Serologic tests for Neurosyphilis

Interpretation of serologic tests for Neurosyphilis

Non-Treponemal Test (VDRL, RPR, ART, TRUST, RST, EIA)	Treponemal Test (TPHA, MHA-TP, FTA-ABS)	Possible Reason
+	+	syphilis - recent or previous yaws or pinta
+	-	no syphilis - false positive
-	+	consistent with syphilis, acute, previously treated or untreated yaws, pinta or Lyme disease
-	-	no syphilis or incubating disease

Comments

The non-treponemal test is a good follow-up indicator because the titer reflects the activity of the disease. Following treatment, it should show a regular decline until it becomes negative or stabilizes at a low level (< 1:8).
Serologic follow-up should be performed at the following intervals:
- congenital syphilis, infectious syphilis (primary, secondary, early latent) or concomitant HIV infection: 1, 3, 6, 12, 24 months
- non-infectious syphilis
  (late latent, tertiary): 12 and 24 months
  (neurosyphilis): 6, 12, 24 months.

Serology may remain positive for life in persons who have previously contracted syphilis and been adequately treated.

The non-treponemal test may be falsely positive in certain clinical situations including viral infections (e.g., mononucleosis), bacterial infections (e.g., pneumonia, tuberculosis), chronic disease (e.g., collagen vascular disease), and in the elderly.
A period of 1 to 4 weeks may elapse between the appearance of the primary chancre and the detection of a non-treponemal reaction. Treponemal reactions become positive before non-treponemal reactions.

Treponemal tests may be falsely positive in certain situations, including viral infections and collagen vascular disease

RPR and/or TPHA positive specimens and those indicated clinically are subsequently tested by the FTA-ABS to differentiate syphilis from non-syphilis and to identify false positives. The RPR is useful in monitoring patient treatment since it declines with time. The FTA-ABS and TPHA, once elevated, are usually retained for life and are of no value to follow treated patients. The EIA IgM is used to differentiate antibodies acquired due to congenital syphilis (IgM positive) from maternally acquired antibody (IgG Positive).

In general, a reactive RPR or VDRL test in CSF is indicative of neurosyphilis in patients who also have pleocytosis and/or elevation of CSF protein. However, if red blood cells are present the result must be interpreted with caution because the antibodies detected in the test are likely to have derived at least in part from blood.

Monitoring response to treatment. With adequate therapy, the RPR or VDRL should become non-reactive by about 12 months in primary syphilis, and 18 months to 24 months for secondary and early latent disease. Many patients with late latent syphilis or late disease will show a decline to non-reactivity over the 5 years following treatment. Some however will remain seropositive. In general a positive RPR one year after treatment for primary syphilis or 2 years after secondary syphilis suggests 1) inadequate therapy, or at least persistent infection, 2) reinfection or 3) a chronic biological false positive reaction.

Biological false positives RPR and VDRL may be found in pregnancy; transiently in eg measles, chicken pox; chronically in e.g. cirrhosis, SLE, the antiphospholipid antibody syndrome, leprosy.

FTA-ABS, TPHA, TPI: positive results confirm the diagnosis of syphilis, but do not indicate whether the disease is active, inactive or cured.