A Imunologia da infecção pelo HIV em pacientes com idade avançada: caracterização fenotípica e funcional da resposta imune mediada pela célula T CD4+ / Immunology of HIV infection in patients with advanced age: phenotypic and functional immune response mediated by CD4+ cell

A proporção de idosos portadores da síndrome da imunodeficiência adquirida (aids) tem aumentado de maneira importante nos últimos anos e, até a presente data, existem poucos estudos que abordam a infecção nessa população especial. As particularidades imunológicas decorrentes do fenômeno da imunossenescência podem acarretar mudanças significativas na evolução da infecção pelo HIV, bem como na resposta ao tratamento. O objetivo maior desta Tese foi avaliar o impacto da idade na recuperação funcional do sistema imune de pacientes com aids acima de 55 anos, quando tratados adequadamente com terapia anti-retroviral, caracterizando a resultante imunológica da idade avançada e da infecção pelo HIV. Para tanto, foram estudados quatro grupos experimentais: indivíduos jovens saudáveis ou com aids, e indivíduos acima de 55 anos saudáveis ou com aids. Todos os pacientes com aids estavam recebendo terapia anti-retroviral, em sucesso terapêutico. No primeiro artigo apresentado, avaliamos resposta linfoproliferativa e produção de citocinas in vitro e resposta humoral in vivo mediante desafio antigênico com toxóide tetânico (TT) em indivíduos previamente vacinados contra o tétano. Os resultados mostraram deficiências imunológicas significativas relacionadas à idade avançada no que diz respeito a produção de IgG anti-TT, resposta linfoproliferativa e produção de IFN-y. Em contrapartida, a produção de IL-10 foi significativamente maior nos indivíduos acima de 55 anos, infectados ou não pelo HIV. No segundo artigo, foram caracterizadas as subpopulações de células T mediante estímulo policlonal ou específico com antígenos do envelope do HIV (Env). Em culturas não-estimuladas de PBMC do grupo com aids e idade avançada, observamos frequência reduzida de células T naive e de memória central, associada a aumento de células T efetoras. Quando estimuladas policlonalmente, essas culturas apresentaram deficiência na produção de IFN-y e hiperprodução de IL-10, como na resposta ao TT...

The proportion of aged persons living with the acquired immunodeficiency syndrome (aids) has importantly increased in recent years and, up to the present moment, there are few studies that address the infection in this particular population. The immunological nuances resulting from the immunosenescence phenomenon may promote significant alterations in the clinical course of HIV infection, as well as in treatment response. The major purpose of this Thesis was to evaluate the impact of age on the functional immune recovery in aids patients aged more than 55 years, when adequately treated with anti-retroviral therapy, characterizing the immunological result of advanced age and HIV infection. Thus, four experimental groups were enrolled: healthy or HIV-infected young adults, and healthy or HIV-infected adults over 55 years old. All the HIV-infected patients had diagnosis of aids and were under anti-retroviral treatment with therapeutic success. In the first presented article, we evaluated the lymphoproliferative response and cytokine production in vitro and humoral response in vivo, after antigenic challenge with tetanus toxoid (TT) in previously immunized individuals against tetanus. The results revealed significant age-related immunological impairments concerning anti-TT IgG production, lymphoproliferative response and production of IFN-y. On the other hand, the production of IL-10 significantly higher in individuals aged more the 55 years, HIV-infected or not. In the second article, T cell subsets were characterized after polyclonal activation or specific stimulus with antigens derived from the HIV envelope (Env). In fresh unstimulated PBMC cultures obtained from the aged aids patients, there was a reduced frequency of naïve and central memory T cells, associated with increased frequency of effector T cells. When polyclonally stimulated, these cultures showed deficient production of IFN-y and hyperproduction of IL-10, like in response to TT...

