Sexually Transmitted Diseases Elizabeth D. Hermsen, Pharm.D. Infectious Diseases Research Fellow University of Minnesota College of Pharmacy Objectives • List signs and symptoms associated with each STD • Recognize disease-specific diagnostic tests • Identify complications associated with each STD • Recommend treatment measures for each STD Spring 2004 PHAR 6124 2 Overview • Non-HIV STDs – – – – – – – – – – – Chlamydia Gonorrhea Syphilis Chancroid Trichomoniasis Vaginal infections Pelvic inflammatory disease (PID) Epididymitis Pediculosis and scabies Genital warts and human papillomavirus (HPV) Genital herpes Spring 2004 PHAR 6124 3 1 Overview (cont.) • Most common reportable communicable diseases in the U.S. • Higher reported incidence in men – more frequent and severe complications in women • 2/3 of all STD cases each year occur in teens and twenties Spring 2004 PHAR 6124 4 Overview (cont.) Ulcers Papules Vesicles Diffuse Crusts Misc. and erythema Bullae HSV, syphilis, trauma, chancroid, gonorrhea, trichomoniasis Warts, scabies, molluscum syphilis HSV, syphilis Trauma, contact dermatitis HSV, scabies Tracts: scabies. Nits/Blue spots: lice Images available at www.healthac.org Spring 2004 PHAR 6124 5 Chlamydia: Epidemiology • Causative organism – Chlamydia trachomatis • Ocular disease • 500 million worldwide affected • 7-9 million worldwide blind • Genital tract infections even more prevalent • CDC estimate of 4 million cases annually (US) • Predominantly found in young women (15 – 19 y.o.) • Co-infection occurs in up to 60% of those with gonorrhea • More C. trachomatis shedding in co-infected Spring 2004 PHAR 6124 6 2 Spring 2004 PHAR 6124 7 Chlamydia: Pathogenesis • Sites – Genital tract (NGU) – Ocular – Lung (pneumonia) • Spread via lymph system / multiply inside mononuclear phagocytes • Asymptomatic partner – less likely transmission Spring 2004 PHAR 6124 8 Chlamydia: Clinical findings • Often asymptomatic – Male – dysuria, urinary frequency, mucoid urethral discharge occurring 7-21 days post-exposure – Female – endocervicitis with mucopurulent discharge (dysuria and frequency are uncommon) • Perinatal • Infant conjunctivitis • Infant pneumonia Spring 2004 PHAR 6124 9 3 Chlamydia: Clinical findings (cont.) • Ocular trachoma • Chronic follicular conjunctivitis • Scarring blindness • Lymphogranuloma venereum (LVG) • Primary stage: painless ulceration at site of inoculation • Secondary stage: painful inguinal lymphadenitis (unilateral), inflammatory masses (buboes) • Third stage: genital abscesses, proctocolitis, lymphatic obstruction (elephantitis) Spring 2004 PHAR 6124 10 Chlamydia: Clinical findings (cont.) • Other ocular/genital infections – Ocular manifestations similar to early trachoma, but without serious complications – Genital infections » Urethritis (NGU) » Epididymitis and prostatitis » Proctitis and proctocolitis » Sexually reactive arthritis » Cervicitis » Endometritis » PID » Pregnancy issues Spring 2004 PHAR 6124 11 Chlamydia: NGU • Usually asymptomatic – Yet 30-50% NGU due to C. trachomatis • Others: 10-20% Ureaplasma urealyticum, Trichomonas vaginalis Gonococcal urethritis Chlamydia NGU 7-14 day incubation 4 day incubation Purulent discharge White/clear/gray discharge • Diagnosis - Gram stain of secretions demonstrating ≥ 5 WBCs per oil immersion field - Positive leukocyte esterase also indicative - Lack of N. gonorrhoeae ‡ NGU Spring 2004 PHAR 6124 12 4 Chlamydia: Complications • Pregnancy problems – Largest published study • Analysis of pregnancy outcomes in 1110 women (infected but not tx’d), 1323 (tx’d with erythromycin), 9111 uninfected (untx’d) women • Significant association in premature membrane rupture (odds ratio 0.56) – ectopic pregnancy, infertility • Cancer risk • Longitudinal, nested case-control study (530,000 women) • 128 cases of squamous cell carcinoma • Risk for SCC development linked to IgG Abs of C. trachomatis JAMA. 2001;285:47-51. Am J Obstet Gynecol. 