In a patient with an initial positive dengue IgM, negative Ross River virus IgG, and repeat testing after one month showing unchanged dengue IgM without dengue IgG seroconversion, what does this result indicate?

Persistent Positive Dengue IgM Without IgG Seroconversion After One Month

This serological pattern—positive dengue IgM at presentation and again one month later without IgG seroconversion—most likely indicates a false-positive IgM result due to cross-reactivity with another flavivirus or non-specific reactivity, rather than true dengue infection. 1

Understanding the Expected Antibody Timeline

In genuine dengue infections, the antibody response follows a predictable pattern:

• Primary dengue infection: IgM appears 3-5 days after symptom onset, while IgG develops around day 5-7 and persists for months to years 1
• By one month post-infection, IgG antibodies should be robustly positive in all true dengue cases, as IgG is produced after 10-12 days and becomes a lifetime marker 2
• The absence of IgG seroconversion after 30 days essentially rules out acute dengue infection 1, 3

Why This Pattern Suggests False-Positive IgM

The failure to develop IgG antibodies over a month-long period is incompatible with true dengue infection. Several mechanisms explain persistent false-positive IgM:

• Cross-reactivity with other flaviviruses: IgM antibodies can cross-react with dengue assays following infection or vaccination with yellow fever, Japanese encephalitis, Zika, West Nile, or tick-borne encephalitis viruses 1, 4
• Non-specific reactivity: IgM assays can produce false positives in the absence of any flavivirus infection, particularly in low-prevalence settings 1
• Persistent IgM from remote infection: While dengue IgM can persist for 2-3 months after initial infection 4, this scenario would still show positive IgG, which is absent in your patient 1

Recommended Diagnostic Approach

Perform plaque reduction neutralization testing (PRNT) against dengue and other endemic flaviviruses to definitively resolve this discordant result. 1, 4

• PRNT is the reference standard for specificity and can distinguish true dengue infection from cross-reactive antibodies 1, 2
• A PRNT titer ≥10 for dengue with titers <10 for other flaviviruses would confirm dengue; conversely, higher titers against another flavivirus would identify the true infecting agent 1, 5
• Document complete vaccination history for all flavivirus vaccines, as prior immunization is a common cause of false-positive IgM 4

Clinical Interpretation Algorithm

If PRNT is unavailable, report this as "indeterminate for dengue infection" and consider alternative diagnoses:

• The negative Ross River virus IgG makes recent Ross River infection unlikely, though acute-phase testing (IgM) would be more informative
• Consider testing for other endemic flaviviruses based on exposure history 1
• If the patient was symptomatic at initial presentation, retrospective NS1 antigen or NAAT testing on stored acute-phase serum (if available) would be definitive, as these tests detect active viral replication 1, 4

Critical Pitfalls to Avoid

• Do not assume acute dengue infection based on positive IgM alone, especially when IgG fails to develop 1, 4
• Do not repeat the same IgM assay expecting different results; the persistent positivity reflects assay characteristics, not evolving infection 1
• In areas with multiple circulating flaviviruses, integrate epidemiologic data about local virus circulation when interpreting results 1, 5

Secondary Dengue Infection Consideration

Secondary dengue infection does not explain this pattern. While IgM levels can be diminished or undetectable in secondary infections (absent in 28% of cases), IgG would be strongly positive from day 4-6 onward and detectable in all cases by day 12 6, 3. Your patient's negative IgG at one month excludes both primary and secondary dengue infection 3.