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Immunization coverage and the knowledge and practice of mothers regarding immunization in rural area.

One hundred and thirty mothers in the age group (15-44) years and 142 children aged (12-59) months were selected by cluster sampling method from nine villages in Wardha district. Out of this 100 mothers and 122 children could be contacted for evaluation of immunization coverage and assessing maternal knowledge and practice regarding immunization. 52.5% children were fully immunized and 45.1% were partially immunized. Vaccine coverage for B.C.G. and primary doses of DPT/OPV was 95.9% and above 85% respectively. It was 57.4% for measles and 63.04% for booster dose of DPT/OPV. Drop-out rate from second to third dose of DPT/OPV was 5.3% and from third to booster dose was 36.96%. Mothers had a fair knowledge regarding need for immunization but a poor knowledge regarding the diseases prevented and doses of the vaccines. Commonest side reactions reported were fever (36%) and pain at injection site (33%). Contraindications listed by mothers were mild cold (41%), mild fever (24%) or loose stools (14%). Health workers were the major source of information and 76% knew the use and maintenance of immunization cards.

Adolescent↗

Mechanisms of action of intravenous immune globulin in immune-mediated diseases.

Intravenous immune globulin (IVIG) exhibits a number of immunomodulatory properties that are mediated by the Fe portion of IgG and by the spectrum of variable (V) regions contained in the immune globulin preparations. Five predominant and non-exclusive mechanisms of action have been proposed to account for the immunomodulatory effects of IVIG in immune-mediated diseases: (i) functional blockade of Fc receptors on splenic macrophages; (ii) inhibition of complement-mediated damage, an effect that is dependent on the ability of IgG to bind C3b and C4b and thus reduce the number of activated complement fragments that may deposit on target surfaces of complement activation; (iii) modulation of the production of cytokines and cytokine antagonists; (iv) neutralization of circulating autoantibodies by complementary (e.g. anti-idiotypic) antibodies in IVIG, a mechanism that accounts for the rapid decrease in titre of circulating autoantibodies that is often observed within hours following the infusion of IVIG; (v) selection of immune repertoires, a complex set of effects that may be observed in individuals receiving IVIG far beyond the half-life of the infused immunoglobulin and that is directly relevant to the ability of IVIG to, for example, suppress autoantibody-producing clones in patients with antibody-mediated autoimmune disease and modulate graft versus host disease (GVHD). IVIG has been shown to downregulate or activate B-cell clones expressing surface IgG that is complementary (anti-idiotypic) to V regions of antibodies present in IVIG. IVIG has been shown also to interact with surface molecules of T cells that are essential to immune regulation, such as the alpha beta TCR, CD5, CD4, non-polymorphic determinants of MHC class I molecules and adhesion molecules of T and B cells. The complex interactions of IVIG with functional molecules of cells of the immune system are relevant to its therapeutic effects in T cell- as well as B cell-mediated diseases and indeed, to our understanding of the physiological role of normal IgG and antibody networks in controlling autoreactivity in healthy individuals.

Adjuvants, Immunologic↗

[Annual testing of immunity in foxes after oral rabies immunization].

Ten young foxes were orally immunized with a "Rabies vaccine for oral immunization of foxes--LYSVULPEN por. a.u.v.," batch 69 10 93, commercially manufactured by the company Bioveta, s.r.o. at Ivanovice in Haná. The vaccine contained 1.8 x 10 of rabies vaccination virus, strain SAD-Bern, in a vaccination dose. Three foxes were used as control animals without vaccination. Blood samples were taken before the beginning of the experiment in all test foxes, and then in three-month intervals. The last blood samples were taken just before the beginning of a challenge experiment and two months after challenge in the foxes that survived. A challenge test was done in all foxes (vaccinated and nonvaccinated ones) a year after single oral immunization against rabies. Challenge virus was prepared from the salivary gland of a naturally infected fox living in the territory of the Czech Republic. Street virus was applied to each fox i.m. to a great depth to both masticatory muscles (musculus masseter) at a total dose of 10,000 MICLD50. The experimental animals were 60 days under observation. Tab. I shows the titers of virus-neutralizing rabies antibodies after oral immunization against rabies in all experimental foxes. Except fox no. 8, the formation of specific virus-neutralizing rabies antibodies was recorded in all animals after they had eaten vaccination baits. The antibodies were detected throughout the whole year of observation. Tab. II shows the results of challenge test. Out of the nine vaccinated foxes (fox no. 9 died before infection) only fox no. 8 died from rabies, the other treated foxes were protected from rabies (89% rate of protection). Tab. III presents the results of laboratory examination. Tetracycline was demonstrated in all treated foxes (a vaccination proof). Death due to rabies was demonstrated in control animals without vaccination and in fox no. 8. The results achieved in the Czech Republic for oral immunization of foxes against rabies with the vaccination strain SAD-Bern document very good efficacy of the vaccine manufactured by the company Bioveta, s.r.o., in Ivanovice in Haná since 1992. Oral immunization largely improved the infection situation in the Czech Republic. A total of 1,501 cases of rabies infection were recorded at the start of vaccination in 1989 while it was only 221 cases in 1994 (a decrease in then number of foci by 85%).

