Diagnosis Of Nephropathia Epidemica Research Articles

Seroprevalence of hantavirus infections in Switzerland in 2009: difficulties in determining prevalence in a country with low endemicity

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Erste in der Schweiz erworbene Nephropathia epidemica

Summary First case of nephropathia epidemica contracted in Switzerland The patient, a 43-year-old male living in western Switzerland, presented with unprecedented prostration, fever, vomiting, diarrhoea, gastric pain, dysuria and severe thrombocytopenia. After wide-ranging differential diagnosis comprising urosepsis among others, the patient was diagnosed as having rapid progressive renal failure due to acute tubulointerstitial nephritis. Extensive laboratory investigations finally revealed hantavirus-specific positive IgM and IgG by immunoblot technique. The diagnosis of nephropathia epidemica was confirmed by a hantavirus serotype-specific focus reduction neutralisation test performed on the convalescent serum obtained 4½ months after the onset of symptoms, revealing serotype Puumala virus as the causative agent. The patient was treated symptomatically and could be discharged in good health 10 days after disease onset. Hantaviruses are rodent-borne. This patient must have been infected in Switzerland since his last stay abroad had been prior to the upper limit of incubation time. Hantavirus infection should therefore be considered in Swiss patients with acute nephritis of unknown origin.

Severe thrombocytopenia and response to corticosteroids in a case of nephropathia epidemica

Nine days after working in the woods, a previously healthy 32-year-old man fell seriously ill. His symptoms included high fever, chills, diffuse myalgia, severe headache, and back pain. On the fifth day of onset of symptoms, blood tests showed creatinine levels of 5.4 mg/dL accompanied by marked proteinuria. After admission to the hospital, a diagnosis of nephropathia epidemica (NE) caused by Puumala virus was made using solid-phase enzyme-linked immunosorbent assay (ELISA). The patient gradually recovered renal function without requiring dialysis. However, he surprisingly experienced a sharp decline in platelet count to a minimum of 2,000/microL with concomitant occurrence of petechiae and conjunctival hemorrhage. Prednisolone was initiated, resulting in a swift rise in platelets. Six days later, when the medication was withdrawn, a sharp decrease in platelets recurred. The steroids were then readministered for the next 3 months, thus reestablishing a stable platelet count. The immediate rise of platelets after administration of prednisolone supports the pathophysiological view of hantavirus infection as an immunologically mediated disease. Corticosteroids in the treatment of hantavirus-associated thrombocytopenia might need further systematic evaluation. (Am J Kidney Dis 1998 Jan;31(1):116-20)

Biotin-labeled antigen: a novel approach for detection of Puumala virus-specific IgM.

A novel enzyme-linked immunosorbent assay, BLA IgM-ELISA, based on baculovirus-expressed Puumala (PUU) virus nucleocapsid protein, was developed for rapid diagnosis of nephropathia epidemica. The recombinant antigen (bac-PUU-N) was purified to homogeneity by HPLC and conjugated to biotin. The biotin-streptavidin system, in combination with the mu-capture technique, rendered the BLA IgM-ELISA a sensitivity similar to or higher than that of PUU virus IgM mu-capture ELISA based on native antigen. The assay was shown to be highly specific when evaluated using a panel of 160 patient and control sera.

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 renal syndrome (HFRS) predominantly encountered in northern Europe, is a febrile disease, commonly associated with acute renal impairment. A rapid and reliable serological diagnosis is required to differentiate NE from other acute febrile illnesses in endemic areas. Objective: To evaluate a Puumala (PUU) virus recombinant nucleocapsid protein (rN) based enzyme-linked immunosorbent assay (ELISA) for the serological diagnosis of NE as compared with an immunofluorescence assay (IFA) in a clinically relevant patient sample. Study design: During a four-month period, 618 serum samples from 512 patients with an illness suggestive of NE, sent to the Department of Clinical Virology for serological analysis, were included in the study. All sera were tested by PUU rN ELISA for presence of specific IgG, IgM and IgA antibodies and by IFA using PUU virus infected cells as antigen for presence of IgG and IgM antibodies. Patients with discordant results by IFA and rN ELISA were further serologically and/or clinically evaluated to assess the probability of NE. Results: Compared to IFA, the specificities of the IgM and IgG rN ELISA were 100% and the corresponding sensitivities were 94.0%. The positive and negative predictive values of the PUU IgM rN ELISA in diagnosing NE infection was 100 and 98.6%, respectively. The positive predictive values for present NE infection of IgG rN ELISA and IFA were 68.3 and 71.4%, respectively. The positive predictive value of IgA rN ELISA was 95.8% and the negative 92.7%. Conclusions: The demonstration of specific IgM by rN ELISA is a highly specific and reliable method for the serological confirmation of NE. Detection of IgG antibodies by rN ELISA or IFA has a low predictive value to diagnose NE in an endemic area. The diagnostic value of IgA determination is in between IgM and IgG determinations.

Incidence and geographic distribution of serologically verified cases of nephropathia epidemica in Sweden.

A nationwide survey of hospitalized, serologically verified adult nephropathia epidemica cases in Sweden from 1978 to 1981 was performed. Serum was collected from 1,063 patients with a diagnosis of nephropathia epidemica or one of 10 other renal diseases with related symptoms. Sera were analyzed by indirect immunofluorescence technique for the presence of immunoglobulin G antibodies to Hantaan virus, causative agent of Korean hemorrhagic fever that cross-reacts with the nephropathia epidemica agent. Antibodies were present in 368 patients, 355 of whom also fulfilled four or more of six criteria for clinical diagnosis of nephropathia epidemica. The male:female ratio was 2.7:1. The total number of cases in Sweden varied between 26 and 144 per year, which coincided with the fluctuations in small rodent populations. The highest incidence was found in Västerbotten County, with a maximum crude incidence rate of 23.5 cases per 100,000 inhabitants per year. Mean crude incidence in Sweden during the study period was 1.3 cases per 100,000 inhabitants per year. The southernmost cases lived in proximity to the 59th parallel. Thus, nephropathia epidemica was found to be prevalent south of the 60th parallel, which was previously assumed to be its southern boundary.