Impact of the Yosemite hantavirus outbreak on hantavirus antibody testing at a national reference laboratory

Abstract

In conjunction with the 2012 Yosemite hantavirus outbreak, the number of sera our facility tested for hantavirus antibodies increased. We tracked test results and used the data set to determine if a more efficient testing algorithm was possible. Sera were screened using laboratory-developed pan-hantavirus IgG and IgM enzyme immunoassays (EIAs), with an index of >1.10 defined as positive. Sera that were IgM positive by screening (screen IgM(+)) were tested for Sin Nombre virus (SNV)-specific IgM using a laboratory-developed EIA; screen IgM(+) IgG(+) sera were also tested for SNV IgG using a laboratory-developed immunoblot assay. SNV antibody-positive samples were sent to state public health laboratories (PHL) or the CDC for confirmation. Of 3,946 sera tested from July through December 2012, 205 were screen IgM(+) IgG negative (IgG(-)); 7/205 were SNV IgM(+), but only 1/5 sent to PHL/CDC was confirmed as SNV IgM(+). Of 61 screen IgM(+) IgG(+) sera, 16 were SNV antibody positive; 13/16 sera (from 11 patients) went to PHL/CDC, where SNV infection was confirmed for all patients. Of 12 confirmed patients, 7 had been exposed at Yosemite. A modified algorithm defining screen indices of ≥2.00 as positive identified 11/12 confirmed cases while reducing the number of sera requiring SNV-specific antibody testing by 65%; the patient missed was not tested until 3 months after the onset of symptoms. Hantavirus antibody testing at our facility identified 12 SNV-infected patients, including 7 exposed at Yosemite. Some screen IgM(+) IgG(-) SNV IgM(+) results were false positives, emphasizing the value of PHL/CDC confirmatory testing. We identified a modified algorithm requiring analysis of fewer specimens for SNV-specific antibodies without loss of sensitivity.

Figures

Fig 1

Hantavirus antibody testing timeline. Patient designations indicating location of exposure (e.g., Y1 or N1) for the 12 patients with confirmed SNV infection are placed at the week of specimen collection.

Fig 2

Confirmatory SNV antibody results for hantavirus IgM screen-positive sera. Values in parentheses indicate the number of samples; orange boxes indicate samples with confirmed SNV infection.