Infections of the central nervous system of suspected viral origin: a collaborative study from Finland.

We studied 3231 patients with acute central nervous system (CNS) symptoms of suspected viral origin to elucidate the current etiologic spectrum. In 46% of the cases, a viral finding was observed. Varicella-zoster virus (VZV) was the main agent associated with encephalitis, as well as meningitis and myelitis. VZV comprised 29% of all confirmed or probable etiologic agents. Herpes simplex virus (HSV) and enteroviruses accounted 11% each, and influenza A virus 7%. VZV seems to have achieved a major role in viral infections of CNS. In encephalitis in our population, VZV is clearly more commonly associated with these neurological diseases than HSV. The increase in VZV findings may in part be a pseudophenomenon due to improved diagnostic methods, however, a true increase may have occurred and the pathogenetic mechanisms behind this should be elucidated.

Maturation of immunoglobulin G avidity after rubella vaccination studied by an enzyme linked immunosorbent assay (avidity-ELISA) and by haemolysis typing.

Two tests were introduced recently for assessment of the avidity of rubella immunoglobulin antibodies. In the quantitative test--avidity-enzyme linked immunosorbent assay (ELISA)--IgG antibodies obtained from individuals shortly after primary infection with rubella virus are distinguished from those with past immunity by their antigen-elution characteristics. This method uses agents that disrupt hydrophobic bonds in proteins [Kamoun PP (1988): Denaturation of globular proteins by urea: Breakdown of hydrophobic bonds? Trends in Biological Sciences 13:424-425.]. In the semiquantitative, presumptive test--haemolysis typing--the low-avidity rubella-IgG antibodies are distinguished from the high-avidity antibodies by the quality of their haemolytic zones in a radial haemolysis test. In the present study, both tests were applied to sera taken before and after vaccination with two different strains (Cendehill or RA 27/3) of live attenuated rubella virus. It was found that after vaccination of previously nonimmune subjects, IgG synthesized during the first 2 months had a very low avidity; IgG avidity increased dramatically during the subsequent 4 months and less markedly between 6 and 12 months after vaccination. On the contrary, the initially high IgG avidity of previous immune vaccinees remained at an elevated level postvaccination. These results provide a basis for identification of recent primary rubella virus infections, or vaccination reactions, by the avidity of specific IgG and also for their separation from rubella reinfections.

Single-serum radial hemolysis to detect recent rubella virus infection.

In the radial hemolysis test for rubella virus-specific antibodies, sera obtained shortly after primary rubella produce a characteristically altered hemolysis zone, termed soft hemolysis. The occurrence of soft hemolysis was analyzed statistically in 6,723 sera. The specificity of soft hemolysis for infection with rubella virus was 99.0%. Its sensitivity in primary infections was 97.3%, and the predictive value for rubella serodiagnosis (increase in IgG level or detectable IgM) was 91.2%. The temporal association of soft hemolysis with rubella was determined with sera obtained from 129 persons during late convalescence (70-310 days after onset of symptoms). Soft hemolysis disappeared by 190 days after the onset of symptoms and the presence of ordinary hemolysis ruled out primary rubella in the preceding 70-100 days. Soft hemolysis was caused by IgG antibody to rubella virus, and thus represents a new serodiagnostic principle. This technique, together with an Igm assay, allows rapid diagnosis of recent rubella from a single serum sample.

Altered hemolysis in single radial hemolysis from a single serum sample as an indicator of recent primary rubella virus infection.

The quality of hemolysis in the single radial hemolysis (SRH) test was observed to be altered in a small proportion (5.7%) of sera (N = 9628) studied for rubella rubella antibodies. Three different types of altered hemolysis were identified. Two of these types, the "soft margin" (SM) or the "soft zone" (SZ), occurred singly or in combination in 97% of paired sera (N = 321) taken 3-30 days after primary rubella infection (diagnostic seroconversion). For comparison, diagnostic increases of rubella antibodies (N = 77), including both primary and reinfections, contained these types of altered hemolysis in 80% of the cases. Of the remaining 20% of the samples (N = 15), rubella antibodies of IgM class were looked for in seven cases but not found. After primary rubella, SZ was always present in the first serum sample and disappeared rapidly within 20 days while SM persisted longer. The predictive value of the different types of hemolysis was estimated from 96 primary sera, which had altered hemolysis. In this material, SZ was followed by a diagnostic increase of antibodies in 87% of the cases; the prognostic value of the SM was significant but lower. These data show that the appearance of SM or SZ in a single serum sample is a useful marker of recent primary rubella. On the other hand, a normal hemolysis in SRH can be used to exclude recent primary rubella, but not reinfection, with a high degree of probability.