Chikungunya Virus RNA and Antibody Testing at a National Reference Laboratory since the Emergence of Chikungunya Virus in the Americas

Abstract

Since first reported in the Americas in December 2013, chikungunya virus (CHIKV) infections have been documented in travelers returning from the Caribbean, with many cases identified by CHIKV antibody and/or RNA testing at our laboratory. We used our large data set to characterize the relationship between antibody titers and RNA detection and to estimate IgM persistence. CHIKV RNA was measured by nucleic acid amplification and CHIKV IgG/IgM by indirect immunofluorescence. Of the 1,306 samples submitted for RNA testing in January through September 2014, 393 (30%) were positive; for 166 RNA-positive samples, CHIKV antibody testing was also ordered, and 84% were antibody negative. Of the 6,971 sera submitted for antibody testing in January through September 2014, 1,811 (26%) were IgM positive; 1,461 IgM positives (81%) were also IgG positive. The relationship between the CHIKV antibody titers and RNA detection was evaluated using 376 IgM-positive samples (138 with RNA testing ordered and 238 deidentified and tested for RNA). RNA detection showed no significant association with the IgM titer but was inversely related to the IgG titer; 63% of the IgG negative sera were RNA positive, compared to 36% of sera with low IgG titers (1:10 to 1:80) and 16% with IgG titers of >1:160. Using second-sample results from 62 seroconverters, we estimated that CHIKV IgM persists for 110 days (95% confidence interval, 78 to 150 days) after the initial antibody-negative sample. These findings indicate that (i) RNA detection is more sensitive than antibody detection early in CHIKV infection, (ii) in the absence of RNA results, the IgG titer of the IgM-positive samples may be a useful surrogate for viremia, and (iii) CHIKV IgM persists for approximately 4 months after symptom onset. C hikungunya virus (CHIKV) is an alphavirus transmitted from one person to another via mosquitos of the genus Aedes (1-3). Nearly all individuals infected with CHIKV become symptomatic, typically exhibiting fever, rash, and debilitating arthralgia (1-3). Most infected individuals show complete recovery within a few weeks; however, 15 to 60% of patients develop chronic arthralgia, which in turn can lead to arthritic joint damage (2, 4-7). Intrapartum mother-to-child transmission has been documented, with serious neurologic and hemorrhagic complications observed in affected infants (8).Since CHIKV was first identified in 1953 (9), there have been multiple epidemics of CHIKV infections throughout Africa and Asia (2). A particularly large CHIKV outbreak began in eastern Africa in late 2004 and then spread to Indian Ocean islands, India, and southeast Asia over the next 2 years. Estimates suggest that nearly 2 million people became infected during this outbreak (2, 10-15).Because the mosquito vectors for CHIKV transmission are present in tropical and temperate regions worldwide and recently infected travelers moving between areas where CHIKV is endemic and not endemic exhibit high levels of viremia (16), epidemiologists have warned that CHIKV could move into new g...

Evaluation of Two Enzyme-Linked Immunosorbent Assay Kits for Chikungunya Virus IgM Using Samples from Deceased Organ and Tissue Donors

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A Case of Diabetic Ketoacidosis Following Chikungunya Virus Infection

“…5 An IgG antibody response is typically detectable 1-2 days after IgM becomes detectable, approximately on day 7 of illness. [13][14][15] IgG levels can persist for years whereas IgM levels can persist for up to 3-4 months. 5 Chikungunya virus infections can cause high levels of viremia for 4-6 days after onset of symptoms but can persist up to 12 days.…”

Diagnostic potential of monoclonal antibodies against the capsid protein of chikungunya virus for detection of recent infection

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