JenniferM. Best

Fetal infection after maternal reinfection with rubella: criteria for defining reinfection.

Five cases of asymptomatic maternal reinfection with rubella are described that occurred in England and Wales during 1985-8 and resulted in intrauterine infection. The criteria for diagnosing reinfection are described. In four cases the rubella contact was with the womans own children. Two women had therapeutic abortions, rubella virus being recovered from the products of conception, and three were delivered of infants with congenitally acquired disease. Though the risks associated with maternal reinfection with rubella are very small and being measured in a prospective study, it is hoped that the recently introduced augmented programme of rubella vaccination will reduce rubella in the community and therefore this small risk still further.

SERUM IgM AND IgG RESPONSES IN POSTNATALLY ACQUIRED RUBELLA

Abstract Sucrose-density-gradient studies on sera from patients recently convalescent from rubella showed that specific IgM could be detected by haemagglutination-inhibition tests for up to 20 days from the onset of illness. This was associated with a significant increase in the concentrations of total IgM but not IgG, the IgM response being maximal 5-14 days after the onset of illness. After a month, only IgG could be detected. Complement-fixation antibodies, even when appearing early, consisted of IgG alone. Serum-total-IgG concentrations showed little variation in healthy patients throughout pregnancy, while IgM concentrations were reduced during the second trimester of pregnancy. The presence of a rubella-infected conceptus did not produce an unusually prolonged IgM response. Reduction in antibody titre in sera after treatment with 2-mercaptoethanol provided a less reliable method for demonstrating recent infection, since reductions in titre were associated usually with significantly raised total-IgM levels.

Rubella vaccination: persistence of antibodies for up to 16 years.

Sera from 123 volunteers vaccinated six to 16 years previously with one of four rubella vaccines (Cendehill, RA27/3, HPV77-DE5, and To-336) were tested for rubella antibodies by single radial haemolysis and radioimmunoassay. By radioimmunoassay 110 (89.4%) of the vaccinees had antibody concentrations greater than the minimum immune titre (that is, greater than 15,000 IU/1), 11 (8.9%) were seropositive but had concentrations less than or equal to 15,000 IU/1, and two (1.6%) were seronegative. Eight (6.5%) were seronegative by single radial haemolysis, of whom five had received Cendehill vaccine. Six to eight years after vaccination subjects who had received Cendehill vaccine had the lowest geometric mean titre of antibody by radioimmunoassay while the subjects who had received HPV77-DE5 vaccine had the highest. Although antibody concentrations less than or equal to 15,000 IU/1 were not detected among subjects given RA27/3 vaccine six to eight years previously, such low levels were detected in two (15.4%) vaccinated 11-16 years previously. These results emphasise the importance of long-term surveillance programmes so that vaccination policies may be reviewed.

MORPHOLOGICAL CHARACTERISTICS OF RUBELLA VIRUS

Abstract Antigen-antibody complexes were used to define and display rubella virus by means of electron microscopy. The virus particles ranged in size between 500 and 750Aand appeared to be ragged, with an amorphous pleomorphic envelope and an internal spherical component.

Epstein-Barr virus-specific IgM in infectious mononucleosis, Burkitt lymphoma, and nasopharyngeal carcinoma.

Abstract Sera were obtained from eight patients with infectious mononucleosis (I.M.). Epstein-Barr (E.B.) virus-specific IgM could be detected for between 7 and 70 days. In one patient who had persistent symptoms it was detected for 6 months. E.B. virus-specific IgM was not detected in sera from patients with nasopharyngeal carcinoma, Hodgkins disease, or Burkitt lymphoma. Patients with Burkitt lymphoma included two untreated and three recently relapsed cases. Total IgM concentrations were increased in the acute-phase sera from patients with I.M., and slightly reduced in patients with Burkitt lymphoma.

HUMAN PAPILLOMAVIRUS TYPE 16 IN INFANTS : USE OF DNA SEQUENCE ANALYSES TO DETERMINE THE SOURCE OF INFECTION

Perinatal transmission of human papillomavirus type 16 (HPV-16) and persistence of virus DNA in infants until 6 months of age has been described. To confirm the origin of infant infections as maternal, we determined the nucleotide sequence of the upstream regulatory region (URR; bp 7540 to 157) of HPV-16 in samples from 13 HPV-16 DNA-positive mothers and their infants at 6 weeks and 2 years of age. Identical HPV-16 variant URR sequences were found in two mother/infant samples and similar variants were found in three sets. Four mothers with samples which contained prototypic HPV-16 sequences delivered infants who also had the prototypic sequence. Four mothers with variant URRs delivered infants who harboured either prototypic or different URR variants. Thus, concordant variants or prototypic sequences were detected in nine of 13 mother/infant samples, indicating that up to 69.2% of HPV-16-positive infants acquire virus from their mothers.

