Measles and Other Virus-specific Immunoglobulins in Multiple Sclerosis

Immunoglobulins M and G specific for meales, herpes simplex, and rubella viruses were assayed by the fluorescent antibody method in sera and cerebrospinal fluids (C.S.F.) obtained simultaneously from 30 patients with multiple sclerosis, 30 patients with other neurological diseases, and 30 “normal” control subjects. Sera of 11 out of 30 patients with multiple sclerosis had IgM which reacted specifically with measles virus-infected cells, compared with 2 out of 30 of the patients with other neurological diseases and none of the 30 normal controls. Virus-specific IgM was not found in C.S.F. by this method.The geometric mean titre of measles virus-specific IgG in serum was significantly higher in the multiple sclerosis group than in either control group, and while IgG specific for all three viruses was found in C.S.F., suggesting transfer across the blood-brain barrier, measles IgG predominated.     

Multiple sclerosis and common viral infections in Iceland

Sero-epidemiological studies on a few common virus infections, including measles, rubella, mumps and varicella-zoster, were carried out on patients with multiple sclerosis (MS) and controls matched for age, sex, and residences since birth. The frequency of antibodies against measles was significantly higher in the MS patients. Where measles preceded the onset of MS, the time interval varied from 3 to 32 years. In two cases, known MS patients contracted measles 9 and 3 years after their onset of MS. Furthermore, three MS patients were vaccinated against measles as adults. Two of these took part in a WHO measles vaccine trial in 1962, 18 and 6 years after the onset of MS. Both of them were seronegative prior to vaccination.     

Evaluation of live trivalent vaccine of measles AIK-C strain, mumps Hoshino strain and rubella Takahashi strain, by virus-specific interferon-gamma production and antibody response

A trivalent measles-mumps-rubella live virus vaccine, containing measles AIK-C strain, mumps Hoshino strain, and rubella Takahashi strain, was evaluated in 229 children, aged 1 to 5 years. The vaccine induced a high seroconversion rate: 221 (98.7%) out of 224 subjects initially seronegative for measles virus, 167 (93.3%) out of 179 initially seronegative for mumps virus, and 212 (99.1%) out of 214 initially seronegative for rubella virus. It also induced a sufficient cellular immunity against each of the three viruses in over 90% of the subjects, as judged by virus-specific interferon-gamma (IFN-gamma) production. Virus-specific IFN-gamma production was observed 10 days after vaccination by stimulation with measles virus and rubella virus and 14 days after vaccination by stimulation with mumps virus. Mumps-virus-specific IFN-gamma production was observed in 7 out of 12 recipients without seroconversion for mumps virus. And measles-virus-specific IFN-gamma production was demonstrated in one out of three recipients without seroconversion for measles virus. A significant correlation was observed between the serum antibody and IFN-gamma production six weeks after vaccination for measles virus (r = 0.201, P less than 0.01) and for mumps virus (r = 0.174, P less than 0.05) but not for rubella virus (r = -0.045, P less than 0.05). The incidence of febrile reactions of greater than or equal to 37.5 C was quite low, 14.4%, and that of greater than or equal to 39 C occurred in only 1.3% of the recipients. These results suggested that the trivalent vaccine induced sufficient humoral and cellular immunity and yet resulted in no more untoward reaction than observed from the measles vaccine alone.     

Platelet Aggregation Test with Measles Antigen in Multiple Sclerosis

With the measles platelet aggregation test, a new technique recently developed for measuring virus antibody, 153 serum specimens from patients with multiple sclerosis and 164 controls were tested. With one of the three measles antigens used in the test a significantly higher positive rate (P<0·001) was obtained in the specimens from the patients with multiple sclerosis (40%) than in those from the controls (11%). The other two measles antigens also yielded slightly but not significantly higher positive rates in the patients with multiple sclerosis.     

