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| '''For patient information on Neurosyphilis, click [[Neurosyphilis (patient information)|here]]'''
| | __NOTOC__ |
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| {{DiseaseDisorder infobox | | | {{DiseaseDisorder infobox | |
| Name = Syphilis | | | Name = Syphilis | |
| Image = Treponema pallidum.jpg | | | Image = Treponema pallidum.jpg | |
| Caption = Image of spiral-shaped organisms responsible for causing syphilis | | | Caption = Image of spiral-shaped organisms responsible for causing syphilis | |
| ICD10 = {{ICD10|A|50||a|50}}-{{ICD10|A|53||a|50}} |
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| ICD9 = {{ICD9|090}}-{{ICD9|097}} |
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| ICDO = |
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| OMIM = |
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| DiseasesDB = |
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| MedlinePlus = 001327 |
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| eMedicineSubj =|
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| eMedicineTopic = |
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| eMedicine_mult =
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| }} | | }} |
| {{Syphilis}} | | {{Neurosyphilis}} |
| {{CMG}}; {{AOEIC}} {{LG}} | | {{CMG}}; {{AE}}{{MMJ}} |
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| ==Overview==
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| *Neurosyphilis refers to a site of infection involving the [[central nervous system]] (CNS).
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| *Neurosyphilis may occur at any stage of syphilis.
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| *Before the advent of antibiotics, it was typically seen in 25-35% of patients with syphilis.
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| *Neurosyphilis is now most common in patients with [[HIV]] infection. Reports of neurosyphilis in HIV-infected persons are similar to cases reported before the HIV [[pandemic]]. The precise extent and significance of neurologic involvement in HIV-infected patients with syphilis, reflected by either laboratory or clinical criteria, have not been well characterized. Furthermore, the alteration of host [[immunosuppression]] by [[antiretroviral drug|antiretroviral therapy]] in recent years has further complicated such characterization.
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| ==Clinical presentation: Four clinical types==
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| *The late forms of neurosyphilis (tabes dorsalis and general paresis) are seen much less frequently since the advent of antibiotics.
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| *The most common manifestations today are asymptomatic or symptomatic meningitis.
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| =====1. Asymptomatic meningitis=====
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| *Asymptomatic neurosyphilis usually has no signs or symptoms and is diagnosed exclusively with the presence or absence of CSF abnormalities notably pleocytosis, elevated protein, decreased glucose.
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| =====2. Symptomatic meningitis=====
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| *develops within 6-months to several years of primary infection
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| *typical meningitis symptoms: [[headache]], [[nausea]], [[vomiting]], [[photophobia]]
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| *Acute syphilitic [[meningitis]] usually occurs within the first year of infection; 10% of cases are diagnosed at the time of the secondary rash.
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| *Patients present with headache, meningeal irritation, and [[cranial nerve]] abnormalities, especially the [[optic nerve]], [[facial nerve]], and the [[vestibulocochlear nerve]].
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| *Rarely, it affects the spine instead of the brain, causing focal muscle weakness or sensory loss.
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| =====3. Meningovascular syphilis=====
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| *Meningovascular syphilis occurs a few months to 10 years (average, 7 years) after the primary syphilis infection.
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| *Meningovascular syphilis can be associated with [[prodromal]] symptoms lasting weeks to months before focal deficits are identifiable.
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| *Prodromal symptoms include:
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| :*unilateral numbness,
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| :*[[paresthesia]]s,
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| :*upper or lower extremity weakness,
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| :*[[headache]],
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| :*[[vertigo (medical)|vertigo]],
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| :*[[insomnia]], and
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| :*psychiatric abnormalities such as personality changes.
