How long after dengue infection do Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibodies become detectable in an antigen test?

Timing of IgM and IgG Antibodies in Dengue Infection

IgM antibodies typically appear 3-5 days after symptom onset, while IgG antibodies develop around day 5-7 in primary infections and earlier in secondary infections. 1, 2

Antibody Development Timeline

IgM Antibodies

• IgM antibodies become detectable during the first week of illness, typically appearing by day 3-5 after symptom onset 1, 2
• By day 8 of illness, nearly 100% of patients will have detectable IgM antibodies 2
• IgM levels peak approximately 2 weeks after symptom onset 3
• IgM antibodies remain detectable for 2-3 months after infection before declining to undetectable levels 1, 3

IgG Antibodies

• In primary infections, IgG antibodies typically appear around day 5-7 after symptom onset, initially at low levels 2, 4
• IgG levels increase more slowly than IgM in primary infections, reaching peak levels between days 22-30 4
• In secondary infections, IgG antibodies appear more rapidly and at higher levels, often detectable from the first few days of illness 3
• IgG antibodies persist for months to years after infection 1

Diagnostic Considerations

Primary vs. Secondary Infections

• Primary dengue infections are characterized by a high molar fraction of anti-dengue IgM and low molar fraction of IgG 3
• Secondary dengue infections show a rapid increase in IgG antibodies with lower levels of IgM antibodies 3
• The IgG3 subclass appears within the first week, peaks at weeks 2-3, and disappears within 4-6 months (mean duration 149 days), making it a potential biomarker for recent infection 5

Optimal Testing Strategy

• For specimens collected ≤7 days after symptom onset, nucleic acid amplification tests (NAATs) and NS1 antigen detection are most sensitive 1
• For specimens collected >7 days after symptom onset, IgM antibody testing becomes more sensitive than molecular methods 1, 6
• A combination of NS1 antigen and IgM antibody testing provides the highest diagnostic yield (96.9-100%) for samples taken after day 3 of illness 2

Common Pitfalls

• A negative IgM test during the first few days of illness does not rule out dengue infection, as antibodies may not have developed yet 1
• IgM and IgG antibodies can cross-react with other flaviviruses, potentially causing false-positive results 1
• For definitive diagnosis in areas with multiple circulating flaviviruses, confirmatory plaque reduction neutralization tests (PRNTs) may be required 1
• IgM antibodies may be dramatically lower in secondary dengue infections, potentially leading to false-negative results 3

Testing Algorithm

1. For patients presenting within 7 days of symptom onset:

   • Perform NAAT and/or NS1 antigen testing as first-line tests 1, 7
   • Consider adding IgM testing if presenting after day 3 2

2. For patients presenting >7 days after symptom onset:

   • IgM antibody testing is the preferred diagnostic method 1
   • Consider IgG testing to distinguish between primary and secondary infections 3

3. For indeterminate results or when definitive diagnosis is needed:

   • Perform confirmatory PRNTs against dengue and other endemic flaviviruses 1