Increases in Asymptomatic Early Syphilis May Reflect Increases in Repeated Episodes of Syphilis and Not Enhanced Screening

To the Editor—In their analysis of men who have sex with men (MSM) attending a national sentinel network of 46 sexual health clinics in Australia between 2007 and 2014, Chow et al [1] found a decline in the proportion of syphilis cases that were secondary syphilis and a corresponding increase in early latent syphilis. These changes occurred during a period of increased coverage and frequency of syphilis testing in MSM. The authors interpret this association as representing an “interruption of syphilis progression” and thereby a reduction in the infectiousness of syphilis. Here I advance an alternative hypothesis to explain these findings. The current outbreak of syphilis in MSM in multiple countries is characterized by an increasing proportion of cases caused by repeated episodes of syphilis (Figure 1) [2, 3]. Magnuson et al [4] showed via inoculation experiments in the 1950s that persons with previous episodes of syphilis had an attenuated clinical and immunological response to intradermal challenge with Treponema pallidum. Others and I have found that patients with repeated episodes of syphilis have an attenuated immune response and are more likely to present with latent-stage disease than patients with an initial episode of syphilis [5–7]. Chow et al did not provide a breakdown of repeated versus initial episodes of syphilis. However, if the proportion of syphilis in MSM due to repeated episodes is increasing in Australia, as surveillance data suggest it is [3], then this increase may be responsible for the increase in the proportion of syphilis cases classified as latent in MSM. Cases of initial and repeated episodes of syphilis by year of diagnosis at the Institute of Tropical Medicine, Antwerp, 1995 to 2012 (adapted from Kenyon et al [2], with permission). Cases of initial and repeated episodes of syphilis by year of diagnosis at the Institute of Tropical Medicine, Antwerp, 1995 to 2012 (adapted from Kenyon et al [2], with permission). Among MSM with human immunodeficiency virus infection, Chow et al [1] found a correlation between decreasing proportion of secondary syphilis and both increasing testing coverage (r = −0.87; P = .005) and testing frequency (r = −0.93; P = .001). These 2 correlations are however almost identical if one substitutes year of testing for testing coverage and frequency (r = −0.86 [P = .006] and r = −0.96 [P < .001], respectively; calculations based on supplementary data [1]). These findings suggest that the decline in the proportion of persons with secondary syphilis is correlated with something that is increasing linearly with time. Increased testing and increases in the proportion of repeated syphilis episodes are both plausible candidates. Further multivariate analyses that include both of these as exposure variables would help determine which factor is more important. This is an important issue to resolve, because if Chow and colleague are correct in their interpretation, then one can conclude that screening at the intensity attained in their surveillance sites is sufficient to have an impact on syphilis progression and transmission. If, however, attenuated immunity induced by repeated infections is responsible, this adds weight to calls for more intensive control strategies. Intensified screening would probably remain a critical component of such comprehensive control strategies. My colleagues and I currently use the evidence of attenuated immunity in repeated syphilis episodes to motivate patients with prior syphilis to continue screening frequently and long term, because this may be the only way to timeously diagnose their repeated infections. Potential conflicts of interest. Author certifies no potential conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.