Biomedical subjects

Robert M Jacobson

Publications and source records attributed to Robert M Jacobson.

45 records · Page 3Linked to original sources

PubMed2003

The overall safety profile of currently available vaccines directed against infectious diseases.

The vaccines currently used worldwide for the prevention of infectious diseases are quite safe in comparison to most pharmaceutical and biological agents. Vaccine components may contribute to inflammatory, allergic or anaphylactic reactions. Most adverse events are transient and well-tolerated. Transient severe adverse reactions occur at rates of one in one thousand vaccinations; permanent severe adverse reactions occur on the order of one in one million. The most common of the severe adverse reactions are syncope and allergic reactions. Providers can take steps to prevent or ameliorate these reactions by pursuing both prelicensure testing (albeit limited) and postlicensure testing and monitoring. Systems that enhance the detection of safety concerns include national passive and active surveillance as well as regional vaccine registries and provider-based patient education. Since vaccines are used in universal programmes, their safety is paramount to their continued acceptance. Healthcare managers, including administrators of hospitals, clinics, practice groups, health maintenance organisations (HMOs) and managed care plans, can and should support providers in minimising adverse events associated with vaccines by supporting postvaccination observation policies, postlicensure testing and surveillance, vaccine registries and patient education systems.

Communicable Diseases↗

PubMed2002

Associations between human leukocyte antigen homozygosity and antibody levels to measles vaccine.

The association between human leukocyte antigen (HLA) homozygosity and measles antibody levels was assessed in a volunteer group of 242 children. Serum samples were tested for measles IgG antibodies, class I and class II HLA alleles were typed, and associations were examined between HLA homozygosity and antibody levels. Children who were homozygous for at least 1 locus were twice as likely to be seronegative (odds ratio, 1.97; 95% confidence interval, 1.08-3.61). Children who were homozygous at >/=1 loci were increasingly likely to be seronegative (chi(2) test for trend; P=.02). When serum antibody levels were examined as continuous variables, children who were homozygous at certain loci tended to have lower mean antibody levels. These results suggest that lack of HLA diversity may limit the range of peptides that can be presented to antibody-producing cells, potentially resulting in a decreased immune response to viral infections.

Adolescent↗

PubMed2002

The challenge of vaccine safety.

Vaccines always will involve some risk, and risk always involves some public concern. Although the benefits of routine vaccination greatly outweigh any adverse effects, our consumer society seeks to eliminate all risk. The balance of risk and benefit appears to falter by the very success of preventing disease: in the immediate absence of the disease, the resolve to vaccinate waivers. We cannot expect the public to think in terms of the decision analyst and carefully weigh probability, risk, and benefit in a numerical fashion. In fact, the public's approach toward vaccination is varied and unscientific. Recognizing these challenges, we propose a program of continued vigilance by increasing our scientific base and methodology, improving vaccine safety communication through research and resources, maintaining a tolerance of conscientious objection as a safety valve for mandated routine vaccination in civilians, and calling for more research funding for the development of new vaccines.

Adverse Drug Reaction Reporting Systems↗

PubMed2002

Prevalence of anti-gelatin IgE antibodies in people with anaphylaxis after measles-mumps rubella vaccine in the United States.

