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1.
BMC Infect Dis ; 21(1): 53, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33430802

RESUMO

BACKGROUND: Vaccinations have been widely used worldwide since their invention to prevent various diseases, but they can also have some adverse effects ranging from mild local reactions to serious side effects. These adverse effects are generally self-limited and resolve within a short time without any treatment. While a sterile abscess following vaccination is a rare condition in adults, many cases have been reported regarding children in the literature. Here, we report a case of recurrent sterile abscesses, which occurred after a Td vaccination, treated with corticosteroids. CASE PRESENTATION: A 22-year old woman was admitted to our department with a complaint of swelling at the site of the vaccination. On physical examination, this mass was about 6 × 6 cm in size and fluctuating, but there were no pain complaints and no redness present. She had received her Td vaccination 3 weeks ago and the swelling had started at the site of the injection 4 days following this immunization. Oral amoxicillin/clavulanic acid and local antibiotic cream were administered for 10 days. The laboratory values were unremarkable. Despite the administration of antibiotics, the swelling did not regress, and on the contrary, continued to increase in size. On ultrasound, two interconnected abscesses were observed in the subcutaneous area, and did not involve the muscle tissue. Later, the abscesses were completely drained, and the samples were cultured. The current antibiotics were continued. The gram staining of the samples revealed abundant leukocytes but no microorganisms. The solid and liquid cultures of the materials remained negative. Despite the administration of multiple drainages and antibiotics, the mass recurred. Finally, the patient was considered to have a sterile abscess due to Td immunization. The antimicrobials were stopped. Local and oral corticosteroids were initiated. The swelling regressed significantly, and the treatments continued for 7 days. The patient has been doing well and has had no recurrence for over a year. CONCLUSIONS: Corticosteroids appeared to improve the patient and therefore we suggest that the efficacy and route of administration of steroids in this situation should be explored further.


Assuntos
Abscesso/tratamento farmacológico , Abscesso/etiologia , Corticosteroides/administração & dosagem , Toxoide Diftérico/efeitos adversos , Toxoide Tetânico/efeitos adversos , Abscesso/diagnóstico por imagem , Adulto , Toxoide Diftérico/administração & dosagem , Feminino , Humanos , Toxoide Tetânico/administração & dosagem , Ultrassonografia , Adulto Jovem
2.
Mol Immunol ; 127: 164-174, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33002728

RESUMO

BACKGROUND AND PURPOSE: Tetanus neurotoxin has many potential therapeutic applications, due to its ability to increase localised muscle tone when injected directly into a muscle. It is a closely related molecule to botulinum neurotoxin (most commonly known as Botox), which has been widely used to release muscle tension for therapeutic and cosmetic applications. However, tetanus toxin has been relegated to the "maybe pile" for protein therapeutics - as most of the population is vaccinated, leading to highly effective antibody-mediated protection against the toxin. The potential for tetanus-based therapeutics remains substantial if the problem of pre-existing immunity can be resolved. EXPERIMENTAL APPROACH: A well-established murine model of localised muscular contraction was utilised. We administered functional tetanus toxin combined with an immunogenic, but functionally inactive, decoy molecule. KEY RESULTS: Incorporation of the decoy molecule greatly reduces the dose of active toxin required to induce a localised increase in muscle tone in mice vaccinated with the human toxoid vaccine. CONCLUSION AND IMPLICATIONS: Our results clearly demonstrate that the barriers to developing a tetanus toxin therapeutic are not insurmountable and the technology presented here is the first major step towards realising the therapeutic potential of this powerful neurotoxin. Opening the therapeutic potential of tetanus toxin will have huge implications for the wide range of diseases caused by low-tone muscle.


Assuntos
Toxoide Tetânico/imunologia , Toxoide Tetânico/uso terapêutico , Animais , Humanos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/isolamento & purificação , Soluções , Tétano/imunologia , Toxoide Tetânico/administração & dosagem , Vacinação
3.
BMC Public Health ; 20(1): 855, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503478

