Serological Criteria for Early Syphilis Treatment Efficacy
Serological Criteria for Early Syphilis Treatment Efficacy
Syphilis rates are increasing in China. In 2009, the incidence of syphilis was 24.66 cases per 100 000 population. In 2010, 358 534 syphilis cases were reported by the Ministry of Public Health of China. Shanghai is among the areas with the highest reported incidence (provided by Shanghai Centers for Disease Control and Prevention).
The aim of treating early syphilis is to prevent progression of disease and prevent sexual and vertical transmission. Assessment of 'cure' can be difficult. Clinical cure implies the disappearance of lesions, which can occur with or without therapy. Biological cure means total eradication of Treponema pallidum, which is difficult to evaluate as treponemes can persist despite effective treatment.
Because there is no test for 'microbiologic cure', evaluation of the patients treated for secondary syphilis depends on quantitative non-treponemal serologic tests. A fourfold decline of non-treponemal antibody titres within 3 to 6 months after therapy indicates effective treatment. A study in the penicillin era suggests that up to 5% of immunocompetent persons treated with BPG for early syphilis failed therapy. Another study reported 18% serological failure to respond to benzathine penicillin (with or without enhancement with amoxicillin) treatment at 6 months, and of those patients, 32/131 (24%) had T pallidum in the CSF pre-treatment and 7/35 (20%) post-treatment. In the antibiotic era, there are limited data on the progression to neurosyphilis of patients who experienced a fourfold decline in serological titres following therapy for early syphilis, but whose titres remained positive.
Our data suggest that both symptomatic and asymptomatic neurosyphilis can occur in immunocompetent patients whose titres remain serofast following therapy for early syphilis. Although current recommended therapeutic regimens remain highly effective for early syphilis, concerns have been raised because invasion of T pallidum into central nervous system occurs in about 40% of early syphilis. Significance of these data in relation to development of neurosyphilis is unknown, given the lack of CSF penetration of most antibiotics used to treat early syphilis. Benzathine penicillin G fails to provide treponemicidal levels in CSF, and patients with either neurosyphilis or detectable T pallidum in CSF can still meet the serological criteria for treatment response.
Our study has several limitations. The possibility of reinfection as a cause of neurosyphilis cannot be excluded though our patients denied high-risk sexual behaviours after treatment, and there was no fourfold increase in their RPR titres following their serofast state. There were multiple different antimicrobial regimens used to treat secondary syphilis, and it was difficult to determine whether some were more likely to result in clinical progression. The clinical significance of asymptomatic neurosyphilis in the antibiotic era is unclear, and most of our patients did not have neurological symptoms. The circumstances under which a CSF evaluation should be conducted for a patient after syphilis treatment are controversial since the benefits are not confirmed. Currently, US Centers for Disease Control and Prevention recommends that the following patients should undergo a CSF examination: (1) neurological signs or symptoms that persist or recur, (2) a sustained fourfold increase of non-treponemal antibody titres when reinfection is ruled out or (3) non-treponemal antibody titres do not decrease by two or more dilutions 6 months after treatment for early syphilis. Most of our patients would not have qualified for a CSF examination based on these criteria. Whether the CSF examination improved their long-term outcomes is unclear.
Our data suggest that neurosyphilis may be detected in immunocompetent patients despite appropriate therapy for early-stage syphilis and appropriate serological responses. Clinicians should be aware of these findings and should consider a CSF examination in any treated patient with evidence of disease progression irrespective of prior treatment history and serological response.
Discussion
Syphilis rates are increasing in China. In 2009, the incidence of syphilis was 24.66 cases per 100 000 population. In 2010, 358 534 syphilis cases were reported by the Ministry of Public Health of China. Shanghai is among the areas with the highest reported incidence (provided by Shanghai Centers for Disease Control and Prevention).
The aim of treating early syphilis is to prevent progression of disease and prevent sexual and vertical transmission. Assessment of 'cure' can be difficult. Clinical cure implies the disappearance of lesions, which can occur with or without therapy. Biological cure means total eradication of Treponema pallidum, which is difficult to evaluate as treponemes can persist despite effective treatment.
Because there is no test for 'microbiologic cure', evaluation of the patients treated for secondary syphilis depends on quantitative non-treponemal serologic tests. A fourfold decline of non-treponemal antibody titres within 3 to 6 months after therapy indicates effective treatment. A study in the penicillin era suggests that up to 5% of immunocompetent persons treated with BPG for early syphilis failed therapy. Another study reported 18% serological failure to respond to benzathine penicillin (with or without enhancement with amoxicillin) treatment at 6 months, and of those patients, 32/131 (24%) had T pallidum in the CSF pre-treatment and 7/35 (20%) post-treatment. In the antibiotic era, there are limited data on the progression to neurosyphilis of patients who experienced a fourfold decline in serological titres following therapy for early syphilis, but whose titres remained positive.
Our data suggest that both symptomatic and asymptomatic neurosyphilis can occur in immunocompetent patients whose titres remain serofast following therapy for early syphilis. Although current recommended therapeutic regimens remain highly effective for early syphilis, concerns have been raised because invasion of T pallidum into central nervous system occurs in about 40% of early syphilis. Significance of these data in relation to development of neurosyphilis is unknown, given the lack of CSF penetration of most antibiotics used to treat early syphilis. Benzathine penicillin G fails to provide treponemicidal levels in CSF, and patients with either neurosyphilis or detectable T pallidum in CSF can still meet the serological criteria for treatment response.
Our study has several limitations. The possibility of reinfection as a cause of neurosyphilis cannot be excluded though our patients denied high-risk sexual behaviours after treatment, and there was no fourfold increase in their RPR titres following their serofast state. There were multiple different antimicrobial regimens used to treat secondary syphilis, and it was difficult to determine whether some were more likely to result in clinical progression. The clinical significance of asymptomatic neurosyphilis in the antibiotic era is unclear, and most of our patients did not have neurological symptoms. The circumstances under which a CSF evaluation should be conducted for a patient after syphilis treatment are controversial since the benefits are not confirmed. Currently, US Centers for Disease Control and Prevention recommends that the following patients should undergo a CSF examination: (1) neurological signs or symptoms that persist or recur, (2) a sustained fourfold increase of non-treponemal antibody titres when reinfection is ruled out or (3) non-treponemal antibody titres do not decrease by two or more dilutions 6 months after treatment for early syphilis. Most of our patients would not have qualified for a CSF examination based on these criteria. Whether the CSF examination improved their long-term outcomes is unclear.
Our data suggest that neurosyphilis may be detected in immunocompetent patients despite appropriate therapy for early-stage syphilis and appropriate serological responses. Clinicians should be aware of these findings and should consider a CSF examination in any treated patient with evidence of disease progression irrespective of prior treatment history and serological response.