Network connectivity is shown to change in C57BL/6 mice during a continuing immune response subsequent to tetanus toxoid hyperimmunization

We have already demonstrated (Stojanovic et al., 2009) a connection between tetanus toxoid (TTd) hyperimmunization and the induction of anti-phospholipid syndrome (APS) in BALB/c mice. Here we show that C57BL/6 mice subjected to an identical procedure do not exhibit any like pathology attributable to anti-phospholipid antibodies; we explain that this absence results from idiotypic connectivity. Six groups of C57BL/6 mice were hyperimmunized with TTd in aluminum hydroxide or glycerol, with or without pretreatments. Pretreated mice had been injected with polyclonal or nonspecific immune stimulators, such as complete Freund's adjuvant (CFA) or glycerol. The epitope specificity of induced antibodies was tested by indirect ELISA using a tetanus toxoid immunogen and these autoantigens: phospholipids, gangliosides, laminin. Idiotypic connectivity was tested by competitive ELISA and gauged from the degree to which the interaction of idiotypic/anti-idiotypic complementary antibodies was inhibited in the presence of immunized sera antibodies. Higher idiotypic connectivity was noted amongst pretreated mice. There was a positive correlation between higher connectivity and autoantibody levels that acted to favor the participation of natural autoantibodies in the inhibitory process. We conclude that idiotypic connectivity plays a protective role in immunization-induced autoimmunity.

Immunogenicity and Safety of Diphtheria-tetanus Vaccine in Adults

This study was conducted to evaluate the immunogenicity and safety of diphtheria-tetanus (Td) vaccine in adults over 40 yr old who had never received a diphtheria-tetanus-pertussis (DTP) vaccination. A total of 242 subject completed three-doses of Td vaccination and subsequent assays for immunogenicity. Before vaccination, 33.9% and 96.7% participants showed antibody levels of diphtheria and tetanus, respectively, which were below protective level ( or =0.1 U/mL) for diphtheria and tetanus, with an increase to 99.6% and 100% after the third dose. Local and systemic adverse events occurred in 37.9% and 15.5% of the subjects. No serious adverse event requiring an unscheduled hospital visit occurred. In conclusion, three-doses of Td vaccination to unimmunized adults are safe and effective in inducing protective immunity against diphtheria and tetanus.

Antigen-specific antibody response in juvenile-onset SLE patients following routine immunization with tetanus toxoid

Infection is now the most common cause of morbidity in Systemic Lupus Erythematosus [SLE]. There is lack of information regarding the specific antibody formation in response to vaccines in young SLE patients. To determine the efficacy of anti-tetanus antibody response in young patients with SLE. Forty SLE patients with mean age of 14.1 years [range: 7-21] and 60 age and sex matched normal controls were enrolled in this study over a period of one year. Diagnosis was made according to the ACR criteria and disease activity was determined based on SLE Disease Activity Index [SLEDAI]. All patients and controls had received the complete schedule of tetanus vaccinations consisting of three primary doses and two boosters by the age of six. Serum immunoglobulins and anti-tetanus antibody titers were determined by Nephelometry and ELISA. Anti-tetanus antibody levels greater than 0.1 IU/ml have been suggested as protective. In all of the patients and controls anti-tetanus antibody titer was > 0.1 IU/ml. IgG, IgA, and IgM levels were in the normal range for their age. Mean disease activity score was 4.9 [range: 0-16]. There was no association between SLEDAI score and anti-tetanus antibody response. School age onset and immunosuppressive therapy does not seem to interfere with development of consistent immunity to tetanus vaccine in young SLE patients

