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Welcome to I-TECH HIV/AIDS Clinical Seminar Series Sexually Transmitted Diseases, Part II: Genital Syndromes in Women Dr. Devika Singh, MD, MPH June 4,

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Presentation on theme: "Welcome to I-TECH HIV/AIDS Clinical Seminar Series Sexually Transmitted Diseases, Part II: Genital Syndromes in Women Dr. Devika Singh, MD, MPH June 4,"— Presentation transcript:

1 Welcome to I-TECH HIV/AIDS Clinical Seminar Series Sexually Transmitted Diseases, Part II: Genital Syndromes in Women Dr. Devika Singh, MD, MPH June 4, 2009 Slides generously borrowed from mentor Jeanne M. Marrazzo, MD, MPH

2 STD as a Cause of Cervicitis and Ulcerative Disease Endocervicitis: ‘classic’ STD pathogens –Gonorrhea –Chlamydia trachomatis Ectocervicitis: often associated w/ vaginitis: –Trichomoniasis Discrete lesions/Genital ulcerative disease/myriad –Herpes simplex virus –Syphilis –Chancroid –Human papillomavirus –LGV

3 Things to Consider Age of patient Change in discharge: increased, malodorous, bloody, purulent Associations: sexual activity/partnerships, cleaning the vagina (including douching/irrigation) Co-infections: HIV or non-HIV Epidemiology/exposures

4 Case I 22 yo woman presents to your clinic. She endorses no particular symptoms. One male partner who is asymptomatic. Condoms used “sometimes” On no hormonal contraception

5 Examination:

6 Bimanual examination reveals no tenderness

7 Differential?

8 Chlamydia trachomatis Neisseria gonorrhoeae HSV HPV Trichomoniasis Syphilis Pregnancy

9 Chlamydia trachomatis Epidemiology Most common bacterial STD worldwide, with approximately 90 million cases each year –Uro-genital disease –Ophthalmologic –Invasive (Lymphogranuloma Venereum)

10 Clinical Syndromes Caused by C. trachomatis Women Infants Conjunctivitis Urethritis Cervicitis Proctitis Conjunctivitis Pneumonia Pharyngitis Rhinitis Endometritis Salpingitis Perihepatitis Infertility Ectopic pregnancy Chronic pelvic pain Chronic lung disease (?)

11 C. trachomatis Cervical Infection  Classic cause of endocervicitis  Mucopurulent discharge  Friability  Edematous ectopy  Cervical signs occur in minority of patients (10-20%)  Most (80-90%) infected women have normal cervix / no signs

12 General Characteristics of Chlamydia  Superficial, mucosal: epithelial cells  Often no (or minimal) signs or symptoms  Chronic in women (months to years)  Chronic inflammatory response  Serious reproductive sequelae in women  Reinfection common

13 Normal Fallopian tubes by Scanning EM Photos courtesy of Dorothy Patton, PhD

14 Fallopian tubes by EM after C. trachomatis infection Photos courtesy of Dorothy Patton, PhD

15 Chlamydia Tests Cell culture Antigen Detection Direct Fluorescent Antibody (DFA) Enzyme Immunoassay (EIA) Unamplified DNA Probe (Gen Probe PACE2) Signal Amplification Tests (Digene Hybrid Capture) Nucleic Acid Amplification (NAAT) Rapid Point of Care Tests

16 What is the recommended treatment for a pregnant woman with chlamydia? 1.Erythromycin 500 mg po QID x 7 days 2.Doxycycline 100 mg po BID x 7 days 3.Azithromycin 1 g po x 1 dose 4.Levofloxacin 500 mg po daily x 7 days

17 Chlamydia Treatment in Pregnancy 2006 Recommended regimens Azithromycin 1 g PO x 1 Amoxicillin 500 mg PO TID x 7 d Alternative regimens Erythromycin base 500 mg PO QID x 7 d Erythromycin base 250 mg PO QID x 14 d Erythro ethylsuccinate 800 mg PO QID x 7 d Erythro ethylsuccinate 400 mg PO QID x 14 d

