Abstract

Arthropod-borne viruses (arboviruses) belonging to the Flavivirus genus of the Flaviviridae family, are a major public health threat in tropical and subtropical regions, and have recently become a medical concern in temperate zones. Most flaviviruses are classified as zoonotic viruses. Human flavivirus infections can be asymptomatic, responsible for unspecific symptoms in the first few days following infection, or responsible for severe complications potentially resulting in death. During the first days following symptom onset, laboratory diagnosis of acute human flavivirus infection is mainly based on molecular detection of the viral genome by RT-PCR methods, followed by the capture of specific antibodies using serological tests after the first week of infection. The detection of antibodies that have virus neutralizing activity can be used to confirm flavivirus infection. However, human flavivirus infections induce the production of cross-reactive antibodies, often making serology inconclusive. Indeed, serological diagnosis of flavivirus infection can be hampered by a patient’s history of flavivirus exposure, particularly in regions where multiple antigenically related flaviviruses co-circulate. We focus our mini review on conventional immunoassays that allow the diagnosis of major flavivirus-associated human infections in basic, routine and high-profile central health centers; and the interpretation of diagnostic serology tests for patients living within different epidemiological situations.

Highlights

  • More than five hundred arthropod-borne viruses are registered in the InternationalCatalog of Arboviruses, 25% of them are confirmed human pathogens [1]

  • Other medically-important flaviviruses such as Japanese encephalitis virus (JEV), which circulates mainly in Southern and Southeastern Asia [9], or tick borne encephalitis virus (TBEV), which is endemic in parts of Eurasia [10], have not yet expanded their global distribution but they have the potential for spread because their vectors are widely distributed

  • reverse transcription (RT)-PCR is a sensitive and specific method that allows rapid and reliable diagnosis of acute phase flavivirus in human diseases, its efficacy is mainly limited to the acute phase of infection, and can be impacted by briefness of the viremic period or a low viral load in the blood in patients infected with flaviviruses such as West Nile virus (WNV) [20] or Zika virus (ZIKV) [34]

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Summary

Introduction

More than five hundred arthropod-borne viruses (arboviruses) are registered in the International. Travelers returning from areas of endemic flavivirus circulation and the transport of infected animals increase the likelihood of introducing a new pathogen into temperate regions where competent arthropod vectors are increasingly present [12]. This was the case with the emergence of WNV in North America [13]. Flavivirus-related human diseases resulting from non-vector-borne transmission, mainly blood transfusion for ZIKV [19], WNV [20] or DENVs [21] as well as sexual and mother-to-child transmission for ZIKV [7], can complicate the individual diagnosis in flavivirus endemic areas. In this review we discuss the place of serology in laboratory diagnosis of flavivirus-related human diseases, and the advantages and limitations of the main serological assays, with a focus on interpretation of serological results in different epidemiological settings

Laboratory Diagnosis of Flavivirus-Associated Human Diseases
Methods
Early Diagnosis of Flavivirus-Associated Human Diseases
First Line Serological Assays
Diagnostic Methods
Confirmatory Serological Assays
Innovative Serological Assays
Serosurvey Studies
Access to Laboratory Tools
Co-Circulation of Flaviviruses
Prevalence of Flaviviruses
Determination of the Onset of Symptoms
Patient’s Past Exposure to Flaviviruses
Findings
Conclusions
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