Gonorrhoea represented 7% of newly diagnosed sexually transmitted infections (STIs) in genitourinary medicine (GUM) clinics in 2013, on a par with genital herpes and genital warts. The vast majority (47%) of infections were due to chlamydia.Neisseria gonorrhoeae is a Gram-negative diplococcus infecting mucous membranes of the urethra, endocervix, rectum, pharynx and conjunctiva.
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 2 and 5 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.
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, is a common sequela worldwide.
In 2013, the total number of new cases of gonorrhoea diagnosed in GUM clinics in England was 29,291. This represented an increase of 15% compared to those diagnosed in 2012. The prevalence of gonorrhoea has increased gradually over a period of ten years, principally in men. There was a disproportionate increase in men who have sex with men (MSM). In 2013, 63% of gonorrhoea diagnoses occurred in MSM, a 26% increase on the previous year. This was thought to be due to a rise in men coming forward for testing as well as an increase in sexually unsafe activity. The use of new diagnostic techniques - rectal and pharyngeal testing using nucleic acid amplification testing (NAAT) - has also improved detection rates. The highest rates of gonorrhoea are amongst the young. In 2013 among heterosexuals diagnosed with gonorrhoea, 56% (8,122/14,647) occurred in those aged 15-24 years.
Urban areas reported higher prevalence rates than rural areas, London having the highest rates. Deprivation and black ethnicity are associated factors.
Uncomplicated gonorrhoea (affecting the lower genital tract) is a reasonably common infection but complicated disease (affecting the upper genital tract) is rarer: in 2008, only 348 cases of complicated gonorrhoeal infection were seen in GUM clinics, compared with over ten times more of complicated chlamydial infections.
Most cases of gonorrhoea are diagnosed by GUM clinics. In 2000, only 5.7% of female cases and 2.9% of male cases were diagnosed in primary care.However, there is increasing emphasis placed on the provision of sexual health services within this sector.
- Young age.
- History of previous STI.
- Co-existent STIs - 40% of MSM with gonorrhoea had co-existing HIV infection.Co-infection with chlamydia was seen in 35% of heterosexual men and 41% of women.
- New or multiple sexual partners.
- Recent sexual activity abroad.
- Certain sexual activities eg anal intercourse, frequent insertive oral sex.
- Inconsistent condom use.
- History of drug use or commercial sex work.
Gonorrhoea is believed to be symptomatic in most men (90-95%) and asymptomatic in half of women.
- Urethral infection - discharge (>80%) and/or dysuria (>50%), asymptomatic (<10%).
- Rectal infection - usually asymptomatic; may cause anal discharge (12%) or perianal/anal pain, pruritus or bleeding (7%).
- Pharyngeal infection - usually asymptomatic (>90%).
- Endocervical infection - frequently asymptomatic (up to 50%); increased or altered vaginal discharge is the most common symptom (up to 50%), although lower abdominal pain may also be present (up to 25%); a rare cause of intermenstrual bleeding or menorrhagia.
- Urethral infection - cause of dysuria (10-15%) without frequency.
- Rectal infection (in women, may develop by spread of infected genital secretions or anal intercourse) - usually asymptomatic.
- Pharyngeal infection - usually asymptomatic (>90%).
- Mucopurulent or purulent urethral discharge.
- Epididymal tenderness/swelling or balanitis (rare).[2, 11]
- Mucopurulent endocervical discharge (not a sensitive predictor of infection).
- Easily induced contact bleeding of the endocervix.
- Pelvic/lower abdominal tenderness (uncommon, 5%).
- Normal examination (very common).
- 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).
- Other causes of penile or vaginal discharge - eg, chlamydia.
- Other causes of pelvic pain - eg, endometriosis, appendicitis.
- Other causes of pharyngitis, arthritis.
Follow local protocols
- Traditionally, culture has been the first-line diagnostic test, confirming diagnosis and allowing for antimicrobial sensitivity testing. It remains necessary in patients with signs and symptoms consistent with gonorrhoea or a positive NAAT result, to ensure resistant strains can be identified. Rapid diagnosis can be undertaken where facilities exist - use light microscopy of Gram-stained genital specimens to look for Gram-negative diplococci.
- Increasingly, NAAT is being used in the diagnosis of gonorrhoea. These can be taken from a range of genital samples - invasive (eg, urethral, endocervical) and non-invasive (eg, first pass urine) - so are frequently more acceptable. However, urine testing in women is inferior to endocervical or vulvovaginal swab-based methods. NAAT is superior to culture for extragenital sites such as the rectum or pharynx. Supplementary NAAT is required to prevent false positive results.
- Ideally, patients should be asked to attend a GUM clinic or other local sexual health clinic. If this is not possible, testing should be considered in primary care. Specimens should be sent to the laboratory as soon as possible.
- It should be noted that the concentration of organisms can be site-dependent. In MSM, far higher concentrations were seen in rectal specimens than in pharyngeal samples, particularly where proctitis was a feature.
