Gonorrhoea (overview) A54.9

Author: Prof. Dr. med. Peter Altmeyer

Co-Autors: Dr. med. Eva Kämmerer, Jeton Luzha, Hadrian Tran, Nico Weinkauf

All authors of this article

Last updated on: 18.03.2021

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Synonym(s)

Gonococcal conjunctivitis; Gonorrhea; gonorrhoea spermatocystitis; Neisser M.; Neisser's disease; posterior urethritis gonorrhoica; Rectal gonorrhea; Two-glass sample; Urethritis gonorrhoica anterior acuta; Urethritis specific

Definition
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One of the most common sexually transmitted infectious diseases worldwide. Gonorrhoea is thus an important indicator of the effectiveness of prevention measures for the human immunodeficiency virus (HIV) and for other "sexually transmitted diseases"(STD). The causative agent is Neisseria gonorrhoeae. The disease usually manifests as urethritis gonorrhoica or cervicitis.

Asymptomatic courses in men and women are possible. Complications may arise from ascending inflammation or haematogenous spread.

Pathogen
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Neisseria gonorrhoeae, gram-negative, obligate aerobic, oxidase-positive diplococci. Adhesive pili localized on the surface are responsible for specific adherence to mucosal cells. Neisseria gonorrhoeae are transmitted by direct mucosal contact with infectious secretions and cause purulent inflammation of the mucosa, especially the cylinder epithelia of the urethra, cervix, rectum and conjunctiva. Hematogenous spread is rare but possible. The disease does not leave any immunity. There is no vaccination.

Occurrence/Epidemiology
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Worldwide there are approx. 300-600 million infected persons. Incidence in the Federal Republic of Germany according to official statistics of the Robert Koch Institute: 2-5/100,000/year (high number of unreported cases!). For Saxony, the incidence in 2008 was 10.1 cases/100,000 inhabitants. With > 32,000 cases/year, gonorrhoea was the second most frequently reported sexually transmitted infection (STI) in Europe in 2010.

In 2014, almost half of those infected were homosexual men. The 2nd half affected heterosexual men and women.

Etiopathogenesis
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Transmission through sexual intercourse, rarely through smear infection.

Manifestation
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Adolescents and young adults between 15 and 24 years of age account for about 1/3 of all cases of illness, 1/3 concerns the age group between 25 and 40 years.

Localization
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Urethra, distal rectal mucosa (approx. 10 cm from ano); ano-rectal transition zone including the Morganian glandular ducts; vagina, labia.

A distinction is made between upper and lower gonorrhoea:

  • Lower gonorrhea (below the cervix; with few symptoms):
    • introitus inflammation (possibly in combination with bartholinitis)
    • Urethritis (about 90%)
    • Proctitis
    • Cervicitis (approx. 80-90%)
  • Upper g onorrhea (above the cervix; symptomatic):
    • Endometritis
    • Salpingitis
    • Pelveoperotinitis
    • Peritonitis

Clinical features
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Incubation period: 2-7 days, usually 3 days.

  • In man:
    • Infection of the pars anterior of the urethra (urethritis gonorrhoica anterior acuta et chronica). Burning on urination, redness of meatus of urethra, yellow-greenish, creamy, purulent fluorine, development of balanitis, possibly paraphimosis.
  • In women:
    • Urethritis gonorrhoica acuta with serous purulent fluor, burning and pain on urination. Possibly trigonum cystitis. Development of urethritis gonorrhoica chronica. Irritation of the mucous membranes in the region of the small and large labia: redness, swelling, impetiginization, erosions, superficial ulcerations. Clinical symptoms remain mildly symptomatic or asymptomatic in > 50% of infected women.
    • See below Cervicitis gonorrhoica;
    • see below Bartholinitis.
  • Anorectal infection (in men and women): often asymptomatic or asymptomatic. Possible symptoms are blood and mucus on the stool, purulent secretion, feeling of pressure and tenesmus, possibly pain during defecation. Itching and soreness may occur as so-called secondary phenomena in the sense of toxic-irritative anal eczema.
  • In girls: see below. Vulvovaginitis gonorrhoica infantum.
  • Pharyngeal gonorrhoea: about 90% of this type of infection is asymptomatic. In this respect, a throat swab should be taken from all STI patients. Pharyngeal gonorrhoea represents a major reservoir in the onward spread of N. gonorrhoeae.
  • Disseminated gonorrhoea: septic gonorrhoea is rare and occurs in about 0.5-3% of patients with local gonorrhoea. It is much more common in women than in men. It is mainly caused by gonococcal strains with the protein IA phenotype. Clinical manifestations are: undulating fevers, acute polyarthritis and acral vasculitic skin manifestations.

