History Of Measles Research Articles

Measles revaccination. Persistence and degree of antibody titer by type of immune response.

During a measles immunization campaign 203 children were enrolled in an antibody response study. Of this group, follow-up clinical data and sera samples were available from 125 children three weeks after immunization and from 90 children ten months later. Seventy-six of the children had been previously vaccinated, ten had a history of measles and 39 denied vaccination or illness. Twenty-six of the children had prevaccination hemagglutination inhibiting antibody titers of less than 5. Of this group 12 had a primary immune response (IgM measles antibody) with geometric mean titers (GMT) of 90 and 40 three weeks and ten months respectively after vaccination. In contrast, the other 14 children with initial titers of less than 5 had secondary immune responses (only IgG measles antibody) with GMTs of 28 and 9 three weeks and ten months after vaccination. Since the antibody responses in these children who had previously been stimulated by measles antigen were modest and transient, it is suggested that booster immunization may not be effective in preventing future secondary vaccine failures. Also noted in this study was a poor correlation between historical data and actual measles antibody.

Epidemiologic Studies of Measles, Measles Vaccine, and Subacute Sclerosing Panencephalitis

Histories obtained in 350 of 375 clinically cofirmed cases of subacute sclerosing panencephalitis (SSPE) reported to a national registry showed that 292 patients had measles and 58 had no history of measles. Forty of the latter patients received live, attenuated measles virus vaccine. In patients with a history of measles, measles illness occurred before age 2 years in 46%, and a mean of 7.0 years before onset of SSPE. In contrast, there was no relationship of SSPE with age at vaccination in 35 of the 40 patients historically associated with measles vaccine, and SSPE occurred a mean of 3.3 years after vaccination. Based on estimated national measles morbidity data and national measles vaccine distribution data, the risk of SSPE following measles vaccination (0.5 to 1.1 cases/106) appears to be less than the risk following measles (5.2 to 9.7 cases/106). Because live measles vaccine is highly effective in preventing measles illness and a high proportion of children in the United States have received measles vaccine, these data are consistent with the observed downward trend in SSPE incidence since 1969.

MEASLES REVACCINATION; THE PERSISTENCE AND DEGREE OF ANTIBODY RESPONSE ANALYZED BY TYPE OF IMMUNE RESPONSE

During a measles immunization campaign blood samples were collected from 203 children before vaccination. Follow up specimens were collected from 125 children 3 wks. later and from 88 children 10 mos. later. Of the 125 children with follow up study, 88 had been previously vaccinatedt 10 had a history of measles and 27 denied vaccination or illness. Measles HAT antibody geometric mean liters (GMTs) were 13, (day 0), 38 (3 wks.), and 23 (10 mos.). Twenty-six of the 125 had HAI liters of – 5 prior to vaccination and showed a ≥4-fold antibody titer rise. IgM measles antibody was detected in 12 of these children after protein-A and 2-ME treatment with a GMT at 3 weeks and 10 months of 61 and 40 respectively. There was no history of measles exposure or vaccination in this group. In the remaining 14 children with initial titers < 5 no IgM antibody response was detected, and despite a 4-fold increase in HAI titer at 3 wks. (GMT 28), the 10 month titer had dropped considerably (GMT 9). Ten of these 14 children had a history of previous measles vaccination. The remaining 99 children had detectable initial titers between 5 and 320. After grouping these according to their pre-booster titers, no significant change in GMTs was observed when day 0, 3 wk. and 10 mo. results were compared. Our study suggests that HAI antibody titers in children previously immunologically stimulated against measles are not altered significantly by revaccination, even when the pre-booster titers are low or not detectable.

Acute Measles Encephalitis in Children With Immunosuppression

Four cases of encephalitis occurring in children treated for lymphatic malignancies by immunosuppressive drugs are reported. Measles virus was isolated from the brain in one case and identified immunologically in another. Nucleocapsids identical to those seen in subacute sclerosing panencephalitis were demonstrated in three cases. Severe immunosuppression was evidenced in two patients by failure of rosette formation and low phytohemagglutinin tests. Pathologically, the inflammatory reaction was absent in one brain and moderate in two. Clinically, epilepsia partialis continua was a prominent feature in three patients. A history of measles or of contact was elicited in three cases, five weeks to three months before onset. All cases ran an acute fatal course. Measles virus can behave as an opportunistic invader of the central nervous system in children and the diagnosis of measles encephalitis should be considered in immunosuppressed patients.

