Gonorrhoea

What is gonorrhoea?

Neisseria gonorrhoeae is a Gram-negative diplococcus infecting mucous membranes of the urethra, endocervix, rectum, pharynx, conjunctiva and, occasionally, joints.¹ Transmission occurs by the direct inoculation of infected secretions from one mucous membrane to another, usually sexually and, less commonly, perinatally. The incubation period is usually taken as being between two and five days but may be up to 10 days.

Virulence varies, as does the tendency to develop disseminated disease. The latter is conferred by the antigenic variation between subtypes. One study found that co-infection with chlamydia in women is associated with higher gonococcal organism loads, potentially increasing chances of transmission.²

Resistance to antibiotics also varies and can be spread rapidly by plasmid transfer of antibiotic resistance genes. Mortality associated with disseminated gonorrhoea is rare but morbidity, primarily associated with pelvic inflammatory disease (PID), is one of the most common sequelae worldwide.

How common is gonorrhoea? (Epidemiology)³

In 2023, there were 401,800 diagnoses of STIs made in England, a 4.7% increase since 2022. The most commonly diagnosed STIs were chlamydia (194,970, 48.5 % of all new STI diagnoses), gonorrhoea (85,223, 21.2 %), first episode genital herpes (27,167, 6.8 %), and first episode genital warts (26,133, 6.5 %). Gonorrhoea cases have increased significantly and the number of cases in 2023 was the highest since records began in the UK in 1918. This is a continuation of the increasing trend seen in recent years: since 2015, gonorrhoea diagnoses have risen by 105% (from 41,382 to 85,223).

The number of cases of STIs reported fell during 2020 and 2021, partly because of the disruption to sexual screening services, and possibly also due to a reduction in actual disease due to fewer sexual encounters. However, gonorrhoea cases fell by a smaller amount than other STIs and the increase in diagnoses of gonorrhoea since 2021 has been higher than other STIs.

About half of gonorrhoea diagnoses in the UK were reported in men who have sex with men but diagnoses are also high in young women and men between the ages of 16 and 24. The majority of cases are diagnosed in people who report only one recent sexual partner.

The rise in cases is thought to be due to an increase in the number of sexual health screens taking place but also high levels of transmission in the community.

In 2023, 97% of councils reported increasing rates of gonorrhoea being diagnosed. Whilst London continues to have the highest rates, with deprivation being a significant risk factor, councils in Dorset, Devon, Cornwall, Wigan and Torbay reported tripling of the previous diagnoses of gonorrhoea.⁴The closure of many local sexual health clinics in the last few years makes the situation even more difficult.

Globally, gonorrhoea infection prevalence has been estimated to be 0.9% in women and 0.7% in men. The prevalence is highest in Africa, North and South America and the Western Pacific and lowest in Europe. Likely due to the reduced availability of screening and treatment, lower income countries tend to have higher rates of infection than higher income countries.⁵

A significant proportion of new cases of gonorrhoea are reported in men who have travelled, particularly to Thailand and the Philippines, but also to Europe (particularly Spain and Germany), and have had sex with a new partner abroad. A third of these are MSM.⁵

Risk factors ⁶

• Young age.

• History of previous STI.

• Co-existent STIs - 44% of MSM with gonorrhoea had co-existing HIV infection.³

• New or multiple sexual partners.

• Recent sexual activity abroad.

• Men who have sex with men.

• Inconsistent or lack of condom use.

• History of drug use or commercial sex work.

Symptoms of gonorrhoea (presentation)

Gonorrhoea is thought to be symptomatic in most men (90-95%) but asymptomatic in half of women.

Symptoms in men ¹⁶

• Urethral infection - yellow purulent discharge and/or dysuria

• Rectal infection - constipation, painful defecation, purulent discharge.

• Pharyngeal infection - pharyngitis, occasionally purulent discharge.

• Prostatitis.

• Epididymitis.

Symptoms in women

• Endocervical infection - frequently asymptomatic but greenish-yellow vaginal discharge is the most common symptom.

• Intermenstrual bleeding or menorrhagia.⁷

• Lower abdominal pain.

• Urethral infection - dysuria.

• Rectal infection.

• Pharyngeal infection.

• Acute cervicitis.

• Pelvic inflammatory disease. In a study involving nearly 4,000 women attending a sexual health clinic in the UK, PID was reported in approximately 14% of those with gonorrhoea.⁸

Symptoms in children

• Acute conjunctivitis in association with purulent discharge, usually bilateral, <48 hours of birth, often accompanied by chemosis and lid oedema.