Administration, Oral↗

Interval mapping of quantitative trait loci controlling humoral immunity to exogenous antigens: evidence that non-MHC immune response genes may also influence susceptibility to autoimmunity.

IgG Ab titers elicited to bovine rhodopsin in CFA differ 8- to 10-fold between H2s identical inbred strains A.SW/snJ (high responder) and SJL/snJ (low responder). This variation in IgG Ab titer resulted from a dramatic difference in the rise in Ab titer occurring during the maturation of the T-dependent humoral immune response. To determine the positions of non-MHC genes controlling this quantitative variation in T-dependent humoral immune responsiveness, 206 reciprocal (A.SW/snJ x SJL/snJ)F2 female progeny were immunized and assayed for anti-rhodopsin responsiveness. The genomes of these progeny were screened with 115 polymorphic simple sequence repeat markers covering >90% of the mouse genome. interval mapping analysis localized the positions of these non-MHC immune response genes to genomic intervals on chromosomes 1, 5, and 13. Interestingly, these three intervals coincide exactly with three intervals recently shown to contain genes contributing to susceptibility to systemic lupus erythematosus and/or the production of autoimmune anti-dsDNA Abs. These results suggest that some genes affecting levels of humoral immune responsiveness to exogenous Ag may also play a role in genetic susceptibility to humoral autoimmune diseases. Analyses of the modes of inheritance demonstrated that high responder alleles were inherited from both parental genomes, indicative of epistatic interactions among genes influencing humoral immune responsiveness.

Animals↗

Intravenous administration of human immune globulin in dogs with immune-mediated hemolytic anemia.

OBJECTIVE: To evaluate the efficacy and safety of intravenous administration of human immune globulin in the treatment of dogs with immune-mediated hemolytic anemia (IMHA). DESIGN: Prospective clinical trial. ANIMALS: 10 dogs with confirmed primary IMHA that had failed to respond to conventional immunosuppressive treatment (administration of prednisone and cyclophosphamide or azathioprine). PROCEDURE: Diagnosis of IMHA was confirmed by detecting spherocytosis or autoagglutination in blood smears and by excluding secondary causes of IMHA. Dogs were treated with human immune globulin (1 g/kg [0.45 g/lb] of body weight, i.v.) during a 6- to 12-hour period. Prednisone treatment was continued in all dogs, and cyclophosphamide treatment was continued in 4. RESULTS: Median duration of prior immunosuppressive treatment was 12.5 days. Short-term response could not be evaluated in 2 dogs, because they were given blood transfusions within 7 days after immune globulin treatment. However, there was a significant increase in mean Hct and hemoglobin concentration in 8 other dogs from day 0 to 28 after treatment. Five dogs had clinically meaningful responses to treatment. Three dogs were alive 12 months after treatment. There were not any adverse effects that could be definitively attributed to immune globulin treatment; however, thrombocytopenia was observed in 6 dogs after treatment, and evidence of thromboembolism was detected at necropsy in 5 of the 7 dogs that died. CLINICAL IMPLICATIONS: Human immune globulin may be useful for short-term stabilization of some dogs with IMHA; however, it did not appear to improve long-term survival.

Anemia, Hemolytic, Autoimmune↗

Comparison of various expression plasmids for the induction of immune response by DNA immunization.

