Serologic testing for CMV, EBV, hepatitis viral infection, HIV, and syphilis

Overview

Serological testing across these four infections illustrates the general IgM (recent/acute)/IgG (past exposure/immunity) framework, with organism-specific nuances - EBV's heterophile antibody test, syphilis's dual treponemal/non-treponemal testing algorithm, and hepatitis serology's multi-marker panels each requiring specific interpretation knowledge beyond the general framework
Amongst the most frequently ordered serological panels in general medical and infectious diseases practice, reflecting the prevalence and clinical importance of these four infections

EBV: heterophile antibody (Monospot) test is a rapid screen but can be falsely negative early in infection or in young children; EBV-specific serology (VCA IgM/IgG, EBNA) provides more definitive staging when the heterophile test is negative but suspicion remains
Syphilis: uses a two-test algorithm (treponemal test e.g. EIA/CLIA, plus non-treponemal test e.g. RPR/VDRL) - the treponemal test remains positive for life after any past infection (treated or not), while the non-treponemal test titre correlates with disease activity and is used to monitor treatment response

CMV/EBV: IgM suggests recent primary infection, though EBV IgM can occasionally persist longer than expected, causing interpretive difficulty in distinguishing recent from more distant infection
Syphilis: a positive treponemal test with negative non-treponemal test may reflect successfully treated past infection or an early/late-stage discordance requiring clinical correlation and, sometimes, a second treponemal test to resolve

Confirmed active/recent infection with each organism directs organism-specific management (see individual disease notes); syphilis non-treponemal titre trend specifically guides confirmation of adequate treatment response (expected 4-fold titre decline)
Hepatitis serology interpretation directs distinguishing acute, chronic, resolved, or vaccine-induced immune status (see )

Syphilis serofast state (persistently low positive non-treponemal titre despite adequate treatment - a recognised, generally benign phenomenon), EBV heterophile-negative infectious mononucleosis, hepatitis B serology interpretation complexity
The treponemal syphilis test stays positive for life after any past infection, treated or not - a positive treponemal test with a low or negative non-treponemal titre in a patient with a clear prior treatment history usually reflects successful past treatment rather than untreated or new infection, and should be interpreted with that history in mind rather than triggering automatic retreatment

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