ROUTINE DIAGNOSIS OF HERPES-SIMPLEX VIRUS (HSV) ENCEPHALITIS BY AN INTERNAL DNA CONTROLLED HSV PCR AND AN IGG-CAPTURE ASSAY FOR INTRATHECALSYNTHESIS OF HSV ANTIBODIES

Background: The development of antiviral therapy increases the need fo r rapid, sensitive and reliable methods or combination of methods for diagnosis and monitoring herpes simplex encephalitis, HSE. Objectives: Evaluation of diagnostic performance of three successively developed HSV PCR assays when combined with a new capture ELISA for HSV intrathe cal antibody production (ITT). Study design: During a 3.6 year period a total of 4.206 CSF and serum samples from about 4.140 hospitalized p atients with a tentative diagnosis of HSE were analyzed by a new ELISA for ITT. 1.962 CSF samples were examined also by PCR. Clinical signs and symptoms and additional tests were obtained on all ITT and/or PCR positive patients. In 1993 the PCR was a double PCR. In 1994 the PCR w as a single PCR with internal inhibition control. Positive samples wer e confirmed by a different confirmative PCR to increase the specificit y. From 1995 the PCR was as in 1994 but samples were no longer divided in the serology routine laboratory. Results: A total of 33 HSE cases was found (incidence 1.8 HSE per million people). All patients were tr eated with aciclovir. Three patients died, 9 patients had primary infe ction, 2 patients had HSE previously, and 2 patients relapsed. Only 11 patients recovered satisfactory. Of all 37 positive ITT 7 were unlike ly positive. False positive PCR was seen in 1993 and 1994, due to samp le-to-sample contamination during division of samples, but was not see n since 1995 when this procedure was changed. The test results depende d on the state of the disease. Thus, the sensitivity, specificity, PPV and NPV for ITT were highest when performed more than 1 week after de but of symptoms whereas these values were highest using PCR within the first week. Conclusion: Routine PCR diagnosis of HSE type 1 and 2 is a highly sensitive and specific method that should be performed togeth er with serological ITT to cover the whole time span from debut of sym ptoms to several weeks after hospitalization. (C) 1998 Elsevier Scienc e B.V. All rights reserved.