ARTHROPOD-BORNE VIRUSES

Abstract

The arthropod-borne viruses (arboviruses) comprise a rather large and heterogeneous number of different virus families like Togaviridae, Flaviviridae, Bunyaviridae, Reoviridae, Rhabdoviridae, and Orthomyxoviridae. More than hundred viruses are currently classified as arboviruses from which the Togaviridae and Flaviviridae are the best known (1). As arthropod borne, all of these viruses share the common feature of the transmission by mosquitoes, ticks, or phlebotomes. Since the frequent accidental transmission of these viruses by an arthropod vector can cause severe clinical and subclinical infections in humans, a quick and reliable diagnosis of the viral infection is very important. In order to provide clear and state-of-the-art information, this chapter concentrates on the most important pathogens with high impact on public health. These viruses include Dengue Virus (DENV), Yellow Fever Virus (YFV), Tick-borne Encephalitis Virus (TBEV), and West Nile (WN) for the Flaviviruses, Chikungunya Virus (CHIKV) as an Alphavirus and the Sandfly Fever Virus (SFV), Crimean Congo hemorrhagic fever virus (CCHFV), and Rift valley Fever virus (RVF) for the Bunyaviruses. Diagnostic testing for arboviruses is mainly limited to patients who are suspected to be infected by these viruses. For example, DENV, displaying four serotypes, has a global distribution in nearly all subtropical areas and have become a major international public health concern in recent years, with about 2.5 billion people at risk for the disease (2). The clinical features of dengue fever vary according to the age of the patient and the DEN strain, ranging from a mild fever to the Dengue hemorrhagic fever (DHF) with potentially deadly complications, or to the Dengue shock syndrome (DSS) that is characterized by rapid signs of circulatory failure and where the patient may die within 12 to 24 hours without proper treatment. Depending on the cause of disease, different measures for virus diagnosis must be initiated to confirm the clinical diagnosis. During acute infection, the direct detection of the viral pathogen itself is the only possibility for a successful diagnosis. This can be achieved only with a limited number of diagnostic assays focusing either on the detection of virus-specific proteins or the virus genome (Fig. 1 ). For particle detection by electron microscopy, virus loads have to exceed 10 6 /mL, which is largely dependent on the virus, the course of infection, and the time point of investigation. Table 1 gives a brief overview on the sensitivity and specificity of the different diagnostic methods. The estimated time required for the different diagnostic methods also gives important information on the practicality of these diagnostic methods in the acutely infected patient. Because of low commercial impact for most of the flaviviruses, specific assays for protein detection do not exist, and such assays are available as in-house assays in only a few laboratories (Table 2). Some assays may involve immunohistochemistry staining of tissue samples with monoclonal antibodies directed against the suspected virus (3). Other assays applied for the detection of virus antigens are specific capture enzyme immunoassays (EIA), but these are rather uncommon and not very sensitive. Owing to the unique genetic code of RNA and DNA, the detection of virus-specific sequences by PCR methods has been the major technology for diagnostic testing for many years. In general, PCR approaches are very rapid, enable extremely low detection limits, and provide genetic material for further characterization (for example, by sequencing). On the other hand, the high specificity due to the exact base pairing of primer and template may lead to false-negative results even after minor changes in the target sequence. Since flaviviruses are prone to frequent sequence aberrations the PCR assays used should be selected carefully. Finally, the exact knowledge of the target virus sequences has to be available for the proper design of reliable assays, a prerequisite that is hard to achieve for flaviviruses. However, nearly all recent cases of acute viral hemorrhagic fevers imported to the western world