1990;162:34-39. Spring 2004 PHAR 6124 13 Chlamydia: Diagnosis • Laboratory findings – Isolate of C. trachomatis – Nucleic acid amplification tests – Cytologic examination (intracytoplasmic inclusions) – Enzyme immunoassay (EIA), DNA hybridization probe, direct fluorescence monoclonal antibody (DFA) test • Clinical presentation Spring 2004 PHAR 6124 14 Chlamydia: Treatment • Uncomplicated genital infection – Doxycycline 100 mg PO BID x7d – Azithromycin 1 g x1 – Erythromycin base 500 mg PO QID x7d or EES 800 mg PO QID x7d – Ofloxacin 300 mg BID x7d or levofloxacin 500 mg QD x 7 d • Pregnant women – Erythromycin base 500 mg QID x7d – Amoxicillin 500 mg TID x7-10d Spring 2004 PHAR 6124 15 5 Gonorrhea: Epidemiology • Causative organism – Neisseria gonorrhoeae • Approximately 600,000 new infections annually in U.S. • Underreported (? Undertreated) • Resistance Spring 2004 PHAR 6124 16 Spring 2004 PHAR 6124 17 Spring 2004 PHAR 6124 18 6 Spring 2004 PHAR 6124 19 Gonorrhea: Clinical findings • Genital infections – Urethritis • Typically in males • Dysuria, frequency, profuse purulent discharge • Untreated spontaneous resolution in few weeks – Cervicitis • Most common gonococcal infection in females • Dysuria, frequency, vaginal discharge, uterine bleeding • Typically asymptomatic until complications (PID) Spring 2004 PHAR 6124 20 Gonorrhea: Clinical findings (cont.) • Other manifestations – Oropharyngeal • Typically asymptomatic • More common in females and MSM • Mimics pharyngitis or tonsillitis – Rectal • Typically asymptomatic • More common in females and MSM • Constipation, itching, rectal pain, rectal discharge – Conjunctivitis Spring 2004 PHAR 6124 21 7 Gonorrhea: Complications • • • • Pelvic inflammatory disease (PID) Epididymitis, prostatitis Opthalmia neonatorum Premature rupture of membranes – 1st trimester • Disseminated infections – – – – Dermatitis Arthritis Endocarditis Meningitis Spring 2004 PHAR 6124 22 Gonorrhea: Diagnosis • Gram stain – G (-) intracellular diplococci • Culture Spring 2004 PHAR 6124 23 Gonorrhea: Treatment • Uncomplicated infections 3rd gen. ceph or FQ PLUS anti-chlamydial Cefixime 400 mg PO X1 Ceftriaxone 125 mg IM X1 Ciprofloxacin 500 mg PO X1 Levofloxacin 250 mg PO x 1 Ofloxacin 400 mg PO X1 Azithromycin 1 gm X1 Doxycycline 100 mg PO Spring 2004 PHAR 6124 BID X7 24 8 Gonorrhea: Treatment (cont.) • Disseminated infections – Also to be given with anti-chlamydial tx – Ceftriaxone 1 g IM/IV q24h – Alternatives • Cefotaxime 1 g IV q 8h • Ceftizoxime 1 g IV q 8h • b-lactam allergic – – – – Levofloxacin 250 mg IV q24h Ciprofloxacin 400 mg IV q 12h Ofloxacin 400 mg IV q 12h Spectinomycin 2g IM q 12h – Continue IV for 1-2 days post clinical improvement, then switch to PO • Cefixime, levofloxacin, ciprofloxacin, ofloxacin Spring 2004 PHAR 6124 25 Gonorrhea: Treatment (cont.) • Gonococcal meningitis and endocarditis – Ceftriaxone 1-2 g IV q 12 h – 10-14 days for meningitis – Minimum 4 weeks for endocarditis • Opthalmia neonatorum prophylaxis – Silver nitrate 1% soln. X1 – Erythromycin 0.5% ointment X1 – Tetracycline 1% ointmentX1 Spring 2004 PHAR 6124 26 Syphilis: Epidemiology • Causative organism – Treponema pallidum • Approx 100,000 cases annually • Strong association with HIV infections • Crosses placenta (any time) Spring 2004 PHAR 6124 27 9 Syphilis: Clinical findings • Primary syphilis – Painless lesion chancre • Incubation period average 3 weeks • Dull, red macule papule erosion and ulceration • Resolves spontaneously in 1-8 weeks • Secondary syphilis – Symmetrical papular eruption (palms/soles of feet + mucous patches in mouth) – Systemic symptoms • Malaise, fever, HA, anorexia, lymphadenopathy – All symptoms disappear in 4-10 weeks (w/out treatment), but may recur Spring 