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Why do we need quality-assured diagnostic tests for sexually transmitted infections?

Key Points

  • Bacterial sexually transmitted infections (STIs) cause a huge burden of morbidity and mortality that is borne disproportionately by women and infants. Three bacterial STIs are discussed in this article: syphilis (caused by Treponema pallidum), gonorrhoea (caused by Neisseria gonorrhoeae) and genital chlamydia (caused by Chlamydia trachomatis).

  • Syphilis causes 30–50% of stillbirths in Africa and kills more than 1-million babies each year worldwide. The biology and pathogenesis of T. pallidum and the clinical manifestations of primary, secondary and tertiary syphilis are briefly reviewed.

  • The diagnostic tests for syphilis are then discussed. These fall into two categories — non-treponemal and treponemal-specific tests. Non-treponemal tests include the rapid plasma reagin (RPR) test. Although these tests can distinguish between active and past infections, they can generate false-negative results from the prozone effect and false-positive results in patients with other diseases including malaria, leprosy and some chronic tissue-damaging diseases.

  • Treponemal-specific tests include the T. pallidum haemagglutination assay, T. pallidum particle agglutination assay and the fluorescent treponemal antibody absorption test. These tests cannot distinguish between active and past infection. Treponemal rapid diagnostic tests (RDTs) are available and can be used in settings where laboratory services and electricity supplies are unreliable or absent. They can use whole blood rather than serum, and have reasonable sensitivities and specificities compared with laboratory-based treponemal tests. The disadvantage of RDTs is that they cannot distinguish between prior treated and active infection.

  • Gonorrhoea and genital chlamydia are the main causes of pelvic inflammatory disease, tubal infertility and ectopic pregnancy in women in developing countries, and the ocular infections gonococcal ophthalmia and trachoma are among the leading preventable causes of blindness. The biology and pathogenesis of C. trachomatis and N. gonorrhoeae and the clinical manifestations of primary, secondary and tertiary syphilis are briefly reviewed.

  • The diagnostic tests for gonorrhoea and chlamydia are then discussed. The reference standard for the laboratory diagnosis of gonococcal infection remains bacterial culture. The available enzyme immunoassays have reasonable specificity but are insufficiently sensitive. The sensitivity and specificity of nucleic-acid amplification tests (NAATs) is good, and non-invasive specimens such as urine or minimally invasive specimens such as vaginal swabs can be used. but there can be cross-reactivity with other Neisseria species.

  • The reference standard for the laboratory diagnosis of genital chlamydial infection is a NAAT. Several chlamydial NAATs are commercially available and some offer duplex testing for both chlamydial and gonococcal infections.

  • RDTs for the diagnosis of chlamydial and gonococcal infection include microscopy of a Gram-stained smear of genital discharge from infected patients for gonorrhoea and point of care (POC) immunoassays for both infections. POC immunoassays are designed as immuno-chromatographic strips (ICSs), often encased in a plastic cassette. Two main disadvantages of these RDTs are they are expensive and require many processing steps.

Abstract

The bacterial sexually transmitted infections (STIs) syphilis, gonorrhoea and chlamydia can all be cured with a single dose of antibiotic. Unfortunately, however, these infections often remain undiagnosed as many infected individuals have few if any symptoms. Diagnostic tests with high sensitivity and specificity are available for all three infections but, owing to their expense and the lack of laboratory capacity, most people in developing countries do not have access to these tests. There is a great need for simple, cheap diagnostic tests for STIs that can be performed at the point of care, enabling treatment to be given immediately. It is hoped that recent advances in our understanding of the pathogenesis of these infections, and the availability of the complete genome sequences for each causative organism, will lead to the development of improved point-of-care tests that will reduce the burden of these diseases in developing countries.

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Figure 1: Estimated new cases of curable sexually transmitted infections among adults.
Figure 2: The rapid plasma reagin test.
Figure 3: The rapid diagnostic test for syphilis.
Figure 4: Schematic representation of a rapid point-of-care test for chlamydia diagnosis.

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Correspondence to Rosanna W. Peeling.

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DATABASES

Entrez Genome Project

C. trachomatis serovar A

C. trachomatis serovar D

Neisseria gonorrhoeae

Treponema pallidum

UniprotKB

TprK

FURTHER INFORMATION

Center for Disease Control and Prevention

Neisseria gonorrhoeae strain FA1090 genome sequence

WHO SDI

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Peeling, R., Mabey, D., Herring, A. et al. Why do we need quality-assured diagnostic tests for sexually transmitted infections?. Nat Rev Microbiol 4, 909–921 (2006). https://doi.org/10.1038/nrmicro1555

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