Measles Virus-Specific IgG in Cerebrospinal Fluid in Multiple Sclerosis

The prevalence of measles virus-specific IgG in cerebrospinal fluid (C.S.F.) of patients with multiple sclerosis (M.S.) has been compared with that in fluids from patients with other neurological diseases and from normal control subjects. The prevalence in the three groups was 58·1%, 24·1%, and 0% respectively. Fivefold concentration of the specimens increased the prevalence in the first two groups to 80·6% and 34·5% respectively, while measles IgG was not detected in any fluids of the normal control group, even after concentration.     

Vaccination against measles, mumps and rubella (MMR): a comparison between the antibody responses at the ages of 18 months and 12 years and between different methods of antibody titration

In connection with the introduction of the trivalent vaccine against measles, mumps and rubella at 18 months and 12 years of age, an evaluation of the seroconversion and booster effects in the two age-groups was carried out. This also comprised different laboratory-test methods appropriate for follow-up studies after large-scale, vaccination studies. The measles, mumps and rubella antibodies were measured by the haemolysis-in-gel (HIG) method. Measles antibodies were also measured by the haemagglutination-inhibition (HI) test. Borderline values or samples negative to measles or mumps were also tested by the serum-neutralization (SN) test. All but four of 150 18-month-old children lacked antibodies against measles by the HI test and one of these by the HIG method. Against mumps, 99% were seronegative in the HIG test and 97% in the SN test and two against rubella prior to vaccination. Among 247 schoolchildren, 60 (24%) lacked antibodies in the HI test and 28 (11%) of these also in the HIG test. Sixty-six schoolchildren (25%) were negative to mumps and 45% to rubella prior to vaccination. The seroconversion rate for the 18-month-old children was 96% against measles, 93% against mumps and 99% against rubella. The figure for the schoolchildren was 82% against measles, 80% against mumps and 100% against rubella. On comparing the titre levels in seroconverting children, the measles-antibody levels were found to be lower among older children, compared with younger, while the opposite was true for rubella.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measles Immunoglobulins in Subacute Sclerosing Panencephalitis

Normal responses of measles specific immunoglobulins M and G (IgM and IgG) were defined in 10 children with measles. Abnormal responses of measles IgM and IgG were found in both sera and cerebrospinal fluids from three cases of subacute sclerosing panencephalitis. In two patients the serum titres of measles IgM and IgG were abnormally high. The measles IgM was present during prolonged illnesses in serum and cerebrospinal fluid, which suggested a correlation with the known persistence of measles virus antigen in the brain of the three patients. It was concluded that both measles IgM and IgG may be produced within the central nervous system in subacute sclerosing panencephalitis.     

ELISA法检测流行性腮腺炎病毒感染特异性IgM抗体的研究

用流行性腮腺炎(流腮)病毒Enders株接种鸡胚尿囊腔培养,尿囊液经聚乙二醇6000处理制备流腮病毒抗原,用ELISA法检测流腮患者血清中特异性IgM抗体,其敏感性,特异性、重复性和稳定性都很高。 79份流腮患者血清,检出特异性IgM72份,阳性率为91％,32例非流腮患者IgM全部阴性、两者有极显著差异(P<0.01)。 10份血清作血清倍比稀释至1∶3200测IgM仍全部阳性,1∶6400稀释仅1例阴性,1∶12800稀释5例中仍有2例阳性。 10份血清作流腮抗原特异性抗体阻断试验,光密度抑制率均大于50％,平均为87％,10份标本作2-ME和SPA阻断后检测IgM抗体,结果2-ME阻断标本全部阴转,而SPA阻断标本仍阳性,证实所检测为流腮特异性抗体。 24份标本2次重复检测流腮IgM,其阴、阳性结果一致,这期间抗原放4℃ 1个月,提示抗原的稳定性和方法的重复性都很好。本方法敏感性明显高于血凝抑制试验,其阳性率分别为91％和61％,两者有显著差异。而且所用试剂简单经济,操作简便,快速,适用于临床早期诊断,易于广泛推广应用。     

Viral Antibodies in Diabetes Mellitus

Sera from 123 patients with diabetes mellitus of recent onset, 155 patients with diabetes of more than two years'' duration, and 250 normal persons were collected over a period of two and a half years. All sera were tested for neutralizing antibody to Coxsackie virus types B1–6, and a sample was tested for complement-fixing antibody to a number of viral, rickettsial, and mycoplasmal antigens.In diabetics of recent onset no evidence was found of any excess of antibodies to mumps virus or some common respiratory viruses. Insulin-dependent diabetes within three months of onset were found to have higher antibody titres to Coxsackie B virus, particularly of type B4, than either normal subjects or patients with diabetes of longer duration.     

