Tuberculin reactivity in a population of schoolchildren with high BCG vaccination coverage

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Bierrenbach Ana L.

2003-01-01

Full Text Available OBJECTIVE: To investigate the influence of BCG vaccination or revaccination on tuberculin skin test reactivity, in order to guide the correct interpretation of this test in a setting of high neonatal BCG vaccination coverage and an increasing BCG revaccination coverage at school age. METHODS: We conducted tuberculin skin testing and BCG scar reading in 1148 children aged 7-14 years old in the city of Salvador, Bahia, Brazil. We measured the positive effect of the presence of one or two BCG scars on the proportion of tuberculin skin test results above different cut-off levels (induration sizes of > 5 mm, > 10 mm, and > 15 mm and also using several ranges of induration size (0, 1-4, 5-9, 10-14, and > 15 mm. We also measured the effects that age, gender, and the school where the child was enrolled had on these proportions. RESULTS: The proportion of tuberculin results > 10 mm was 14.2% (95% confidence interval (CI = 8.0%-20.3% for children with no BCG scar, 21.3% (95% CI = 18.5%-24.1% for children with one BCG scar, and 45.0% (95% CI = 32.0%-58.0% for children with two BCG scars. There was evidence for an increasing positive effect of the presence of one and two BCG scars on the proportion of results > 5 mm and > 10 mm. Similarly, there was evidence for an increasing positive effect of the presence of one and two scars on the proportion of tuberculin skin test results in the ranges of 5-9 mm and of 10-14 mm. The BCG scar effect on the proportion of results > 5 mm and > 10 mm did not vary with age. There was no evidence for BCG effect on the results > 15 mm. CONCLUSIONS: In Brazilian schoolchildren, BCG-induced tuberculin reactivity is indistinguishable, for results under 15 mm, from reactivity induced by Mycobacterium tuberculosis infection. BCG revaccination at school age increases the degree of BCG-induced tuberculin reactivity found among schoolchildren. This information should be taken into account in tuberculin skin test surveys intended to

BCG and BCG/DNAhsp65 Vaccinations Promote Protective Effects without Deleterious Consequences for Experimental Autoimmune Encephalomyelitis

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Sofia Fernanda Gonçalves Zorzella-Pezavento

2013-01-01

Full Text Available A prime-boost strategy conserving BCG is considered the most promising vaccine to control tuberculosis. A boost with a DNA vaccine containing the mycobacterial gene of a heat shock protein (pVAXhsp65 after BCG priming protected mice against experimental tuberculosis. However, anti-hsp65 immunity could worsen an autoimmune disease due to molecular mimicry. In this investigation, we evaluated the effect of a previous BCG or BCG/pVAXhsp65 immunization on experimental autoimmune encephalomyelitis (EAE development. Female Lewis rats were immunized with BCG or BCG followed by pVAXhsp65 boosters. The animals underwent EAE induction and were daily evaluated for weight loss and clinical score. They were euthanized during recovery phase to assess immune response and inflammatory infiltration at the central nervous system. Previous immunization did not aggravate or accelerate clinical score or weight loss. In addition, this procedure clearly decreased inflammation in the brain. BCG immunization modulated the host immune response by triggering a significant reduction in IL-10 and IFN-γ levels induced by myelin basic protein. These data indicated that vaccination protocols with BCG or BCG followed by boosters with pVAXhsp65 did not trigger a deleterious effect on EAE evolution.

Comparative Proteomic Profiling of Mycobacterium bovis and BCG Vaccine Strains

KAUST Repository

Gao, Ge

2013-09-01

BCG is the only licensed human vaccine currently available against TB. Derived from a virulent strain of M. bovis, the vaccine was thought to have struck a balance between reduced virulence and preserved immunogenicity. Nowadays, BCG vaccine strains used in different countries and vaccination programs show clear variations in their genomes and immune protective properties. The aim of this study was to characterize the proteomic profile on Mycobacterium bovis and five BCG strains Pasteur, Tokyo, Danish, Phipps and Birkhaug by Tandem Mass Tag® (TMT®)-labeling quantitative proteomic approach. In total, 420 proteins were identified and 377 of them were quantitated for their relative abundance. We reported the number and relationship of differential expressed proteins in BCG strains compared to M. bovis and investigated their functions by bioinformatics analysis. Several interesting up-regulated and down-regulated protein targets were found. The identified proteins and their quantitative expression profiles provide a basis for further understanding of the cellular biology of M. bovis and BCG vaccine strains, and hopefully would assist in the design of better anti-TB vaccine and drugs.

Comparative performance of public and private sector delivery of BCG vaccination: evidence from Sub-Saharan Africa.

