VAGINAL DISCHARGE MANAGEMENT OF VAGINAL DISCHARGE

Vaginal discharge may be entirely normal, or a sign of infection. In either case, it is a relatively common presentation in general practice and deserves some attention.

The normal anatomy, physiology and microbial ecology of the vagina are age- dependent as are the sources of vaginal infections. In the neonatal period, the vagina is influenced by maternal oestrogen and has a stratified squamous epithe- lium. Later, and until puberty, the vagina is lined by cuboidal cells and the pH is around 7.0. Following puberty, oestrogen causes a change to stratified squa- mous epithelium. The predominant microbial flora at this age are lactobacilli such as L. crispatus and L. jensenii, which produce lactic acid, and the pH falls to 4.0 - 4.5. The other vaginal flora include diphtheroids, β-haemolytic strepto- cocci, coliforms and coagulase-negative staphylococci.1

VAGINAL DISCHARGE IN PRE-PUBERTAL GIRLS Vaginal symptoms including a discharge in pre-pubertal girls ought to be investi- A A HOOSEN gated microbiologically as the sexually transmitted (ST) pathogens Neisseria gon- 2 MSc, MB ChB, MMed, FCPath orrhoeae and Chlamydia trachomatis may be isolated. Chief Specialist and Head Other non-ST pathogens include β-haemolytic streptococci Group A (S. pyo- Department of Microbiological Pathology genes), Shigella flexneri and Enterobius vermicularis. MEDUNSA Professor Anwar Hoosen is currently Head of VAGINAL DISCHARGES IN POST-PUBERTAL WOMEN the NHLS’s Microbiology Laboratory for the Vaginal infection is one of the top 25 reasons for women to consult doctors in the Northern Branch. He has conducted numerous USA. The 3 most common types of vaginal infections include bacterial vaginosis, clinical trials and has a research interest in trichomoniasis and candidiasis and these may or may not be associated with cer- vical infection. Other vaginal syndromes are due to chemical toxins or physical infectious diseases with special emphasis on agents (Fig. 1). sexually transmitted infections. He is a recipi- ent of the NRFs grant for research in sexually VAGINAL DISCHARGE IN POSTMENOPAUSAL WOMEN transmitted diseases and is also the principal In this age group, the vaginal epithelium becomes thin along with an increase in investigator for a phase III vaginal microbicide pH. Besides ST pathogens, a number of chronic vulvovaginal syndromes occur. An important one is desquamative inflammatory vaginitis, a syndrome associated study to be conducted at GaRankuwa and with purulent vaginal discharge, vaginal cell exfoliation, increase in pH and Soshanguve. Gram-positive cocci being observed in vaginal fluid. This syndrome responds to 2% clindamycin cream intravaginally.3

VAGINAL DISCHARGE IN ADULT WOMEN Of the 3 common infective causes of vaginal discharge, bacterial vaginosis is the commonest. However, in certain populations trichomoniasis may be as common. Yeast infections also occur commonly and host factors ranging from genetic to acquired such as pregnancy, diabetes mellitus, use of corticosteroids, immunosup- pressive therapy and systemic antimicrobials may predispose to colonisation and infection.

A summary of the symptoms, signs and diagnostic features of common vaginal infections in adult women is presented in Table I.