A measles outbreak among adolescents

In a May, 1975, outbreak, 147 adolescents, ages 12 to 19 years, were identified as having measles by a physician or school nurse. One junior high school, with an enrollment of 1,122, contributed 131 of the cases. Of the 147 students, 54 were seen by physicians who also supplied their immunization records; 19 of 54 (35%) had received live measles virus vaccine without measles immune globulin, after age one year. The remaining 35 received: killed virus vaccine only (1), K + L (4), L + MIG (4), L at less than 1 year of age (4), L + ? MIG (4), immune serum globulin only, for exposure (6), no vaccine but history of measles previously (9); history uncertain (3). Hemagglutination-inhibition antibody titers were consistent with the diagnosis of acute measles in 11 children. No index case was identified and no secondary cases occured within the families of the 54 cases. This measles outbreak among seemingly immunized adolescents raises a serious question as to the duration of such protection.

Application of microassay technique in cell-mediated immunity to measles virus infection.

A microassay technique for the detection of cell-mediated immunity to measles virus is described. Lymphocytotoxicity of peripheral blood lymphocytes was determined employing the percent reduction of target cells surviving on the microtissue culture plate. Simultaneously, subpopulation of peripheral blood lymphocytes was also measured. Significant measles specific cytotoxicity was only demonstrated in the subjects with prior histories of measles but no reactivity was observed in the children without the history. Cell-mediated immunity appeared slightly earlier than the elevation of hemagglutination inhibition antibody titer. Both reactivities progressively increased and exhibited the maximal responses at the reconvalescent period of 2nd to 3rd week after skin rash. Depletion of T lymphocyte was most prominent at the stage of Kopliks enanthema or the early stage of exanthema.

EVALUATION OF A MEASLES-SMALLPOX VACCINATION CAMPAIGN BY A SERO-EPIDEMIOLOGIC METHOD1

An assessment technique has been devised whereby children from 30 randomly chosen sampling sites are visited within three days of measles-smallpox vaccination and one month later. Vaccination coverage is measured at house visits and immunologic status is determined by collection of early and late blood samples on filter papers from substratified children in priority age-groups, and by looking at vaccination scars. The methodology was employed in a rural area of the Ivory Coast during the maintenance phase of a measles-smallpox vaccination program; 1762 children from 0--72 months old were inspected. Children in the target age groups, 6--24 months, had a vaccination coverage of 53.6% whereas children outside of the target group had a 10.5% coverage. Of 571 target age children, 94.6% had a measles hemagglutination-inhibition antibody titer of less than 1:10 dilution at the first visit, and were presumed susceptible to measles or vaccine. Of 247 substratified children 6--8 months, 98.3% were susceptible to measles before vaccination; 84.3% of 127 vaccinated children in this age-group sero-converted when re-tested. Of 324 children 9--24 months, 91.7% were susceptible before the campaign; 94.7% of 170 vaccinated children in this age-group converted. A positive history of prior measles or prior measles-vaccination was not a good indicator of measles serologic status. The smallpox vaccination major reaction rate was 93.2%; 91.4% of children with a recent vaccination scar sero-converted to measles vaccine. Thus, the smallpox scar read at the second visit proved the best clinical marker for determining both coverage and immunologic effectiveness of the campaign.

Measles (rubeola) susceptibility among elementary schoolchildren.

Measles (rubeola) immunity among 479 elementary schoolchildren from suburban Minneapolis was serologically surveyed in December 1971. Of the 479 children, 25 (5.2%) had hemagglutination-inhibition (HI) titers less than 2. These children were considered susceptible to measles. For the 233 immunized children with no measles history, 13 (5.6%) had rubeola HI titers less than 2 while 5 (5.1%) of the 98 youngsters with a history of clinical measles had rubeola HI titers less than 2. Of the 454 immune children, 73 (16%) had measles HI titers between 2 and 8. These findings confirm durable immunity and a low rate of vaccine failure following live attenuated measles vaccination but demonstrate the importance of testing sera beginning at a dilution of 2 in order to detect children with low antibody levels. This survey also suggests that maternal antibody interferes with the active immune response in youngsters immunized when less than 1 year of age because this group of children had significantly lower geometric mean titers and significantly more susceptibles than the children immunized when greater than or minus 2 years.

Cell-associated immunity to measles (rubeola): The demonstration of in vitro lymphocyte tritiated thymidine incorporation in response to measles complement fixation antigen

Lack of a reliable in vitro assay for lymphocyte responsiveness to measles (rubeola) has hampered our understanding of the cell-associated response in diseases caused by, or related to, the measles virus. We report a reliable and reproducible system for demonstrating specific lymphocyte incorporation of 3H-thymidine in response to measles complement fixation antigen (CFA). Seventeen patients with positive histories of measles as children demonstrated a dose-response curve that varied between individuals but was constant for each individual. Kinetic data disclosed maximal responsiveness on day 7, and viral inactivation experiments disclosed that live virus was neither necessary for nor inhibitory to the reaction. The implications of this assay in terms of our understanding of the cell-associated response to measles virus in clinical measles and SSPE are discussed. The concept is explored that membrane-associated antigen is crucial in demonstrating the host's cellular immune response to viruses that can grow by cell-to-contiguous cell spread.

