PubMed Health⌕ Search

Biomedical subjects

G A Poland

Publications and source records attributed to G A Poland.

At least 19 recordsLinked to original sources
PubMed1999

Current paradoxes and changing paradigms in vaccinology.

Other than the provision of clean water, food and sanitation, no other deliberate human intervention has prolonged the human life span as much as the provision of vaccines and the control of infectious disease. Since 1950, 25 vaccines have been licensed in the US, 15 of these for routine universal use in the population. On the horizon are vaccines not only to prevent infectious diseases, but also vaccines against cancer and a host of other human ills. Despite these public health and scientific accomplishments however, the manner in which we think about, develop and apply vaccines to the public health has common heuristic flaws which prevent realizing the full benefits of vaccines to society. This paper will discuss a number of current paradoxes and changing paradigms related to the field of vaccinology.

Humans↗
PubMed1999

Immunogenetic mechanisms of antibody response to measles vaccine: the role of the HLA genes.

Measles is the most transmissible human disease known to date. In the prevaccine era, virtually every member of each birth cohort was infected with this virus, leading to substantial morbidity and mortality, with millions of deaths on a global scale. At the current time, measles causes an estimated 1 to 1.5 million deaths per year world-wide. Since the advent of live, attenuated measles vaccines measles has been controlled, but not eradicated. Central to the goal of measles eradication are data relating to the influence of immunogenetics on vaccine immunogenicity. In this paper, the results of studies are reviewed executed in my laboratory examining the role of the class I and II HLA genes on the antibody response to measles vaccine.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

The burden of pneumococcal disease: the role of conjugate vaccines.

The pneumococcus remains a major cause of morbidity and mortality in both underdeveloped and developed countries. Although there are licensed, safe vaccines against invasive pneumococcal disease currently available in the US and Europe, several major dilemmas are apparent. First, the efficacy of these vaccines in high risk immunocompetent adults is only moderate, with limited or no immunogenicity in very high risk, immunocompromised adults. Secondly, efficacy of the vaccine against pneumococcal pneumonia in adults is controversial. Thirdly, the current vaccines are not efficacious in children < 2 years of age, which is problematic given the high rate of invasive disease among this age group. The solution to these dilemmas may lie in the development of protein conjugate-polysaccharide vaccines. This paper briefly reviews the role of conjugate pneumococcal vaccines.

Adult↗
PubMed1999

Measles antibody seroprevalence rates among immunized Inuit, Innu and Caucasian subjects.

Measles antibody seroprevalence was compared in Innu, Inuit, and Caucasian peoples of northern Newfoundland, Canada, who were immunized with a single dose of M-M-R-II (Merck Research Laboratories) vaccine. Healthy, volunteer schoolchildren (n = 606) were enrolled. Measles antibody was measured with a whole virus measles-specific IgG EIA. Native (Innu and Inuit) schoolchildren (n = 253) had a significantly higher seropositive rate (83%) after a single dose of measles vaccine compared to Caucasian (n = 353) children (76%; p = 0.025), and higher mean antibody levels after immunization compared to Caucasian children (1.74 EIA units, vs. 1.63; p = 0.06). Caucasian children were more likely to have been immunized after age 15 months (20.6% vs. 9.6%; p = 0.001). There was no significant difference in the mean time interval between immunization and blood sampling for natives versus Caucasian (8.0 years vs. 7.95 years; p = 0.49). After adjustment for time from immunization and age at immunization, there remained a marginally significant racial difference in seropositivity (OR = 1.65, 95% CI 0.96, 2.83, p = 0.068). The unadjusted odds ratio for seropositivity (comparing natives vs. non-natives, combining negative and equivocal results) was 1.66 (95% CI 1.06-2.59, p = 0.018). The higher measles-seropositive rate found among native compared to non-native Canadian children suggests that genetic and/or environmental factor(s) affect circulating antibody levels following immunization. The determination of these sources of variability may lead to the development of more efficacious vaccines or delivery strategies.

Adolescent↗
PubMed1999

Concurrent administration of inactivated hepatitis A vaccine with immune globulin in healthy adults.

301 healthy adult volunteers were randomized to one of three treatment groups: inactivated hepatitis A vaccine alone; inactivated hepatitis A vaccine with immune globulin (Ig) concurrently; or Ig alone. The first two treatment groups received a second dose of hepatitis A vaccine at week 24. Anti-HAV was measured 4, 8, 12, 24 and 28 weeks after the primary immunization. When comparing subjects receiving inactivated hepatitis A vaccine alone to those receiving vaccine and Ig, the seropositivity rates were not significantly different at 4, 8, 12 and 28 weeks, but at week 24 the seropositivity rate was lower in the group receiving both vaccine and Ig compared to the group receiving vaccine alone (92.0% compared to 97.0%). At weeks 8, 12 and 24 the geometric mean titers (GMTs) were significantly lower for subjects receiving both vaccine and Ig. The GMTs were not significantly different after the second dose of vaccine. At all time points, the lower serum antibody concentrations observed in subjects receiving both inactivated hepatitis A vaccine and Ig were nevertheless substantially higher than the cutoff for assay seropositivity and much higher than after Ig alone; these differences are therefore clinically insignificant.