Evaluation of SD BIOLINE Tetanus Kit / 대한진단검사의학회지

BACKGROUND: Point-of-care-testing (POCT) kits for tetanus toxoid antibody are used in emergency departments to evaluate the immunization status of patients with tetanus. The objective of this study was to evaluate the analytical performance and the utility of SD BIOLINE tetanus kit (Standard Diagnostic Inc., Yongin, Korea), as a POCT. METHODS: A total of 326 peripheral blood specimens (whole blood, 319; serum, 326) from healthy subjects and patients were used. SD BIOLINE tetanus kit was evaluated for precision, accuracy, effect of specimens, operator variance, and the total processing time. The results from SD BIOLINE tetanus kit were compared with those from 2 quantitative ELISA kits. RESULTS: Compared with ELISA kits, SD BIOLINE tetanus kit revealed a sensitivity of 88-97%, specificity of 87-92%, positive predictive value of 81-89%, negative predictive value of 90-98%, and kappa agreement of 0.78-0.82. SD BIOLINE tetanus kit also showed an excellent precision and a high accuracy. It showed a high concordance rate between whole blood and serum specimens. The total processing time of SD BIOLINE tetanus kit was 30-40 min. CONCLUSIONS: SD BIOLINE tetanus kit showed an excellent analytical performance. With its rapid turnaround time and the ease of handling and interpretation, SD BIOLINE tetanus kit seems appropriate for the evaluation of tetanus immunization status as a POCT device. However, education for operators and standardized guidelines for result interpretation should be emphasized.

Three suitable antigens for delayed-type hypersensitivity skin testing in a tropical country like Thailand.

Delayed type hypersensitivity (DTH) skin test is a standard tool to assess in vivo cell-mediated immunity. Mantoux method using 4-5 common recalled antigens is recommended. However, not all antigens are widely available and appropriate antigens for tropical countries are not known. The objective of this study is to investigate what and how many antigens should be included in the DTH testing panel that suitable for Thailand and may be for this region. The DTH skin tests were done by Mantoux method in a double blinded fashion. Average induration size of > or = 5 mm defined as a positive test. Antigens included purified protein derivative (PPD), Candida albicans, tetanus toxoid (TT), Trichophyton mentagrophytes and hepatitis B vaccine (HBV). The negative control was normal saline. Of 95 healthy subjects, all showed DTH positive to > or = 1 antigen. The positivity to C. albicans, tetanus toxoid, PPD, T. mentagrophytes, and HBV was 92.6%, 83.2%, 82.1%, 50.5%, and 5.3%, respectively. When three antigens: PPD, TT and C. albicans were analyzed, 100% of subjects showed a positive response to > or = 1 antigen and 96.8% showed a positive response to > or = 2 antigens. When only PPD and TT were analyzed, 100% of subjects showed > or = 1 antigen positive and 68.4% showed both antigens positive. C. albicans antigen at 1:100 was associated with a high incidence of fever (2/20) and large local reaction (7/20), 1:500 was found to be the optimal concentration. PPD, TT and C. albicans are suitable to be included in a DTH skin testing in a tropical country like Thailand. However, in a setting where C. albicans extract is not available, testing with only two antigens of PPD and tetanus toxoid may be an alternative, but with a lower sensitivity.

Delayed hypersensitivity skin testing in the Thai adult population.

OBJECTIVE: The present study was carried out in healthy Thai subjects to determine the types and concentrations of standard antigens used in delayed-type hypersensitivity (DTH) skin testing as an evaluation of cell-mediated immunity. MATERIAL AND METHOD: One hundred subjects were tested with three antigens including tuberculin (purified protein derivative), tetanus toxoid, 1:10 and 1:100 dilutions, and Candida albicans, 1:10 and 1:100 dilutions. RESULTS: We found that 92% of the subjects responded to tuberculin and/or tetanus toxoid at a 1:10 dilution, 77% responded to tetanus toxoid at a 1:10 dilution, and 35% responded to a 1:100 dilution. There was only one subject who responded to Candida albicans at a 1:10 dilution, and none to a 1:100 dilution. The size of tuberculin reactions varied from 5 mm to over 20 mm without any evidence of active tuberculosis. CONCLUSION: Tuberculin and tetanus toxoid at a 1:10 dilution are probably sufficient to be used in DTH skin testing to evaluate T-cell function.