RESUMO

BACKGROUND: Immunization of women during pregnancy to protect them and their infants against tetanus, pertussis and influenza is recommended by the World health Organization (WHO). However, there is limited information about the coverage rate and associated factors in low-income countries. The aim of this study was to measure the prevalence and predictors of taking tetanus toxoid among pregnant women in Sierra Leone. METHODS: This study was based on the fifth round of Multiple Indicator Cluster Survey (MICS 5) conducted in Sierra Leone in 2017. In total 8722 women aged between 15 and 49 years were included in this study. Outcome variable was taking of Tetanus Toxoid vaccination during the last pregnancy. Data were analyzed using cross-tabulation and logistic regression methods. RESULTS: The overall prevalence of receiving TT immunization during women's last pregnancy was 96.3% and that of taking at least two doses was 82.12%. In the regression analysis, women from Mende ethnicity had a 0.48 fold lower chance of being immunized (OR = 0.480, 95% CI = 0.385,0.59768) than those from the other ethnicity. In addition, women who attended at least four ANC visits had higher odds of receiving TT vaccine (OR = 1.919, 95% CI = 1.639,2.245) compared to those who attended less ANC visits. Stratified by areas, this association was observed in both urban (OR = 2.661, 95% CI = 1.924,3.679) and rural areas (OR = 1.716, 95% CI = 1.430,2.059). Attending at least four ANC visits showed a positive association with receiving at least two doses TT (OR = 2.434, 95% CI = 1.711,3.464) in both urban (OR = 2.815, 95% CI = 1.413,5.610) and rural areas (OR = 2.216, 95% CI = 1.463,3.356) as well. CONCLUSION: Higher number of ANC visits, mass media exposure and higher wealth quintile increased the odds of receiving TT immunization. In addition, minimum two doses which were identified to reduce neonatal mortality. Therefore, immunization campaigns targeting improved utilization of healthcare and immunization services by women of childbearing age in Sierra Leone are strongly recommended.


Assuntos
Cuidado Pré-Natal/estatística & dados numéricos , Toxoide Tetânico/administração & dosagem , Tétano/prevenção & controle , Cobertura Vacinal/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Pobreza/estatística & dados numéricos , Gravidez , Prevalência , Serra Leoa/epidemiologia , Inquéritos e Questionários , Tétano/mortalidade , Adulto Jovem
4.
MMWR Morb Mortal Wkly Rep ; 69(17): 515-520, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32352953

RESUMO

Maternal and neonatal tetanus* (MNT) remains a major public health problem, with an 80%-100% case-fatality rate among neonates, especially in areas with poor immunization coverage and limited access to clean deliveries (i.e., delivery in a health facility or assisted by medically trained attendants in sanitary conditions) and umbilical cord care (1). In 1989, the World Health Assembly endorsed the elimination† of neonatal tetanus (NT), and in 1999, the initiative was relaunched and renamed the MNT elimination§ initiative, targeting 59¶ priority countries (1). Elimination strategies include 1) achieving ≥80% coverage with ≥2 doses of tetanus toxoid-containing vaccine (TTCV) among women of reproductive age through routine immunization of pregnant women and supplementary immunization activities (SIAs)** in high-risk areas and districts††; 2) achieving care at ≥70% of deliveries by a skilled birth attendant (SBA)§§; and 3) enhancing surveillance for NT cases (1). This report summarizes progress toward achieving MNT elimination during 2000-2018. Coverage with ≥2 doses of TTCV (2 doses of tetanus toxoid [TT2+] or 2 doses of tetanus-diphtheria toxoid [Td2+]) among women of reproductive age increased by 16%, from 62% in 2000 to 72% in 2018. By December 2018, 52 (88%) of 59 priority countries had conducted TTCV SIAs, vaccinating 154 million (77%) of 201 million targeted women of reproductive age with TT2+/Td2+. Globally, the percentage of deliveries assisted by SBAs increased from 62% during 2000-2005 to 81% during 2013-2018, and estimated neonatal tetanus deaths decreased by 85%, from 170,829 in 2000 to 25,000 in 2018. By December 2018, 45 (76%) of 59 priority countries were validated by WHO as having achieved MNT elimination. To achieve elimination in the remaining 14 countries and sustain elimination in countries that have achieved it, implementation of MNT elimination strategies needs to be maintained and strengthened, and TTCV booster doses need to be included in country immunization schedules as recommended by the World Health Organization (WHO) (2). In addition, integration of maternal, newborn, and child health services with vaccination services is needed, as well as innovative approaches to target hard-to-reach areas for tetanus vaccination and community engagement to strengthen surveillance.


Assuntos
Erradicação de Doenças , Saúde Global/estatística & dados numéricos , Vigilância da População , Tétano/prevenção & controle , Feminino , Humanos , Programas de Imunização , Recém-Nascido , Gravidez , Tétano/epidemiologia , Toxoide Tetânico/administração & dosagem
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(2): 167-172, 2020 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-32164124

RESUMO

Post-traumatic tetanus is the main type of non-neonatal tetanus. To reduce the incidence and mortality rateof tetanus and guide the primary medical institutions to prevent and control tetanus after trauma, the National Immunization Planning Technical Working Group of the Chinese Center for Disease Control and Prevention has compiled this document in the reference with Position Paper by World Health Organization, and the latest research progress both at home and abroad. The guidelines focus on the basic procedures for the prevention and treatment of post-traumatic tetanus, the application of tetanus vaccines and immune preparation, and pre-exposure immunization in high-risk populations of trauma.


