Screening and Diagnostic Methods for Gonorrhea
Published on: October 11, 2024
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Bibek Rana Chhetri

Masters in Science- Biomedical Sciences, <a href="https://www.chester.ac.uk/" rel="nofollow">University of Chester, UK</a>

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Alejandra Briones

Bsc in Biomedical Sciences, University of Bristol

Did you know that regular gonorrhoea screening can lower the risk of severe health complications, such as pelvic inflammatory disease and infertility, significantly? In addition, early detection and treatment can prevent the spread of antibiotic-resistant strains and reduce the risk of HIV transmission. This article discusses the importance of effective screening and diagnostic methodologies for a highly contagious sexually transmitted infection caused by Neisseria gonorrhoeae.

The article aims to increase awareness among readers regarding recent best practices and innovative technologies involved in the diagnosis of gonorrhoea. However, the three most important take-home points include the following: the critical role of routine screening, particularly in asymptomatic and high-risk populations, the effectiveness of advanced diagnostic tools, like NAATs, and the necessity of addressing challenges, like antibiotic resistance and accessibility to testing.

Gonorrhea and the significance of screening and diagnosis

Gonorrhea is a highly prevalent sexually transmitted infection caused by the bacterium Neisseria gonorrhoeae. It mainly infects mucous membranes of the urethra, cervix, rectum, throat, and eyes. The mode of transmission of the disease is through sexual contact, including vaginal, anal, and oral intercourse.1

Why screening and diagnosing?

Public health impact: Gonorrhea is highly infective and can lead to significant complications like pelvic inflammatory disease in females and epididymitis in males, which can result in infertility. It also increases the risk of HIV transmission.

Asymptomatic infections: Most infections are asymptomatic, spreading unnoticed. Regular screening, especially in high-risk populations, is essential to detect and treat these unnoticed infections.

Bacterial resistance to antibiotics: Neisseria gonorrhoeae has developed resistance to many antibiotics, presenting a treatment challenge. Early diagnosis and appropriate treatment are crucial to controlling resistance and preventing complications.

Pregnancy and neonatal care: Untreated gonorrhoea can be transmitted from mother to baby during delivery, causing severe neonatal complications. Routine screening and treatment in pregnancy care are necessary to avoid further complications in neonatal health.

Target population 

High-risk groups

  • Sexually active adolescents and young adults (15-24 years)
  • Men having sex with other men 
  • People with multiple sex partners
  • People with a history of other sexually transmitted infections
  • Sex workers and their clients2

General population

People are at risk of sexual exposure in areas with a high prevalence of gonorrhoea. Further, sexually active women <25 years of age and older women with risk factors, such as new or multiple sex partners or a sex partner with an STI

Screening tests

Nucleic acid amplification tests (NAATs)

NAATs identify the genetic material (DNA or RNA) of Neisseria gonorrhoeae. These are highly sensitive and specific tests and thus, are the gold standard for screening and diagnosis. Types of NAATs commonly used: Polymerase chain reaction (PCR), Transcription-mediated amplification (TMA), Strand displacement amplification (SDA).3,4

Culture

Neisseria gonorrhoeae is a fastidious bacteria that grows on selective culture media. Culture is, therefore, one of the ways of isolating the organism. Although cultures are considered a gold standard, they require proper sample handling and laboratory facilities. Cultures are highly specific and offer added benefits in terms of antimicrobial resistance testing, but are less sensitive than NAATs and take longer to produce results.

Point-of-care tests (PoCT)

PoCT provides quick results, often within one visit. This is essential when immediate treatment is necessary for a patient. Examples include immunochromatographic assays. The disadvantage is that they generally have lower sensitivity than do the nucleic acid amplification tests. They are, however, useful in settings where it is important to make quick decisions.5

Guidelines for screening

Recommendations by CDC and WHO

The CDC recommends annual screening for sexually active women <25 years of age, older women with risk factors, and MSM.6

Recommendation by the WHO, and the need for the screening is more in the area with high prevalence and in the high-risk groups.

Frequency

High-risk groups: Ideally, it should be yearly, but for MSM and the ones involved with multiple or anonymous partners, the time gap is 3–6 months.

General population: Again the time frame of screening will depend on the individual risk assessment and local epidemiology, but for those with higher risk, sexually active people in a high-risk area should be screened annually.

Diagnostic methods

Common symptoms in male

Common symptoms in female 

However, among many women, the symptoms could be absent, while among others, they might remain very mild, such that they tend to ignore them.

Asymptomatic cases- A considerable percentage of the population, of both males and females, remains asymptomatic. This makes routine screening for the infection critical in the population that one expects such silent cases.

