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PubMed1995

Immunization status of hospitalized preschool children: risk factors associated with inadequate immunization.

OBJECTIVES: The purposes of this study were to determine the accuracy of the immunization histories of hospitalized preschool children, assess the sociodemographic factors associated with delayed immunizations, and interview parents or guardians concerning their views on ways of improving immunization delivery. METHODS: The immunization status of 215 preschool children admitted to a pediatric hospital was determined by interviewing parents or guardians regarding their children's immunization histories. The patient's immunization records were subsequently reviewed for confirmation. The admitting physician's history also was reviewed to determine whether the patient's immunization status had been noted. Finally, parents or guardians of all children studied were interviewed to assess their views on ways of improving the delivery of immunization services. RESULTS: Only 44% of the 215 preschoolers evaluated were adequately immunized. Among those between 2 and 5 years of age, 52% were fully immunized. Only 17% of those who were inadequately immunized could have been completely updated if given an immunization at discharge. The admitting physician failed to document the immunization status of 22% of the patients. Thirty percent of the parents gave inaccurate information concerning the immunization status of their children. Most parents felt that the provision of transport (30%) or formal remainders (21%) would enhance immunization rates. Multiple regression analysis showed that a history of missed opportunity to immunize, male gender, lack of transportation, and lack of day care attendance were significant predictors of delayed immunization. CONCLUSIONS: Resident physicians should be more stringent in documenting the immunization status of all admitted preschoolers so that those found to be delayed could be updated before discharge. A hospital policy of updating underimmunized children at discharge and reporting the immunization status of all discharged patients to their primary care provider could help improve the immunization coverage in this population. Transportation for routine health maintenance and telephone or mailed remainders might further improve the immunization status of inner-city children.

Adolescent↗

PubMed2026

Immune subtyping of colorectal adenoma identifies a subtype with activated adaptive immunity ahead of progressing to cancer.

BACKGROUND: Colorectal adenomas (CRA) represent precursor lesions with varying risks of malignant transformation. However, molecular subtyping, particularly immune-related classification, remains underexplored in adenomas. This study aims to characterize the immune landscape of CRA through immune subtyping and evaluate its association with cancer progression, gene expression signatures, and functional pathways. METHODS: We conducted a retrospective analysis of transcriptomic data from multiple cohorts of CRA samples. Immune subtypes were identified using non-negative matrix factorization (NMF) based on immune-related genes. Diverse deconvolution algorithms were used to estimate immune cell infiltration. The immune status alteration in premalignant lesion was further consolidated by single-cell transcriptome data. Differential gene expression analysis was performed between subtypes, followed by functional enrichment analyses (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes [KEGG]). RESULTS: Two distinct immune subtypes were identified: an immune-enriched subtype characterized by high lymphocyte infiltration and elevated expression of immune-related genes, and an immune-deficient subtype with suppressed immune activity. Differential expression analysis revealed significant upregulation of immune response genes (e.g., CD4, CD86, HLA-DRA) in the immune-enriched subtype. GO and KEGG analyses highlighted enrichments in leukocyte transendothelial migration, chemokine signaling, and antigen processing and presentation pathways. Single-cell result revealed an early occurrence of TIGIT activation and exhausted CD8 T cell features in adenoma when compared to normal tissue. CONCLUSION: This study delineates distinct immune subtypes within CRAs. The immune-enriched subtype demonstrates activated adaptive immunity and may reflect a higher potential for immune surveillance, while the immune-deficient subtype exhibits stromal features suggestive of progressive transformation. These findings provide insights into early immune microenvironment alterations and may inform strategies for risk stratification and immunoprevention in colorectal carcinogenesis.

Colorectal adenoma↗

PubMed1995

Immune reactions following systemic immunization prior or subsequent to intrastriatal transplantation of allogeneic mesencephalic tissue in adult rats.