Assuntos
Imunização Passiva , Toxoide Tetânico/administração & dosagem , Tétano/prevenção & controle , China , Humanos , Tétano/imunologia
6.
J Trop Pediatr ; 66(2): 201-209, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31397484

RESUMO

BACKGROUND: Although tetanus is a vaccine-preventable disease, reports indicate that it remains a significant cause of morbidity and mortality in both neonatal and post-neonatal periods especially in most developing countries. AIM: This study aimed to determine the prevalence and case fatality rates of post-neonatal tetanus among children managed at the Federal Medical Centre Asaba, Delta State, Nigeria over 8 years. METHOD: The study was a retrospective review of the records of the children above 1 month of age admitted into Federal Medical Centre, Asaba, with a clinical diagnosis of tetanus from January 2008 to May 2016. Data analysis was conducted on descriptive and inferential statistics using Statistical Package for Social Sciences version 22.0. Mean, standard deviation and other relevant parameters were calculated. Level of significance was set at p < 0.05. RESULTS: During the study period, 32 out of 3693 admitted Paediatric patients had post-neonatal tetanus: giving a prevalence rate of 0.9%. The male : female ratio was 1.9 : 1 and patients' ages ranged from 2 to 15 years with a mean age 8.9 ± 3.1 years. Twenty-nine percent of them had complete immunization during infancy, but none had booster doses. Also, 60.9% of them presented with lower limb injuries as the portal of entry. Over 17.4% of the patients had very severe tetanus. Of the 32 patients studied, 62.5% resided in the neighbouring rural communities, while 50.0% were admitted for ≤10 days. The calculated case fatality rate was 50%. CONCLUSION: The prevalence and case fatality rates of post-neonatal tetanus are still relatively high in this clime. Given the prevalent nature of the disease in children aged 5 years and above, there is a need to include the booster doses of tetanus toxoid in the country's National Programme on Immunization schedule.


Assuntos
Tempo de Internação/estatística & dados numéricos , Tétano/diagnóstico , Tétano/mortalidade , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imunização , Lactente , Masculino , Mortalidade , Nigéria/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Tétano/terapia , Toxoide Tetânico/administração & dosagem , Resultado do Tratamento , População Urbana
7.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(12): 1203-1205, 2019 Dec 06.
Artigo em Chinês | MEDLINE | ID: mdl-31795575

RESUMO

Neonatal tetanus has been basically eliminated in China, but the incidence of non-neonatal tetanus is still high. Tetanus after trauma is the main type of non-neonatal tetanus. The correct application of tetanus toxoid containing vaccine (TTCV) has been neglected in the prevention of tetanus after trauma in China. On May 9, 2019, National Advisory Committee of Experts on Immunization Planning (NIAC) reviewed and approved the first guidelines for the use of TTCV and passive immune preparation after trauma, which clarified the basic process of treatment of tetanus after trauma, as well as the pointer to the use of TTCV and passive immune preparation after trauma. The main measure to prevent tetanus after trauma is to use TTCV for active immunization, and to use passive immune preparation for those without TTCV immune history. Through the construction of the top-down control and prevention system of tetanus, the change of the concept of tetanus immunoprophylaxis of medical staff is promoted. Active immunization is the main measure, but passive immunization is an added measure for the prevention of tetanus after trauma, which is of great significance to reverse the mistake of prevention of tetanus in China.


Assuntos
Imunização , Guias de Prática Clínica como Assunto , Toxoide Tetânico/administração & dosagem , Tétano/prevenção & controle , China , Humanos , Vacinação
8.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(12): 1212-1217, 2019 Dec 06.
Artigo em Chinês | MEDLINE | ID: mdl-31795577

RESUMO

Post-traumatic tetanus is the main type of non-neonatal tetanus. To reduce the incidence and mortality rate of tetanus and guide the primary medical institutions to prevent and control tetanus after trauma, National Immunization Planning Technical Working Group of the Chinese Center for Disease Control and Prevention has compiled this document in the reference with Position Paper by World Health Organization, the latest research progress from home and abroad. The guidelines focus on the basic procedures for the prevention and disposition of post-traumatic tetanus, the application of tetanus vaccines and immune preparation, and the pre-exposure immunization in high-risk populations of trauma.


