7 June 2019

Shining a spotlight on gonorrhoea and syphilis

Clinical Communicable Disease

Two cases of multi-drug resistant gonorrhoea in Australia put STIs into the national spotlight last year. Additionally, an outbreak of syphilis in rural and remote Aboriginal communities spanning three states and a territory is transpiring.

GONORRHOEA

Incidence

Notifications for gonorrhoea have been increasing in Australia over the past decade with men who have sex with men (MSM) in urban areas, and Indigenous Australians in remote communities being disproportionately affected.

Between 2013 and 2017, there was an 80% increase in national notification rates from 65.5 per 100,000 in 2013 to 118 per 100,000 in 2017. Of the 28,875 gonorrhoea notifications in Australia in 2017, 74% of notifications were diagnosed in men, 74% were in people living in major cities and 15% were among the Aboriginal and Torres Strait Islander population. The gonorrhoea notification rate in Aboriginal and Torres Strait Islander population in remote and very remote areas was 29 times higher than the rates in the non-Indigenous population.1

Multi-drug resistant gonorrhoea

Last year there were two cases of multi-drug resistant gonorrhoea infection detected in Australia. This is a major public health concern given that these gonococcal strains were resistant to ceftriaxone, azithromycin, ciprofloxacin, penicillin and tetracycline.2 One case was a man who had acquired the infection in South East Asia, while the other case was in a woman who had no recent overseas travel.3

Lack of treatment would have serious public health consequences; gonorrhoea can lead to pelvic inflammatory disease in women, which has negative reproductive health consequences and adverse pregnancy outcomes.4 Furthermore, gonorrhoea is a risk factor for HIV because it increases the susceptibility to acquiring HIV infection and increases the transmissibility of HIV infection.5

The Gonococcal Antimicrobial Surveillance Program monitors antimicrobial resistance in the isolates of  Neisseria gonorrhoea across Australia and reduced susceptibility to ceftriaxone is emerging in urban Australia. 

The latest annual report from 2017 demonstrated that there was decreased susceptibility to ceftriaxone nationally in 1.06% of isolates, which is lower than the 2016 percentage of 1.7%. However, resistance to azithromycin was found in 9.3% of isolates which is double the proportion reported in 2016.6

Transmission and symptoms

Gonorrhoea is caused by the bacterium Neisseria gonorrhoea. It is transmitted by sexual contact and from mother to child at the time of birth. Additionally there is some evidence that it may be transmitted through tongue-kissing.

The transmission occurs via direct mucous membrane to mucous membrane contact or via infected genital secretions on a susceptible mucous membrane surface. It targets the columnar cells in the mucous membranes of the urethra, endocervix, rectum, pharynx and conjunctiva.4

The infection triggers a local immune response with production of cytokines and the influx of many polymorphonulcear lymphocytes, leading to visible signs of inflammation such as urethritis and cervicitis.

It’s usually only infection in the male urethra, which produces early detectable symptoms of dysuria and purulent discharge.4 Approximately 10-15% of men and 80% of women will have no symptoms.8

Incubation is usually from two to 10 days for male urethral discharge, but can be up to weeks.4 Cervical, anal and throat infections are usually less likely to show recognisable symptoms, at least in the first few weeks. Rectal gonorrhoea can lead to proctitis in which there is discharge, irritation, painful defecation or disturbed bowel function.9

In women, gonorrhoea can cause dysuria and vaginal discharge with cervicitis. It can then initiate an ascending infection to the fallopian tubes, surrounding ligaments and adjoining organs. The infection can cause an acute pelvic inflammatory disease leading to symptoms such as intermenstrual or post-coital bleeding, dyspareunia or abdominal pain.

Without early treatment, healing occurs with damaging scar tissue formation and fibrosis of the fallopian tubes, which can cause interference with normal function and lead to an ectopic pregnancy and infertility.4

Untreated gonorrhoea in men causes infection, which spreads to the epididymis and testis resulting in an acute epididymo-orchitis. It can rarely cause prostatitis.

When infected body fluid is transmitted to the eyes, it can lead to sight-threatening conjunctivitis.

A small number of gonococcal strains can invade the blood stream and cause bacteraemia and disseminated disease with a macular rash that can include necrotic pustules, as well as a septic arthritis. 4,9

Diagnosis

Diagnosis of gonorrhoea is via NAAT testing and culture on specimens collected at relevant sites (ano-rectal, throat, eye, urethral and first-pass urine) based on sexual practices.

