Overview
Nongonococcal urethritis (NGU) is an inflammation of the urethra and the most common sexually transmitted disease in people assigned to males at birth (AMAB).1 The term “nongonococcal” indicates that the gonorrhoea bacteria are not the source of this infection. NGU is more prevalent in people with AMAB than people assigned female at birth (AFAB) and is mostly transferred through oral, anal, and vaginal intercourse.2 However, in many cases (20–50% of cases), the cause of the infection is not identified.3 Medical treatment of NGU can be challenging due to its various etiologies and syndromic management. Furthermore, the effectiveness of syndromic management could vary depending on the aetiology. Read along to find out more about the causes, symptoms, and treatment of this sexually transmissible infection (STI).
Causes and risk factors
NGU can be brought on by a variety of pathogens, including but not exclusive to:
- Chlamydia trachomatis (most prevalent)
- Ureaplasma urealyticum
- Mycoplasma genitalium
- Trichomonas vaginalis (rare)
- Herpes simplex virus (rare)
- Haemophilus vaginalis
Sometimes, friction during sex or getting irritants like soap in the urethra might also result in NGU.4
Bacterial causes of NGU
Chlamydia trachomatis is a bacterial agent for urethritis that is regularly tested for and identified in 20–50% of cases.5 It is a tiny, obligately intracellular parasitic gram-negative bacteria. Typically, the incubation phase lasts 7 to 14 days.6 When a person with NGU caused by Chlamydia trachomatis engages in unprotected intercourse (without wearing a condom), the infection can be easily transferred.
With 10–30% of infections being caused by Mycoplasma genitalium, this pathogen has become the second most frequent aetiological agent. This organism is a microscopic self-replicating bacteria without a cell wall that can be hard to observe due to its slow growth.7 According to one investigation, M. genitalium and C. trachomatis were strongly related to acute symptomatic NGU but not to asymptomatic NGU.8
There are still many discrepancies regarding the pathogenic role of Ureaplasma spp., especially Uraeplasma urealyticum and Uraeplasma parvum, in NGU, despite increasing evidence of their involvement in this illness.
Viral causes of NGU (less common)
NGU is mostly caused by a bacterial infection, but it can also occur via a virus or protozoa. Few studies have investigated adenoviruses and the herpes simplex virus (HSV) as probable viral causes of acute NGU.9,12
Non-infectious causes and risk factors
In addition to bacterial and viral infections, certain behaviours may also raise the risk. Multiple sex partners increase the risk of NGU in people AMAB between the ages of 15 and 30.13 Furthermore, individuals AMAB who specifically engage in anal sex with other people AMAB may be more susceptible to urogenital pathogens other than gonorrhoea and chlamydia that may cause urethritis.14
Additionally, non-gonococcal urethritis risk is higher in those with weakened immune systems or immune-compromising conditions like HIV/AIDS.15
Among the non-sexual causes of NGU are:
- Phimosis, which refers to an overly tight foreskin
- Catheterization - the term used when a medical operation requires inserting a tube into the penis
Symptoms and clinical presentation
Symptoms of urethritis in people AMAB include:
- Urethral discharge (although it doesn't happen in every case, a white fluid (discharge) from the end of the penis is common)
- Dysuria (discomfort or burning during urinating. This could be mistaken for a urine infection)
- Urethral itching or discomfort
- Pelvic pain
- Tenderness
- Underwear stain
- In a small percentage of cases, the infection can move up the urethra to the testicles, where it can cause pain and swelling in one or both of them.
NGU typically shows no symptoms in people AFAB, but it has the potential to move up the reproductive organs and result in pelvic inflammatory disease, which can be extremely unpleasant and have an impact on fertility. Pelvic or lower abdominal pain, fever, irregular periods, irregular vaginal discharge, pain during sexual activity, and trouble passing urine are all possible symptoms.16
Diagnosis
If you have symptoms of NGU or believe you may have been exposed to an STI, visit a nearby genitourinary medicine (GUM) clinic or sexual health clinic where an NGU diagnosis can be performed.
An NGU diagnosis is made when a patient has urethritis (inflammation of the urethra), or any of the symptoms mentioned above, but gonorrhoea is ruled out due to a negative test result. A gram stain devoid of gram-negative diplococci or any negative gonorrhoea test (culture, nucleic acid testing, among others) can be employed to rule out gonorrheal infection.17
To attempt to pinpoint the source of the disease, the patient will likely be requested to make a urine or swab test:
- A urine test - you will be requested to hold off on peeing for at least two hours before supplying a urine sample to increase the reliability of the test results.
- A swab test involves taking a sample of fluid from your urethra using a little cotton bud-like instrument called a swab. The swab may contain a little plastic loop or cotton tip at the bottom; it isn't painful. However, it might be irritating for a brief period.