Assuntos
Guias de Prática Clínica como Assunto , Toxoide Tetânico/administração & dosagem , Tétano/prevenção & controle , Humanos , Imunização , Programas de Imunização , Tétano/imunologia , Vacinação
9.
Ciênc. Saúde Colet ; 24(12): 4655-4664, dez. 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1055729

RESUMO

Abstract This article aims to identify the prevalence and factors associated with influenza vaccination in pregnant women. This is a cross-sectional study conducted in a municipality in the southernmost region of Brazil, which included all women giving birth in 2016. The outcome was having received the vaccine against influenza during pregnancy. Sociodemographic, behavioral and prenatal care characteristics and morbidities were analyzed. The analysis included sample description, the prevalence of vaccination for each independent variable and a multivariate analysis. Two thousand six hundred ninety-four pregnant women were interviewed, of which 53.9% reported having been vaccinated. Factors associated with increased prevalence of vaccination were mother's higher schooling, prenatal care, tetanus vaccination and prenatal care performed in a public service. On the other hand, prenatal care onset after the first quarter reduced the prevalence of vaccination. The results point to the need to reinforce the importance of vaccination against influenza among pregnant women and among health professionals, regardless of the severity of the current epidemiological setting.


Resumo O objetivo deste artigo é identificar a prevalência da imunização contra a gripe em mulheres grávidas e seus fatores associados. Estudo transversal realizado em um município no extremo sul do Brasil, que incluiu todas as mulheres que deram à luz no ano de 2016. O desfecho foi ter recebido a vacina contra a gripe durante a gravidez. Características sociodemográficas, comportamentais, do pré-natal e morbidades foram analisadas como fatores associados à vacinação. A análise constou de descrição da amostra, prevalência da vacinação para cada uma das variáveis independentes e análise multivariada. Foram entrevistadas 2.694 parturientes, das quais 53,9% informaram ter recebido a vacina. Os fatores associados a uma maior prevalência de imunização foram: maior escolaridade materna, realização do pré-natal, ter realizado a vacina antitetânica e fazer o pré-natal em um serviço público. Por outro lado, o início do pré-natal após o primeiro trimestre reduziu a prevalência de imunização. Os resultados apontam para a necessidade de reforçar a importância da imunização contra a Influenza entre mulheres grávidas e entre profissionais da saúde, independentemente da gravidade do atual cenário epidemiológico.


Assuntos
Humanos , Feminino , Gravidez , Adulto , Adulto Jovem , Complicações Infecciosas na Gravidez/prevenção & controle , Vacinas contra Influenza/administração & dosagem , Vacinação/estatística & dados numéricos , Gestantes , Influenza Humana/prevenção & controle , Cuidado Pré-Natal , Brasil , Toxoide Tetânico/administração & dosagem , Conhecimentos, Atitudes e Prática em Saúde , Estudos Transversais , Análise Multivariada , Escolaridade
10.
Pediatr. aten. prim ; 21(84): e193-e200, oct.-dic. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-191973

RESUMO

INTRODUCCIÓN: el tétanos es una enfermedad aguda grave cuyo tratamiento es difícil y, por tanto, es fundamental su prevención. La administración de cinco dosis de vacuna antitetánica es suficiente para conferir una protección a largo plazo. En los últimos años se ha observado cierta disminución en las coberturas, lo que supone la existencia de población no suficientemente inmunizada. El objetivo de este estudio es analizar la cobertura vacunal de la dosis de recuerdo frente al tétanos en adolescentes en la localidad de Santa Amalia, provincia de Badajoz (España), durante los últimos 20 años (1996-2016). MATERIAL Y MÉTODOS: estudio observacional transversal. Se revisaron las tarjetas de vacunación y los registros de las dosis administradas en los documentos manuscritos y registro informático en el entorno JARA Atención Sanitaria (JARA-AS). Entre 1996 y 2001, la vacunación se hacía en el centro escolar, con registro manual. Desde 2002, se administró la vacuna en el centro de salud, con registro manual (2002-2007) e informático (2008-2016). RESULTADOS: analizada la cobertura de forma agrupada, los peores resultados de vacunación se apreciaron en centro de salud utilizando registro manual (35,6%), mientras que las mejores cifras de vacunación se encontraron en centro de salud con registro informático (100%), seguido por el grupo de centro escolar (83,0%). CONCLUSIONES: este estudio pone de manifiesto una alta cobertura de vacunación frente a tétanos en la dosis de recuerdo en adolescentes de 14 años en Santa Amalia, similar a la cobertura nacional, a diferencia de la baja cobertura existente en el resto de Extremadura


INTRODUCTION: tetanus is a severe acute disease that is difficult to treat, and therefore its prevention is essential. The administration of 5 doses of tetanus vaccine suffices to confer long-term protection. In recent years, there has been evidence of a decrease in vaccination coverage, which entails that immunization in the population is insufficient. The aim of this study was to analyse the vaccination coverage rate for the booster dose of tetanus vaccine in adolescents residing in the town of Santa Amalia in the province of Badajoz (Spain) in the past 20 years (1996-2016). MATERIALS AND METHODS: the study had a cross-sectional and observational design and involved the review of vaccination cards and records of the administered doses of vaccine, both manual and electronic (JARA Primary Care system). Between 1996 and 2001, vaccination was performed in the school setting and documented manually. Since 2002, vaccination was performed in the primary care centre, and documented manually between 2002 and 2007 and in the electronic health records system between 2008 and 2016. RESULTS: the analysis of vaccination coverage by groups found the poorest results in the period that vaccination was performed in the primary care centre and documented manually (35.6%), while the best results corresponded to the period when vaccination was made in the primary care centre and documented in the electronic health records (100%), followed by the period of vaccination in the school with manual documentation (83.0%). CONCLUSIONS: the study found a high vaccination coverage for the booster dose of tetanus vaccine in adolescents aged 14 years residing in Santa Amalia, similar to the national average coverage, despite the low coverage rates documented in the rest of Extremadura


