6: Sexually transmitted infections: new diagnostic approaches and treatments

Francis J Bowden, Sepehr N Tabrizi, Suzanne M Garland and Christopher K Fairley
Med J Aust 2002; 176 (11): 551-557. || doi: 10.5694/j.1326-5377.2002.tb04554.x
Published online: 3 June 2002
Chlamydial infection

Infection with Chlamydia trachomatis is often asymptomatic and causes cervicitis, endometritis and pelvic inflammatory disease in women, with the sequelae of tubal factor infertility and ectopic pregnancy. In men, it causes urethritis, epididymo-orchitis and prostatitis (Box 2). Infection with C. trachomatis is the third most common notifiable disease in Australia, with 16 770 cases reported in 2000 (Communicable Diseases System, personal communication1). As most infections in women are asymptomatic, notification data may under-represent the true incidence of disease in the community. There are no agreed national screening guidelines for C. trachomatis infection, but candidates for screening include sexually active young women attending for Pap smears, contraceptive advice, antenatal care or termination of pregnancy, if indicated by their sexual history (case history, Box 3).

Laboratory diagnosis

Nucleic acid amplification techniques have largely replaced tissue culture, non-amplification DNA probe assays and other rapid antigen assays (eg, direct immunofluorescence and enzyme immunoassay) as the "gold standard" for diagnosis of C. trachomatis because of their greater sensitivity.2 Nucleic acid amplification techniques may use samples collected from the cervix and vagina, but are also easily adapted to self-sampling with self-inserted swabs, tampons or first-void urine.3,4 Most laboratories use PCR, ligase chain reaction or strand displacement amplification. These techniques can be performed in less than 24 hours, but most tests are "batched" and performed several times a week.


A major advance in treatment of C. trachomatis infection has been the introduction of azithromycin (Box 4); clinical trials have found that a single oral dose of this drug has equivalent efficacy to a seven-day course of twice-daily oral doxycycline when compliance is high.5 Both drugs achieve cure rates greater than 95%. If compliance is likely to be suboptimal, then azithromycin is more cost effective.6 Azithromycin is also effective for treatment of non-specific urethritis (ie, cases with negative results for chlamydia and gonococcus).7 Its risk in pregnancy is categorised as B1, and it can be used safely during pregnancy and breastfeeding.8 A seven-day course of erythromycin, roxithromycin or amoxycillin has been recommended for use in pregnancy, but, as these agents are less effective, careful follow-up and retesting after three weeks is highly recommended.9

Complicated chlamydial infections, such as epididymitis or pelvic inflammatory disease (PID), require longer therapy, but treatment recommendations vary greatly. For PID in general, broad-spectrum antimicrobials have been advised (Box 4), as the infection usually involves mixed endogenous vaginal flora, particularly if it occurs postpartum or after gynaecological instrumentation, miscarriage, termination of pregnancy, or insertion of an intrauterine contraceptive device. If PID is sexually acquired, an antibiotic to cover Neiserria gonorrhoeae is also required. As the definitive diagnosis of PID requires laparoscopy, and as the severity and number of episodes of untreated disease contribute to the risk of subsequent complications (chronic pelvic pain, infertility and ectopic pregnancy),10 therapy must be based on clinical features.


Gonorrhoea has similar symptoms, signs and sequelae to chlamydial infection, although symptomatic disease may be more common, especially in men. Rates of gonorrhoea in Australia are currently at their highest for nearly 20 years and double those of 10 years ago.11 Three groups are primarily affected: men who have sex with men (the group with the greatest increase), Indigenous Australians in remote settings, and people who have heterosexual contact overseas. Other heterosexual cases are uncommon.11


Treatment is summarised in Box 4. Infections acquired in remote Australia are almost universally penicillin-sensitive (although the minimum inhibitory concentration for new isolates has been slowly rising over time), and oral amoxycillin with probenecid can be used. Infections acquired in other parts of Australia are often penicillin-resistant,13 and intramuscular ceftriaxone or the oral quinolone ciprofloxacin should be used. However, there has been a recent increase in the incidence of quinolone resistance in isolates obtained from homosexually active men in New South Wales,13 and from heterosexual people infected in South East Asia. Where local data indicate that quinolone resistance is rare, ciprofloxacin can be used for empirical therapy; otherwise, intramuscular ceftriaxone should be used in the first instance. When treating gonococcal infection, antibiotic therapy should also cover possible chlamydial co-infection.

