2024 VanSchooneveld - STD 1 SyphilisGUD PDF

Sexually Transmitted Diseases Trevor Van Schooneveld, MD Professor, Infectious Diseases  Block Objectives 3.3 Gather and synthesize information to formulate differential diagnoses for diseases of the bladder, ureter, urethra and renal tumors. 4.6 Gather and sy...

Sexually Transmitted Diseases Trevor Van Schooneveld, MD Professor, Infectious Diseases  Block Objectives 3.3 Gather and synthesize information to formulate differential diagnoses for diseases of the bladder, ureter, urethra and renal tumors. 4.6 Gather and synthesize information to formulate differential diagnoses for diseases of the male genital system. 4.8 Identify determinants of population health as they relate to diseases of the male genital system and formulate prevention strategies. 5.6 Gather and synthesize information to formulate differential diagnoses for diseases of the female genital system. 5.9 Identify determinants of population health as they relate to diseases of the female genital system and formulate prevention strategies.  Lecture Objectives Describe the epidemiology of common sexually transmitted diseases Differentiate common sexually transmitted diseases based on their presentation Be able to select an appropriate treatment regimen for common sexually transmitted diseases  STD/STI Bacterial Viral – Gonorrhea – HSV – Chlamydia – HPV – Syphilis – Molluscum – Granuloma inguinale – HIV – Chancroid – Hepatitis B (C, D ??) Protozoal Parasitic – Trichomoniasis – Pubic lice Not really STDs – Scabies – Candidiasis – Bacterial Vaginosis  Genital Ulcer Disease Causes – Chancroid, granuloma inguinale, syphilis, HSV, lymphogranuloma venereum (LGV), monkeypox! Increase risk of HIV transmission 2-5 fold – HIV shed from lesions – Portal of entry for HIV – Cellular targets of HIV present in large numbers Population attributable risk of HIV – 7-18% in US – 44-69% low-income countries Syphilis  Syphilis Poem There was a young man from Back Bay His heart is cavorting, Who thought syphilis just went away His wife is aborting, He believed that a chancre And he squints through his gun barrel sight. Was only a canker Arthralgia cuts into his slumber; That healed in a week and a day. His aorta is in need of a plumber; But now he has “acne vulgaris”- But now he has tabes, (Or whatever they call it in Paris); And saber-shinned babies, On his skin it has spread While of gummas he has quite a number. From his feet to his head, He's been treated in every known way, And his friends want to know where his hair is. But his spirochetes grow day by day; There's more to his terrible plight: He's developed paresis, His pupils won't close in the light Has long talks with Jesus, And thinks he's the Queen of the May.  Syphilis Treponema pallidum – Spirochete can’t be cultured Before treatment was leading cause of cardiovascular and neurologic disease – Prevalence 8-14% in 1930s – Unusual therapies – arsenic, salvarsan, mercury, induced fever (hot box, malaria) Multiple phases of illness – Incubating, primary, secondary, early latent, late latent, and late tertiary Syphilis — Rates of Reported Cases by Year, United States, 1941–2022 * Per 100,000 NOTE: Total syphilis includes all stages of syphilis and congenital syphilis 9 Primary and Secondary Syphilis — Rates of Reported Cases by Jurisdiction, United States and Territories, 2013–2022 * Per 100,000 10 Primary and Secondary Syphilis — Rates of Reported Cases by Race/Hispanic Ethnicity, United States, 2018–2022 * Per 100,000 ACRONYMS: AI/AN = American Indian or Alaska Native; Black/AA = Black or African American; NH/PI = Native Hawaiian or other Pacific Islander 11 Primary and Secondary Syphilis — Rates of Reported Cases by Age Group and Sex, United States, 2022 * Per 100,000 NOTE: Total includes cases of all ages, including those with unknown age. 12 Primary and Secondary Syphilis — Reported Cases by Sex, Sex of Sex Partners, and HIV Status, United States, 2022 ACRONYMS: MSM = Men who have sex with men; MSW = Men who have sex with women only; MSU = Men with unknown sex