Introduction

Gonorrhoea is a sexually transmitted disease that affects people of all sexes. The infectious agent is Neisseriagonorrhoea, a bacteria that exclusively infects humans. The acute infection may be asymptomatic, especially in those assigned female at birth (AFAB). If not well treated, gonorrhoea can lead to long-term reproductive problems and an increased risk of contracting and transmitting HIV (Human immunodeficiency Virus). Undiagnosed asymptomatic infections increase the spread of the disease amongst the population and hinder control efforts. Gonorrhoea is treatable with antibiotics, however, there is an increasing level of resistance to antibiotics thus making this disease an emerging public health threat. 

Epidemiology of gonorrhoea

Gonorrhoea is largely underreported and underdiagnosed globally, often because the infection can be asymptomatic. Undiagnosed asymptomatic infections lead to an increased risk of transmission and delays in treatment. Underdiagnosis is more pronounced in low- and middle-income countries due to delayed presentation, a lack of effective and reliable diagnostic methods, and the use of syndromic management of sexually transmitted infections. One systematic review of global prevalence reporting trends found that at the time of the review, only four countries had national population-based data on gonorrhoea infection.¹ In 2020, the World Health Organization(WHO) reported an estimated 82.4 million new infections among adults globally.² Most cases were in the WHO African Region and the Western Pacific Region. In the United States, gonorrhoea is the second most commonly reported notifiable disease.³ The high incidence may be a consequence of increased testing, but it may also indicate increased transmission within the population. 

The populations at high risk include adolescents, people assigned male at birth (AMAB) who have sex with AMAB people, sex workers, people with multiple sexual partners, and transgender women.^2,3 There is also a higher incidence among adults living in low-income countries.⁴ 

Socioeconomic and cultural factors, neighbourhood instability, low socio-economic status within minority ethnic groups, and lack of education are all associated with the spread of gonorrhoea.^5.6 

Health consequences of gonorrhoea

The organism Neisseria gonorrhoea infects parts of the body that are lined with columnar epithelium. The cervix and the urethra are the most commonly affected organs but it can also affect the throat (pharynx) or the anus.

It is usually asymptomatic in AFAB people but symptomatic in AMAB people. In both AFAB and AMAB people, it can spread to involve other organs like the liver and joints. The disease is associated with long-term sequelae (long-term health impacts) if poorly treated.

Immediate health effects

Symptoms in AFAB people 

When symptomatic in AFAB people, gonorrhoea presents with;

• Vaginal discharge 
• Painful urination 
• Pain during sex 
• Abnormal bleeding from the genital tract
• Pain in the anus and lower abdomen ³

These symptoms result from inflammation of the genital tract and if not well treated may lead to pelvic inflammatory disease and associated health problems.

Symptoms in AMAB people

In AMAB people, gonorrhoea presents with;

• Discharge from the penis or itching
• Pain when urinating 
• Pain at the testis or anus

Long term complications

If untreated in AFAB people, gonorrhoea may lead to pelvic inflammatory disease with subsequent damage to the reproductive tract and blockage of the fallopian tube. These long-term complications result from damage to the lining of the affected organs and subsequent distortion of their structure. This may lead to infertility, ectopic pregnancy, and chronic pain in the lower abdomen. It also increases the risk of contracting and transmitting HIV. There can also be vertical transmission to the newborn baby manifesting as eye inflammation and discharge (ophthalmia neonatorium).

Long-term effects in AMAB people result from damage to the affected parts of the urogenital system. They include chronic epididymo-orchitis (inflammation of the testis and epidydimis), urethral stricture (narrowing of the lumen of the urethra), urinary obstruction, arthritis, and infertility.

Public health challenges

Detection and diagnosis

Availability of testing

The trend in the diagnosis of gonorrhoea has moved in recent times from culture to molecular diagnosis (using a DNA (Deoxyribonucleic acid) probe or PCR (Polymerase Chain Reaction) test). Molecular diagnosis is now recommended as the gold standard for diagnosis, but this unfortunately is not available or affordable in most low-resource settings.

