Dengue (DENV)

Primary infection in a flavirus-naive individual

Note: based on individual host response and test sensitivity in some cases individual biomarkers might be detected earlier or later. Therefore in addition clinical parameters should always be considered. Categorizing primary and secondary infections should not change patient management according to PAHO-WHO, Dengue guidelines for patient care in the Region of the Americas, 2016.

Diagnostic Dengue markers and disease stages

days from symptoms onset 1–5
Symptoms
  • Sudden high-grade fever
  • Headache, retro-orbital pain, myalgia, arthralgia
  • Nausea, vomiting are common
  • Progressive decrease in total white cell count
  • Potential for dehydration
RT-PCR (Dengue RNA) +
Dengue NS1 Antigen +
Dengue IgM -
Dengue IgG -
Interpretation Confirmed Acute Primary Dengue (Early Febrile Phase). This result indicates viral replication before a detectable antibody response has mounted.
days from symptoms onset 5-7
Symptoms
  • After a defervescence (fever drops to ≤37.5°C), the critical phase might arise and warning signs may appear
  • Plasma leakage begins, leading to rising hematocrit and a rapid drop in platelets
  • Period of significant plasma leakage, usually lasting 24–48 hours
  • High risk of shock from critical plasma volume loss
  • Pleural effusion and ascites may be clinically detectable
  • Severe hemorrhage can occur, especially with prolonged shock
RT-PCR (Dengue RNA) -
Dengue NS1 Antigen +/-
Dengue IgM +
Dengue IgG -
Interpretation Probable Acute Primary Dengue. Viremia has likely cleared , but the IgM response is present. Confirmation requires a second serum sample.
days from symptoms onset >7
Symptoms
  • Gradual reabsorption of extravascular fluid over 48–72 hours
  • General well-being improves, appetite returns
  • Hematocrit stabilizes or lowers due to hemodilution
  • Platelet count begins to recover
  • Risk of fluid overload if IV fluids are excessive
RT-PCR (Dengue RNA) -
Dengue NS1 Antigen -
Dengue IgM +
Dengue IgG +
Interpretation Probable Acute or Recent Secondary Dengue. The combination of positive IgM and IgG after the viremic phase is highly suggestive of a secondary infection.
days from symptoms onset /
Symptoms
  • Patient is typically asymptomatic, having recovered from a past infection
RT-PCR (Dengue RNA) -
Dengue NS1 Antigen -
Dengue IgM -
Dengue IgG +
Interpretation Past Dengue Infection. Does not signify current acute illness unless a second, paired serum sample shows a ≥4-fold increase in IgG titer.

Adapted from:

  1. PAHO-WHO, Dengue: guidelines for patient care in the Region of the Americas, 2016. Available at: https://iris.paho.org/handle/10665.2/31207 [Accessed July 11,2025]
Product Description Tests Product page
Elecsys® Dengue Ag Immunoassay for the in vitro qualitative detection of dengue virus NS1 antigen in human serum and plasma. The Elecsys Dengue Ag assay is intended to be used as an aid in the diagnosis of an acute dengue virus infection in patients with suspected dengue virus infection. 100
Elecsys® Dengue IgM Launch is planned in 2026 100
Elecsys® Dengue IgG Launch is planned in 2026 100
TIB MOLBIOL LightMix® Modular Dengue Virus (CE-IVD) is intended to be used to diagnose an infection by detection of the pathogen genome in a Total-NA nucleic acid extract obtained from specimen from patients with symptoms of tropical disease and respective exposition history.
cobas® CHIKV/DENV (CE) qualitative in vitro test for the direct detection of chikungunya virus (CHIKV) RNA and dengue virus (DENV) serotypes 1-4 RNA in human plasma.
cobas® omni utility channel DENV serotype DENV 1-4 (RUO)
cobas® omni utility channel ZIKA/CHIKV/DENV/WNV (RUO)

Adapted from:

  1. Source: WHO/PAHO 2016 Guidelines [internet; cited 2025 Jul 11]. Available from: https://iris.paho.org/handle/10665.2/31207
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Days Since Symptom Onset

5 Days Since Symptom Onset
< ≥
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Recommended test

RT-PCR
NS1 Antigen
Viral Isolation
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Recommended test

RT-PCR
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Step 3

Recommended test

NS1 Antigen
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Step 3

Recommended test

Viral Isolation
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Summary

Acute Dengue

This result indicates viral replication. Follow viral isolation by identifying serotype & genotype if required.