We have previously found that dissociated mesencephalic tissue, which differs from the host at both major histocompatibility complex and non-major histocompatibility complex gene loci, can survive stereotaxic transplantation to the striatum of adult rats. We have now studied the outcome of intrastriatal neural allografts in rats that were systemically immunized by an orthotopic skin allograft either prior or subsequent to intracerebral implantation surgery. Dissociated mesencephalic tissue from Lewis rat embryos was stereotaxically injected into the dopamine-depleted striatum of hemi-parkinsonian Sprague-Dawley rats. One group was immunized by an orthotopic allogeneic skin graft of the same genetic origin as the neural graft, six weeks before the neural transplantation (the pre-immunized group). Another group was post-immunized by an orthotopic skin allograft, six weeks after the neural transplantation (the post-immunized group). A control group of rats was not challenged by a skin allograft. Marked behavioural recovery was observed in six of seven rats in the control group, in six of eight rats in the post-immunized group, and in none of the pre-immunized rats. Tyrosine hydroxylase-immunopositive cells were found in rats from the two behaviourally compensated groups, but not in the pre-immunized group. The immune responses were evaluated by OX-18 (monoclonal antibody against major histocompatibility complex class I antigen), OX-6 (major histocompatibility complex class II antigen), OX-42 (microglia and macrophages), glial fibrillary acidic protein (astrocytes), OX-8 (cytotoxic T-lymphocytes) and W3/25 (helper T-lymphocytes) immunocytochemistry. All the neural allografts in the pre-immunized group were rejected, leaving scars only. There were more intense immune responses to the allografts in the post-immunized group than the control group, in terms of immunocytochemically higher expression of major histocompatibility complex class I and II antigens and more intense cellular reactions consisting of macrophages, activated microglia and astrocytes, in addition to CD8- and CD4-positive lymphocytes. In summary, the results show the following: (i) systemic pre-immunization leads to complete rejection of intrastriatal neural allografts, implying that the status of the host immune system before transplantation determines the outcome for intrastriatal neural allografts; (ii) established intrastriatal neural allografts can survive for at least six weeks after systemic immunization, in spite of increased host immune responses in and around the allografts; (iii) there are no marked immune reactions against intrastriatal neural allografts 13 weeks after implantation in rats which have not been systemically immunized by a skin allograft; (iv) pre-immunized rats may provide a very useful animal model to investigate the role of inflammatory lymphokines in immune rejection and to test alternative immunosuppressive drugs.

Animals↗

PubMed1999

Immunization performance measurement in a changing immunization environment.

OBJECTIVE: The measurement of performance in the delivery of recommended vaccinations for children is used frequently as a marker for quality of care and as an outcome for studies of interventions to improve immunization coverage levels. The critical element of immunization performance measurement is the determination of immunization status. This methodologic review 1) discusses immunization status as a measure of quality of primary care for children, 2) describes immunization status measures used in immunization intervention studies, and 3) examines selected technical issues of immunization status measurement. METHODS AND TOPICS: 1) Description of the characteristics of immunization status measurements obtained by a systematic review of studies published between 1980 and 1997 on interventions to raise immunization coverage, and 2) illustration of technical considerations for immunization status measurement using one local database and one national database of immunization histories. Technical issues for immunization status measurement include 1) the need to use documented immunization histories rather than parental recall to determine immunization status, 2) the need to link records across providers to obtain complete records, 3) the sensitivity of immunization status to missing immunization data, and 4) the potential of measures incorporating combinations of immunizations to underestimate the degree of vaccination in a population. CONCLUSIONS: Immunization performance measurement has many characteristics of a robust quality of care measure, including high acceptance by primary care providers of routine vaccination, association of immunization status with the conduct of other clinical preventive services, agreed-on technical and programmatic standards of care, and legislative requirements for medical record documentation. However, it is not without challenges. Careful attention to technical issues has potential to improve immunization delivery health services research.

Child↗

PubMed1994

Immunization practices of primary care practitioners and their relation to immunization levels.

OBJECTIVES: To assess variations in immunization practices and attitudes among primary care providers and to relate these characteristics to the immunization levels of their patients. SETTING: Monroe County, New York. DESIGN: Survey of pediatricians (n = 96) and family practitioners (n = 44) to assess immunization practices and attitudes and medical chart reviews for 1884 patients of 32 physicians who practice in the city of Rochester to measure immunization levels. ANALYSIS: Tabular analyses for survey responses (chi 2 test and Fisher's Exact Test); logistic regression to assess the relation between provider responses and measured immunization levels. RESULTS: Responses by pediatricians and family practitioners were similar. Most providers did not routinely immunize during acute-illness visits but did immunize during follow-up or chronic-illness visits. Few used tracking systems to identify underimmunized children. Most practitioners immunized children who had colds but withheld immunizations from children who had fevers or otitis media. Most providers agreed with expanding immunization programs to include sick visits, health department clinic visits, and community site visits, but most thought that they should not be provided at emergency department visits, except for very-high-risk children. Immunization levels at 10 months of age were positively correlated with private practice setting (P = .001) but negatively correlated with immunizing at acute- (P < .01) or chronic-illness (P < .05) visits, Medicaid coverage (P < .05), and high rates of appointments that were not kept (P < .001). CONCLUSIONS: Primary care providers' immunization practices and attitudes vary and do not always follow established guidelines for immunization delivery. Many providers of high-risk children are already attempting to improve immunization delivery by using patient reminders and by immunizing children at acute- or chronic-illness visits. Improving provider immunization practices to deliver childhood immunizations more effectively must be part of our efforts to resolve this nation's childhood immunization problem.

