Editor’s Note: As the incidence of syphilis continues to rise, clinicians are faced with an increasing number of patients with complex clinical presentations, posing significant challenges in patient management. At the 31st Conference on Retroviruses and Opportunistic Infections (CROI), Dr. Khalil Ghanem from the Johns Hopkins University School of Medicine delivered a keynote on the diagnosis and treatment of syphilis. In this issue of Infectious Disease Frontier, we are fortunate to have Dr. Ghanem discuss the diagnostic challenges of neurosyphilis, the value of the DoxyPEP prevention strategy, and the future outlook for syphilis management.
Infectious Disease Frontier: Neurosyphilis is one of the most severe clinical forms of syphilis. What are the challenges in the diagnosis and treatment of Neurosyphilis?
Dr. Khalil Ghanem: The main challenge in diagnosing Neurosyphilis lies in the absence of a singular test that offers both high sensitivity and specificity. We’re compelled to rely on a suite of tests to diagnose accurately. For instance, pleocytosis in the CSF indicates inflammation but isn’t specific to syphilis. Similarly, while a positive CSF VDRL is very indicative of syphilis, it lacks sensitivity, leaving us without a definitive answer in many cases. The diagnosis of ocular and otic syphilis, often categorized under Neurosyphilis, requires distinct considerations, primarily relying on physical examination and symptoms due to the commonality of normal CSF results in these conditions. Regarding treatment, penicillin remains our best tool, with ceftriaxone as an alternative. However, the challenge intensifies for patients allergic to beta-lactam antibiotics, underlining a pressing need for additional treatment options.
Infectious Disease Frontier: The shortage of penicillin is still serious. How do you think we should deal with this problem? Including how to find more alternative treatment options for penicillin?
Dr. Khalil Ghanem: The benzathine penicillin shortage, especially significant in the United States, predominantly affects pregnant patients due to the lack of alternative treatments. For uncomplicated syphilis in non-pregnant patients, doxycycline offers a viable alternative. However, for pregnant patients, our options are severely limited. This situation necessitates urgent exploration of alternative treatments, potentially including oral amoxicillin plus probenecid, cefixime, or azithromycin. Excitingly, in vitro model systems are emerging as a promising avenue for identifying new therapeutic compounds, such as linezolid, although determining the optimal dosage and treatment duration requires further research.
Infectious Disease Frontier: How do you think of the value of DoxyPEP in the prevention of syphilis?
Dr. Khalil Ghanem: Doxycycline post-exposure prophylaxis (DoxyPEP) has proven exceptionally effective in preventing syphilis, with studies demonstrating a significant reduction in incidence rates. This strategy represents a major advancement in syphilis prevention. However, the impact of intermittent doxycycline exposure on serological testing for syphilis remains unclear. It’s imperative that clinicians approach syphilis serologies with caution in patients utilizing DoxyPEP, as the implications of doxycycline exposure on these tests have yet to be fully understood.
Infectious Disease Frontier: What other conundrums do you think exist in the management of syphilis?
Dr. Khalil Ghanem: A significant quandary in syphilis management is interpreting serological titers post-treatment, highlighting the need for more accurate biomarkers of disease activity. The current discrepancy between serological and microbiological activity complicates patient monitoring and treatment efficacy assessments. The development of new syphilis models promises to aid in identifying more precise biomarkers, potentially accelerating the path towards an effective vaccine. I’m optimistic about the future, anticipating that we’ll witness substantial progress in syphilis management and prevention in the coming decade.
Dr. Khalil Ghanem
Deputy Director of Education, Department of Medicine, Johns Hopkins Bayview Medical Center
Professor of Medicine
