Rational and effective diagnosis of enterovirus disease

Background and objective: Demonstration of the causative pathogen by isolating the virus in cell culture is taken as the standard in the diagnosis of diseases caused by enterovirus. When diagnosing the virus in cerebrospinal fluid (CSF), isolation of the virus has been largely replaced by the rapid demonstration of the virus using the reverse transcriptase polymerase chain reaction (RT-PCR), because of its greater sensitivity. The serological diagnosis is mostly made with the complement binding reaction (CBR). A new enzyme immunoassay for demonstrating anti-enterovirus IGM antibodies (IgM-EIA) allows a more rapid diagnosis from a single serum sample. It was the aim of this study to compare the diagnostic value of these various tests. Method: Several methods for demonstrating virus from faeces, swabs and CSF (virus isolation in cell culture and RT-PCR) and of antibodies in serum (IgM-EIA and CBR) were compared. The clinical material was obtained largely from children under the age of 10 years, many of whom had serous meningitis, flu-like symptoms or enteritis. In one cohort (C1), only stool or throat swabs were available for each of 154 patients. In the other cohort (CZ) of 164 patients, CSF and gt least one serum sample were available in addition to occasional stool samples. Results: From C1 enteroviruses were isolated from 32 patients, rotavirus twice from stool or throat swab and rotavirus once from stool or throat swab, and herpes simplex once from throat swab. RT-PCR was positive 55 times for enterovirus, five times false-negative when the virus had been isolated. In CZ enterovirus nucleic acid was demonstrated in 43 patients from CSF. Parallel serological tests gave positive IgM values for 15 patients, while CBR titres were raised in nine. Conclusions: Complementary tests of CSF, stool, swabs and serum samples by all possible combinations of viral isolation, RT-PCR and IgM-EIA improve the diagnosis of enterovirus-associated diseases. RT-PCR is the method of choice. The serological diagnosis should be confirmed by the demonstration of virus in stool OF swab.