Adolescent↗
PubMed1998

The association between HLA class I alleles and measles vaccine-induced antibody response: evidence of a significant association.

While the Moraten strain measles vaccine is an excellent, safe, and immunogenic vaccine, vaccine failure occurs, presumably when an individual develops an inadequate immune response. In this study, we examined the association of HLA class I genes and measles vaccine-induced antibody levels. We found that the allele distribution of HLA-B alleles differed between non-responders and hyper-responders (p = 0.002). Several class I alleles were associated with non-response (HLA-B13, -B44, and -C5); whereas several other alleles were associated with hyper-response (HLA-B7 and -B51). In addition, non-responders were more likely to be HLA-B homozygous than normal responders (odds ratio 2.1), and more likely to be homozygous than hyper-responders (odds ratio 3.7, p = 0.031 Mantel-Haenzel for trend). Finally, we found evidence of an allele dose-response phenomenon for HLA-B7. We conclude that there are important associations between class I HLA genes and measles antibody levels following immunization.

Adolescent↗
PubMed1998

The role of sodium bisulfite in the 1996-1997 USA influenza vaccine recall.

During the 1996-1997 influenza season, all the lots of influenza vaccine manufactured by Parke-Davis were recalled. This voluntary recall by the manufacturer was prompted by the finding of decreasing potency of the A/Nanchang/933/95 (H3N2) component of the vaccine. The primary cause of this lowered potency has been identified as primarily due to the presence of sodium bisulfite which was used to neutralize residual formaldehyde which in turn is used to inactivate the live influenza vaccine strains. This paper reviews these events and what we have learned.

Drug Contamination↗
PubMed1998

The genetic basis for variation in antibody response to vaccines.

Following a brief review of important concepts of vaccine response and vaccine immunology, recent reports on genetic determinants of vaccine response are reviewed. Recent data demonstrating significant associations with particular human leukocyte antigen genes and responsiveness to measles and hepatitis B vaccines are discussed, along with the influence of Km and Gm allotype genes on pneumococcal polysaccharide vaccines. These recent findings have important considerations for research, vaccine development, and clinical practice.

Antibody Formation↗
PubMed1998

The impact of a simulated immunization registry on perceived childhood immunization status.

We developed a simulated immunization registry to assess the impact on the perceived immunization status in a population-based sample of 2-year-olds living in Olmsted County, MN, in 1995. We compiled records of all immunizations by abstracting immunization data from all medical care facilities in the county. The data collected from each facility were analyzed separately to provide the immunization rate as perceived by each facility. This perceived rate was compared to the rate obtained by combining all recorded immunizations from all facilities (simulated registry). Information on children not receiving any carefrom facilities in Olmsted County was compiled from birth certificate data and community school lists. Data from the simulated registry indicated that 69.1% of all children in Olmsted County with medical records were up-to-date on their immunizations by 20 months of age. By 24 months, this increased to 74.2%. The immunization rate of 24-month-old children recorded at individual healthcare facilities in Olmsted County ranged from 24.3% to 79.5%. The addition of data from the simulated registry increased the immunization rate at each site: a 27.7% relative increase in the site with the lowest recorded immunization rate, a 14.0% increase in the site with the intermediate immunization rate, and a 6.9% increase in the site with the highest internally perceived immunization rate. The registry also identified excess immunizations in 5% of the county's 2-year-olds. Each healthcare facility in this community gained an immediate benefit from the development of a simulated immunization registry. This immediate improvement in one quality-of-care measure (up-to-date immunization rate) should be factored into the cost/benefit assessment of immunization registries.

Birth Certificates↗
PubMed1997

Determination of deltoid fat pad thickness. Implications for needle length in adult immunization.

