a propensity for bacteremia – Skin lesions, hepatitis, arthritis, myo/endocarditis, • Abused boys more commonly affected in meningitis anorectum, pharynx (not urethritis)

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Mycoplasma genitalium (Mgen)

• An “Emerging Issue”, estimated as • Estimated prevalence in US female second most common cause of population 3.1% urethritis – Rates as high as 8.7% in women • Consider with treatment failure, undergoing testing for GC/CT, 13.3% persistent symptoms of urethritis, in some studies of AA females cervicitis, PID • Most infections are asymptomatic • Testing not readily available, but – Test with vaginal swab or urine NAAT NAAT exists • Treatment: metronidazole or tinidazole 2gm PO x1 dose or • If persistent urethritis or cervicitis Source: Infectious Disease Advisor treatment failures, consider empiric metronidazole 500mg PO BID x7 treatment with moxifloxacin 400mg days daily for 7-14 days

Pelvic Inflammatory Disease Risk factors for PID

• Clinical syndrome affecting upper genital tract • Age <20 years or younger sexual debut of females. Any combination of • Number of sexual partners (3x greater risk with – Endometritis 10 or more lifetime partners) • History of prior PID – Salpingitis • – Questionable increased risk with bacterial Tubo-ovarian abscess vaginosis, vaginal douching – Pelvic peritonitis • IUD placed during episode of mucopurulent • Can lead to infertility, chronic pelvic pain, cervicitis increased risk of ectopic pregnancy • Oral contraceptive use

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Pelvic Inflammatory Disease Pelvic inflammatory disease • Polymicrobial – Gonorrhea, chlamydia are most common causes but decreasing infrequency with increasing screening Acute salpingitis Source: CDC Picture Cards – Gram negative rods, anaerobes, streptococcal sp. – Mycoplasma genitalium and • General trend is declining rates of PID in spite of rising rates of STIs

Impact of Chlamydia on fallopian tube Diagnostic Criteria for PID tissue in PID • Treat presumptively in appropriate context if one or more of CDC minimal criteria is present: – Cervical motion tenderness – Uterine tenderness – Adnexal tenderness • Additional Symptoms: – Fever, endocervical discharge, lower abdominal Source: University of Washington via CDC Normal Ciliated Cells Ciliated cells affected by C. pain trachomatis

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Perihepatitis Treatment of PID

• AKA Fitz-Hugh-Curtis • Pelvic infection can be successfully treated in Syndrome most women with outpatient antibiotics • of liver capsule from untreated • Typically does not require intrauterine device pelvic infection with removal gonorrhea or chlamydia • RUQ pain, N/V, fever in • Sample outpatient regimen for PID: the context of PID – Ceftriaxone 250mg IM once PLUS doxycycline 100mg • May require surgical orally twice daily WITH OR WITHOUT metronidazole management of 500mg orally BID for 14 days adhesions • Refer to CDC 2015 STD Treatment Guidelines for parenteral regimens

Laboratory Testing for Chlamydia and Testing for Chlamydia and Gonorrhea Gonorrhea at Multiple Anatomic Sites • Complete sexual history is important for determining • Nucleic Acid Amplification testing which sites to test for GC/CT • FDA approval: – 70% – 88% of rectal chlamydia and gonorrhea infections have no concurrent urethral infection – urine specimens from men and women (first • Test for: catch) – Urethral disease with urine for men who had insertive – Urethral swabs in men intercourse in the past year – Rectal infections in men who have had receptive anal – Endocervical (sometimes vaginal) swabs in women intercourse in the past year – Pharyngeal gonorrhea infection in men who had receptive • Female patients may prefer self-collection of oral intercourse in the past year. vaginal samples • Consider patient-collected samples