Adolescent↗

PubMed1998

Influence of mucosal and parenteral immunization with a replication-defective mutant of HSV-2 on immune responses and protection from genital challenge.

Herpes simplex virus (HSV) most frequently initiates infection at a mucosal surface; thus mucosal immune responses are likely to be important in defense against HSV infection. We have examined the effects of eliciting mucosal as well as systemic immune responses on protection against genital challenge infection with virulent HSV-2 in mice immunized with a replication-defective mutant of HSV-2. In addition, we have examined the types of immune responses elicited by immunization by the different routes under conditions known to provide protection. We observed that immunizations at parenteral and distal mucosal sites generate immune responses that have an additive effect in protection against challenge infection with virulent HSV-2. Immunization at either of these sites alone prevented paralysis and death after challenge virus infection and reduced replication of the challenge virus in the genital mucosa, although subcutaneous immunization was more effective in reducing virus replication. Simultaneous immunization at the two sites led to the greatest reduction in mucosal replication of challenge virus. The type of response generated was also affected by the route of immunization. Subcutaneous immunization results in a strong systemic immune response that is somewhat biased toward a Th1 T cell response, while intranasal immunization induces mucosal as well as systemic immunity, as evidenced by HSV-specific IgA in vaginal secretions, and a stronger bias toward a Th1 response. These results suggest that mucosal immunization may complement protective immunity against HSV-2 genital infection generated by parenteral immunization with replication-defective mutant virus.

Animals↗

PubMed2003

The immunization delivery effectiveness assessment score: a better immunization measure?

BACKGROUND: Childhood immunization measures, such as the Health Employer Data Information Set (HEDIS) or the National Immunization Survey, assess the percentage of children up-to-date for a specified series of vaccinations. In particular, the HEDIS assesses immunization delivery to children enrolled in managed care organizations (MCO). Such measures do not assess the timeliness of immunization delivery with reference to recommended age standards. To achieve maximal protection against vaccine-preventable diseases, children should receive all immunizations within recommended age intervals-fully "on-time." OBJECTIVE: The Immunization Delivery Effectiveness Assessment (IDEA) is a novel immunization measure that assesses, on a continuous scale, the timeliness of administration of each vaccination with reference to recommended age intervals. Specifically we ask: 1) Do absolute immunization rates differ between HEDIS and IDEA? 2) Does relative MCO performance differ when assessed by the 2 performance measures? 3) How well do MCOs perform relative to the standard of fully on-time immunization? The health services implications of using the timeliness standard to assess childhood immunization delivery is discussed. METHODS: A vaccine-dose IDEA score was developed for each of the 14 vaccination events in the 4:3:1:3:3 combination series (4 diphtheria-pertussis-tetanus:3 polio:1 measles-mumps-rubella:3 Haemophilus influenzae type B:3 hepatitis B). Assessing the actual age of administration with reference to the recommended age of administration generates the vaccine-dose IDEA score. A child's composite IDEA score is obtained by averaging the 14 vaccine-dose IDEA scores. These composite IDEA scores, when averaged among children sampled within the MCO, constitute the MCO's immunization score. SETTING: Retrospective analysis of childhood immunization datasets from a convenience sample of 6 MCOs in 5 states. RESULTS: HEDIS rates ranged from 57% to 75%. IDEA scores ranged from 80% to 90%. Relative rankings of MCO immunization performance were different using HEDIS rates and IDEA scores, respectively. At most, 16% of children in any of these MCOs received all of their immunizations fully on-time. From 47% to 77% of children experienced at least 3 delayed immunizations. CONCLUSIONS: An immunization measure based on timeliness of administration yields both absolute and relative differences in MCO childhood immunization performance when compared with HEDIS rates. By assessing delivery of each component vaccination, the IDEA score permits more detailed analysis of immunization patterns within an MCO and focuses improvement efforts.

