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Indication - Sexually transmitted infections
Qualitative nucleic acid test (NAT) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections
Facility level:
2. Laboratory
Assay formats
NAT
Status history
First added in 2019
Changed in 2020
Purpose type
Diagnosis
Purpose
To diagnose chlamydial and/or gonorrhoeal urogenital disease and extragenital infection
Specimen types
Urine, urethral swabs, endocervical swabs, vaginal swabs, rectal swabs, oropharyngeal swabs, Liquid cytology
WHO prequalified or recommended products
N/A
WHO supporting documents
WHO sexually transmitted infection laboratory manual https://apps.who.int/iris/handle/10665/85343; Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations https://apps.who.int/iris/handle/10665/246200
Codes
ICD11 code: 1A9Z

Summary of evidence evaluation

The accuracy of these tests is difficult to assess in the absence of a good reference standard; assessments rely on methods such as latent class analyses or comparison with panels of alternative tests. No good systematic review of the accuracy of these tests was provided. One sound study with a reasonable sample size supports the claim made in non-systematic reviews that laboratory-based tests are highly accurate (4). Many of the other supporting primary studies are based on very few cases. Additional evaluations are required, particularly for new cartridge-based methods.

Summary of SAGE IVD deliberations

Although the analytical performance varies by assay, the sensitivity of tests for C. trachomatis is 91–100%, the specificity is 98–100%, the positive predictive value for symptomatic patients is > 90%, and the negative predictive value is > 98.8%; and the sensitivity of tests for N. gonorrhoeae is 97.7–100%, the specificity is 99.6–100%, the positive predictive value for symptomatic patients is 89.4–100%, and the negative predictive value is ≥ 99.9%. The tests are FDA- approved or CE-marked, although local vendors might require validation or verification. No evidence was provided of the impacts of these tests in clinical practice. There are UNAIDS/WHO guidelines for the test for N. gonorrhoeae, and both organisms are high priorities for surveillance.

SAGE IVD recommendation

The SAGE IVD recommended inclusion on the EDL of nucleic acid testing for C. trachomatis and N. gonorrhoeae. They noted that the tests are reliable, with high diagnostic accuracy, that appropriate tests with high sensitivity are essential for surveillance of these diseases and that the tests have been on the market for a number of years. The Group considered that the test should be included only for testing in tertiary laboratories but that it could be considered for use at primary care level in the future.

Details of submission from 2020

Background

Disease condition and impact on patients: Sexually transmitted infections compromise fertility, reproductive health and birth outcomes. Testing and treatment of these infections prevent these sequelae. Untreated women have chronic pelvic pain and may have ectopic pregnancies and be infertile. Infants born to untreated pregnant women may have eye infections (gonococcal ophthalmia) or pneumonia and be premature, with a low birth weight. Does this test meet a medical need? Diagnosis of gonorrhoea and chlamydia in symptomatic and asymptomatic people guides treatment and management of both patients and partners. High-risk women on HIV pre-exposure prophylaxis should be tested for these infections for prevention of mother-to- child transmission. How the test is used: Single test for symptomatic testing and asymptomatic screening.

Public health relevance

Prevalence: The prevalence of C. trachomatis is estimated at 3.8% in women and 2.7% in men, whereas that of N. gonorrhoeae is estimated to be 0.9% in women and 0.7% in men (1). Socioeconomic impact: Costs are related to complications of untreated infections. N. gonorrhoeae shows AMR.

WHO or other clinical guidelines relevant to the test

The WHO Reproductive Health and Research department is conducting an independent evaluation in several countries of a molecular-based IVD for diagnosis of chlamydia and gonorrhoea to improve access to testing in populations mainly in LMICs. Guidelines for sexually transmitted infections (2) recommend etiological diagnosis for N. gonorrhoeae (minimal standard); both C. trachomatis and N. gonorrhoeae are high-priority pathogens for surveillance.

Evidence for clinical usefulness and impact

These IVDs are the primary means of screening for and diagnosing chlamydia and gonorrhoea in most countries with the necessary laboratory infrastructure. Evidence of impact may not be relevant. According to the US Centers for Disease Control and Prevention (3): The sensitivity and specificity of the NAATs are higher than those of any other test, and there is no justification for use of tests such as EIAs or DNA probe assays, which have inferior performance. No point‐of‐care assays are available that are suitable for routine use, although some may be used in high-risk populations who require immediate treatment because of poor follow-up. Testing for both gonorrhoea and chlamydia should be available in at least some reference laboratories, as N. gonorrhoeae culture is the only method for monitoring resistance to current treatment regimens.

Evidence for economic impact and/or cost–effectiveness

Some training is required to conduct these tests, which are the gold standard for screening and diagnosis of chlamydia and gonorrhoea. Their inclusion in a health care system might require resources, particularly in countries where access to these diagnostics is not yet available or is limited. The cost varies by manufacturer, but the health benefits override the potential costs because of reduced cost for complications of untreated infection. In high-prevalence settings, the cost–benefit ratio is acceptable. As infections may be asymptomatic, prevention of their spread and the associated morbidity justifies testing in all risk categories, as the ontological risk may be greater than the epistemological risk.

Ethical issues, equity and human rights issues

Consent is required to obtain a sample.
1. Rowley J, Vander Hoorn S, Korenromp E, Low N, Unemo M, Abu-Raddad LJ, et al. Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016. Bull World Health Org. 2019;97:548–62. 2. UNAIDS/WHO Working Group on Global HIV/AIDS and STI Surveillance. Strategies and laboratory methods for strengthening surveillance of sexually transmitted infections. Geneva: UNAIDS, World Health Organization; 2012 (https://apps.who.int/iris/bitstream/handle/10665/75729/ 9789241504478_eng.pdf?sequence=1, accessed September 2019). 3. Laboratory diagnostic testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Expert consultation meeting summary report. Atlanta (GA): Centers for Disease Control and Prevention; 2009. 4. Van Der Pol B, Liesenfeld O, Williams JA, Taylor SN, Lillis RA, Body BA, et al. Performance of the cobas CT/NG test compared to the Aptima AC2 and Viper CTQ/GCQ assays for detection of Chlamydia trachomatis and Neisseria gonorrhoeae. J Clin Microbiol. 2012;50(7):2244–9.