Syphilis Dr Rajsrinivas Parthasarathy Syphilis Dr Parthasarathy is a Neurology trainee within the Yorkshire and Humber deanery. he undertook undergraduate medical training at Coimbatore Medical College, affiliated to the Dr MGR medical University, Tamil Nadu, India. His Postgraduate medical training was in England and is an elected member of the Royal College of Physicians of the UK. Edited by Prof Tom Solomon and Dr Agam Jung Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions This session will discuss syphilis within the context of an appropriate clinical encounter and outline the management of a patient with suspected neurosyphilis.

Learning Objectives Syphilis By the end of this session you will be able to: Explain the changing trend in the incidence of syphilis and its clinical importance. Describe the pathogenesis and natural history of syphilis and compare and contrast the various stages of syphilis. Outline the diverse clinical manifestations of neurosyphilis and extrapolate and employ information to appropriate clinical encounters. List diagnostic tests and use tests appropriately to diagnose Neurosyphilis. Demonstrate an understanding of treatment and follow up of a patient with neurosyphilis. Define the key differences in managing a patient with co-infection with HIV and managing their sex partners. Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

Introduction Syphilis Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum. It is a systemic infection that can virtually affect any organ system. Man is the only known natural host for the spirochete. Syphilis has a variety of clinical manifestations and can mimic many other infections and immune-mediated processes in the advanced stages of the infection. There has been a recent increase in the incidence and prevalence of syphilis among Men who have sex with Men (MSM) in developed countries. Syphilis is prevalent in developing countries and is a major source for morbidity and mortality. Early recognition and treatment is vital in order to avoid disability and death. Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

Pathogenesis and Pathological Findings The organism gains entry through minute abrasions on skin/mucous membranes. It then attaches to host cells by the action of an enzyme mucopolysaccharidase. This results in obliterative endarteritis of terminal arterioles with resultant inflammatory and necrotic changes. Pathological Findings Vascular involvement with endarteritis and periarteritis is the key finding in all stages. Meningovascular syphilis- vessel wall inflammation resulting in occlusion Gummatous stage- in the gummatous stage there is granulomatous inflammation. Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Dark field Micrograph of T. Pallidum- from Centers for Disease Control and Prevention’s Public Health Image Library (PHIL), 2335

Natural History of Syphilis Syphilis is a sexually transmitted disease cause by Treponema Pallidum. Man is the only known natural host for the Spirochete. The organism multiplies at the site of entry and then disseminates to various organ systems including the Central Nervous System. In Primary Syphilis a chancre develops at the site of infection and there is associated regional lymphadenopathy. The patient then enters the Secondary stage, the characteristic features of which are a generalized rash, lymphadenopathy, Condylomata lata and Central Nervous System involvement. The next phase is the latent stage which comprises of the early and late latent stages. A proportion of the patients can have a recurrence of the Secondary syphilis symptoms during this stage. Around a third of the patients would then develop Tertiary syphilis which includes Gumma, Cardiovascular Syphilis and late Neurological complications. Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

Primary Syphilis Syphilis The typical presentation is that of a chancre at the site of the inoculation with moderate regional lymphadenopathy in majority of patients. Incubation period is usually 3 weeks. The distinctive features of a chancre include an indurated base, purulence involving less than a third of the base, variable size and a sharply demarcated border. The chancre usually heals in 4 to 6 weeks time. Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

Secondary Syphilis I Syphilis Learning Objectives Introduction Manifestations occur within 3 months of initial infection. The most common manifestations are: Disseminated mucocutaneous rash which includes the palms and soles Generalised lymphadenopathy Patchy alopecia- In a small proportion of patients the infection can involve the hair follicles resulting in patchy alopecia. Condylomata lata- Highly infectious, painless, warty lesions occurring in warm and moist areas including perineum and anus. Neurological manifestations- Neurological manifestations including acute meningitis and cranial nerve involvement can occur at this stage. Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Patchy alopecia Maculopapular erythematous rash Condylomata lata

Secondary Syphilis II: CNS involvement After gaining entry into the host, the treponemes circulate to various organ systems including the Central Nervous System. The host immune system is able to overcome the infection in the majority. A few may however go on to develop neurological manifestations. Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