Intramuscular injection of plasmid DNA is an efficient method to introduce a foreign gene into a live animal. We investigated several factors affecting the gene transfer efficiency and the following immune response by intramuscular injection of plasmid DNA. When the strength of several highly efficient viral promoters was compared in muscle by using the chloramphenicol acetyltransferase (CAT) gene as an indicator, cytomegalovirus (CMV) immediate early promoter was found to be stronger than any other viral promoters including Rous sarcoma virus (RSV), murine leukemia virus (SL3-3) and simian virus 40 (SV40) early promoters. Inclusion of adenovirus tripartite leader (TPL) sequences and a synthetic intron in the 5' untranslated region of mRNA moderately stimulated the CAT expression. On the other hand, the expression of encephalomyocarditis virus (EMCV) VP1 gene was greatly enhanced by the TPL sequences and an intron. The level of humoral immune response by intramuscular injection of various VP1 expression plasmids was compared. The seroconversion rate was highly dependent on the strength of the expression vector. However, the ratio of IgG1 and IgG2a immune response was not significantly variable depending on the strength of the expression vector. Also, the efficiency of the sindbis virus-based DNA vector was examined for the gene expression and immune response. Although a high level of CAT expression was obtained in muscle by using this system, VP1 was not produced as much as the conventional expression vectors. Furthermore, little humoral immune response was elicited by intramuscular injection of VP1-expressing sindbis vector, suggesting that this system was not superior to the conventional vector for DNA immunization.

Animals↗

Factors involved in regulating primary and secondary immunity to infection with Histoplasma capsulatum: TNF-alpha plays a critical role in maintaining secondary immunity in the absence of IFN-gamma.

Primary infection to Histoplasma capsulatum often results in a self-limited upper respiratory infection in humans; however, in immunocompromised hosts, disseminated infection can occur through reactivation of a previous infection. Since disseminated histoplasmosis has emerged as a difficult clinical entity to treat in individuals infected with HIV, it was of interest to study the mechanisms involved in maintaining an effective memory immune response. It has been previously shown in a murine model of disseminated histoplasmosis that IL-12, IFN-gamma, and TNF-alpha were important factors in mediating primary protection. To study whether these and other factors were involved in maintaining a protective immune response following secondary infection, normal C57BL/6 mice were first infected with a sublethal dose of H. capsulatum (1 x 10(5)) and then reinfected 3 wk later with a lethal dose of H. capsulatum (6 x 10(5)). Under these conditions, all mice developed an effective immune response with sterilizing immunity. Moreover, normal C57BL/6 mice treated with neutralizing Abs against either IL-12, TNF-alpha, or IFN-gamma, depleted of neutrophils or treated with aminoguanidine at the time of reinfection, maintained an effective immune response. The ability of animals to survive a secondary infection in the absence of IFN-gamma was verified by showing that IFN-gamma(-/-) mice previously immunized with H. capsulatum and treated with amphotericin B at the time of primary infection had prolonged survival following reinfection with a normally lethal dose. It was further shown that enhancement of TNF-alpha production in IFN-gamma(-/-) mice was the major mechanism by which these mice were effective in controlling secondary infection.

Animals↗

Specific immune induction following DNA-based immunization through in vivo transfection and activation of macrophages/antigen-presenting cells.

The initiation of an adaptive immune response requires Ag presentation in combination with the appropriate activation signals. Classically, Ag presentation and immune activation occur in the lymph node and spleen, where a favorable organ architecture and rich cellular help can enhance the process. Recently, several investigators have reported the use of DNA expression cassettes to elicit cellular and humoral immunity against diverse pathogens. Although the immune mechanisms involved are still poorly understood, plasmid inoculation represents a model system for studying immune function in response to invading pathogens. In this report, we demonstrate the presence of activated macrophages or dendritic cells in the blood lymphocyte pool and peripheral tissues of animals inoculated with DNA expression cassettes. These cells are directly transfected in vivo, present Ag, and display the surface proteins CD80 and CD86. Our studies indicate that these cells function as APC and can activate naive T lymphocytes. They may represent an important first step APC in genetic immunization and natural infection.

Animals↗

[Immune response of elderly persons depending on the number of annual seasonal immunizations of live and inactivated influenza vaccines].