of sex partners 13 Primary and Secondary Syphilis — Reported Cases Among Men Who Have Sex with Men by HIV Status, United States, 2013–2022 14 Primary and Secondary Syphilis — Reported Cases by Sex and Sex of Sex Partners, United States, 2013–2022 ACRONYMS: MSM = Men who have sex with men; MSU = Men with unknown sex of sex partners; MSW = Men who have sex with women only 15 Primary and Secondary Syphilis — Rates of Reported Cases by Sex and Male-to-Female Rate Ratios, United States, 1990–2022 * Per 100,000 † Log scale 16  Early Syphilis Incidence Comparing Women and Men Who Have Sex with Men Berzkalns A, et al. Open Forum Infect Dis. 2023;10:ofad481. Congenital Syphilis — Reported Cases by Year of Birth and Rates of Reported Cases of Primary and Secondary Syphilis Among Women Aged 15–44 Years, United States, 2013–2022 * Per 100,000 ACRONYMS: CS = Congenital syphilis; P&S Syphilis = Primary and secondary syphilis 18 Primary and Secondary Syphilis — Percentage of Cases Reporting Selected Sexual Behaviors*, United States, 2018–2022 * Proportion reporting sex with PWID, sex with anonymous partners, sex while intoxicated/high on drugs, or exchanging drugs or money for sex within the last 12 months calculated among cases with known data (cases with missing or unknown responses were excluded from the denominator). ACRONYMS: PWID = Person who injects drugs 19 Primary and Secondary Syphilis — Percentage of Cases Reporting Selected Substance Use Behaviors*, United States, 2018–2022 * Proportion reporting injection drug use, methamphetamine use, heroin use, crack use, or cocaine use within the last 12 months calculated among cases with known data (cases with missing or unknown responses were excluded from the denominator). 20 Syphilis Cases in Nebraska 364% increase in men and 813% increase in women since 2017 4 cases of congenital syphilis  Syphilis Epidemiology Rates continue to climb – Driven initially and primarily by MSM but … – Increased incidence in women (422% over last 10 years; 09 to 4.7 per 100K) Risk groups – MSM (especially those having sex with anonymous partners, while intoxicated) – HIV infected (up to 50% of cases co-infected) – Minorities (esp. AI and AA males) Transmission – Infectious during primary and secondary Contact with infectious lesions Infectious patient averages 3 contacts (50% transmission rate) – No sexual spread after 4 year – Congenital usually in utero Increasing rate congenital syphilis  Sentinel events  Pathogenesis Infection through mucus membrane or abraded skin – Organism disseminates – Incubation ~3 weeks (3-90 days) Primary lesion  chancre Secondary 2-8 weeks later (25% develop) – Rash, constitutional symptoms, many other signs Latent – No symptoms but serologic evidence of infection – Early (1 year or unknown) Late or Tertiary (25-40%) at 1-30 years – Cardiovascular (most common), gummas, CNS disease  Pathologic Findings Obliterative endarteritis with concentric endothelial and fibroblastic proliferative thickening – Lesions in vaso vasorum of CV and CNS system are cause of disease manifestations  Clinical Presentation: Primary Primary Chancre – Papule  painless ulcer Indurated, smooth base, raised cartilaginous borders – At site of inoculation – Painless regional LAD – Heals 3-6 weeks without scar Can develop secondary syphilis while still present Primary Syphilis  Clinical Presentation: Secondary Widespread dissemination and multiplication Constitutional symptoms – fever, malaise, diffuse LAD Skin – Rash  widespread, maculopapular, palms/soles – Patchy alopecia – Condylomata lata – intertrigenous areas of painless, moist, gray-white plaques – Mucous patches – painless silver-gray oral lesions CNS (40%) – Headache, meningismus, CSF abnormalities, aseptic meningitis, CN abnormalities Glomerulonephritis, hepatitis, arthritis, uveitis, otic – Increasing incidence ocular syphilis (ocular=neurosyphilis) Rash Secondary Syphilis Alopecia  Secondary Syphilis Condylomata lata Mucus Patches  Clinical Presentation: Tertiary Cardiovascular – aneurysm Gummas – Rare granulomatous