Penicillin alone is not sufficient for pharyngeal and anorectal infections, even with penicillin-sensitive strains. Therefore, in homosexually active men, ceftriaxone or ciprofloxacin is required. Urethral and anorectal infection will be cured in over 98% of cases, whereas for pharyngeal infection the cure rate is lower (about 90%).9

Human papillomavirus infection

Infection with one of the 30 human papillomavirus (HPV) types that infect the genital epithelium is very common, although the vast majority of these infections are asymptomatic.17 A study of women attending a United States university found that the proportion with HPV detected by PCR was 30% in the first year after initiation of sexual intercourse and 80% after 56 months.18 The most common virus type was HPV 16, followed by 6 and 11.

The most usual manifestation of HPV infection, when one occurs, is genital warts. Indeed, genital warts are the most common symptomatic STI. They are usually caused by HPV types 6 and 11 and develop in about half the women infected with these types.

Infection with "oncogenic" strains of HPV has been identified as one of the main risk factors for developing cervical and other anogenital cancers.19 HPV types 16 and 18 account for about 80% of the "high-risk" types, with the remainder being 31, 33, 35, 45, 51, 52, 58 and 59.19

Herpes simplex

Genital herpes may be caused by herpes simplex viruses 1 or 2 (HSV-1 or HSV-2) and may be recurrent in up to 20% of those infected. Serological surveys in Australia indicate that about 15% of women attending antenatal clinics and up to 55% of those attending STI clinics have been infected with HSV-2.20 Genital herpes caused by HSV-1 is often transmitted by oral sex, but tends to be milder than that caused by HSV-2 and recurs uncommonly. Some people with evidence of past HSV-2 infection recall no symptoms.20 HSV transmission may uncommonly occur in the absence of genital lesions (risk, about 10% per year). The risk of acquiring genital HSV-2 from a regular partner is greater for women with no previous HSV-1 infection (20% per year) and least for men with previous HSV-1 exposure (5% per year).20


Aciclovir, valaciclovir and famciclovir are all effective for the treatment of primary and recurrent episodes and for suppression20 (Box 5). The least expensive option is aciclovir (now available in a generic formulation). Primary episodes should be treated regardless of duration of symptoms. On the other hand, symptoms of a recurrence are ameliorated and duration shortened by one to two days if treatment begins within 72 hours of symptom onset. Suppressive therapy prevents at least 75% of attacks and substantially reduces asymptomatic shedding. If recurrent attacks are mild and infrequent then long term suppressive therapy may not be warranted.


Presentations of syphilis include genital ulceration (primary disease) and disseminated rash and glandular fever-like illness (secondary disease), but clinically evident syphilis is very uncommon in Australia. Most detected disease is latent infection. Tertiary syphilis (which includes cardiovascular syphilis and neurosyphilis) is exceptionally rare.

Laboratory diagnosis

The diagnostic approach to syphilis has changed considerably in the past five years. Traditional screening strategies use an initial non-treponemal test (eg, rapid plasma reagin [RPR] or Venereal Disease Research Laboratory [VDRL]), and follow-up positive results with a specific treponemal test (eg, Treponema pallidum particle agglutination or haemagglutination assay, or fluorescent treponemal antibody absorption). However, many laboratories now screen with an automated EIA, which detects treponemal IgG and is therefore equivalent to the specific treponemal tests. EIAs appear to be as sensitive and specific as the traditional tests.22

Unless treatment is instituted in the very early stages of infection, the EIA usually remains positive for life (as does the T. pallidum haemagglutination assay), unlike the non-treponemal tests, which show falling levels (or may become non-reactive) after treatment or spontaneously over time. This means that a small group of people who have been successfully treated for syphilis in the past and have previously had negative RPR results will now test positive on the new screening assays. Conversely, people with untreated syphilis whose RPR has fallen spontaneously to unreactive will now be routinely detected (this group includes up to 25% of patients with neurosyphilis). The cost benefit of the EIA will be less in populations with a high background prevalence of prior syphilis,23 as a significant proportion of people will have a positive EIA result and require further assessment, including an RPR.

