Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases.

In a joint prospective study in Germany and the United Kingdom between 1980 and 1993, 1373 women who had varicella and 366 who had herpes zoster during the first 36 weeks of gestation were followed up. 9 cases of congenital varicella syndrome were identified, all occurring after maternal varicella during the first 20 weeks of gestation. The highest risk (2.

Slow maturation of IgG1 avidity and persistence of specific IgM in congenital rubella: implications for diagnosis and immunopathology.

Without appropriately timed specimens, serological confirmation of congenital rubella infection may be a problem. We have compared the persistence of specific IgM and low avidity specific IgG1 in 141 sera from 120 cases of serologically confirmed congenital rubella infection with the known time scales for postnatal primary rubella. The results demonstrate that the maturation of the immune response to the rubella virus is abnormally slow in congenital rubella cases both in terms of the isotype switch and especially the development of high avidity specific IgG1.

Outcome in newborn babies given anti-varicella-zoster immunoglobulin after perinatal maternal infection with varicella-zoster virus.

281 newborn babies whose mothers had chickenpox and 25 whose mothers had herpes zoster during the perinatal period were investigated. IgG antibody was present at birth in all babies born more than 7 days after the onset of maternal chickenpox. When the mother's rash appeared 7-3 days before delivery progressively fewer babies were born with antibody, and no infant born less than 3 days after the onset had antibody at birth.

Detection of rubella virus in fetal and placental tissues and in the throats of neonates after serologically confirmed rubella in pregnancy.

From 35 therapeutic abortions performed because rubella had occurred at 2-19 weeks of pregnancy, 120 fetal organs, 12 specimens of mixed products of conception, and 15 placentae were tested for rubella virus. Virus was isolated from 10 out of 11 fetuses (91 per cent) from women infected at 2-8 weeks, from 5 out of 8 (63 per cent) infected at 9-10 weeks, and from 2 out of 16 (13 per cent) infected at 11-19 weeks. Hybridization tests for viral RNA on 39 fetal organs from eight cases revealed infection in four additional fetuses.

Detection of specific IgM in varicella and herpes zoster by antibody-capture radioimmunoassay.

A simple and sensitive M antibody-capture radioimmunoassay (MACRIA) is described which utilizes crude commercial VZV antigen and a single monoclonal anti-VZV antibody. This was compared to the immunofluorescence (IF) test for IgM antibody and was used to study IgM responses in sera from 261 patients with varicella and 220 patients with herpes zoster. With MACRIA, IgM antibodies were detected in all patients with varicella.

Outcome of confirmed periconceptional maternal rubella.

61 pregnant women in whom confirmed rubella occurred from 5 weeks before to 6 weeks after the last menstrual period (LMP) were followed up prospectively. In 39, the pregnancy was terminated and the fetal tissues or mixed products of conception were examined for rubella virus. In 22, the pregnancy continued to term and cord serum was tested for specific IgM antibody.

Natural and artificial immunity to varicella zoster virus.

The live varicella vaccine has been recommended for use in immunocompromised subjects and in adults who are susceptible to chickenpox. However, we do not know how humoral and cell-mediated immune responses induced after vaccination differed from those obtained after natural infection. To answer this, 45 previously infected subjects (23 chickenpox, 22 vaccinated) were tested for their varicella zoster virus (VZV)-specific antibody levels and for their lymphocyte stimulation responses to VZV antigen.

Effect of selective vaccination on rubella susceptibility and infection in pregnancy.

The effect of school and adult vaccination on susceptibility to rubella in women of childbearing age was assessed in the Manchester area, where the population attending antenatal clinics is over 40 000 a year. Between 1979 and 1984 the proportion susceptible fell from 6.4% to 2.

Immunisation of nurses with a live varicella vaccine.

34 nurses who had no previous history of chickenpox and were seronegative to varicella zoster virus (VZV) were immunised with a live attenuated varicella vaccine (OKA-RIT strain) and followed up for up to 36 months. No major vaccine reactions were observed. At 5 months and at 1 year, 94% of the nurses had seroconverted but at 3 years only 64% had detectable antibody.

Prenatal detection of rubella-specific IgM in fetal sera.

Serum specimens were obtained by fetoscopy at 19-25 weeks' gestation from four fetuses whose mothers had had confirmed rubella earlier in pregnancy. They were tested for rubella-specific IgM by antibody capture radioimmunoassay. No specific IgM was detected in one fetus and a healthy infant was delivered at term.

Live varicella immunization in healthy non-immune nurses.

Thirty-four varicella-zoster virus (VZV) seronegative nurses were vaccinated with the live varicella vaccine (Varilrix) and followed for periods of up to 36 months. No major vaccine reactions were observed. At 5 and 12 months, 94% of the nurses had seroconverted but at 3 years, only 64% retained antibody activity.

A comparison of indirect immunofluorescence and radioimmunoassay for detecting antibody to varicella-zoster virus.

Immunofluorescence (IF) and radioimmunoassay (RIA) were found to be more sensitive methods than complement fixation (CF) for detecting antibody to varicella-zoster (V-Z) virus. RIA yielded titres about 30 times greater than those obtained by IF, but for screening purposes RIA was only about six times more sensitive since the minimum serum dilutions that could be tested were 1/100 and 1/16 respectively. When 539 sera from subjects of different ages were screened for V-Z antibody, IF and RIA gave concordant results with 527 specimens (98%).

