I searched PubMed to identify peer-reviewed articles published in English between Jan 1, 2005, and June 30, 2016, using the terms “syphilis”, “syphilis epidemiology”, and “syphilis treatment”. I also referred to older literature on management and clinical presentations of the disease written in the pre-penicillin era.
SeminarSyphilis
Introduction
Syphilis is a chronic bacterial infection caused by Treponema pallidum, subspecies pallidum. The disease has been recognised by clinicians and the general public for hundreds of years. Over the same period, the disease has been highly stigmatised, which has hampered intervention strategies such as screening and partner notification.1 In low-income and middle-income countries (LMICs), syphilis infection is a relatively common problem that is a source of substantial morbidity, including adverse pregnancy outcomes and acceleration of HIV transmission.2 By contrast, in western Europe and the Americas, disease rates have tended to fluctuate periodically, challenging both clinicians and public health practitioners during highs then declining after strengthened control efforts, only to re-emerge after a period of lower disease incidence.3, 4, 5 Syphilis incidence has again begun to increase dramatically in western Europe and the Americas, and now disproportionately occurs among men who have sex with men (MSM).3, 4, 5
Clinical manifestations, transmissibility to others, and recommended treatment vary over the natural history of infection.6 Although readily recognisable in name to both clinicians and the general public, control efforts have sometimes been hampered by poor familiarity with syphilis clinical manifestations, diagnosis, and management. In this Seminar I will review the current epidemiology of syphilis and diagnosis and management strategies for general clinicians; a group who are now increasingly likely to see patients with current or past infection.
Section snippets
Epidemiology
Worldwide more than 5 million new cases of syphilis are diagnosed every year, with most infections occurring in LMICs where infections are endemic and congenital infections are not uncommon.2, 3 Led by WHO, antenatal screening programmes have reduced maternal and infant syphilis by more than one third, and congenital syphilis has been eliminated in at least one nation (Cuba).3 By contrast, in higher-income countries, infection is less common and occurs disproportionately in people living on the
Pathogenesis
Syphilis is caused by Treponema pallidum, subspecies pallidum, a long thin (from 0·15 μm by 6 μm to 15 μm), slowly growing bacterium that cannot be cultured for clinical purposes. T pallidum, subsp pallidum is closely related (>99% DNA homology) to other pathogenic spirochaetes including T pallidum subsp pertenue, the causative agent of yaws, and Treponema carateum, the organism that causes pinta.18 The high degree of DNA homology between subspecies has permitted use of syphilis serological
Clinical presentations and natural history
The natural history of syphilis is one of a chronic infection that can cause a series of highly variable clinical manifestations during the first 2–3 years of infection, followed by a typically prolonged latent stage that can evolve into clinically apparent tertiary infection stage years or even decades after initial infection.6, 20 Because syphilis lesions are often asymptomatic and can occur in regions of the body where they might go unnoticed, not all infected people have classic signs of
Neurological involvement in syphilis
Neurosyphilis is a feared but poorly understood complication of infection that can occur at any time during the course of infection.20, 24 T pallidum and cerebrospinal fluid (CSF) abnormalities can be detected in the CNS in a substantial proportion of patients with early syphilis, many of whom do not have obvious neurological signs or symptoms.25, 26 The importance of invasion and its impact on therapeutic decision making, particularly in the earlier stages of infection remains a subject of
Diagnosis
Sustained culture of T pallidum is difficult and usually used only in research. Animal models, most often using rabbit inoculation, have been valuable for isolation of T pallidum, as well as to study host response to infection.28 Direct detection of T pallidum from lesion exudate collected from patients with primary and secondary syphilis is preferable, but these tests are not readily accessible in many settings. Darkfield microscopy has traditionally been used for detecting T pallidum;
Diagnosis of neurosyphilis
Because neurosyphilis can be asymptomatic or present in many different ways, analysis of CSF is often helpful to confirm its presence. However, lumbar puncture and CSF analysis are presently only recommended for diagnosis of neurosyphilis in individuals with appropriate clinical syndromes, for evaluation of possible treatment failures, and for some patients with latent syphilis.23 In these situations, a reactive CSF VDRL test is diagnostic of neurosyphilis, while detection of an elevated CSF
Management
Penicillin has long been the drug of choice for treatment of syphilis. In recent years, manufacturing shortfalls have sometimes limited the availability of benzathine benzylpenicillin, the preferred formulation for most syphilis therapy.39 Long-acting formations of benzathine benzylpenicillin are the most commonly recommended drugs for syphilis treatment. Alternate therapy using multiple doses of procaine penicillin, doxycycline, or ceftriaxone can be used when intravenous therapy might be
Response to therapy
Response to therapy is indicated by a two (four-fold) or more dilution decline in non-treponemal serological test titres or, if initial titres are positive at a 1:1 or 1:2 dilution, by becoming non-reactive.23, 31, 32 However, serological response to therapy is not universal in successfully treated patients and 15–20% of patients with early syphilis might have so-called serofast titres, which do not change substantially (ie, remain positive at the initial titre or only decline a single
Control strategies
Beyond primary prevention using avoidance strategies and condoms, approaches for control of diagnosed syphilis are based on adaptation of recommendations made by US Surgeon General, Thomas Parran: widespread testing (screening), professional and public education and engagement, timely treatment, and continuing research to improve these efforts.19 In LMICs, syphilis management is most often started after presentation for evaluation of genital ulceration or as a result of prenatal care testing.38
Notification and partner management strategies
Other than for congenital syphilis, transmission of syphilis is thought to be transmitted almost entirely by individuals with early stage infection. For such patients, administration of preventive therapy (2·4 million units of benzathine benzylpenicillin administered parenterally) is recommended for all recent (30–90 days) sexual partners.23 Since lesions have not been present for some time in individuals with later latent syphilis (ie, latent syphilis of more than 1–2 year duration),23, 38
Conclusion and future research
Research is continuing into T pallidum biology and host response to infection as part of efforts to develop vaccines for syphilis prevention.46 At present, understanding for and the principles used to guide syphilis management are based on data collected in the pre-penicillin era when the disease was far more common than it is today. The clinical and prognostic significance of CNS invasion by T pallidum in patients with early syphilis and associated CSF abnormalities remains an area of great
Search strategy and selection criteria
This online publication has been corrected. The corrected version first appeared at thelancet.com on March 7, 2019
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2023, The Lancet Regional Health - Europe