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==Diagnosis== [[File:Syphilis false shame and fear may destroy your future.png|thumb|upright=1.2|alt=Poster for testing of syphilis, showing a man and a woman bowing their heads in shame|This [[Works Progress Administration]] poster ({{circa}} 1936) acknowledges the social stigma of syphilis, while urging those who possibly have the disease to be tested]] [[File:Micrograph of secondary syphilis.jpg|thumb|[[Micrograph]] of secondary syphilis skin lesions. (A/B) H&E stain of SS lesions. (C/D) IHC staining reveals abundant bacteria embedded within a mixed cellular inflammatory infiltrate (shown in the red box) in the papillary dermis. The blue arrow points to a tissue histiocyte and the read arrows to two dermal lymphocytes<ref>{{cite journal|last1=Lukehart|first1=Sheila|authorlink1=Sheila Lukehart|last2=Cruz|first2=Adriana R.|last3=Ramirez|first3=Lady G.|last4=Zuluaga|first4=Ana V.|last5=Pillay|first5=Allan|last6=Abreu|first6=Christine|last7=Valencia|first7=Carlos A.|last8=La Vake|first8=Carson|last9=Cervantes|first9=Jorge L.|last10=Dunham-Ems |first10=Star |last11=Cartun |first11=Richard |last12=Mavilio |first12=Domenico |last13=Radolf|first13=Justin D.|last14=Salazar|first14=Juan C.|title=Immune Evasion and Recognition of the Syphilis Spirochete in Blood and Skin of Secondary Syphilis Patients: Two Immunologically Distinct Compartments|journal=PLOS Neglected Tropical Diseases |volume=6 |issue=7 |year=2012 |pages=e1717 |issn=1935-2735 |pmid=22816000 |pmc=3398964 |doi=10.1371/journal.pntd.0001717 |doi-access=free}}</ref>]] Syphilis is difficult to diagnose clinically during early infection.<ref name=Pri2008/> Confirmation is either via [[blood tests]] or direct visual inspection using [[Dark-field microscopy|dark field microscopy]].<ref name=Kent08/><ref>{{cite journal |last1=Ratnam |first1=S |title=The laboratory diagnosis of syphilis. |journal=Canadian Journal of Infectious Diseases and Medical Microbiology |date=January 2005 |volume=16 |issue=1 |pages=45–51 |doi=10.1155/2005/597580 |pmid=18159528|pmc=2095002 |doi-access=free}}</ref> Blood tests are more commonly used, as they are easier to perform.<ref name=Kent08/> Diagnostic tests are unable to distinguish between the stages of the disease.<ref name="Orgin10">{{cite journal |last=Farhi |first=D |author2=Dupin, N |date=September–October 2010 |title=Origins of syphilis and management in the immunocompetent patient: facts and controversies |journal=Clinics in Dermatology |volume=28 |issue=5 |pages=533–8 |doi=10.1016/j.clindermatol.2010.03.011 |pmid=20797514}}</ref> ===Blood tests=== Blood tests are divided into [[Nontreponemal tests for syphilis|nontreponemal]] and treponemal tests.<ref name=Pri2008/> Nontreponemal tests are used initially and include [[venereal disease research laboratory]] (VDRL) and [[rapid plasma reagin]] (RPR) tests. [[False positive#Type I error|False positives]] on the nontreponemal tests can occur with some viral infections, such as [[varicella]] (chickenpox) and [[measles]]. False positives can also occur with [[lymphoma]], [[tuberculosis]], [[malaria]], [[endocarditis]], [[connective tissue disease]], and [[pregnancy]].<ref name="RedBookSyphilis"/> Because of the possibility of false positives with nontreponemal tests, confirmation is required with a treponemal test, such as [[Treponema pallidum particle agglutination assay|''Treponema pallidum'' particle agglutination assay]] (TPHA) or [[fluorescent treponemal antibody absorption test]] (FTA-Abs).<ref name="Kent08"/> Treponemal antibody tests usually become positive two to five weeks after the initial infection<ref name="Pri2008"/> and remain positive for many years.<ref>{{cite journal |last= Singh|first= Ameeta E.|author2=Barbara Romanowski|date=1 April 1999|title= Syphilis: Review with Emphasis on Clinical, Epidemiologic, and Some Biologic Features|journal= Clinical Microbiology Reviews|volume= 12|issue= 2|pages= 187–209 |pmid= 10194456 |pmc= 88914 |doi=10.1128/CMR.12.2.187}}</ref> Neurosyphilis is diagnosed by finding high numbers of [[leukocytes]] (predominately [[lymphocytes]]) and high protein levels in the [[cerebrospinal fluid]] in the setting of a known syphilis infection.<ref name="Kent08"/><ref name="RedBookSyphilis"/> ===Direct testing=== [[Dark field microscopy]] of [[serous fluid]] from a chancre may be used to make an immediate diagnosis.<ref name=Pri2008/> Hospitals do not always have equipment or experienced staff members, and testing must be done within 10 minutes of acquiring the sample.<ref name=Pri2008/> Two other tests can be carried out on a sample from the chancre: [[direct fluorescent antibody]] (DFA) and [[polymerase chain reaction]] (PCR) tests.<ref name=Pri2008/> DFA uses [[antibodies]] tagged with [[fluorescein]], which attach to specific syphilis proteins, while PCR uses techniques to detect the presence of specific syphilis [[gene]]s.<ref name=Pri2008/> These tests are not as time-sensitive, as they do not require living bacteria to make the diagnosis.<ref name=Pri2008/>
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