A total of 159 subjects aged 65-87 years were immunized with live cold-adapted reassortant influenza vaccine (CRIV), inactivated influenza vaccine (IIV), and with both vaccines (CRIV + IIV) one year, two and three years running. The frequency and intensity of accumulation of postvaccinal secretory and humoral antibodies in elderly subjects depend on the scheme of immunization and history of vaccinations. Combination of the two vaccines effectively stimulated both components of immunity and ensured a longer persistence of postvaccinal antibodies in high concentrations. Immunization with CRIV + IIV for three years resulted in a gradual increase of the intensity of prevaccination secretory and humoral immunity. Before the third seasonal immunization the majority (63-75%) of vaccinees had antibodies in protective titers.

Aged↗

Assessment of immunization registry databases as supplemental sources of data to improve ascertainment of vaccination coverage estimates in the national immunization survey.

OBJECTIVE: To evaluate the use of immunization registry data to supplement missing or incomplete vaccination data reported by immunization providers (referred to as "providers" hereafter) in the National Immunization Survey. DESIGN: Cross-sectional, random-digit-dialing, telephone survey to measure vaccination coverage among children aged 19 to 35 months in the United States. SETTING: Four sites with mature (with >67% of provider participation in the area) immunization registries. PARTICIPANTS: Of the 639 children with complete household interviews, interviewers had consent from the respondents for 569 (89.0%) children to contact their providers and for 556 (87.0%) children to contact both providers and registries. MAIN OUTCOME MEASURES: Percentages of children up-to-date for vaccines based on data from providers, registries, and both sources combined. RESULTS: According to provider-reported data, weighted estimates of coverage for the recommended childhood vaccine series 4:3:1:3 at the 4 sites were 65.6%, 78.8%, 81.6%, and 77.0%. According to registry data, these coverage rates were consistently lower: 31.7% (P<.05), 65.4%, 71.9%, and 61.8%, respectively. When all unique vaccine doses were combined from both sources, the pooled 4:3:1:3 coverage rates increased to 72.0%, 92.0%, 88.7%, and 80.2%, respectively. The quality and completeness of vaccination histories from the registries were inconsistent and varied by sites. CONCLUSIONS: Vaccination coverage estimates were the lowest when only registry-reported data were used and were the highest when provider- and registry-reported histories were combined. Although registries enrolled and matched more children, vaccination histories were missing, incomplete, and inconsistent. The quality and completeness of the registry data must be improved and must be comparable across all states before further consideration may be given to supplement or replace the provider-reported National Immunization Survey data.

Child, Preschool↗

T cell-mediated immunity to oncornavirus-induced tumors. IV. Preliminary evidence for a specific suppression of anti-Moloney cell-mediated immune response by autoimmune T cells.

Previous reports have demonstrated that adult C57BL/6 mice infected with murine sarcoma virus (MSV) develop a strong cell-mediated immune response against Friend, Moloney, Rauscher virus-induced type-specific (FMR) antigens and reject their tumors. To demonstrate a possible role for auto-anti-MSV T blasts, syngeneic C57BL/6 mice were immunized with highly enriched anti-FMR cytolytic T cells. One of 3 pools of these autoimmune T cells prepared from 12 surviving immunized mice (a) inhibited specifically the in vitro anti-MSV cytolysis generation and (b) enhanced drastically the MSV tumor growth in vivo. The possibility for such an immunization procedure to induce anti-idiotype T cells, the repeatability of this effect and the relationship of the suppressor cells with antigen-specific suppressor cells and other components of the anti-MSV immune response are discussed.

Animals↗

Measurement of cell-mediated immunity with a Varicella-Zoster Virus-specific interferon-gamma ELISPOT assay: responses in an elderly population receiving a booster immunization.

An interferon-gamma ELISPOT assay has been developed for assessment of cellular immune responses to Varicella-Zoster Virus (VZV) in large, multi-center clinical vaccine trials. We show that the assay performed best when testing peripheral blood mononuclear cells (PBMCs) that had been isolated and then frozen on the same day as blood was drawn, and that freezing PBMCs from blood that was stored overnight before processing resulted in dramatically reduced responses. This assay was used to monitor cell-mediated immunity (CMI) in response to a booster immunization with an investigational live, attenuated VZV vaccine in an elderly population that had been vaccinated 8-10 years previously. The booster vaccine elicited a 1.6- to 1.7-fold rise in the VZV-specific cellular immune response as measured by the ELISPOT assay. The increase from pre to post booster vaccination response was more pronounced (approximately 2.2-fold rise) in a subset of subjects who had received two prior immunizations with a live, attenuated vaccine.