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| *The focal deficits initially are intermittent or progress slowly over a few days.
| | ==[[Neurosyphilis overview|Overview]]== |
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| *However, it can also present as an infectious [[arteritis]] and cause an [[ischemia|ischemic]] [[stroke]], an outcome more commonly seen in younger patients.
| | ==[[Neurosyphilis pathophysiology|Pathophysiology]]== |
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| *[[Angiography]] may be able to demonstrate areas of narrowing in the blood vessels or total occlusion.
| | ==[[Neurosyphilis causes|Causes]]== |
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| =====4. Parenchymatous neurosyphilis===== | | ==[[Neurosyphilis differential diagnosis|Differentiating Neurosyphilis from other Diseases]]== |
| *develops 15-20 years after primary infection
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| *[[argyll robertson pupil]]: small irregular pupil
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| *clinical presents as '''[[general paresis]]''' or '''[[tabes dorsalis]]''' with resultant [[ataxia]]
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| :*General paresis<ref name=AMN>{{cite journal | author = Richard B. Jamess, MD, PhD | title = [http://www.health.am/sex/syphilis/ Syphilis- Sexually Transmitted Infections], 2006. | journal =Sexually transmitted diseases treatment guidelines | volume = | issue = | pages = | year = 2002}}</ref>, otherwise known as general paresis of the insane, is a severe manifestation of neurosyphilis.
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| :*It is a chronic [[dementia]] which ultimately results in death in as little as 2-3 years.
| | ==[[Neurosyphilis risk factors|Risk Factors]]== |
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| :*Patients generally have progressive personality changes, memory loss, and poor judgment.
| | ==[[Neurosyphilis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| :*More rarely, they can have [[psychosis]], [[clinical depression|depression]], or [[mania]].
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| :*Imaging of the brain usually shows atrophy.
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| ==Diagnosis== | | ==Diagnosis== |
| *Clinical signs of neurosyphilis (i.e., cranial nerve dysfunction, [[meningitis]], [[stroke]], [[altered mental status|acute or chronic altered mental status]], loss of vibration sense, and auditory or ophthalmic abnormalities) warrant further investigation and treatment for neurosyphilis.
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| *Approximately 35% to 40% of persons with secondary syphilis have [[asymptomatic]] [[central nervous system]] (CNS) involvement, as demonstrated by any of these on [[cerebrospinal fluid]] (CSF) examination:
| | [[Neurosyphilis history and symptoms|History and Symptoms]] | [[Neurosyphilis physical examination|Physical Examination]] | [[Neurosyphilis laboratory findings|Laboratory Findings]] | [[Neurosyphilis MRI|MRI]] | [[Neurosyphilis other imaging findings|Other Imaging Findings]] | [[Neurosyphilis other diagnostic studies|Other Diagnostic Studies]] |
| :*An abnormal leukocyte cell count, protein level, or glucose level
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| :*Demonstrated reactivity to Venereal Disease Research Laboratory ([[VDRL]]) antibody test
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| *Laboratory testing is helpful in supporting the diagnosis of neurosyphilis; however, no single test can be used to diagnose neurosyphilis in all instances.
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| ===CSF analysis===
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| *[[CSF analysis|Cerebrospinal fluid (CSF) abnormalities]] are common in persons with early syphilis.
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| *Diagnosed by finding '''''high numbers of [[leukocytes]]''''' in the CSF or abnormally '''''high protein''''' concentration in the setting of syphilis infection.
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| *[[VDRL]] in [[cerebrospinal fluid]] (CSF-VDRL), which is highly specific but insensitive, is the standard serologic test for CSF. Although some advocate using the [[FTA-ABS|FTA-ABS test]] to improve sensitivity.
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| *When reactive in the absence of substantial contamination of CSF with blood, it is considered diagnostic of neurosyphilis; however in early syphilis, it can be of unknown prognostic significance.<ref name="pmid3056164">{{cite journal |author=Lukehart SA, Hook EW, Baker-Zander SA, Collier AC, Critchlow CW, Handsfield HH |title=Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment |journal=[[Annals of Internal Medicine]] |volume=109 |issue=11 |pages=855–62 |year=1988 |month=December |pmid=3056164 |doi= |url= |accessdate=2012-02-16}}</ref>
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| *Most other tests are both insensitive and nonspecific and must be interpreted in relation to other test results and the clinical assessment. Therefore, the laboratory diagnosis of neurosyphilis usually depends on various combinations of reactive serologic test results, CSF cell count or protein, and a reactive CSF-VDRL with or without clinical manifestations.
