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Serologic tests for syphilis can be quite complex. The screening and confirmatory tests, which number at least eight, are mathematically interpreted as a total of 16 possible combinations, if we choose one test from each of two sets of four. However, this bewildering complexity is simplified if we apply certain principles. We reiterate and propose four axioms. First, we distinguish between treponemal versus non-treponemal tests. The former, the treponemal test, is specific for the spirochete, treponema pallidum, and is used as a confirmatory test. It rarely declines over time. The latter, the non-treponemal test, is a screening test and reflects treponemal or tissue damage, is reported as a titer, and is used to monitor disease activity. We usually need both for screening and confirmatory diagnostic testing. Secondly, for rapid plasma reagin (RPR) tests, a non-treponemal serology test titer of at least 1:8 is suggestive of syphilis, but not necessarily neurosyphilis. A false-negative test usually registers below this dilution level and may be due to the “prozone phenomenon”. Serum RPR titers are usually greater than 1:32. Thirdly, a negative treponemal test in the cerebrospinal fluid excludes neurosyphilis and a positive test is highly sensitive but lacks specificity, usually due to blood contamination. Most patients with neurosyphilis will have a positive non-treponemal test in the cerebrospinal fluid (CSF) with elevated protein and pleocytosis. Fourthly, a serological cure is defined as at least a four-fold decline in a non-treponemal test titer at three and six months, or a persistently low titer after treatment. Patients who do not fulfill these criteria are known as “serofast”. We describe the case of a 38-year-old man with human immunodeficiency virus-type 1 who developed bilateral optic disc edema with photopsias and transient visual obscurations.

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Decomplexifying Serum and Cerebrospinal Fluid (CSF) Serologic Testing of Neurosyphilis: A Case Report of Ocular Syphilis and Highlights of the Principles of Serologic Testing