• Vaginal discharge and vulval erythema (prepubertal vulvovaginal epithelium is more susceptible to infection compared with that of adult women).

Widespread infection

Disseminated infection is rare, as most gonococci strains have limited ability to proliferate in the blood. However, some strains can spread and haematogenous dissemination may occur from infected mucous membranes to cause skin lesions, arthralgia, arthritis and tenosynovitis (disseminated gonococcal infection).¹

Differential diagnosis

• Other causes of penile or vaginal discharge - eg, chlamydia.

• Other causes of pelvic pain - eg, endometriosis, appendicitis.

• Other causes of pharyngitis, arthritis.

Diagnosing gonorrhoea (investigations)⁷

Follow local protocols

The diagnosis of gonorrhoea is established by the detection of N. gonorrhoeae at an infected site, either by nucleic acid amplification tests (NAATs) or by culture. The approach and method used to test for gonorrhoea will be influenced by the clinical setting, storage and transport system to the laboratory, local prevalence of infection and the range of tests available in the laboratory. No test for gonorrhoea offers 100% sensitivity and specificity.

Microscopy

• Penile urethra: microscopy of urethral or meatal swab smears has good sensitivity (90-95%) in people with discharge from the penile urethra and is recommended to facilitate immediate presumptive diagnosis in these individuals. Microscopy of penile urethral smears in those without symptoms is less sensitive (50-75%); therefore, it is not recommended in asymptomatic individuals.

• Female urethra and endocervix: microscopy has only 37-50% and 20% sensitivity compared with culture for detecting gonorrhoea from endocervical and female urethral smears. The sensitivity of cervical microscopy compared to NAATs in a more recent study was only 16% and is therefore not routinely recommended.

• Rectum and pharynx: ano-rectal smears and microscopy should be offered if rectal symptoms are present. The sensitivity of microscopy for detecting asymptomatic rectal infection is low and is not routinely recommended.

Nucleic acid amplification tests (NAATs)

NAATs are more sensitive than culture, particularly for oropharyngeal and rectal sites. NAATs show high sensitivity (>95%) in both symptomatic and asymptomatic infection. Therefore, although NAATs are not licensed for use at extra-genital sites, their use is recommended.

• Penile urethra: NAATs show equivalent sensitivity in urine and urethral swab specimens from men, although a first-pass urine specimen is the preferred sample.

• Female urethra and endocervix: self-collected or clinician-collected vulvovaginal swabs (VVS) perform better than endocervical swabs and significantly better than urine for women. VVS are therefore the recommended specimen. For people who have had a hysterectomy, there is no evidence on optimal sampling site. Urine and VVS for NAAT is recommended, with subsequent culture from that site if positive.

• Rectum and pharynx: rectal and pharyngeal sampling should be routine in all MSM (as recommended by the BASHH guideline on the sexual healthcare of MSM), be considered in women who are sexual contacts of gonorrhoea and be guided by an assessment of risk and symptoms in everyone else.

The primary role of culture is for antimicrobial susceptibility testing, which is of increasing importance as antimicrobial resistance in N. gonorrhoeae continues to evolve and spread.

Approximately 19% of patients with gonorrhoea have concurrent chlamydial infection. Therefore, testing for other STIs should be carried out in line with guidelines.⁹

NB: Where a patient has had sexual contact with an individual with confirmed gonorrhoea within the previous three days, a further interval set of tests (usually two weeks later) should be considered if empirical treatment with antimicrobial therapy is not undertaken.

Management of gonorrhoea⁷

General management

• Opportunistic screening for STIs is something that is often provided by GP surgeries, often because the patient has presented with vague symptoms or requests a test during an appointment for something else. This provides a useful service, although limited by time and resources.

• However, patients with positive STI tests must be advised to attend the GUM clinic so that a sample can be taken for culture and sensitivities obtained before treatment, as well as for contact tracing, follow up and further advice.

• Where a patient has tested positive for gonorrhoea, or where an individual has suggestive symptoms/is at high risk, referral to a GUM clinic or service offering an enhanced sexual health service is essential, particularly as the recommended treatment is an IM injection of ceftriaxone.

• Emergency medical admission may be required if there is evidence of disseminated gonorrhoea or severe PID.

• The GUM clinic will allow time to provide a detailed explanation of the condition and its long-term implications for the patient and their partner's/partners' health, reinforced with written information. Advise on safer sexual practices for the future.

• Advise patients to avoid unprotected sexual intercourse until seven days after both they and their partner(s) have completed treatment.

• Advise routine screening for other STIs in all patients with or at risk of gonorrhoea. Co-infection with other STIs, particularly chlamydia, is common.