18 Recommended –Azithromycin 1 g PO, single dose, directly observed –Doxycycline 100 mg PO BID x 7 d Alternatives –Ofloxacin 300 mg PO BID or levofloxacin 500 mg PO qD x 7 d –Erythromycin 500 mg PO QID x 7 d 2006 CDC STD Treatment Guidelines: Uncomplicated Chlamydial Infection

19 Counseling as Part of Chlamydia Treatment  Abstain for at least 7 days and until partner(s) treated  Consistent condom use  Get your partner treated  Return if not improved over next 7-14 days

20 A Word about Screening UNITED STATES l <24 years old: screen all sexually active women annually l 25 and older: Annual testing if ‘at increased risk’ l Defined liberally: inconsistent condom use, new or multiple partners, prior STD or CT, sex work, certain demographics l If pregnant: l <24 years old  screen l 25 and older – only screen if “at increased risk”

21 Severity Extent Sigmoidoscopy Biopsy Comp-fix AB LGV strains Severe Proctocolitis Blood, ulcers, pus Granulomas Increased (>1/64) Non-LGV Mild Proctitis Normal, pus PMNs Normal Chlamydia Proctitis

22 LGV (Serovars L1, L2, L3 of Chlamydia) Proctitis Settings: developing context traditionally, but trend recently has included West (MSM) Diagnosis – Cell culture OK if available – NAAT not cleared by FDA for rectal specimens – Can be used if validated by local laboratory – ID of LGV serovars requires culture serotyping or NAAT genotyping; neither widely available – Serologic tests: recommended, reference laboratories; titers not well-defined for LGV proctocolitis and not highly predictive of infection Biopsy showing crypt destruction by diffuse histiocytic and lymphocytic infiltrate Ratelle; Liu 2006

23 LGV (Serovars L1, L2, L3 of Chlamydia) Proctitis Consider presumptive treatment Doxycycline 100 mg bid PO x 21 d Ratelle; Liu 2006

24 Chronic lymphogranuloma venereum in female. Genital elephantiasis

25 Case II 33 yo woman presents with change in vaginal discharge. One new male sex partner for past three months. Previously was with one steady male partner x four years.

26 Regardless… ALWAYS do an examination Presumptive treatment is inappropriate

27

28 Next step is gram stain

29 Diagnosis?

30 Neisseria gonorrhoeae

31 Purulent cervicitis When seen, tends to be MOST likely –C. trachomatis –N. gonorrhea

32 Gonorrhea Treatment, 2007 Recommended regimens: n Ceftriaxone 125 mg IM x 1 n Cefixime 400 mg PO x 1 n Ciprofloxicin 500 mg PO x 1 n Ofloxacin 400 mg PO x 1 n Levofloxacin 250 mg PO x 1 Alternative regimens:  Cefpodoxime 400 mg po x 1  Cefuroxime 1 g po x 1 n Spectinomycin 2 g IM x 1: not available n Single-dose injectable cephalosporin regimens n Single-dose oral quinolone regimens Co-treat for chlamydia unless ruled out with highly sensitive test (NAAT) MMWR April 13, 2007; 56 (14)

33 Case III 37 yo woman presents with pain while having intercourse with her husband. She denies any vaginal discharge. He is asymptomatic.

34 Physical exam

35 Anatomy

36 Bartholin’s abscess Aerobic organisms Neisseria gonorrhoeae Staphylococcus aureus Streptococcus faecalis Escherichia coli Pseudomonas aeruginos Chlamydia trachomatis Anaerobic organisms Bacteroides fragilis Clostridium perfringens Peptostreptococcus species Fusobacterium

37 Treatment Placement of Word catheter Culture/analysis fluid to ensure no co- infection or other findings (rarely, malignancy) Treatment is generally broad-spectrum (including for C. trachomatis and N. gonorrhea)

38

39 Case IV 24 y.o. woman presents with increased, malodorous vaginal discharge for 5 days. She has two sex partners: one man and one woman She practices no safe sex precautions

40 Vaginal examination

41 Cervical examination

42 Microscopy reveals

43 Diagnosis?

44 Trichomoniasis Single-celled protozoan parasite, Trichomonas vaginalis. The vagina is the most common site of infection in women, and the urethra (urine canal) is the most common site of infection in men.

