Sexually Transmitted Diseases: Diagnosis and Management Department of Internal Medicine, Division of Infectious Diseases University of New Mexico
A 21 year old woman comes to your clinic asking to be checked for STD, although she has no symptoms. What tests will you order? What do you want to ask her? What else can you do for her sexual health? Different for a young man?
STD: Common, Serious and Overlooked Increasing in recent years Serious outcomes, especially for women Serious outcomes for fetuses/infants Often without symptoms, so require active screening May facilitate transmission of HIV May act differently in those infected with HIV Affect those with barriers to health
STI are on the increase http://www.cdc.gov/nchhstp/newsroom/2016/std-surveillance-report-2015-press-release.html Chlamydia: steady increase, partly due to increased screening Gonorrhea: historic low 2009, increase since, especially MSM, and in West Doubled in NM from 2010 to 2015 Syphilis: Historical low 2000 increase since, everywhere Largely MSM, but also women and infants (628 US congenital 2015) 51% of MSM syphilis cases are HIV+; 11% of MSW; 6% of women
Chlamydia Gonorrhea Urethritis Cervicitis Pelvic Inflammatory Disease Epididymitis Proctitis, prostatitis? Conjunctivitis, trachoma Reactive arthritis Neonatal pneumonia and conjunctivitis Urethritis Cervicitis Pelvic Inflammatory Disease Epididymitis Proctitis Conjunctivitis Pharyngitis Disseminated infection Neonatal conjunctivitis Most common presentation for both: no symptoms!
Cervicitis: vaginal discharge, bleeding, or no symptoms Urethritis: urethral discharge, dysuria Pelvic Inflammatory Disease: abdominal pain, scarring of fallopian tubes
Chlamydia Rates of Reported Cases by County, United States, 2016 NOTE: Refer to the NCHHSTP Atlas for further county-level rate information: https://www.cdc.gov/nchhstp/atlas.
CHLAMYDIA: Complications in Women Untreated genital CT infection 20-50% Acute PID or Silent PID 9% 18% Ectopic pregnancy Chronic pelvic pain 14-20% Infertility CDC estimates 24,000 US women/yr become infertile because of chlamydia and gonorrhea
Chlamydia in Pregnancy Conjunctivitis and pneumonia in neonates Screen ALL pregnant women Rescreen in 3 rd trimester those < 25yo or with new or multiple partners https://www.cdc.gov/std/tg2015/chlamydia.htm
Chlamydia Screening Proven to reduce pelvic inflammatory disease (Scholes et al., NEJM 334:1362, 1996) Screen ALL women yearly sexually active and < 25 Screen women of any age who: Has had an STD before OR Has more than one sexual partner OR Does not use condoms consistently and correctly Who recommends? USPS Task Force, CDC, AMA, Am. Acad. Peds, ACOG, HEDIS, etc.! Screen men who have sex with men What about heterosexual men?
Nucleic-acid Amplification Tests for gonorrhea and chlamydia Very sensitive Urine, urethral, cervical, vaginal, anal, pharyngeal Acceptable to patients Can screen asymptomatic males Can use in non-clinical settings Can self-collect For women, cervical and vaginal slightly more sensitive then urine. For males, urine equal to urethral swab DOESN T assess resistance
% of sexually active female enrollees 16-25 screened for Chlamydia Healthcare Effectiveness Data and Information Set (HEDIS), 2000-2008 http://www.cdc.gov/std/chlamydia/female-enrollees-00-08.htm#figure1 Similar results by women s self-report - Tao G et al., STD 39:605, 2012
Pelvic Inflammatory Disease Initial MD Office Visits by Women 15-44 Ectopic Pregnancy Hospitalizations of Women 15 44
Chlamydia Treatment: CDC 2015 guidelines Recommended regimens: Azithromycin 1 g PO x 1 (watch for vomiting) Doxycycline 100 mg PO BID x 7 d (watch for nonadherence) Alternatives: 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
Gonorrhea Rates of Reported Cases by County, United States, 2016 NOTE: Refer to the NCHHSTP Atlas for further county-level rate information: https://www.cdc.gov/nchhstp/atlas/.