• Partner notification should be performed by a trained health adviser. For male patients with symptomatic urethral infection, all partners with whom they have had sexual contact in the previous two weeks or their last partner (if longer than two weeks). With asymptomatic infection or infection at other sites, sexual partners of the preceding three months should be notified. These partners should receive a full STI screen and receive empirical treatment for gonorrhoea and chlamydia in advance of results.

• Patients should be followed up by the GUM clinic to check compliance with treatment, to make sure symptoms have resolved, to explore the risk of re-infection and to further partner notification and health promotion.

Medication

• Ceftriaxone 1 g intramuscularly as a single dose is given when sensitivity to antimicrobials is unknown.

• Ciprofloxacin 500 mg orally as a single dose when sensitivities are known. Gonorrhoea is a serious infection and the potential benefit of using ciprofloxacin in people with susceptible infection will outweigh the potential risks. However, it should not be used first line without sensitivities being known as resistance is high in the UK (>36%).

A test of cure (with culture >72 hours or with NAAT >2 weeks following antibiotic treatment) is recommended in all cases.

Alternative treatments may be given because of allergy, needle phobia or other absolute or relative contra-indications. In patients with penicillin allergy there is ample evidence to allow the safe use of all but a few early generation cephalosporins (eg, cefalexin, cefaclor and cefadroxil), and third-generation cephalosporins such as cefixime and ceftriaxone have been shown to have low cross-allergy with penicillin's.

Alternatives include:

• Cefixime 400 mg orally as a single dose plus azithromycin 2 g orally. Only advisable if an intramuscular injection is contra-indicated or refused by the patient. Resistance to cefixime is currently low in the UK.

• Gentamicin 240 mg intramuscularly as a single dose plus azithromycin 2 g orally. RCTs have examined the efficacy and safety of gentamicin for the treatment of gonorrhoea, prescribing gentamicin in combination with 1 g of azithromycin.¹⁰ Microbiological cure (negative NAAT two weeks after treatment) was achieved in 91% of urogenital infections. Another randomised trial used a 2 g dose of azithromycin in combination with gentamicin.¹¹ This found 100% clearance of infection; however, few extragenital infections were included and culture was used to confirm clearance (i.e. it is likely to overestimate the effectiveness).

• Azithromycin 2g as a single dose but azithromycin is less effective in vivo than in in vitro studies and azithromycin resistance is high in the UK.

Pregnancy and breastfeeding

• Ceftriaxone 1 g intramuscularly as a single dose.

• Azithromycin 2 g as a single oral dose. However, the manufacturer of azithromycin advises use only if adequate alternatives are not available.

Pharyngeal infection

• Ceftriaxone 500 mg intramuscularly with azithromycin 1 g orally as a single dose.

• Oral cefixime (400 mg loading dose, followed by 200 mg twice a day for three days) plus azithromycin 1 g orally as a single dose can be used where intramuscular injections are contra-indicated or refused (off-label use).

• Ciprofloxacin 500 mg orally or ofloxacin 400 mg orally (if N. gonorrhoeae known to be quinolone-sensitive) is an option for patients in whom cephalosporins are contra-indicated.

Pelvic inflammatory disease⁹
Ceftriaxone 1 g intramuscularly as a single dose, in addition to the regimen chosen to treat PID (see the BASHH PID guideline).

Gonococcal epididymo-orchitis

Ceftriaxone 1 g intramuscularly as a single dose, in addition to the regimen chosen to treat the epididymo-orchitis.

Gonococcal conjunctivitis

Systemic treatment is recommended as the cornea may be involved and the eye is relatively avascular:

• Wash the eye with saline/water.

• Ceftriaxone 1 g intramuscularly as a single dose

• There is a lack of evidence to guide treatment options if there is a history of penicillin anaphylaxis or established cephalosporin allergy. Treatment should be based on antimicrobial susceptibility results where available.

Children

Ophthalmia neonatorum (neonatal conjunctivitis)¹²

• During the first year of life, gonorrhoea can cause ophthalmia neonatorum, pharyngitis, rectal infections and pneumonia. Signs develop within two to five days following birth, because exposure to infection tends to have occurred during delivery.

• Babies with true conjunctivitis (ie signs of conjunctival inflammation as opposed to a simple 'sticky eye') should be referred by GPs for same-day hospital assessment.

• Gram-stain conjunctival exudates followed by culture are the investigations of choice. Treatment should be prompt to prevent corneal ulceration and permanent visual loss - usually parenteral benzylpenicillin or cephalosporin, in combination with saline lavage and topical antibiotic (eg, erythromycin, azithromycin).

• Both parents should be screened.