In-house PCR tests for syphilis are available in a number of laboratories, but their role in routine diagnosis has not been validated against standard assays. A commercial multiplex PCR test for genital ulcer disease (which tests for T. pallidum, H. ducreyi and HSV) has shown promise in field testing but is yet to be released.24


Donovanosis is a genito-ulcerative disease caused by a gram-negative organism, Klebsiella granulomatis (formerly Calymmatobacterium granulomatis). It is principally confined to indigenous populations in the tropics,26 and is becoming increasingly rare in Australia since the introduction of azithromycin. The standard diagnostic technique is the identification of Donovan bodies in histological or cytological specimens from lesions. A PCR test has also been developed which is sensitive and specific but is not commercially available.27


Two Australian studies have demonstrated the utility of azithromycin.28,29 The agent is highly effective and can be used in pregnancy and in children. Primary cure rates are high, and relapse appears rare.


With the increasing availability of new diagnostic technologies, we are on the verge of a major change in the approach to STI control in Australia. An effective control strategy is based on an accessible and well-trained healthcare workforce, suitable infrastructure, partner notification, disease surveillance, health promotion and outbreak investigation. Primary care physicians will continue to play a central role to ensure the success of such an important program.

1: Common presentations of sexually transmitted infections and recommended investigations*


Possible causes


Urethritis (dysuria, discharge, frequency)

Common causes Chlamydia trachomatis (most important cause in heterosexual contact; commonly asymptomatic)

Neisseria gonorrhoeae (especially in homosexually active men and after heterosexual contact overseas)

Trichomonas vaginalis (consider in remote populations and if overseas contact)

Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum (importance as pathogens not clear: associated with urethritis but considered normal flora)

Herpes simplex virus (HSV) types 1 and 2 (uncommon cause of intermittent, recurrent attacks of urethritis)

Other bacterial causes

Neisseria meningitidis

Cervicitis (usually asymptomatic)

C. trachomatis

N. gonorrhoeae

Vaginal discharge (usually not sexually transmitted)

Candida albicans (most common cause)

Bacterial vaginosis (caused by changes in normal vaginal flora)

T. vaginalis (sexually transmitted)

Pelvic inflammatory disease (pelvic pain, menstrual irregularities, dyspareunia, may be silent)


C. trachomatis

N. gonorrhoeae


Mixed pathogens — anaerobes, facultative bacteria and Mycoplasma spp.

Genital warts (typical warty lesions in anogenital area)

Human papillomavirus (most commonly types 6 and 11; occasionally other types)

Anogenital ulceration

Infective causes

HSV-1 and HSV-2 (most common cause outside remote Australia)

Syphilis (Treponema pallidum)

Donovanosis (Klebsiella granulomatis)

Chancroid (Haemophilus ducreyi) (not endemic in Australia)

Lymphogranuloma venereum (rare)

Non-infective causes

Aphthous ulceration

Behçet's disease


Drug reaction

PCR = polymerase chain reaction. LCR = ligase chain reaction. STI = sexually transmitted infection. * Routine screening for other STIs (including HIV) should also be offered to patients with any of these presentations.

3: Case history — opportunistic screening for sexually transmitted infections

Presentation: A 17-year-old female student from an inner-city high school presented to her general practitioner requesting a first prescription for the oral contraceptive pill.

History: The GP took a thorough sexual history. The patient began sexual activity 6 months previously, had had five sexual partners and never used condoms. She had no genital symptoms.

Management: The GP explained to the patient that she was at risk of having acquired a sexually transmitted infection and suggested that, as she was reluctant to undergo a speculum examination, she obtain a self-inserted swab specimen for a polymerase chain reaction (PCR) test for Chlamydia trachomatis.

A week later, the patient returned for the result of the PCR test, which was positive for C. trachomatis. She was treated with a single oral dose of azithromycin (1 g). The GP discussed with her the need to contact her sexual partners, gave her a "form" letter for them and explained that, as chlamydia is a notifiable disease, the laboratory would report a positive result to the local public health unit. The GP also discussed the need for a Pap smear in the next 12 to 18 months, counselled the patient about safer sex practices and arranged a follow-up visit in two weeks.

At follow-up, the girl reported that she had contacted one partner but was too embarrassed to talk to the others. The GP obtained her permission to contact the other partners and their phone numbers.

4: Treatment of sexually transmitted infections (1)*

Chlamydial and other non-gonococcal urethritis and cervicitis

Azithromycin (1 g orally, as a single dose) or doxycycline (100 mg orally, 12-hourly for 7 days).