2004 PHAR 6124 28 Syphilis: Clinical findings (cont.) • Latent syphilis – Serologic evidence without manifestations – Early latent: <1 year since onset • Infectious – Late latent: > 1 year since onset • Non-infectious Spring 2004 PHAR 6124 29 Syphilis: Clinical findings (cont.) • Tertiary (late) syphilis – 20-30% of patients progress to this point – Skeletal system • Gummas – CV • Aortic insufficiency, aortitis, aortic aneurysm • Neurosyphilis – – – – – – Meningitis Strokes Seizures Blindness Deafness Dementia Spring 2004 PHAR 6124 30 10 Syphilis: Diagnosis • Early syphilis – Darkfield examination of ulcer exudate – Direct fluorescent antibody test (DFA-TP) • Later stages – Non treponemal (VDRL slide test and RPR card test) • Detection of reagin – Treponemal (FTA-ABS) • Detection of antibody to T. pallidum • Remains positive in latent syphilis • Cross reactive with Lyme disease Spring 2004 PHAR 6124 31 Syphilis: Treatment • Primary, secondary, and early latent syphilis – Benzathine PCN G 2.4 million units IM X1 • Late latent – Benzathine PCN G 2.4 million units IM q week X3 • Neurosyphilis – Aqueous crystalline PCN G 3-4 million units IV q4h X 10-14d – Alternative: procaine PCN 2.4 mu IM/d + probenecid 500 mg PO QID for 10-14d Spring 2004 PHAR 6124 32 Syphilis: Treatment (cont.) • Non-pregnant PCN allergic – Primary, secondary, and early latent syphilis • Doxycycline 100 mg PO BID or TCN 500 mg PO QID X 2 weeks – Late latent or tertiary syphilis • Doxycycline 100 mg PO BID or TCN 500 mg PO QID X 4 weeks – Ceftriaxone, azithromycin??? Spring 2004 PHAR 6124 33 11 Syphilis: Treatment (cont.) • Pregnant women – PCN is the ONLY recommended Tx • Skin testing and desensitization are indicated if allergic • Jarisch-Herxheimer Spring 2004 PHAR 6124 34 Chancroid: Epidemiology • Causative organism – H. ducreyi • Endemic in many areas in US • Occurs as outbreaks – Commonly co-infection with syphilis or HSV • Cofactor for HIV transmission – Test for HIV at baseline and at 3 mos. Spring 2004 PHAR 6124 35 Chancroid: Clinical findings • Painful genital lesions • Tender inguinal lymphadenopathy Spring 2004 PHAR 6124 36 12 Chancroid: Diagnosis • Special culture media – 80% sensitivity • Exclusion diagnosis + ulcers not typical of HSV – Negative darkfield exam serological test for syphilis – Ulcer exudate is negative for HSV Spring 2004 PHAR 6124 37 Chancroid: Treatment • • • • Azithromycin 1g PO x1 Ceftriaxone 250 mg IM x1 Ciprofloxacin 500 mg PO BID x3d Erythromycin base 500 mg PO TID x7d Spring 2004 PHAR 6124 38 Trichomoniasis • Causative organism – Trichomonas vaginalis • Nonsexual transmission possible • Clinical Findings – Typically asymptomatic • 90% men • 50% women – Symptoms in women • Profuse, frothy,malodorous, yellow-green/grayish discharge • Itchy, irritation • Dysuria • Worsen during menstruation Spring 2004 PHAR 6124 39 13 Trichomoniasis (cont.) • Complications – Weak association with PID – Weak association with preterm labor – Bacterial overgrowth (bacterial vaginosis) • Diagnosis – Culture – Wet mount examinations of secretions Spring 2004 PHAR 6124 40 Trichomoniasis (cont.) • Treatment – Metronidazole 2g PO X1 • Alternative: Metronidazole 500 mg BID X 7d – Pregnant women • ? Don’t treat in 1st trimester • Treat after 1st trimester if symptoms continue Spring 2004 PHAR 6124 41 Vaginal infections • Characterized by vaginal discharge and/or vulvar itching and irritation • Trichomoniasis, bacterial vaginosis, and candidiasis • Role of sexual transmission is unimportant in vulvovaginal candidiasis and unclear in bacterial vaginosis – Sulfa creams and other “broad spectrum” vaginal preparations not reliable – Douching not effective for prevention or treatment Spring 2004 PHAR 6124 42 14 Vaginal infections: Bacterial vaginosis • Normal Lactobacillus spp. replaced typically by – Gardnerella