Gonorrhea: evolution of resistance and CDC recommended treatment Sulfonamides Penicillin resistant GC in US Tetracycline resistance widespread Quinolone resistant GC in Hawaii Q not recommended in Calif 1930 1940 1950 1960 1970 1980 1990 2000 Penicillin drug of choice Penicillin no longer recommended Q recommended Q not recommended Adapted from Workowski et al., Ann.Int.Med 2008, 148(8):606
Neisseria gonorrhoeae Distribution of Isolates with Penicillin, Tetracycline, and/or Ciprofloxacin Resistance, Gonococcal Isolate Surveillance Project, 2016 NOTE: PenR = penicillinase-producing Neisseria gonorrhoeae and chromosomally-mediated penicillin-resistant N. gonorrhoeae; TetR = chromosomally- and plasmid-mediated tetracycline-resistant N. gonorrhoeae; and QRNG = quinolone-resistant N. gonorrhoeae.
Gonorrhea Treatment: www.cdc.gov/std/gonorrhea/ Uncomplicated gonorrhea of cervix, urethra, or rectum Ceftriaxone 250 mg IM once PLUS Azithromycin or doxycycline as for chlamydia (EVEN if chlamydia test negative) Alternative regimens: ONLY IF ceftriaxone not available: Cefixime 400 mg single oral dose PLUS Azithromycin or doxycycline as for chlamydia PLUS Test-of-cure in 1 week Serious cephalosporin allergy: Consult expert
Primary and Secondary Syphilis: Rates of Reported Cases by County, 2016 * In 2016, 1,699 (54.1%) of 3,140 counties in the United States reported no cases of primary and secondary syphilis. Refer to the NCHHSTP Atlas for further county-level rate information: https://www.cdc.gov/nchhstp/atlas/.
Syphilis: Natural History Infection Neuroinvasion 2-6 weeks Primary Chancre, regional adenopathy Early Neurosyphilis 1-3 months Secondary Rash, generalized adenopathy Lifetime latency > 70% Latent 1-3 months months - decades Tertiary Gumma Cardiovascular Late Neurosyphilis
Determining Stage: Critical for Treatment and Partner Tracing Careful history and physical exam Has pt EVER had symptoms of syphilis? Has pt EVER definitely had test, or known negative? Has pt ever given blood or plasma? Ever been pregnant? RPR titer may be helpful, but not definitive E.g. low titer could mean very early OR late disease Disease Prevention Specialists at Public Health can help: Find old results from medical or DOH records here or elsewhere Trace partners, create timeline, revisit staging with more info
Syphilis: Primary Chancre Where organism entered Firm; clean base Usually painless Usually single Local painless lymph node STD Atlas, 1997
Secondary Syphilis rash can look like anything! May have any of: Rash General painless lymphadenopathy Fatigue, malaise Liver involvement, high alkaline phosphatase Nephritis Neurosyphilis including stroke Eye involvement Note similarity to primary HIV infection!! STD Atlas, 1997
Secondary Syphilis: other manifestations Condyloma lata Erosive lesions Hair loss Mucous patches
Ocular Syphilis Uveitis, chorioretinitis, retinal vasculitis, optic neuritis/atrophy, keratitis Prevalence unclear; uveitis in 4-9% in secondary stage in some series MAY be more common in HIV+ than HIV- Many patients with ocular syphilis have neurosyphilis; all need LP MUST treat like neurosyphilis with IV penicillin, for eye penetration Coordinate management with ophthalmology Image source: VisualDx (www.visualdx.com).