OBJECTIVE: Anaphylaxis after immunization, although rare, is serious and potentially life-threatening. Understanding risk factors for this reaction is therefore important. Gelatin is added to many vaccines as a heat stabilizer. Japanese researchers have demonstrated a strong association between immediate hypersensitivity reactions to measles, mumps, rubella, varicella, and Japanese encephalitis immunizations and subsequent detection of anti-gelatin immunoglobulin E (IgE) antibodies. They suggested that previous receipt by these patients of diphtheria-tetanus-acellular pertussis vaccines with trace amounts of gelatin was responsible for the sensitization. We aimed to assess whether a similar association exists for vaccinees in the United States who reported anaphylaxis after receipt of measles-mumps-rubella (MMR) or measles vaccines and to review recent trends in reporting of hypersensitivity reactions. METHODS: We conducted a retrospective case-control study. Cases of anaphylaxis that met a predefined case definition were identified from the US Vaccine Adverse Event Reporting System (VAERS). Mayo Clinic patients who received MMR vaccine uneventfully served as controls. The study subjects were interviewed to obtain the history of allergies. Sera from study subjects and their matched controls were tested for IgE antibodies to gelatin, whole egg, and vaccine viral antigens using solid-phase radioimmunoassay. Data from the Biologics Surveillance System on annual numbers of doses of MMR and varicella vaccines distributed in the United States were used to evaluate possible changes in reporting of selected allergic adverse events. RESULTS: Fifty-seven study subjects were recruited into the study and interviewed. Of these, 22 provided serum samples for IgE testing. Twenty-seven subjects served as a comparison group and provided a sample for IgE testing; 21 of these completed an allergy history questionnaire. Self-reported history of food allergies was present more frequently in the interviewed study subjects than in the controls, whereas the proportions of people with other characteristics were similar in both groups. None of the interviewed people had a history of food allergy to gelatin. The level of anti-gelatin IgE antibodies was significantly higher among study subjects than among controls, whereas the levels of IgE antibodies against egg and all 3 viral antigens did not differ significantly. Of 22 study subjects, 6 (27%) tested positive for anti-gelatin IgE, whereas none of the 27 controls did. The rate of anaphylactic reactions reported to VAERS after measles virus-containing immunization in the United States between 1991 and 1997 is 1.8 per 1 million doses distributed. No substantial increase in the number of reported allergic events after frequently used gelatin containing MMR and varicella vaccines could be observed during the first 4 years (1997-2000) since the introduction of diphtheria-tetanus-acellular pertussis vaccines for use in infancy. CONCLUSION: Anaphylactic reactions to MMR in the United States are rare. The reporting rate has the same order of magnitude as estimates from other countries. Almost one fourth of patients with reported anaphylaxis after MMR seem to have hypersensitivity to gelatin in the vaccine. They may be at higher risk of developing anaphylaxis to subsequent doses of other gelatin-containing vaccines. These people should seek an allergy evaluation before such immunization.

Anaphylaxis↗

PubMed2002

Universal vaccination of healthy children against influenza: a role for the cold-adapted intranasal influenza vaccine.

The incidence of influenza in children well exceeds that of the elderly and has been identified as the basis for 20% of doctor visits for children during the winter. The disease results in over 100 hospitalizations per 100000 person-months in children <2 years of age. Furthermore, children serve as the major vector in the community; thus, influenza in children results in significant costs to society. Although efficacious, the current intramuscular, inactivated influenza vaccine is infrequently used in children, and is currently targeted only at children at high risk and those who are household members of such individuals. Experts believe that vaccinating only high risk individuals has little impact on the cycle of annual epidemics, but that universal vaccination of children may very well have a substantial impact. Experimental data support this. A recently published cost-benefit analysis indicated that routine, school-aged vaccination through individual visits to a clinician would save 4 US dollars per child vaccinated. A group program such as a school-based one would save 35 US dollars. One obstacle to universal vaccination includes the real and perceived resistance to the addition of yet another annual injection to the already crowded schedule of routine childhood immunizations. Nearing licensure is an intranasal, live attenuated, cold-adapted intranasal influenza vaccine. Cold-adaptation prevents replication in the lower respiratory tract. Trials have demonstrated immunogenicity, safety, and tolerability in adults as well as children. Placebo-controlled trials have shown efficacy rates of 83 to 94%. This novel vaccine addresses obstacles to universal childhood immunization and would permit a program of routine use that would dramatically reduce transmission and stem epidemics of influenza.

Administration, Intranasal↗

PubMed2002

Association of parental vaccination reports with measles, mumps, and rubella protective antibody levels: comparison of Somali immigrant, Hispanic migrant, and US children in Rochester, Minn.

OBJECTIVES: To compare measles, mumps, and rubella antibody levels in Somali immigrant, Hispanic migrant, and US children in Rochester, Minn, and to determine whether parental vaccination reports predict seropositivity. SUBJECTS AND METHODS: From 1995 to 1997, we conducted a cross-sectional analysis using measles, mumps, and rubella antibody levels obtained from a sample of Somali, Hispanic, and Rochester children. Volunteers provided blood samples, vaccination histories, and demographic information. We assessed differences in measles, mumps, and rubella antibody levels among the 3 groups of children and calculated positive and negative predictive values to determine whether parental report of vaccination predicted seropositivity. RESULTS: Study participants included 79 Hispanic migrant, 69 Somali immigrant, and 730 Rochester children. Somali children reported vaccination at significantly older ages compared with Hispanic or Rochester children (P<.001). Most children were seropositive for all 3 antibodies. Parental reports of vaccination had high positive predictive values (71%-100%) but low negative predictive values (0%-50%). CONCLUSION: Somali and Hispanic children were as likely as Rochester children to be seropositive for measles, mumps, and rubella antibodies despite poor documentation of vaccination. Somali children, however, tended to receive vaccinations at significantly older ages than Hispanic and Rochester children.