Assuntos
Humanos , Masculino , Feminino , Adolescente , Cobertura Vacinal/tendências , Tétano/prevenção & controle , Toxoide Tetânico/administração & dosagem , Imunização Secundária/estatística & dados numéricos , Espanha/epidemiologia , Tétano/epidemiologia , Estudos Transversais
11.
Cien Saude Colet ; 24(12): 4655-4664, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31778515

RESUMO

This article aims to identify the prevalence and factors associated with influenza vaccination in pregnant women. This is a cross-sectional study conducted in a municipality in the southernmost region of Brazil, which included all women giving birth in 2016. The outcome was having received the vaccine against influenza during pregnancy. Sociodemographic, behavioral and prenatal care characteristics and morbidities were analyzed. The analysis included sample description, the prevalence of vaccination for each independent variable and a multivariate analysis. Two thousand six hundred ninety-four pregnant women were interviewed, of which 53.9% reported having been vaccinated. Factors associated with increased prevalence of vaccination were mother's higher schooling, prenatal care, tetanus vaccination and prenatal care performed in a public service. On the other hand, prenatal care onset after the first quarter reduced the prevalence of vaccination. The results point to the need to reinforce the importance of vaccination against influenza among pregnant women and among health professionals, regardless of the severity of the current epidemiological setting.


Assuntos
Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Gestantes , Vacinação/estatística & dados numéricos , Adulto , Brasil , Estudos Transversais , Escolaridade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Análise Multivariada , Gravidez , Cuidado Pré-Natal , Toxoide Tetânico/administração & dosagem , Adulto Jovem
12.
Vaccine ; 37(43): 6441-6446, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31522805

RESUMO

BACKGROUND: Immunization coverage for three doses of the diphtheria-tetanus-pertussis and poliomyelitis vaccines in infants is high worldwide, therefore despite the lack of documentation of past vaccinations, most migrant children do not require complete revaccination. Our strategy was to administer a single dose of a tetanus toxoid containing vaccine (TTCV) to migrant children followed by anti-tetanus toxoid (TT) serology to determine whether additional vaccine doses were required. Our goal was to estimate the basic TTCV coverage and to identify potential determinants of the vaccination response. METHODS: Newly arrived migrant children were prospectively enrolled between October 2014 and August 2017. We included patients aged 1-18 years with no proof of past vaccinations who accepted a single dose of TTCV. Anti-TT serology was performed after 4-6 weeks, and an anti-TT level ≥ 1 IU/mL was considered a booster-type antibody response with no need for additional doses of TTCV. Potential determinants of the vaccination response were identified using univariate and multivariate linear regression analyses. RESULTS: Two hundred and eight children were eligible for analysis. The mean age of the children was 9 (±4.5) years and 100 (48%) were female. The majority (n = 129, 62%) of the children came from the WHO Eastern Mediterranean region. Only three patients (1.4%) required additional vaccine doses. A Syrian origin (p < 0.001) and direct arrival primarily by airplane into Switzerland without transiting through other European countries (p = 0.029) associated with higher anti-TT levels in a multivariate regression model (multiple r2 = 0.210, p < 0.001). CONCLUSION: A single dose of TTCV is enough to generate long-term protection in most migrant children. In the context of high basic vaccination coverage, the strategy, which consists of administration of a single dose of TTCV followed by anti-TT serology, can be considered where serotesting is available and economical.


Assuntos
Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Vacina Antipólio Oral/administração & dosagem , Vacina Antipólio Oral/imunologia , Toxoide Tetânico/imunologia , Tétano/prevenção & controle , Adolescente , Anticorpos Antibacterianos/sangue , Formação de Anticorpos , Criança , Pré-Escolar , Difteria/prevenção & controle , Esquema de Medicação , Europa (Continente) , Feminino , Humanos , Lactente , Masculino , Poliomielite/prevenção & controle , Estudos Prospectivos , Testes Sorológicos , Suíça , Centros de Atenção Terciária , Toxoide Tetânico/administração & dosagem , Migrantes/estatística & dados numéricos , Cobertura Vacinal , Coqueluche/prevenção & controle
13.
Life Sci Space Res (Amst) ; 22: 16-28, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31421845