Latent Syphilis of Unknown Duration Try and define duration! History: ever had symptoms of any stage? Risk? Examine for signs History and Contact Tracing may help determine time of infection collaborate with your Disease Prevention Specialist Ever tested for syphilis? - Including blood donation, pregnancy Ever treated for syphilis? RPR titer may be helpful, but don t rely on number to determine stage Rule out neurosyphilis - i.e., decide if LP needed Neurologic exam and review of systems Seek advice if any suspicion
Congenital Syphilis Miscarriage (25%) Neonatal death (25%) Early or late disease (50%) Hepatomegaly Meningitis Rash Abnormal blood counts Bone changes blindness deafness Neurologic damage ~400 US cases/year Increasing recently, esp. US West Should NEVER happen! Image source: VisualDx (www.visualdx.com).
Determining stage is critical for treatment and partner management Incubating syphilis Recent exposure; patient may be infected; test may not be positive yet Primary: 3-6 weeks after infection - Chancre, localized lymphadenopathy Secondary: 6-12 weeks after infection Rash, lymphadenopathy, fever, mucous patches, alopecia, headache, hepatitis, nephritis, etc.! Early Latent No signs and symptoms, < 1 year after infection Can still be infectious; secondary signs may recur Late Latent No signs and symptoms, > 1 year after infection Less infectious, symptoms probably will not recur Latent unknown duration Positive serology, no signs/symptoms, unknown time of infection Tertiary Syphilis many years later: neurological, cardiovascular, or gummatous lesions Neurosyphilis Can happen at ANY stage, though different symptoms Eye or ear disease should be treated same as neurosyphilis
Syphilis Serology: New Approach Traditionally: -screen with a non-treponemal test (such as RPR) -confirm with a treponemal test (TPPA, FTA) Many labs now screen with treponemal test first -new EIA tests Trep-Chek, Trep-Sure -lower personnel cost -detects latent cases Positives are then confirmed with non-treponemal test (RPR) BUT, we must learn how to interpret results!
CDC Suggested Algorithm if using Treponemal test first No syphilis diagnosis. (Does not rule out recent infection) Treponemal EIA Test - - + RPR + Positive Treponemal, negative RPR may mean: Old treated case Old untreated case False positive Get good history and physical! If false-positive suspected, or if not previously treated, retest with different treponemal test. If 2nd treponemal test positive - treat unless previously treated. If 2nd treponemal test neg, get 3rd treponemal, or consult expert. Syphilis - old or new. Treatment indicated unless previously treated. Consult expert and report to public health. If using RPR first: request treponemal test if suspect early or late syphilis! http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6005a1.htm
Neurosyphilis T. pallidum invades CNS early in many patients Many patients have abnormal CSF in early infection ~ 3/4 of patients clear CNS infection ~1/4 are at risk for neurosyphilis though not all will get it NO GOLD STANDARD for diagnosis CSF VDRL can be negative Bottom line: if any CSF abnormalities, consider treating for neurosyphilis
Syphilis Management Get RPR on or near treatment day Labs vary get RPR in your system If suspect syphilis and RPR negative, repeat in 1-2 weeks Instruct pt: followup RPR at 6 and 12 months Treat: ensure correct benzathine penicillin (LA Bicillin) Early: (primary, secondary, early latent): 2.4 MU IM X 1 Late: (late latent, tertiary, or latent unknown dur.): 2.4 MU IM weekly X 3 Current Bicillin shortage! Call Public Health if you can t get Test all syphilis cases for HIV and again in 2-3 months
How are STDs different in HIV patients? Syphilis: May have more neurosyphilis diagnosis difficult as HIV can cause abnormal CSF RPR falls more slowly after treatment Chlamdyia and gonorrhea: Screen MSM at rectum and throat as well as urine; yearly or more often Herpes: Common; more frequent and severe outbreaks, atypical lesions HPV: More likely to persist and cause cervical or anal dysplasia
