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Zika virus – Wikipedia, Dengue virus – Wikipedia, West Nile fever – Wikipedia, Chikungunya – Wikipedia, Yellow fever – Wikipedia belong to the same virus family, Flavivirus – Wikipedia and are endemic (Endemism – Wikipedia) in overlapping regions of the world.

  • One consequence of these viruses being related is structural similarity of their Antigen – Wikipedia. This in turn means antibodies against one of these flaviviruses can cross-react (Cross-reactivity – Wikipedia) with another flavivirus.
  • Chances of such antibody cross-reactivity increase in regions endemic for these flaviviruses since a person suspected of being currently infected with Zika in Brazil for example may in the past have been infected with Dengue or Chikungunya or may have been vaccinated with Yellow fever vaccine – Wikipedia.

Under such circumstances, it becomes difficult to conclude whether Zika-reactive antibody detected in a current serological (blood) test truly indicates current Zika infection. In other words, are such antibodies Zika-specific or cross-reactive to antigen bits (Epitope – Wikipedia) Zika shares with other flaviviruses such as Dengue?

Thus, structural similarity with other related viruses and spread across similar geographic regions of the world, these are the two main factors that make a serological (blood) diagnosis test for Zika-specific antibodies particularly thorny. This is why Zika diagnosis gold standard currently consists of Reverse transcription polymerase chain reaction – Wikipedia (RT-PCR) for Zika virus RNA in serum or urine collected < 2 weeks after symptom onset (1).

That said, a study published in Science in July 2016 (2) isolated novel antibody candidates from Zika-infected patients. While this study found that most of the circulating antibodies elicited by Zika in these patients cross-reacted with Dengue, antibodies against Zika’s non-structural protein 1 (NS1) were largely Zika-specific.

  • These results suggest that assays to identify and measure antibodies specific for Zika NS1 might have specific diagnostic potential for Zika.
  • Of course, it remains to be seen if other studies concur with these results.
  • Also important to keep in mind that cross-reactivity with Dengue may not be the only confounder. Rather depending on the region and an individual’s life history, cross-reactivity with Chikungunya, Yellow fever, West Nile fever, etc., may also need to be ruled out in serological (blood) antibody-based diagnostic tests.


1. Oduyebo, Titilope. “Update: interim guidance for health care providers caring for pregnant women with possible Zika virus exposure—United States, July 2016.” MMWR. Morbidity and Mortality Weekly Report 65 (2016). https://www.cdc.gov/mmwr/volumes…

2. Stettler, Karin, et al. “Specificity, cross-reactivity and function of antibodies elicited by Zika virus infection.” Science (2016): aaf8505. http://icmr.nic.in/zika/publicat…