ReviewAccelerating worldwide syphilis screening through rapid testing: a systematic review
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
References (45)
- et al.
Avoiding HIV and dying of syphilis
Lancet
(2004) - et al.
Global control of sexually transmitted infections
Lancet
(2006) - et al.
Diagnostic value of interferon-γ in tuberculous pleurisy: a metaanalysis
Chest
(2007) - et al.
Diagnostic accuracy of nucleic acid amplification tests for tuberculous meningitis: a systematic review and meta-analysis
Lancet Infect Dis
(2003) Global prevalence and incidence of selected curable sexually transmitted infections: overview and estimates
(2001)- et al.
Syphilis in pregnancy and the neonatal period
Int J STD AIDS
(2006) - et al.
Syphilis and HIV infection: an update
Clin Infect Dis
(2007) - et al.
The pathogenesis of syphilis: the Great Mimicker, revisited
J Pathol
(2006) A blood-result turn-around time survey to improve congenital syphilis prevention in a rural area
S Afr Med J
(1996)- et al.
Rapid tests for sexually transmitted infections (STIs): the way forward
Sex Transm Infect
(2006)
Prospective, multi-centre clinic-based evaluation of four rapid diagnostic tests for syphilis
Sex Transm Infect
USPSTF recommendations for STI screening
Am Fam Physician
What's new in management of sexually transmitted infections? Canadian Guidelines on Sexually Transmitted Infections, 2006 Edition
Can Fam Physician
Developing evidence-based guidelines for the management of sexually transmitted diseases in former Soviet Union countries
Int J STD AIDS
UK National Guidelines on the Management of Syphilis 2008
Int J STD AIDS
Performance of rapid syphilis tests in venous and fingerstick whole blood specimens
Sex Transm Dis
Diagnostic accuracy of a point-of-care syphilis test when used among pregnant women in Bolivia
Sex Transm Infect
Performance and costs of a rapid syphilis test in an urban population at high risk for sexually transmitted infections
J Prev Med Hyg
Field evaluation of the performance and testing costs of a rapid point-of-care test for syphilis in a red-light district of Manaus, Brazil
Sex Transm Infect
Field evaluation of simple rapid tests in the diagnosis of syphilis
Int J STD AIDS
Performance of the rapid plasma reagin and the rapid syphilis screening tests in the diagnosis of syphilis in field conditions in rural Africa
Sex Transm Infect
Maternal and congenital syphilis in two Mexican hospitals: evaluation of a rapid diagnostic test
Rev Invest Clin
Cited by (0)
- ‡
These authors contributed equally