Infectious Disease Serology: Key Tests and Interpretation

Four clinical questions answered by infectious disease serology

Is the patient immune to reinfection; Does the patient have an acute infection; Has the patient had a past infection explaining complications; Is the patient immunodeficient

Criteria for rubella immunity

Rubella IgG >10 IU/mL; documented MMR after 1st birthday; born before 1957 (not sufficient for women who may become pregnant)

Purpose of rubella IgG test

Determines immunity, NOT acute infection

Serologic test for acute rubella infection

Rubella IgM

Rubella IgM significance

Indicates current or recent rubella infection

Nonspecific tests for infectious mononucleosis

Paul-Bunnell heterophile test; Monospot

Heterophile antibody tests detect

Antibodies not specific to EBV antigens

Sensitivity of heterophile tests in adults vs children

~90% positive in adults; ~50% in children under 4 years

EBV-specific serologic tests

VCA-IgM; VCA-IgG; EBNA; EA

Antigenic basis of Paul-Bunnell test

Heterophile antibodies agglutinate sheep RBCs; absorbed by ox RBCs; not absorbed by guinea pig kidney cells

Purpose of absorption pattern in heterophile testing

Distinguishes EBV heterophile antibodies from serum sickness heterophile antibodies

Steps of heterophile antibody test

Mix patient serum with indicator RBCs; optional absorption; observe agglutination

Monospot test characteristics

Uses horse RBCs; no absorption step; positive early; persists for months

Limitation of heterophile antibody testing

Low sensitivity in children under 4 years

First antibody to rise in acute EBV infection

VCA-IgM

Timing of VCA-IgG in EBV infection

Rises 4-7 days after symptom onset and persists

Heterophile antibody timing in EBV infection

Appears during acute phase; absent in many young children

EBNA antibody significance

Appears late; indicates past EBV infection

EBV antibody pattern in acute infection

Heterophile positive; VCA-IgM positive; VCA-IgG rising; EBNA absent

EBV antibody pattern in convalescent phase

Heterophile decreasing; VCA-IgM decreasing; VCA-IgG high; EBNA positive

EBV antibody pattern in past infection

Heterophile absent; VCA-IgM absent; VCA-IgG positive; EBNA positive

Primary syphilis clinical features

Painless chancre; appears 10-90 days after exposure; heals in 3-6 weeks

Secondary syphilis clinical features

Rash on palms/soles; mucous lesions; fever; lymphadenopathy; patchy hair loss

Tertiary syphilis clinical features

Neurosyphilis; cardiovascular damage; blindness; dementia; paralysis

Non-treponemal syphilis tests

RPR; VDRL

What non-treponemal tests detect

Antibodies to cardiolipin from host cell damage

Uses of non-treponemal syphilis tests

Screening and monitoring treatment via titers

Causes of false-positive non-treponemal tests

Pregnancy; autoimmune disease

Treponemal syphilis tests

FTA-ABS; TP-IgG

Treponemal test characteristics

Detect antibodies specific to Treponema pallidum; remain positive for life

Use of treponemal tests

Confirm syphilis diagnosis

Syphilis test used to monitor therapy response

Non-treponemal tests (RPR, VDRL)

Why treponemal tests cannot monitor therapy

Remain positive for life and do not reflect disease activity

Non-organism specific test for Mycoplasma pneumoniae

Cold agglutinin test

Post-Group A strep immune complications

Rheumatic fever; post-streptococcal glomerulonephritis

Streptococcal antibody tests for prior infection

ASO; Anti-DNase B

Most sensitive test after throat infection

ASO

Most sensitive test after skin infection (pyoderma)

Anti-DNase B

Reason ASO is low after skin infection

ASO often not produced following pyodermaMain purpose of infectious disease serology Determine immunity, acute infection, past infection, or immunodeficiency

Rubella immunity test

Rubella IgG (>10 IU/mL)

Rubella IgG indicates

Immunity, not acute infection

Rubella acute infection marker

Rubella IgM

Evidence of rubella immunity

Positive IgG, documented MMR, born before 1957

Heterophile antibody tests

Monospot, Paul-Bunnell

Heterophile antibodies are

Not specific for EBV antigens

Heterophile test sensitivity

90% adults; ~50% children <4 years

EBV-specific antibodies

VCA-IgM, VCA-IgG, EBNA, EA

First EBV antibody to appear

VCA-IgM

EBV acute infection pattern

VCA-IgM+, VCA-IgG rising, EBNA-

EBV past infection pattern

VCA-IgG+, EBNA+, VCA-IgM-

EBNA antibody significance

Indicates past EBV infection

Monospot test 특징

Uses horse RBCs; no absorption; early positive

Paul-Bunnell test basis

Agglutination of sheep RBCs by heterophile antibodies

Primary syphilis hallmark

Painless chancre

Secondary syphilis hallmark

Rash on palms and soles

Tertiary syphilis hallmark

Neuro/cardiovascular damage

Non-treponemal syphilis tests

RPR, VDRL

Non-treponemal tests detect

Anti-cardiolipin antibodies

Use of non-treponemal tests

Screening and monitoring therapy

Syphilis test to monitor treatment

RPR or VDRL titer

Treponemal syphilis tests

FTA-ABS, TP-IgG

Treponemal test 특징

Specific for T. pallidum; positive for life

Why treponemal tests not for monitoring

Remain positive despite treatment

Mycoplasma pneumoniae non-specific test

Cold agglutinin test

Group A strep immune complications

Rheumatic fever; post-strep glomerulonephritis

Tests for prior Group A strep infection

ASO; Anti-DNase B

Best test after strep throat infection

ASO

Best test after strep skin infection

Anti-DNase B