2020 European Guideline for the Diagnosis and Treatment of Gonorrhoea in Adults (Unemo M, Et Al
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Guidelines International Journal of STD & AIDS 0(0) 1–17 2020 European guideline for the diagnosis ! The Author(s) 2020 Article reuse guidelines: and treatment of gonorrhoea in adults sagepub.com/journals-permissions DOI: 10.1177/0956462420949126 journals.sagepub.com/home/std M Unemo1 , JDC Ross2, AB Serwin3, M Gomberg4, M Cusini5 and JS Jensen6 Abstract Gonorrhoea is a major public health concern globally. Increasing incidence and sporadic ceftriaxone-resistant cases, including treatment failures, are growing concerns. The 2020 European gonorrhoea guideline provides up-to-date evidence-based guidance regarding the diagnosis and treatment of gonorrhoea. The updates and recommendations emphasize significantly increasing gonorrhoea incidence; broad indications for increased testing with validated and quality-assured nucleic acid amplification tests and culture; dual antimicrobial therapy including high-dose ceftriaxone and azithromycin (ceftriaxone 1 g plus azithromycin 2 g) OR ceftriaxone 1 g monotherapy (ONLY in well-controlled settings, see guideline for details) for uncomplicated gonorrhoea when the antimicrobial susceptibility is unknown; recommendation of test of cure (TOC) in all gonorrhoea cases to ensure eradication of infection and identify resistance; and enhanced surveillance of treatment failures when recommended treatment regimens have been used. Improvements in access to appropriate testing, test performance, diagnostics, antimicrobial susceptibility surveillance and treatment, and follow-up of gonorrhoea patients are essential in controlling gonorrhoea and to mitigate the emergence and/or spread of ceftriaxone resistance and multidrug-resistant and extensively drug-resistant gonorrhoea. For detailed back- ground, evidence base and discussions, see the background review for the present 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults (Unemo M, et al. Int J STD AIDS. 2020). Keywords Neisseria gonorrhoeae, gonorrhoea, sexually transmitted infection, Europe, management, diagnosis, antimicrobial resis- tance, treatment Date received: 14 July 2020; accepted: 16 July 2020 1WHO Collaborating Centre for Gonorrhoea and other STIs, National The present evidence-based guideline represents an Reference Laboratory for STIs, Department of Laboratory Medicine, updated version of the ‘2012 European guideline on Microbiology, Orebro€ University Hospital and Faculty of Medicine and € € the diagnosis and treatment of gonorrhoea in Health, Orebro University, Orebro, adults’.1 For detailed background, evidence base and Sweden 2University Hospital Birmingham NHS Foundation Trust, Birmingham, UK discussions, see the background review for the present 3Department of Dermatology and Venereology, Medical University of 2020 European guideline for the diagnosis and treat- Białystok, Białystok, Poland ment of gonorrhoea in adults (Unemo M, et al. Int J 4Moscow Scientific and Practical Center of Dermatovenereology and STD AIDS. 2020). Cosmetology, Moscow, Russia 5Department of Dermatology, Fondazione IRCCS Ca’ Granda Ospedale Policlinico, Milano, Italy Aetiology, transmission, and epidemiology 6Infection Preparedness, Research Unit for Reproductive Tract Microbiology, Statens Serum Institut, Copenhagen, Denmark • Gonorrhoea (gonococcal infection) is caused by the obligate human pathogenic, Gram-negative bacteri- Corresponding author: um Neisseria gonorrhoeae;2 M Unemo, WHO Collaborating Centre for Gonorrhoea and other STIs, • National Reference Laboratory for STIs, Department of Laboratory Infection predominantly involves the epithelium of Medicine, Microbiology, Orebro€ University Hospital, Orebro,€ Sweden. the urethra, endocervix, rectum, oropharynx, and Email: [email protected] 2 International Journal of STD & AIDS 0(0) conjunctivae. Infection can ascend to the upper gen- the cervix, sometimes accompanied with hyperaemia ital tract to cause pelvic inflammatory disease (PID) and contact bleeding of the endocervix. and epididymo-orchitis;1–3 • Transmission is by direct inoculation of infected Complications and sequelae secretions from one mucosa to another, i.e., • PID in women, potentially resulting in ectopic preg- genital-urogenital, urogenital-anorectal, oro- urogenital, or oro-anal contact, or by mother-to- nancy and infertility, and epididymo-orchitis in men child transmission at birth;1–7 are complications of infection ascending to the • In the European Union (EU)/European Economic upper genital tract; • 17,18 Area (EEA), gonorrhoea is the second (after Gonococcal bacteraemia is generally rare, but Chlamydia trachomatis infection) most frequently can be more common in high-prevalent gonorrhoea reported bacterial sexually transmitted