Co-infection with chlamydia¹³

Treatment for confirmed or suspected chlamydial co-infection should follow the current guideline for the management of chlamydia. If an individual has already received azithromycin 2 g for the treatment of gonorrhoea then this should be sufficient to treat chlamydia and no further doses of azithromycin are required.

Disseminated gonococcal infection

• Ceftriaxone 1 g intramuscularly or intravenously every 24 hours; or

• Cefotaxime 1 g intravenously every eight hours; or

• Ciprofloxacin 500 mg intravenously every 12 hours (if the infection is known to be susceptible); or

• Spectinomycin 2 g intramuscularly every 12 hours.

Therapy should continue for seven days but may be switched 24-48 hours after symptoms improve to one of the following oral regimens guided by sensitivities:

• Cefixime 400 mg twice daily; or

• Ciprofloxacin 500 mg twice daily; or

• Ofloxacin 400 mg twice daily.

Sexual abuse

• Consider the possibility of sexual abuse or grooming in those underage or vulnerable. Follow local child protection guidance and seek expert advice.

• After the neonatal period, it is thought that genital and pharyngeal gonorrhoea are almost always due to sexual abuse by an infected adult. However, there are cases, particularly of conjunctivitis, that appear to have been acquired non-sexually. All cases of gonorrhoea post-infancy must be investigated thoroughly.

Complications of gonorrhoea⁶

Complications in men

• Gonococcal urethritis may cause urethral scarring and stricture, resulting in bladder-outflow obstruction.

• Local spread causing acute epididymitis, prostatitis, seminal vesiculitis, penile lymphangitis, peri-urethral abscess and infection of Tyson's and Cowper's glands.

Complications in women

The main concerns of PID are infertility and peri-hepatitis caused by ascending infection.

• Bartholin's abscess (usually multiple pathogens).

• PID - thought to occur in 10-20%, causing infertility, chronic pelvic pain and ectopic pregnancy.

• Peri-hepatitis (Fitz-Hugh Curtis syndrome).

• In pregnancy it may be associated with premature labour and miscarriage.

• Corneal scarring and severe sight impairment from neonatal ophthalmic infection.

General complications

• Haematogenous dissemination (uncommon - <1%) causing:

  • Skin lesions (papules, bullae, petechiae and necrotic skin lesions).

  • Arthralgia, arthritis and tenosynovitis of the ankles, wrists, hands and feet (reactive arthritis).

  • Meningitis, endocarditis or myocarditis, with risk of death or permanent sequelae (extremely rare).

• Increased risk of acquiring and transmitting HIV infection.

Prognosis

Where treatment is rapidly received for a recently acquired gonorrhoeal infection, prognosis is good with full recovery as normal. Continuing symptoms are more likely to be due to re-infection than persistence of the original infection. However, the emergence of a new multidrug-resistant strain is causing increasing global public health concern.

The risk of infertility increases with repeated episodes.

Prevention of gonorrhoea

• Promotion of safer sex methods.

• Consistent use of condoms significantly reduces the risk of acquiring gonorrhoea and other STIs.¹

• Testing for those sexually active and at risk of acquiring gonorrhoea - in the UK there is no current evidence base to support widespread unselected screening for gonorrhoea and only very limited evidence for selective community screening. Localised interventions targeted on high-risk groups (inner-city residents, GUM attendees, military personnel, prisoners and MSM) are more likely to be cost-effective and beneficial than unselected screening.

• Quicker partner referral and treatment can substantially reduce re-infection rates. Novel partner notification technologies like accelerated partner therapy may be helpful but need further evaluation.

• In 2023, the Joint Committee on Vaccination and Immunisation (JCVI) advised that the 4CMenB vaccine should be used for the prevention of gonorrhoea. The MenB vaccine is currently used in the routine childhood programme for the prevention of meningococcal disease (meningitis and septicaemia); meningococcal disease (Neisseria meningitidis) and gonorrhoea (Neisseria gonorrhoeae) are closely genetically related, with evidence showing that MenB vaccine provides some cross-protection against gonorrhoea. The JCVI noted that, even with the modest vaccine documented effectiveness against gonorrhoea (between 32.7% to 42%) many cases of gonorrhoea could be prevented, particularly given that the disease itself doesn’t protect from future infection and affected individuals are commonly reinfected. The government is considering these recommendations.¹⁴

National guidelines recommend that:¹³

• Male patients with symptomatic urethral infection should notify all sexual partners from the preceding two weeks or their last partner if longer than two weeks.

• People with infection at other sites or asymptomatic infection should contact all partners within the preceding three months.

• Partners should be offered testing and treatment.