Child↗

PubMed1986

Cells involved in the immune response. XXXIV: Suppressor cells in the thymus of the immunized rabbit capable of secreting a factor which can suppress the secretion of antibodies from antibody-forming cells in vitro.

Outbred rabbits were immunized intravenously with 10(9) sheep erythrocytes (SRBC) and/or horse erythrocytes (HRBC) and sacrificed 1 to 60 days later. At the height of the immune response (Day 7 postimmunization), antibody-forming cells identified by their ability to form hemolytic plaques in the plaque-forming cell (PFC) assay were detected only in the spleen. The splenic PFCs were totally inhibited if they were first incubated with the autologous thymus cells (immune thymus suppressor cells or ITSCs) for 4 hr prior to assaying for PFCs. Incubation of the spleen mononuclear cells with cells of any of the other lymphoid organs of the immunized rabbit for up to 6 hr did not inhibit the PFCs to any significant degree. There is no MHC restriction in the suppressor activity of the ITSCs since they could totally suppress the PFCs of autologous and allogeneic 7-day immune spleen cells. Neither thymus cells nor cells of any of the other lymphoid organs of the unimmunized rabbit could inhibit allogeneic 7-day immune splenic PFCs. The ITSCs from rabbits immunized with SRBC could be isolated by rosetting with the immunizing antigen, SRBC, but not with the non-cross-reacting antigens HRBC, human erythrocytes (HuRBC), and rabbit erythrocytes (RRBC), and vice versa, thus demonstrating the antigenic specificity of the suppressor cells. The thymus cells, but not the cells of any of the other lymphoid organs of the SRBC-immunized rabbit, secreted a factor referred to as immune thymus suppressor factor (ITSF) during incubation for 4 hr at 37 degrees C which could, by itself, totally suppress the splenic PFC. ITSF could be absorbed out of solution by incubation with the immunizing antigen, SRBC, but not with the non-cross-reacting antigens HRBC, HuRBC, and RRBC. Similarly, the ITSF secreted by the thymus cells of the HRBC-immunized rabbit could be absorbed out of solution by incubation with the immunizing antigen, HRBC, but not with the SRBC, HuRBC, and RRBC. ITSF is therefore antigen specific as is its parent ITSC. The cells of the lymphoid organs of unimmunized rabbits did not secrete a suppressor factor during incubation in vitro. ITSCs capable of totally inhibiting the PFCs were detected in the immunized rabbits by Day 5 post-primary-immunization; the ITSCs were capable of secreting ITSF which could totally inhibit the PFCs by Day 7 post-primary-immunization. Although the ITSCs were detected in a suppressive state up to Day 40 post-primary-immunization, they lost their capacity to secrete ITSF by Day 21 post-primary-immunization.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Vaccination with Legionella pneumophila membranes induces cell-mediated and protective immunity in a guinea pig model of Legionnaires' disease. Protective immunity independent of the major secretory protein of Legionella pneumophila.

We have examined the capacity of Legionella pneumophila membranes to induce cell-mediated immune responses and protective immunity in a guinea pig model of Legionnaires' disease. Guinea pigs immunized by aerosol with L. pneumophila membranes developed strong cell-mediated immune responses to L. pneumophila membranes as demonstrated by cutaneous delayed-type hypersensitivity and in vitro splenic lymphocyte proliferation. Guinea pigs immunized by aerosol or by subcutaneous inoculation with L. pneumophila membranes developed strong protective immunity against lethal aerosol challenge with L. pneumophila. Overall, in six independent experiments, 39 of 49 (80%) guinea pigs immunized with L. pneumophila membranes survived challenge compared with 2 of 40 (5%) sham-immunized controls (P = 2 x 10(-13). In contrast, guinea pigs immunized by aerosol with formalin-killed L. pneumophila did not develop either a strong cell-mediated immune response to L. pneumophila antigens or protective immunity to lethal aerosol challenge. The capacity of L. pneumophila membranes to induce protective immunity was independent of the major secretory protein of L. pneumophila, which we previously demonstrated is an immunoprotective molecule. Purified L. pneumophila membranes did not contain detectable major secretory protein (MSP) on immunoblots; immunization of guinea pigs with L. pneumophila membranes did not induce anti-MSP antibody; and guinea pigs developed comparable protective immunity after immunization with membranes from either an L. pneumophila strain that secretes the major secretory protein or an isogenic mutant that does not. This study demonstrates that (a) immunization with L. pneumophila membranes but not formalin-killed L. pneumophila induces strong cell-mediated immune responses and protective immunity, (b) L. pneumophila membranes contain immunoprotective molecules distinct from the major secretory protein of L. pneumophila, and (c) L. pneumophila membranes have potential as a vaccine against Legionnaires' disease.