Immunogenicity of a combined DTPa-HB vaccine co-administered with Haemophilus influenzae type B conjugate vaccine (PRP-T) for primary and booster vaccinations

OBJECTIVE: To evaluate the immunogenicity of a combined DTPa-HB vaccine co-administered with Haemophilus influenzae type b conjugate vaccine (PRP-T) in Brazilian infants. MATERIAL AND METHODS: A prospective and open clinical study, in which 110 infants were immunized with a three-dose primary vaccination regime at two, four and six months of age and with a single booster vaccination. Blood samples were drawn immediately before the first dose, one month after the third dose, at the time of the booster dose and one month after the booster to assess seropositivity and antibody geometric mean titers (GMTs) of antibodies for diphtheria, tetanus, hepatitis B, Haemophilus influenzae type b and for the three pertussis antigens: Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN). RESULTS: Among the original 110 infants, 93 completed the study. Seropositivity was 100 percent for all seven involved antibodies, after the primary vaccination course. At the time of the booster dose, all antibodies (except diphtheria 33.7 percent and anti-PT 59 percent) were seropositive for more than 94 percent of subjects. After the booster, seropositivity increased to 100 percent for all antibodies. The GMT of these antibodies followed a similar pattern, with a strong increase after the primary course, followed by a second increase after the booster dose. At this time, GMT was2- to 7-fold higher than after the primary course, for all vaccine components. CONCLUSIONS: Concomitant administration of DTPa-HB and Hib vaccines elicited strong seroprotection for all the antigenic components. No interference with antibody response was evident. The vaccines provided high immunogenicity, following both the primary vaccinations and the booster dose.

Knowledge regarding tetanus toxoid immunization among persons attending health mela in Delhi.

Although vaccine against tetanus has been in use for more than two decades, often people are not aware of tetanus immunization schedules and its significance in preventing tetanus. The current cross-sectional study was carried out to (1) assess knowledge about tetanus immunization (in relation to injury) among persons attending a health mela and (2) To assess their knowledge about tetanus immunization schedules in children, pregnant women and adults. Every tenth person above 15 years of age, who came to health post in the mela was interviewed. A total of 231 persons attending a health mela in Delhi in October 2003 were interviewed. About two third of them were males. Majority (55%) were graduates or above. Only half of them indicated that they would give tetanus immunization after an injury, two fifth indicated it after animal bite and only one fourth indicated it after burns. Knowledge was higher among females and with higher education. However, knowledge regarding correct immunization schedules, prevention of tetanus by DPT and when to give booster in case of injury after primary immunization was poor. There is need to create greater awareness among people about immunization against tetanus, duration of immunity and disease prevented by it. This is to ensure immunization when it is needed and avoid unnecessary repeated immunization.

Influence of placental malaria infection and maternal hypergammaglobulinaemia on materno-foetal transfer of measles and tetanus antibodies in a rural west African population.

Placental malaria infection jeopardizes pregnancy outcome, and its influence may also impair the transplacental transfer of some antibodies. Two hundred and thirteen Gambian mother-baby pairs were studied to determine the influence of placental malaria infection and maternal hypergammaglobulinaemia on transplacental transfer of measles and tetanus antibodies in Gambian population. Placental blood and tissue were collected for placental malaria diagnosis. Cord and maternal sera were tested for total IgG concentration by laser nephelometry and for IgG antibody to tetanus toxoid and measles by ELISA. The prevalence of placental malaria infection was 51.1%. Mothers whose placentae were parasitized had a significantly higher mean total serum IgG (22.0 g/L vs 11.3 g/L, p < 0.001) and measles antibody level (4.02 IU/mL vs 1.21 IU/mL, p < 0.01), but not tetanus antibody, than mothers with non-parasitized placentae. Results of multiple regression analysis showed that placental malaria infection and maternal hypergammaglobulinaemia were associated with the reduction of 72% (95% CI 67.84) and 86% (95% CI 76.91) in transplacental transfer of measles antibody respectively but did not influence the transfer of tetanus antibody. It is concluded that the combined influence of placental malaria infection and maternal hypergammaglobulinaemia is significantly associated with the transfer of impaired measles antibody in this population.