infection areas and may be expected to increase when the 19 (STI), and the incidence has increased by 240% gonorrhoea incidence increases. This is usually since 2008.8 In 2018, 76% of gonorrhoea cases manifested by skin lesions, fever, arthralgia, acute were reported in men,8 reflecting the high prevalence arthritis, and tenosynovitis (disseminated gonococ- 3,17–21 in men who have sex with men (MSM) and the cal infection [DGI]). higher proportion of diagnosed symptomatic uro- genital infections in men. In 2018, the highest inci- Indications for testing [2C] dence of gonorrhoea in the EU/EEA was among 25– • 34 year olds, closely followed by 15–24 year olds Symptoms or signs of urethral discharge in men; • and, in many countries, there is a disproportionate Cervical or vaginal discharge with a risk factor for < burden of infection in MSM and/or ethnic minority STI (age 30 years, new sexual contact in the last 8,22–24 groups.8–10 year, or more than one partner in the last year); • Mucopurulent cervicitis; • 1–3,11–16 Persons newly diagnosed with other STIs; Clinical features • Sexual contact of persons with an STI or PID; Symptoms and physical signs of gonorrhoea reflect • Acute epididymo-orchitis in a male aged <40 years localised inflammation of infected mucosal surfaces in or with other risk factors for STIs (e.g., new sexual the urogenital tract and several other STIs cause simi- contact in the last year, or more than one partner in lar symptoms. the last year);8,22–24 • Acute pelvic pain or signs of PID; Symptoms • When performing an STI screen in young adults (<25 years of age) or MSM; • In men, acute urethritis is predominant with symp- • When performing an STI screen in individuals with toms of urethral discharge (>80%) and dysuria > new or multiple recent sexual contacts; ( 50%), usually starting within 2–8 days of expo- • Purulent conjunctivitis in a neonate or adult; sure. Asymptomatic urethral infection in men is rare • Mother of a newborn with ophthalmia neonatorum; < ( 10% of infections); • Unplanned termination of pregnancy in areas or • In women, endocervical and urethral infection populations of high gonorrhoea prevalence; include symptoms such as increased or altered vag- • Any intrauterine interventions or manipulations in inal discharge (50%), lower abdominal pain areas or populations of high gonorrhoea (25%), dysuria (10–15%), and occasionally inter- prevalence.25,26 menstrual bleeding or menorrhagia. Endocervical infection is frequently asymptomatic (50%); • Rectal and oropharyngeal infections in men and Testing and diagnosis women are usually asymptomatic. Rare symptoms • Diagnosis of uncomplicated gonorrhoea is estab- include anal discharge and perianal/anal pain or dis- lished by identification of N. gonorrhoeae in urogen- comfort and sore throat, respectively. ital, rectal, oropharyngeal, or ocular secretions;2,27 • N. gonorrhoeae can be detected by nucleic acid Physical signs amplification tests (NAATs) or culture. The bacte- • In men, mucopurulent urethral discharge is most rium can also be visualized by microscopy of a common, which may be accompanied by erythema stained anogenital tract smear to facilitate rapid of the urethral meatus; diagnosis in symptomatic patients; • In women, urogenital examination may be normal • Microscopy (31000) using Gram or methylene blue or a mucopurulent discharge may be evident from staining for identification of characteristic Unemo et al. 3 intracellular diplococci within polymorphonuclear gonorrhoea,1,2,27,32,35–38,46,49,50,56–62 and appropri- leukocytes offers adequate sensitivity (90-95%) and ately-validated and quality-assured NAATs are rec- specificity (>99%) as a rapid diagnostic test in ommended for testing and/or screening for symptomatic men with urethral discharge [1C].1– infections at these sites.1,2,35–38,63,64 However, most 3,12,27,28 Microscopy has a low sensitivity in asymp- commercially available gonococcal NAATs are not tomatic men (50-75%) and from endocervical (16- licensed for testing oropharyngeal and rectal speci- 50%) or rectal (40%) sites, and microscopy is not mens, and differ in their sensitivity and especially recommended as a test of exclusion in these patients specificity,1,2,27,33,37,65–69 particularly when examin- [1C].1–3,12,14,27–31 Microscopy is also not recom- ing oropharyngeal specimens due to the frequent mended for detection of oropharyngeal gonorrhoea presence of non-gonococcal Neisseria species. due to low specificity and sensitivity; • NAAT confirmatory testing: The positive predictive • Culture, including appropriate species confirmation, value (PPV) of NAAT testing to detect N. gonor- is a highly specific test, and relatively sensitive for rhoeae should exceed 90%. The PPV is highly influ- urogenital specimens, provided that specimen collec- enced by the gonorrhoea prevalence