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| ===HIV Co-infection===
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| *There is anecdotal evidence that the incidence of neurosyphilis is higher in [[HIV|HIV patients]], and some have recommended that all HIV-positive patients with syphilis should have a [[lumbar puncture]] to look for asymptomatic neurosyphilis.<ref>{{cite journal | author=Walter T, Lebouche B, Miailhes P, ''et al.'' | title=Symptomatic relapse of neurologic syphilis after benzathine penicillin G therapy for primary or secondary syphilis in HIV-infected patients | journal=Clin Infect Dis | year=2006 | volume=43 | issue=6 | pages=787-90 | id=PMID 16912958 }}</ref>
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| *Among persons with HIV infection, the [[Lumbar puncture#Diagnostics|CSF leukocyte count]] usually is elevated (>5 white blood cell count [WBC]/mm3); using a higher cutoff (>20 WBC/ mm3) might improve the specificity of neurosyphilis diagnosis.<ref name="pmid14745693">{{cite journal |author=Marra CM, Maxwell CL, Smith SL, Lukehart SA, Rompalo AM, Eaton M, Stoner BP, Augenbraun M, Barker DE, Corbett JJ, Zajackowski M, Raines C, Nerad J, Kee R, Barnett SH |title=Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features |journal=[[The Journal of Infectious Diseases]] |volume=189 |issue=3 |pages=369–76 |year=2004 |month=February |pmid=14745693 |doi=10.1086/381227 |url=http://www.jid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=14745693 |accessdate=2012-02-16}}</ref>
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| *The [[VDRL|CSF-VDRL]] might be non-reactive even when neurosyphilis is present.
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| *Therefore, additional evaluation using [[FTA-ABS|FTA-ABS testing]] on CSF can be considered. The [[FTA-ABS|CSF FTA-ABS test]] is less specific for neurosyphilis than the [[VDRL|CSF-VDRL]] but is highly sensitive; neurosyphilis is highly unlikely with a negative [[FTA-ABS|CSF FTA-ABS test]].<ref name="pmid343742">{{cite journal |author=Jaffe HW, Larsen SA, Peters M, Jove DF, Lopez B, Schroeter AL |title=Tests for treponemal antibody in CSF |journal=[[Archives of Internal Medicine]] |volume=138 |issue=2 |pages=252–5 |year=1978 |month=February |pmid=343742 |doi= |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=343742 |accessdate=2012-02-16}}</ref>
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| ==Treatment== | | ==Treatment== |
| *CNS involvement can occur during any stage of syphilis. However, [[Syphilis laboratory tests#CSF analysis|CSF laboratory abnormalities]] are common in persons with [[Syphilis pathophysiology#Primary syphilis|early syphilis]], even in the absence of clinical neurological findings. No evidence exists to support variation from recommended treatment for early syphilis for patients found to have such abnormalities.
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| *If clinical evidence of neurologic involvement is observed (e.g., cognitive dysfunction, motor or sensory deficits, ophthalmic or auditory symptoms, cranial nerve palsies, and symptoms or signs of [[meningitis]]), a [[Syphilis laboratory tests#CSF analysis|CSF examination]] should be performed.
| | [[Neurosyphilis medical therapy|Medical Therapy]] | [[Neurosyphilis primary prevention|Primary Prevention]] | [[Neurosyphilis secondary prevention|Secondary Prevention]] | [[Neurosyphilis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Neurosyphilis future or investigational therapies|Future or Investigational Therapies]] |
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| *[[uveitis|Syphilitic uveitis]] or other ocular manifestations frequently are associated with neurosyphilis and should be managed according to the treatment recommendations for neurosyphilis. Patients who have neurosyphilis or syphilitic eye disease (e.g., [[uveitis]], [[neuroretinitis]], and [[optic neuritis]]) should be treated with the recommended regimen for neurosyphilis; those with eye disease should be managed in collaboration with an ophthalmologist. A [[Syphilis laboratory tests#CSF analysis|CSF examination]] should be performed for all patients with syphilitic eye disease to identify those with abnormalities; patients found to have abnormal CSF test results should be provided follow-up CSF examinations to assess treatment response.
| | ==Case Studies== |
| | [[Neurosyphilis case study one|Case #1]] |
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| *For patients diagnosed with neurosyphilis including ocular or auditory syphilis with or without [[Syphilis laboratory tests#CSF analysis|positive CSF results]], [[Penicillin#Benzylpenicillin (penicillin G)|aqueous crystalline penicillin G]] is the treatment of choice.
| | ==Related Chapters== |
| :*The recommended regimen is intravenous treatment every 4 hours or continuously for 10-14 days
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| :*If intravenous administration is not possible, then [[Pencillin#Procaine benzylpenicillin|procaine penicillin]] is an alternative (administered daily with [[probenecid]] for two weeks).