Latent & Tertiary stages The latent stage can be further subdivided into: Early: Up to a year after resolution of primary or secondary syphilis. There can be a recurrence of secondary manifestations. Late: Asymptomatic infection lasting beyond a year with positive serology. In pregnancy in-utero infection can occur. It can last from a few years to 2 or 3 decades, It then progresses to the tertiary stage The tertiary stage can be further subdivided into: Gumma: Granulomatous inflammation (central necrotic area with coagulative necrosis surrounded by inflammatory tissue) It can occur from one year post infection to many decades later. Predominantly affects skin and bone, but can develop in any organ. It is usually benign and hence termed “late benign syphilis” and the inflammmation resolves with antibiotic treatment. Neurosyphilis Cardiovascular syphilis (Aortitis) Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Gumma of the nose due to long standing tertiary syphilis

Neurosyphilis I Syphilis Learning Objectives Introduction Pathogenesis Spread of treponemes to the Central Nervous System can occur soon after inoculation. Symptomatic CNS involvement can occur as early as primary syphilis. Acute Syphilitic Leptomeningitis commonly occurs during the secondary stage. It predominantly affects the base of the brain and Cranial nerve involvement can occur. Rarely obstructive hydrocephalus can occur as result of blockade of the fourth ventricular foramina. In Meningovascular Syphilis, a sub-acute diffuse encephalitic process usually precedes a stroke like syndrome.  Inflammatory changes occurring in the vessel wall result in occlusion of the blood vessels.  Brain infarction in the vascular territory results in focal neurological deficits. General Paresis is a neuropsychiatric disorder characterised by personality change, progressive cognitive impairment, seizures and paralysis. It results from cortical damage secondary to the infection. This is a late complication and occurs a few decades after the initial infection. Tabes Dorsalis results from progressive damage to the dorsal roots and dorsal columns. Sensory ataxia, lower limb paraesthesia and Argyll Robertson pupils are commonly seen in this condition. Similar to general paresis it is a late complication. Optic atrophy is also a recognised late complication. Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

Neurosyphilis II Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Adapted from: Singh and Romanowski. Clinical Microbiology Reviews. Apr 1999, p. 187-209.

Diagnostic tests I Syphilis Diagnostic tests include: Dark field microscopy (the most specific test) Serological tests DNA PCR/Reverse transcriptase PCR CSF tests Serological tests- Treponemal tests They are specific antibodies directed against Treponema pallidum. The chief tests include: FTA-ABS [Fluorescent treponemal antibody –absorption] TPI [Treponema pallidum Immobilisation] TPHA [Treponema pallidum Hemagglutination] TPPA [Treponema pallidum Particle agglutination] Key facts: Treponemal tests are more sensitive and specific than Non treponemal tests and hence false positive reactions occur rarely. The tests remain reactive indefinitely and hence useful in diagnosing late stages of Syphilis. The test is qualitative and hence not helpful in documenting response to therapy. Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

Diagnostic tests II Syphilis Serological tests- Non-Treponemal tests These tests detect non-specific antibodies (reagins) directed to lipoidal antigens on surface of Treponema pallidum. The tests include: VDRL Rapid Plasma Reagin [RPR]. This is preferred because of ease. The antigenic target for the above tests is host derived lipids (lecithin, cholesterol and cardiolipin) incorporated on surface of metabolically limited Treponema pallidum. Non treponemal tests are quantitative in their assessment and hence can be helpful in assessing treatment response (Titres will fall with treatment). Pitfalls: A non reactive test result in very early and late stages of Syphilis False positive reaction in patients with Acute Infection, Pregnancy and Autoimmune conditions False Negative test result as a consequence of Prozone phenomenon Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

Diagnostic tests III: CSF Antibodies A positive CSF VDRL test almost certainly indicates neurosyphilis The FTA-ABS test is very sensitive but less specific for neurosyphilis. This is because there can be passive transfer of antibodies from the blood to CSF. A negative FTA-ABS test virtually excludes neurosyphilis Biochemical A CSF cell count of more than 5, a protein level greater than 0.45 g/l and CSF IgG index greater than 0.6 are suggestive, but neither of them need to be elevated to make a diagnosis Indications for Lumbar Puncture A patient with syphilis presenting with neurological or ophthalmological features Tertiary Syphilis HIV infection and RPR > 1:32 Treatment failure Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

