1. Genital Tract Infections XU JIAN xuj@zju.edu.cn

2. The Normal Vagina The normal vaginal flora is mostly aerobic, with an average of six different species of bacteria the most common of which is hydrogen peroxide (H 2 O 2 ) producing lactobacilli. The pH level of the normal vagina is lower than 4.5, which is maintained by the production of lactic acid.

3. The Normal Vagina Vaginal self-purification Estrogen-stimulated vaginal epithelial cells are rich in glycogen. Vaginal epithelial cells break down glycogen to monosaccharides, which can then be converted by the cells themselves, and lactobacilli to lactic acid.

4. Trichomonas Vaginitis is caused by the sexually transmitted, flagellated parasite, Trichomonas vaginalis. The transmission rate is high; 70% of men contract the disease after a single exposure to an infected woman, The parasite, which exists only in trophozoite form, is an anaerobe that has the ability to generate hydrogen to combine with oxygen to create an anaerobic environment. It often(60%) accompanies BV.

5. Trichomonas Vaginitis

6. Trichomonas Vaginitis-Diagnosis Vaginal discharge: thin, purulent, malodorous. Strawberry cervix may be observed. The pH usually higher than 5.0 Motile trichomonads. Clue cells may be present (when accompany BV) The whiff test may be positive (when accompany BV)

7. Trichomonas Vaginitis-Diagnosis Because of the sexually transmitted nature of trichomonas vaginitis, women with this infection should be tested for other sexually transmitted diseases (STDs), particularly Neisseria gonorrhoeae Chlamydia trachomatis. Syphilis Human immunodeficiency virus (HIV)

8. Trichomonas Vaginitis-Treatment Metronidazole :first choice for treatment (cure rates 95%) single-dose (2 g orally) OR multidose (500 mg twice daily for 7 days) The sexual partner should also be treated. Metronidazole gel (effective for the treatment of BV) should not be used for the treatment of TV. Treatment of pregnancy women…

9. Trichomonas Vaginitis-Treatment Not respond to initial therapy? Treated again with metronidazole, 500 mg, Bib X 7 ds. Repeated treatment not effective? Treated with a single 2-g dose of metronidazole Qd X5 ds or tinidazole, 2 g, Qd X5 ds. Still not effective? Exclude the possibility of reinfection Expert consultation. Culture of the parasite to determine its susceptibility to metronidazole and tinidazole.

10. Vulvovaginal Candidiasis(VVC)

11. An estimated 75% of women experience at least one episode of VVC. Candida albicans is responsible for 85% to 90% of vaginal yeast infections. Other species of Candida, such as C. glabrata and C. tropicalis, can cause vulvovaginal symptoms and tend to be resistant to therapy.

12. Vulvovaginal Candidiasis(VVC) Candida are dimorphic blastospores, responsible for transmission and asymptomatic colonization mycelia, result from blastospore germination and enhance colonization and facilitate tissue invasion.

13. Vulvovaginal Candidiasis(VVC) Factors that predispose women to the development of symptomatic VVC include: Long-term antibiotic use ： Disequilibrium of of normal vaginal flora. Pregnancy: decrease in cell-mediated immunity Diabetes : decrease in cell-mediated immunity

14. Vulvovaginal Candidiasis(VVC) Classification of VVC UncomplicatedComplicated Sporadic or infrequent in occurrence Recurrent symptoms Mild to moderate symptoms Severe symptoms Likely to be Candida albicans Non-albicans Candida Immunocompetent womenImmunocompromised, e.g., diabetic women

15. VVC-Diagnosis Symptoms: Vulvar pruritus associated with a vaginal discharge that typically resembles cottage cheese. Others:Vaginal soreness, dyspareunia, vulvar burning, and irritation. Examination: Erythema and edema of the labia and vulvar skin. The vagina may be erythematous with an adherent, whitish discharge. The cervix appears normal.

16. VVC-Diagnosis The pH is usually normal (<4.5). Fungal elements, either budding yeast forms or mycelia, appear in as many as 80% of cases. The results of saline preparation of the vaginal secretions usually are normal. The whiff test is negative. A fungal culture is recommended to confirm the diagnosis.