tumor-like, destructive lesions of skin, bone, other sites CNS disease – can occur at any time (secondary most common) – Acute neurosyphilis – common secondary, usually asymptomatic – Late neurosyphilis Meningovascular, Parenchymatous, Tabes dorsalis  Late Neurosyphilis Meningovascular (5-10 yrs post infection) – Multiple small infarcts due to vessel occlusion Parenchymatous – General paresis (15-20 yrs) Psychiatric and neurologic findings Personality (emotional lability, paranoia), Affect (carelessness in appearance), Reflexes (hyper), Eye (Argyll Robertson pupil; accommodates but doesn’t react), Sensorium (illusions, delusions, hallucinations), Intellect (decreased memory, judgment, insight), and Speech (slurred) – Tabes dorsalis (25-30 yrs) Demyelination of spinal cord (posterior column, dorsal root) Ataxia gait, paresthesias, shooting/lightning pains, bowel/bladder incontinence, decreased reflexes, + Romberg Denervation leads to Charcot joints and foot ulcers  Latent Syphilis Latent syphilis = Asymptomatic syphilis – Positive serology but no evidence of disease – No history of treatment Early vs. Late (or unknown) – Early = evidence disease occurred within last year – Late or unknown = >1 year or unknown duration  Diagnosis Can’t culture Dark-field microscopy not performed Nontreponemal tests (RPR, VDRL) – React to cardiolipin-cholesterol-lecithin (non-specific) – Titer  1:16, 1:64, etc. – Titer declines over time (faster with treatment) – False positives – pregnancy, IVDU, TB, endocarditis, CTD, mono Treponemal tests (FTA-ABS, TP-PA, variety of EIAs) – Detect antibodies to specific syphilis antigens – More specific, only + or - – Once positive, always positive Traditional Testing Algorithms Or VDRL Reliable with high prevalence Low specificity Low throughput Reverse Testing Algorithm More specific Rapid throughput How to interpret? Or VDRL  Testing Scenarios Patient History Syphilis IgG RPR FTA-ABS Interpretation Follow-up TP-PA No known history Neg NA NA No syphilis None (unless very early) No known history Pos Pos NA Active syphilis Treat per guidelines No known history Pos Neg Neg False positive None No known history Pos Neg Pos Possible (latent History/clinical or prev treated) info required Known history Pos Neg Pos/NA Treated syphilis None  Treatment Early = < 1yr (primary, secondary, early latent) – Benzathine penicillin G 2.4 million units IM once Allergy = Doxycycline 100mg BID X 14 days – Azithromycin 2g once  Increased resistance (esp. MSM) – Consider desensitization in pregnancy Late latent or late (>1 year or unknown and not neurosyphilis) – Benzathine penicillin G 2.4 million units IM Qweek X 3 doses Allergy = Doxycycline 100mg BID X 28 days Neurosyphilis – Penicillin G IV 3-4 million units Q4H X 10-14 days  Treatment Jarisch-Herxheimer reaction – Fever, chills, myalgia, HA, flushing, decreased BP – Lasts 12-24 hours Follow RPR/VDRL at 6, 12, 24 months – Looking for 4-fold decrease in 1 year Sex partners – Treat all contacts in last 90 days Always check for HIV  Genital Herpes Etiology – Herpes Simplex Virus type 2 (70-95%) or HSV 1 Epidemiology – at least 50 million US infected – Frequently asymptomatic - true incidence unknown – HSV-2 seropositivity varies by location, risk, sex 18% men, 26% women, STD clinic 31-64%, Africa 41-74% – Risk factors  female, number of sex partners, black – Previous HSV-1 infection no impact on transmission, but 3-fold increase in asymptomatic infection HSV Pathogenesis Reactivation 90% recur 1 yr Median 4-5/yr and decreases over time HSV-2 > HSV-1 Immunocompromised – esp. cell mediated immunity (HIV, Tx)  HSV Transmission and Shedding Both symptomatic and asymptomatic can transmit – Discordant couples 3-12% per year (median 3 month, 24 sex acts) – Transmission decreased 50% if partner knew of HSV-2 status Increasing incidence HSV-1 genital infection – Changes in sex practices vs. declines in HSV-1 seroprevalence Viral shedding frequent Usually asymptomatic Occurred 1 in 4 days (2-75%) Viral levels high enough to transmit  HSV Clinical Presentation Primary – incubation 