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| :*Procaine injections are painful, however, and patient compliance may be difficult to ensure.
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| :*To approximate the 21-day course of therapy for [[Syphilis pathophysiology#Latent syphilis|late latent disease]] and to address concerns about slowly dividing treponemes, most experts now recommend 3 weekly doses of [[Penicillin#Benzylpenicillin (penicillin G)|benzathine penicillin G]] after the completion of a 14-day course of aqueous crystalline or aqueous [[Pencillin#Procaine benzylpenicillin|procaine penicillin G]]] for neurosyphilis.
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| *No oral antibiotic alternatives are recommended for the treatment of neurosyphilis. The only alternative that has been studied and shown to be effective is intramuscular [[ceftriaxone]] daily for 14 days.
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| ===CDC Recommendations: Pharmacotherapy [http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm]===
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| {{cquote|
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| ====Recommended Regimen====
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| '''1.''' [[Penicillin#Benzylpenicillin (penicillin G)|Aqueous crystalline penicillin G]] 18-24 million units per day, administered as 3-4 million units IV every 4 hours or continuous infusion, for 10-14 days.
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| ====Alternative Regimen====
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| '''1.''' [[Pencillin#Procaine benzylpenicillin|Procaine penicillin]] 2.4 million units IM once daily, '''''plus''''' [[probenecid]] 500 mg orally four times a day, both for 10-14 days.}}
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| *If compliance with therapy can be ensured, the following alternative regimen might be considered.
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| *The durations of the recommended and alternative regimens for neurosyphilis are shorter than the duration of the regimen used for late syphilis in the absence of neurosyphilis. Therefore, [[Penicillin#Benzylpenicillin (penicillin G)|benzathine penicillin]], 2.4 million units IM once per week for up to 3 weeks, can be considered after completion of these neurosyphilis treatment regimens to provide a comparable total duration of therapy.
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| ===Other Management Considerations===
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| *Other considerations in the management of patients who have neurosyphilis are as follows:
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| :*All persons who have syphilis should be tested for HIV.
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| :*Although systemic steroids are used frequently as adjunctive therapy for otologic syphilis, such drugs have not been proven to be beneficial.
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| ===Special Considerations===
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| =====Penicillin Allergy=====
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| *Limited data suggest that [[ceftriaxone]] 2 g daily either IM or IV for 10-14 days can be used as an alternative treatment for patients with neurosyphilis.<ref name="pmid3764632">Hook EW, Baker-Zander SA, Moskovitz BL, Lukehart SA, Handsfield HH (1986) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=3764632 Ceftriaxone therapy for asymptomatic neurosyphilis. Case report and Western blot analysis of serum and cerebrospinal fluid IgG response to therapy.] ''Sex Transm Dis'' 13 (3 Suppl):185-8. PMID: [http://pubmed.gov/3764632 3764632]</ref><ref name="pmid14573840">Shann S, Wilson J (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14573840 Treatment of neurosyphilis with ceftriaxone.] ''Sex Transm Infect'' 79 (5):415-6. PMID: [http://pubmed.gov/14573840 14573840]</ref>
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| *However, the possibility of cross-reactivity between [[ceftriaxone]] and [[penicillin]] exists.
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| *Other regimens have not been adequately evaluated for treatment of neurosyphilis. Therefore, if concern exists regarding the safety of [[ceftriaxone]] for a patient with neurosyphilis, [[Syphilis medical therapy#Pencillin allergy: Penicillin skin test|skin testing]] should be performed (if available) to confirm [[Syphilis medical therapy#Pencillin allergy|penicillin allergy]] and, if necessary, [[desensitize]] the patient.