Algorithm for diagnosing syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

Treatment and Follow up Treatment and follow up are outlined below: Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

HIV and Syphilis Co-infection I A considerable proportion of patients with Syphilis are co-infected with HIV. Treponemal infection can result in an increase in HIV transmission and acquisition by increasing seminal viral load and disrupting mucosal barrier respectively. It can also increase HIV viral load and transmission by suppressing cellular immunity. Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

HIV and Syphilis Co-infection II Key facts based on CDC sexually transmitted disease treatment guidelines 2002: All patients with syphilis should be encouraged to have HIV testing HIV-positive patients who have early syphilis may be at increased risk for neurologic complications and may have higher rates of treatment failure with currently recommended regimens Some specialists recommend CSF examination before treatment of HIV-infected persons with early syphilis, with follow-up CSF examination following treatment in persons with initial abnormalities HIV-infected patients who meet the criteria for treatment failure should be managed in the same manner as HIV-negative patients (i.e., a CSF examination and re-treatment) CSF examination and re-treatment also should be strongly considered for patients whose nontreponemal test titers do not decrease fourfold within 6--12 months of therapy Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

Management of sexual partners I Sexual transmission of Treponema pallidum occurs only when mucocutaneous syphilitic lesions are present. However, any person who has had sexual contact  with a person  who has syphilis, in any stage should be evaluated clinically and serologically.  Long-termed sex partners of patients who have latent syphilis should be treated on the basis of clinical and serological evaluation findings. For identification of at-risk partners, the time periods before treatment are: 3 months plus duration of symptoms for primary syphilis 6 months plus duration of symptoms for secondary syphilis 1 year for early latent syphilis Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

Management of sexual partners II Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Based on Sexually transmitted diseases treatment guidelines. CDC Guidance 2002.

Key points Syphilis is a multisystem infection and can mimic other disease processes Central Nervous system seeding can occur as early as in Primary Syphilis A combination of 'appropriate clinical setting', 'positive serological tests' and 'abnormal CSF parameters' are required to diagnose Neurosyphilis Regular follow up with repeat Lumbar punctures at appropriate intervals are required to document successful treatment Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

Summary Having completed this session you will now be able to: Explain the changing trend in the incidence of syphilis and its clinical importance Describe the pathogenesis and natural history of syphilis and compare and contrast the various stages of syphilis Outline the diverse clinical manifestations of neurosyphilis and extrapolate and employ information to appropriate clinical encounters List diagnostic tests and employ appropriate tests to diagnose neurosyphilis Demonstrate an understanding of treatment and follow up of a patient with neurosyphilis Define the key differences in managing a patient with co-infection with HIV and managing sex partners Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

References Syphilis Learning Objectives Introduction Pathogenesis Sexually Transmitted Diseases Treatment Guidelines (2002) CDC guidance. Singh A.E., Romanowski . B. (1999) Syphilis: Review with Emphasis on Clinical, Epidemiologic, and Some Biologic Features; Clinical Microbiology Reviews. p187–209. Rebecca E. LaFond and Sheila A. Lukehart. (2006). Biological Basis for Syphilis; Clinical Microbiology Reviews, p. 29-49, Vol. 19, No. 1. Narula. T., Kamboj. S., Martinez.J., Engel.L.S.(2010 ).Co-infection: HIV and the great mimic syphilis. HIV Clinician. Vol. 22, No. 2, 7-10. Zetola NM, Engelman J, Jensen TP, Klausner JD. (2007) Syphilis in the United States: an update for clinicians with an emphasis on HIV co-infection. Mayo Clin Proc;82(9):1091-1102. Gjestland, T. 1955. The Oslo study of untreated syphilis; an epidemiologic investigation of the natural course of the syphilitic infection based upon a re-study of the Boeck-Bruusgaard material. Acta Derm. Venereol. 35:3-368. Holmes M. D., Brant-Zawadzki M. M.,Simon R. P. (1984) Clinical features of meningovascular syphilis. Neurology 34:553–556 Merritt H. H., Adams R. D., Solomon H. C. (1946) Neurosyphilis. (Oxford University Press, New York, N.Y). Simon R. P.  (1985) Neurosyphilis. Arch. Neurol. 42:606–613. Larsen S.A, Steiner B.M, Rudolph A.H. (1995).  Laboratory diagnosis and interpretation of tests for syphilis. Clin. Microbiol. Rev., 8(1):1. Buchacza et al. (2004). Syphilis increases HIV viral load and decreases CD4 cell counts in HIV-infected patients with new syphilis infections. AIDS . 18 (15), p 2075 – 2079. Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions

