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Test Catalog

Test ID: DENVP    
Dengue Virus Antibody/Antigen Panel, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Aiding in the diagnosis of dengue virus infection by detection of IgM and IgG antibodies and the nonstructural protein 1 (NS1)

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Mosquito-borne Disease Laboratory Testing in Special Instructions.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Dengue virus (DV) is a globally distributed flavivirus with 4 distinct serotypes (DV-1, -2, -3, -4) and is primarily transmitted by the Aedes aegypti mosquito, which is found throughout the tropical and subtropical regions of over 100 countries. DV poses a significant worldwide public health threat with approximately 2.5 to 3 billion people residing in DV endemic areas, among whom 100 to 200 million individuals will be infected and approximately 30,000 patients will succumb to the disease annually.

 

Following dengue infection, the incubation period varies from 3 to 7 days and while some infections remain asymptomatic, the majority of individuals will develop classic dengue fever. Symptomatic patients become acutely febrile and present with severe musculoskeletal pain, headache, retro-orbital pain, and a transient macular rash, most often observed in children. Fever defervescence signals disease resolution in most individuals. However, children and young adults remain at increased risk for progression to dengue hemorrhagic fever and dengue shock syndrome, particularly during repeat infection with a new DV serotype.

 

Detection of dengue-specific IgM and IgG-class antibodies remains the most commonly utilized diagnostic method. Seroconversion occurs approximately 3 to 7 days following exposure and therefore testing of acute and convalescent sera may be necessary to make the diagnosis. Detection of the DV nonstructural protein 1 (NS1) has emerged as an alternative biomarker to both serologic- and molecular-based techniques for diagnosis of acute DV infection. NS1 antigenemia is detectable within 24 hours and up to 9 days following symptoms onset. This overlaps with the DV viremic phase and NS1 is often detectable prior to IgM seroconversion. Concurrent evaluation (as performed in this profile) for the NS1 antigen alongside testing for IgM- and IgG-class antibodies to DV provides optimal diagnostic potential for both early and late dengue disease.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

IgG: negative

IgM: negative

NS1: negative

Reference values apply to all ages.

Interpretation Provides information to assist in interpretation of the test results

The presence of IgG-class antibodies to dengue virus (DV) is consistent with exposure to this virus sometime in the past. By 3 weeks following exposure, nearly all immunocompetent individuals should have developed IgG antibodies to DV.

 

The presence of IgM-class antibodies to DV is consistent with acute-phase infection.

 

IgM antibodies become detectable 3 to 7 days following infection and may remain detectable for up to 6 months or longer following disease resolution.

 

The absence of IgM-class antibodies to DV is consistent with lack of infection. However, specimens collected too soon following exposure may be negative for IgM antibodies to DV. If DV remains suspected, a second specimen, collected approximately 10 to 12 days following exposure should be tested.

 

 

The presence of dengue nonstructural protein 1 (NS1) antigen is consistent with acute-phase infection with dengue virus.

 

The NS1 antigen is typically detectable within 1 to 2 days following infection and up to 9 days following symptom onset.

 

NS1 antigen may also be detectable during secondary dengue virus infection, but for a shorter duration of time (1-4 days following symptom onset).

 

The absence of dengue NS1 antigen is consistent with the lack of acute-phase infection.

 

The NS1 antigen may be negative is samples collected immediately following dengue virus infection (<24-48 hours) and is rarely detectable following 9 to 10 days of symptoms.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Test results should be used in conjunction with clinical evaluation, including exposure history and clinical presentation.

 

False-positive results, particularly with the dengue virus (DV) IgG enzyme-linked immunosorbent assay (ELISA), may occur in persons infected with other flaviviruses, including Zika virus, West Nile virus, and St. Louis encephalitis virus. Obtaining a detailed exposure history and further laboratory testing may be necessary to determine the infecting virus.

 

Positive test results may not be valid in persons who have received blood transfusions or other blood products within the last several months.

 

The significance of a negative result in an immunosuppressed patient is unclear.

 

Results should be used in conjunction with clinical presentation and exposure history.

 

Though uncommon, false-positive nonstructural protein 1 (NS1) results may occur in individuals with active infection due to other flaviviruses, including West Nile virus and yellow fever virus.

 

Negative NS1 antigen results may occur if the specimen was collected more than 7 days following symptom onset. Serologic testing for the presence of IgM and IgG antibodies to DV is recommended in such cases.