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Wagner, Zachary; Szilagyi, Peter G; Sood, Neeraj

2014-07-31

The private sector is an important source of health care in the developing world. However, there is limited evidence on how private providers compare to public providers, particularly for preventive services such as immunizations. We used data from Sub-Saharan Africa (SSA) to assess public-private differences in Bacillus Calmette-Guérin (BCG) vaccine delivery. We used demographic and health surveys from 102,629 children aged 0-59 months from 29 countries across SSA to measure differences in BCG status for children born at private versus public health facilities (BCG is recommended at birth). We used a probit model to estimate public-private differences in BCG delivery, while controlling for key confounders. Next, we estimated how differences in BCG status evolved over time for children born at private versus public facilities. Finally, we estimated heterogeneity in public-private differences based on wealth and rural-urban residency. We found that children born at a private facility were 7.1 percentage points less likely to receive BCG vaccine in the same month as birth than children born at a public facility (95% CI 6.3-8.0; pprivate providers (as opposed to NGOs) where the BCG provision rate was 10.0 percentage points less than public providers (95% CI 9.0-11.2; pprivate for-profit facilities remained less likely to be vaccinated up to 59 months after birth. Finally, public-private differences were more pronounced for poorer children and children in rural areas. The for-profit private sector performed substantially worse than the public sector in providing BCG vaccine to newborns, resulting in a longer duration of vulnerability to tuberculosis. This disparity was greater for poorer children and children in rural areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

BCG vaccination in patients with severe combined immunodeficiency: complications, risks, and vaccination policies.

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Marciano, Beatriz E; Huang, Chiung-Yu; Joshi, Gyan; Rezaei, Nima; Carvalho, Beatriz Costa; Allwood, Zoe; Ikinciogullari, Aydan; Reda, Shereen M; Gennery, Andrew; Thon, Vojtech; Espinosa-Rosales, Francisco; Al-Herz, Waleed; Porras, Oscar; Shcherbina, Anna; Szaflarska, Anna; Kiliç, Şebnem; Franco, Jose L; Gómez Raccio, Andrea C; Roxo, Persio; Esteves, Isabel; Galal, Nermeen; Grumach, Anete Sevciovic; Al-Tamemi, Salem; Yildiran, Alisan; Orellana, Julio C; Yamada, Masafumi; Morio, Tomohiro; Liberatore, Diana; Ohtsuka, Yoshitoshi; Lau, Yu-Lung; Nishikomori, Ryuta; Torres-Lozano, Carlos; Mazzucchelli, Juliana T L; Vilela, Maria M S; Tavares, Fabiola S; Cunha, Luciana; Pinto, Jorge A; Espinosa-Padilla, Sara E; Hernandez-Nieto, Leticia; Elfeky, Reem A; Ariga, Tadashi; Toshio, Heike; Dogu, Figen; Cipe, Funda; Formankova, Renata; Nuñez-Nuñez, M Enriqueta; Bezrodnik, Liliana; Marques, Jose Gonçalo; Pereira, María I; Listello, Viviana; Slatter, Mary A; Nademi, Zohreh; Kowalczyk, Danuta; Fleisher, Thomas A; Davies, Graham; Neven, Bénédicte; Rosenzweig, Sergio D

2014-04-01

Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications. Published by Mosby, Inc.

[BCG vaccination in low risk tuberculosis; first experiences after the suspension of BCG vaccination of newborns in Czechoslovakia].

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Trnka, L; Danková, D

1989-01-01

With the steadily declining risk of tuberculosis infection in CSR the question arose whether vaccination of infants remains worthwhile considering not only resources spent but also complications to vaccination vis-a-vis benefits derived. A prospective study has been designed in which BCG vaccination of newborns is discontinued in an area with 30,000 newborns yearly. In the period from April 1, 1986 to January 31, 1988 there were not vaccinated 43,428 children (84.8% of the newborns). The collaboration of mothers was good. The one year old non-vaccinated children were tested with 2 TU PPD RT 23 with Tween 80. The distribution of positive tuberculin reactions appears unimodal, relatively large reactions being absent. 8 children had reactions with 6 or more mm induration. That corresponds to a risk of infection of 0.04%. The project continues in the research area and might be extended to another area.

Randomized trial of BCG vaccination at birth to low-birth-weight children

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Aaby, Peter; Roth, Adam Anders Edvin; Ravn, Henrik

2011-01-01

Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG.......Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG....

Neonatal BCG-vaccination and atopic dermatitis before 13 months of age. A randomised clinical trial

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Thøstesen, Lisbeth Marianne; Kjaergaard, Jesper; Pihl, Gitte Thybo

2017-01-01

Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational...... in the control group (RR=0.90 (95% confidence intervals 0.80 to 1.00)). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition (RR 0.84 (0.74 to 0.95)) and children without atopic predisposition (RR 1.09 (0.88 to 1.37)) (test of no interaction, p=0.04). Among...... children with atopic predisposition, the number-needed-to-treat with BCG to prevent one case of atopic dermatitis was 21 (12 to 76). This article is protected by copyright. All rights reserved....

Socio-demographic determinants of timely adherence to BCG, Penta3, measles, and complete vaccination schedule in Burkina Faso.

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Schoeps, A; Ouédraogo, N; Kagoné, M; Sié, A; Müller, O; Becher, H