17. VVC-Treatment Topically applied azole ( 吡咯 ) drugs are the most commonly available treatment and are more effective than nystatin ( 制霉菌素 ) fluconazole ( 氟康唑 ), used in a single 150-mg dose (orally), has been approved for the treatment of VVC. miconazole 咪康唑 200mg qd X 7ds

18. VVC-Treatment Patients with complicated VVC : an additional 150-mg dose of fluconazole given 72 hours after the first dose. or with a more prolonged topical regimen lasting 10 to 14 days. Adjunctive treatment with a weak topical steroid, such as 1% hydrocortisone cream, may be helpful in relieving some of the external irritative symptoms.

19. Recurrent VVC Definition: four or more episodes in a year. Symptoms :persistent irritative of the vestibule and vulva. Burning replaces itching Diagnosis: should be confirmed by direct microscopy of the vaginal secretions and by fungal culture. Many women with RVVC presume incorrectly they have a chronic yeast infection. Many of these patients have chronic atopic dermatitis or atrophic vulvovaginitis.

20. Recurrent VVC-treatment A remission of chronic symptoms with fluconazole (150 mg every 3 days for 3 doses). Then be maintained on a suppressive dose of this agent (fluconazole, 150 mg weekly) for 6 months. On this regimen, 90% of women with RVVC will remain in remission. After suppressive therapy, approximately one half will remain asymptomatic. Recurrence will occur in the other half and should prompt reinstitution of suppressive therapy

21. Bacterial Vaginosis (BV)

22. BV has previously been referred to as nonspecific vaginitis or Gardnella vaginitis. The loss of hydrogen peroxide producing lactobacilli Overgrowth of predominantly anaerobic bacteria, as well as G. vaginalis and Mycoplasma hominis ( 支原体人型 )

23. Bacterial Vaginosis (BV) It is not known what triggers the disturbance of normal vaginal flora. Alkalinization of the vagina, which occurs with frequent sexual intercourse or use of douches, plays a role. After normal hydrogen peroxide producing lactobacilli disappear, it is difficult to reestablish normal vaginal flora, and recurrence of BV is common.

24. Bacterial Vaginosis (BV) Sequelae: Pelvic inflammatory disease (PID) Postabortal PID Postoperative cuff infections after hysterectomy ; Abnormal cervical cytology ; Premature rupture of the membranes ; Preterm labor and delivery; Chorioamnionitis; Postcesarean endometritis

25. Bacterial Vaginosis-Diagnosis A fishy vaginal odor Vaginal discharge are present. The pH is higher than 4.5 (usually 4.7 to 5.7). Increased number of clue cells Leukocytes are conspicuously absent. The whiff test releases a fishy, aminelike odor.

26. Bacterial Vaginosis-Treatment Ideally, treatment of BV should inhibit anaerobes but not vaginal lactobacilli. Metronidazole: an antibiotic with excellent activity against anaerobes but poor activity against lactobacilli, is the drug of choice for the treatment of BV. 500 mg, orally twice daily for 7 days Clindamycin, 300 mg, orally twice daily for 7 days Treatment of the male sexual partner has not been shown to improve therapeutic response

27. Bacterial Vaginosis- Differential Diagnosis BVVVCTV Symptomsasymptomatic vulvar pruritus & burning pruritus Vaginal discharge gray, fishy odor white, cottage cheese Yellow,purulent, malodorous Vaginal wallnormalErythema, edemaerythema pH >4.5(4.7 to 5.7)<4.5>5 whiff testpositivenegative microscopyclue cells budding yeast forms or mycelia trichomonads, leukocytes

28. Acute Cervicitis

29. The cause of cervical inflammation depends on the epithelium affected. The ectocervical epithelium can become inflamed by the same micro-organisms that are responsible for vaginitis. Trichomonas, candida, and HSV can cause inflammation of the ectocervix. Conversely, N. gonorrhoeae and C. trachomatis infect only the glandular epithelium

30. Acute Cervicitis-Diagnosis The diagnosis of cervicitis is based on the finding of a purulent endocervical discharge, generally yellow or green in color and referred to as mucopus

31. Acute Cervicitis-Diagnosis Endocervical canal green or yellow color of the mucopus. Cervix is friable or easily induced to bleed. An increased number of neutrophils (30 per high-power field). Intracellular gram-negative diplococci:gonococcal endocervicitis? negative for gonococci, chlamydial cervicitis? Tests for both gonorrhea and chlamydia, preferably using PCR, should be performed.