Ceftriaxone (250 mg intramuscularly) or ciprofloxacin (500 mg orally, as a single dose)

plus either azithromycin (1 g orally, as a single dose) or doxycycline (100 mg orally, 12-hourly for 7 days).

Where prevalence of penicillin-resistant N. gonorrhoeae is low (eg, remote areas of Australia) use Amoxycillin (3 g) plus probenecid (1 g) plus azithromycin (1 g orally, as a single dose).

Pelvic inflammatory disease (sexually acquired)

Mild to moderate infection Doxycycline (100 mg orally, 12-hourly for 14 days)

plus either metronidazole (400 mg orally, 12-hourly) or tinidazole (500 mg orally, daily for 14 days)

plus either ceftriaxone (250 mg intramuscularly) or ciprofloxacin (500 mg orally, as a single dose).

If adherence to a 2-week course of doxycycline is likely to be suboptimal, doxycycline may be replaced by azithromycin (1 g orally on Days 1 and 8), although no clinical trial has assessed this.

Severe infection Metronidazole (500 mg intravenously, 12-hourly)

plus doxycycline (100 mg orally, 12-hourly)

plus either cefotaxime (1 g intravenously, 8-hourly) or ceftriaxone (1 g intravenously, daily).

Continue until there is substantial clinical improvement, and then use oral therapy (as for mild to moderate infection) to complete 2 weeks of total treatment.

Pelvic inflammatory disease (non-sexually acquired)

Mild to moderate infection Amoxycillin clavulanate (875/125 mg orally, 12-hourly for 7–10 days)

plus doxycycline (100 mg orally, 12-hourly for 7–10 days).

Azithromycin is being investigated as an alternative.

If the patient is pregnant or breastfeeding Substitute roxithromycin (300 mg orally, daily for 14 days) for doxycycline.


Tinidazole or metronidazole (2 g orally, as a single dose).


Clotrimazole (2% vaginal cream for 3 nights or 500 mg pessary as a single dose).

* Adapted from Therapeutic guidelines: antibiotic.8

5: Treatment of sexually transmitted infections (2)*

Genital warts

Clinic-based therapy Cryotherapy, cautery/laser ablation, podophyllin solution (25%) or trichloroacetic acid.

Self-administered therapy Podophyllotoxin paint (0.5%) (applied twice daily) for 3 consecutive days per week until warts resolve

or imiquimod cream (5%) applied on alternate days for up to 3 months.

Herpes simplex types 1 and 2

Initial infection Famciclovir (125 mg) or valaciclovir (500 mg) (both orally, 12-hourly) for 5–10 days or until symptoms resolve

or aciclovir (200 mg orally, 5 times daily, or 400 mg 8-hourly) for 5 days or until symptoms resolve.

Episodic therapy Famciclovir (125 mg) or valaciclovir (500 mg) (both orally, 12-hourly) for 5–10 days or until symptoms resolve

or aciclovir (400 mg orally, 3 times daily) for 5 days or until symptoms resolve.

Suppressive therapy Famciclovir (250 mg orally, 12-hourly) or valaciclovir (500 mg orally daily [if < 10 recurrences per year] or 1 g daily [if 10 recurrences per year])

or aciclovir (200 mg orally 8-hourly or 400 mg orally 12-hourly) for up to 6 months.


Primary, secondary or latent disease (up to two years' duration) Procaine penicillin (1.0 g intramuscularly, daily for 10 days)

or benzathine penicillin (1.8 g intramuscularly, as a single dose).

Late latent syphilis (asymptomatic disease over two years' duration) Procaine penicillin (1.0 g intramuscularly, daily for 15 days)

or benzathine penicillin (1.8 g intramuscularly, once-weekly for three doses).

Pregnant patients should be treated with penicillin in the dosage schedule recommended for non-pregnant patients at a similar stage of disease.


Azithromycin (1 g orally once-weekly for 4 weeks or 500 mg orally once-daily for 7 days).

* Adapted from Therapeutic guidelines: antibiotic.8

  • Francis J Bowden1
  • Sepehr N Tabrizi2
  • Suzanne M Garland3
  • Christopher K Fairley4

  • 1 Canberra Sexual Health Centre, Canberra Hospital, Canberra, ACT.
  • 2 Microbiology and Infectious Diseases, Royal Women's and Children's Hospital, Melbourne, VIC.
  • 3 Melbourne Sexual Health Centre, Melbourne, VIC.


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