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Chlamydia Treatment Gonorrhea Treatment • CDC recommended treatments for urogenital, oropharygeal, or rectal chlamydia: ● Only 1 CDC-recommended treatment regimen – Azithromycin 1g PO in a single dose ○ 250mg ceftriaxone (intramuscular injection) PLUS 1 – Doxycycline 100mg PO BID for 7 days gram azithromycin (oral); to be given same day • May have better efficacy for rectal chlamydia ● Alternative regimens • Pregnancy Category D ○ For persons with severe (anaphylactic) allergic – Alternative treatments with erythromycin, reactions to cephalosporins: levofloxacin, ofloxacin ■ 240mg gentamicin (intramuscular injection) PLUS 2 grams • See CDC STD guidelines for treatment of azithromycin (oral); to be given same day ○ For persons for whom an intramuscular injection is Opthalmia neonatorum, Chlamydial pneumonia, not feasible: pediatric patients ■ 400mg cefixime (oral) PLUS 1 gram azithromycin (oral); to be given same day

Prevalence of Tetracycline, Penicillin, or Fluoroquinolone Resistance or Elevated Cefixime, Ceftriaxone or Azithromycin Partner Treatment MIC, by Year — GISP, 1987–2017 • All sex partners with whom they had sexual contact in the preceding 60 days should be referred for evaluation, testing, and presumptive treatment • Most recent partner should be evaluated and treated even if time of last contact was greater than 60 days • Both partners should be abstinent for at least 7 days after treatment initiation • Repeat testing for re-infection in 3 months

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Presumptive and Preventive Approach Expedited Partner Therapy to Treatment • Patients should have presumptive STI • Antibiotics for chlamydia or gonorrhea are treatment if they know their partner has a provided for patient’s partner without a diagnosis separate visit or exam • 20% reduction in chlamydial reinfection • 50% reduction in gonococcal reinfection • EPT recommendation for gonorrhea is with second line treatment: cefixime and azithromycin

In whom should EPT be used? Iowa Code Allowing for EPT

• Male partners of females diagnosed with gonorrhea or Iowa Code 139A.41 CHLAMYDIA AND GONORRHEA chlamydia TREATMENT ○ Notwithstanding any other provision of law to the contrary, a • Less strongly recommended for female partners, physician, physician assistant, or advanced registered nurse contraindicated if signs or symptoms suggestive of PID practitioner who diagnoses a sexually transmitted chlamydia or gonorrhea infection in an individual patient may prescribe, • Not recommended for dispense, furnish, or otherwise provide prescription oral antibiotic drugs to that patient's sexual partner or partners – Pregnant women without examination of that patient's partner or partners. If – MSM population given high rates of concurrent infection the infected individual patient is unwilling or unable to deliver such prescription drugs to a sexual partner or partners, a • Provision of appropriate antibiotics for GC/CT should physician, physician assistant, or advanced registered nurse include educational information on exposure, possible practitioner may dispense, furnish, or otherwise provide the prescription drugs to the department or local disease complications, risks of therapy prevention investigation staff for delivery to the partner or partners.

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Syphilis in Iowa 2006-2016

Number of New Cases Annually

Source: JAMA

The great imitator. SYPHILIS

50

Primary Syphilis Secondary and Tertiary Syphilis

• Secondary syphilis • Characterized by rash ● Primary Syphilis (variable appearance) and ◦ Characterized by swollen lymph nodes, painless chancres condyloma lata (sores) at the site of • Resolves with or without infection (e.g., treatment (approx. 4 genitals, rectum, weeks). throat). • Highly infectious ◦ Highly infectious. • Tertiary Syphilis (rare) ◦ Resolves with or • 10-30 years after infection without treatment • Symptoms depend on (approx. 3 weeks) organ system affected (brain, nerves, eyes, heart,

Source: George blood vessels, liver, bones, Walton/CDC and joints)