As per the STIGMA guidelines, MSM are encouraged to do a first-pass urine, throat and ano-rectal swabs up to four times per year. This is because infections of the throat and ano-rectal sites are usually asymptomatic. Hence regular screening may be the only way to detect infections. Heterosexual males may only require a first-pass urine if asymptomatic. 9

In MSM exhibiting anorectal symptoms suggestive of proctitis, additional swabs for Lymphogranuloma venereum, herpes simplex virus, and chlamydia should be taken.9 Blood tests to detect other STIs, such as HIV, syphilis and Hepatitis B, should also be obtained.

In women, a self-collected vaginal NAAT swab or a first-pass urine can be collected.  If there is discharge or dysuria present, then an endocervical swab should be taken. In women, a pharyngeal swab is obtained if there is a history of sex work.  If the female patient had anal sex or ano-rectal symptoms then an ano-rectal NAAT and culture swab are collected.9

It is important to always take a culture swab at the relevant site if there are symptoms or urethral discharge to determine antibiotic sensitivities and resistance. After a positive NAAT swab or first-pass urine, culture samples should also be taken from the sites to determine antibiotic susceptibility prior to starting therapy. This will also contribute to antimicrobial resistance surveillance.

Populations that should be screened 2,9

Men who have sex with men should be screened up to four times per year

Travellers returning from high prevalence areas overseas (eg. India, South East Asia)

All sexually-active Aboriginal and Torres Strait Islander patients

Sex workers

Overseas people, particularly from South-East Asia 

Management

Previously used treatment for gonorrhoea such as penicillin, quinolones and tetracycline are now largely ineffective in Australia due to resistance.

The current recommended treatment for genital, anogenital and conjunctival infection is: Ceftriaxone 500mg IM in 2ml of 1% lignocaine into a large muscle such as a gluteal muscle and Azithromycin 1g oral stat.9

Recently changed Australian guidelines recommend pharyngeal gonorrhoea is treated with Ceftriaxone 500mg IM in 2ml of 1% lignocaine and Azithromycin 2g oral stat. 9

In some remote Australian locations there are alternative treatments recommended due to low levels of resistance to penicillin.

Patients can be reviewed after one week to follow-up on contact tracing and to provide further sexual health education and prevention counselling. Sexual partners should be contact-traced back for a period of two months to be given treatment.10 There are helpful websites to assist with contact tracing. The Let Them Know and Drama Down Under websites are useful for anonymous notification.

Further advice from the local sexual health service should be sought if there are allergies to the empirical treatment, rectal co-infection, or the patient is from a regional or remote location.

A test of cure should be done two weeks after treatment is completed.

SYPHILIS

Syphilis is caused by the spirochaete bacterium Treponema palladium and is transmitted by sexual contact or by vertical transmission. During sexual transmission, lesions, which contain active treponemes, penetrate the moist mucosal or cutaneous surfaces of the sexual partner via microscopic abrasions, leading to establishment of infection.4

Untreated syphilis can have detrimental consequences. Syphilis enhances the transmission of HIV by two-to-five fold when it causes genital ulcer disease. It also increases the viral load of the HIV-positive individual, which in turn promotes the spread of HIV.

In pregnancy, maternal syphilis can lead to preterm labour, stillbirth and congenital abnormalities of the child. Furthermore, untreated syphilis in the individual can progress to tertiary syphilis and can cause cardiovascular and neurological complications.4

Incidence

From 2013 to 2017, the notification rate of infectious syphilis increased by 135% from 7.8 per 100 000 in 2013 to 18.3 per 100 000 in 2017.

Of the 4398 infectious syphilis notifications in 2017, 18% were among the Aboriginal and Torres Strait Islander population, 37% were in people aged 15-29 years of age and 73% were in people residing in major cities.  The rate of notification of infectious syphilis in the Aboriginal and Torres Strait Islander population in 2017 was 6.6 times higher than the non-Indigenous population. The notification rate has increased five-fold from 19.5 per 100 00 in 2013 to 102.5 per 100 0000 in 2017, compared with only a doubling in the non-indigenous population.1

Currently there is an outbreak of infectious syphilis affecting indigenous Australians living in remote and rural areas of northern and central Australia. The outbreak began in northern Queensland in January 2011 and has extended to Queensland, Western Australia, Northern Territory and South Australia. Two-thirds of cases are in indigenous Australians aged between 15 and 29, and, since 2011, there have been 15 congenital cases and seven deaths.12

Populations that should be screened 4,13

Aboriginal and Torres Strait Islanders under 35 years of age, especially in outer regional and remote areas