Consequences of confirmed maternal rubella at successive stages of pregnancy.

Over a thousand women with confirmed rubella infection at different stages of pregnancy were followed up prospectively. Two-thirds of the women were multiparous. Pregnancy continued in 40%, and the infants were followed up after birth both clinically and serologically.

A comparison of antibody capture radio- and enzyme immunoassays with immunofluorescence for detecting IgM antibody in infants with congenital rubella.

IgM antibody capture radioimmunoassay (MACRIA) and enzyme immunoassay (MACEIA) were compared with immunofluorescence (IF) for detecting specific IgM antibody in 99 sera from 76 infants with confirmed congenital rubella, and 61 sera from a comparative group of 59 infants who had miscellaneous abnormalities but in whom congenital rubella was not confirmed. All of 35 specimens collected from confirmed cases within 12 weeks of birth were positive by all three methods and all but one of 17 specimens collected after the age of 18 months were uniformly negative. At intermediate ages discrepancies occurred in 18 specimens, of which eight were positive and 10 negative by IF.

Outcome of asymptomatic infection with rubella virus during pregnancy.

We have tried to detect prenatal infection in 34 infants whose mothers were re-infected with rubella virus during pregnancy and in six infants whose mothers had primary subclinical rubella during pregnancy. Two methods of assessment were used: first, serum obtained soon after birth was tested for IgM antibody; secondly, serum obtained after the age of 8 months was tested for specific IgG. The 34 women with re-infections had increases in IgG antibody titre but no IgM response.

Fetal infection resulting from maternal rubella after the first trimester of pregnancy.

We have tried to measure the incidence of prenatal infection in 304 infants whose mothers had had rubella at various times after the first 12 weeks of pregnancy. Two methods of assessment were used: first, serum obtained soon after birth was tested for specific IgM antibody; secondly, serum obtained after the age of eight months was tested for specific IgG. When maternal rubella occurred 12-16 weeks after the last menstrual period specific IgM antibody was detected in 28 out of 50 infants (56%).

Human anti-chickenpox immunoglobulin in the prevention of chickenpox.

Human anti-chickenpox immunoglobulin (zoster immune globulin, ZIG) was largely ineffective in preventing infection in forty-three high-risk contacts of chickenpox. Twenty-nine of these non-immune infants and children who had been in close contact with cases of varicella became infected, and symptoms developed in twenty-four. Since ZIG may modify chickenpox it should continue to be given to high-risk contacts until the availability of a simple and sensitive test makes it possible to identify those who are susceptible.

Comparison of immunofluorescence and radioimmunoassay for detecting IgM antibody in infants with the congenital rubella syndrome.

Immunofluorescence (IF) and radioimmunoassay (RIA) have been compared as methods for detecting IgM antibody in 124 infants with confirmed or suspected congenital rubella. IF was used to test sucrose density gradient fractions and RIA to test fractions and whole serum. When fractions were tested IF and RIA were equally specific and distinguished clearly between IgM and IgG, but RIA was the more sensitive method.

Specific immunoglobulin responses after varicella and herpes zoster.

The indirect immunofluorescence technique has been used to titrate the specific immunoglobulins in 200 sera from 64 patients with varicella, and 195 sera from 67 patients with herpes zoster. IgG and IgM antibodies were detected in all patients with varicella, and IgA in 59 (92%). All three classes of antibody appeared 2--5 days after the onset of the rash, increased virtually simultaneously and reached maximum titres during the second and third weeks.

Comparison of methods for detecting specific IgM antibody in infants with congenital rubella.

Serum specimens from 14 infants with congenital rubella were examined for specific IgM antibody by six different methods. IgM-containing fractions were separated either by sucrose density-gradient centrifugation or by gel filtration through Sephadex G-200, and were then tested by the indirect immunofluorescence technique and by the haemagglutination-inhibition (HI) test (long-and short-incubation methods). Immunofluorescence staining of density-gradient fractions detected specific IgM in all 14 infants.

Antibody titres in women six to eight years after the administration of RA2713 and Cendehill rubella vaccines.

Titres of haemagglutination-inhibiting antibody have been measured repeatedly in young women during a period of 6-8 years after the administration of RA27/3 and Cendehill attenuated rubella vaccines. Mean antibody titres were initially 217 after RA27/3 and 159 after Cendehill, but the difference diminished after the first year. Antibody titres were subsequently well maintained in both groups and did not reveal any need for regular revaccination.

Specific immunoglobulins in infants with the congenital rubella syndrome.

The indirect immunofluorescent technique has been used to detect and titrate the specific immunoglobulins in serum specimens from 154 infants with confirmed or suspected congenital rubella. IgM antibody was stained more efficiently in sucrose density gradient fractions than in whole serum and was detected in this way in 27 out of 40 patients with confirmed congenital rubella at ages ranging from birth to 2 years. It was present in 48 out of 50 serum specimens during the first 6 months of life and in 11 out of 38 specimens obtained at ages between 6 1/2 months and 2 years.