Antibody response to a single tetanus toxoid booster in young women in rural south India.

BACKGROUND: Tetanus toxoid immunization is an integral part of the maternal and child health programme in developing countries. It is likely that many women may have had childhood immunization and so already have antitetanus antibodies at the time of their first antenatal visit. A single dose of tetanus toxoid injection can boost the levels of antitetanus antibodies in these women. This study was undertaken to assess the previous immunization status by verbal history and assess the effect of a single tetanus toxoid injection in young women. METHODS: Ninety-nine unmarried women between 18 and 22 years of age were enrolled for the study. The history of childhood immunization was obtained from their mothers. Blood samples were collected to measure IgG antibody levels to tetanus using ELISA. Antibody levels were also measured on day 14 after a dose of tetanus toxoid injection. RESULTS: Of the 99 women studied, 81 had a history of childhood immunization while 18 did not. Overall, 92% of the women had protective levels of antibodies at the time of first testing and 99% of the women were protected with a single dose of tetanus toxoid. CONCLUSION: In areas with good maternal and child health services, a single booster dose of tetanus toxoid can be considered adequate for primigravidae with a history of childhood immunization.

Cobertura de inmunización con antitetánica y antihepatitis B en estudiantes del primer y cuarto curso del Instituto Dr. Andrés Barbero de la Carrera de Enfermería del año 2001

Estudio descriptivo con un universo de 128 estudiantes y una muestra de 86, para analizar la inmunización con antitetánica y antihepatitis en las estudiantes del primero y cuarto curso del Instituto Dr. Andrés Barbero-Carrera de Enfermería. Determina el porcentaje de alumnos inmunizados y las causas de la no inmunización

An antibody induction method in mice for the potency assays of diphtheria and tetanus components in combined vaccines.

Eleven batches of Adsorbed Diphtheria-Tetanus (DT) vaccines and thirteen batches of Adsorbed Diphtheria-Pertussis-Tetanus (DTP) vaccines were tested for the potency of diphtheria and tetanus components by an Antibody Induction Method (AIM) developed in mice. The potency results obtained were found comparable and did not show any statistically significant difference with those obtained by WHO recommended lethal challenge tests for diphtheria in guinea pigs and for tetanus in mice. AIM in mice is more economical as both diphtheria and tetanus components of combined vaccine can be tested in the same experiment and the procedure also eliminates the use of guinea pigs required in the lethal challenge/conventional tests. The data obtained while testing tetanus component by the conventional antibody induction (IP) method in guinea pigs suggests that minimum requirements laid down in i.p. is too low which may be fixed as at least 3 out of 9 guinea pig sera and should contain > or = 4 units of tetanus antitoxin per ml.

Alternative approach and evaluation of three potency assay methods for testing adsorbed tetanus toxoid.

Thirteen batches of adsorbed Tetanus Toxoid (TT) from different manufacturers were tested for potency by three different methods viz: (i) An Antibody Induction Method (AIM) developed in mice: (ii) WHO lethal challenge in mice; and (iii) Conventional Antibody Induction (I.P). Method in guinea pigs. The potency results obtained in AIM, by serological evaluation of immunized mice were found identical and correlated significantly with those obtained by WHO recommended lethal challenge test in mice. The potency data obtained in the present study was found comparable with other studies. An AIM in mice thus offers an alternative to lethal challenge tests and can replace guinea pig model. Out of 107 serum samples obtained from immunized guinea pigs in the conventional antibody induction method, 90% samples contained more than 4 units of tetanus antitoxin per ml. End point titres of 42 serum samples belonging to 5 batches of TT also showed much higher tetanus antitoxin content when determined by TN test. The potency data obtained thus suggest revision of the minimum requirement in Indian Pharmacopoeia which is too low and which may be increased as indicated by the present study.