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.
- 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 strongly encouraged.
- Emergency medical admission may be required if there is evidence of disseminated gonorrhoea or severe pelvic inflammatory disease.
- 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 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 preferably 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 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.
- Recommended treatment for confirmed, uncomplicated gonococcal anogenital infection in adults is ceftriaxone 500 mg IM stat plus azithromycin 1 g orally stat.
- National guidance is informed by the Gonococcal Resistance to Antimicrobials Programme (GRASP) which monitors emerging patterns of resistance in the UK.
- Combinations of existing antimicrobials and the development of novel antimicrobials are being explored.
- Treatment failures to cephalosporins should be reported to Public Health England.
A test of cure (with culture >72 hours or with NAAT >2 weeks following antibiotic treatment) is recommended in all cases.
Resistance to antimicrobial therapy is an ongoing issue with widespread resistance to penicillins, tetracyclines and ciprofloxacin in in the UK and worldwide.[19, 20] Resistance to third-generation cephalosporins is emerging in England and Wales. Whilst most resistant infections are acquired at home, sex abroad carries a higher risk of acquiring a resistant strain. Use local guidelines which should take account of local patterns of antimicrobial sensitivity to N. gonorrhoeae.
Genome sequencing combined with epidemiological metadata may help to inform strategies to tackle this issue.
Alternative treatments which can be prescribed in primary care for suspected or confirmed cases include:
- Cefixime 400 mg single oral dose - this is only indicated if IM treatment is contra-indicated or refused by the patient.
- Cefotaxime 500 mg IM as a single dose or cefoxitin 2 g IM as a single dose plus probenecid 1 g orally are suitable single-dose options.
- Quinolones are no longer recommended as first-line treatment but may be considered in patients whose infection has previously responded to them. In such cases, ciprofloxacin 500 mg orally as a single dose or ofloxacin 400 mg orally as a single dose is generally used in combination with azithromycin 1g orally.
- High-dose azithromycin (2 g as a single dose) is effective but has a high incidence of gastrointestinal side-effects. Resistance can also be a problem.
- This list is not exhaustive but reflects current UK practice.
Pregnancy and breast-feeding
- Ceftriaxone 500 mg IM stat with azithromycin 1g orally as a single dose.
- Cefixime 400 mg as a single oral dose plus azithromycin can be given as an alternative.
- For patients in whom cephalosporins are contra-indicated (eg, true penicillin allergy), specialist advice should be sought.
- Ceftriaxone 500 mg IM 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 IM 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 disease
Ceftriaxone 500 mg IM stat followed by oral or IV erythromycin 100 mg twice daily plus metronidazole 400 mg twice daily for 14 days (this regime may be altered depending on local sensitivities).
Ceftriaxone 500 mg IM plus doxycycline 100 mg twice daily for 10-14 days.
Systemic treatment is recommended as the cornea may be involved and the eye is relatively avascular:
- Wash the eye with saline/water.
- Ceftriaxone 500 mg IM daily for three days.
- If there is history of penicillin anaphylaxis, use azithromycin 2 g orally stat plus doxycycline 100 mg twice daily for one week plus ciprofloxacin 250 mg daily for three days.
Ophthalmia neonatorum (neonatal conjunctivitis)
- 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.
- Prophylaxis is widely used in some parts of the world (although not in the UK) and involves the topical use of silver nitrate or antibiotics. One meta-analysis found that failure rates of universal eye prophylaxis support warranted re-examination of this approach where the prevalence of maternal infection was low.
Disseminated gonococcal infection
- Ceftriaxone 1 g IM or IV every 24 hours; or
- Cefotaxime 1 g IV every 8 hours; or
- Ciprofloxacin 500 mg IV every 12 hours (if the infection is known to be sensitive).
The following oral therapy may be substituted after 24-48 hours:
- Cefixime 400 mg twice daily; or
- Ciprofloxacin 500 mg twice daily; or
- Ofloxacin 400 mg twice daily.
Therapy should continue for a total of seven days.
A history of sensitivity to cephalosporins or severe hypersensitivity to a penicillin or other beta-lactam drug may present a problem. In such cases the following may be used:
- Azithromycin 2 g orally as a single dose.
- Ciprofloxacin 500 mg orally as a single dose when the infection is known to be quinolone-sensitive.
- Consider the possibility of sexual abuse in those underage and 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.
- 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.
The main concerns of pelvic inflammatory disease are infertility and peri-hepatitis caused by ascending infection.
- Bartholin's abscess (usually multiple pathogens).
- Pelvic inflammatory disease - 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 blindness from neonatal ophthalmic infection.
- Haematogenous dissemination (uncommon - <1%) causing:
- Increased risk of acquiring and transmitting HIV infection.
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 ('superbug') is causing increasing global public health concern.
The risk of infertility increases with repeated episodes.
- Promotion of safer sex methods.
- Consistent use of condoms reduces the risk of acquiring gonorrhoea and other STIs.
