A circannual rhythm in rubella antibody titers

Abstract

Rubella antibody titers were assayed from 191 blood samples taken during seven years (1973–1979) from a human female who had contracted German measles in 1965. The antibody dilutions, transformed to integers, fit a first‐order harmonic function with an assumed period of 365 days. The levels about which the titers oscillated decreased from 1973 to 1975 and remained stable thereafter. Amplitudes averaged 31% on either side of the level of oscillation. At certain times of the years 1977–1979 at the trough of the rhythm the subject would have been considered to be lacking in immunity against rubella despite history to the contrary. This example of a long‐term, circannual rhythm in an immunologic assay supports previous suggestions that immunity cycles over the seasons.     

Seven-year follow-up study of rubella syndrome in Ryukyu with special reference to persistence of rubella hemagglutination inhibition antibodies.

Rubella hemagglutination inhibition (HI) antibodies in 266 children with rubella syndrome born in 1965 in the Ryukyu Islands and their mothers were followed for seven years. Titers of rubella HI antibody in the mothers declined slowly, while those in the children declined rapidly up to 40 months of age. Thereafter decline of titers became extremely slow and only seven cases (three per cent) became seronegative for rubella HI antibody. Rubella HI antibody titers seemed to have no particular correlation to the severity of clinical manifestations.     

IgM antibodies in rubella infections: absorption with staphylococcal protein A of sera examined by immunofluorescence and haemagglutination inhibition.

A similar frequency of positive results for rubella IgM antibodies in the sera of rubella patients and persons contacting such patients was obtained by immunofluorescence after separation of IgM is sucrose gradient and after absorption of the sera with Staphylococcus aureus and immunoglobulin aggregates. Compared to the immunofluorescence method, the haemagglutination method for rubella IgM antibodies performed after absorption of the sera with S. aureus and reduction of immunoglobulins M with 2-mercaptoethanol was less sensitive for serum samples taken in the acute phase of the disease and 5 weeks after the appearance of rubella symptoms.     

Evaluation of the incidence of congenital rubella in GDR]

Annual number of congenital rubellas in GDR was evaluated by means of a mathematic model. Dates of inmunity rate of rubella in L. and P. districts obtained by means of haemagglutination inhibition reaction were taken into account. From these dates of a number of possible primary cases of rubella infection in wifes in the first 3 months of pregnancy as well as literary dates on mean number of monsters determined after the infection, i.e. 10--15--25% cases, were evaluated. There were obtained in relation with different mean numbers of monsters 37--56--93 cases of congenital rubellas for live born children from mothers at the age of 14 to 45 years. It results in total that the incidence of disease for live born children from mothers up to 45 years, is 0,2--0,5%, i.e. 2--5 children with congenital rubella on 10 000 live born children. Compared with literary data, it results a good correlation between proper evaluations and numbers of congenital rubella incidence quoted by other authors. In view of these evaluations, a conclusion to introduce protective rubella vaccination, is fully justified.     

Reinfection after rubella and congenital polymalformation syndrome

A case is reported of a term newborn with intra uterine growth retardation and numerous malformations such as complex heart disease, abnormalities of distal limbs, cleft palate. Death occurred after two days. The diagnosis of rubella embryopathy was confirmed by the following criteria: a high level of rubella antibodies in mother and newborn (1/1000) an isolation of rubella virus from the infant's urine. Diagnosis of rubella after reinfection was documented by a high level of antibodies in the mother three years before this pregnancy. Other observations reported in literature confirm the extreme rarity of congenital rubella after reinfection.     

The preparation of bacterial luciferase conjugates for immunoassay and application to rubella antibody detection

Bacterial luciferase has been modified with the thiolating reagent S-acetylmercaptosuccinic anhydride and covalently crosslinked to either Staphylococcus aureus protein A or anti-human immunoglobulin G (IgG) with the heterobifunctional reagent m-maleimidobenzoic acid N-hydroxysuccinimide ester. The conjugates retain enzymatic light-emitting activity and have the ability to bind IgG antibody. The ability of these conjugates to detect human IgG has been demonstrated by application to rubella immunity screening. Rubella antibodies are isolated from serum on the surface of rubella antigen-coated tubes and subsequently determined by light emitted from bound conjugate. In a preliminary study, the bioluminescent immunoassay has been compared to a commercial rubella antibody radioimmunoassay and found to be comparable in the ability to determine rubella immunity.     