Potency estimation of measles, mumps and rubella trivalent vaccines with quantitative PCR infectivity assay.

The quantitative PCR infectivity assay is a combination of virus propagation and quantitative PCR. Previously [Schalk JAC, van den Elzen C, Ovelgonne H, Baas C, Jongen PMJM. Estimation of the number of infectious measles viruses in live virus vaccines using quantitative real-time PCR. J Virol Methods 2004;117:179-87.], we used this assay to estimate the titer of infectious measles virus in trivalent, live, measles, mumps, rubella vaccines (MMR). Here we describe the further improvement and development of the assay for simultaneous potency estimation of measles, mumps and rubella viruses. The potency of measles and mumps virus is estimated within one assay after 1 day of cell culture. The potency of rubella virus is estimated in a separate assay after 2 days of cell culture. Compared to conventional CCID50 and plaque assays, the quantitative PCR infectivity assay has the advantage in being fast because the assay is not dependent on the formation of cytopathic effect. Furthermore assay design is simplified: serological neutralization can be omitted because PCR is virus-specific and, under the conditions used, the individual components of trivalent measles, mumps, rubella vaccines do not interfere with each other. The assay was validated and compared to the performance of a plaque assay.     

Characterization of antigen-specific T cells in multiple sclerosis twins with elevated proliferative responses to measles virus

The proliferative response to measles virus in normal individuals is low compared with the response to mumps virus. This is probably due to a low precursor frequency of OKT4+, IL 2-secreting helper cells. The presence of a measles high-responder state has previously been identified in some twin individuals with multiple sclerosis. Further characterization of the measles response in these high-responder individuals has demonstrated that the enhanced measles responses are due to a greater response by OKT4+ cells, which secrete higher levels of IL 2; this contrasting with the low levels of IL 2 secretion and OKT4+ cell proliferation seen in the unaffected twins. No evidence for suppression by either accessory or T cells, which would account for the quantitative differences between the high responders with multiple sclerosis and their unaffected low-responder twin siblings, was detected. The results indicate that a clonally expanded population of measles-specific responder cells is responsible for the high-responder state in these twins with multiple sclerosis. The mechanism producing this state may have relevance to possible immunoregulatory abnormalities producing autoimmunity in multiple sclerosis.     

Puvalluttuq: An Epidemic of Tuberculosis at Eskimo Point,Northwest Territories

An explosive epidemic of tuberculosis in a small isolated settlement is described. This outbreak, in a population of 329 Eskimos and 16 whites, produced 80 cases of active tuberculosis, involving 55% of all the house-holds. Forty-five of these patients were children under 10 years of age and only five were persons over 30. These patients probably were infected by one highly infectious individual.The contributing causes of poor housing, overcrowding and poor nutrition, coupled with the debilitating effect of recent epidemics of virus diseases, measles, mumps and German measles, are discussed.Since this article was written, a third resurvey in the same year, conducted in November 1963, revealed 11 more cases among the 279 members of the population who underwent radiological examination; all are hospitalized.     

Swedish experience of two dose vaccination programme aiming at eliminating measles,mumps, and rubella.