32. Acute Cervicitis -Treatment Treatment Regimens for Gonococcal Infections Neisseria gonorrhoeae endocervicitis: Cefixime 头孢克肟, 400 mg orally (single dose) or Ceftriaxone 头孢曲松, 125 mg im (single dose), or Ciprofloxacin 环丙沙星, 500 mg orally (single dose) or Ofloxacin, 400 mg orally (single dose) or Levofloxacin 250 mg orally (single dose)

33. Acute Cervicitis -Treatment Treatment Regimens for Chlamydial Infections Chlamydia trachomatis endocervicitis Azithromycin, 1 g orally (single dose), or Doxycycline, 100 mg orally twice daily for 7 days, or Ofloxacin, 300 mg orally twice daily for 7 days, or Levofloxacin, 500 mg orally for 7 days

34. Acute Cervicitis -Treatment It is imperative that all sexual partners be treated with a similar antibiotic regimen. Cervicitis is commonly associated with BV, which, if not treated concurrently, leads to significant persistence of the symptoms and signs of cervicitis.

35. Chronic Cervicitis

36. Pathology: Cervical erosion: three types and three degrees Cervical polyp Naboth cyst Endocervicitis Cervical hypertrophy

37. Chronic Cervicitis-Diagnosis Symptoms Discharge Lower abdominal pain Sourness Infertility Bleeding Others Signs

39. Chronic Cervicitis-Treatment Physical treatment: the main way. Electrocautery Laser Freezing HIFU Medicine Operation?

40. Pelvic Inflammatory

42. PID is a clinical diagnosis implying that the patient has upper genital tract infection and inflammation. The inflammation may be present at any point along a continuum that includes endometritis, salpingitis, and peritonitis

43. Pelvic Inflammatory PID commonly is caused by the sexually transmitted micro-organisms N. gonorrhoeae and C. trachomatis Endogenous micro-organisms found in the vagina, particularly the BV micro-organisms, also often are isolated from the upper genital tract of women with PID, which include anaerobic bacteria such as Prevotella and peptostreptococci as well as G. vaginalis.

44. Pelvic Inflammatory BV often occurs in women with PID, and the resultant complex alteration of vaginal flora may facilitate the ascending spread of pathogenic bacteria by enzymatically altering the cervical mucus barrier. Less frequently, respiratory pathogens such as Haemophilus influenzae, group A streptococci, and pneumococci can colonize the lower genital tract and cause PID.

45. Pelvic Inflammatory -Diagnosis In the diagnosis of PID, the goal is to establish guidelines that are sufficiently sensitive to avoid missing mild cases but sufficiently specific to avoid giving antibiotic therapy to women who are not infected.

46. Pelvic Inflammatory -Diagnosis Traditionally, the diagnosis of PID has been based on a triad of symptoms and signs. It is now recognized that there is wide variation in many symptoms and signs. Some women may develop PID without having any symptoms.

47. Pelvic Inflammatory -Diagnosis PID should be considered in women with any genitourinary symptoms, including, but not limited to, lower abdominal pain, excessive vaginal discharge, menorrhagia, metrorrhagia, fever, chills, urinary symptoms. Pelvic organ tenderness, (uterine alone or uterine with adnexal ) Cervical motion tenderness Direct or rebound abdominal tenderness

48. Pelvic Inflammatory -Diagnosis Evaluation of both vaginal and endocervical secretions is a crucial part of the workup of a patient with PID. An increased number of polymorphonuclear leukocytes may be detected in a wet mount of the vaginal secretions or in the mucopurulent discharge.

49. Pelvic Inflammatory -Diagnosis More elaborate tests may be used,including Endometrial biopsy to confirm the presence of endometritis, Ultrasound or radiologic tests to characterize a tubo- ovarian abscess, Laparoscopy to confirm salpingitis visually.

52. Pelvic Inflammatory -Diagnosis Symptoms None necessary Signs Pelvic organ tenderness Leukorrhea and/or mucopurulent endocervicitis Additional criteria to increase the specificity Endometrial biopsy showing endometritis Elevated C-reactive protein Elevated erythrocyte sedimentation rate Temperature higher than 38°C Leukocytosis Positive test for gonorrhea or chlamydia Elaborate criteria Ultrasound documenting tubo-ovarian abscess Laparoscopy visually confirming salpingitis Clinical Criteria for the Diagnosis of PID

53. Pelvic Inflammatory -Treatment Therapy regimens for PID must provide empirical, broad- spectrum coverage of likely pathogens,including N. gonorrhoeae, C. trachomatis, gram-negative facultative bacteria, anaerobes, and streptococci.

