Introduction

Sexually transmitted infections (STIs) are diseases which are caused by different pathogens and can be transmitted via sexual activity, for example, through vaginal, anal, or oral sex. According to the World Health Organisation, more than 1 million STIs are being diagnosed every day around the world in people aged 15 to 49 years old.¹ Gonorrhoea is one of the most common STIs, specifically caused by the bacterium Neisseria gonorrhoeae. This bacterium predominantly affects young adults, both those assigned female at birth (AFAB) and those assigned male at birth (AMAB). Gonorrhoea in people AFAB mostly affects the cervix, manifesting as cervicitis, though symptoms may not be present, as observed in 50% of the cases. Contrarily, more than 90% of those AMAB present gonococcal urogenital infections with clinical symptoms. Even in the absence of symptoms, gonorrhoea is still transmissible and although it is curable with the use of antibiotics, undetected or untreated cases may lead to complications including infertility and ectopic pregnancy. Thus, regular testing and safe sex practices are pivotal for limiting the risk of infection.²

According to programmes surveilling STIs in the European Union, gonorrhoea displayed increasing rates in the past few years, with 17.9 cases per 100,000 people being reported in 2022. Notably, people AFAB and AMAB in the age group of 20 to 24 years old presented the highest infection rate. 60% of gonorrhoea cases in 2022 were reported in men who have sex with men (MSM).³ Interestingly, gonorrhoea co-infections with other STIs have been reported by various online studies, which found a particular correlation with chlamydia and syphilis. Furthermore, gonococcal infections were found to increase the risk of contracting and transmitting human immunodeficiency virus (HIV).^4-6

How does gonorrhoea affect the body?

A gonococcal infection occurs when N. gonorrhoeae enters the body through sexual intercourse. Vaginal, anal, and oral sex, are common routes through which this bacterium can infect the body. N. gonorrhoeae cannot live in the environment hence needs a human host to survive. Upon infection, it activates the innate and adaptive immune systems of its host and combats the related immune mechanisms, managing to colonise and proliferate inside the human body. Typically, the bacterium impacts the urogenital tracts (particularly the urethra and cervix), rectum, pharynx, or eyes, depending on the route of transmission, but further spread is possible. Ejaculation during intercourse heightens the risk of infection as millions of bacteria can be found in the semen of infected people AMAB. Moreover, people AFAB can transmit the infection to neonates during birth, specifically occurring as an eye infection.^2,7

Symptoms

As mentioned above, gonococcal infection of the genitals may be asymptomatic, particularly in people AFAB, however, certain symptoms may occur based on the site of infection. In case of cervix infection resulting in cervicitis in people AFAB, symptoms can include:^2,8

• Vaginal discharge
• Pain during urination (dysuria)
• Pelvic pain
• Bleeding between periods or sexual intercourse

In case of infection in specific glands called Bartholin’s glands, located in the vaginal opening, symptoms may include:^2,8

• Labial swelling
• Formation of abscesses
• Pain

People AMAB present symptoms of a gonococcal infection more commonly, including:^2,8

• Penile discharge, mostly purulent (white, yellow, or greenish discharge)
• Dysuria
• Pain, discomfort, or swelling in the testicles

Infection of the pharynx or rectum typically lacks specific symptom manifestation or presents only slight symptoms. In case of a pharynx infection, symptoms may include redness, pain, and sore throat. An untreated rectum infection may present with symptoms such as pain, bleeding, discharge, and proctitis.^2,8

Potential complications

If gonorrhoea is left untreated it can lead to various complications predominantly affecting the reproductive system of individuals. 

Cervical infections can lead to: 

• pelvic inflammatory disease
• chronic pain
• ectopic pregnancies
• infertility due to defects in the fallopian tubes. 

Pregnant people AFAB with active infections may also exhibit potential complicationsincluding: 

• premature births 
• spontaneous abortions

Infants with eye infections, transmitted from the mother during birth, can develop conjunctivitis, leading to corneal damage, which, if left untreated, can lead to blindness. 

Additionally, people AMAB with untreated infections may develop: 

• swelling in the testicles
• urethra stricture
• prostatitis
• infertility

In rare cases, gonococcal infections can result in systemic problems such as septic arthritis, endocarditis, and meningitis.^2,8

Gonorrhoea and other STIs

Co-infections of gonorrhoea with other STIs are a possible scenario, observed in diverse cases around the world, although further scientific studies are needed to understand in depth the exact correlation.

