THE CLINICAL USEFULNESS OF A PUUMALAVIRUS RECOMBINANT NUCLEOCAPSID PROTEIN-BASED ENZYME-LINKED-IMMUNOSORBENT-ASSAY IN THE DIAGNOSIS OF NEPHROPATHIA-EPIDEMICA AS COMPARED WITH AN IMMUNOFLUORESCENCE ASSAY

Background: Nephropathia epidemica (NE), a hemorrhagic fever with rena l syndrome (HERS) predominantly encountered in northern Europe, is a f ebrile disease, commonly associated with acute renal impairment. A rap id and reliable serological diagnosis is required to differentiate NE from other acute febrile illnesses in endemic areas, Objective: To eva luate a Puumala (PUU) virus recombinant nucleocapsid protein (rN) base d enzyme-linked immunosorbent assay (ELISA) for the serological diagno sis of NE as compared with an immunofluorescence assay (IFA) in a clin ically relevant patient sample. Study design: During a four-month peri od, 618 serum samples From 512 patients with an illness suggestive of NE, sent to the Department of Clinical Virology for serological analys is, were included in the study. All sera were tested by PUU rN ELISA f ur presence of specific IgG, IgM and IgA antibodies and by IFA using P UU virus infected cells as antigen for presence of IgG and IgM antibod ies. Patients with discordant results by IFA and rN ELISA were further serologically and/or clinically evaluated to assess the probability o f NE, Results: Compared to IFA, the specificities of the IgM and IgG r N ELISA were 100% and the corresponding sensitivities were 94.0%, The positive and negative predictive values of the PUU IgM rN ELISA in dia gnosing NE infection was 100 and 98.6%, respectively. The positive pre dictive values for present NE infection of Ige rN ELISA and IFA were 6 8.3 and 71.4%, respectively. The positive predictive value of IgA rN E LISA was 95.8% and the negative 92.7%, Conclusions: The demonstration of specific IgM by rN ELISA is a highly specific and reliable method f or the serological confirmation of NE. Detection of IgG antibodies by rN ELISA or IFA has a low predictive value to diagnose NE in an endemi c area. The diagnostic value of IgA determination is in between IgM an d IgG determinations.