54. Pelvic Inflammatory -Treatment Hospitalization is recommended only when the diagnosis is uncertain, pelvic abscess is suspected, clinical disease is severe, or compliance with an outpatient regimen is in question.

55. Pelvic Inflammatory -Treatment Hospitalized patients can be considered for discharge when their fever has lysed (37.5°C for more than 24 hs), the white blood cell count has become normal, rebound tenderness is absent, and repeat examination shows marked amelioration of pelvic organ tenderness. Sexual partners of women with PID should be evaluated and treated for urethral infection with chlamydia or gonorrhea (Table 16.3). One of these STDs usually is found in the male sexual partners of women with PID not associated with chlamydia or gonorrhea (42,43).

56. Pelvic Inflammatory -Treatment Sexual partners of women with PID should be evaluated and treated for urethral infection with chlamydia or gonorrhea. One of these STDs usually is found in the male sexual partners of women with PID not associated with chlamydia or gonorrhea.

57. Pelvic Inflammatory – Tubo-ovarian Abscess Tubo-ovarian abscess, an end-stage process of acute PID, is diagnosed when a patient with PID has a pelvic mass that is palpable during bimanual examination. The condition usually reflects an agglutination of pelvic organs (tube, ovary, bowel) forming a palpable complex. Occasionally, an ovarian abscess can result from the entrance of micro-organisms through an ovulatory site.

58. Pelvic Inflammatory – Tubo-ovarian Abscess Tubo-ovarian abscess is treated with an antibiotic regimen administered in a hospital. About 75% of women with tubo-ovarian abscess respond to antimicrobial therapy alone. Failure of medical therapy suggests the need for drainage of the abscess

59. Pelvic Inflammatory -Treatment USA-CDC Guidelines Outpatient Treatment Regimen A Cefoxitin, 2 g im, + probenecid, 1 g orally concurrently, Or Ceftriaxone, 250 mg im, Or Equivalent cephalosporin + Doxycycline, 100 mg bid x 14 ds With or without: Metronidazole, 500 mg orally bid x 14 ds a Regimen B Ofloxacin, 400 mg orally bid x 14 ds Or Levofloxacin, 500 mg orally once daily for 14 days With or without: Metronidazole, 500 mg orally bid x 14 ds a

60. Pelvic Inflammatory -Treatment USA-CDC Guidelines Inpatient Treatment Regimen A Cefoxitin, 2 g iv q6h, Or Cefotetan, 2 g iv q12h, + Doxycycline, 100 mg orally or iv q12h Regimen B Clindamycin, 900 mg iv q8h + Gentamicin, loading dose iv or im (2 mg/kg of body weight) followed by a maintenance dose (1.5 mg/kg) q8h Use of metronidazole recommended in those cases in which BV is diagnosed concurrently with PID.

61. Sequelae of PID Diagnosis Medical history Chronic Infertility Recurrent acute PID Ectopic pregnancy Signs

62. Genital tuberculosis

63. Way of infection Blood flow: main way Direct spread: some times lymph vesse ： less sexually transmitted ： very rarely

64. Genital tuberculosis Pathology Tuberculosis of fallopian tube: 90%-100%,bilateral usually Endometrial tuberculosis: 50%-80% Ovarian tuberculosis: 20%-30% Tuberculosis of cervix: rarely Pelvic peritoneal tuberculosis: common

65. Genital tuberculosis-Diagnosis Symptoms Infertility Abnormal menstruation Lower abdominal pain Symptoms of tuberculosis Signs

66. Genital tuberculosis-Diagnosis Auxiliary diagnosis Dilatation & curettage ： frequent giant cells, caseous necrosis, and granuloma formation (time, site, streptomycin) X-ray Laproscopy Tubercle bacillus: microscopy, culturing, PCR Tuberculin test ：（-），(+) and (+++）

67. Genital tuberculosis-Treatment Antitubercular agent Isoniazid （ H, 异烟肼 ） Rifampicin (R, 利福平 ) Streptomycin (S, 链霉素 ) Ethambutol (E, 乙胺丁醇 ) Pyrazinamide (Z, 吡嗪酰胺 ) Regimen A: 2SHRZ/4HR or 2SHRZ/4H 3 R 3 Regimen B: 2SHRZ/6HRE or 2SHRZ/6H 3 R 3 E 3