RESUMO

Spaceflight is known to impact the immune system in multiple ways. However, its effect on the antibody repertoire, especially in response to challenge, has not been well characterized. The development of the repertoire has multiple steps that could be affected by spaceflight, including V-(D-)J-gene segment rearrangement and the selection of complementarity determining regions (CDRs); specifically, CDR3, responsible for much of the diversity in the repertoire. We used skeletal unloading with the antiorthostatic suspension (AOS) model to simulate some of the physiological effects associated with spaceflight. Animals ± AOS were challenged with tetanus toxoid (TT) and/or CpG, an adjuvant. Two weeks after challenge, bone marrow was collected and sequenced using the Illumina MiSeq 2 × 300 platform. The resulting antibody repertoire was characterized, including V-, D- (heavy only), and J-gene segment usage, constant region usage, CDR3 length, and V(D)J combinations. We detected changes in gene-segment usage in response to AOS, TT, and CpG treatment in both the heavy and light chains. Additionally, changes were seen in the class-switched VH-gene repertoire. Alterations were also detected in V/J pairing for both the heavy and light chains, and changes in CDR3 length. We also detected lower levels of CDR3 AA overlap than detected in the splenic repertoire. These results demonstrate that AOS, TT, and CpG alter the bone marrow antibody repertoire however, it is still unclear from the data whether there is a loss of host antigen-specific responsiveness because of the change in gene use.


Assuntos
Anticorpos/imunologia , Medula Óssea/imunologia , Oligodesoxirribonucleotídeos/administração & dosagem , Voo Espacial , Toxoide Tetânico/administração & dosagem , Animais , Anticorpos/genética , Linfócitos B/imunologia , Células da Medula Óssea , Feminino , Switching de Imunoglobulina , Cadeias Pesadas de Imunoglobulinas , Memória Imunológica , Camundongos Endogâmicos C57BL , Plasmócitos/imunologia
14.
Int Immunopharmacol ; 75: 105756, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31344556

RESUMO

Long-term graft survival after organ transplantation is difficult to achieve because of the development of chronic rejection. One cause of chronic rejection arises from antibody-mediated rejection (AMR), which is dependent on the production of donor-specific antibodies (DSA). Current immunosuppression in organ transplantation is effective in preventing acute T cell-mediated rejection, but the risk of DSA production and graft loss due to AMR remains unchanged. Phosphatidylinositol-3-kinase p110δ (PI3Kδ), a member of the family of PI3K lipid kinases, is a key mediator of B cell activation, proliferation and antibody production. AS2541019 is a novel PI3Kδ selective inhibitor that prevents antibody production by inhibiting B cell immunity. The purpose of this study was to evaluate the inhibitory effect of AS2541019 on DSA production in preclinical rodent and non-human primate allotransplant models. Concomitant administration of AS2541019 with tacrolimus and mycophenolate mofetil (MMF) inhibited de novo DSA production in an ACI-to-Lewis rat cardiac allotransplant model. To predict the efficacy of AS2541019 in clinical practice, we evaluated its effects in cynomolgus monkeys. AS2541019 inhibited B cell proliferation and major histocompatibility complex (MHC) class II expression on B cells in cynomolgus monkeys. Oral administration of AS2541019 inhibited MHC class II expression on peripheral B cells and anti-tetanus toxoid antibody production. In cynomolgus monkey renal allotransplant model, concomitant administration of AS2541019 with tacrolimus and MMF significantly inhibited de novo DSA production. Together, our findings indicate that the PI3Kδ selective inhibitor AS2541019 is a potential candidate for preventing AMR development by inhibiting DSA production.


Assuntos
Formação de Anticorpos/efeitos dos fármacos , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Transplante de Coração , Transplante de Rim , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Memória Imunológica , Imunossupressores/farmacologia , Macaca fascicularis , Masculino , Ácido Micofenólico/farmacologia , Ratos , Ratos Endogâmicos ACI , Ratos Endogâmicos Lew , Tacrolimo/farmacologia , Toxoide Tetânico/administração & dosagem
16.
AAPS PharmSciTech ; 20(7): 257, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31332640

RESUMO

Transcutaneous immunization using a microneedle device presents a promising alternative to syringe-based injection of vaccines. The aim of this study was to investigate the effective immune response elicited after application of tetanus toxoid antigen-loaded dissolvable microneedles (TT-MN) in mice model. Dissolvable microneedles were prepared using 20% w/v of polyvinyl alcohol and polyvinyl pyrrolidone polymer mixture by micromolding technique. TT-MN were prepared by addition of tetanus toxoid to polymer mixture before casting microneedles. TT-MN were characterized using texture analyzer, stereomicroscope, and scanning electron microscope. Tetanus toxoid loading was found to be 77 ± 2 µg per microneedle array. Confocal microscopic analysis showed that the microneedles penetrated to a depth of 130 µm inside mouse skin. Complete dissolution of microneedles was achieved within 1 h after insertion in skin. Immunization studies in Swiss albino mice demonstrated significantly (p < 0.001) greater IgG, IgG1, and IgG2a antibody titers for TT-MN and intramuscular injection groups compared with naïve control. Splenocyte proliferation assay confirmed effective re-stimulation on exposure to tetanus toxoid in microneedle treatment groups. Taken together, TT-MN can be developed as minimally invasive system for transcutaneous delivery of tetanus toxoid antigen.