2-12 days (avg. 4) – Prolonged and more severe symptoms – Fever, HA, malaise, local pain/itching, dysuria, tender inguinal LAD – Painful vesicles, ulcers, pustules (duration avg. 19d) Non-Primary – less severe Recurrent – less severe – Prodromal tingling, shooting pains – Lesion duration ~10d Other forms – Proctitis, aseptic meningitis, Whitlow, ocular Vesicles Severe Primary Ulcers  HSV: Diagnosis Scraping for smear – Tzanck prep – Multinucleated giant cells, intra-nuclear inclusions Culture – Cell based looking for cytopathic effect (CPE) PCR – Most sensitive method Serology – Limited use Direct Fluorescent Antibody (DFA) – Fluorescein-labeled HSV-1/HSV-2 antibody (VZV also)  HSV: Treatment Primary – always treat to decrease duration/severity – Acyclovir, valacyclovir or famciclovir for 7-10 days Recurrent – start as soon as possible – Acyclovir 800mg TID for 2 days – Famciclovir 1g BID for 1 day – Valacyclovir 500mg BID for 3 days Suppressive – Use if 6 or more recurrences per year or severe distress/disease – Decreases risk of transmission by 50% – Acyclovir 400mg BID, famciclovir 250mg BID, valacyclovir 500mg daily (1g daily if >9 recurrences yearly)  Granuloma Inguinale (Donovanosis) Etiology – Klebsiella granulomatis – Previously Donovania and Calymmatobaterium – Gram-negative with bipolar staining (Donovan bodies) Epidemiology – India, New Guinea, Caribbean, Brazil Presentation (incubation 8-80 days) – Nodule  Ulcer – Beefy, granulomatous, rolled edges, bleeds easily, painless Diagnosis – Smear or crush prep (Donovan bodies) Treatment – continue until healed – Tetracycline/doxycycline – Azithromycin 1g weekly?? Granuloma Inguinale (Donovanosis)  Chancroid Etiology – Haemophilus ducreyi Epidemiology (highly infectious) – Rare US (under-recognized?) – Common Sub-Saharan Africa, SE Asia, L. America Presentation (incubation 4-10 days) – Papule  Painful deep ulcer, ragged edges, no induration, base with exudate and bleeds easily – Painful LAD Diagnosis – gram-stain helpful – Culture on special supplemented media Treatment – Azithromycin 1g PO – Alternatives – ceftriaxone IM once, cipro PO X 5 days – Buboes require aspiration Genital Ulcer Disease Summary Disease Ulcer Painful Lymph Nodes Syphilis Single, indurated, cartilagionous No Enlarged, non-tender border, clean base LGV Single, small, often heals rapidly No Enlarged, tender without being noticed (groove sign) Chancroid Single, deep, ragged edges, Yes Enlarged, tender extensive exudate Granuloma Inguinale Single, beefy, granulomatous, No Non-enlarged rolled edges, bleeds easily HSV Multiple, small, shallow, Yes Enlarged, tender surrounding erythema  Mpox Virus (Previously Monkeypox) Orthopoxvirus Previously a zoonoses from animals in Africa (squirrels, rats, monkeys) Large outbreak recognized May 2022 – First US case 5/17/22 – Clade II virus >80,000 cases to date 29,055 US cases (11/16/22) Nebraska 31 Douglas County 25  Mpox Transmission Previously from dead or live animals in or from Africa Primarily person-to-person spread via skin-to-skin contact and contact with infectious lesions – Current outbreak associated with sexual activity – Close non-sexual contact can also transmit Indirect transmission via contaminated material (clothing or linens) or surfaces possible (but rare) Clade II outbreak occurred primarily in men who sex with men – 99% men, 98% men who have sex with men, median age 36 Decreased incidence but still circulating in US  Monkeypox Symptoms May have a prodrome of fevers, chills, swollen LN, followed by rash starting on head and progressing down (similar smallpox) Initial symptoms are usually lesions on the genitals or perianal region – May then go on to develop fevers, LAD and diffuse rash Patients may have other STIs and manifestations of these diseases – HSV, syphilis, gonorrhea, chlamydia, HIV  Key Characteristics for Identifying Monkeypox Lesions are well circumscribed, deep seated, and often develop umbilication (resembles a dot on the top of the lesion) Relatively same size and same stage of development on a single site