Flavivirus infections and diagnostic challenges for dengue, West Nile and Zika Viruses

Abstract Flaviviruses are arthropod-borne viruses, belonging to the Flaviviridae family. Dengue virus (DENV), West Nile virus (WNV), and Zika virus (ZIKV) are members of the Flavivirus genus, which are primarily transmitted by mosquitos. These viruses result in infections that are predominantly (80–85%) asymptomatic. Clinical manifestations of DENV, WNV, and ZIKV range from mild, self-limiting illnesses, to severe life-threatening diseases for which no therapeutics are available. They have caused extensive outbreaks worldwide, resulting in approximately 400 million cases annually and posing a significant global health threat. Standard diagnostic methods for these viruses rely on nucleic acid test (NAT) and serological assays. However, these approaches have notable limitations. NAT is limited due to the short duration of viremia and low viral loads, which restricts the detection of viral RNA. Serological assays are hindered by antibody cross-reactivity among DENV, WNV, and ZIKV, leading to inaccurate differential results and misdiagnosis. This review provides an overview of DENV, WNV, and ZIKV while addressing ongoing challenges in the differential diagnosis of these viruses, highlighting advancements in technologies. In this review, we aim to increase awareness of the limitations of DENV, WNV, and ZIKV diagnostics. It is our hope that the culmination of these insights will help to facilitate the identification of areas in need of innovation and increased study, which can aid in the development of new approaches to mitigate the global impact of these viruses and improve health outcomes.