Assuntos
Antígenos/administração & dosagem , Imunização/métodos , Agulhas , Toxoide Tetânico/administração & dosagem , Animais , Fosfatos de Cálcio/química , Feminino , Injeções Subcutâneas , Camundongos , Polímeros/química , Álcool de Polivinil/química , Solubilidade , Toxoide Tetânico/imunologia
17.
Pediatr Infect Dis J ; 38(6S Suppl 1): S28-S32, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31205241

RESUMO

Maternal vaccination provides a method for protecting the pregnant woman, fetus and neonate during a period when there is increased susceptibility to infectious diseases. A dynamic state of immune tolerance during pregnancy and the need to develop adaptive memory to a new foreign antigen-rich environment lead to windows of vulnerability to infection for the mother and neonate, respectively. Passive transfer of humoral immunity through the placenta and breast milk from the mother can bridge the gap in immunity for the neonate. Studies on boosting this natural process of antibody transfer have led to the recommendation for administering inactivated influenza, diphtheria, tetanus toxoid and acellular pertussis vaccines during pregnancy. Several new maternal vaccine candidates are on the horizon.


Assuntos
Imunidade Materno-Adquirida , Imunização/normas , Mães , Complicações Infecciosas na Gravidez/prevenção & controle , Gestantes , Difteria/prevenção & controle , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Vacinas contra Difteria, Tétano e Coqueluche Acelular/imunologia , Feminino , Humanos , Imunização/métodos , Recém-Nascido , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Leite Humano/imunologia , Gravidez , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/imunologia , Coqueluche/prevenção & controle
18.
Pediatr Infect Dis J ; 38(6): 643-650, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31116180

RESUMO

BACKGROUND: We assessed immunogenicity, antibody persistence and safety of the meningococcal serogroups A, C, W and Y-tetanus toxoid (TT) conjugate vaccine (MenACWY-TT) in children primed as toddlers with MenC vaccine. METHODS: This open, multicenter extension study enrolled children 84-95 months of age who had received one dose of the combined Haemophilus influenzae type b (Hib)-MenC-TT conjugate vaccine (HibMenC group) or Hib-TT and monovalent MenC (MCC)-CRM197 vaccines (Hib+MCC group) at 12-18 months of age, in the primary study. All participants received one dose of MenACWY-TT. We assessed immunogenicity against MenA, MenC, MenW and MenY at 1 month and 2 years postvaccination by serum bactericidal assay using baby rabbit complement (rSBA). Safety and reactogenicity were evaluated. RESULTS: Six years post-MenC vaccination, <20% of children retained rSBA-MenC titers ≥1:8. At 1 month post-MenACWY-TT vaccination, vaccine response rates against all serogroups were high for both groups with ≥97.1% of children having rSBA ≥1:8. Two years postvaccination, ≥63.6% of children retained rSBA-MenA ≥1:8, and ≥87.9% for other serogroups. Geometric mean titers for all serogroups declined at 2 years post-MenACWY-TT vaccination, but remained ≥13 times higher than prevaccination levels. For both groups, pain (≤58.5%), redness (≤51.4%) and fatigue (≤27.0%) were the most frequently reported adverse events. No serious adverse events were reported. CONCLUSIONS: One dose of MenACWY-TT boosts protection against MenC in primed children, is safe and extends protection against MenA, MenW and MenY. Immunogenicity and safety were comparable in infants vaccinated with conjugated vaccine (HibMenC-TT) or the separate vaccines (Hib-TT and MCC-CRM197).