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Vaginal symptoms including Bacterial vaginosis BV was previously considered to be a discharge in pre-pubertal Bacterial vaginosis (BV) is the result of merely an inconvenience for women. girls ought to be investigat- overgrowth of the resident vaginal However, there is increasing evidence linking BV with adverse outcomes in ed microbiologically as the flora, which comprises Gardnerella vaginalis, Mobiluncus, Bacteroides, pregnancy, such as chorioamnionitis, sexually transmitted (ST) and Prevotella species and preterm labour, prematurity and post- 4,5 pathogens Neisseria gonor- Mycoplasma hominis. There is simul- partum fever. rhoeae and Chlamydia tra- taneous loss of the normal resident lac- chomatis may be isolated. tobacilli of the vagina. There is no The diagnosis of BV is made using inflammation of the vaginal epithelium bedside tests fulfilling at least 3 of the and therefore BV represents a change following criteria: Of the 3 common infective in the vaginal ecosystem. The cause •presence of grey, white homoge- causes of vaginal dis- for this overgrowth is unknown. It is nous discharge charge, bacterial vaginosis felt that normal vaginal lactobacilli are • positive amine test (addition of 1 drop of 10% KOH to 1 drop of is the commonest. hydrogen peroxide (H2O2)-producing and this restricts proliferation of the vaginal secretions releasing a char- However, in certain popu- organisms associated with BV. A loss acteristic fishy odour) lations trichomoniasis may • vaginal pH > 4.5 and presence of in H2O2-producing lactobacilli leads to be as common. Yeast the development of BV. clue cells on microscopic examina- infections also occur com- tion of vaginal secretions or by per- monly and host factors The bacterial overgrowth in BV results formance of a Gram stain on vagi- in production of amines by anaerobes nal secretions and using a scoring ranging from genetic to 6 and when potassium hydroxide is system proposed by Nugent et al. acquired such as pregnan- added to the vaginal fluid, a typical A score of 7 is diagnostic of BV; 3 cy, diabetes mellitus, use of fishy odour is produced. The bacterial is negative and 4 - 6 indicates an corticosteroids, immunosup- amines together with organic acids indeterminate diagnosis. Cultures pressive therapy and sys- such as acetic and succinic are cyto- of G. vaginalis do not offer any temic antimicrobials may toxic leading to exfoliation of vaginal advantage for diagnosis, as they are positive in nearly 60 - 70% of predispose to colonisation epithelial cells. G. vaginalis adheres to exfoliated epithelial cells and this women without infection. and infection. creates shaggy-looking clue cells, which are a characteristic feature of Ampicillin has been used with some BV. success. However, the drug of choice

VAGINAL DISCHARGE

PHYSIOLOGICAL PATHOLOGICAL

¥Sexual arousal ¥ Pregnancy INFECTIOUS NON-INFECTIOUS ¥ Pre-menses ¥ Detergents e.g. Nonoxynol 9 ¥Foreign bodies e.g. cervical caps ¥ Viral antiseptics e.g. Policresulin Vaginal causes ¥Traditional herbal preparations e.g. Snuff ¥Tumours e.g. carcinoma of the cervix Cervical causes ¥Trichomoniasis

¥ Bacterial vaginosis

¥ Candidiasis

Endocervicitis / Ectocervicitis mucopurulent cervicitis

¥ Neisseria gonorrhoeae ¥ Herpes simplex virus ¥ Chlamydia trachomatis ¥Trichomoniasis ¥ Herpes simplex virus Fig. 1. Overview of the aetiology of vaginal discharge in adult women.

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Table I. Diagnostic features of vaginal discharge in adult women

Normal Candidiasis Trichomoniasis Bacterial vaginosis

Microbiology Mainly lactobacilli Candida albicans Trichomonas Associated with L. jensenii, L. crispatus C. glabrata vaginalis Gardnerella vaginalis, Mycoplasma hominis, Mobiluncus species Bacteroides and Prevotella Symptoms None Vulval itching and Purulent Malodorous discharge irritation discharge Discharge characteristics • amount Scant/none Scanty to moderate Profuse Moderate • colour Clear White Yellow Grey/milky • consistency Non-homogenous Curd-like, adherent Frothy Homogenous, non-adherent Vaginal epithelium Normal Erythema Erythema No inflammation pH Usually < 4.5 > 4.5 > 5.0 > 4.5 Amine/whiff test with 10% KOH Negative Negative May be positive Positive Microscopy Normal epithelial cells, Leucocytes, epithelial Leucocytes, motile Clue cells, mixed flora lactobacilli cells, ovoid budding trichomonads predominantly Gram- yeast and mycelia variable bacilli including curved rods