of the body (ex: pustules on face or vesicles on legs) Disseminated rash is centrifugal (more lesions on extremities, face) ​with lesions on palms, soles​ Lesions are often described as painful until the healing phase when they become itchy (crusts) Lymphadenopathy common Treatment  investigational antiviral created to treat smallpox JYNNEOS Vaccine  vaccine targeting smallpox moderately effective  Trichomoniasis Etiology – Trichomonas vaginalis Epidemiology – ~4 million US infections/yr – 30-40% male partners infected women Presentation – Most with infection have no or minimal symptoms – Vaginal discharge, pruritis/irritation, dysuria, dyspareunia, “strawberry cervix” – Males usually asymptomatic (can have urethritis) Diagnosis – PCR of urine or vaginal specimen (preferred) – Wet mount (low sensitivity 51-65%), culture Cervical Petechiae Treatment – Women = Metronidazole 500mg BID X 7d – Men = Metronidazole 2g once – Alternative Tinidazole 2g once  Bacterial Vaginosis Epidemiology – Most common cause vaginitis – Increased risk of other STDs, HIV, and preterm delivery Etiology – vaginal dysbiosis – Loss of normal lactobacilli flora  replacement with Gardnerella vaginalis and other anaerobes, biofilm development  Increase in vaginal pH Presentation – Vaginal discharge (gray) and “fishy” odor Clinical diagnosis = Amsel Criteria (3 of 4=BV) Gray/white vaginal discharge pH > 4.5 Positive amine (Whiff) test Clue cells present (at least 20%) – Variety of rapid point of care and PCR based diagnostics Bacterial Vaginosis Treatment – Don’t treat if asymptomatic – Metronidazole 500mg BID X 7 days – Intra-vaginal metronidazole or clindamycin  Candidal Vulvovaginitis Etiology – alterations in normal vaginal flora/environment NOT an STI – Risk factors: diabetes, antibiotic use, immunosuppression, high estrogen levels, contraceptive device use Presentation – Pruritus, irritation, dyspareunia, dysuria – Vaginal erythema with white “curd-like” discharge Diagnosis – pH 4.0-4.5 and negative whiff test (rules out trichomonas, BV) – Microscopy with yeast (although many negative) Treatment – Many topical and oral options (Fluconazole 150mg once)  Molluscum contagiosum Etiology – pox virus Epidemiology – Common children, spread by skin-to-skin contact – Adult can be sexual transmission Presentation – Firm, dome-shaped papule with umbilication Trunk in kids Groin, genitals with sexual transmission Diagnosis – clinical but can biopsy Treatment – depends on risk of transmission – Local destructive therapy Cryo, curettage, etc.  Genital Warts/Condyloma acuminata Etiology – Human Papilloma Virus (HPV) Epidemiology – Lifetime risk sexually active is at least 50% – Cervical CA types 16, 18, 31, 33, 35, 45 – Genital warts types 6, 11 Presentation – Flesh-colored or gray hyperkeratotic exophytic papules Diagnosis – Clinical – Tissue examination with acetic acid improves detection Treatment – many options – Chemical – Podophyllin, trichloroacetic acid, 5-FU – Immunological - Imiquimod – Surgical – cyro, laser, excision  HPV Prevention Vaccines – Cervarix (16, 18), Gardasil (6, 11, 16, 18), Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) – ~ 100% effective vs. vaccine types – >90% efficacy preventing cervical CA precursors Must be given before acquire HPV OK to vaccinate even if has cervical abnormalities or warts – 3 IM injections (0, 1-2, 6 months) Age 9-14 can use 2 injections (0, 6-12 months) Age 15-26 and all immunocompromised (3 shots) Recommended – All adolescents at age 11-12 13-26 if not previously vaccinated Age 27-45 safe but minimal benefit  CDC Screening Recommendations Everyone 13-64 for HIV once MSM – yearly – HIV, syphilis, GC, Chlamydia (include rectum, pharynx if appropriate) – More frequent (q3-6 mo.) if multiple or anonymous partners or on PrEP Sexually active men – Screen high risk (MSM, STD clinics, correctional facilities) for chlamydia and HIV Pregnancy – HIV, Hep B, Syphilis, Chlamydia, (GC, Hep C if increased risk) – No screening for BV, Trichomonas, HSV Sexually active women – Chlamydia and gonorrhea (age