Question 1 Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Select the single best answer from the options given. Click on the answer to see if it is correct and read an explanation. Which of the following statements is incorrect: The incidence of syphilis is increasing amoungst MSM. The hallmark finding in all stages of syphilis is gummatous inflammation. Gummatous syphilis occurs in tertiary syphilis. Spread to various tissues, including the CNS, occurs soon after infection. Secondary stage manifestations can occur in up to a quarter of patients with early latent syphilis.

Question 1 Syphilis Which of the following statements is incorrect: Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Which of the following statements is incorrect: The incidence of syphilis is increasing amoungst MSM. The hallmark finding in all stages of syphilis is gummatous inflammation. Gummatous syphilis occurs in tertiary syphilis. Spread to various tissues, including the CNS, occurs soon after infection. Secondary stage manifestations can occur in up to a quarter of patients with early latent syphilis. INCORRECT Try one of the alternative answers in order to progress or read more by using the links on the left hand side

Question 1 Syphilis Which of the following statements is incorrect: Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Which of the following statements is incorrect: The incidence of syphilis is increasing amongst MSM. The hallmark finding in all stages of syphilis is gummatous inflammation. Gummatous syphilis occurs in tertiary syphilis. Spread to various tissues, including the CNS, occurs soon after infection. Secondary stage manifestations can occur in up to a quarter of patients with early latent syphilis. CORRECT b) Is the correct answer as Gummatous inflammation only classically occurs in tertiary syphilis. Click here to move on to the next question.

Question 2a Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Case study: A 25-year-old male presented with a rash and headache. General examination reveals a generalised maculopapular erythematous, inguinal and axillary lymphadenopathy and warty lesions in the perianal region. Neurological examination revealed  photophobia, neck stiffness and a positive kernigs sign. Meningeal involvement in a patient with secondary syphilis is the correct clinical picture. TRUE FALSE

Question 2a Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Case study: A 25-year-old male presented with a rash and headache. General examination reveals a generalised maculopapular erythematous, inguinal and axillary lymphadenopathy and warty lesions in the perianal region. Neurological examination revealed  photophobia, neck stiffness and a positive kernigs sign. Meningeal involvement in a patient with secondary syphilis is the correct clinical picture. TRUE FALSE CORRECT TRUE is the correct answer, the clinical features are suggestive of syphilis and meningism. Click here to move on to the next question.

Question 2a Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Case study: A 25-year-old male presented with a rash and headache. General examination reveals a generalised maculopapular erythematous, inguinal and axillary lymphadenopathy and warty lesions in the perianal region. Neurological examination revealed  photophobia, neck stiffness and a positive kernigs sign. Meningeal involvement in a patient with secondary syphilis is the correct clinical picture. TRUE FALSE INCORRECT TRUE is the correct answer as the clinical features are suggestive of both syphilis and meningism. Click here to move on to the next question.

Question 2b Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Case study: A 25-year-old male presented with a rash and headache. General examination reveals a generalised maculopapular erythematous, inguinal and axillary lymphadenopathy and warty lesions in the perianal region. Neurological examination revealed  photophobia, neck stiffness and a positive kernigs sign. What other key information would you want to know? History suggestive of primary disease Sexual orientation and recent sexual exposure Both of the above

Question 2b Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Case study: A 25-year-old male presented with a rash and headache. General examination reveals a generalised maculopapular erythematous, inguinal and axillary lymphadenopathy and warty lesions in the perianal region. Neurological examination revealed  photophobia, neck stiffness and a positive kernigs sign. What other key information would you want to know? History suggestive of primary disease Sexual orientation and recent sexual exposure Both of the above CORRECT Both of these areas of the history are crucial to assessing the patient and determining the correct management, including treatment of partners. Click here to move on to the next question.