is metronidazole (Table II). The major- tozoan destroys epithelial cells by Treatment of trichomonal infection is ity of studies have shown better direct contact. with metronidazole or tinidazole. response and fewer recurrences with Metronidazole is the commonest multiple-dose therapy, rather than a The clinical features of infection range nitroimidazole currently used for thera- single 2 g dose. from asymptomatic to profuse malodor- py. Oral therapy is preferred because ous vaginal discharge. The character- there is concurrent infection of the ure- The treatment of asymptomatic BV is istic feature is a frothy greenish-yellow, thra and periurethral glands. Single- recommended in pregnancy especially purulent discharge. The vaginal walls dose therapy of 2 g oral metronida- in women with poor obstetric histories. are erythematous and in severe infec- zole has shown cure rates of greater tion, punctuate haemorrhages on the than 90% and is preferred as it Trichomoniasis ectocervix give the cervix a strawberry ensures compliance. Disadvantages Trichomoniasis is a sexually transmit- appearance. Untreated trichomoniasis of the single-dose regimen are nausea, ted infection (STI). The prevalence of in pregnancy may predispose to pre- a metallic taste in the mouth, disulfi- trichomoniasis in South African women mature rupture of membranes. ram-like effect with alcohol and also ranges from 5% to 49% in the differ- the need to treat sexual partners simul- ent groups studied. Higher preva- Diagnosis is by demonstration of the taneously. Treatment in early pregnan- lences appear to occur in pregnant organism by wet smear microscopy or cy is a problem because of the safety women. Being an STI, trichomoniasis staining techniques such as acridine of metronidazole, and in such a set- commonly occurs together with gonor- orange, Giemsa, etc. or by culture in ting the use of vaginal clotrimazole or rhoea and chlamydia. media such as modified Diamond’s. povidone iodine may be beneficial. Wet smear microscopy relies on visual- The main vaginal defence mechanism isation of flagellated, pear-shaped pro- Candidiasis is production of local vaginal leuco- tozoa with their characteristic jerky Prevalence studies from developed cytes, which attempt to kill the movement in the presence of numerous countries show yeast infections to be causative agent. The virulence mecha- leucocytes (Table I). the second most common cause of nism of Trichomonas vaginalis is poor- vaginal infections while these appear ly understood and it is felt that the pro- to be the least common of the 3 main

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in erythema of the vaginal epithelium. Table II. Regimens for the treatment of bacterial vaginosis Clinical diagnosis is easily confirmed by doing a wet saline mount or 10% Oral regimens potassium hydroxide (KOH) prepara- tion (Table I). Cultures may be per- Metronidazole formed in cases where microscopy is 400 mg po bid for 7 days negative. 200 mg po tid for 7 days 2 g po as a single dose For the management of vulvovaginal Clindamycin candidiasis various topical formula- 300 mg po bid for 7 days tions such as creams, pessaries, Vaginal regimens tablets, ovules, etc. are available. There is no evidence favouring any Clindamycin particular formulation or any particular 2% vaginal cream, 5 g vaginally nightly for 7 days azole preparation. However, in the Metronidazole* presence of vulval inflammation local 0.75% vaginal gel, 5 g vaginally bid for 5 days application of a cream is beneficial. There is also a marginal benefit of *Not available in South Africa. using azole preparations over the polyene, nystatin. For ensuring compli- causes of infection in women in devel- may also be soreness, vulval burning, ance, there is a trend towards using oping countries. Candida albicans is dyspareunia and dysuria. higher antifungal doses for a shorter the most common species of yeast iso- duration. Some commonly available lated from the vagina (±90%) while Recurrent candidal vaginitis may be preparations are shown in Table III. C. glabrata and C. tropicalis are due to a number of factors but it is dif- found less frequently. The germination ficult to identify the exact precipitating of yeast forms enhances colonisation mechanism. More than one host fac- The oral agents for the treatment of and tissue invasion. Pregnant women tor may be involved and there is no vulvovaginal candidiasis include keto- are predisposed to infection, evidence of defect in local immunity. conazole (400 mg for 5 days), itra- especially in the third trimester, as are For the prevention of recurrent candidi- conazole (200 mg bd for 1 day) and women on oral contraceptives, asis in women using systemic antibi- fluconazole (150 mg single dose).7 systemic antibiotics, corticosteroid or otics, an oral antifungal should be The latter is the only single-dose regi- immunosuppressive therapy and those used weekly, e.g. 100 mg flucona- men recommended. These agents may 7 with uncontrolled diabetes mellitus. zole. be preferred by patients for conven- ience but should not be prescribed in The common presenting symptom is The discharge of candidiasis is curd- pregnancy. Ketoconazole has been vulval itching and irritation. There like and adherent due to direct hyphal associated with hepatotoxicity and invasion of epithelial tissues resulting caution should be exercised when using this agent. Table III. Commonly available topical treatment regimens for vaginal candidiasis Women who have recurrent vulvovagi- nal candidiasis may have predispos- Agent Formulation Regimens ing factors, which need to be addressed. However, in many women Clotrimazole Vaginal cream, tablets 5 g nightly for 6 - 12 days with recurrent infection, no underlying 2 tabs (200 mg) nightly for or predisposing factors are identified. 3 days These women are best managed with Single dose 500 mg long-term suppressive prophylaxis and Miconazole Vaginal cream, capsules 200 mg capsule or 5 g cream this may be achieved with a weekly nightly for 7 days dose of 100 mg fluconazole or weekly Single dose 1 200 mg capsule vaginal insertion of 500 mg clotrima- Econazole Vaginal cream, ovules 50 mg ovule/night for 14 days zole. 150 mg ovule/night for 3 days CERVICITIS Depot ovule 150 mg single dose Cervicitis implies an infection of the cervix and this may be either an ecto- Nystatin Vaginal cream, tablets 1 tablet/day for 14 days cervicitis due to ST pathogens such as 4 - 8 g cream/night for 14 days