In 1982 a two dose regimen was introduced in Sweden for the combined vaccination against measles, mumps, and rubella of children aged 18 months and 12 years. Since 1977 about half of the preschool children were vaccinated against measles annually, and since 1974 about 80% of 12 year old girls were vaccinated against rubella. During the period 1982 to 1985 90-93% of the eligible age cohorts of 18 month old children and 88-91% of the 12 year old children were immunised with the new combined vaccine. A study in 1982 of about 140 18 month old children who were nearly all seronegative before vaccination showed that 96%, 92%, and 99% seroconverted against measles, mumps, and rubella, respectively. A second study was carried out in 1983 of 247 12 year old children, of whom 11% lacked antibodies to measles, 27% to mumps, and 45% to rubella. This showed seroconversion in 82% and 80% against measles and mumps, respectively, and all children seroconverted against rubella. In the latest study in 1985 of 496 12 year olds 9% and 13% were seronegative against measles and mumps before vaccination, and 41% against rubella. Of these, 88% seroconverted to measles and 80% to mumps, and all converted to rubella when sera were tested by the haemolysis in gel method. After a neutralisation test against measles as well all children showed immunity to the disease. A low incidence of measles and declining figures for mumps and rubella were reported in 1984 to 1986. An outbreak of rubella during 1985 affected mainly boys in age cohorts in which only the girls had been vaccinated during the 1970s.     

Immune response to acute otitis media in children III. Implications of viral antibody in middle ear fluid.

With the technique of radioimmunodiffusion and indirect FA staining, IgA antibody to measles, mumps, rubella, and polio-1 were determined in serum and middle ear fluid (MEF) of 103 patients with otitis media. The occurrence of IgA viral antibody in MEF and its absence in simultaneously drawn serum was used as an indicator of local antibody production. Of the 401 assays performed, 41 instances of IgA antibody exclusively in MEF were found. Only four of these occurred in specimens from unimmunized patients and were directed against rubella virus. Of the 37 remaining cases, 16 each were directed against measles and polio-1 and four and one, respectively, for mumps and rubella viruses. The mean specific IgA titers were from 8- to 17-fold higher in MEF from immunized individuals than in the unimmunized and persisted for at least 9 to 19 months after immunization. The data thus indicate 1) specific immunologic sensitization of the middle ear mucosa can be achieved by parenteral as well as oral routes of immunization, and 2) specific immunologic memory exists in the middle ear mucosa. These two factors are crucial to feasibility of immunization against acute otitis media.     

Studies on live rubella vaccine. V. Quantitative aspects of interference between rubella, measles and mumps viruses in their trivalent vaccine

Rubella vaccine combined with measles and mumps vaccines was administered in a single injection to children of 1 to 5 years of age. All three vaccines were serologically effective, and the clinical reactions caused by measles vaccine were considerably alleviated, when 6 x 10(3) PFU of rubella and 10(4) TCD50 per dose of mumps vaccines were combined with 5 x 10(4) TCD50 of measles vaccine. When a larger amount of mumps vaccine (3 x 10(5) TCD50/dose) was used, it caused interference with the rubella and measles viruses, i.e., the antibody response to rubella virus became poor and the incidence of clinical reactions to measles virus decreased. On the other hand, when 5 x 10(5) TCD50/dose of measles vaccine was combined with 10(4) TCD50/dose of mumps vaccine, the clinical reactions to measles virus were decreased but were almost the same as those induced by this vaccine alone.     

Intrathecal, polyspecific antiviral immune response in oligoclonal band negative multiple sclerosis

Background

Oligoclonal bands (OCB) are detected in the cerebrospinal fluid (CSF) in more than 95% of patients with multiple sclerosis (MS) in the Western hemisphere. Here we evaluated the intrathecal, polyspecific antiviral immune response as a potential diagnostic CSF marker for OCB-negative MS patients.

Methodology/Principal Findings

We tested 46 OCB-negative German patients with paraclinically well defined, definite MS. Sixteen OCB-negative patients with a clear diagnosis of other autoimmune CNS disorders and 37 neurological patients without evidence for autoimmune CNS inflammation served as control groups. Antibodies against measles, rubella, varicella zoster and herpes simplex virus in paired serum and CSF samples were determined by ELISA, and virus-specific immunoglobulin G antibody indices were calculated. An intrathecal antibody synthesis against at least one neurotropic virus was detected in 8 of 26 (31%) patients with relapsing-remitting MS, 8 of 12 (67%) with secondary progressive MS and 5 of 8 (63%) with primary progressive MS, in 3 of 16 (19%) CNS autoimmune and 3 of 37 (8%) non-autoimmune control patients. Antibody synthesis against two or more viruses was found in 11 of 46 (24%) MS patients but in neither of the two control groups. On average, MS patients with a positive antiviral immune response were older and had a longer disease duration than those without.