2013-12-17

To identify the determinants of timely vaccination among young children in the North-West of Burkina Faso. This study included 1665 children between 12 and 23 months of age from the Nouna Health and Demographic Surveillance System, born between September 2006 and December 2008. The effect of socio-demographic variables on timely adherence to the complete vaccination schedule was studied in multivariable ordinal logistic regression with 3 distinct endpoints: (i) complete timely adherence, (ii) failure, and (iii) missing vaccination. Three secondary endpoints were timely vaccination with BCG, Penta3, and measles, which were studied with standard multivariable logistic regression. Mothers' education, socio-economic status, season of birth, and area of residence were significantly associated with failure of timely adherence to the complete vaccination schedule. Year of birth, ethnicity, and the number of siblings was significantly related to timely vaccination with Penta3 but not with BCG or measles vaccination. Children living in rural areas were more likely to fail timely vaccination with BCG than urban children (OR=1.79, 95%CI=1.24-2.58 (proximity to health facility), OR=3.02, 95%CI=2.18-4.19 (long distance to health facility)). In contrast, when looking at Penta3 and measles vaccination, children living in rural areas were far less likely to have failed timely vaccinations than urban children. Mother's education positively influenced timely adherence to the vaccination schedule (OR=1.42, 95%CI 1.06-1.89). There was no effect of household size or the age of the mother. Additional health facilities and encouragement of women to give birth in these facilities could improve timely vaccination with BCG. Rural children had an advantage over the urban children in timely vaccination, which is probably attributable to outreach vaccination teams amongst other factors. As urban children rely on their mothers' own initiative to get vaccinated, urban mothers should be

Effectiveness of BCG vaccination to aged mice

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Ito Tsukasa

2010-09-01

Full Text Available Abstract Background The tuberculosis (TB still increases in the number of new cases, which is estimated to approach 10 million in 2010. The number of aged people has been growing all over the world. Ageing is one of risk factors in tuberculosis because of decreased immune responses in aged people. Mycobacterium bovis Bacillus Calmette Guérin (BCG is a sole vaccine currently used for TB, however, the efficacy of BCG in adults is still a matter of debate. Emerging the multidrug resistant Mycobacterium tuberculosis (MDR-TB make us to see the importance of vaccination against TB in new light. In this study, we evaluated the efficacy of BCG vaccination in aged mice. Results The Th1 responses, interferon-γ production and interleukin 2, in BCG inoculated aged mice (24-month-old were comparable to those of young mice (4- to 6-week-old. The protection activity of BCG in aged mice against Mycobacterium tuberculosis H37Rv was also the same as young mice. Conclusion These findings suggest that vaccination in aged generation is still effective for protection against tuberculosis.

Tuberculosis: looking beyond BCG vaccines.

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Mustafa Abu S

2003-01-01

Full Text Available Tuberculosis (TB is an infectious disease of international importance and ranks among the top 10 causes of death in the World. About one-third of the world′s population is infected with Mycobacterium tuberculosis. Every year, approximately eight million people develop active disease and two million die of TB. The currently used BCG vaccines have shown variable protective efficacies against TB in different parts of the world. Moreover, being a live vaccine, BCG can be pathogenic in immunocompromised recipients. Therefore, there is an urgent need to develop new vaccines against TB. The comparative genome analysis has revealed the existence of several M. tuberculosis-specific regions that are deleted in BCG. The work carried out to determine the immunological reactivity of proteins encoded by genes located in these regions revealed several major antigens of M. tuberculosis, including the 6 kDa early secreted antigen target (ESAT6. Immunization with ESAT6 and its peptide (aa51-70 protects mice challenged with M. tuberculosis. The protective efficacy of immunization further improves when ESAT6 is recombinantly fused with M. tuberculosis antigen 85B. In addition, ESAT6 delivered as a DNA vaccine is also protective in mice. Whether these vaccines would be safe or not cannot be speculated. The answer regarding the safety and efficacy of these vaccines has to await human trials in different parts of the world.

Targeted BCG Vaccination Against Severe Tuberculosis in Low-prevalence Settings Epidemiologic and Economic Assessment

NARCIS (Netherlands)

Altes, Hester Korthals; Dijkstra, Frederika; Lugnèr, Anna; Cobelens, Frank; Wallinga, Jacco

2009-01-01

Background: BCG vaccine protects against the severe forms of tuberculosis (TB) in children. Several low-prevalence countries are reviewing their policy, usually shifting from universal vaccination to vaccination of infants in high-risk groups only. We combined an epidemiologic analysis with a

BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination.

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Chen, Fan; Yan, Qinying; Yu, Yang; Wu, Mei X

2017-06-10

Live attenuated Bacille Calmette-Guerin (BCG) bacillus is the only licensed vaccine for tuberculosis prevention worldwide to date. It must be delivered intradermally to be effective, which causes severe skin inflammation and sometimes, permanent scars. To minimize the side effects, we developed a novel microneedle array (MNA) that could deliver live attenuated freeze-dried BCG powder into the epidermis in a painless, lesion-free, and self-applicable fashion. The MNA was fabricated with biocompatible and dissolvable hyaluronic acid with a deep cave formed in the basal portion of each microneedle, into which BCG powder could be packaged directly. Viability of BCG vaccine packaged in the caves and the mechanical strength of the powder-laden MNA did not alter significantly before and after more than two months of storage at room temperature. Following insertion of the MNA into the skin, individual microneedle shafts melted away by interstitial fluid from the epidermis and upper dermis, exposing the powder to epidermal tissues. The powder sucked interstitial fluid, dissolved slowly, and diffused into the epidermis in a day against the interstitial fluid influx. Vaccination with BCG-MNA caused no overt skin irritation, in marked contrast to intradermal vaccination that provoked severe inflammation and bruise. While causing little skin irritation, vaccination efficacy of BCG-MNAs was comparable to that of intradermal immunization whether it was evaluated by humoral or cellular immunity. This powder-laden and dissolvable MNA represents a novel technology to sufficiently deliver live attenuated vaccine powders into the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development

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Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie

2016-01-01

MEASURES: Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age Developmental assessment was available for 3453/4262 (81%). RESULTS......OBJECTIVES: To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development. DESIGN: This is a pre-specified secondary outcome from a randomised, clinical trial. SETTING: Maternity units and paediatric wards at three university hospitals...... was -7.8 points (-20.6 to 5.0, p = 0.23), d = -0.23 (-0.62 to 0.15). CONCLUSIONS: A negative non-specific effect of BCG vaccination at birth on psychomotor development was excluded in term children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01694108....

Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines.

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Libraty, Daniel H; Zhang, Lei; Woda, Marcia; Acosta, Luz P; Obcena, Anamae; Brion, Job D; Capeding, Rosario Z

2014-01-01

Neonatal Bacille Calmette Guérin (BCG) vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1) immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2-3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ) producing spot-forming cells (SFC) to tetanus toxoid 2-3 months later. The frequency of IFN-γ producing SFC to polioviruses 1-3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α)+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA)/Ionomycin was higher in 2-3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3)+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2-3 months later.

Viral booster vaccines improve Mycobacterium bovis BCG-induced protection against bovine tuberculosis.

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Vordermeier, H Martin; Villarreal-Ramos, Bernardo; Cockle, Paul J; McAulay, Martin; Rhodes, Shelley G; Thacker, Tyler; Gilbert, Sarah C; McShane, Helen; Hill, Adrian V S; Xing, Zhou; Hewinson, R Glyn

2009-08-01

Previous work with small-animal laboratory models of tuberculosis has shown that vaccination strategies based on heterologous prime-boost protocols using Mycobacterium bovis bacillus Calmette-Guérin (BCG) to prime and modified vaccinia virus Ankara strain (MVA85A) or recombinant attenuated adenoviruses (Ad85A) expressing the mycobacterial antigen Ag85A to boost may increase the protective efficacy of BCG. Here we report the first efficacy data on using these vaccines in cattle, a natural target species of tuberculous infection. Protection was determined by measuring development of disease as an end point after M. bovis challenge. Either Ad85A or MVA85A boosting resulted in protection superior to that given by BCG alone: boosting BCG with MVA85A or Ad85A induced significant reduction in pathology in four/eight parameters assessed, while BCG vaccination alone did so in only one parameter studied. Protection was particularly evident in the lungs of vaccinated animals (median lung scores for naïve and BCG-, BCG/MVA85A-, and BCG/Ad85A-vaccinated animals were 10.5, 5, 2.5, and 0, respectively). The bacterial loads in lymph node tissues were also reduced after viral boosting of BCG-vaccinated calves compared to those in BCG-only-vaccinated animals. Analysis of vaccine-induced immunity identified memory responses measured by cultured enzyme-linked immunospot assay as well as in vitro interleukin-17 production as predictors of vaccination success, as both responses, measured before challenge, correlated positively with the degree of protection. Therefore, this study provides evidence of improved protection against tuberculosis by viral booster vaccination in a natural target species and has prioritized potential correlates of vaccine efficacy for further evaluation. These findings also have implications for human tuberculosis vaccine development.

Proteomic profile of culture filtrate from the Brazilian vaccine strain Mycobacterium bovis BCG Moreau compared to M. bovis BCG Pasteur

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Degrave Wim M

2011-04-01

Full Text Available Abstract Background Bacille Calmette-Guerin (BCG is currently the only available vaccine against tuberculosis (TB and comprises a heterogeneous family of sub-strains with genotypic and phenotypic differences. The World Health Organization (WHO affirms that the characterization of BCG sub-strains, both on genomic and proteomic levels, is crucial for a better comprehension of the vaccine. In addition, these studies can contribute in the development of a more efficient vaccine against TB. Here, we combine two-dimensional electrophoresis (2DE and mass spectrometry to analyse the proteomic profile of culture filtrate proteins (CFPs from M. bovis BCG Moreau, the Brazilian vaccine strain, comparing it to that of BCG Pasteur. CFPs are considered of great importance given their dominant immunogenicity and role in pathogenesis, being available for interaction with host cells since early infection. Results The 2DE proteomic map of M. bovis BCG Moreau CFPs in the pH range 3 - 8 allowed the identification of 158 spots corresponding to 101 different proteins, identified by MS/MS. Comparison to BCG Pasteur highlights the great similarity between these BCG strains. However, quantitative analysis shows a higher expression of immunogenic proteins such as Rv1860 (BCG1896, Apa, Rv1926c (BCG1965c, Mpb63 and Rv1886c (BCG1923c, Ag85B in BCG Moreau when compared to BCG Pasteur, while some heat shock proteins, such as Rv0440 (BCG0479, GroEL2 and Rv0350 (BCG0389, DnaK, show the opposite pattern. Conclusions Here we report the detailed 2DE profile of CFPs from M. bovis BCG Moreau and its comparison to BCG Pasteur, identifying differences that may provide relevant information on vaccine efficacy. These findings contribute to the detailed characterization of the Brazilian vaccine strain against TB, revealing aspects that may lead to a better understanding of the factors leading to BCG's variable protective efficacy against TB.