Diagnosis
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Microscopic detection: Intraleukocytic, gram-negative diplococci ( methylene blue and Gram stain).

Cultural detection from urethral, cervical or anal swab.

Detection by nucleic acid amplification techniques (NAAT). NAAT diagnostics are significantly more sensitive than culture diagnostics. Both symptomatic and asymptomatic infections can be sensitively detected. In addition, NAAT-based tests are not very costly in clinical practice. Samples obtained from the patient can also be used.

Serology: GO complement binding reaction in metastatic inflammation (arthritis gonorrhoica).

To exclude co-infections, if necessary, syphilis serology before treatment and 6 weeks later, PCR for chlamydia, mycoplasma and ureaplasma, HIV ELISA, hepatitis serology.

Rectoscopy/proctoscopy: inflammatory changes of the distal rectal mucosa and the anorectal transition zone. These manifest as redness and oedema with increased vulnerability (contact bleeding) or fibrinous coatings. Rarely ulcerations. Crypts and anal papillae may also show inflammatory changes. If necessary, endoscopic smear collection.

Diagnosis of gonorrhea is made by pathogen detection in culture or by nucleic acid amplification techniques (NAAT). NAAT diagnostics are significantly more sensitive than culture diagnostics and both symptomatic and asymptomatic infections can be sensitively detected. In addition, NAAT-based tests are not very costly in clinical practice and samples obtained from the patient can also be used.

N. gonorrhoeae is a genetically highly variable bacterium with the ability to take up and exchange DNA and to form mutations. This fact plays a crucial role in the development of antibiotic resistance. It also has significance for pathogen diagnostics using NAAT, as the sensitivity of a molecular biological diagnostic test can be reduced if the target region is genetically altered.( Ison CA et al. 2013; Unemo M et al. 2011)

Complication(s)
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Male: Subsequent infection of the posterior urethra pars (posterior urethritis gonorrhoica, two-lens specimen), prostatitis, vesiculitis, funiculitis, epididymitis, spermatocystis, cowperitis, cavernitis, anal infection, gonococcal sepsis, perihepatitis gonorrhoica, endocarditis, meningitis and gonarthritis.

Woman: Endometritis gonorrhoica, salpingitis, perioophoritis, oophoritis, peritonitis gonorrhoica, pelvic gonorrhoica, rectal gonorrhoea, vulvovaginitis gonorrhoica adultorum, gonococcal sepsis, perihepatitis gonorrhoica, endocarditis, meningitis and gonarthritis.

Therapy
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Worldwide increase in plasma-borne penicillin resistance (in Germany 5%) and chromosomal tetracycline resistance, therefore use of cephalosporins, aminoglycosides is recommended (see table). Due to the increasing development of resistance to fluoroquinolones, especially in the USA, fluoroquinolones can no longer be recommended, contrary to the recommendations of the German STD Society.

Increase in highly resistant gonococci: In recent years, the danger of a potentially hardly treatable, highly resistant pathogen(multidrug-resistant N. gonorrhoeae, MDR-NG, and extensively drug-resistant N. gonorrhoeae, XDR-NG) has been taken very seriously worldwide. For example, in 2017, WHO classified N. gonorrhoeae as a high priority pathogen for which new antibiotics are urgently needed due to a worrying resistance situation. Resistance has been demonstrated to all antibiotics used for treatment to date (WHO 1990).

Currently, ceftriaxone as an injectable 3rd generation extended-spectrum cephalosporin is the only remaining empirical monotherapy for gonorrhoea in most countries. However, case reports of individual treatment failures and resistance to 3rd generation cephalosporins are found worldwide. Therefore, dual antimicrobial therapy, mainly ceftriaxone plus azithromycin, is recommended in most treatment guidelines (Brooks B et al 2013;Weston EJ et al 2018).

In addition to high-level resistance, multidrug resistance is increasingly being observed. XDR-NG isolates with combined high-level resistance for azithromycin and resistance for ceftriaxone were reported from the UK and Australia in early 2018. The infections were travel-associated and acquired in Southeast Asia (Eyre DW et al. 2018; Whiley DM et al. 2018).

Caveat. Co-treatment of sexual partner to avoid the so-called ping-pong effect and mutual re-infection. Repeated controls are imperative!

See also p. 12/13 of the current guidelines of the STI Society.