RUBELLA-SPECIFIC SERUM AND NASOPHARYNGEAL IMMUNOGLOBULIN RESPONSES FOLLOWING NATURALLY ACQUIRED AND VACCINE-INDUCED INFECTION PROLONGED PERSISTENCE OF VIRUS-SPECIFIC IgM

Rubella-specific immunoglobulin responses in sera and nasopharyngeal secretions were compared in groups of adult females who had experienced naturally acquired rubella or infection induced by Cendehill, HPV77.DE-5, RA27/3 (subcutaneously and intranasally), and To-336 vaccines. Serum IgG and IgA and nasopharyngeal IgA responses after vaccination by RA27/3 intranasally most closely resembled those induced by naturally acquired infection. However, the other vaccines failed to induce a persistent local IgA response. Levels of local antibody induced by HPV77.DE-5 were especially poor. Virus-specific IgM was detected for prolonged periods. The highest levels and the most persistent response followed vaccination by HPV77.DE-5, four of five volunteers still having rubella-specific IgM at 1 year. Virus-specific IgM persisted for 6 months in seventeen of twenty-five (68%) and for a year in nine of twenty-four (38%) vaccinees. It was still present in four of nine (44%) naturally infected patients at a year.

Nucleotide sequence analysis of a major antigenic domain of the E1 glycoprotein of 22 rubella virus isolates.

We have determined the nucleotide sequence of the region of the rubella virus genome which encodes amino acids 195-296 of the E1 glycoprotein (E1-195-296) from a panel of 22 rubella viruses obtained from Europe, USA and Asia between 1963-1995. E1-195-296 contains neutralizing and haemagglutinating determinants, and may represent a major antigenic domain. The nucleotide sequence divergence of the 22 rubella viruses compared to the Therien strain sequence ranged from 0.65-7.14%. The greatest sequence divergence occurred in two rubella viruses of Indian origin, and was more than twofold greater than that previously reported for rubella virus. The majority of nucleotide changes occurring in the 22 viruses did not effect the deduced amino acid sequence of E1-195-296. Two rubella viruses isolated from cases of reinfection in pregnancy did not exhibit nucleotide sequence variation resulting in changes in the deduced amino acid sequence of E1-195-296, suggesting that antigenic change within this region of E1 is not associated with rubella reinfection. A rubella virus isolated from a synovial fluid sample exhibited a nucleotide substitution in a putative neutralization domain contained within E1-195-296. Phylogenetic analysis was performed to study the relationship between E1-195-296 coding sequences of the 22 viruses in this report and corresponding sequences of other rubella viruses in the databank.

RUBELLA VACCINATION: PERSISTENCE OF ANTIBODIES FOR 10-21 YEARS

Sera from 123 volunteers vaccinated six to 16 years pre? viously with one of four rubella vaccines (Cendehill, RA27/3, HPV77-DE5, and To-336) were tested for rubella antibodies by single radial haemolysis and radioimmuno assay. By radioimmunoassay 110 (89 4%) of the vaccin?es had antibody concentrations greater than the minimum immune titre (that is, > 15 000 IU/1), 11 (8 9%) were seropositive but had concentrations ^15 000 IU/1, and two (1-6%) were seronegative. Eight (6-5%) were sero? negative by single radial haemolysis, of whom five had received Cendehill vaccine. Six to eight years after vaccination subjects who had received Cendehill vaccine had the lowest geometric mean titre of antibody by radio? immunoassay while the subjects who had received HPV77-DE5 vaccine had the highest. Although antibody concentrations ^15 000 IU/1 were not detected among subjects given RA27/3 vaccine six to eight years pre? viously, such low levels were detected in two (15-4%) vaccinated 11-16 years previously. These results emphasise the importance of long-term surveillance programmes so that vaccination policies may be reviewed.

Specific IgM responses after rubella vaccination; potential application following inadvertent vaccination during pregnancy.

between these two variables for the two groups might be expected if the conversion of angiotensin I to angiotensin II was a rate-limiting step. The absence of any difference in the correlations in patients with sarcoidosis and in normal subjects reported here suggests that converting enzyme does not have a regulatory role in the reninangiotensin system. Increased concentrations of angiotensin-converting enzyme therefore have no apparent physiological consequences, although when the enzyme is inhibited a fall in blood pressure may occur.