Comparative Tuberculosis (TB) Prevention Effectiveness in Children of Bacillus Calmette-Guérin (BCG) Vaccines from Different Sources, Kazakhstan

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Favorov, Michael; Ali, Mohammad; Tursunbayeva, Aigul; Aitmagambetova, Indira; Kilgore, Paul; Ismailov, Shakhimurat; Chorba, Terence

2012-01-01

Background Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG) in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia) or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. Methods/Findings We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan), the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. Limitations Potential limitations included considerations that 1) the methodology used was retrospective, 2) multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3) most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4) small variations in reported population TB burden could have affected relative risk of exposure for cohorts. Conclusions/Significance All three BCG vaccines evaluated were protective against TB, and prevention effectiveness varied by

Comparative tuberculosis (TB prevention effectiveness in children of Bacillus Calmette-Guérin (BCG vaccines from different sources, Kazakhstan.

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Michael Favorov

Full Text Available BACKGROUND: Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. METHODS/FINDINGS: We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan, the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. LIMITATIONS: Potential limitations included considerations that 1 the methodology used was retrospective, 2 multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3 most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4 small variations in reported population TB burden could have affected relative risk of exposure for cohorts. CONCLUSIONS/SIGNIFICANCE: All three BCG vaccines evaluated were protective against TB, and prevention effectiveness

Comparative tuberculosis (TB) prevention effectiveness in children of Bacillus Calmette-Guérin (BCG) vaccines from different sources, Kazakhstan.

Science.gov (United States)

Favorov, Michael; Ali, Mohammad; Tursunbayeva, Aigul; Aitmagambetova, Indira; Kilgore, Paul; Ismailov, Shakhimurat; Chorba, Terence

2012-01-01

Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG) in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia) or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan), the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. Potential limitations included considerations that 1) the methodology used was retrospective, 2) multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3) most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4) small variations in reported population TB burden could have affected relative risk of exposure for cohorts. All three BCG vaccines evaluated were protective against TB, and prevention effectiveness varied by manufacturer. When setting national immunization policy, consideration

Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines

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Daniel H. Libraty

2014-01-01

Full Text Available Neonatal Bacille Calmette Guérin (BCG vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1 immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ producing spot-forming cells (SFC to tetanus toxoid 2–3 months later. The frequency of IFN-γ producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later.

Oral Polio Vaccine Influences the Immune Response to BCG Vaccination. A Natural Experiment

DEFF Research Database (Denmark)

Sartono, E.; Lisse, I.M.; Terveer, E.M.

2010-01-01

not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. Methods and Findings: We compared the in vitro and the in vivo response to PPD in the infants who received OPV and BCG with that of infants who received BCG...... only. At age 6 weeks, the in vitro cytokine response to purified protein derivate (PPD) of M. Tuberculosis was reduced in LBW and NBW infants who had received OPV with BCG. In a pooled analysis receiving OPV with BCG at birth was associated with significantly lower IL-13 (p = 0.041) and IFN-gamma (p...... = 0.004) and a tendency for lower IL-10 (p = 0.054) in response to PPD. Furthermore, OPV was associated with reduced in vivo response to PPD at age 2 months, the prevalence ratio (PR) of having a PPD reaction being 0.75 (0.58-0.98), p = 0.033, and with a tendency for reduced likelihood of having a BCG...

Oral polio vaccine influences the immune response to BCG vaccination. A natural experiment

DEFF Research Database (Denmark)

Sartono, Erliyani; Lisse, Ida M; Terveer, Elisabeth M

2010-01-01

not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. METHODS AND FINDINGS: We compared the in vitro and the in vivo response to PPD in the infants who received OPV and BCG with that of infants who received BCG...... only. At age 6 weeks, the in vitro cytokine response to purified protein derivate (PPD) of M. Tuberculosis was reduced in LBW and NBW infants who had received OPV with BCG. In a pooled analysis receiving OPV with BCG at birth was associated with significantly lower IL-13 (p = 0.041) and IFN-gamma (p...... = 0.004) and a tendency for lower IL-10 (p = 0.054) in response to PPD. Furthermore, OPV was associated with reduced in vivo response to PPD at age 2 months, the prevalence ratio (PR) of having a PPD reaction being 0.75 (0.58-0.98), p = 0.033, and with a tendency for reduced likelihood of having a BCG...

Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults.

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Szpakowski, Piotr; Biet, Franck; Locht, Camille; Paszkiewicz, Małgorzata; Rudnicka, Wiesława; Druszczyńska, Magdalena; Allain, Fabrice; Fol, Marek; Pestel, Joël; Kowalewicz-Kulbat, Magdalena

2015-01-01

Tuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we constructed recombinant BCG producing human IL-18 (rBCGhIL-18) and investigated whether human IL-18 produced by rBCGhIL-18 modulates DC functions and enhances Th1 responses to mycobacterial antigens in humans. We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective. In contrast, both BCG strains decreased the DC-SIGN expression on human DCs. The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG. In a coculture system of CD4(+) T cells and loaded DCs, rBCGhIL-18 favoured strong IFN-γ but also IL-10 production by naive T cells but not by memory T cells. This was much less the case for nonrecombinant BCG. Thus the expression of IL-18 by recombinant BCG increases IL-23, IP-10, and IL-10 expression by human DCs and enhances their ability to induce IFN-γ and IL-10 expression by naive T cells, without affecting the maturation phenotype of the DCs.

Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults

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Piotr Szpakowski

2015-01-01

Full Text Available Tuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG, the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we constructed recombinant BCG producing human IL-18 (rBCGhIL-18 and investigated whether human IL-18 produced by rBCGhIL-18 modulates DC functions and enhances Th1 responses to mycobacterial antigens in humans. We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective. In contrast, both BCG strains decreased the DC-SIGN expression on human DCs. The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG. In a coculture system of CD4+ T cells and loaded DCs, rBCGhIL-18 favoured strong IFN-γ but also IL-10 production by naive T cells but not by memory T cells. This was much less the case for nonrecombinant BCG. Thus the expression of IL-18 by recombinant BCG increases IL-23, IP-10, and IL-10 expression by human DCs and enhances their ability to induce IFN-γ and IL-10 expression by naive T cells, without affecting the maturation phenotype of the DCs.

Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates

DEFF Research Database (Denmark)

Benn, Christine Stabell; Fisker, Ane Baerent; Napirna, Bitiguida Mutna

2010-01-01

OBJECTIVE: To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates. DESIGN: Randomised, placebo controlled, two by two factorial trial. SETTING: Bissau, Guinea-Bissau. PARTICIPANTS: 1717 low birthweight neonates born at the national hospital...... months of age for infants who received vitamin A supplementation compared with those who received placebo. RESULTS: No interaction was observed between vitamin A supplementation and BCG vaccine allocation (P=0.73). Vitamin A supplementation at birth was not significantly associated with mortality......: the MRR of vitamin A supplementation compared with placebo, controlled for randomisation to "early BCG" versus "no early BCG" was 1.08 (95% CI 0.79 to 1.47). Stratification by sex revealed a significant interaction between vitamin A supplementation and sex (P=0.046), the MRR of vitamin A supplementation...

Differential Adverse Event Profiles Associated with BCG as a Preventive Tuberculosis Vaccine or Therapeutic Bladder Cancer Vaccine Identified by Comparative Ontology-Based VAERS and Literature Meta-Analysis.

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Jiangan Xie

Full Text Available M. bovis strain Bacillus Calmette-Guérin (BCG has been the only licensed live attenuated vaccine against tuberculosis (TB for nearly one century and has also been approved as a therapeutic vaccine for bladder cancer treatment since 1990. During its long time usage, different adverse events (AEs have been reported. However, the AEs associated with the BCG preventive TB vaccine and therapeutic cancer vaccine have not been systematically compared. In this study, we systematically collected various BCG AE data mined from the US VAERS database and PubMed literature reports, identified statistically significant BCG-associated AEs, and ontologically classified and compared these AEs related to these two types of BCG vaccine. From 397 VAERS BCG AE case reports, we identified 64 AEs statistically significantly associated with the BCG TB vaccine and 14 AEs with the BCG cancer vaccine. Our meta-analysis of 41 peer-reviewed journal reports identified 48 AEs associated with the BCG TB vaccine and 43 AEs associated with the BCG cancer vaccine. Among all identified AEs from VAERS and literature reports, 25 AEs belong to serious AEs. The Ontology of Adverse Events (OAE-based ontological hierarchical analysis indicated that the AEs associated with the BCG TB vaccine were enriched in immune system (e.g., lymphadenopathy and lymphadenitis, skin (e.g., skin ulceration and cyanosis, and respiratory system (e.g., cough and pneumonia; in contrast, the AEs associated with the BCG cancer vaccine mainly occurred in the urinary system (e.g., dysuria, pollakiuria, and hematuria. With these distinct AE profiles detected, this study also discovered three AEs (i.e., chills, pneumonia, and C-reactive protein increased shared by the BCG TB vaccine and bladder cancer vaccine. Furthermore, our deep investigation of 24 BCG-associated death cases from VAERS identified the important effects of age, vaccine co-administration, and immunosuppressive status on the final BCG

BCG vaccination drives accumulation and effector function of innate lymphoid cells in murine lungs.

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Steigler, Pia; Daniels, Naomi J; McCulloch, Tim R; Ryder, Brin M; Sandford, Sarah K; Kirman, Joanna R

2018-04-01

The tuberculosis (TB) vaccine bacille Calmette-Guérin (BCG) prevents disseminated childhood TB; however, it fails to protect against the more prevalent pulmonary TB. Limited understanding of the immune response to Mycobacterium tuberculosis, the causative agent of TB, has hindered development of improved vaccines. Although memory CD4 T cells are considered the main mediators of protection against TB, recent studies suggest there are other key subsets that contribute to antimycobacterial immunity. To that end, innate cells may be involved in the protective response. In this study, we investigated the primary response of innate lymphoid cells (ILCs) to BCG exposure. Using a murine model, we showed that ILCs increased in number in the lungs and lymph nodes in response to BCG vaccination. Additionally, there was significant production of the antimycobacterial cytokine IFN-γ by ILCs. As ILCs are located at mucosal sites, it was investigated whether mucosal vaccination (intranasal) stimulated an enhanced response compared to the traditional vaccination approach (intradermal or subcutaneous). Indeed, in response to intranasal vaccination, the number of ILCs, and IFN-γ production in NK cells and ILC1s in the lungs and lymph nodes, were higher than that provoked through intradermal or subcutaneous vaccination. This work provides the first evidence that BCG vaccination activates ILCs, paving the way for future research to elucidate the protective potential of ILCs against mycobacterial infection. Additionally, the finding that lung ILCs respond rigorously to mucosal vaccination may have implications for the delivery of novel TB vaccines. © 2018 Australasian Society for Immunology Inc.