Point-of-care testing which utilises molecular methods is being adopted as a way to combat delays in diagnosis and the risk of antibiotic resistance due to syndromic management. The ideal point-of-care test should be affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free and deliverable to end users (known as the ASSURED criteria).⁷ Remarkable progress has been made in this regard, however, none of the currently available tests meet all of these criteria. Some of the available point-of-care texts include GeneXpert CT/NG, Binx io platform and Resistance plus GC assay. These are largely not available or affordable in low-resource settings.

Laboratory culture tests were the most common diagnostic method before the advent of molecular methods. These can still be useful when the diagnosis is unclear or when treatment fails. In addition, it finds its place in epidemiological investigations and in predicting drug resistance in the different phenotypes. The complex nature of the organism and the need for special transport and culture media make laboratory culture testing difficult in low-resource settings.⁸ Delayed diagnosis leads to an increased risk of transmission and increased risk of the development of long-term symptoms with a consequent increase in the public health burden.

Barriers to diagnosis

Delays in diagnosis and inappropriate diagnosis of gonorrhoea substantially increase the public health burden as these result in underreporting of its prevalence and inappropriate treatment of patients with gonorrhoea.

In low-resource settings, the unavailability of accurate diagnostic methods is a major drawback. To combat these challenges, syndromic management (diagnosis and treatment based on symptoms alone) of sexually transmitted infections (STI) has been implemented as a way to prevent delays in diagnosis, and further health problems caused by gonorrhoea. Though beneficial in fast-tracking treatment, this method does not provide laboratory diagnosis and also leads to the overuse of antibiotics. This affects the reported prevalence of gonorrhoea and increases the risk of antibiotic resistance. 

The asymptomatic nature of gonorrhoea in some patients may pose a barrier to diagnosis: this is why screening is recommended in high-risk populations. The lack of an affordable sensitive test suitable for mass screening is an impeding factor.

Point-of-care diagnostic methods are being developed, but are still largely unavailable in low-resource countries due to lack of affordability.⁹ Poor socio-economic status influences health-seeking behaviour and this leads to delayed or lack of presentation at the health facilities. The delay in the presentation may also be due to the social stigma associated with the disease and the need to collect samples for testing from private areas of the body.⁸ Providing self-care testing kits would help to counter this challenge. 

Antimicrobial resistance and treatment difficulties

Gonorrhoea is gradually emerging as a public health threat because of the increasing challenge of drug resistance. This raises concerns about the potential development and emergence of gonorrhoea untreatable with current antibiotics. Data from the China Gonococcal Resistance Surveillance Program (China-GRSP) shows that prevalences of resistance to cefixime, azithromycin, tetracycline, penicillin, and ciprofloxacin were 16.0%, 16.9%, 77.1%, 77.8%, and 97.6%, respectively.¹⁰

The incidence of antibiotic-resistant strains has been rising since the 1940s. This has been an increasing trend with each new antibiotic that has been introduced. In the past decade, we have witnessed a sharp increase in fluoroquinolone resistance.¹¹ Antimicrobial resistance would lead to higher healthcare costs as the available antibiotics become more costly.

Consequently, fluoroquinolones and tetracyclines are no longer recommended as first-line therapy due to the increased prevalence of resistant strains.¹² 

The preferred first line of treatment for uncomplicated gonorrhoea is intramuscular ceftriaxone. Oral doxycycline can also be used if infection with Chlamydia trachomatis (a sexually transmitted pathogen responsible for chlamydia) has not been ruled out. 

Antibiotic resistance is a great matter of concern as there are few new antibiotics with potential to treat gonorrhoea given the emerging resistance to the extended-spectrum cephalosporins.

The increasing resistance to treatment is of global concern and this has led to the modification of treatment guidelines in some countries to include dual therapy (treatment with a combination of medications, rather than one singular antibiotic) as the first line of treatment.¹¹

This emerging resistance to high-profile antibiotics (cephalosporins and macrolides) and a limited antimicrobial drug development pipeline pose a threat to gonorrhoea control and management.¹² This is because it prolongs the infection in more people and increases the number of people with long-term complications of gonococcal infections.