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| =====Pregnancy=====
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| Pregnant patients who are [[Syphilis medical therapy#Pencillin allergy|allergic to penicillin]] should be [[desensitized]] and treated with [[penicillin]].
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| ===Follow-up===
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| *If [[Lumbar puncture#Diagnostics|CSF pleocytosis]] was present initially, a [[Syphilis laboratory tests#CSF analysis|CSF examination]] should be repeated every 6 months until the cell count is normal.
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| *Follow-up CSF examinations also can be used to evaluate changes in the [[Syphilis laboratory tests#CSF analysis|CSF-VDRL or CSF protein]] after therapy; however, changes in these two parameters occur more slowly than cell counts, and persistent abnormalities might be less important.<ref name="pmid15034833">Marra CM, Maxwell CL, Tantalo L, Eaton M, Rompalo AM, Raines C et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15034833 Normalization of cerebrospinal fluid abnormalities after neurosyphilis therapy: does HIV status matter?] ''Clin Infect Dis'' 38 (7):1001-6. [http://dx.doi.org/10.1086/382532 DOI:10.1086/382532] PMID: [http://pubmed.gov/15034833 15034833]</ref><ref name="pmid18715154">Marra CM, Maxwell CL, Tantalo LC, Sahi SK, Lukehart SA (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18715154 Normalization of serum rapid plasma reagin titer predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of neurosyphilis.] ''Clin Infect Dis'' 47 (7):893-9. [http://dx.doi.org/10.1086/591534 DOI:10.1086/591534] PMID: [http://pubmed.gov/18715154 18715154]</ref>
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| *The leukocyte count is a sensitive measure of the effectiveness of therapy. If the cell count has not decreased after 6 months or if the CSF cell count or protein is not normal after 2 years, '''''retreatment''''' should be considered.
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| *Limited data suggest that in immunocompetent persons and [[HIV|HIV-infected persons]] on highly active [[AIDS medical therapy#Anti Retroviral Therapy (ART)|antiretroviral therapy]], normalization of the [[Rapid plasma reagent|serum RPR titer]] predicts normalization of CSF parameters.<ref name="pmid18715154">Marra CM, Maxwell CL, Tantalo LC, Sahi SK, Lukehart SA (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18715154 Normalization of serum rapid plasma reagin titer predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of neurosyphilis.] ''Clin Infect Dis'' 47 (7):893-9. [http://dx.doi.org/10.1086/591534 DOI:10.1086/591534] PMID: [http://pubmed.gov/18715154 18715154]</ref>
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| ==Neurosyphilis Among HIV-Infected Persons==
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| ====Treatment====
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| [[HIV]]-infected patients with [[neurosyphilis]] should be treated according to the recommendations for HIV-negative patients with neurosyphilis.
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| ====Special considerations====
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| *HIV-infected, [[Syphilis medical therapy#Pencillin allergy|penicillin-allergic]] patients who have [[neurosyphilis]] should be managed according to the recommendations for penicillin-allergic, HIV-negative patients with neurosyphilis.
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| *Several small observational studies conducted in HIV-infected patients with neurosyphilis suggest that [[ceftriaxone]] 1-2 g IV daily for 10-14 days might be effective as an alternate agent.<ref name="pmid1442850">Dowell ME, Ross PG, Musher DM, Cate TR, Baughn RE (1992) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=1442850 Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus.] ''Am J Med'' 93 (5):481-8. PMID: [http://pubmed.gov/1442850 1442850]</ref><ref name="pmid15117503">Smith NH, Musher DM, Huang DB, Rodriguez PS, Dowell ME, Ace W et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15117503 Response of HIV-infected patients with asymptomatic syphilis to intensive intramuscular therapy with ceftriaxone or procaine penicillin.] ''Int J STD AIDS'' 15 (5):328-32. [http://dx.doi.org/10.1258/095646204323012823 DOI:10.1258/095646204323012823] PMID: [http://pubmed.gov/15117503 15117503]</ref><ref name="pmid18532887">Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18532887 Antiretroviral therapy is associated with reduced serologic failure rates for syphilis among HIV-infected patients.] ''Clin Infect Dis'' 47 (2):258-65. [http://dx.doi.org/10.1086/589295 DOI:10.1086/589295] PMID: [http://pubmed.gov/18532887 18532887]</ref>
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| ====Follow-up====
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| *If [[Lumbar puncture#Diagnostics|CSF pleocytosis]] was present initially, a [[Syphilis laboratory tests#CSF analysis|CSF examination]] should be repeated every 6 months until the cell count is normal.