Aerosols↗

PubMed2000

Immunization levels and risk factors for low immunization coverage among private practices.

OBJECTIVES: Previous studies have indicated that provider characteristics are an important determinant of immunization coverage. The objectives of this study were to: 1) assess immunization coverage levels among 2-year-old children receiving care in private practices in 3 California counties; and 2) evaluate practice and patient risk factors for low immunization coverage. STUDY DESIGN: Cross-sectional chart review of immunization histories and provider survey of immunization policies. SETTING: Forty-five randomly selected, private medical practices in 3 counties in California. PATIENTS: Children 12 to 35 months old, followed by the participating practices. METHODS: Providers underwent a detailed assessment of their immunization coverage and completed a questionnaire describing their immunization policies and procedures. Immunization data were abstracted from randomly selected medical charts of children 12 to 35 months old. Only patients who met the criteria for active status (>/=2 visits and >/=1 visit during the preceding 18 months) were included in analyses. Immunization coverage levels were calculated and logistic regression was used to estimate the risk of underimmunization associated with different practice and child characteristics. RESULTS: Of the 72 eligible practices that were contacted, 45 participated in the study, yielding a participation rate of 62%. The median immunization coverage of participating offices was 54% (range: 0%-91%). Multivariate analysis revealed 5 independent risk factors for underimmunization. The strongest predictors were having fewer than 50% active children in the practice and children having fewer than 8 visits to the provider. Other significant predictors were the percentage of patients in the practice on Medicaid, administering diphtheria-tetanus-pertussis 4 at a separate visit from the Haemophilus influenzae type b booster, and practice location. CONCLUSIONS: These data provide new insights into immunization practices in an important clinical setting that has been poorly characterized previously. Immunization coverage levels were found to be low and significant risk factors for underimmunization were identified. Recommendations are made for immunization policy changes and targeting of immunization improvement interventions at practices that may be at risk for low immunization coverage. immunization, vaccination, immunization programs, primary prevention, private practice, child, preschool, pediatrics, family practice.

California↗

PubMed2007

The economics of routine childhood hepatitis A immunization in the United States: the impact of herd immunity.

OBJECTIVES: Because of the herd-immunity phenomenon, the benefits of immunization against hepatitis A extend beyond those received by those who are vaccinated. This analysis estimates the impact of herd immunity on the cost-effectiveness of routine hepatitis A immunization among US children. PATIENTS AND METHODS: In an economic model, the costs and benefits of hepatitis A immunization were estimated for immunizing all US children at age 1 year over a 10-year period starting in 2005. The future burden of disease from hepatitis A was also estimated with this model, and the fraction that would be prevented by herd immunity was modeled by using a previously published analysis of the relationship between hepatitis A vaccination coverage and declines in hepatitis A incidence. RESULTS: Without accounting for herd-immunity effects, the costs of routine immunization would average 32,000 dollars per quality-adjusted life-year gained for the first 10 cohorts immunized starting with the 2005 birth cohort. Herd-immunity effects would be expected to produce substantial additional benefits, lowering the cost of the immunization program to 1000 dollars per quality-adjusted life-year gained for the first 10 cohorts. Herd-immunity benefits would be greatest for the first few cohorts, more than doubling the benefits of immunization, and would decline over time. In a univariate sensitivity analysis, estimates were most sensitive to vaccination costs but remained below 20,000 dollars per quality-adjusted life-year under all of the assumptions. CONCLUSIONS: Herd-immunity effects more than double the savings from hepatitis A immunization during the first 10 years of the program. After accounting for these effects, immunization is close to cost-neutral on a cost-per-quality-adjusted-life-year basis.

Child, Preschool↗

PubMed1996

Effect of emergency department immunizations on immunization rates and subsequent primary care visits.