The socio-economic impact of gonorrhoea infection

Gonorrhoea is a short-term disease with the possibility of long-term associated health problems. Whether short-term or long-term, the economic impact is profound. The economic impact can be either direct or indirect:

Direct costs

Direct costs are due to funds spent on purchasing medications and funding hospitalisation. These costs have been increasing with the growing problem of antibiotic resistance. The cost spent on the management of long-term sequelae like infertility is significant, especially in AFAB people. One study found that the main costs for AFAB people were from treatment for gonorrhoea sequelae, while the main costs for AMAB people were from treatment for gonococcal infections.¹⁴ 

Indirect costs

Indirect costs are due to the loss of hours worked due to time spent in laboratories and clinics receiving medical attention and treatment, leading to reduced workforce productivity. The diagnosis and treatment of gonorrhoea infection also place a huge economic burden on the healthcare system. Long-term disability, and adverse reproductive health outcomes, and sequelae such as chronic pelvic pain and infertility also lead to a poor quality of life in people who suffer or have suffered from gonorrhoea.

Strategies for control and prevention

Public health strategies

Prevention of gonorrhoea requires primary, secondary, and tertiary prevention strategies.

Primary prevention involves:

• Community health education on the importance of safer sex practices with emphasis on the use of barrier contraception (such as condoms), and limiting the number of sexual partners
• Improvement of socio-economic status through education and economic empowerment
• Provision of good living conditions, as gonorrhoea is prevalent in overcrowded settlements

Secondary prevention involves:

• Screening of asymptomatic high-risk individuals
• Early diagnosis of symptomatic patients
• Contact tracing and treatment
• Test of cure

Tertiary prevention involves:

• Proper case management of symptomatic patients
• Treatment failure monitoring
• Management of long-term complications

While primary prevention prevents the development of the disease, secondary prevention allows for early diagnosis and tertiary prevention gives room for the management of complications. Without a strong public health system, these preventive strategies would be suboptimally implemented.

Policy measures

The global public health threat from antimicrobial-resistant gonococcal strains is increasing, therefore international initiatives, cooperation, political will, campaigning, research, and support are required.^15,16

The WHO has identified gonorrhoea as a significant public health threat and has set ambitious targets to reduce the infection burden by 90% in 2030.¹⁵

The WHO global action plan to control the spread and impact of antimicrobial resistance in Neisseria gonorrhoea includes these recommendations:

• Increase in awareness of the appropriate use of antimicrobials 
• Improved prevention, diagnosis and treatment
• Systematic monitoring, early detection and follow-up for treatment failures
• Building of regional laboratory network for gonococcal culture and susceptibility testing
• Effective drug prescription policies
• Quality antimicrobial susceptibility surveillance
• Research to identify model diagnostic methods, antimicrobials, and effective vaccines

If fully implemented, these guidelines will contribute to improved antimicrobial stewardship through rational antibiotic prescribing. They would also help identify gonorrhoea antimicrobial resistance patterns. Global collaboration and a strong political will is needed to actualise this.

FAQ’s

How does gonorrhoea affect reproduction in women?

Gonorrhoea can extend to the uterus and fallopian tubes, resulting in pelvic inflammatory disease (PID). PID can cause scarring of the tubes, an increased risk of pregnancy problems, and infertility.

Does gonorrhoea reduce sperm count?

Gonorrhoea does not cause a reduction in the production of sperm. The inflammation that is associated with the infection may cause scarring of the passage leading to obstruction of the release of sperm.

Does gonorrhoea infection confer immunity?

It is known that gonorrhoea can be acquired repeatedly without the development of protective immunity from earlier infections. However, research is being performed to find a suitable vaccine.

Summary

Gonorrhoea remains a growing public health concern due to challenges in inappropriate diagnosis and treatment. Preventive strategies using the public health approach and cross-country policy interventions are crucial. There have been multiple failed attempts at developing an effective vaccine but recent evidence shows that the meningococcal vaccine may provide some level of cross-protection: this holds promise for the future. Robust epidemiological surveillance is needed to track trends globally.