Conclusion

Determination of the intrathecal, polyspecific antiviral immune response may allow to establish a CSF-supported diagnosis of MS in OCB-negative patients when two or more of the four virus antibody indices are elevated.     

Factors affecting uptake of measles,mumps, and rubella immunisation.

OBJECTIVE--To study factors affecting uptake of measles, mumps, and rubella immunisation. DESIGN--Cohort study using data from computerised child health systems. SETTING--10 health districts in North East Thames and North West Thames regions. SUBJECTS--7841 children born in January to March 1990 and resident in the districts up till the end of October 1991. MAIN OUTCOME MEASURES--Overall uptake of measles, mumps, and rubella immunisation, variation of uptake among groups of children, and odds ratio of being vaccinated against measles, mumps, and rubella. RESULTS--The overall uptake rate of measles, mumps, and rubella immunisation for the study cohort in the 10 districts was 82%. Wide variation was identified among children with different demographic characteristics. Lower uptake was associated with absent or incomplete primary immunisation, including omission of pertussis vaccine. Other factors affecting uptake included the type of resident district, birth order, where registered for immunisation (general practitioner or clinic), and one parent family status. CONCLUSIONS--Many districts have difficulties in meeting the 90% target for measles, mumps, and rubella immunisation, mainly because of the characteristics of their local population. To increase overall coverage, the health service should target families with adverse factors, especially those whose children have missed previous immunisations.     

Detection of IgG antibody to measles virus by radioimmunoassay technique

A highly sensitive procedure of solid-phase radioimmunoassay (RIA) was developed for the detection of measles IgG antibody. HeLa cells persistently infected with measles virus were used as a solid-phase antigen. This technique was applied to the detection of measles IgG antibody in patients with subacute sclerosing panencephalitis (SSPE) and multiple sclerosis. Normal subjects having experienced natural measles or measles vaccination and patients with various neurological diseases of non-virus nature were also examined as control groups. Measles antibody was detected at high titers in both the sera and cerebrospinal fluid of SSPE patients. Moreover, RIA/HI ratios of SSPE patients were significantly higher than those of normal subjects, suggesting the presence in the formers of antibodies to nucleocapsids at high titers as well as to viral envelopes. On the other hand, no significant difference was found in both RIA and HI titers between the sera of multiple sclerosis and those of various neurological diseases.     

Parvovirus B19 infections in state of Rio de Janeiro, Brazil: 526 sera analyzed by IgM-enzyme-linked immunosorbent assay and polymerase chain reaction

In this study were analyzed 526 sera; the patients aged from two days to 65 years old presenting exanthema, which was the most frequent symptom observed, besides fever, adenomegaly, and arthralgia. These sera were negative by enzyme-linked immunosorbent assay (IgM-ELISA) for either rubella (495), toxoplasma (41), cytomegalovirus (12), measles (40), dengue (56), and they were submitted to nested polymerase chain reaction (PCR) for B19 DNA and commercial IgM-ELISA for B19. In 39 abortion cases, IgM or DNA were not detected, therefore they were not took into account for analysis. Specific DNA and IgM were detected respectively in 71 (14.5%) and IgM in 62 (12.7%) sera from 487 sera analyzed. IgM and DNA were simultaneously detected in 43 (8.8%), while agreement among the results by PCR and IgM-ELISA was observed in 440 (90.4%). The sera were collected from January 1999 to December 2000, most of them in 1999 (325), during winter and spring. The major number of clinical cases was observed in the age group from one to ten years old. IgM or DNA were detected in 23 from 51 municipal districts of the state of Rio de Janeiro, where the samples were collected.