MSM at least annually or up to four times per year

HIV-positive MSM up to four times per year or at least on each occasion of CD4/viral load monitoring

Pregnant women or those planning a pregnancy

repeat antenatal testing at 24-28 weeks for all pregnant indigenous women in the context of the current outbreak or if at risk of infection/reinfection

Sex workers

As part of a routine immigration screen

Symptoms

The natural history of syphilis is divided into three stages: primary, secondary and tertiary syphilis, however, about 50% of people will have no symptoms and are only diagnosed via serological testing.14

Primary syphilis

Primary syphilis starts with a chancre that is typically a non-tender ulcer with a well-defined margins and an indurated base located at the site of inoculation. The chancre can be located on the genitals, perianally or orally. Regional lymph nodes are usually enlarged.14

The average incubation period is 30 days but can range from nine to 90 days. If untreated, a chancre will spontaneously resolve within a few weeks.15

Secondary syphilis

Secondary syphilis is when the bacterium spreads throughout the body to produce systemic symptoms and may present with fever, malaise, headache and lymphadenopathy.4

There may be a generalised rash involving the trunk but it can also just affect the palms of the hands and soles of the feet. Other secondary symptoms include alopecia, condylomata lata, neurological signs of cranial nerve palsy, ophthalmic signs and meningitis.14

The average incubation period is six weeks but it can be anywhere from 30 to 150 days.15

The symptoms usually resolve over several weeks, however about 25% of untreated people continue to have relapses of secondary syphilis over the first two years after infection.4

A person without clinical signs or symptoms of syphilis, but having positive syphilis serology and no history of having been treated, has latent syphilis.

Early latent syphilis

Early latent syphilis indicates recent infection of less than two years duration. There will be positive syphilis serology from the last two years but no clinical symptoms or signs. The patient is considered potentially infectious.4

Non-infectious syphilis

If it’s not known how long an individual has had syphilis infection, then the patient is treated as late-latent syphilis. After 24 months, the individual is no longer infectious to sexual partners, but a pregnant woman can transmit vertically to her unborn fetus.4,15

Tertiary syphilis

Tertiary syphilis may develop in later years in untreated individuals. About 30% of cases can develop skin lesions called gummas, cardiovascular (aortic dilatation and aortic valve regurgitation) or neurological disease (including hearing, vision loss and dementia). The incubation period for developing tertiary syphilis can be from five to 35 years. Syphilis should be suspected when a patient presents with: 4

a painless ulcer in the genital, anal or oral areas

a persistent or unexplained rash anywhere on the body but particularly affecting the palms of hands or soles of the feet

genital rashes or symptoms in MSM

pyrexia of unknown origin

unexplained persistent lymphadenopathy

unexplained abnormal liver function tests

alopecia

Diagnosis

The diagnosis of syphilis is based on serology, history and clinical assessment. If there is a suspected chancre, then the base of ulcer should be swabbed with a PCR/NAAT swab.

It may also be necessary to do a viral swab for herpes if any genital ulcer is present. 

Serology for syphilis as well as for HIV and hepatitis B testing should be collected. The NAAT test may be positive prior to a blood test being positive in early syphilis.

Serology is screened with an immunoassay (although some laboratories still screen with TPPA and TPHA) and if reactive, then RPR (or VDRL) and TPHA (or TPAA) will be performed as confirmatory testing.

Patients who have had prior treated syphilis will continue to have the immunoassay and TPPA tests positive for life.  A rise in the RPR titre is required to detect reinfection.

If there is strong clinical suspicion of syphilis but the serology is negative, then repeat testing after two weeks and then again in 12 weeks to account for the incubation period.14 If there is uncertainty regarding serology interpretation, then specialist advice should be sought from the local sexual health service.

Treatment

In several developed countries, there are macrolide-resistant strains of treponema pallidum, however there are no reported cases of resistance to first-line therapy of penicillin for syphilis in Australia. 11,19

The recommended treatment for infectious syphilis (primary, secondary, early-latent syphilis) is benzathine penicillin 1.8g IM stat that comes as two 900mg IM injections. 

For non-infectious syphilis (late-latent syphilis), treatment is benzathine penicillin 1.8g IM weekly for three weeks.14

On day one of treatment, an RPR titre blood test should be taken to ensure there is an accurate baseline.

Follow-up testing involves repeating the RPR titres at three, six and 12 months.

If there is a rise in the RPR titre, this can indicate re-infection or inadequate treatment.