vaginalis, Mycoplasma hominis, Mobiluncus spp., or Prevotella spp. • Associated with having multiple sex partners and douching – Unclear whether BV is sexually transmitted • Complications – Premature labor – Delivery complications Spring 2004 PHAR 6124 43 Vaginal infections: Bacterial vaginosis (cont.) • Diagnosis – Gram stain – A homogeneous, white, noninflammatory discharge that smoothly coats the vaginal walls – The presence of clue cells on microscopic examination – A pH of vaginal fluid >4.5 – A fishy odor of vaginal discharge before or after addition of 10% KOH (i.e., the whiff test) Spring 2004 PHAR 6124 44 Vaginal infections: Bacterial vaginosis (cont.) • Treatment – Metronidazole 500 mg PO BID X7d – Metronidazole gel (.75%) 5 g intravaginally QD X5d – Clindamycin cream (2%) 5 g intravaginally qHS X7d – Pregnant women • • Spring 2004 Metronidazole 250 mg PO TID x7d Clindamycin 300 mg PO BID x7d PHAR 6124 45 15 Vaginal infections: Vulvovaginal candidiasis (VVC) • Causative organism – Candida spp. (usually C. albicans) • NOT usually sexually transmitted • ~75% of women will have at least one episode • Clinical findings – Pruritus, vaginal discharge, vaginal soreness, vulvar burning, dysuria • Diagnosis – Gram stain – culture Spring 2004 PHAR 6124 46 Vaginal infections: VVC (cont.) • Uncomplicated – – – – • Complicated Sporadic, infrequent Mild-to-moderate C. albicans immunocompetent Spring 2004 – – – – Recurrent Severe Non-albicans Diabetes, pregnant, and/or immunosuppressed PHAR 6124 47 Vaginal infections: VVC (cont.) Treatment • Uncomplicated • Complicated – Many topical OTC preparations for 1-7d (butoconazole, clotrimazole, miconazole, tioconazole, nystatin) – Fluconazole 150 mg PO x1 Spring 2004 PHAR 6124 – Recurrent, severe, immunocompromised – same therapy, longer duration – Non-albicans -- ???; longer duration with a non-fluconazole azole – Pregnant – topical agents only (7d) 48 16 Pelvic inflammatory disease (PID): Epidemiology • Estimated 1 million cases annually • Risk factors – – – – Youth Multiple sex partners IUD use ? Douching • Spectrum of inflammatory disorders – – – – Endometritis Salpingitis Tubal ovarian abscesses Pelvic peritonitis Spring 2004 PHAR 6124 49 PID: Epidemiology (cont.) • Causative organisms – C. trachomatis – N. gonorrhoeae – G. vaginalis, anaerobes, enteric GNB, S. agalactiae – Others • CMV, M. hominis, U. urealyticum Spring 2004 PHAR 6124 50 PID: Clinical issues • Clinical findings – – – – Variable Lower abdominal tenderness (often bilateral) General aches Vaginal discharge • Complications – – – – Tubal damage + scarring‡ ectopic pregnancy Sepsis Chronic pelvic pain Recurrence Spring 2004 PHAR 6124 51 17 PID: Diagnosis • Minimal criteria – Lower abdominal/uterine tenderness – Tenderness with motion of cervix • Additional criteria – Fever, leukocytosis – Abnormal cervical or vaginal discharge – Elevated ESR and CRP • Laparoscopy • Endovaginal ultrasound • Endometrial biopsy Spring 2004 PHAR 6124 52 PID: Treatment • Broad coverage for likely pathogens • Hospitalize select patients – – – – – – – – – Possibility of surgical emergency (e.g., appendicitis) Suspected pregnancy Ectopic pregnancy Pelvic abscess HIV (+) Severe illness, nausea & vomiting, or high fever Clinically unresponsive to oral therapy Unwilling/unable to tolerate outpatient treatment 72-h follow-up cannot be guaranteed Spring 2004 PHAR 6124 53 PID: Treatment (cont.) • Oral – Ofloxacin 400 mg PO BID or levofloxacin 500 mg PO QD ± metronidazole 500 mg PO BID x 14d – Ceftriaxone 250 mg IM x1 or cefoxitin 2 g IM and probenecid 1 g PO x1 plus doxycycline 100 mg PO BID x 14d ± metronidazole 500 mg PO BID x 14d Spring 2004 PHAR 6124 54 18 PID: Treatment (cont.) • IV – Cefoxitin 2 g IV q6h PLUS doxycycline 100 mg IV/PO q12h – Cefotetan 2 g IV q12h PLUS doxycycline 100 mg IV/PO q12h – Clindamycin 900 mg IV q8h