Supportive Data

A total of 200 prospective serum samples submitted for dengue virus (DV) IgM and IgG testing by the Focus Diagnostics DV IgM and IgG EIAs were also tested by the InBios IgM and IgG DV assays. The results were compared and the data summarized in Tables 1 and 2.

 

Table 1. Comparison of the InBios and Focus Diagnostics DV IgM EIA

 

Focus Diagnostics DV IgM EIA

 

 

Positive

Negative

InBios

DV IgM EIA

Positive

14

0

Negative

1

184

Equivocal

1

0

 

Sensitivity: 87.5% (14/16); 95% CI 62.7%-97.7%

Specificity: 100% (184/184); 95% CI 97.5%-100%

Agreement: 99% (198/200); 95% CI 96.1%-99.9%

 

Table 2. Comparison of the InBios and Focus Diagnostics DV IgG EIA

 

Focus Diagnostics DV IgG EIA

 

 

Positive

Negative

InBios

DV IgG EIA

Positive

34

0

Negative

0

164

Equivocal

2

0

 

Sensitivity: 94.4% (34/36); 95% CI 80.9%-99.4%

Specificity: 100% (164/164); 95% CI 97.2%-100%

Agreement: 99% (198/200); 95% CI 96.1%-99.9%

 

An additional 42 serum samples positive for IgG-class antibodies to West Nile virus (n=24), St. Louis encephalitis virus (n=9) and California (LaCrosse) virus (n=9) were also tested by the InBios DV IgG EIA and the data are summarized below in Table 3.

 

Table 3. Cross-reactivity of the InBios DV IgG EIA with antibodies to West Nile virus, St. Louis encephalitis virus and California (LaCrosse) virus

West Nile Virus IgG Positive

St. Louis Encephalitis Virus Positive

California (LaCrosse) Virus Positive

InBios

DV IgG EIA

Positive

18

7

1

Negative

2

0

8

Equivocal

4

2

0

 

Note that the InBios DV IgG EIA shows significant cross-reactivity with antibodies to West Nile virus and St. Louis encephalitis virus.

 

The presence of nonstructural protein 1 (NS1) antigen overlaps with the DV viremic phase for the first 4 to 5 days following infection and therefore, the performance characteristics of the InBios DV NS1 EIA were compared to the Focus Diagnostics DV real-time PCR (RT-PCR), which detects RNA from all 4 DV serotypes. Seventy-seven serum samples previously evaluated by the Focus Diagnostics RT-PCR assay were also tested by the InBios DV NS1 EIA and the results are compared in Table 4 below. Discordant samples were also tested by the Platelia NS1 Ag EIA (BioRad Laboratories, Marnes-la-Coquette, France).

 

Table 4. Comparison of the InBios NS1 EIA to RT-PCR for DV Detection

 

Focus Diagnostics DV RT-PCR

 

 

Positive

Negative

InBios

DV NS1 EIA

Positive

24

7(b)

Negative

1(a)

43

Equivocal

0

2(c)

 

a. This sample was negative by the Platelia NS1 EIA

b. Five samples were also positive by the Platelia NS1 EIA

c. One sample was negative and 1 sample was indeterminate by the Platelia NS1 EIA

 

Sensitivity: 96% (24/25); 95% CI: 79.1%-100%

Specificity: 82.7% (43/52); 95% CI: 70.1%-90.9%

Overall Agreement: 87.1% (67/77); 95% CI: 77.6%-93%

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Bhatt S, Gething PW, Brady OJ, et al: The global distribution and burden of dengue. Nature. 2013 Apr 25;496:504-507 doi: 10.1038/nature12060

2. Dengue--an infectious disease of staggering proportions. Lancet. 2013 Jun 22;381(9884):2136 doi: 10.1016/S0140-6736(13)61423-3

3. Rigau-Perez JG, Clark GG, Gubler DJ, et al: Dengue and dengue haemorrhagic fever. Lancet. 1998 Sep 19;352:971-977

4. Tang KF, Ooi EE: Diagnosis of dengue: an update. Expert Rev Anti Infect Ther. 2012 Aug;10:895-907 doi: 10.1586/eri.12.76

5. Guzman MG, Kouri G: Dengue diagnosis, advances and challenges. Int J Infect Dis. 2004 Mar;8:69-80

Special Instructions Library of PDFs including pertinent information and forms related to the test