- 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.
- Progress in the area of vaccine research has been slow but recent development of a murine model facilitated advances in this field.
National guidelines recommend that:
- Male patients with symptomatic urethral infection should notify all sexual partners within 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.
Further reading and references
Remmele CW, Xian Y, Albrecht M, et al; Transcriptional landscape and essential genes of Neisseria gonorrhoeae. Nucleic Acids Res. 2014 Aug 20. pii: gku762.
Walker CK, Sweet RL; Gonorrhea infection in women: prevalence, effects, screening, and management. Int J Womens Health. 20113:197-206. Epub 2011 Jul 19.
Infection reports HIV-STIs, Sexually transmitted infections and chlamydia screening in England, 2013, Volume 8 Number 24; Public Health England, June 2014
Gonorrhoea; NICE CKS, November 2011 (UK access only)
Stupiansky NW, Van Der Pol B, Williams JA, et al; The natural history of incident gonococcal infection in adolescent women. Sex Transm Dis. 2011 Aug38(8):750-4.
UK National Guideline on Gonorrhoea Testing; British Association for Sexual Health and HIV (2012)
Cassell JA, Mercer CH, Sutcliffe L, et al; Trends in sexually transmitted infections in general practice 1990-2000: population based study using data from the UK general practice research database. BMJ. 2006 Feb 11332(7537):332-4. Epub 2006 Jan 26.
Gonorrhoea; Public Health England
International Union Again Sexually Transmitted Infections; European Guideline on the Diagnosis and Treatment of Gonorrhoea in Adults, 2012.
Bignell C et al; 2012 European guideline on the diagnosis and treatment of gonorrhoea in adults, International Union against Sexually Transmitted Infections (IUSTI)
Trojian TH, Lishnak TS, Heiman D; Epididymitis and orchitis: an overview. Am Fam Physician. 2009 Apr 179(7):583-7.
Management of gonorrhoea; British Association for Sexual Health and HIV (2011)
Miller KE; Diagnosis and treatment of Neisseria gonorrhoeae infections. Am Fam Physician. 2006 May 1573(10):1779-84.
Guidance for the detection of gonorrhoea in England; Public Health England (2014)
Bissessor M, Tabrizi SN, Fairley CK, et al; Differing Neisseria gonorrhoeae bacterial loads in the pharynx and rectum in men J Clin Microbiol. 2011 Sep 28.
Ison CA, Town K, Obi C, et al; Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007-2011. Lancet Infect Dis. 2013 Sep13(9):762-8. doi: 10.1016/S1473-3099(13)70143-9. Epub 2013 Jun 11.
Unemo M, Nicholas RA; Emergence of multidrug-resistant, extensively drug-resistant and untreatable gonorrhea. Future Microbiol. 2012 Dec7(12):1401-22. doi: 10.2217/fmb.12.117.
Reporting gonorrhoea treatment failure; Public Health England, 2014
Kirkcaldy RD, Ballard RC, Dowell D; Gonococcal resistance: are cephalosporins next? Curr Infect Dis Rep. 2011 Apr13(2):196-204.
Cole MJ, Chisholm SA, Hoffmann S, et al; European surveillance of antimicrobial resistance in Neisseria gonorrhoeae. Sex Transm Infect. 2010 Nov86(6):427-32.
UK National Guideline for the Management of Pelvic Inflammatory Disease; British Association for Sexual Health and HIV (2011)
Conjunctivitis - infective; NICE CKS, August 2012 (UK access only)
Ophthalmia neonatorum; The College of Optometrists, 2013
Darling EK, McDonald H; A meta-analysis of the efficacy of ocular prophylactic agents used for the prevention of gonococcal and chlamydial ophthalmia neonatorum. J Midwifery Womens Health. 2010 Jul55(4):319-27.
Whaitiri S, Kelly P; Genital gonorrhoea in children: determining the source and mode of infection. Arch Dis Child. 2011 Mar96(3):247-51. Epub 2010 Jun 3.
Goodyear-Smith F; What is the evidence for non-sexual transmission of gonorrhoea in children after the neonatal period? A systematic review. J Forensic Leg Med. 2007 Nov14(8):489-502. Epub 2007 Jul 30.
Fowler T, Caley M, Johal R, et al; Previous history of gonococcal infection as a risk factor in patients presenting Int J STD AIDS. 2010 Apr21(4):277-8.
Low N, Heijne JC, Herzog SA, et al; Reinfection by untreated partners of people treated for Chlamydia trachomatis and Neisseria gonorrhoeae: mathematical modelling study. Sex Transm Infect. 2014 May90(3):254-6. doi: 10.1136/sextrans-2013-051279. Epub 2014 Jan 21.
Jerse AE, Bash MC, Russell MW; Vaccines against gonorrhea: current status and future challenges. Vaccine. 2014 Mar 2032(14):1579-87. doi: 10.1016/j.vaccine.2013.08.067. Epub 2013 Sep 6.
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