Review
Accelerating worldwide syphilis screening through rapid testing: a systematic review

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Summary

Syphilis is a persistent public health issue in many low-income countries that have limited capacity for testing, which traditionally relies on a sensitive non-treponemal test and then a specific treponemal test. However, the development of a new rapid treponemal test provides an opportunity to scale up syphilis screening in many settings where traditional tests are unavailable. This systematic review of immunochromatographic strip (ICS) syphilis tests describes the sensitivity and specificity in two important clinical settings: sexually transmitted infection (STI) clinics and antenatal clinics. Clinical data from more than 22 000 whole blood, plasma, or fingerstick ICS tests obtained at STI or antenatal clinics were retrieved from 15 studies. ICS syphilis tests have a high sensitivity (median 0·86, interquartile range 0·75–0·94) and a higher specificity (0·99, 0·98–0·99), both comparable with non-treponemal screening test characteristics. Further research evaluating ICS syphilis tests among primary syphilis cases and among patients infected with HIV will be essential for the effective roll-out of syphilis screening programmes.

Introduction

Syphilis continues to be a major global health threat causing an estimated 12 million infections each year,1 despite the known adverse effects on pregnancy2 and the synergistic relation with HIV infection.3 About 90% of these syphilis cases are in low-income countries4, 5 where traditional syphilis tests are often unreliable6 or unavailable.7, 8 The mismatch between syphilis burden and diagnostic capacity in many regions has stalled efforts to meet syphilis control guidelines9, 10, 11, 12 that call for more widespread screening of syphilis. New point-of-care rapid treponemal diagnostic tests hold promise for syphilis screening at a range of clinical8, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 and non-clinical settings,7, 23 providing an opportunity to accelerate syphilis screening.24, 25 Although there are several rapid tests for syphilis,7, 26 this Review focuses on syphilis testing that uses an immunochromatographic strip (ICS) to detect Treponema pallidum antibody, because the test has been evaluated in more clinical settings than have others.8 ICS syphilis tests are simple, inexpensive, and do not need refrigeration or highly trained laboratory personnel (figure 1).27

Although laboratory research suggests treponemal rapid tests have specificity and sensitivity similar to those of traditional non-treponemal tests, no systematic analysis of rapid syphilis tests in clinical settings exists (table 1). Treponemal tests will remain positive for an individual's life, which has important implications for the interpretation of syphilis tests. Previous reviews of syphilis testing were done before the development of rapid tests,28 focused on WHO rapid test benchmarks,7 and reviewed the clinical use in diagnostic algorithms.31 We systematically analysed ICS syphilis testing with a focus on low-income countries that are challenged by the provision of traditional serological syphilis testing. The ASSURED criteria,29 from the WHO Sexually Transmitted Diseases Diagnostic Initiative, established benchmarks for evaluating rapid tests for sexually transmitted infections (STIs): a cost of less than US$3·0, user friendly (3–4 steps), rapid (20-min turnaround) and robust (stored at 8–30°C), equipment free, and deliverable. STI clinics and antenatal clinics were chosen instead of non-clinical settings because they are important in current syphilis control programmes and are the most common sites in which ICS syphilis testing is used. The purpose of this Review is to first analyse the test characteristics of new ICS syphilis tests and then do subgroup analyses to establish if syphilis clinical stage of infection, non-treponemal syphilis titre, HIV co-infection, clinic type (antenatal vs STI), specimen type, or ICS syphilis test manufacturer affected test characteristics.

Section snippets

Search strategy and selection criteria

The search strategy selected research papers that retrospectively analysed ICS syphilis test characteristics at STI clinics and antenatal clinics. The search of published work was done in several phases and PRISMA guidelines were used. Potentially relevant articles were selected from PubMed and Embase. Search terms included “syphilis” OR “Treponema pallidum” combined with the subject headings: “immunochromatographic”, “rapid”, “test”, “screening”, “serology”, “serologic”, and “diagnostic”.

Results

The initial search identified a total of 823 citations, including both published work and conference abstracts (figure 2). Most studies were excluded because they used archived blood samples instead of samples collected and immediately tested at clinics. Archived samples were not included in the analysis because ICS syphilis test manufacturers recommend immediate testing and studies of other treponemal tests suggest that this would influence test characteristics.27 Several studies reported

Discussion

Syphilis control programmes have increasingly adopted initial treponemal tests in high-income countries because of their high specificity28, 39, 40, 41 and potential for scale-up in commercial laboratories,42 but dependence on skilled laboratory staff and tertiary laboratory facilities28 continue to make traditional treponemal testing impractical in the low-income countries disproportionately affected by syphilis. ICS syphilis tests are simple, rapid, inexpensive, and might help expand syphilis

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    These authors contributed equally

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