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IgM antibody testing can identify most recent dengue infections after day 3 of illness. These tests should be run on samples with negative NS1 ELISA and PCR results, particularly after day 3 of illness. Interpreting positive IgM results is complicated because of cross-reactivity with other flaviviruses, like Zika.
Plaque Reduction Neutralization Tests (PRNT) can resolve false-positive IgM antibody results caused by non-specific reactivity, and, in some cases, can help identify the infecting virus. However, in areas with high prevalence of dengue and Zika virus neutralizing antibodies, PRNT may not confirm a significant proportion of IgM positive results.
Cross reactivity is a limitation of dengue serological tests and is seen when antibodies against other flaviviruses react on the dengue IgM ELISA test. For people living in or traveling to an area with concurrently circulating flaviviruses, clinicians will need to order plaque reduction neutralization test (PRNT) to rule out dengue on IgM-positive specimens. Physicians may consult with state or local public health laboratories or CDC for guidance. Zika, Japanese encephalitis, St. Louis encephalitis, West Nile, and yellow fever viruses are examples of other flaviviruses to be considered when ruling out dengue by PRNT. PRNT does not always a give conclusive diagnostic result, particularly in patients that have previously been exposed to more than one flavivirus. Current dengue molecular tests (E.g., RT-PCR) and NS1 ELISA tests do not have cross-reactivity with other flaviviruses of concern.
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