Question 2b Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Case study: A 25-year-old male presented with a rash and headache. General examination reveals a generalised maculopapular erythematous, inguinal and axillary lymphadenopathy and warty lesions in the perianal region. Neurological examination revealed  photophobia, neck stiffness and a positive kernigs sign. What other key information would you want to know? History suggestive of primary disease Sexual orientation and recent sexual exposure Both of the above INCORRECT Both of these areas of the history are crucial to assessing the patient and determining the correct management, including treatment of partners. Click here to move on to the next question.

Question 2c Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Case study: A 25-year-old male presented with a rash and headache. General examination reveals a generalised maculopapular erythematous, inguinal and axillary lymphadenopathy and warty lesions in the perianal region. Neurological examination revealed  photophobia, neck stiffness and a positive kernigs sign. Which of the following combinations of tests would be most appropriate in this patient to diagnose the condition? Cell count & biochemistry, CSF VDRL and FTA ABS CSF VDRL, FTA ABS and TPPA Cell count & biochemistry, CSF VDRL, serum VDRL and FTA ABS Cell count & biochemistry, CSF VDRL, serum VDRL and TPPA

Question 2c Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Case study: A 25-year-old male presented with a rash and headache. General examination reveals a generalised maculopapular erythematous, inguinal and axillary lymphadenopathy and warty lesions in the perianal region. Neurological examination revealed  photophobia, neck stiffness and a positive kernigs sign. Which of the following combinations of tests would be most appropriate in this patient to diagnose the condition? Cell count & biochemistry, CSF VDRL and FTA ABS CSF VDRL, FTA ABS and TPPA Cell count & biochemistry, CSF VDRL, serum VDRL and FTA ABS Cell count & biochemistry, CSF VDRL, serum VDRL and TPPA INCORRECT Try one of the alternative answers in order to progress or read more by using the links on the left hand side

Question 2c Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Case study: A 25-year-old male presented with a rash and headache. General examination reveals a generalised maculopapular erythematous, inguinal and axillary lymphadenopathy and warty lesions in the perianal region. Neurological examination revealed  photophobia, neck stiffness and a positive kernigs sign. Which of the following combinations of tests would be most appropriate in this patient to diagnose the condition? Cell count & biochemistry, CSF VDRL and FTA ABS CSF VDRL, FTA ABS and TPPA Cell count & biochemistry, CSF VDRL, serum VDRL and FTA ABS Cell count & biochemistry, CSF VDRL, serum VDRL and TPPA CORRECT c) is the correct answer. A positive CSF VDRL almost certainly indicates neurosyphilis and should be considered alongside the serum results. A negative FTA ABS on the other hand virtually excludes neurosyphilis and cell count and biochemistry should be performed. Click here to move on to the next question.

Question 2d Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Case study: The patient has a positive serum VDRL, positive FTA-Abs, negative CSF VDRL and a positive CSF FTA Abs. Can you diagnose this patient with neurosyphilis based on these laboratory test results? YES NO

Question 2d Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Case study: The patient has a positive serum VDRL, positive FTA-Abs, negative CSF VDRL and a positive CSF FTA Abs. Can you diagnose this patient with neurosyphilis based on these laboratory test results? YES NO CORRECT This patient can not be diagnosed based on these results. There can be a passive transfer of FTA –Abs from the blood to CSF compartment and hence one cannot diagnose Neurosyphilis based on available information  The clinical picture and LP findings are key to making a positive diagnosis. Click here to move on to the next question.

Question 2d Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Case study: The patient has a positive serum VDRL, positive FTA-Abs, negative CSF VDRL and a positive CSF FTA Abs. Can you diagnose this patient with neurosyphilis based on these laboratory test results? YES NO INCORRECT This patient can not be diagnosed based on these results. There can be a passive transfer of FTA –Abs from the blood to CSF compartment and hence one cannot diagnose Neurosyphilis based on available information  The clinical picture and LP findings are key to making a positive diagnosis. Click here to move on to the next question.