BACKGROUND: The Standards for Pediatric Immunization Practices recommend the routine use of emergency department (ED) encounters for screening the immunization status of children and, if indicated, immunizing them. OBJECTIVE: To test the hypothesis that ED immunizations will improve immunization rates without decreasing subsequent primary care visits. DESIGN: A randomized controlled trial of 2 interventions. Children (aged 6-36 months) (n = 1835) were enrolled in the study in the ED; informed consent was obtained from their parents. They were randomized into 1 of 3 groups: (1) the control group (n = 614), in which no intervention was undertaken; (2) the letter group (n = 610), in which a letter to the primary care physician was written indicating the child's estimated likelihood of being underimmunized; and (3) the ED vaccination group (n = 611), in which, based on a decision rule, those likely to be underimmunized were offered immunizations in the ED. After randomization, parents were interviewed in the ED using a decision rule to estimate the likelihood of the child being underimmunized. One year after enrollment in the study, the medical records of the children at their primary care sites were reviewed to determine the immunization status of the children and primary care use patterns. SETTING: An urban ED and 54 primary care sites in Monroe County, New York. RESULTS: The mean age of the participants was 17.9 months. Medical record review-verified underimmunization rates at the time of the ED visit were 33%, 31%, and 28% for the control, letter, and ED vaccination groups, respectively. The demographic characteristics and baseline immunization rates were not different among study groups. According to the decision rule, 248 children (41%) in the ED vaccination group were likely to be underimmunized. Parents of these 248 children were offered immunizations for their children; 117 (47%) accepted, and their children were immunized (with 230 separate immunizations). One month after the ED visits, the underimmunization rates of the study groups were 31%, 28% (P = .40 compared with the control group), and 23% (P = .002). One year later, these rates were 28%, 25% (P = .20), and 25% (P = .20). No clinically meaningful differences were present at either of these times. One year after the ED visit, no differences in the rates of primary care use were found among groups. CONCLUSIONS: This study provides evidence that the immunization of children in this ED was ineffective at raising their immunization rates; primary care attendance was also unaltered. Major obstacles were as follows: (1) an inability to ascertain accurately the immunization status in the ED and (2) a high rate of parental refusal to accept immunizations in the ED. The standards should be modified to de-emphasize the ED as a routine immunization site for children with access to primary care. Efforts and resources should be directed toward strengthening the primary care system and tracking immunization status.

Child, Preschool↗

PubMed1997

Effect of 2 urban emergency department immunization programs on childhood immunization rates.

BACKGROUND: Emergency departments (EDs) are recommended as sites for immunizing children. However, there is little information about the effect of ED immunization programs on immunization rates. OBJECTIVES: To assess the ability of 2 ED immunization programs to vaccinate children and to measure the effect of the programs on immunization rates after the ED visit and 6 months later. DESIGN: A prospective cohort study. Emergency department patients were screened for immunization status, and vaccinations were offered to patients who either were documented to be eligible or were eligible by age and had no documented records. A systematic, sequential sample of those accepting vaccinations (study patients) was compared with a systematic, sequential sample of those not vaccinated (control subjects). Telephone interviews and medical record reviews were performed 6 months after the ED visit to verify dates of immunizations. Results were weighted to reflect the sampling frames of patients screened by the 2 programs. SETTING: Two EDs in New York City (in Manhattan and the Bronx) and the surrounding primary care offices. PATIENTS: Children (aged 0-6 years) screened for immunization status by the ED immunization program during a 10-week period; these included 210 children from the Manhattan ED (106 vaccinated in the ED) and 274 children from the Bronx ED (129 vaccinated in the ED). INTERVENTION: Emergency department immunizations. MAIN OUTCOME MEASURES: Proportion of patients (vaccinated, not vaccinated, and ED population) up-to-date for immunizations (1) at the time of the ED visit, (2) 1 day later, and (3) 6 months later. RESULTS: Two thirds of the patients in each ED had Medicaid, and one tenth were uninsured. At the time of the ED visit, 20% of the vaccinated children in each ED were actually up-to-date and were unnecessarily vaccinated; 74% (Manhattan ED) and 72% (Bronx ED) of the not vaccinated children were up-to-date (the remainder were later determined to have been eligible for vaccinations). One day after the ED visit, and 6 months later, the immunization rates of the vaccinated and not vaccinated children were similar. The results of the weighted analysis were as follows: for the entire ED population screened for immunization status, compared with up-to-date rates at the time of the ED visit, rates 1 day later were 11% (Manhattan ED) and 8% (Bronx ED) higher in each ED (P < .05); and rates 6 months later were the same in the Manhattan ED and 10% lower in the Bronx ED (P < .01). Eighteen percent of all children screened for immunization status were vaccinated; 10 to 15 children were screened and 2 to 4 children were vaccinated per 8-hour ED shift. CONCLUSIONS: This ED immunization program temporarily improved the immunization rates of the ED population, but substantial personnel time was required to achieve these small gains. Urban ED immunization programs are unlikely to be cost-effective.