Physical examination findings- Patients might present with the following signs of infection: cervical motion tenderness, adnexal tenderness, mucopurulent cervical, or urethral discharge in females and purulent discharge in males.7

Laboratory diagnosis

Specimen collection

Types of specimens: Specimens for gonorrhoea testing may include

  • Urine
  • Urethral swabs (male)
  • Cervical swabs (females)
  • Rectal and pharyngeal swabs, especially in MSM and other individuals with oral or anal sex

Proper collection techniques: Specimen collection is the most critical step as far as the diagnosis is concerned. Urine specimens must be first-void urine of the day, while swabs must be collected from the target site using appropriate techniques.

Nucleic acid amplification tests (NAATs)

NAATs are designed to be very sensitive and specific for detecting Neisseria gonorrhoea. They can detect the presence of either bacterial DNA or RNA in several specimen types.8

Culture methods

Isolation of Neisseria gonorrhoeae- Neisserial cultures may grow on selective media. Cultures are used to confirm infection. They are also used for the purpose of antimicrobial susceptibility testing. In the light of growing antibiotic resistance, such testing is paramount to help in determining the best options for treatment.9

Gram stain

In Gram staining, bacteria are stained and viewed under a microscope. This method can be used to diagnose the disease quickly, and it is particularly useful among symptomatic men who have urethral discharge. These tests are highly specific if positive; its sensitivity, however, is relatively lower as compared to NAATs. This method is therefore less reliable, especially in asymptomatic cases and women.9

Serological tests

Serological tests are not widely used to diagnose gonorrhoea simply because they are not very effective if used to diagnose current infections. These tests are mostly of relevance in the case of other STIs.9

Emerging diagnostic technologies

CRISPR-based detection: Development of diagnostic tools from CRISPR/Cas systems best known for their genome-editing functions. CRISPR-based diagnostic systems can target very specific segments of the genetic material in Neisseria gonorrhoeae. It demonstrates high sensitivity and specificity. May be rapidly done at the point-of-care and can, therefore, be used in different settings.10

Multiplex PCR: Simultaneous detection of a variety of pathogens, including Neisseria gonorrhoeae and Chlamydia trachomatis. Better diagnostic efficiency since multiple tests are done at the same time, consequently enables clinician better management of patients and facilitating provision of necessary treatment.11

Biosensors: Biosensors are the analytical device that converts a biological response into an electrical signal. In Gonorrhoea, its detection is based on the identification of the specific bacterial constituent or its sequence. This offers rapid, accurate and inexpensive diagnostics and is, therefore, perfectly designed for widespread use in both clinical and non-clinical settings.12

Whole-genome sequencing: It involves the sequencing of the entire genome of the Neisseria gonorrhoeae bacteria to provide highly detailed information regarding the bacterial strain and its resistance patterns. Thereby aids in understanding the mechanisms of antibiotic resistance and tracking the epidemiology of infections in a bid to guide public health interventions and effective treatment.13

Challenges in screening and diagnosis

Antibiotic resistance

increased prevalence of antibiotic-resistant strains of Neisseria gonorrhoeae complicates the process of the disease treatment and proves to be an efficient challenge for the proper management of the disease. Resistance may cause failures in treatment and that is impossible to rely only on traditional methods of diagnostics to provide proper therapy.14

Need for susceptibility testing

It is necessary to conduct antimicrobial susceptibility testing in the case of the treatment of resistant strains beside routine diagnostic procedures. This is implemented with the help of the use of culture techniques that will reveal the strains of the bacteria susceptible to this or that antibiotic and hence lead to the targeted and efficacious treatment.

Asymptomatic infections

Gonorrhea is asymptomatic in most cases, especially among women; the screening and treatment procedure of this disease must not be based solely on clinical manifestations of issues: Asymptomatic carriers can spread the disease unknowingly further. 

Strategies for improving the detection

  • Increased level of general screening, public health campaigns, and patient education regarding the risks of STI
  • Periodic screening of high-risk groups, the use of highly sensitive diagnostic tests, like NAATs, and general increasing of awareness have to be implemented to provide the detection of asymptomatic carriers
  • Access for testing: Inadequate access to screening and diagnostic services, particularly in rural and low-income areas, due to the lack of healthcare system establishments and economic constraints

Summary

Overall, effective gonorrhoea screening and diagnostic strategies are necessary for the control of this sexually transmitted infection of serious public health concern. The majority of these infections are asymptomatic, hence, there is an importance of regular screening, especially among high-risk populations. NAATs are the preferred approach due to their excellent sensitivity and specificity.

The most promising methods for rapid and reliable diagnosis are multiplex PCR, CRISPR-based technologies, and smartphone diagnostics. To ensure prompt and efficient treatment, reduce transmission, and improve outcomes, it is imperative to address issues such as antibiotic resistance, asymptomatic patients, and access constraints.