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| *Follow-up CSF examinations also can be used to gauge response after therapy.
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| *Limited data suggest that changes in CSF parameters might occur more slowly in HIV-infected patients, especially those with more advanced immunosuppression.<ref name="pmid15034833">Marra CM, Maxwell CL, Tantalo L, Eaton M, Rompalo AM, Raines C et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15034833 Normalization of cerebrospinal fluid abnormalities after neurosyphilis therapy: does HIV status matter?] ''Clin Infect Dis'' 38 (7):1001-6. [http://dx.doi.org/10.1086/382532 DOI:10.1086/382532] PMID: [http://pubmed.gov/15034833 15034833]</ref><ref name="pmid18525260">Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18525260 Neurosyphilis in a clinical cohort of HIV-1-infected patients.] ''AIDS'' 22 (10):1145-51. [http://dx.doi.org/10.1097/QAD.0b013e32830184df DOI:10.1097/QAD.0b013e32830184df] PMID: [http://pubmed.gov/18525260 18525260]</ref>
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| *If the cell count has not decreased after 6 months or if the CSF is not normal after 2 years, retreatment should be considered.
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| ==Related chapters== | |
| *[[Syphilis]] | | *[[Syphilis]] |
| *[[Congenital syphilis]] | | *[[Congenital syphilis]] |
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| ==Resources== | | ==External Links== |
| *[http://hivinsite.ucsf.edu/InSite?page=kb-05-01-04 UCSF HIV InSite Knowledge Base Chapter: Syphilis and HIV]
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| *[http://colman.net/eadv/index.html "A New Gold Standard For Syphilis?" Poster Presentation for European Academy of Dermatology and Venereology 2004 Spring Symposium]
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| *[http://www.stdhelp.org/about/syphilis.php Syphilis Pictures and Information]
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| *[http://medinfo.ufl.edu/other/histmed/clancy/ Kipkeepers, Pox and Gleet Vendors: A Rapid History of Syphilis]
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| *[http://www.poxhistory.com/ POX: Genius, Madness, and the Mysteries of Syphilis]
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| *[http://www.yourstdhelp.com/syphilis.html Syphilis Informational resource ]
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| *[http://www.pbs.org/wnet/secrets/case_syphilis/index.html Secrets of the Dead (PBS): The Syphilis Enigma]
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| *[http://www.cbc.ca/ideas/Aids Syphilis and AIDS: Lessons from history]
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| *[http://www.cdc.gov/std/Syphilis/STDFact-Syphilis.htm "Syphilis fact sheet" from the Center for Disease Control] | | *[http://www.cdc.gov/std/Syphilis/STDFact-Syphilis.htm "Syphilis fact sheet" from the Center for Disease Control] |
| *[http://www.nobel.se/medicine/laureates/1927/wagner-jauregg-lecture.html The treatment of dementia paralytica by malaria inoculation (A Nobel Prize lecture, December 13, 1927)]
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| *[http://www.niaid.nih.gov/factsheets/stdsyph.htm National Institute of Allergy and Infectious Diseases Factsheet]
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| *[http://uk.reuters.com/article/oddlyEnoughNews/idUKN1443055520080115 New study blames Columbus for syphilis spread from Reuters Jan 15, 2008]
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| ==References==
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| {{reflist|2}}
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| {{Diseases of the skin and appendages by morphology}} | | {{Diseases of the skin and appendages by morphology}} |
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| [[Category:Gynecology]] | | [[Category:Gynecology]] |
| [[Category:Infectious disease]]
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| [[Category:Bacterial diseases]] | | [[Category:Bacterial diseases]] |
| [[Category:Sexually transmitted diseases]] | | [[Category:Sexually transmitted diseases]] |