The epidemiology and natural history of measles in Denmark.

The epidemiology and natural history of measles in Denmark.

Subacute sclerosing panencephalitis: Elevated epstein-barr virus antibody titers and failure of amantadine therapy

Twelve new cases of subacute sclerosing panencephalitis were seen over a period of 2 years in Montreal (and 2 additional cases since the preparation of this report) indicating a high incidence (1.0 per million per year) of this disease in the Province of Quebec with a total population of 6 million inhabitants. A history of measles was obtained in 10 cases and of live attenuated measles vaccination in the other 2 cases. Measles occurred at or under the age of 2 years in 7 cases and the mean age of onset of SSPE was 7.3 years. A few unusual observations were made: (1) The finding of EBV antibodies in 8 cases tested, 5 of which had titers above 1 80 ; (2) The isolation and/or electron microscopy detection of a presumably latent herpes and adenovirus 21 following co-cultivation of biopsy or autopsy material; (3) The failure of amantadine in 3 cases to alter the course of the disease.

Studies of cell-mediated immunity to measles virus by in vitro lymphocyte-mediated cytotoxicity.

An in vitro lymphocyte-mediated cytotoxicity assay of cell-mediated immunity to measles virus is described that uses tissue culture lines persistently infected with measles virus. Morphologic and 51Cr-release methods were used to measure lymphocyte reactivity; they gave comparable results. Significant measles-specific cytotoxicity was observed only with lymphocytes from measles-seropositive individuals with prior histories of measles; no reactivity was demonstrable with lymphocytes from seronegative individuals and two seropositive adults with negative histories of measles. The capacity to measure measles-specific cell-mediated immunity may provide useful information in the normal host as well as an explanation for the abnormal reactivity of the host predisposed to subacute sclerosing panencephalitis.

Detection of Cell-mediated Immunity to Measles Virus with &lt;sup&gt;51&lt;/sup&gt;Cr Release Cytotoxic Assay in Patients with Natural Measles

Results of a preliminary study of cell-mediated immunity to measles virus employing 51Cr release lymphocytotoxic assay are described. The subjects consist of 5 patients with typical measles, 4 with measles encephalomyelitis, and 11 children and adults with or without prior histories of measles. Specific cytotoxic reactivity to target cells carrying measles specific surface membrane antigen is observed with lympho-cytes from all of measles patients and seropositive individuals. Lymphocytes from 3 out of 4 seronegative individuals without prior histories of measles failed to exhibit specific reactivity to measles virus. No relation was found between serum antibody titers and values of specific lymphocyte reactivity to measles virus. There seems to be no significant difference in cell-mediated immunity between the patients with typical measles and those with complicated encephalitis as evaluated from the results of this study.

Measles in previously vaccinated children. Evaluation of an outbreak.

Investigation of 37 cases of measles in an Alabama elementary school revealed that 25 patients (68%) had been vaccinated, suggesting measles vaccine failure. Attack rates based on a measles history and immunization survey indicated that 16.2% (six of 37) of measles susceptibles who responded acquired disease compared with only 4.0% (20 of 505) of vaccinated respondents. Analysis showed that 17.6% (12 of 68) of children vaccinated at less than 12 months of age contracted measles compared with only 1.9% (eight of 419) of those vaccinated at 12 or more months of age. It is inferred that vaccination at less than 1 year of age may not be effective, because maternal antibody may persist and interfere with immune response to vaccine virus. This would explain the higher incidence in this epidemic of measles among children vaccinated as infants.

An interim report on the production of colonic diverticula in the rabbit

Six New Zealand white rabbits were given gas induction anaesthetics and maintained on glucochloralose (Merck) 60 mg/kg given intravenously. Intracolonic pressures were measured after a standard dose of prostigmine, 0.05 mg/kg, using fluid-filled, open-tipped, narrow-bore polythene tubes. Then the rabbits were put on a diet of white bread, butter, milk, and sugar supplemented by vitamins for four months. All six rabbits had put on weight but their general condition deteriorated; they had become constipated and the colon contracted. After stimulation with prostigmine 0.05 mg/kg scattered intertaenial wide-necked diverticula appeared which were thinner than the normal haustra and looked like a blackcurrant in colour, size, and shape. Repeat pressure measurements showed that the colonic motility index was increased up to 10 times from predietary levels with a highly significant mean increase from 5299 to 33151 (p < 0.0005).

Intensified reactions to measles vaccine in unexposed populations of american Indians.