Chlamydia

Chlamydia is one of the most common STIs worldwide, caused by an infection with the bacterium Chlamydia trachomatis, sharing similar modes of transmission and infection locations with gonorrhoea. Various studies have documented co-infections with the two diseases, indicating a potential biological link between them that augments their transmissibility and infection risk. Approximately 10-40% of individuals with gonorrhoea also present a chlamydia infection, with this range being lower in people with chlamydia co-infected with gonorrhoea. It has been suggested that the vaginal microbiome is a significant factor influencing the risk of gonorrhoea and chlamydia infections, also potentially affecting their concomitance. Furthermore, studies suggest the presence of a higher bacterial load in cases of co-infection compared to a gonococcal infection alone. Nevertheless, further investigation into the mechanisms of their co-existence is necessary to obtain a clearer image and aid treatment strategies and vaccine development.⁹

HIV

Gonorrhoea has been found to increase the risk of infection and transmission of HIV, especially observed in MSM. In detail, a gonococcal infection renders individuals more susceptible to contracting HIV, particularly through rectal infection. HIV-negative individuals also present a higher risk of acquiring HIV from HIV-positive partners who are co-infected with gonorrhoea.¹⁰ Various immune mechanisms triggered by a gonococcal infection have been suggested to facilitate HIV infectivity, although further studies are crucial for decoding this relationship. Specific studies on HIV-1 have demonstrated that the association of specific immune responses which cause inflammation, the reduction in adaptive immune responses, and the recruitment of neutrophils due to gonococcal infections may reduce the body’s ability to prevent gonorrhoea while also affecting HIV-1 transmission and replication. Additionally, immune cells such as macrophages, dendritic cells, and T-cells are affected by a gonococcal infection and can potentially increase the viral load and transmission of HIV-1. A better understanding of these molecular relations could reveal effective prevention techniques and treatment options, mitigating HIV-1 spread.¹¹

Syphilis

Apart from chlamydia and HIV, a notable rate of co-infection between gonorrhoea and other STIs has also been reported. For instance, a study on the evaluation of gonorrhoea spread and its association with other STIs in a specific clinic found a significant co-infection rate (6.3%) of syphilis in gonorrhoea patients.⁴ Furthermore, in another research conducted in Portugal among 6,506 people with confirmed gonorrhoea, chlamydia, or syphilis, 13.2% of the cases were reported as co-infections.¹²

Trichomoniasis

Gonorrhoea can be associated with trichomoniasis, an infection caused by the parasite Trichomonas vaginalis. Specifically, patients with trichomoniasis have a significantly higher risk of co-infection with gonorrhoea and chlamydia, with triple infections also being common, impacting the diseases’ progression and potential associated complications.¹³

Human papillomavirus (HPV)

Studies indicate that gonorrhoea and HPV co-infections are common and can contribute to implications concerning the cervical health of individuals. For example, co-infections between HPV and other STIs, including gonorrhoea, were observed in a significant proportion of cases, complicating the clinical outcomes, and influencing the progression of cervical lesions. Notably, individuals with co-infections seem to have a higher likelihood of contracting oncogenic HPV strains. Moreover, the inflammation of the cervical epithelium and the secretion of various immune mediators caused by gonorrhoea can create an opportunistic environment for HPV, supporting its persistence and progression and increasing the risk of lesions evolving into cervical cancer.¹⁴

Other infections

Another STI that has been associated with gonorrhoea is genital herpes. The coexistence of gonorrhoea with human simplex virus (HSV) that causes genital herpes is rare but possible and complicates the symptomatology and treatment strategies for STIs. Particularly, since both HSV and gonococcal infections may not appear with any clinical symptoms, thorough laboratory evaluations are critical for diagnosing these STIs to minimise the risk of potential complications and transmission.⁴

Lastly, gonorrhoea has also been linked to other non-STIs like candidiasis, and bacterial vaginosis.⁴

Summary

In summary, gonorrhoea, caused by N. gonorrhoeae, is one of the most common STIs, which poses significant public health challenges. Gonococcal infections primarily affect young adults and may be asymptomatic, particularly in people AFAB, thereby being transmitted unknowingly through sexual intercourse. Despite being treatable, gonorrhoea can lead to severe complications predominantly affecting the reproductive health of individuals. 

Gonorrhoea, as well as other STIs, has shown increasing rates in the past years, probably attributed to the elevated number of screenings in high-risk populations. Its association with other STIs through the presence of coinfections has been observed in various studies but is still poorly analysed. Chlamydia, syphilis, HIV, HPV, and other infections have all been linked to gonorrhoea with different levels of frequency, exacerbating health outcomes and treatment strategies. Therefore, preventive measures and regular testing, especially in case of contact with a high-risk network, not only for gonorrhoea but for potential co-infections as well, could mitigate the spread and impact of STIs on global health.