Child↗

PubMed2003

Immunity to cancer through immune recognition of altered self: studies with melanoma.

The adaptive immune system is capable of recognizing cancer through T- and B-cell receptors. However, priming adaptive immunity against self antigens is potentially a difficult task. Presentation of altered self to the immune system is a strategy to elicit immunity against poorly immunogenic antigens. We have shown that immunization with conserved paralogues of tumor antigens can induce adaptive immunity against self antigens expressed by cancer. Remarkably, cancer immunity elicited by closely related paralogues can generate distinct adaptive immune responses, either antibody or T-cell dependent. Cancer immunity induced by xenogeneic immunization follows multiple and alternative pathways. The effector phase of tumor immunity can be mediated by cytotoxic T cells or macrophages and perhaps natural killer cells for antibody-dependent immunity. Helper CD4+ T cells are typically, but not always, required to generate immunity. Autoimmunity is frequently observed following immunization. Cancer immunity and autoimmunity use overlapping mechanisms, and therefore they are difficult to uncouple, but distinct pathways can be discerned that open the eventual possibility of uncoupling tumor immunity from autoimmunity. Studies examining the molecular basis for immunogenicity of conserved paralogues are facilitating the development of new strategies to rationally design vaccines that trigger adaptive immune responses to cancer.

Animals↗

PubMed1997

[Acute and chronic immune reactions after penetrating keratoplasty with normal immune risk].

BACKGROUND: For diagnostic and therapeutic reasons it is important to differentiate between acute and chronic immune reactions. Up to now in the literature as well as in clinical follow-up such a differentiation has been performed only very insufficiently. We analysed retrospectively frequency and type of immune reactions after penetrating keratoplasties with normal immune risk in order to have a data basis for comparison with the corresponding data from our high risk keratoplasties. PATIENTS AND METHODS: The clinical courses of 646 penetrating keratoplasties with good prognosis performed between 11/1986 and 6/1994 were analysed. The mean patient age was 58 (12-89) years. Only endothelial and stromal immune reactions were recorded. RESULTS: 18% of the grafts suffered from at least one immune reaction during the first 3 postoperative years (Kaplan Meier value). 94% of the grafts without immune reactions remained clear in contrast to 45% of the grafts with immune reactions during this period of time (Kaplan Meier values, Log Rank Test: p < 0.001). 81 immune reactions were observed after 62 keratoplasties. 45 immune reactions (56%) had an acute course (43 endothelial, 2 stromal). 36 (44%) were chronic (31 endothelial, 5 stromal). 93.7% of the grafts without clinical signs of immune reactions, 100.0% of the grafts with only chronic immune reactions and 38.7% of the grafts with only acute immune reactions were clear 3 years postoperatively (Kaplan Meier values). No graft with a combination of acute and chronic immune reactions was clear 3 years postoperatively. 56% of all acute immune reactions occurred during the first postoperative year, 82% during the first 2 and 91% during the first 3 postoperative years. For chronic immune reactions the corresponding values reached 51%, 94% and 100%. CONCLUSIONS: After penetrating normal-risk keratoplasty acute immune reactions occur more often than chronic immune reactions, but the latter are in fact far more frequent than anticipated. If they are diagnosed in time and treated correctly they do not lead to graft failure in the mean run. Both types occur predominantly during the first 3 postoperative years and only rarely thereafter.

Acute Disease↗

PubMed2004

Structure-function analysis of immunity proteins of pediocin-like bacteriocins: C-terminal parts of immunity proteins are involved in specific recognition of cognate bacteriocins.