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Neurosyphilis, Otosyphilis, Ocular Syphilis Reverse Sequence Algorithm syphilis • Neurosyphilis 1. Total Syphilis Antibodies (IgG and IgM) screen – Headache, altered behavior, poor coordination, – Fewer false positives than starting with the rapid dementia, paralysis, tabes dorsalis (foot slap gait) plasma reagin (RPR) – Thorough neurologic exam and need to obtain CSF if – Detects more early and latent cases than RPR there is any concern • Ocular syphilis 2. Positive tests followed by RPR for confirmation – Vision changes, decreased acuity, blindness – If RPR is positive, titers performed and reported • Otosyphilis – Confirmation is by T. pallidum tissue agglutination – Tinnitus, acute onset deafness (TPPA) testing – Treated as neurosyphilis

Syphilis (all stages) among women in Congenital syphilis in Iowa, 2007- Iowa, 2007-2017 2018*

Number of New Cases Annually Number of New Cases Annually

55 56 Source: George Walton, IDPH *2018 data are preliminary Source: George Walton, IDPH

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Congenital syphilis Syphilis Treatment

• Complications of untreated • Primary and secondary syphilis – maternal syphilis in Benzathine PCN G 2.4 million units IM once • Early latent (acquired <12mo prior) pregnancy are severe – As above – Fetal loss, premature birth, • Late latent (>12 mo, or unknown duration) low birth weight, neonatal – Benzathine PCN G 2.4 million units IM for three doses death at one week intervals • Neurosyphilis – Treatment must cross blood brain barrier – Aqueous crystalline PCN G, 18-24 million units daily, continous or in divided doses q4h, for 10-14 days

Syphilis Treatment

• For patients who have been treated for syphilis, RPR titers should be followed. – Treponemal specific tests will be positive for life • Successful treatment is generally indicated by a 4-fold or more reduction in RPR titer HIV, HSV, HPV – e.g. 1:32 to 1:8 VIRAL SEXUALLY TRANSMITTED INFECTIONS

Shutterstock

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Human Immunodeficiency Virus (HIV) HIV Risk in Iowa

• Approximately 2400 Iowans were living with • Risk factors for acquisition of HIV/AIDS in Iowa (self-reported an HIV diagnosis at the end of 2015 – 54% MSM – Estimated that more than 500 people with – 18% heterosexual contact undiagnosed HIV currently living in Iowa – 8% injection drug use – 7% injection drug use and MSM – 11% with “no risk factor identified” • Demographics (cases per 100,000): – 22.9 cases in African American Iowans – 9 cases in Hispanic Iowans – 2.7 cases in White Iowans

Testing for HIV Pre-Exposure Prophylaxis (PrEP)

• 50-90% of infections begin with acute retroviral • Daily oral prophylaxis with combination of two syndrome (flu-like symptoms) within 2-4 weeks of antiretroviral medications, tenofovir disoproxil acquisition fumarate and emtricitabine (Truvada) – Antibody testing alone may be negative at this stage – Reduces risk of HIV acquisition in high risk – Ensure use of antigen/antibody combo testing populations • Verbal consent from adults, written consent • Can be prescribed by any licensed provider from minors who have been informed that their guardian will be notified of a positive result

Source: AIDSinfo-NIH

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Who should consider PrEP? Iowa TelePrEP

• Injection drug users • Telemedicine/telepharmacy – Especially if sharing equipment • Assist in financing PrEP • Heterosexual men and women, or men who – Truvada typically covered by most major insurances, have sex with men (MSM) if: 100% covered by Iowa Medicaid; Manufacturer coupon covers co-pay – HIV positive partner(s) – STI testing and visit costs are more challenging than – Sex work medication costs – Recent bacterial STI • Patients can self-refer to TelePrEP – High prevalence network – History of inconsistent use

Additional Screening for Patients on (Genital HSV) PrEP • Variable clinical manifestations • At least every 3 months (more depending on immune status of often if necessary) patient • Most significant manifestations – Test for HIV, pregnancy; confirm Cr during primary infection clearance >60 • Genital HSV facilitates acquisition and – Assess current risks transmission of HIV • Complications include but are not • At least every 6 months limited to: – Aseptic meningitis – other STIs at all appropriate sites Primary HSV – Transverse myelitis Source: National STD Curriculum • Annually, reassess need for PrEP – Neonatal herpes • Stigma

