1. Bacterial vaginosis is a common cause of vaginal discharge in women of reproductive age, caused by a shift in vaginal bacteria from predominantly lactobacillus to other bacteria like Gardnerella vaginalis and anaerobes. 2. It is diagnosed based on clinical criteria like increased vaginal pH, presence of clue cells on microscopy, or a positive amine test. Treatment involves oral or topical antibiotics like metronidazole or clindamycin. 3. Bacterial vaginosis in pregnancy is associated with risks like preterm labor, so pregnant women are often screened and treated, especially those at high risk of preterm labor. Oral metronidazole is the

1. Bacterial vaginosis Prof. Aboubakr Elnashar Benha University Hospital, Egypt E-mail: elnashar53@hotmail.com

2. Non-specific vaginitis: Haemophilus vaginalis Gardnerella vaginitis: Gardnerella vaginalis Anaerobic vaginosis: Gardnerella vaginalis & anaerobic bacteria Bacterial vaginosis: polymicrobial alteration in vaginal flora causing an increase in vaginal pH, sometimes associated with an homogenous discharge, but in the absence of a demonstrable inflammatory response (Eschenbach et al, 1988 ) History

3. BV is the most common cause of vaginal discharge in young women of reproductive age. Prevalence between 5% & 35% depends on method of screening & the locality. Prevalence

4. Polymicrobial: G. vaginalis (coccobacilli, surface pathogen), Anaerobic bacteria (Bacteroids, Mobiluncus, Prevotella) & Mycoplasma hominis. There is synergistic relationship between the acquired organisms. They replace lactobacilli Aetiology

5. Their metabolism produces volatile amines & organic acids other than lactic acids leading to smell & increase pH. Mobiluncus produce trimethylamine giving the smell of rotting fish. Mobiluncus & Bacteroids produce succinate (Keto-acid) which raises vaginal pH. Absence of lactic acid & the production of succinate blunt the chemotactic response of polymorphnuclear leukocytes & reduce their killing ability. This explains absence of cellular inflammatory response.

6. Gram stain b= bacteroids, c= mobilincus, g= gardenerlla, p=peptostreptococci

7. Electron micrograph of Mobiluncus

8. 1. Increase vaginal pH: Semen, after menstruation when estradiol levels increase. 2. Decrease lactobacilli: Douching, change of sexual partner (change of vaginal environment), episodes of candida . Predisposing factors

9. 3. Smoking: suppresses the immune system facilitating infection. 4. IUCD: 5. Black ethnic groups 6. Lesbians It is not STD: Treatment of the husband is not beneficial in preventing recurrence of BV. Detection of BV in 12% of virgins after menarche.

10. The reason for the alteration in flora is unclear. 1. Hormonal changes: the mechanism is unclear 2. Enzymatic changes: Mucinase & siallidase are elevated in vaginal discharge of BV. Breaking down the mucosal barrier 3. Bacteriophage ( virus that infects bacteria) Pathogenesis

11. Up to half the women diagnosed with BV are asymptomatic . . Discharge: thin, homogenous, whitish-grey, frothy & fishy. Absence of discharge does not imply the absence of BV. It is not accepted as a reliable indicator on its own as it is neither sensitive nor specific to BV.(Deborah et al,2003) . Seldom associated with mucosal inflammation or irritation of the vagina or vulval itch. Clinical picture

12. 1. pH of discharge: 5.7 A low pH virtually excludes BV. An elevated pH is the most sensitive but least specific as an increase can also associated with menstruation, recent sexual intercourse, or infection with T. vaginalis Diagnosis

13. 2. Whiff test (amine test). Addition of 10% KOH to a sample of vaginal discharge produces fishy odor. It has a positive predictive value of 90% & specificity of 70%

14. 3. Wet film (drop of vaginal secretion & drop of saline): clue cells (epithelial cells covered by coccobacilli, borders are indistinct), No WBC. It is the single most sensitive & specific criterion for BV. , but it is operator dependent. Debris & degenerated cells may be mistaken for clue cells & lactobacilli may adhere to epithelial cells in low numbers. .

15. 4. Gram stain: 90% sensitivity, highly sensitive & specific (Gr. Variable c.bacilli, no WBC, no lactobacilli). Scoring systems which weight numbers of lactobacilli & numbers of G vaginalis & Mobiluncus. It is simple & objective method. However the cost & need for microscopist. .

16. 5. Rapid tests: . Diamine test: rapid, sensitive & specific . Proline aminopeptidase test (Pip Activity test Card) . A card test for detection of elevated pH & trimethylamine (FemExam test card) . DNA probe based test for high concentration of G. vaginalis (Affirm VP III) may have clinical utility.

17. . Pap. smear: clue cells. Limited clinical utility because of low sensitivity . Culture: It is not recommended as a diagnostic tools because it is not specific.

18. Amsel’s criteria 3 of the following: . Homogenous discharge. . pH> 4.5. . Amine test. . Clue cells. Gram stain alone corresponds well to Amsel’s criteria & to the presence of the associated bacteria.