As part of the NGU diagnosis, patients will also be encouraged to get tested for HIV and syphilis as well as other STIs. Blood testing may be necessary for this. Individuals AMAB who engage in sexual activity with people AMAB may also be encouraged to have a swab taken from the pharynx (back of the throat) and the rectum.
Complications
Although they occur rarely, complications of NGU in people AMAB are possible and include: epididymitis, prostatitis, the development of an abscess, and reactive arthritis. Untreated epididymis inflammation can result in infertility because it affects the long, cord-like tissue that runs around the back of the testicles.
People AFAB frequently show no symptoms of NGU. Nevertheless, if chlamydia is the cause of NGU and if it is not treated, it may develop into pelvic inflammatory disease (PID). A higher risk of infertility is linked to repeated PID episodes.18
Infections brought on by anal sex can cause severe proctitis (inflamed rectum) in both people AMAB and people AFAB.19
Conjunctivitis, iritis, and pneumonia are possible consequences in children born to mothers who have chlamydia urethritis. The frequency of these infections has been greatly reduced by administering antibiotic eye ointment to all newborns regularly.20
Treatment and management
NGU is treated with antibiotics. These drugs eliminate the pathogens that are causing the disease. A healthcare professional might prescribe:
- Doxycycline 100 mg orally twice a day for 7 days
- Antibiotics known as macrolides, such as azithromycin, which is taken as a single dose
Sometimes it could take two or three weeks for the NGU symptoms to go away.
After receiving the recommended course of treatment for NGU, often, recurrent or chronic symptoms can occur. Before starting new antibiotic treatment, patients should be assessed for adherence to previous regimens and risk of relapse. Therapy should be focused on M. genitalium if they continue to show symptoms of urethritis, as the most frequent cause of persistent or recurrent NGU is M. genitalium.18
Since NGU can be spread during sex, it's common to treat all cases of NGU as STIs while also ensuring that all recent sexual partners have received treatment.
Vaginal, anal, and oral sex should all be avoided for at least 7 days and until symptoms resolve.21
There are several techniques to stop the spread of NGU, including:
- Abstinence - The best defence against contracting NGU and other Sexually Transmitted Diseases (STD) is to avoid having sex
- Every time you engage in sexual activity, use latex condoms appropriately and consistently
- Have sex solely with one healthy partner (mutual monogamy)
- If you are a sexually active person, have regular checks
- Don't have oral, vaginal, or anal intercourse if you have an STD until all partners have received treatment
- To stop the progression of the condition, seek immediate, qualified, and appropriate medical intervention, therapy, and follow-up
- Know your partner(s). All partners engaged may be shielded from infection by consideration and open communication
Public health and prevention
STIs can raise the risk of HIV and have a direct influence on sexual and reproductive health through stigma, infertility, malignancies, and pregnancy difficulties.
WHO advises countries to gradually incorporate laboratory testing to support the diagnosis of STIs. It is advised to treat STIs based on laboratory results in contexts where quality-assured molecular assays are available. STI screening programs are also crucial for those who are more likely to contract the disease, including pregnant women, sex workers, very sexually active people.22
News, education, and counselling can help people detect the signs of STIs more easily, which will enhance the possibility that they will get medical attention and persuade a sexual partner to do the same.
Summary
Nongonococcal urethritis (NGU) is an inflammation of the urethra that is not caused by gonorrhoea bacteria. The most common cause of NGU is a germ known as Chlamydia trachomatis. Since the organisms causing this infection are sexually transmitted and the female urethra is rarely infected during intercourse, people AMAB between the ages of 15 and 30 who have multiple sex partners are most at risk for this infection. The primary symptoms of NGU include a mild discomfort or burning feeling during urination, which is occasionally accompanied by a light discharge (drip) from the urethra. Antibiotics such as doxycycline and azithromycin are the main medicines used in the treatment of NGU. If NGU is left untreated, a person might experience complications like infection of the prostate gland and testicular enlargement (epididymitis). More importantly, they might spread the disease to sexual partners. The easiest strategy to prevent NGU when you're sexually active is to use condoms or another barrier device for oral, vaginal, and anal intercourse. If you or your partner(s) have STI symptoms or may have been exposed to STIs, avoid having any sexual contact. Visit a healthcare professional or an STI testing facility.
References
- Territo H, Ashurst JV. Nongonococcal Urethritis (NGU) [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535411/
- NGU [Internet]. www.ashasexualhealth.org. 2014. Available from: https://www.ashasexualhealth.org/ngu/
- Bradshaw Catriona S, Tabrizi Sepehr N, Read Timothy R H., Garland Suzanne M, Hopkins Carol A, Moss Lorna M, et al. Etiologies of Nongonococcal Urethritis: Bacteria, Viruses, and the Association with Orogenital Exposure. The Journal of Infectious Diseases. 2006 Feb;193(3):336–45.