Viral antibodies in infectious mononucleosis

Abstract Patients with Epstein-Barr virus (EBV) infectious mononucleosis (IM) usually develop heterophilic antibodies and some autoantibodies. Antibodies to rubella, measles, adeno-, entero-, herpes simplex, cytomegalo- and varicella-zoster viruses were titrated in sera from IM patients and matched healthy controls using the complement fixation test (CFT) and the haemagglutination inhibition test. Except for herpes simplex virus and cytomegalovirus, the IM sera had significantly higher arithmetical and geometrical mean antibody titres and showed in most cases higher antibody prevalences in the CFT. The titre rise was most pronounced for rubella and measles antibodies, between 2- and 3-fold. There were no cases of very high titres occasionally seen in IM. The IM sera had higher total IgG serum levels than the controls, 17.27 g/1 and 11.8 g/1, respectively ( P < 0.001). The present data show that in addition to previously reported high levels of some autoantibodies and of heterophilic antibodies, there is a more general increase in IgG antibodies to commonly occurring viruses. This increase is most likely due to the polyclonal activation of B-lymphocytes following the binding of EBV to the complement receptor CR2 (CD21). When due consideration is given to the possible occasional occurrence of a false positive rubella IgM test, the raised antibody-titres will most likely not interfere with routine diagnostics.     

The present prophylactic trends of rubella and measles

Starting from the epidemiological investigation on a sample of 22.560 subjects of different chronological age classes in the Latium region with the research of hemoagglutinoinhibiting antibodies of the Rubella virus, and of 9.800 subjects with the research of hemoagglutinoinhibiting antibodies of the Measles virus, the authors observe that the diffusion of the seroprotection presents on an average 82.5% for Rubella and 79.8% for Measles. On the strength of the results, referred also according to the established chronological age classes, any obligatory treatment against Rubella is excluded in prepuberal age. In order to prevent the risk of congenital malformation in cases of pregnant and not seroprotected subjects who, during the first three months of gestation might come into contact with sick affected by Rosolia or with healthy carriers, the authors suggest the vaccination three months before the conception. Evidently, this involves a screening of the adult female population before their marriage. On the contrary as concerns Measles, the vaccination within the second year of life is being hypothesized exactly on the basis of the consideration that this is a matter of a serious illness and not always free from grave complications. In these cases, after shortly referring on the results of the experiments of different authors, the mixed anti-Measles and anti-Rubella vaccination might be taken into consideration, though with all the precautions that are suggested.     

Rubella Virus Infections During Pregnancy,Toronto, 1963-66

Among 670 pregnant women who attended the antenatal clinics of two Toronto city hospitals and one suburban hospital between May 1963 and January 1966, 29 of 550 patients apparently acquired rubella neutralizing antibodies, including 12 whose initial sera were collected during the first trimester. None developed overt rubella. Although rubella antibodies were detected in 61 to 79% of mothers aged 20 years or more, and antibody conversions were detected in 4 to 10% of mothers in each five-year age group between 16 and 39 years, tho rubella syndrome did not appear among any of their offspring. Five of seven other infants, aged 4 to 22 weeks, with the rubella syndrome excreted rubella virus. Rubella neutralizing antibodies were detected in all seven of these infants; these persisted at least 56 weeks in one subject. One mother who received gamma globulin during the first trimester was delivered of an infant who showed signs of the rubella syndrome.     

The use of ion exchange chromatography for demonstration of rubella-specific IgM antibodies

IgM and IgG immunoglobulins of human sera were separated by stepwise column chromatography in QAE-Sephadex A-25 ion exchanger gel bed. The procedure resulted within 30 min in a fraction suitable for direct titration of rubella-specific IgM antibodies by haemagglutination inhibition test. The method proved to be a useful diagnostic tool for primary rubella. Serum samples of 13 individuals with previously acquired immunity, 152 patients with a recent rubella-like illness, and 194 pregnant women exposed to rubella infection were tested for the presence of rubella-specific IgM antibodies. Sera of individuals with previous immunity proved to be negative for specific IgM antibodies. Specific IgM titre was demonstrated in the blood of all the 25 patients with significant titre-rise tested because of rubella-like illness, and also in the sera of additional 8 patients whose serum samples were taken too late for demonstration of a rise in titre. Significant titre-rises were found in 5 women exposed to rubella infection, but only two of them exhibited rubella-specific IgM antibodies. The absence of specific IgM antibodies refers presumably to subclinical reinfection in the other three cases.     

Rubella-neutralizing and haemagglutinin-inhibiting antibodies in children of different ages

Rubella neutralization and haemagglutinin-inhibition tests were used to determine the incidence of rubella antibodies in the sera of 235 children and adolescents aged 1 month to 20 years. The tests showed good agreement in the detection of rubella antibodies resulting from acute infection. Maternal antibodies became undetectable within six months after birth. The proportion of children possessing rubella antibodies was found to be about 23% by the age of 5 years, rising sharply to 80% in the 6–12 years age group and 83% in the 13–20 years age group. Results indicate that the incidence of rubella infection may be higher in females than in males. The correlation between statements concerning a past history of rubella and immune status was poor, particularly in the older age groups. Any policy for vaccination against rubella must take into account the difficulties of identifying nonimmune persons in a large population.     