Percent of tests Positive GC Positivity among Men Tested at Alternate Sites, NM DOH, 2012 15% Oropharynx Rectum 10% 5% 5.1% 6.8% 9.2% 10.90% 13.30% 13.30% 12.50% 2.7% 0% 2009 2010 2011 2012
Barriers to Screening in the HIV clinic? Barbee LA et al., STD 42:590, 2015 Large renowned HIV specialty clinic at Univ of Wash STD Screening in last 18 mo: 72% syphilis 30% extragenital GC and CT (Patients reported some testing elsewhere) Provider reasons for not screening: Lack of time, discomfort with exam, patient reluctance, unsure how to test Patient reasons for not screening Not prepared, tested elsewhere, prefer same-sex provider Reasons pts tested outside primary care: easier, anonymous, more frequent, more convenient Note: self-collected anal swabs acceptable and accurate (STD 36:493, 2009)
What should HIV providers do about STDs? Ask about sexual risk at every visit meth, ecstasy, ED drugs, alcohol multiple partners, casual, internet Ensure patients know STDs increase HIV transmission Risk reduction counseling Syphilis serology yearly more if high risk Prevention: vaccines, herpes suppression Screen ALL exposed sites for gonorrhea and chlamydia Treat according to guidelines Report cases to Public Health and communicate re: partner treatment Follow up to ensure cure and prevent new infections
Herpes Simplex Type 1 usually oral, type 2 usually genital But genital disease increasingly is type 1 US adult HSV-2 Seroprevalence (NHANES): 17% More prevalent in women, minorities, older age Most don t know they have it; can transmit without lesions Can seriously infect neonates - But reassure women this is rare Acyclovir: can take only for outbreaks, or daily for suppression
Trichomonas (a CDC neglected parasite ) Prevalence: 2-3% young adults; May not have symptoms Associated with: postpartum endometritis, low birth weight, preterm labor HIV transmission/acquisition Metronidazole resistance increasing Higher dose metronidazole or tinidazole may cure No great options for women with true metronidazole allergy 500 mg BID x 7 days better than 2 gm x1 for HIV+ women, maybe for all Soper D, AJOG 190:281, 2004 - review Cudmore SL et al., Clin. Micro Rev 17:783, 2004 resistance
Human Papillomavirus: Cervicovaginal Prevalence of Types 6, 11, 16 and 18 Among Females 14 34 Years, National Health and Nutrition Examination Survey Warts also decreased in younger women. Vaccine works! Markowitz LE, Liu G, Hariri S, et al. Prevalence of HPV After Introduction of the Vaccination Program in the United States. Pediatrics 2016; 137(3):e20151968.
Expedited Partner Therapy All partners of STD case should be tested and treated 1/3 to 2/3 of partners never come So, some providers provide medicine for partner Historically, was illegal most places Studies show it can be effective e.g., Golden MR, et al. N Engl J Med 2005;352:676-85. Reduced CT or GC reinfection of index patient CDC guideline: www.cdc.gov/std/ept/default.htm All states in our region now allow NM Guideline: https://nmhealth.org/publication/view/help/1602/
Discussion Confusing points? Tips for success to share? Challenges you ve had? What will you do differently because of today s talk?
Resources and Reading CDC STD 2015 Treatment Guideline: www.cdc.gov/std/treatment/default.htm Epidemiologic data: http://www.cdc.gov/std/stats/default.htm MMWR 2016 Jul 15;65:1. Neisseria gonorrhoeae Antimicrobial Susceptibility Surveillance - Gonococcal Isolate Surveillance Project, 27 Sites, United States, 2014. Herpes review: Gupta et al., Lancet 370:2127, 2007 Chlamydia review: Piepert JF, NEJM 349:2424, 2003 National STD Prevention Training Centers have many resources, for example: http://californiaptc.com/online-learning/ USPS Task Force recommendation: https://www.uspreventiveservicestaskforce.org/page/name/uspstf-recommendations-forsti-screening