Does a positive Immunoglobulin G (IgG) test for Rickettsia conorii indicate current or past infection with Mediterranean spotted fever?

Positive IgG for Rickettsia conorii: Current vs. Past Infection

A positive IgG alone cannot definitively distinguish between current and past infection with R. conorii—you must interpret the titer level, timing of sample collection, presence of IgM, and clinical context together. 1

Interpretation Framework

Single IgG Result Interpretation

• IgG ≥1:128 alone suggests possible infection but requires clinical correlation and is insufficient for definitive diagnosis of acute disease 1
• IgG ≥1:128 with IgM ≥1:64 provides stronger evidence of recent/current infection and scores 10 points in diagnostic criteria (vs. 5 points for IgG alone) 1
• IgG without IgM more likely represents past infection, though timing matters critically 1

Timing Considerations

• Both IgG and IgM typically appear 7-15 days after symptom onset in Mediterranean spotted fever 1
• Samples collected in first 7 days of illness will be negative despite active infection—serology is unreliable early 2
• Sensitivity increases dramatically with time: 46% at days 5-9,90% at days 20-29, and 100% after day 29 1

Critical Diagnostic Pitfall

Early treatment with doxycycline within 7 days can completely prevent antibody development, resulting in persistently negative serology despite true infection 1, 2, 3. This means a treated patient may never seroconvert, and you cannot rule out recent infection based on negative or low titers alone. 2, 3

Definitive Diagnosis Algorithm

For Suspected Acute Infection:

1. Obtain paired sera 2-3 weeks apart to demonstrate four-fold rise in IgG titer—this is the gold standard for confirming acute infection 2
2. A four-fold rise scores 20 points in diagnostic criteria and is highly specific for recent infection 1
3. Convalescent serology at 4-6 weeks post-onset is essential for definitive diagnosis 2

Clinical Context Integration:

A positive diagnosis requires ≥25 points from the following scoring system 1:

• Clinical triad (fever >39°C, eschar, maculopapular/purpuric rash): 5 points each
• Epidemiological factors (endemic area, May-October occurrence, dog tick contact): 2 points each
• Serological criteria: IgG ≥1:128 alone (5 points), IgG ≥1:128 + IgM ≥1:64 (10 points), four-fold rise (20 points)
• Bacteriological confirmation (culture or PCR): 25 points

Cross-Reactivity Warning

Spotted fever group rickettsiae exhibit extensive cross-reactivity—antibodies to R. conorii will react with R. africae, R. parkeri, and other spotted fever group members 1, 2. This means:

• Single antigen testing cannot definitively identify the causative species 1
• Cross-reactive antibodies target lipopolysaccharide antigens shared across the group 1, 2
• Western blot with cross-absorption is required for species-specific diagnosis but is only available in reference laboratories 1

IgM Interpretation Caution

IgM has significantly lower specificity than IgG and may be detected in patients without true rickettsiosis 2. The CDC explicitly warns that IgM should never be used as a stand-alone diagnostic method and may persist or rise paradoxically without true infection 2. Always correlate with IgG seroconversion and clinical features. 2

Practical Clinical Approach

If you encounter an isolated positive IgG:

• With compatible clinical syndrome (fever, rash, eschar) and epidemiological exposure: likely represents recent infection, especially if IgM also positive 1
• Without clinical syndrome: more likely past infection or cross-reactivity from related rickettsiae 2
• After recent doxycycline treatment: may represent suppressed immune response to true infection despite low/negative titers 2, 3
• Always obtain convalescent serology at 4-6 weeks to look for IgG rise—this is non-negotiable for definitive diagnosis 2

Never delay treatment waiting for serologic confirmation—clinical illness nearly always precedes laboratory diagnosis, and empiric doxycycline should be initiated immediately based on clinical suspicion 2. One case report demonstrated PCR-confirmed R. conorii infection with initially negative serology that only became positive after treatment, illustrating that serology can lag behind true infection 4.