plus gentamicin – Alternative • Ofloxacin or levofloxacin ± metronidazole or ampicillin/sulbactam plus doxycycline – Continue IV for at least 24 hours after clinical improvement, then PO doxy or clinda for 14-d total Spring 2004 PHAR 6124 55 Conclusion –Chlamydia –Gonorrhea –Syphilis –Chancroid –Trichomoniasis –Vaginal infections –PID Spring 2004 PHAR 6124 56 Questions??? Spring 2004 PHAR 6124 57 19 Genital warts and Human Papillomavirus (HPV) • Most common STD – 10 – 20% of sexually active individuals (15 – 49 y.o.) showing evidence of infection – 60% show evidence of prior infection • Most asymptomatic and self-limiting – Minority develop anogenital warts – ~10% develop chronic infection Most used • Predisposed to anogenital cancer Spring 2004 PHAR 6124 58 Genital warts and HPV (cont.) • External genital warts – Typically HPV type 6 or 11 • Dysplasia of cervix, anus, genital skin – Typically HPV 16, 18, others – HPV DNA has been detected in association with up to 93% of cervical cancers Spring 2004 PHAR 6124 59 Genital Warts and HPV (cont.) • Treatment – No form of treatment shown to eradicate virus or modify risk for cancer – – – – – Spring 2004 Trichloracetic acid Podophyllin Cryotherapy with liquid nitrogen or cryoprobe Imiquimod 5% Podofilox 0.5% soltn. PHAR 6124 60 20 Genital herpes (HSV): Epidemiology • 2 serotypes – HSV-1: herpes labialis, herpes keratitis, herpetic encephalitis – HSV-2: genital herpes and neonatal herpes • Recurrent, incurable • Incidence increasing – > 50 million people in the US Spring 2004 PHAR 6124 61 HSV: Clinical findings • Up to 50% HSV-2 asymptomatic • Prodromal symptoms – Tingling – Itching – Burning • Lesions – Multiple, widely-spaced, bilateral, midline, ulcerative, painful Spring 2004 PHAR 6124 62 HSV: Clinical findings (cont.) • Systemic – – – – HA Fever Malaise Flu-like symptoms • Infective period – 10-14 days after onset (viral shedding) • Complications – Spontaneous abortion, malformation, pre-term labor – Neonatal infection – ? Cervical CA Spring 2004 PHAR 6124 63 21 HSV: Diagnosis • Clinical presentation • Viral culture – Sensitivity declines as lesions heal • Type-specific serology Spring 2004 PHAR 6124 64 HSV: Treatment • 1st clinical episode – Acyclovir 400 mg PO TID x7-10 d – Acyclovir 200 mg PO 5x/d x7-10 d – Famciclovir 250 mg PO TID x7-10 d – Valacyclovir 1 g PO BID x7-10 d May extend duration if healing is incomplete after 10 days Spring 2004 PHAR 6124 65 HSV: Treatment (cont.) • Recurrent (Initiate within 1 day of lesion onset or during prodrome) – Acyclovir 400 mg PO TID x 5d – Acyclovir 200 mg PO 5x/d x 5d – Acyclovir 800 mg PO BID x 5d – Famciclovir 125 mg BID x 5d – Valacyclovir 500 mg PO BID x 3-5d – Valacyclovir 1000 mg PO QD x 5d Spring 2004 PHAR 6124 66 22 HSV: Treatment (cont.) • Daily suppressive therapy – Reduces frequency of infection by > 75% in patients with recurrence >6X/yr. • • • • Acyclovir 400 mg PO BID Famciclovir 250 mg PO BID Valacyclovir 500 mg PO QD Valacyclovir 1000 mg PO QD – DOES NOT eliminate viral shedding Spring 2004 PHAR 6124 67 HSV: Treatment (cont.) • Severe disease – Acyclovir 5-10 mg/kg IV q 8h x 2-7 d or until resolution, followed by PO therapy to complete 10 days of therapy • Immunocompromised (HIV) – – – – Acyclovir 400 mg PO TID x5-10 d Acyclovir 200 mg PO 5x/d x5-10 d Famciclovir 500 mg PO BID x5-10 d Valacyclovir 1 g PO BID x5-10 d Spring 2004 PHAR 6124 68 HSV: Treatment (cont.) • Pregnant – 1st episode near term: systemic acyclovir advocated – Recurrence near term: ??? – ? Safety – no major teratogenic effects have been documented, but data are insufficient Spring 2004 PHAR 6124 69 23 HSV: Resistance • Strains resistant to acyclovir also resistant to valacyclovir and mostly resistant to famciclovir. – Foscarnet 40 mg/kg IV q8 hr – Cidofovir gel 1% QD x 5d Spring 2004 PHAR 6124 70 24
© Copyright 2024