45 Trichomoniasis The parasite is sexually transmitted through penis-to-vagina intercourse or vulva-to-vulva contact with an infected partner. Women can acquire the disease from infected men or women, but men usually contract it only from infected women.

46 Trichomoniasis Signs or symptoms of infection which include a frothy, yellow-green vaginal discharge with a strong odor. May cause discomfort during intercourse and urination, as well as irritation and itching of the female genital area. In rare cases, lower abdominal pain can occur. Symptoms usually appear in women within 5 to 28 days of exposure.

47 Trichomoniasis Treatment 2006 Recommended regimen: – Metronidazole 2 g PO x 1 –Tinidazole 2 g po x 1 Alternative regimen: – Metronidazole 500 mg PO BID x 7d Metronidazole safe at all stages of pregnancy; tinidazole Category C (don’t use) Vaginal therapy is ineffective Treat sex partner(s): male and female

48 Case V 28 y.o. woman comes to your clinic because she has noted increased, malodorous vaginal discharge for about a week. No history of known STD. In your history you note that she washes her vagina with a “special rinse” every month She has been monogamous with a male partner, who is asymptomatic, for 1 year.

49 Case V She and her sex partner do not use condoms on most occasions but practice “withdrawal” method.

50 What do you advise? 1) She probably has a yeast infection because she is at low STD risk 2) She probably has trichomoniasis, and you’ll call in a prescription for tinidazole/metronidazole. 3) Come in for examination. 4) Stop irrigating vagina

51 Rationale for office visit l While most women with malodorous discharge have either BV or trichomoniasis, management of these two processes differ – Both are treated with metronidazole, but need to know whether or not to treat partner(s) – Therefore, specific diagnosis is useful – Overall, BV most common l Unfortunately, syndromic diagnosis of abnormal vaginal discharge is poorly predictive of the actual cause – Examination required (vaginal pH at a minimum)

52 Bacterial Vaginosis: An Ecosystem Out of Balance l Overgrowth of commensal anaerobic flora (classically defined as G. vaginalis, Prevotella, Mobiluncus, M. hominis) relative to H 2 O 2 -producing lactobacilli that predominate in the healthy vaginal ecosystem Gram stain of normal vaginal fluid: many lactobacilli, normal epithelial cells Nugent Score: 0 Gram stain of BV: no lactobacilli, many other bacteria, and clue cells Nugent Score: 10

53 Bacterial Vaginosis Wet Prep: Clue Cell Vaginal Discharge

54 Diagnosis of Bacterial Vaginosis Gram stain findings (Nugent scale): based on number of lactobacilli and other bacterial morphotypes Clinical findings (Amsel criteria): 3 of the following must be present: –homogeneous discharge –pH >4.5 –clue cells (>20%) –amine odor on addition of KOH (+whiff test)

55 BV Complications in Non- Pregnant Women PID Post-abortal PID Post-hysterectomy infection

56 BV and Adverse Outcomes in Pregnancy Data support that BV promotes: –postabortal infections –preterm labor and delivery* –premature rupture of membranes –intramniotic infection –histological chorioamnionitis –postpartum endometritis –spontaneous abortion in first trimester (IVF) *infection implicated in up to 10% of cases

57 2006 CDC STD Treatment Recommendations Bacterial Vaginosis Nonpregnant Women l Recommended - Metronidazole 500 mg PO bid x 7 d - Metronidazole gel 0.75% intravag qHS x 5 d - Clindamycin cream 2% intravag qHS x 7 d l Alternatives* - Clindamycin 300 mg PO bid x 7 d - Clindamycin ovules 100 g intravag qHS x 3 d * Metronidazole 2 g PO, single dose deleted