Adolescent↗

PubMed2002

Effect of differing immunization policies on circulating measles antibody levels in US and Canadian children.

OBJECTIVE: To examine the effect of differing age-at-immunization policies on measles antibody levels in US children immunized at the age of 15 months compared with Canadian children immunized at the age of 12 months. SUBJECTS AND METHODS: Healthy, volunteer US and Canadian children aged 6 to 11 years who had been immunized with a single dose of the measles vaccine were enrolled from 1991 to 1993. Measles antibody was measured with a whole-virus, measles-specific IgG enzyme-linked immunoassay. Age, race, sex, country of residence, general health status, age at time of measles immunization, and time from immunization to sampling were recorded. RESULTS: Of the 1052 children enrolled in the study, US children (n=719) had a significantly higher measles seroprevalence (87%) compared with Canadian children (n=333) (76%; P<.001). After adjustment for time from immunization and age at immunization, the differences in seropositive rates were no longer significant (odds ratio [OR], 1.53; 95% confidence interval, 0.87-2.69; P=.15). We found a significant dose-response relationship between age at the time of immunization and the odds of being seropositive after immunization, with ORs varying from 1 with immunization at 13 months or younger to 2.30 with immunization at 16 months of age (P=.01). CONCLUSIONS: The current US policy of immunizing with the first dose of measles at the age of 12 months may be less effective than a policy of immunizing at 12 to 15 months of age. These findings may be highly significant as we move toward an era in which measles exposure may be rare and policies are developed to eradicate measles.

Age Factors↗

PubMed2001

Score tests for association between traits and haplotypes when linkage phase is ambiguous.

A key step toward the discovery of a gene related to a trait is the finding of an association between the trait and one or more haplotypes. Haplotype analyses can also provide critical information regarding the function of a gene; however, when unrelated subjects are sampled, haplotypes are often ambiguous because of unknown linkage phase of the measured sites along a chromosome. A popular method of accounting for this ambiguity in case-control studies uses a likelihood that depends on haplotype frequencies, so that the haplotype frequencies can be compared between the cases and controls; however, this traditional method is limited to a binary trait (case vs. control), and it does not provide a method of testing the statistical significance of specific haplotypes. To address these limitations, we developed new methods of testing the statistical association between haplotypes and a wide variety of traits, including binary, ordinal, and quantitative traits. Our methods allow adjustment for nongenetic covariates, which may be critical when analyzing genetically complex traits. Furthermore, our methods provide several different global tests for association, as well as haplotype-specific tests, which give a meaningful advantage in attempts to understand the roles of many different haplotypes. The statistics can be computed rapidly, making it feasible to evaluate the associations between many haplotypes and a trait. To illustrate the use of our new methods, they are applied to a study of the association of haplotypes (composed of genes from the human-leukocyte-antigen complex) with humoral immune response to measles vaccination. Limited simulations are also presented to demonstrate the validity of our methods, as well as to provide guidelines on how our methods could be used.

Algorithms↗

PubMedDate not supplied

Measles virus receptors: SLAM and CD46.

The success of vaccination against measles in developed countries has significantly reduced the incidence of measles-related morbidity and mortality. However, measles is still the leading cause of mortality in children from underdeveloped countries due to low vaccination coverage, high transmissibility of the measles virus as well as primary and secondary vaccine failure. As with any viral disease, the identification of the host molecule to which the measles virus binds and gains entry into the host cell is a major step in understanding the molecular pathology of the disease. Two cell surface receptors, CD46 and signaling lymphocyte-activation molecule (SLAM), have been identified as measles virus receptors. CD46 is ubiquitously expressed on all nucleated cells and acts as a receptor for the Edmonston strain and all vaccine strains derived from it. SLAM is selectively expressed on some T and B cells and is utilised by the Edmonston strain and wild-type strains that cannot use CD46 for cell entry. Understanding the structural and functional variations in measles virus receptors with regard to host response can facilitate the development of new vaccines as well as provide new insights into measles virus tropism and pathogenesis and, importantly, into possible mechanisms for vaccine non-response. Our review focuses on the structure of measles virus receptors, measles virus receptor function, isoforms and polymorphic forms.

Animals↗