Question 3a Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false Non-treponemal specific tests are quantitative tests which are useful to assess treatment response. TRUE FALSE

Question 3a Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false Non-treponemal specific tests are quantitative tests which are useful to assess treatment response. TRUE FALSE CORRECT TRUE is the correct answer. Click here to move on to the next question.

Question 3a Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false Non-treponemal specific tests are quantitative tests which are useful to assess treatment response. TRUE FALSE INCORRECT TRUE is the correct answer. Click here to move on to the next question.

Question 3b Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false Treponemal specific tests are not quantitative and can remain reactive indefinitely. TRUE FALSE

Question 3b Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false Treponemal specific tests are not quantitative and can remain reactive indefinitely. TRUE FALSE CORRECT TRUE is the correct answer. Click here to move on to the next question.

Question 3b Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false Treponemal specific tests are not quantitative and can remain reactive indefinitely. TRUE FALSE INCORRECT TRUE is the correct answer. Click here to move on to the next question.

Question 3c Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false False positive test are more common with treponemal specific  tests as opposed to non specific tests. TRUE FALSE

Question 3c Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false False positive test are more common with treponemal specific  tests as opposed to non specific tests. TRUE FALSE CORRECT FALSE is the correct answer. Click here to move on to the next question.

Question 3c Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false False positive test are more common with treponemal specific  tests as opposed to non specific tests. TRUE FALSE INCORRECT FALSE is the correct answer. Click here to move on to the next question.

Question 3d Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false A positive CSF FTA Abs test almost always suggests neurosyphilis. TRUE FALSE

Question 3d Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false A positive CSF FTA Abs test almost always suggests neurosyphilis. TRUE FALSE CORRECT FALSE is the correct answer. CSF FTA Abs is not very specific, although a negative test can often exclude neurosyphilis. Click here to move on to the next question.

Question 3d Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false A positive CSF FTA Abs test almost always suggests neurosyphilis. TRUE FALSE INCORRECT FALSE is the correct answer. CSF FTA Abs is not very specific, although a negative test can often exclude neurosyphilis. Click here to move on to the next question.

Question 3e Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false A positive CSF VDRL almost always indicates neurosyphilis. TRUE FALSE

Question 3e Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false A positive CSF VDRL almost always indicates neurosyphilis. TRUE FALSE CORRECT TRUE is the correct answer. CSF VDRL is very specific for neurosyphilis. Click here to finish the session.

Question 3e Syphilis Learning Objectives Introduction Pathogenesis Natural History Primary Syphilis Secondary Syphilis Latent & Tertiary stages Neurosyphilis Diagnostic tests Diagnostic algorithm Treatment HIV co-infection Management of sexual partners Key Points Summary References Questions Answer the following question either true or false A positive CSF VDRL almost always indicates neurosyphilis. TRUE FALSE INCORRECT TRUE is the correct answer. CSF VDRL is very specific for neurosyphilis. Click here to finish the session.

Congratulations on completing this module and thank you for using NeuroID: elearning. We hope to see you at a NeuroID: Liverpool Neurological Infectious Diseases Course soon. Download a certificate and then to finish the session CLICK HERE.

NeuroID 2013: Liverpool Neurological Infectious Diseases Course To learn more about neurological infectious diseases… NeuroID 2013: Liverpool Neurological Infectious Diseases Course Liverpool Medical Institution, UK Provisional date: May 2013 Ever struggled with a patient with meningitis or encephalitis, and not known quite what to do? Then the  Liverpool Neurological infectious Diseases Course is for you! For Trainees and Consultants in Adult and Paediatric Neurology, Infectious Diseases, Acute Medicine, Emergency Medicine and Medical Microbiology who want to update their knowledge, and improve their skills. Presented by Leaders in the Field Commonly Encountered Clinical Problems Practical Management Approaches Rarities for Reference Interactive Case Presentations State of the Art Updates Pitfalls to Avoid Controversies in Neurological Infections Feedback from previous course: “Would unreservedly recommend to others” “An excellent 2 days!! The best course for a long time” Convenors: Prof Tom Solomon, Dr Enitan Carrol, Dr Rachel Kneen, Dr Nick Beeching, Dr Benedict Michael For more information and to REGISTER NOW VISIT: www.liv.ac.uk/neuroidcourse