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Table IV. Diagnostic tests for confirmation of endocervicitis

Neisseria gonorrhoeae Chlamydia trachomatis Herpes simplex virus

Culture Gold standard Sensitivity varies and at Gold standard best 60 - 70% accurate Antigen tests Not accurate, poor Variable, some tests Fairly accurate, but not sensitivity showing 70 - 80% accuracy widely used Molecular tests Commercial assays e.g. PCR and strand displacement No commercial assay on assay (SDA) available and currently recommended as the market yet tests of choice for C. trachomatis diagnosis. Can also be performed on non-invasive specimens such as initial stream of urine and self-administered swabs

herpes simplex virus or T. vaginalis or ≥ 30 polymorphonuclear cells per MANAGEMENT PROTOCOL an endocervicitis also called mucopu- high-power field. To detect the underly- Comprehensive investigation rulent cervicitis (MPC) due mainly to ing cause one has to use more defini- and management N. gonorrhoeae and C. trachomatis. tive tests such as culture, antigen All patients with a complaint of vagi- The presence of a purulent exudate detection and molecular assays such nal discharge ought to have a specu- from the cervical os has been highly as DNA probe tests and polymerase lum examination to determine whether associated with N. gonorrhoeae and chain reaction (PCR). The diagnosis of the vagina alone or the vagina and C. trachomatis infection. An important gonococcal infection can easily be cervix are affected. This also assists in pathogen which also infects the cervix made with culture, but for diagnosing specimen collection for bedside and is the human papillomavirus but this is chlamydial infection, culture alone is laboratory tests. These investigations not associated with cervicitis. not sensitive. The newer molecular and the respective management strate- tests such as PCR are popular as they gies have been discussed above. The risk factors for endocervical infec- are more sensitive, specific and even tion are the same for all ST pathogens, allow for testing on non-invasive speci- Syndromic management namely young age, unmarried per- mens such as urine, self-administered In view of the inability to carry out sons, lower socioeconomic status, swabs and tampons (Table IV). extensive, comprehensive assessment increased number and recent changes of patients presenting to primary in sexual partner, prostitution and Antimicrobial agents currently recom- health care facilities in many public drug use. Cervicitis may be asympto- mended for the management of endo- health clinics, there is a dire need to matic and detected only during specu- cervicitis or mucopurulent cervicitis are provide adequate care in an organ- lum examination, or it may be recog- as follows: ised, structured manner. Syndromic nised in the presence of concurrent • For N. gonorrhoeae — either a management has been widely advo- vaginal discharge. However, occasion- quinolone in a single-dose regimen, cated world-wide for developing com- ally mucopurulent cervicitis may pro- e.g. ciprofloxacin 500 mg, munities, and allows management of duce a vaginal discharge on its own. ofloxacin 400 mg or a parenteral patients at the time of first contact, A clinical diagnosis may be helped by preparation, e.g. ceftriaxone 125 ensuring treatment of the most likely detecting friability of the cervix or con- mg as an intramuscular injection. causes. This also allows time to com- tact bleeding when examining with a • For C. trachomatis — oral prepara- ply with the 4Cs for prevention of swab and with the visualisation of a tions of a macrolide, e.g. erythro- STIs: counselling, condom promotion, greenish-yellow exudate. The two- mycin 500 mg qid for 7 days or contact management and encouraging swab test has also been proposed for tetracycline, e.g. doxycycline 100 compliance. symptomatic women, i.e. the use of mg bd for 7 days or a single 1 g the first swab for removal of cervical dose of azithromycin. The protocol for syndromic manage- mucus and insertion of the second • For herpes simplex infection — acy- ment of vaginal discharge according swab into the endocervical canal, then clovir 400 mg tid for 10 days for a to the National Department of Health removing it and observing for a colour primary episode and for 5 days for (Directorate for HIV/AIDS and STDs) is change against a white background. recurrence, or valaciclovir 500 mg presented in Fig. 2. bd for 10 days and for 5 days for The laboratory test for diagnosing recurrence. References available on request. MPC is based on a simple Gram stain of the cervical exudate, which yields

