Indication - Sexually transmitted infections
Antibodies to T. pallidum and to HIV-1/2 (anti-HIV Ab)
First added in 2019
Changed in 2020
Aid to diagnosis, Diagnosis
To diagnose or to aid in the diagnosis of HIV-1/2 infection and/or syphilis
Venous whole blood, Plasma, Serum
WHO prequalified or recommended products
Public reports of WHO prequalified IVDs https://extranet.who.int/pqweb/vitro-diagnostics/prequalification-reports/whopr?field_whopr_category=57
WHO supporting documents
WHO Information note on the use of dual HIV/syphilis rapid diagnostic tests (RDT) (2017) http://apps.who.int/iris/handle/10665/252849/ ; Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations https://apps.who.int/iris/handle/10665/246200
ICD11 code: 1A9Z
Summary of evidence evaluation
Supporting evidence is provided in the WHO guideline, which is based on many systematic reviews. The guideline provides appropriate testing algorithms with rapid plasma reagin, VDRL, TPPA and TPHA, which are based on a cost– effectiveness model. Few relevant data were provided on the performance of each test.
Summary of SAGE IVD deliberations
Untreated syphilis in pregnancy is a major cause of death and stillbirths, preterm or low-birth-weight infants, neonatal death and syphilis infections in infants. Use of rapid plasma reagin, VDRL, TPPA and TPHA for the detection of T. pallidum is recommended in an evidence-based WHO guideline. A systematic review indicated high sensitivity of the qualitative point-of-care rapid plasma reagin test, and the accuracy of the rapid syphilis test is estimated to be higher. Accuracy is difficult to determine, however, as it depends on the stage of syphilis and the type of test.
SAGE IVD recommendation
The SAGE IVD recommended inclusion in the EDL of serological tests for detection of T. pallidum, noting that the five proposed tests would be valuable for other uses. The rapid plasma reagin test is useful for screening, the VDRL for diagnosis of neurosyphilis, EIA for testing large blood volumes before transfusion and TPPA and TPHA for screening blood and for confirmatory testing.
Details of submission from 2020
Disease condition and its impact on patients: Over 50% of women with untreated syphilis will experience an adverse birth outcome. If left untreated, syphilis causes damage to the brain, eyes and nerves. Does the test meet a medical need? The tests allow accurate diagnosis and differentiation between acute, latent and tertiary infections and other treponematoses. As a consequence of diagnosis, appropriate treatment and follow-up to prevent transmission, including mother-to-child transmission, may be given. How the test is used: Syphilis testing can be performed in a laboratory with an algorithm that includes treponemal and non-treponemal antibody assays. Patients are usually screened with a non-treponemal test, and positive results are confirmed by treponemal testing.
Public health relevance
Prevalence: Syphilis is the second most common infectious cause of stillbirth globally (1). Over 50% of women with untreated syphilis will experience an adverse birth outcome. In 2016, WHO estimated that > 350 000 adverse birth outcomes occurred among 1 million pregnant women with syphilis and 6.3 million new syphilis infections occurred among adults. Socioeconomic impact: Untreated syphilis in pregnancy is a major cause of deaths and stillbirths, preterm or low-birth-weight infants, neonatal death and syphilis infections in infants. An IVD for diagnosis of treponemal disease would advance efforts towards the global elimination of congenital syphilis.
WHO or other clinical guidelines relevant to the test
2013. Laboratory diagnosis of sexually transmitted infections, including human immunodeficiency virus. 2016. Global health sector strategy on sexually transmitted infections 2016–2021: towards ending STIs 2016. Report on global sexually transmitted infection surveillance. 2016. Guidelines for the treatment of Treponema pallidum (syphilis) 2017. Global guidance on criteria and processes for validation: elimination of mother-to-child transmission of HIV and syphilis. 2017. Guideline on syphilis screening and treatment for pregnant women. The recommended strategies include use of a rapid syphilis test (not included in the EDL submission), the rapid plasma reagin test, the VDRL test, TPPA and TPHA. EIA is not mentioned.
Evidence for clinical usefulness and impact
The tests allow accurate diagnosis and differentiation between acute, latent and tertiary syphilis as well as other treponematoses. As a consequence of diagnosis, appropriate treatment and follow-up can be given to treat infections and prevent transmission, including from mother to child.
Evidence for economic impact and/or cost–effectiveness
The additional cost for extension of use of these tests will be outweighed by the cost of negative health outcomes.
Ethical issues, equity and human rights issues
Consent is required to obtain a blood sample. Lack of access to these essential testing modalities can result in inequitable care and treatment.
1. Laboratory diagnosis of sexually transmitted infection, including human immunodeficiency virus. Geneva: World Health Organization; 2013 (http://www.who.int/reproductivehealth/publications/ rtis/9789241505840/en/, accessed September 2019).