There should be a four-fold decrease in RPR titre which indicates adequate response to treatment. Furthermore HIV and STI testing should be considered at the three-month follow-up appointment and sexual health education and prevention counselling should be provided.

It is important to discuss treatment reactions which include the Jarisch-Herxheimer reaction that occurs six to 12 hours following treatment with penicillin and presents as fever, headache, malaise, rigors, and joint pain. It is managed by simple analgesia and rest. 14

Further advice from the local sexual health service should be sought for those who are pregnant, allergic to penicillin, HIV-positive or who have neurological, ophthalmic or suspected tertiary disease.

Contact tracing

All sexual contacts of patients with primary or secondary syphilis should be presumptively treated regardless of serology. 

Contacts of early-latent syphilis can be treated presumptively, but if the contact was greater than three months previously, then treatment can be given according to serology result. 15 The following provides a time-frame for how far to trace back for contact tracing and treatment: 15

Primary syphilis – three months plus duration of symptoms

Secondary syphilis – six months plus duration of symptoms

Early Latent syphilis – 12 months

Late latent syphilis – long-term partners only

A useful resource for young Indigenous Australians includes the “Young deadly and free” website offering resources for young people and health professionals about STIs.

CONCLUSION

With knowledge about the populations at greatest risk, disease symptoms and management, GPs have an important role in diagnosing and treating gonorrhoea and syphilis.

Antimicrobial resistance in STIs is a growing concern, and with increased awareness, reliable information and antimicrobial resistance surveillance, we can work together in preventing further cases.

Further assistance and support is always available for clinicians and patients from the local sexual health service to discuss any concerns.

Dr Wee-Sian Woon is a GP based in Sydney. He has worked at the Royal Prince Alfred Sexual Health Clinic in Sydney as a sexual health registrar and is currently working in two inner Sydney GP clinics which have a large caseload of HIV positive patients and patients presenting for STI-related issues. 

References:

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Sheppeard, V.  Gonorrhea – antimicrobial resistance. Information for NSW clinicians [Internet]. Sydney: NSW health; April 2018 [cited 2019 30 March]. Available from:  https://www.health.nsw.gov.au/Infectious/alerts/Documents/2018/gono-amr-clinician-april2018.pdf

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Ngan, V. Dermnet – Gonorrhoea. [Internet]. Czech Republic: Derment [2018; cited 2019 May 5]. Available from:

https://www.dermnetnz.org/topics/gonorrhoea/

Australasian Society of HIV Medicine .Australian STI management Guidelines For use in Primary Care  – Gonorrhoea [Internet]. Australasian Society of HIV Medicine. [updated 2018 December 11; cited 2019 April 11].  Available from: http://www.sti.guidelines.org.au/sexually-transmissible-infections/gonorrhoea

Australasian Society of HIV Medicine. Australasian Contact Tracing Guidelines – Gonorrhoea [Internet]. Australasian Society of HIV Medicine; 2016. [cited 2019 April 30]. Available from: http://contacttracing.ashm.org.au/conditions/when-contact-tracing-is-recommended/gonorrhoea

Stamm LV. Global challenge of antibiotic-resistant Treponema pallidum. Antimicrob Agents Chemother. 2010;54(2):583–589

Australian Government Department of Health. Multijurisdicational Syphilis Outbreak Surveillance Report: March 2019 [Internet]. Commonwealth government.;March 2019 [cited 2019 April 10]. 2p. Report No.: 12. Available from: https://www.health.gov.au/internet/main/publishing.nsf/Content/71E8A32E7518E532CA25801A0009A217/$File/12th-Surveil-Report-Mar2019.pdf

Sheppeard, V.  Infectious syphilis alert, Information for Aboriginal Medical Services, Sexual health clinicians, general practitioners and antenatal services [Internet]. Sydney: NSW Ministry of health; 23 January 2019 [cited 2019 29 March]. Available from: https://www.health.nsw.gov.au/Infectious/alerts/Documents/infectious-syphilis-alert-23Jan2019.pdf

Australasian Society of HIV Medicine. Australian STI management Guidelines for use in Primary Care – Syphilis [Internet]. Australasian Society of HIV Medicine. [updated 2018 March 29;  cited 2019 April 11]. Available from: http://www.sti.guidelines.org.au/sexually-transmissible-infections/syphilis

Australasian Society of HIV Medicine. Australasian Contact Tracing Guidelines – Syphilis [Internet].  Australasian Society of HIV Medicine; 2016  [cited 2019 April 30]. Available from: http://contacttracing.ashm.org.au/conditions-where-contact-tracing-is-recommended/syphilis

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