Study of interaction between IgG and IgM antibodies against rubella virus by the immunofluorescence method.

In immunoglobulin fractions or after elimination of IgG by absorption the immunofluorescence test for rubella IgM antibodies is more sensitive than in whole serum. Blocking of IgM activity by IgG antibodies was eliminated when the time of incubation of the serum with virus antigen was prolonged. After prolonged incubation higher titres of rubella antibodies were also obtained in the IgM immunoglobulin fractions. Protein A in Staphylococcus aureus suspension effectively absorbs antibodies of IgG class. The IgM antibody titres in absorbed sera of patients infected with rubella were in some cases 2 to 4 times higher than in unabsorbed sera.     

A rubella haemagglutination inhibition test not requiring removal of non-specific inhibitors. 1. Elaboration of the test

The rubella haemagglutination inhibition (HI) test can be simplified and the probelm of non-specific inhibitors circumvented by allowing the haemagglutinin to react with erythrocytes before addition of the serum specimen. The elaboration of the test procedure is described, and preliminary studies indicate that the new method may prove useful both in the diagnosis of rubella infection and for determination of immunity status.     

Clinical and Serological Assessment of Children Exposed in Utero to Confirmed Maternal Rubella

As a result of the work of the Public Health Laboratory Service Working Party on Rubella (1970) it was possible to examine the children of 60 susceptible women who were in contact with rubella during their pregnancy and who subsequently showed serological evidence of the infection, despite immunoglobulin prophylaxis. When the children were assessed between 8 months and 4 years 8 months of age a blood sample was also taken and tested for rubella antibodies so that a retrospective diagnosis of congenital rubella infection could be made. Only 19% of children exposed to subclinical maternal rubella showed evidence of intrauterine infection compared with 53% of those born to mothers who had clinical rubella. One of the 26 children exposed to subclinical maternal infection had a rubella defect, compared with 9 of the 34 children exposed to clinical maternal rubella.     

Avidity of immunoglobulin G to rubella virus in post-vaccination and post-infection immunity

Comparative evaluation of avidity of IgG to rubella virus in vaccinated persons, in patients with rubella or other exanthematous illness, and in healthy persons revealed similar patterns in post-vaccination and post-infection immunity. Virus specific low avidity IgG (index of avidity < or =30%) were detected in patients with rubella during 7 weeks after symptoms appeared as well as in vaccinated persons which were tested 6 weeks after vaccination. Low avidity antibodies in sera were detected in 96% of patients with rubella and in 75% of vaccinated persons which were not immune before immunization. Live attenuated vaccines Ervevax, Priorix, and MMR-II had similar ability to induce low avidity IgG to rubella virus. Increase of low avidity antibodies concentration was noted after immunization of children with low levels of antibodies before vaccination. After immunization of persons with high avidity antibodies in serum, index of avidity remained above threshold. Anamnestic high avidity IgG (index of avidity 51-100%) were detected in majority of immune healthy persons (96.4%) as well as in patients with exanthematous illnesses not related to rubella infection (93.6%). ELISA test-systems for detection of low avidity IgG to rubella virus allow to obtain reliable information about seroconversion rate and characteristics of immune response in vaccines. Detection of low avidity IgG in serum obtained 5-6 weeks after immunization points to primary immune response, whereas identification of high avidity antibodies reveals already immune persons.     

Single-serum diagnosis of recent rubella infection with the use of hemagglutination inhibition test and enzyme-linked immunosorbent assays

Single-serum diagnosis of recent rubella infection was attempted with the use of hemagglutination inhibition (HI) test and two commercially available enzyme-linked immunosorbent assays (ELISAs). The period during which IgM antibody was detectable by IgM capture ELISA was 4 to 30 days after the onset of rash. Rubella IgG ELISA values relative to HI titer were lower in the sera from the patients with recent infection than in the sera from the subjects with remote infection. IgM ELISA and the combined use of IgG ELISA and HI test are two useful methods of single-serum diagnosis of recent rubella infection.     