Quantitation of tetanus and diphtheria antitoxins in mouse sera by indirect haemagglutination.

Serum samples obtained from 75 groups of mice immunized with various doses of adsorbed tetanus vaccine, adsorbed diphtheria-tetanus vaccine and adsorbed diphtheria-tetanus-pertussis vaccine were titrated for tetanus antitoxin content by an in-vitro indirect haemagglutination (IHA) and by toxin neutralization test (TN) in mice. From these serum samples of 49 groups of mice which were immunized with combined vaccine containing diphtheria toxoid were titrated for their diphtheria antitoxin content by IHA and by i.d. toxin neutralization test (TN) in guinea pigs. Good correlations were found between the estimates obtained by in-vitro IHA and in vivo TN tests in both tetanus and diphtheria antitoxin titrations. The minimum level of tetanus or diphtheria antitoxin detectable by IHA was 0.00039 IU/ml. It is concluded that IHA is a simple, sensitive and reproducible alternative test which can replace the animal TN tests for the estimation of tetanus and diphtheria antitoxins and could reliably be used in the potency assay of tetanus and diphtheria toxoids of combined vaccines based on antibody induction in mice.

Campaña Nacional de Vacunación: Nicaragua, Abril 1996 / National campaing for vaccination and immunization

Presenta los objetivos, metas, la implementación de la actividad y los resultados de la Jornada Nacional de salud, realizada del 13 al 28 de Abril de 1996 en Nicaragua. Asimismo presenta un informe preliminar de la Jornada y graficas y estadísticas de los niños atendidos y la cantidad de vacunas aplicadas: antisarampión, antipolio, D.P.T., T.T., vitamina A, desparasitación, sulfato ferroso a acido fólico.

Estudo clínico do tétano: revisäo; 1994 / Clinical aspects of tetanus: review

O autor fez uma revisäo sobre o tétano abordando os principais estudos referentes a etiologia, epidemiologia, patologia, diagnóstico, quadro clínico, diagnósticos diferenciais, exames laboratoriais subsidiários, tratamento, complicaçöes e profilaxias

Estabelecimento da concentracao antimicrobiana eficaz de tiomersal em toxoide tetanico / Determination of effective antimicrobial concentration of thimerosal in tetanus toxoid

Amostras de taxoide tetanico, contendo quatro concentracoes de tiomersal (0,005; 0,010; 0,015 e 0,020%) dentro dos limites recomendados oficialmente,foram submetidos ao teste de eficacia antimicrobiana do conservante. Com relacao as exigencias da Farmacopeia Americana XXII, apenas Staphylococcus aureus se mostrou resistente as quatro concentracoes, enquanto que para Pseudomonas aeruginosa, Candida albicans e Aspergillus niger o sistema conservador atendeu as exigencias oficiais, mesmo na menor concentracao. O teor de tiomersal em toxoide tetanico podera ser de 0,005%

Vacunas duple: estudio de la reactogenicidad e inmunogenicidad de las preparaciones importada y cubanas (con diferentes dosis de toxoides) / Duplex vaccine: study on reactogenicity and immunogenicity of cuban and imported preparations(with different doses of toxoid)

Se realiza un estudio de la reactogenicidad e inmunogenicidad de vacunas combinadas contra la difteria y tétanos, importadas y de producción nacional(con diferentes dosis de toxoides), en un grupo de 40 escolares. Se comparan los efectos colaterales producidos por las preparaciones utilizadas. Sedetermina el estado inmunitario previo a la vacunación con respecto a la difteria y el tétano, así como el incremento de los títulos de antitoxina. Se utiliza el método ultra micro ELISA(UME) en el sistema ultra micro analítico (SUMA). Se comprueba la tolerancia y poder inmunogénico de las vacunas. Se recomienda continuar las investigaciones y utilizar el método UME en el SUMA, para los trabajos de terreno