Evaluation of a pan-reactive hantavirus enzyme immunoassay and of a hantavirus immunoblot for the diagnosis of nephropathia epidemica.
BACKGROUND
Nephropathia epidemica (NE) caused by the hantavirus serotype Puumala (PUUV) is endemic in large parts of Europe. The prognosis of this disease is usually good. However, a rapid serological diagnosis is important to differentiate NE from potentially more severe renal conditions.


OBJECTIVE
To evaluate the diagnostic usefulness of a novel pan-reactive hantavirus enzyme immunoassay (EIA) and of a novel hantavirus immunoblot (IB).


METHODS
Three groups of serum samples were tested with both assays: 79 samples from 43 patients with acute NE, 27 samples from healthy adults, and 29 tricky samples from patients with autoantibodies, with acute Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infections, and from pregnant women.


RESULTS
With the EIA, all but two of the early samples of the NE patients and all of the follow-up samples were positive for hantavirus IgG. All control samples were negative. The IgM EIA was positive in 42 of the 43 primary NE samples. Weak IgM EIA reactions were observed for some of the serum samples from patients with acute EBV and CMV infections. Optimal sensitivity and specificity values for the EIA were achieved when both the IgG and the IgM results were considered for the diagnosis of acute NE. All of the early NE samples reacted with the hantavirus nucleocapsid proteins in the IgG IB and all but one of these samples in the IgM IB. Cross reactions between the PUUV and the Hantaan antigens were very common. Several of the control samples did show borderline or positive bands, but these were mostly bands against only one hantavirus antigen in either the IgG or the IgM IB. The presence of at least three hantavirus bands (PUUV or HTNV) in the IgG and IgM assays was highly predictive of acute NE.


CONCLUSIONS
Both assays were highly sensitive for the diagnosis of acute NE. However, the specificity of the IB IgM was only 76%. The specificity of both the IB and the EIA can be increased by modifications of the result interpretation.
Institute of Virology and Immunology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany.
J
J
Schubert
F
F
Tollmann
B
B
Weissbrich
D000208:Acute Disease; D000914:Antibodies, Viral / Q000097:blood*; D003429:Cross Reactions; D005260:Female; D005500:Follow-Up Studies; D018063:Hantaan virus / Q000276:immunology*; D018778:Hantavirus Infections / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D015151:Immunoblotting / Q000379:methods*; D007124:Immunoenzyme Techniques / Q000379:methods*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D019251:Nucleocapsid / Q000276:immunology; D011247:Pregnancy; D012680:Sensitivity and Specificity
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M