BCG vaccination status of children with tuberculous meningitis and ...

African Journals Online (AJOL)

From 1985 to 1992, 193 children with tuberculous meningitis (TBM) with a median age of 26 months were admitted to the Department of Paediatrics and Child Health, Tygerberg Hospital. Of these children 143 (74%) were documented to have received BCG, either by reference to 'Road to Health' cards or by contact with ...

BCG vaccination status of children with tuberculous meningitis and ...

African Journals Online (AJOL)

From 1985 to 1992, 193 children with tuberculous meningitis (TBM) with a median age of 26 months were admitted to the Department of Paediatrics and Child. Health, Tygerberg Hospital. Of these children 143 (74%) were documented to have received BCG, either by reference to 'Road to Health' cards or by contact with.

Murine immune responses to oral BCG immunization in the presence or absence of prior BCG sensitization.

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Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

2010-02-01

Oral delivery of live Mycobacterium bovis BCG in a lipid matrix invokes cell-mediated immune (CMI) responses in mice and consequent protection against pulmonary challenge with virulent mycobacteria. To investigate the influence of prior BCG sensitization on oral vaccine efficacy, we assessed CMI responses and BCG colonization of the alimentary tract lymphatics 5 months after oral vaccination, in both previously naive mice and in mice that had been sensitized to BCG by injection 6 months previously. CMI responses did not differ significantly between mice that received subcutaneous BCG followed by oral BCG and those that received either injected or oral BCG alone. In vivo BCG colonization was predominant in the mesenteric lymph nodes after oral vaccination; this colonizing ability was not influenced by prior BCG sensitization. From this murine model study, we conclude that although prior parenteral-route BCG sensitization does not detrimentally affect BCG colonization after oral vaccination, there is no significant immune-boosting effect of the oral vaccine either.

Vaccination of cattle with Mycobacterium bovis BCG by a combination of systemic and oral routes.

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Buddle, Bryce M; Denis, Michel; Aldwell, Frank E; Martin Vordermeier, H; Glyn Hewinson, R; Neil Wedlock, D

2008-11-01

Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine delivered to calves by the subcutaneous (s.c.) or by the oral route in a formulated lipid matrix has been previously shown to induce similar levels of protection against bovine tuberculosis. The current study was aimed at determining whether a combination of delivering BCG by s.c. and oral routes would enhance levels of protection, compared to only one route of vaccination. Forty calves were randomly divided into four groups (10/group). Calves were vaccinated with 10(6)colony forming units (CFU) of BCG Pasteur by the s.c. route or orally with 10(9)CFU BCG incorporated into a lipid formulation. One group received a combination of BCG administered by both the s.c. and oral routes and a non-vaccinated group served as a control. The two groups of calves that received s.c. BCG produced strong IFN-gamma responses in whole blood cultures stimulated with bovine purified protein derivative (PPD) 3 weeks after vaccination. Cattle vaccinated just with oral BCG in a lipid matrix produced a strong IFN-gamma response 8 weeks after vaccination, and peaking at 11 weeks after vaccination. All calves were challenged by the intratracheal route with M. bovis 15 weeks after vaccination and were euthanized and necropsied to assess protection at 17 weeks following challenge. BCG given s.c. or orally induced significant and comparable levels of protection against the virulent challenge. Vaccination of cattle by a combination of s.c./oral routes did not enhance protection beyond that achieved by s.c. or oral vaccination alone. We conclude that vaccination of cattle with BCG by a combination of routes has no beneficial additive effects, compared to a single s.c. administration of BCG or BCG given orally in a lipid formulation.

The effect of BCG vaccine from protection of type 1 diabetes mellitus

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Mehmet Karaci

2012-03-01

As a result, we concluded that if BCG is vaccine is applied at least twice and , the first dose is gives in the newborn period may exert a protective effect for the development of type I DM in children . [J Contemp Med 2012; 2(1.000: 1-8

Immune response profiles of calves following vaccination with live BCG and inactivated Mycobacterium bovis vaccine candidates.

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E M D L van der Heijden

Full Text Available Conventional control and eradication strategies for bovine tuberculosis (BTB face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle. Twenty-four mixed breed calves (Bos taurus aged 4-6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live M. bovis BCG (Danish 1331, formalin-inactivated M. bovis BCG, heat-killed M. bovis or PBS/Montanide™ (control. Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live M. bovis BCG. The animals in the heat-killed M. bovis group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed M. bovis group. In conclusion, the parenteral heat-killed M. bovis vaccine proved to be clearly immunogenic in cattle in the present study

Evolution of M. bovis BCG Vaccine: Is Niacin Production Still a Valid Biomarker?