58 Normal Vaginal pH is Important! l pH <4.7 favors growth of acidophilic organisms, inhibits growth of other organisms (residents and invaders) l Maintained primarily by human Lactobacillus that produce hydrogen peroxide l Elevated vaginal pH associated with: l loss of H2O2-producing lactobacilli l bacterial vaginosis, trichomoniasis l enhanced transmission of HIV l acquisition of gonorrhea

59 Case VI 23 yo woman with HIV (last CD4 310) comes to see you with complaint of vulvar pain. She has no prior history of this. She has one male sex partner (also HIV positive). They have been together for about 3 months. They do not use condoms.

60 Physical exam

61 Differential?

62 Differential for Genital Ulcerative Manifestations in Women HSV Syphilis Chancroid CMV HPV

63 What about non-STI causes for genital ulcers? Behcet’s syndrome Crohn’s disease Erosive lichen planus Pemphigus Trauma

64 What is most likely in this patient?

65 HSV

66 HSV: Clinical Features lMany patients recognize subtle or non- ulcerative symptoms when educated (vulvar fissures; vulvitis; urethral irritation) lGenital herpes due to HSV2  lMore severe primary infections, when they occur lMore likely to recur lPersistent subclinical shedding months-years post- infection lGenital-genital transmission usual route of acquisition

67 HSV: Clinical Features lGenital herpes due to HSV1  lMost don’t recur (1 at most); subclinical shedding does not persist lOral-genital probably important route of transmission

68 Recurrent Genital Herpes lesions

69 Cervical exam

70

71 l Seroprevalence strongly associated with increasing lifetime nos. of sex partners, female sex, black race Xu, JAMA 2006 HSV-2 Seroprevalence in the U.S.

72 1. CDC Sexually Transmitted Diseases Guidelines Wald A, Link K. J Infect Dis. 2002;185: Catotti DN et al. Sex Transm Dis. 1993;20: Brown Z et al. JAMA. 2003;289: Significance of Genital Herpes Physical and psychological concerns HSV-2 infection increases the risk of HIV-1 infection by 2-fold Source of transmission to uninfected partners –89% expressed concern about transmitting to a partner in one study

73 1. CDC Sexually Transmitted Diseases Guidelines Wald A, Link K. J Infect Dis. 2002;185: Catotti DN et al. Sex Transm Dis. 1993;20: Brown Z et al. JAMA. 2003;289: Significance of Genital Herpes Transmission of herpes to newborn during pregnancy or delivery –Occurs in 1 per 3,200 live births –May lead to serious complications such as seizures, blindness, psychomotor retardation, spasticity, learning disabilities, and death

74 Which of the following statements is correct regarding diagnosis of genital herpes? 1.Direct viral culture of a genital lesion can determine whether HSV-1 or HSV-2 is the etiology. 2.Cytology (Tzanck versus Pap) is one of the most useful methods of HSV testing. 3.The odds of getting a positive herpes test from a genital lesion increase the older the lesion gets.

75 Diagnostic Tests for HSV Culture: usual test of choice –Widely available, relatively inexpensive –Distinguishes HSV-1 and HSV-2 –Sensitivity declines as lesions age Polymerase chain reaction (PCR) –Most sensitive Antigen tests, e.g. direct FA –Sensitivity similar to culture –Only direct FA distinguishes HSV-1 from HSV-2

76 Diagnostic Tests for HSV Cytology (Pap, Tzanck preparation) –Insensitive, nonspecific; no role in clinical management Serology –Detects serum antibody

77 Uses of Herpes Serology l Definite Indications: – Diagnosis of genital ulcers or lesions, especially when lesions cannot be sampled or are unlikely to yield virus – Management of sex partners of persons w/ herpes Implications for counseling, antiviral therapy in infected partner – Screen persons at risk for HIV transmission (HIV+) Guerry CID 2005, Strick CID 2006