OBJECTIVE: To measure deltoid fat pad thickness and determine the optimal needle length for deltoid intramuscular immunization in healthy adults. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 220 healthy health care workers (126 women, 94 men) at the Mayo Medical Center, Rochester, Minn. MAIN OUTCOME MEASURES: Deltoid fat pad thickness determined by high-resolution ultrasound scanning, weight, height, and mid-deltoid arm circumference. RESULTS: We found a highly significant difference between women and men in deltoid fat pad thickness, with women having a thicker deltoid fat pad (11.7 vs 8.3 mm; P<.001). Women had a greater deltoid skin-fold thickness than men (34.7 vs 17.2 mm, P<.001) and an equal body mass index. According to the ultrasound findings, a standard 16-mm (5/8-in) needle would not have reached 5 mm into muscle in 17% (16/94) of men and 48.4% (61/126) of women in this study. CONCLUSIONS: Among healthy adults of the age range we studied, the following needle lengths appear to be appropriate for true deltoid intramuscular immunization: For men across the weight ranges we studied (59-118 kg), use of a 25-mm (1-in) needle would result in at least 5 mm of muscle penetration in all subjects. For women who weighed less than 60 kg, a 16-mm (5/8-in) needle would be sufficient to achieve muscle penetration of 5 mm. For women between 60 and 90 kg, a 25-mm (1-in) needle would be sufficient, and women greater than 90 kg would require a 38-mm (1.5-in) needle to ensure intramuscular administration.

Adult↗
PubMed1997

Measles reimmunization in children seronegative after initial immunization.

OBJECTIVE: To evaluate the success of measles reimmunization in children without measles antibody after the initial dose of measles vaccine. DESIGN AND SETTING: A prospective clinical trial in Olmsted County, Minnesota, and Northern Newfoundland and Labrador in Canada. SUBJECTS: A total of 130 healthy white, Innu, and Inuit schoolchildren. All subjects had received the post-1980 Moraten measles vaccine 4 to 11 years earlier. METHODS: Children previously identified as measles antibody seronegative or equivocal after 1 dose of measles vaccine were entered into the trial and reimmunized. Measles antibody was measured a minimum of 6 weeks later using a whole-virus IgG measles-specific enzyme-linked immunoassay (EIA). RESULTS: Of the 130 children reimmunized, 106 (81.5%) became measles antibody seropositive, but 24 children (18.5%) remained seronegative. Younger age at initial immunization (<13 months vs > or = 13 months) was significantly associated with lack of seropositive antibody levels following reimmunization (odds ratio, 3.9; 95% confidence interval, 1.5-9.7). In addition, antibody levels after reimmunization were significantly reduced with increasing time since initial immunization (P=.001). CONCLUSIONS: After 2 doses of measles vaccine, 98.2% of all subjects in this study were seropositive for measles antibody, despite the fact that almost 20% of children did not have measurable antibodies 4 to 11 years following a first dose. These findings suggest that the current public health policy recommending a 2-dose measles immunization strategy, with the second dose given at school entry, will provide high levels of immunity in the community.

Antibodies, Viral↗
PubMed1997

Hypercalcemia in a patient with hypoparathyroidism and Nocardia asteroides infection: a novel observation.

Hypercalcemia is associated with numerous chronic granulomatous processes and chronic infections. Increased production of 1,25-dihydroxyvitamin D by activated macrophages has been shown to be the cause in most cases. In this article, we describe a case of hypercalcemia related to infection with Nocardia asteroides. In a 34-year-old woman who previously had hypocalcemia, acute hypercalcemia developed coincident with Nocardia pericarditis. The hypercalcemia resolved after treatment of N. asteroides with sulfisoxazole. Parathyroid hormone and phosphorus levels were within normal limits, and total 25-hydroxyvitamin D levels were only mildly increased. After successful treatment of the Nocardia infection, the patient required supplemental calcium and vitamin D. Her hypercalcemia was temporally related to the duration of the N. asteroides infection. We believe this is the first reported case of hypercalcemia associated with N. asteroides infection.

Adult↗
PubMed1997

Polymorphisms of the TAP2 gene may influence antibody response to live measles vaccine virus.

The transporter associated with antigen processing (TAP) gene products transport peptides from the cytosol to the endoplasmic reticulum for processing by the immune system. We hypothesized that polymorphisms within the TAP genes may influence measles vaccine antigen processing and hence antibody response. TAP genotypes were determined for subjects who were measles vaccine nonresponders (n = 32) and hyper-responders (n = 28). TAP1 and TAP2 alleles were determined by PCR amplification of specific alleles (PASA). Measles vaccine nonresponders were more likely to be homozygous at TAP2 position 665 than were hyper-responders (OR = 5.0, P = 0.016). Lastly, a trend was found in the overall distribution of all TAP2 genotype frequencies between hyper-responders and nonresponders (P = 0.08). No association was found between TAP1 polymorphisms and vaccine response. These data reveal an association between TAP2 genotype and measles vaccine antibody response which may explain one mechanism behind vaccine failure.

ATP Binding Cassette Transporter, Subfamily B, Mem↗