Assuntos
Anticorpos Antibacterianos/sangue , Imunização Secundária , Imunogenicidade da Vacina , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Toxoide Tetânico/imunologia , Criança , Feminino , Humanos , Lactente , Masculino , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/administração & dosagem , Neisseria meningitidis Sorogrupo C/imunologia , Toxoide Tetânico/administração & dosagem , Vacinação , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia
19.
Acta Biomed ; 90(2): 269-278, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31125007

RESUMO

BACKGROUND: Since 1963 Italian law (Law 292/1963, Legislative Decree n.81/2008), defines Tetanus Vaccination (TeV) as mandatory for defined occupational categories, including Construction Workers (CWs). MATERIALS AND METHODS: An institutional survey on of CWs was performed in the Autonomous Province of Trento (Oct. 2016 - Apr. 2017). Vaccination booklets/certificate were retrieved recalling: TeV status (1), and TeV settings (2), i.e. basal schedule; year of last shot, healthcare providers who performed TeV, and TeV formulate(s). RESULTS: Data about 205 CWs were collected (mean age 40.6±10.3 years; 78.0% <50 year-old, 71.7% born in Italy). Overall, 38.5% of CW had received last vaccination shot >10 years before the survey (mean: 8.8 ± 8.2 years). The majority of boosters had been administered by Vaccination Services of the Local Health Unit (47.3%), followed by Occupational Physicians (20.0%) and General Practitioners (11.2%). In 85.9% of CWs, a monovalent formulation was used. Combined TeV were mainly reported in CW who had received last vaccination shot in Vaccination Services (96.2%; p<0.001). CONCLUSIONS: TeV coverage rates in CWs are insufficient, and vaccination shots are frequently performed with inappropriate, monovalent formulates. As only professionals from Vaccination Services systematically employ combined vaccines and particularly Tdap, our results not only stress the opportunity for promoting TeV among CWs, but also the importance of improving reception of up to date official recommendations in Occupational Physicians, General Practitioner and professionals of Emergency Departments.


Assuntos
Indústria da Construção , Programas de Imunização/legislação & jurisprudência , Toxoide Tetânico/administração & dosagem , Tétano/prevenção & controle , Vacinação/legislação & jurisprudência , Adulto , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Saúde do Trabalhador , Inquéritos e Questionários
20.
Arthritis Res Ther ; 21(1): 102, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30999933

RESUMO

BACKGROUND: Clinical guidelines recommend pneumococcal and tetanus vaccinations in patients with rheumatoid arthritis (RA). Baricitinib is an oral, selective Janus kinase (JAK) 1/JAK 2 inhibitor and is approved for the treatment of moderately to severely active RA in adults in over 50 countries including European countries, the USA, and Japan. This substudy evaluated pneumococcal conjugate and tetanus toxoid vaccine (TTV) responses in patients with RA receiving baricitinib. These vaccines elucidate predominantly T cell-dependent humoral antibody response. METHODS: Eligible RA patients receiving baricitinib 2 mg or 4 mg with or without concomitant methotrexate (MTX) were enrolled in a phase 3 long-term extension trial (RA-BEYOND; ClinicalTrials.gov, NCT01885078) in USA/Puerto Rico. Patients were vaccinated with 13-serotype pneumococcal conjugate vaccine (PCV-13) and TTV. Primary endpoints were the proportion of patients achieving a satisfactory humoral response for PCV-13 (≥ 2-fold increase in anti-pneumococcal antibody concentrations in ≥ 6 serotypes) and TTV (≥ 4-fold increase in anti-tetanus concentrations) at 5 weeks post-vaccination. Secondary endpoints included humoral responses at 12 weeks and functional responses of serotypes 4, 6B, 14, and 23F (twofold and fourfold increases in opsonic indexes at 5 and 12 weeks). RESULTS: Of 106 patients with a mean duration of RA of approximately 12 years, 80% were female, 30% were taking corticosteroids, and 89% (N = 94) were taking baricitinib plus MTX; most patients (97% PCV-13/96% TTV) completed the evaluations. Overall, 68% (95% CI 58.4, 76.2) of patients achieved a satisfactory response to PCV-13, 43% (34.0, 52.8) achieved a ≥ 4-fold increase in anti-tetanus concentrations, and 74% (64.2, 81.1) achieved a ≥ 2-fold increase. PCV-13 response was similar for patients taking corticosteroids (71%; 53.4, 83.9) vs those not (67%; 55.2, 76.5). The percentage of sera with a ≥ 2-fold increase in post-vaccination opsonic indexes at week 5 ranged from 47% (serotype 14) to 76% (serotype 6B). Through 12 weeks post-vaccination, seven patients (6.6%) reported injection-site events. There were no deaths during the substudy, and three patients experienced a serious adverse event. CONCLUSIONS: Approximately two thirds of patients on long-term baricitinib achieved satisfactory humoral and functional responses to PCV-13 vaccination, while TTV responses were less robust. PCV-13 response was not diminished in those taking concomitant corticosteroids. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01885078 . Registered on 24 June 2013.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Azetidinas/administração & dosagem , Imunidade Celular/efeitos dos fármacos , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/efeitos dos fármacos , Sulfonamidas/administração & dosagem , Toxoide Tetânico/administração & dosagem , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Feminino , Humanos , Imunidade Celular/imunologia , Masculino , Pessoa de Meia-Idade , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/isolamento & purificação , Resultado do Tratamento
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