Evidence concerning the theory that certain populations, specifically American Indians and Eskimos, are unusually susceptible to measles is reviewed. The early history of measles as a disease introduced into the New World is summarized, and mortality rates in virgin-soil epidemics are examined. With the measles-vaccine reaction as a model for the natural disease, the postvaccinal febrile reactions in eleven different Amerind populations are compared with reactions in a standardized series of studies in Caucasian populations. The average fever in the Amerinds was higher by 0.4 C. No consistent pattern of intercurrent disease or immunologic variation that might have contributed to this difference was found. Genetic differences in these populations remain a hypothetical alternative explanation.

A new test of delayed hypersensitivity to measles virus in vitro

The purpose of these studies was to develop an in vitro method for the demonstration of delayed hypersensitivity to measles virus. Using cell lines chronically infected with measles virus, a lymphocyte-target cell interaction was studied, using morphology or Cr51 release as an end point. Preliminary morphologic studies employing control and chronically infected HeLa cells indicated a greater cytotoxic effect with lymphocytes from children previously immunized with live measles vaccine than in unimmunized controls. All subsequent studies employed two human fibroblast lines, one infected (WI-M1) and one normal (WI-38). The WI-Ml carries measles antigen at the cell surface in steady state replication. Modifying the cytotoxic method of Holm and Perlmann, lymphocytes purified by glass bead adsorption were added to Cr51 labelled target cells in a ratio of 100:1. The release of Cr51 in excess of background was interpreted as a measure of lymphocytotoxic factor. The percentage release of Cr51 from WI-M1-38 and WI-38 cells was determined in a group of 8 seropositive adults with no history of clinical measles. The results showed that lymphocytes from the adults with measles effected as much as a 13% increase in Cr51 release from WI-M1 as compared to WI-38 cells. The lymphocytes from the two individuals with negative histories showed a much diminished release. These results indicate that the measurement of lymphocytotoxic response may be a useful in vitro method for studying delayed hypersensitivity to measles virus.

SUBACUTE SCLEROSING PANENCEPHALITIS: A ZOONOSIS FOLLOWING ABERRANT MEASLES

Evidence is accumulating that among patients with subacute sclerosing panencephalitis (S.S.P.E.) measles occurs at an unusually early age. Further, in a small group of patients with measles antibody there was no history of clinical measles despite documented exposure. We interpret these observations as suggesting that in S.S.P.E. patients measles occurred in the presence of passive maternal antibody and, although subsequent immunity was sufficient to prevent a second clinical attack of measles, the balance between the host and virus was altered. The observation that S.S.P.E. occurred at least three times as frequently among boys and at a much lower rate among true urban dwellers is interpreted as evidence that the pathogenesis of S.S.P.E. involves a zoonotic agent. Our hypothesis, therefore, is that S.S.P.E. occurs among individuals in whom there is an abnormal balance between the measles virus and the host immune mechanism, which permits the measles virus to persist in cells, and the precipitating event is an infection with an animal virus. This virus could be the papova-like agent recently observed in tissue-cultures inoculated with S.S.P.E. brain material.

Lymphangiomatosis of bone.

Solitary Hemangioma of bone and the more recently accepted dysplastic disorder of hemangiomatosis, which may lead to “vanishing bones,” are established clinical, pathological, and radiological entities. Much less commonly described are the lymphangiomatous counterparts, solitary lymphangioma and generalized lymphangiomatosis. The latter is quite variable in both the bone changes and the associated lymphatic abnormalities. We have studied 3 additional cases which illustrate these features. Case Reports CASE I: A l0-year old Indian boy with a previous history of measles and whooping cough was admitted with an eighteen-hour history of abdominal pain. The boy had been unwell and had lost weight over the previous three months. One brother was alive and well, while 3 siblings had died in infancy of unestablished causes. The patient had moved from India to England and had lived there for the last nine months. Investigation revealed a left pleural effusion and signs of appendicitis. The appendix was found to be g...

Measles Skin Test and Serologic Response to Intradermal Measles Antigen

History of clinical measles is unreliable as an index of immunity because of subclinical infections, formes frustes, and other exanthems which may masquerade as measles. A skin test for reliably identifying individuals susceptible to measles could be useful for both selecting those requiring vaccination and for testing success of vaccination. This study was designed to relate reactivity to the intradermal injection of a measles antigen to history of clinical measles, to prior vaccination, and to the level of neutralizing and hemagglutination-inhibition antibodies. Another purpose was to determine whether a booster response in serum antibodies resulted from the skin test. Methods and Materials Skin Test Antigen.— The antigen was a tenfold concentration of formaldehyde-inactivated measles virus vaccine produced in chick-embryo tissue culture. The titer of virus before inactivation and concentration was 1 × 10 3.59 infectious doses per 0.5 ml. It did not contain adjuvant, but was preserved with 1:20,000 thimerosal