Aged↗

Tools for immunization guideline knowledge maintenance. I. Automated generation of the logic "kernel" for immunization forecasting.

IMM/Def is a prototype computer program designed to facilitate the building and maintenance of a rule-based program which performs childhood immunization forecasting. An immunization forecasting program takes as input a child's immunization history and produces recommendations as to which vaccinations are due and which should be scheduled next. A significant amount of the knowledge required for immunization forecasting can be expressed in tabular form, including the parameters that indicate the minimum age when each dose may be given and the minimum intervals between doses. The choice of which of these sets of parameters apply to a particular case depends upon additional clinical logic. To perform forecasting, this logic must be applied in three temporal contexts: (1) a dose is due now, (2) a dose is not yet due, and (3) a dose must be scheduled to follow a dose which is due now. Building and maintaining this logic by hand is a formidable challenge. IMM/Def demonstrates how this task can be simplified by first defining immunization "definition logic" which can be automatically translated into if-then rules for each of the three contexts. The approach has been applied successfully to the six childhood vaccination series which are routinely administered. A key advantage is that IMM/Def allows one to have two specifications of the logic that can be examined independently and that can be cross-checked to help assure completeness, consistency, and accuracy of the logic. The paper describes how IMM/Def performs its translation and discusses several design issues and lessons learned.

Child↗

Sequential immunization of macaques with two differentially attenuated vaccines induced long-term virus-specific immune responses and conferred protection against AIDS caused by heterologous simian human immunodeficiency Virus (SHIV(89.6)P).

Four rhesus macaques were sequentially immunized with live vaccines DeltavpuDeltanefSHIV-4 (vaccine-I) and Deltavpu SHIV(PPC) (vaccine-II). The vaccine viruses did not replicate productively in the peripheral blood mononuclear cells (PBMCs) of the vaccinated animals. All four animals developed binding antibodies against both the vaccine-I and -II envelope glycoproteins but neutralizing antibodies only against vaccine-I. They developed vaccine virus-specific CTLs that also recognized homologous as well as heterologous pathogenic SHIVs. Thirty weeks after the last immunization, the vaccinated animals and three unvaccinated control animals were challenged iv with a highly virulent heterologous SHIV(89.6)P. As expected, the three unvaccinated control animals developed large numbers of infectious PBMCs, high plasma viremia, and precipitous loss of CD4(+) T cells. Two controls did not develop any immune response and succumbed to AIDS in about 6 months. The third control animal developed neutralizing antibodies and had a more chronic disease course, but eventually succumbed to AIDS-related complications 81 weeks after inoculation. The four vaccinated animals became infected with challenge virus as indicated by the presence of challenge virus-specific DNA in the PBMCs and RNA in plasma. However, virus in these animals replicated approximately 200- to 60,000-fold less efficiently than in control animals and eventually, plasma viral RNA became undetectable in three of the four vaccinates. The animals maintained normal CD4(+) T-cell levels throughout the observation period of 85 weeks after a transient drop at Week 3 postchallenge. They also maintained CTL responses throughout the observation period. These studies thus showed that the graded immunization schedule resulted in a safe and highly effective long-lasting immune response that was associated with protection against AIDS by highly pathogenic heterologous SHIV(89.6)P.

AIDS Vaccines↗

Transfer of tumor specific immunity with "immune" RNA: prospects for the treatment of human cancer.

