Aids in the diagnosis of dengue virus infection
See Mosquito-borne Disease Laboratory Testing in Special Instructions.
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. As an adjunct to serologic testing, identification of early DV infection may be made by detection of the DV NS1 antigen. NS1 antigenemia is detectable within 24 hours of infection and up to 9 days following symptom onset. The DV NS1 antigen can be detected by ordering DNSAG / Dengue Virus NS1 Antigen, Serum.
IgG: negative
IgM: negative
Reference values apply to all ages.
IgG:
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.
IgM:
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 drawn too soon following exposure may be negative for IgM antibodies to DV. If DV remains suspected, a second specimen, drawn approximately 10 to 12 days following exposure should be tested.
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.
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% Confidence Intervals (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.
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