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VAGINAL DISCHARGE SYNDROME

Patient complains of vaginal discharge/dysuria or vulval itching/burning

Take history and examine (external genitalia and bi-manual, use speculum)

Abnormal discharge or Any other STI vulval itching or burning NO syndrome

YES

YES Use appropriate flow chart, manage appropriately

Treat with: Lower abdominal ¥ Ciprofloxacin 500 mg stat tenderness or NO ¥Doxycycline 100 mg 2 x daily for 7 days pain? ¥ Metronidazole 2 g stat In pregnancy / during breast-feeding: YES ¥ Cefriaxone 125 mg imi stat ¥ Erythromycin 500 mg 4 x daily for 7 days ¥ Metronidazole 2 g stat

Use lower abdominal pain flow chart If vulval oedema/curd-like discharge, erythema, excoriations present, add:

¥ Cotrimazole vaginal pessary 500 mg inserted stat

Ask patient to return in 7 days if symptoms persist

¥ Symptoms/signs improved? Treatment ¥ Re-infection (new episode)? NO failure: ¥ Poor compliance? Refer second level of care

YES

Repeat treatment

ALL PATIENTS: Educate, ensure compliance, and counsel Promote abstinence from penetrative sex during the course of treatment Promote and demonstrate condom use, provide condoms Stress the importance of partner treatment and issue one notification slip for each sexual partner, follow up partner treatment during review visits Promote HIV counselling and testing, for negative test results repeat test after 3 months

Fig. 2. Protocol for syndromic management of vaginal discharge.

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IN A NUTSHELL

Vaginal discharges are a common problem in adult women.

The discharges may be physiological or pathological.

The common pathological causes are due to infection occurring in the cervix (cervicitis) or in the vagina (vaginitis and vaginosis).

The common causes of endocervicitis are the sexually transmitted pathogens of Neisseria gonorrhoeae and Chlamydia trachomatis.

The important causes of vaginal infection are trichomoniasis due to Trichomonas vaginalis, candidiasis due to Candida albicans and bacterial vaginosis due to proliferation of endogenous vaginal flora of Gardnerella vaginalis, anaerobes and Mycoplasma hominis.

Bedside tests of pH determination, whiff test and wet smear microscopy can easily diagnose vaginal infection.

Laboratory tests are required to confirm the causes of endocervicitis or mucopurulent cervicitis (MPC).

Syndromic management of vaginal discharge attempts to treat both cervical and vaginal causes.

Syndromic management is widely acclaimed for use in developing communities as it covers the common causes of infection at the point of first contact.

SINGLE SUTURE

CANNABIS RELIEVES SYMPTOMS OF MS — BUT ONLY JUST

In what has been described as a 'limited victory for med- ical cannabis' Zajicek and colleagues have published a paper in The Lancet which claims that cannabis relieves the subjective symptoms of multiple sclerosis (MS). Patients with MS received either a delta-9-tertahydrocannabinol (THC), or cannabis extract or placebo. Standard objective tests to measure spasticity suggested that the drugs were no more effective than placebo. But, 60% of patients receiving cannabis reported improvements in spasticity compared with 46% on placebo. Pain relief was also an important effect noted by those on cannabis.

As Zajicek points out, there is now as much evidence to support the use of cannabis as there is for more convention- al treatments such as baclofen. The Lancet asks the question — will attitude continue to limit the use of cannabis? Difficult to say, particularly when use and possesion of cannabis is still illegal in most countries.

Zajicek J, et al. Lancet 2003; 362: 1517-1526.

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