Ribonucleic acids extracted from specifically sensitized lymphoid cells (I-RNA) have been shown to transfer specific immunoreactivity to normal non-immune lymphoid cells. Evidence for the transfer by I-RNA, of immune responses to tumor-associated antigens of animal and human neoplasms, in vivo and in vitro, is reviewed. Results obtained in our laboratory and in other laboratories indicate that xenogeneic, allogeneic and syngeneic I-RNA extracts mediate specific cytotoxicity to tumor cells, in vitro, and mediate transplantation resistance and tumor rejection responses in vivo. Our results suggest that I-RNA preparations fail to elicit immune responses directed against "self" antigens. By contrast, I-RNA's directed against "non-self" tumor-associated antigens appear to induce lymphocytes to effect specific anti-tumor immune responses. The mechanisms responsible for the failure of I-RNA to initiate immune responses against "self" antigens are not known at present and demand investigation. Preliminary results of a clinical Phase I trial of immunotherapy with xenogeneic I-RNA in selected cancer patients are reviewed. I-RNA might offer promise as a new modality for the immunotherapy of human cancer.

Animals↗

[Plasmacytoid monocytes and plasmacytoid dendritic cells. Immune system cells linking innate and acquired immunity].

Plasmacytoid monocytes (PM), originally described by pathologists as cells occurring in the interfollicular area of human lymph nodes, are emerging cells in the scenario of the immune system. PM normally circulate between peripheral blood, lymphoid organs and sites of inflammation using specific migratory pathways and signalling; PM are easily recognizable on the basis of their distinctive morphology and phenotype (CD3-, CD11c-, CD14-, CD20-, CD36+, CD56-, CD68+, CD123+, BD-CA2+). Recently it has been shown that PM produce high levels of type I interferon, thus corresponding to natural interferon-producing cells. Furthermore, PM or their precursors may differentiate in vitro towards a new subset of dendritic cells, supporting a function in antigen-dependent T cell priming. Taken together, these data suggest PM play a relevant role in the immune system, linking innate and acquired immunities. In fact, PM seem to be crucial in the pathogenesis of different immune-mediated human diseases including viral infections and autoimmune disorders, and to be involved in the immune control of some malignant neoplasms. The issue concerning the cell lineage of PM remains unresolved, but the frequent association between a tumoral expansion of PM and myelo-monocytic leukemia, together with cytogenetic identity between the two cell populations identified in rare cases, corroborates the myeloid origin of PM.

Animals↗

Leishmania major: nature of immunity induced by immunization with a mutagenized avirulent clone of the parasite in mice.

A chemically mutagenized avirulent form of Leishmania major was used to immunize BALB/c and C57B1/6 mice against challenge with virulent L. major. Immunity was elicited when the avirulent parasite was injected intravenously or intraperitoneally, but not subcutaneously. In fact, the latter route of immunization sometimes resulted in exacerbation of a subsequent infection with virulent L. major. Mice immunized with avirulent L. major developed upon challenge with virulent L. major cutaneous lesions which were significantly smaller and contained substantially fewer parasites than lesions on control nonimmune animals. Finally, the protection conferred by immunization with avirulent L. major could be adoptively transferred with T cells of the CD4+ lineage but not the CD8+ lineage.

Animals↗

Intrasplenic immunization for the induction of humoral and cell-mediated immunity to nitrocellulose-bound antigen.

Intrasplenic immunization of mice has been shown to induce both specific humoral and cell-mediated immunity to minute amounts of nitrocellulose-bound antigen, electroblotted from sodium dodecyl sulfate-polyacrylamide gels. The test antigens used were aberrantly expressed molecules immunoprecipitated from the lysate of highly immunogenic ('xenogenized') murine lymphoma cells, derived by mutagenesis from a parental, nonimmunogenic cell line. The stained bands of nitrocellulose blots corresponding to the appropriate molecular weights were cut out and the resulting strips deposited in the spleens of recipient mice on three occasions at 15 day intervals. 2 weeks later, the antibody response in the serum was analyzed using a standard ELISA procedure. Cell-mediated immunity was investigated in vitro in terms of cytotoxic T lymphocyte (CTL) activity to radiolabeled xenogenized tumor target cells. In vivo, the immunized mice were assayed for their ability to mount a delayed-type hypersensitivity (DTH) response following footpad challenge with the xenogenized tumor. Our results confirm previous data that the intrasplenic deposition of minute amounts of protein immobilized on a solid matrix effectively stimulates production of specific antibodies. In addition, our results demonstrate that this procedure may also result in the development of T cell-dependent responses detectable in in vitro and in vivo assays of cell-mediated immunity.

Animals↗