References

  1. Gonorrhoea [Internet]. 2010 [cited 2024 Jun 6]. Available from: https://www.ecdc.europa.eu/en/gonorrhoea
  2. Kirkcaldy RD, Weston E, Segurado AC, Hughes G. Epidemiology of gonorrhea: a global perspective. Sex Health [Internet]. 2019 Sep [cited 2024 Jun 6];16(5):401–11. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064409/
  3. US Preventive Services Task Force. Screening for chlamydia and gonorrhea: us preventive services task force recommendation statement. JAMA [Internet]. 2021 Sep 14 [cited 2024 Jun 6];326(10):949–56. Available from: https://doi.org/10.1001/jama.2021.14081
  4. Bachmann LH, Johnson RE, Cheng H, Markowitz LE, Papp JR, Hook EW. Nucleic acid amplification tests for diagnosis of neisseria gonorrhoeae oropharyngeal infections. J Clin Microbiol [Internet]. 2009 Apr [cited 2024 Jun 6];47(4):902–7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668347/
  5. Gaydos CA, Melendez JH. Point-by-point progress: gonorrhea point of care tests. Expert Rev Mol Diagn [Internet]. 2020 Aug [cited 2024 Jun 6];20(8):803–13. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483383/1.
  6. National Academies of Sciences E, Division H and M, Practice B on PH and PH, States C on P and C of STI in the U, Crowley JS, Geller AB, et al. Sti screening and treatment guidelines issued by health professional societies. In: Sexually Transmitted Infections: Adopting a Sexual Health Paradigm [Internet]. National Academies Press (US); 2021 [cited 2024 Jun 6]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK573163/1.
  7. Van Ommen CE, Malleson S, Grennan T. A practical approach to the diagnosis and management of chlamydia and gonorrhea. CMAJ [Internet]. 2023 Jun 19 [cited 2024 Jun 6];195(24):E844–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281205/
  8. Whiley DM, Tapsall JW, Sloots TP. Nucleic acid amplification testing for neisseria gonorrhoeae. J Mol Diagn [Internet]. 2006 Feb [cited 2024 Jun 6];8(1):3–15. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1871692/
  9. Ng LK, Martin IE. The laboratory diagnosis of Neisseria gonorrhoeae. Can J Infect Dis Med Microbiol [Internet]. 2005 [cited 2024 Jun 6];16(1):15–25. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095009/1.
  10. Tu Q, Cao X, Ling C, Xiang L, Yang P, Huang S. Point-of-care detection of Neisseria gonorrhoeae based on RPA-CRISPR/Cas12a. AMB Express [Internet]. 2023 May 27 [cited 2024 Jun 6];13:50. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10224890/
  11. O’Callaghan I, Corcoran D, Lucey B. Design of a multiplex PCR assay for the simultaneous detection and confirmation of Neisseria gonorrhoeae. J Clin Pathol. 2010 May;63(5):431–3.
  12. Singh R, Sumana G, Verma R, Sood S, Pandey MK, Gupta RK, et al. DNA biosensor for detection of Neisseria gonorrhoeae causing sexually transmitted disease. J Biotechnol. 2010 Nov;150(3):357–65.
  13. Abrams AJ, Trees DL. Genomic sequencing of Neisseria gonorrhoeae to respond to the urgent threat of antimicrobial-resistant gonorrhea. Pathog Dis [Internet]. 2017 Jun 1 [cited 2024 Jun 6];75(4):10.1093/femspd/ftx041. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956991/1.
  14. Unemo M, Del Rio C, Shafer WM. Antimicrobial resistance expressed by neisseria gonorrhoeae : a major global public health problem in the 21st century. Scheld WM, Hughes JM, Whitley RJ, editors. Microbiol Spectr [Internet]. 2016 May 6 [cited 2024 Jun 6];4(3):4.3.35. Available from: https://journals.asm.org/doi/10.1128/microbiolspec.EI10-0009-2015

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Bibek Rana Chhetri

Masters in Science- Biomedical Sciences, University of Chester, UK

Bibek, from Nepal, is a burgeoning scholar in the field of Biomedical Sciences, currently advancing his studies with a Master’s degree at the University of Chester, UK. His academic journey began with a Bachelor’s degree in Microbiology from St. Xavier’s College, Nepal, where he first cultivated his deep-seated enthusiasm for microbiology. With a robust background as a public health content writer back home, Bibek has successfully bridged the gap between scientific inquiry and public engagement. He has contributed to diverse research projects, including original research, narrative reviews, systematic reviews, and meta-analyses, demonstrating a keen aptitude for critical scientific evaluation and data synthesis. Bibek’s commitment to the microbiological sciences continues to grow as he contributes to the scientific community and healthcare advancements.

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