Tables
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Therapy of gonorrhoea

antibiotic

Example preparations

Dosage

Duration

Uncomplicated gonorrhoea

ceftriaxone +azithromycin

Rocephin + Zithromax

1,0 g i.m. or i.v. + 1,5g p.o.

once only

cefixim +azithomycin Suprax, Cephoral 800 mg p.o. + 1.5g p.o. once only

Complicated gonorrhoea or chronic gonorrhoea (endometritis, pelvic inflammatory disease, rectal gonorrhoea, vulvovaginitis, etc.)

Ceftriaxone

Rocephin

1-2 g/day i.m.

over 7 days, depending on the clinic longer

Cefotaxime

Claforan

1-2 g/day i.v.

Cefuroxime

Zinacef

1-2 g/day i.m.

Erythromycin

Erythromycin Wolff

4 times 500 mg/day p.o.

Gonorrhoea, oropharyngeal

Ceftriaxone

Rocephin

250 milligrams I.M.

once

Azithromycin

Zithromax

1 g p.o.(Development of increasing resistance!)

once

Gonococcal Conjunctivitis

Erythromycin

Ecolicin eye ointment, eye drops

Local therapy: Apply initially every half hour, later every hour

at least 5-6 days

Ceftriaxone

Rocephin

System therapy: 1 g/day i.m.

7 days

Gonococcal sepsis (for endocarditis)

Ceftriaxone

Rocephin

2-4 g/day i.v.

over 2-3 weeks

Cefotaxime

Claforan

4-6 g/day i.v.

over 2-3 weeks

Cefuroxime

Zinacef

4-6 g/day i.v.

over 2-3 weeks

Note(s)
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Pregnant women and nursing mothers receive Ceftriaxone 1g i.v.

Literature
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  1. Brooks B et al. (2013) European Collaborative Clinical Group (ECCG). The 2012 International Union against Sexually Transmitted Infections European Collaborative Clinical Group report on the diagnosis and management of Neisseria gonorrhoeae infections in Europe. Int J STD AIDS 24:419-422.
  2. Burstein GR et al (2002) Ciprofloxacin for the treatment of uncomplicated gonorrhea infection in adolescents: does the benefit outweigh the risk? Clin Infect Dis 35(Suppl 2): S191-199
  3. Eyre DW et al. (2018) Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 2018. Euro Surveill 23(27).
  4. Golden MR et al. (2003) Partner notification for HIV and STD in the United States: low coverage for gonorrhea, chlamydial infection, and HIV. Sex Transm Dis 30: 490-496
  5. Ison CA et al. (2013) Evolution of Neisseria gonorrhoeae is a continuing challenge for molecular detection of gonorrhoea: false negative gonococcal porA mutants are spreading internationally. Sex Transm Infect 89:197-201.
  6. Lutz AR (20159 Screening for Asymptomatic Extragenital Gonorrhea and Chlamydia in Men Who Have Sex with Men: Significance, Recommendations, and Options for Overcoming Barriers to Testing. LGBT Health 2:27-34.
  7. Palusci VJ et al (2003) Testing for genital gonorrhea infections in prepubertal girls with suspected sexual abuse. Pediatr Infect Dis J 22: 618-623
  8. Rietmeijer CA et al (2003) Increases in gonorrhea and sexual risk behaviors among men who have sex with men: a 12-year trend analysis at the Denver Metro Health Clinic. Sex Transm Dis 30: 562-567
  9. Sena Corrales G et al.(2016) Gonococcal arthritis in human immunodeficiency virus-infected patients. Review of the literature. Reumatol Clin doi: 10.1016/j.reuma.2015.12.001.
  10. Wong ML et al (2002) Promoting condoms for oral sex: impact on pharyngeal gonorrhea among female brothel-based sex workers. Sex Transm Dis 29: 311-318.
  11. Unemo M et al. (2011) Review and international recommendation of methods for typing neisseria gonorrhoeae isolates and their implications for improved knowledge of gonococcal epidemiology, treatment, and biology. Clin Microbiol Rev 24:447-458.
  12. Weston EJ et al. (2018) Adherence to CDC Recommendations for the Treatment of Uncomplicated Gonorrhea - STD Surveillance Network, United States, 2016. MMWR Morb Mortal Wkly Rep 67:473-476.
  13. Whiley DM et al. (2018) Genetic characterisation of Neisseria gonorrhoeae resistant to both ceftriaxone and azithromycin. Lancet Infect Dis18:717-718.
  14. World Health Organization (WHO) 1990. global surveillance network for gonococcal antimicrobial susceptibility Geneva: WHO; 1990. WHO/VDT/90-452. available from: http://apps.who.int/medicinedocs/documents/s16348e/s16348e.pdf6

Disclaimer

Please ask your physician for a reliable diagnosis. This website is only meant as a reference.