- Looking after your sexual health Your Guide to Chlamydia, Gonorrhoea and Non-Gonococcal Urethritis (NGU) 2 [Internet]. [cited 2023 Oct 1]. Available from: https://www.unitysexualhealth.co.uk/wp-content/uploads/2023/05/FPA-Chl_Gon_NGU-combo-leaflet.pdf
- Gaydos C, Maldeis NE, Hardick A, Hardick J, Quinn TC. Mycoplasma genitalium compared to chlamydia, gonorrhoea and trichomonas as an aetiological agent of urethritis in men attending STD clinics. Sexually Transmitted Infections. 2009 Apr 20;85(6):438–40.
- Young A, Toncar A, Wray AA. Urethritis [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537282/
- Totten Patricia A, Schwartz Margot A, Sjöström Karen E, Kenny George E, Handsfield H Hunter, Weiss Judith B, et al. Association of Mycoplasma genitalium with Nongonococcal Urethritis in Heterosexual Men. The Journal of Infectious Diseases. 2001 Jan 15;183(2):269–76.
- Horner PJ, Thomas BJ, Gilroy CB, Egger M, Taylor-Robinson D. Role of Mycoplasma genitalium and Ureaplasma urealyticum in Acute and Chronic Nongonococcal Urethritis. Clinical Infectious Diseases. 2001 Apr 1;32(7):995–1003.
- Bradshaw CS. Characteristics of adenovirus-associated urethritis. Sexually Transmitted Infections. 2002 Dec 1;78(6):445–7.
- Azariah S, Reid M. Adenovirus and non-gonococcal urethritis. International Journal of STD & AIDS [Internet]. 2000 Aug 1 [cited 2023 Oct 4];11(8):548–50. Available from: https://pubmed.ncbi.nlm.nih.gov/10990341/
- Harnett GB, Phillips PA, Gollow MM. Association of genital adenovirus infection with urethritis in men. The Medical Journal of Australia [Internet]. 1984 Sep 15 [cited 2023 Oct 4];141(6):337–8. Available from: https://pubmed.ncbi.nlm.nih.gov/6094996/
- Swenson PD, M Sylvan Lowens, Celum C, Hierholzer JC. Adenovirus types 2, 8, and 37 associated with genital infections in patients attending a sexually transmitted disease clinic. 1995 Oct 1;33(10):2728–31.
- Urethritis & Men [Internet]. Cleveland Clinic. Available from: https://my.clevelandclinic.org/health/diseases/4426-nongonococcal-urethritis-in-men
- Balcan D, Colizza V, Goncalves B, Hu H, Ramasco JJ, Vespignani A. Multiscale mobility networks and the spatial spreading of infectious diseases. Proceedings of the National Academy of Sciences. 2009 Dec 14;106(51):21484–9.
- Non-gonococcal urethritis: What you need to know [Internet]. www.vinmec.com. [cited 2023 Oct 4]. Available from: https://www.vinmec.com/en/news/health-news/general-health-check/non-gonococcal-urethritis-what-you-need-to-know/
- What is urethritis? | Non-gonococcal Urethritis [Internet]. patient.info. Available from: https://patient.info/sexual-health/sexually-transmitted-infections-leaflet/non-gonococcal-urethritis
- Centres for Disease Control and Prevention. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae--2014. MMWR Recommendations and reports: Morbidity and mortality weekly report Recommendations and reports [Internet]. 2014 Mar 14;63(RR-02):1–19. Available from: https://pubmed.ncbi.nlm.nih.gov/24622331/
- NHS 111 Wales [Internet]. nhs. uk. 2018 [cited 2023 Oct 4]. Available from: https://111.wales.nhs.uk/encyclopaedia/u/article/urethritis
- Non-Gonococcal Urethritis (NGU) [Internet]. dph.illinois.gov. Available from: https://dph.illinois.gov/topics-services/diseases-and-conditions/diseases-a-z-list/non-goncoccal-urethritis.html
- Numazaki K, Wainberg MA, McDonald J. Chlamydia trachomatis infections in infants. CMAJ: Canadian Medical Association journal = journal de l’Association medicale canadienne [Internet]. 1989 Mar 15 [cited 2023 Oct 4];140(6):615–22. Available from: https://pubmed.ncbi.nlm.nih.gov/2645987/
- Chambers LC, Hughes JP, Glick SN, Morgan JL, Lowens MS, Robinson TS, et al. Resolution of Symptoms and Resumption of Sex After Diagnosis of Nongonococcal Urethritis Among Men Who Have Sex With Men. Sexually Transmitted Diseases [Internet]. 2019 Oct 1 [cited 2023 Oct 5];46(10):676–82. Available from: https://pubmed.ncbi.nlm.nih.gov/31356530/
- World Health Organization. Sexually transmitted infections (STIs) [Internet]. Who. int. World Health Organization: WHO; 2023. Available from: https://www.who.int/news-room/fact-sheets/detail/sexually-transmitted-infections-(stis)