78 Uses of Herpes Serology l Other Uses: – Pregnant women and partners – Patient request – Not clear whether all sexually active persons should be screened (cost vs. benefit) BUT AVAILABILITY/COST are issues Guerry CID 2005, Strick CID 2006

79 Antiviral treatment: valacyclovir 500 mg PO QD Indications may include: –Discordant couples (the only evidence-based indication) –Persons with multiple partners –Men who have sex with men –HIV-infected Reassess discordant partner annually for seroconversion Counsel regarding condoms, disclosure, abstinence Genital Herpes: Prevention of Sexual Transmission, 2006 CDC STD Treatment Guidelines

80 Acyclovir 400 mg TID x 7-10 d Acyclovir 200 mg 5x/d x 7-10 d Famciclovir 250 mg TID x 7-10 d Valacyclovir 1.0 g BID x 7-10 d 2006 CDC STD Treatment Guidelines Genital Herpes: First Episode HIV- and HIV+ HHH /20/1998

81 HIV-infected: Acyclovir 400 mg TID x 5-10 d Famciclovir 500 mg bid x 5-10 d Valacyclovir 1 gm bid x 5-10 d 2006 CDC STD Treatment Guidelines Genital Herpes: Episodic Treatment of Recurrences HHH /20/1998 * 5x daily acyclovir regimen deleted

82 HIV-negative: Acyclovir 400 mg TID x 5 d Acyclovir 800 mg BID x 5 d Acyclovir 800 mg TID x 2 d* Famciclovir 125 mg BID x 5 d Famciclovir 1 g BID x 1 d Valacyclovir 500 mg BID x 3 d Valacyclovir 1 g qD x 5 d 2006 CDC STD Treatment Guidelines Genital Herpes: Episodic Treatment of Recurrence HHH /20/1998 * 5x daily acyclovir regimen deleted

83 HIV-infected Acyclovir mg bid/tid Famciclovir 500 mg bid Valacyclovir 500 mg bid HIV-negative: Acyclovir 400 mg BID Famciclovir 250 mg BID Valacyclovir 500 mg qD Valacyclovir 1.0 g qd (if >10 episodes /year) 2006 CDC STD Treatment Guidelines Genital Herpes: Suppressive Therapy HHH /20/1998

84 Management of Patients Consider daily suppressive therapy for patients who: –Are bothered by their outbreaks, regardless of their relationship status –Are sexually active with an uninfected partner* –Are newly diagnosed and concerned about transmitting genital herpes to their partner* Consider episodic therapy for patients who: –Are not sexually active and not concerned about their outbreaks –Are sexually active with a partner who has genital herpes * Studied in immunocompetent heterosexual adults

85 Subclinical Shedding: Key Points Frequency of shedding is not related to the frequency of symptomatic outbreaks (8% vs 7% of days by culture in people with 0-3 vs. 4-9 annual outbreaks, respectively) Up to 70% of transmission occurs during subclinical shedding periods (Mertz 1992)

86 Condoms Reduce HSV2 Transmission 528 monogamous couples discordant for HSV2 infection followed for 18 mos. –Condom use for >25% of sex acts associated with 92% reduction in HSV2 acquisition for women 1862 people in HSV2 vaccine study followed over 18 mos. –Condom use for >65% of sex acts associated with 34% reduction in HSV2 acquisition in women and 41% in men Wald 2001

87 A complete STD screen for a young, sexually active woman includes: All women: –External genital and speculum exam –Vaginal pH, KOH whiff –Cervical Pap if not done recently –Chlamydia test –HSV serology –HIV serology –Pregnancy test Selected patients –Bimanual exam –Vaginal fluid microscopy –Gonorrhea test –Syphilis serology

88 A complete STD screen for a young, sexually active woman includes: Information on PREVENTION and CONTRACEPTION!

89 Acknowledgments Jeanne Marrazzo Hunter Handsfield Matthew Golden

90 Thank you! Next session: June 11, 2009 Listserv:

91 Thank you! Next session: June 11 th, 2009 Jose Jeronimo New Tools for Cervical Cancer Prevention


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