The immunity proteins of pediocin-like bacteriocins show a high degree of specificity with respect to the pediocin-like bacteriocin they recognize and confer immunity to. The aim of this study was to identify regions of the immunity proteins that are involved in this specific recognition. Six different hybrid immunity proteins were constructed from three different pediocin-like bacteriocin immunity proteins that have similar sequences but confer resistance to different bacteriocins. These hybrid immunity proteins were then tested for their ability to confer immunity to various pediocin-like bacteriocins. The specificities of the hybrid immunity proteins proved to be similar to those of the immunity proteins from which the C-terminal halves were derived, thus revealing that the C-terminal half of immunity proteins for pediocin-like bacteriocins contains a domain that is involved in specific recognition of the bacteriocins they confer immunity to. Moreover, the results also revealed that the effectiveness of an immunity protein is strain dependent and that its functionality thus depends in part on interplay with strain-dependent factors. To further investigate the structure-function relationship of these immunity proteins, the enterocin A and leucocin A immunity proteins (EntA-im and LeuA-im) were purified to homogeneity and structurally analyzed under various conditions by Circular dichroism (CD) spectroscopy. The results revealed that both immunity proteins are alpha-helical and well structured in an aqueous environment, the denaturing temperature being 78.5 degrees C for EntA-im and 58.0 degrees C for LeuA-im. The CD spectra also revealed that there was no further increase in the structuring or alpha-helical content when the immunity proteins were exposed to dodecylphosphocholine micelles or dioleoyl-L-alpha-phosphatidyl-DL-glycerol (DOPG) liposomes, indicating that the immunity proteins, in contrast to the bacteriocins, do not interact extensively with membranes. They may nevertheless be loosely associated with the membrane, possibly as peripheral membrane proteins, thus enabling them to interact with their cognate bacteriocin.

Amino Acid Sequence↗

PubMedDate not supplied

Measles immunization coverage determined by serology and immunization record from children in two Chicago communities.

OBJECTIVES: We compared the prevalence of measles immunization determined by serology with the prevalence of measles immunization determined by immunization records, and identified factors predictive of measles immunization among a sample of children from two Chicago communities. METHODS: We collected demographic information and blood specimens from a sample of children aged 12-71 months in two Chicago communities at risk for low measles immunization coverage levels. We collected immunization information from provider records, parent-held records, and the statewide immunization registry. We compared evidence of immunization determined by serology with evidence of immunization from these three sources of immunization records. RESULTS: The sample of children from the two communities had serologic measles immunity levels of 85% and 90%. Significantly fewer children had evidence of immunization by record in both communities (45% and 63%, respectively). CONCLUSIONS: Immunization coverage levels determined using immunization records were significantly lower than immunization coverage determined using serology. A fully populated immunization registry used by all immunization providers could prevent the problems of record loss and scatter.

Chicago↗

PubMed2003

A DNA-priming protein-boosting regimen significantly improves type 1 immune response but not protective immunity to Trypanosoma cruzi infection in a highly susceptible mouse strain.

BALB/c or C57Bl/6 mice immunized with plasmids containing Trypanosoma cruzi genes developed specific immune responses and protective immunity against lethal parasitic infection. In contrast, in the highly susceptible mouse strain A/Sn, DNA vaccination reduced the peak parasitemia but promoted limited mouse survival after challenge. In the present study, we tested whether the immunogenicity and protective efficacy of vaccination could be improved by combining DNA and recombinant protein immunization regimens. A/Sn mice immunized with plasmid p154/13 which harbours the gene encoding Trypanosoma cruzi trans-sialidase developed a predominant type 1 immune response. In contrast, immunization with the recombinant Trypanosoma cruzi trans-sialidase protein adsorbed to alum generated a typical type 2 immune response. Simultaneous administration of both p154/13 and recombinant Trypanosoma cruzi trans-sialidase protein also led to a predominant type 2 immune response. Sequential immunization consisting of two priming doses of p154/13 followed by booster injections with recombinant Trypanosoma cruzi trans-sialidase protein significantly improved specific type 1 immune response, as revealed by a drastic reduction of the serum IgG1/IgG2a ratio and by an increase in the in vitro interferon-gamma secretion by CD4 T cells. Our observations confirm and extend previous data showing that a DNA-priming protein-boosting regimen might be a general strategy to enhance type 1 immune response to DNA vaccines. Upon challenge with Trypanosoma cruzi, no improvement in protective immunity was observed in mice immunized with the DNA-priming protein-boosting regimen when compared to animals that received DNA only. Therefore, our results suggest that in this experimental model there is no correlation between the magnitude of type 1 immune response and protective immunity against Trypanosoma cruzi infection.

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