Burden of congenital rubella syndrome (CRS) in India based on data from cross-sectional serosurveys, 2017 and 2019–20

BackgroundIndia has set a goal to eliminate measles and rubella/Congenital Rubella Syndrome (CRS) by 2023. Towards this goal, India conducted nationwide supplementary immunization activity (SIA) with measles-rubella containing vaccine (MRCV) targeting children aged between 9 months to <15 years and established a hospital-based sentinel surveillance for CRS. Reliable data about incidence of CRS is necessary to monitor progress towards the elimination goal.MethodsWe conducted serosurveys in 2019–20 among pregnant women attending antenatal clinics of 6 hospitals, which were also sentinel sites for CRS surveillance, to estimate the prevalence of IgG antibodies against rubella. We systematically sampled 1800 women attending antenatal clinics and tested their sera for IgG antibodies against rubella. We used rubella seroprevalence data from the current survey and the survey conducted in 2017 among antenatal women from another 6 CRS surveillance sites to construct a catalytic models to estimate the incidence and burden of CRS.ResultThe seroprevalence of rubella antibodies was 82.3% (95% CI: 80.4–84.0). Rubella seropositivity did not differ by age group and educational status. Based on the constant and age-dependent force of infection models, we estimated that the annual incidence of CRS in India was 225.58 per 100,000 live births (95% CI: 217.49–232.41) and 65.47 per 100,000 live births (95% CI: 41.60–104.16) respectively. This translated to an estimated 14,520 (95% CI: 9,225–23,100) and 50,028 (95% CI: 48,234–51,543) infants with CRS every year based on age-dependent and constant force of infection models respectively.ConclusionsOur findings indicated that about one fifth of women in the reproductive age group in India were susceptible for rubella. The estimates of CRS incidence will serve as a baseline to monitor the impact of MRCV SIAs, as well progress towards the elimination goal of rubella/CRS.     

The shapin of psychiatry by science and humanism. II. An emerging synthesis of science and humanism.

Serological surveys of rubella antibody were carried out using the hemagglutination-inhibition test, with a view to studying the distribution of seroimmune individuals according to age and intermingling with other populations. Specimens were collected from different age groups including infants, children and adults, among the inhabitants of Montreal from 1963 to 1968. From the results obtained it was possible to establish the pattern of rubella antibody development in this urban community. Surveys were also conducted among the inhabitants of Les Iles de la Madeleine, a Canadian island in the Gulf of St. Lawrence, and among the population of Easter Island, an isolated island in the South Pacific remote from any large land mass.It was seen that, among the inhabitants of Montreal, presumably maternally acquired rubella antibody was present in 95% or more of the infants, the same percentage of seroimmune individuals as was found among the adult women 25 to 30 years of age. Passively acquired rubella antibodies decreased rapidly, attaining their lowest levels among children 1 to 2 years old. Rubella infection occurred in young children and its incidence rose steeply from school age to adolescence, leaving 7 to 9% of the adults without antibody. The highest geometric mean antibody titres were found among children 4 to 10 years of age.The same pattern of rubella antibody development was found among the population of Les Iles de la Madeleine, except that in adults the percentages of seropositives reached practically 100%. Antibody titres decreased with advancing age and became lower than those found among children.Detection of rubella antibody in serum samples derived from the inhabitants of Easter Island indicated that this population had experienced rubella infection not long before the Canadian Medical Expedition of 1964-1965. This status is determined from the high proportion of seroimmune individuals in each age group and the uniformly high antibody titre.Island populations appear to represent the ideal subjects for estimating the duration of the immunity conferred by any attenuated rubella vaccine that will eventually be licensed.     

Seven-Year Follow-Up Study of Rubella Syndrome in Ryukyu with Special Reference to Persistence of Rubella Hemagglutination Inhibition Antibodies

Rubella hemagglutination inhibition (HI) antibodies in 266 children with rubella syndrome born in 1965 in the Ryukyu Islands and their mothers were followed for seven years. Titers of rubella HI antibody in the mothers declined slowly, while those in the children declined rapidly up to 40 months of age. Thereafter decline of titers became extremely slow and only seven cases (three per cent) became seronegative for rubella HI antibody. Rubella HI antibody titers seemed to have no particular correlation to the severity of clinical manifestations.     

Serological survey of rubella in Yemen in 1985

476 sera from subjects of 6 age groups were investigated using the HI test for rubella, the sera originating from 5 distinct regions of Yemen, namely highland, coastal the agricultural area Abijan, Vadi Hadramot and the capital Aden. The positivity rate among children aged 1-6 ys was 46.2%, the values obtained for girls aged 15-18, women in the 19-24 and 25-29 ys age group being 81%, 86.3% and 89.9%, respectively. When the findings of the immunological survey were evaluated with respect to the five different regions studied, the positivity rate in the highlands was found to be significantly higher among girls under 18 ys of age. The geometric means of HI titres for rubella antibodies proved to be the lowest in 1-3-year-old children (1: 59) and the highest in girls aged 15-18 ys (1: 163). The authors discuss the comparatively high risks of contracting rubella during pregnancy in four regions of Yemen.