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Test Code DNSAG Dengue Virus NS1 Antigen, Serum

Useful For

An aid in the diagnosis of dengue virus infection

Profile Information

Test ID Reporting Name Available Separately Always Performed
DENS1 Dengue NS1 Ag, S No Yes
DNAGI Dengue Ag Interpretation No Yes

Reporting Name

Dengue Virus NS1 Ag, S

Specimen Type

Serum


Specimen Required


Container/Tube: 

Preferred: Serum gel

Acceptable: Red top

Specimen Volume: 0.5 mL


Specimen Minimum Volume

0.4 mL

Specimen Stability Information

Specimen Type Temperature Time
Serum Refrigerated (preferred) 14 days
  Frozen  14 days

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross reject

Icterus

Mild OK; Gross reject

Other

NA

Clinical Information

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, 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 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 for the NS1 antigen alongside testing for IgM- and IgG-class antibodies to DV (DENGM) provides optimal diagnostic potential for both early and late dengue disease.

Reference Values

Negative

Reference values apply to all ages.

Interpretation

Positive:

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).

 

Negative:

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

 

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

Cautions

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 >7 days following symptom onset. Serologic testing for the presence of IgM and IgG antibodies to DV is recommended in such cases.

Supportive Data

The presence of nonstructural protein 1 (NS1) antigen overlaps with the dengue virus (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 1 below. Discordant samples were also tested by the PlateliaTM NS1 Ag EIA (BioRad Laboratories, Marnes-la-Coquette, France).

 

Table 1. 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 one sample was indeterminate by the Platelia NS1 EIA

 

Sensitivity: 96% (24/25); 95% Confidence Intervals (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

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

2. Dengue--an infectious disease of staggering proportions. Lancet 2013 Jun 22;381(9884):2136

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

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

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

Method Description

The InBios NS1 enzyme-linked immunosorbent assay (ELISA) is a 2-step sandwich-format colorimetric immunoassay for qualitative detection of nonstructural protein 1 (NS1) antigen in serum. Testing is performed according to manufacturer’s instructions on the Triturus automated EIA analyzer (Grifols, Miami, FL). Diluted patient samples and controls incubated in wells coated with purified capture antibody, specific for the dengue NS1 antigen. Following incubation, wells are washed, incubated with a horseradish peroxidase-conjugated polyclonal antibody specific to NS1 antigen and reincubated. Wells are subsequently washed and 3,3’,5,5’-tetramethlbenzidine substrate is added and incubated in the dark at room temperature. Stop solution is added next and the optical density (OD) of the reaction is measured at 450/620 nm. The immune status ratio (ISR) for each sample is calculated from the ratio of the OD obtained with the test sample divided by the OD from the calculated cutoff value (determined by the cutoff control sample).(Package insert: InBios DENV DetectTM NS1 ELISA, Seattle, WA)

Day(s) and Time(s) Performed

Tuesday; 9 a.m.

Analytic Time

Same day/1 day

Performing Laboratory

Mayo Medical Laboratories in Rochester

CPT Code Information

86790-NS1 Ag

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DNSAG Dengue Virus NS1 Ag, S 75377-2

 

Result ID Test Result Name Result LOINC Value
DENS1 Dengue NS1 Ag, S 75377-2
DNAGI Dengue Ag Interpretation 69048-7

Method Name

Enzyme-Linked Immunosorbent Assay (ELISA)

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.