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Summary

Acute Dengue

This result indicates viral replication. Follow viral isolation by identifying serotype & genotype if required.

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Summary

Acute Dengue

This result indicates viral replication. Follow viral isolation by identifying serotype & genotype if required.

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Summary

Inconclusive Case

Proceed to 2nd sample (≥ 5 days) for serology.

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Summary

Inconclusive Case

Proceed to 2nd sample (≥ 5 days) for serology.

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Summary

Inconclusive Case

Proceed to 2nd sample (≥ 5 days) for serology.

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IgM and IgG Serology

IgM
IgG
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Summary

Probable Case

Requires 2nd sample to confirm.

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Summary

Probable Case

Requires 2nd sample to confirm.

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Summary

Negative Case

If clinical suspicion is high, repeat with 2nd sample.

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Summary

Confirmed Case

Primary or Secondary Infection

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Summary

Probable Case

Requires 2nd sample to confirm.

Back
Next Restart simulation
Step
Result
Interpretation
1
Days since symptom onset = ...
waiting for input
1
Days since symptom onset ≥5
Probable critical or recovery phase (recent infection).
1
Days since symptom onset <5
Probable early febrile phase (acute infection)
2
Recommended test = ...
waiting for input
2
RT-PCR
Perform RT-PCR
2
NS1 Antigen
Perform NS1 Antigen
2
Viral Isolation
Perform Viral Isolation
3
RT-PCR = ...
waiting for input
3
RT-PCR = negative
Inconclusive case.
A new sample taken after day 5 of the illness should be tested by serology (to be tested for IgM and IgG antibodies) before ruling out dengue infection.
3
RT-PCR = positive
Acute Dengue.
This result indicates viral replication. Follow viral isolation by identifying serotype & genotype if required.
3
NS1 Antigen = ...
waiting for input
3
NS1 Antigen = negative
Inconclusive case.
A new sample taken after day 5 of the illness should be tested by serology (to be tested for IgM and IgG antibodies) before ruling out dengue infection.
3
NS1 Antigen = positive
Acute Dengue.
This result indicates viral replication. Follow viral isolation by identifying serotype & genotype if required.
3
Viral Isolation = ...
waiting for input
3
Viral Isolation = negative
Inconclusive case.
A new sample taken after day 5 of the illness should be tested by serology (to be tested for IgM and IgG antibodies) before ruling out dengue infection.
3
Viral Isolation = positive
Acute Dengue.
This result indicates viral replication. Follow viral isolation by identifying serotype & genotype if required.
2
IgM and IgG Serology = ...
waiting for input
2
IgM positive, IgG positive
Probable case.
This pattern could be a sign of a secondary infection, which occurs in a person who has previously been infected with a different dengue serotype. Nevertheless, it could be a primary infection taken in the recovery window where IgM are positive but decreasing and IgG are also positive but increasing. A definitive confirmed diagnosis is established by analyzing paired serum samples. An increase in IgG antibody titers between the acute (first) sample and a convalescent (second) sample confirms a recent infection
2
IgM positive, IgG negative
Probable case.
This pattern is characteristic of a person's first-ever infection with a dengue virus. In a primary infection, IgM antibodies are the first to be produced by the immune system, becoming detectable around days 3-5 after symptoms begin. IgG antibodies appear later. Therefore, having detectable IgM without IgG is expected in the later stage of a primary infection. According to the guidelines, a single positive IgM result is sufficient to classify the case as "probable" or "highly suggestive" of a recent dengue infection. For a definitive confirmed diagnosis, a second (convalescent) serum sample is needed. This sample, collected 14-21 days after the first, is used to demonstrate IgG seroconversion (a change from negative to positive)
2
IgM negative, IgG negative
Negative Case
If the clinical case is very florid, request 2nd sample and repeat
2
IgM negative, IgG positive
Probable case.
Past Dengue Infection is the most common interpretation, so it usually indicates that the person had a dengue infection at some point in the past and is not acutely ill with dengue now. Nevertheless, it could also be a secondary infection (an infection in someone who has previously had dengue). During secondary infection, the IgG antibody response is very rapid and strong, often appearing at high levels within a few days of fever onset. In these cases, the IgM antibody response can be low, delayed, or sometimes completely undetectable.

Because a single test result can be ambiguous, the definitive next step is to analyze paired sera. A second sample should be collected, typically 14-21 days after the first one. If there is an increase in IgG antibody titers between the two samples, it confirms a recent dengue infection. If there is no significant change in the IgG level, it confirms a past infection.
End of test sequence