Dengue virus infection produces a broad spectrum of symptoms, many of which are non-specific. Thus, a diagnosis based only on clinical symptoms is unreliable. Early laboratory confirmation of clinical diagnosis may be valuable because some patients progress over a short period from mild to severe disease and sometimes to death. Early intervention may be life-saving.
Before day 5 of illness, during the febrile period, dengue infections may be diagnosed by virus isolation in cell culture, by detection of viral RNA by nucleic acid amplification tests (NAAT), or by detection of viral antigens by ELISA or rapid tests. Virus isolation in cell culture is usually performed only in laboratories with the necessary infrastructure and technical expertise. NS1 antigen detection kits now becoming commercially available can be used in laboratories with limited equipment and yield results within a few hours.
After day 5, dengue viruses and antigens disappear from the blood coincident with the appearance of specific antibodies. NS1 antigen may be detected in some patients for a few days after defervescence. Dengue serologic tests are more available in dengue-endemic countries than are virological tests.
For serology, the time of specimen collection is more flexible than that for virus isolation or RNA detection because an antibody response can be measured by comparing a sample collected during the acute stage of illness with samples collected weeks or months later. Low levels of a detectable dengue IgM response – or the absence of it – in some secondary infections reduces the diagnostic accuracy of IgM ELISA tests.
A four-fold or greater increase in antibody levels measured by IgG ELISA or by haemagglutination inhibition (HI) test in paired sera indicates an acute or recent flavivirus infection.
Interpretation of Dengue Diagnostic Tests
Highly suggestive
One of the following:
- IgM + in a single serum sample
- IgG + in a single serum sample with a HI titre of 1280 or greater
Confirmed
One of the following:
- PCR +
- Virus culture +
- IgM seroconversion in paired sera
- IgG seroconversion in paired sera or fourfold IgG titer increase in paired sera
Both the identification of virus/viral RNA/viral antigen and the detection of an antibody response are preferable for dengue diagnosis to either approach alone
References:
- Laughlin CA, Morens DM, Cassetti MC, Costero-Saint Denis A, San Martin JL, Whitehead SS, Fauci AS. Dengue research opportunities in the Americas. J Infect Dis. 2012 Oct 1;206(7):1121-7. [Medline]
- WHO. Dengue guidelines, for diagnosis, treatment, prevention and control. ISBN 978 92 4 1547871 (2009) [Full text]
Created: Sep 22, 2016.