19. Gynecological 1. Psychological disturbance 2. PID: The microorganisms of BV & PID are similar. There is 10 fold-increased risk of PID in females with BV. 3. Tubal infertility: 1/3 of women with tubal factor infertility had BV compared to 16% of male factor infertility (Wilson et al, 2000). Complications

20. 4. Post-hysterectomy vaginal cuff infection. 5. Uretheral syndrome. 6. HIV susceptibility infection . The presence of BV increases susceptibility to HIV infection BV is not associated with CIN

21. Obstetric 1. Miscarriage: Women with BV had a higher rate of first trimester miscarriage than those with normal vaginal flora. Recurrent first trimester miscarriage has not been associated with BV. The incidence of late miscarriage (13-23 w) is higher in women with BV. 2. Postabortal sepsis. The use of antibiotic prophylaxis before surgical termination of pregnancy demonstrates a protective effect.

22. 3. Preterm labour. The earlier in pregnancy that BV is detected the greater the risk of PTL. Treatment of high risk, BV positive pregnant women has resulted in reduction of PTL by 40-50%. 4. Bactraemia after instrumental delivery 6. Chorioamnionitis. 7. Postpartum endometritis, post cesarean wound infection

23. A. Non pregnant Benefits of treatment: . relieve vaginal symptoms & signs of infection. . Reduce the risk for infectious complications after hysterectomy or abortion. . Reduction of other infectious complications e.g., HIV, STD Indications 1. Symptomatic women (Grade A recommendation). 2. Women undergoing some surgical procedures(Grade A recommendation). Treatment

24. Recommended regimens (CDC,2002) Metronidazole 500 mg orally twice a day for 7 days, OR Metronidazole gel 0.75%, one full applicator (5g) intravaginally, once a day for 5 days OR Clindamycin cream 2%, one full applicator (5g) intravaginally at bed time for 7 days.

25. Alternative regimens (CDC,2002) Metronidazole 2 g orally in a single dose, OR Clindamycin 300 mg orally twice a day for 7 days, OR Clindamycin ovules 100 mg intravaginally once at bedtime for 3 days.

26. Notes: The recommended metronidazole regimens are equally effective. Metronidazole gel is more expensive than tablets The vaginal clindamycin is less effective than the metronidazole regimens. The alternative regimens have lower efficacy for BV. No data support the use of non-vaginal lactobacilli or douching for treatment of BV.

27. Clindamycin cream or oral is preferred in case of allergy or intolerance to metronidazole. Theoretically, Metronidazole has an advantage because it is less active against lactobacilli than clindamycin. Conversely, clindamycin is more active than metronidazole against most of the bacteria associated with bacterial vaginosis

28. .Follow up Follow-up visits are unnecessary if symptoms resolve. Another recommended treatment regimen may be used to treat recurrent disease. Management of husband is not recommended

29. B. Pregnant Natural history: BV is present in up to 20% of pregnant women depending on how often the population is screened. The majority is asymptomatic. It may spontaneously resolve without treatment, although the majority is likely to have persistent infection later in pregnancy.

30. Recommended regimen Metronidazole 250 mg orally three times a day for 7 days, OR Clindamycin 300 mg orally twice a day for 7 days

31. Notes: Existing data do not support the use of topical agents during pregnancy. Evidence from three trials suggests an increase in adverse events (e.g. prematurity & neonatal infection), particularly in newborns, after use of clindamycin cream (McGregor et al,1994; Joesoef et al,1995; Vermeulen et al,1999).

32. Multiple studies & meta-analysis have not demonstrated a consistent association between metronidazole during pregnancy & teratogenic or mutagenic effects in newborns (Caro-Paton et al,1997).

33. Indications 1. All symptomatic pregnant women should be tested & treated. 2. Asymptomatic pregnant women at high risk for PTL ( previous history), should be screened early in pregnancy & treated (Cochrane library,2002)

34. 3. Asymptomatic pregnant females at low risk for PTL: Data are conflicting whether treatment reduces adverse outcomes of pregnancy. One trial, using oral clindamycin demonstrated a reduction in PTL & postpartum infectious complications (Hay et al, 2001). Oral clindamycin early in the second trimester significantly reduced the rate of late miscarriage & PTL in general obstetric population (Ugwumadu et al, 2003).

35. How to screen for BV ? (Gierdingen et al, 2000) Ask about symptoms & pH of the vagina is determined frequently during pregnancy. If pH > 4.5 ( BV or TV in 84%), do wet mount. Follow-up of pregnant women One month after treatment to evaluate whether therapy was effective is recommended.

36. C. lactation Metronidazole enters breast milk & may affect its taste. The manufacturer recommend avoiding high doses if breast feeding. Small amounts of clindamycin enter breast milk. It is prudent therefore to use an intravaginal treatment for lactating women (Grade C recommendation)

37. Thank you Prof. Aboubakr Elnashar Benha University Hospital, Egypt E-mail: elnashar53@hotmail.com