Beyond Fever and Pain: Diagnostic Methods for Chikungunya Virus

Abstract

Chikungunya virus (CHIKV) is an alphavirus that is primarily transmitted by Aedes species mosquitoes. Though reports of an illness consistent with chikungunya date back over 200 years, CHIKV only gained worldwide attention during a massive pandemic that began in East Africa in 2004. Chikungunya, the clinical illness caused by CHIKV, is characterized by a rapid onset of high fever and debilitating joint pain, though in practice, etiologic confirmation of CHIKV requires the availability and use of specific laboratory diagnostics. Similar to infections caused by other arboviruses, CHIKV infections are most commonly detected with a combination of molecular and serological methods, though cell culture and antigen detection are reported. This review provides an overview of available CHIKV diagnostics and highlights aspects of basic virology and epidemiology that pertain to viral detection. Although the number of chikungunya cases has decreased since 2014, CHIKV has become endemic in countries across the tropics and will continue to cause sporadic outbreaks in naive individuals. Consistent access to accurate diagnostics is needed to detect individual cases and initiate timely responses to new outbreaks.

Keywords: Chikungunya virus; alphavirus; molecular diagnostics; serology; viral culture.

FIG 1

(A) Diagram of the CHIKV genome indicating the relative length of the genes encoding nonstructural (green) and structural (blue) proteins. CHIKV molecular diagnostics have predominantly targeted the nsP1 and E1 genes (underlined), accounting for 10 and 14 of the 32 assays referenced in this review, respectively. (B) The structure of the CHIKV virion determined by electron microscopy is shown, highlighting the E1/E2 glycoprotein spikes on the virion surface, transmembrane domains, and the viral capsid (republished from PDBj.org under the Creative Commons Attribution 4.0 International license [190, 191]).

FIG 2

Countries with autochthonous cases of CHIKV (reported through 16 May 2018, dark purple). Inset maps display the geographical spread of CHIKV in the Americas between 2014 and 2017, though overall case numbers decreased ∼6-fold during this time period. Regions in dark purple reported autochthonous CHIKV transmission at any time through the year shown. Light purple highlights countries with any CHIKV transmission. Countries in gray had no autochthonous cases; asterisks represent imported cases. Maps were modified from those available at CDC.gov and PAHO.org. Notably, the categorization of Cuba differs between these sources, as autochthonous cases have not been reported to PAHO.

FIG 3

Case definitions and diagnostic approach to suspected chikungunya cases. The proposed time course for CHIKV diagnosis using serum was derived from published reports (103–106). The sensitivity of RNA detection in serum declines between days 4 and 7 as anti-CHIKV IgM becomes detectable. Anti-CHIKV IgG may become detectable at a similar time point (105). RT-LAMP, reverse transcription–loop-mediated isothermal amplification; CRP, C-reactive protein.