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Genital HSV Treatments – Refer to CDC STD Treatment HPV Guidelines • Primary HSV • Vaccinate (females 9-26, males 9-21) – All patients should receive antiviral therapy for their • Timely screening first episode to prevent prolonged clinical illness – Two possible treatments are acyclovir 400mg TID for 7-10 days or valacyclovir 1g orally BID for 7-10 days • Recurrent HSV – Suppressive: acyclovir 400mg PO BID or valacyclovir 500mg-1g daily – Episodic: Acyclovir 800mg PO BID for 5 days or

Testing and Empiric Treatment after Sexual Assault • Tests: – NAATs for chlamydia and gonorrhea at sites of penetration or attempted penetration in adults – NAAT for trichomonas, testing for BV and candidiasis – Serum samples for HIV, Hep B, syphilis • Treatment – Empiric antimicrobial treatment for gonorrhea, chlamydia, trichomonas – Consider post-exposure prophylaxis for Hep B and HIV RISK REDUCTION depending on risk – Start vaccines series for Hep B, HPV

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Risk Reduction Counseling Summary

• Discuss prevention strategies such as • All reportable STIs are increasing abstinence, monogamy with an uninfected • Remember to take a sexual history, site specific, and screen for STIs, as many infections are partner, and limiting the number of sex asymptomatic. partners. • Key populations include adolescents and young • Latex , when used consistently and adults, MSM, and pregnant women. correctly, can reduce the risk of transmission • Know your available resources for assistance with PrEP, Expedited Partner Therapy of most STIs • Seek help as needed from your local and state health departments.

Resources for your practice References

• Sexually Transmitted Diseases Treatment Guidelines, 2015. Centers for Disease Control Morbidity and Mortality • CDC STD 2015 Treatment Guidelines (available as Weekly Report. 5 June 2015. • National STD Curriculum, A collaborative initiative of University of Washington, The University of Alabama at an app) Birmingham, funded by the CDC: https://www.std.uw.edu/ • CDC Statement on Expedited Partner Therapy: https://www.cdc.gov/std/ept/default.htm • CDC How to take a sexual history: https://www.cdc.gov/std/treatment/sexualhistory.pdf • ASCCP “Pap App” for HPV Management and • UIHC lab handbook: https://www.healthcare.uiowa.edu/path_handbook/handbook/test3487.html • Preexposure Prophylaxis for HIV Prevention in the United States – 2017 Update: A Clinical Practice Guideline: cervical cancer screening https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2017.pdf • Iowa Department of Public Health STD References and Resources for Clinicians: • Iowa PrEP: https://www.prepiowa.org/teleprep https://idph.iowa.gov/hivstdhep/std/resources • Iowa Comprehensive HIV Plan: https://idph.iowa.gov/Portals/1/userfiles/105/Combined%202017%20Plan%20for%20HRSA%20CDC- • Your friends at your state and local county health compressed.pdf • IDPH PrEP Provider Information: department https://idph.iowa.gov/Portals/1/userfiles/40/PrEP%20Provider%20Brochure%202-17.pdf • Turok DK, Eisengerg DL, Teal SB, Keder LM, Creinin, MD. A prospective assessment of pelvic infection risk following same-day sexually transmitted infection testing and levonorgestrel intrautirine system placement. Am J Obstet • National STD Curriculum for CME or CNE: Gynecol. 2016;215:599.e1-599.36. • Lin JS, Eder ML, Bean SI. Screening for Syphilis Infection in Pregnant Women Updated Evidence Report and https://www.std.uw.edu/ Systematic Review for the US Preventive Services Task Force. JAMA. 2018;320(9):918–925. doi:10.1001/jama.2018.7769 • Your local lab handbook • Livingstone, E. Managing Syphilis in 2018. JAMA Clinical Review Podcast. 4 September 2018. https://jamanetwork.com/learning/audio-player/16746566?resultClick=1

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