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Sarman Singh

2015-01-01

Full Text Available BCG vaccine is usually considered to be safe though rarely serious complications have also been reported, often incriminating contamination of the seed strain with pathogenic Mycobacterium tuberculosis. In such circumstances, it becomes prudent to rule out the contamination of the vaccine seed. M. bovis BCG can be confirmed by the absence of nitrate reductase, negative niacin test, and resistance to pyrazinamide and cycloserine. Recently in India, some stocks were found to be niacin positive which led to a national controversy and closer of a vaccine production plant. This prompted us to write this review and the comparative biochemical and genotypic studies were carried out on the these contentious vaccine stocks at the Indian vaccine plant and other seeds and it was found that some BCG vaccine strains and even some strains of M. bovis with eugenic-growth characteristics mainly old laboratory strains may give a positive niacin reaction. Most probably, the repeated subcultures lead to undefined changes at the genetic level in these seed strains. These changing biological characteristics envisage reevaluation of biochemical characters of existing BCG vaccine seeds and framing of newer guidelines for manufacturing, production, safety, and effectiveness of BCG vaccine.

Uptake of newly introduced universal BCG vaccination in newborns.

LENUS (Irish Health Repository)

Braima, O

2012-01-31

Universal neonatal BCG vaccination was discontinued in Cork in 1972. Following an outbreak of TB in 2 creches in the HSE South, a universal BCG vaccination program was re-introduced in October 2008. The aim of this study was to determine the vaccination process (in-hospital and community) and the in-hospital uptake of the vaccine. Following informed parental consent, babies of birth weight > 2.5 Kg were eligible for in-hospital vaccination if they were not: febrile, jaundiced on phototherapy, on antibiotics and if not born to HIV- positive mothers. Parents of babies not vaccinated in-hospital were asked to book an appointment in either of the 2 Cork community clinics. The immunisation nurse collected data on BCG vaccination, prospectively. This study examined vaccination uptakes in-hospital and community over a 6 month period (October 2008 to March 2009). There were 4018 deliveries during the study period. In-hospital consent was declined in only 16 babies (<1%) while the in-hospital vaccination uptake was 80% of total liv births. Although 635 newborns were admitted to the NICU, only 46 (8%) were vaccinated while in the NICU. At least 48% of planned community vaccination has been achieved to date. In conclusion, in-hospital consent was almost universal and vaccination uptake was satisfactory. NICU exclusion criteria accounted for a significant proportion of non-vaccination in-hospital. These criteria need to be readdressed considering that all premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight.

Uptake of newly introduced universal BCG vaccination in newborns.

LENUS (Irish Health Repository)

Braima, O

2010-06-01

Universal neonatal BCG vaccination was discontinued in Cork in 1972. Following an outbreak of TB in 2 creches in the HSE South, a universal BCG vaccination program was re-introduced in October 2008. The aim of this study was to determine the vaccination process (in-hospital and community) and the in-hospital uptake of the vaccine. Following informed parental consent, babies of birth weight > 2.5 Kg were eligible for in-hospital vaccination if they were not: febrile, jaundiced on phototherapy, on antibiotics and if not born to HIV- positive mothers. Parents of babies not vaccinated in-hospital were asked to book an appointment in either of the 2 Cork community clinics. The immunisation nurse collected data on BCG vaccination, prospectively. This study examined vaccination uptakes in-hospital and community over a 6 month period (October 2008 to March 2009). There were 4018 deliveries during the study period. In-hospital consent was declined in only 16 babies (<1%) while the in-hospital vaccination uptake was 80% of total liv births. Although 635 newborns were admitted to the NICU, only 46 (8%) were vaccinated while in the NICU. At least 48% of planned community vaccination has been achieved to date. In conclusion, in-hospital consent was almost universal and vaccination uptake was satisfactory. NICU exclusion criteria accounted for a significant proportion of non-vaccination in-hospital. These criteria need to be readdressed considering that all premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight.

Protection against bovine tuberculosis induced by oral vaccination of cattle with Mycobacterium bovis BCG is not enhanced by co-administration of mycobacterial protein vaccines.

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Wedlock, D Neil; Aldwell, Frank E; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M

2011-12-15

Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral

Tuberculosis vaccine strain Mycobacterium bovis BCG Russia is a natural recA mutant

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Böttger Erik C

2008-07-01

Full Text Available Abstract Background The current tuberculosis vaccine is a live vaccine derived from Mycobacterium bovis and attenuated by serial in vitro passaging. All vaccine substrains in use stem from one source, strain Bacille Calmette-Guérin. However, they differ in regions of genomic deletions, antigen expression levels, immunogenicity, and protective efficacy. Results As a RecA phenotype increases genetic stability and may contribute restricting the ongoing evolution of the various BCG substrains while maintaining their protective efficacy, we aimed to inactivate recA by allelic replacement in BCG vaccine strains representing different phylogenetic lineages (Pasteur, Frappier, Denmark, Russia. Homologous gene replacement was achieved successfully in three out of four strains. However, only illegitimate recombination was observed in BCG substrain Russia. Sequence analyses of recA revealed that a single nucleotide insertion in the 5' part of recA led to a translational frameshift with an early stop codon making BCG Russia a natural recA mutant. At the protein level BCG Russia failed to express RecA. Conclusion According to phylogenetic analyses BCG Russia is an ancient vaccine strain most closely related to the parental M. bovis. We hypothesize that recA inactivation in BCG Russia occurred early and is in part responsible for its high degree of genomic stability, resulting in a substrain that has less genetic alterations than other vaccine substrains with respect to M. bovis AF2122/97 wild-type.

Revaccination of Guinea Pigs With the Live Attenuated Mycobacterium tuberculosis Vaccine MTBVAC Improves BCG's Protection Against Tuberculosis.

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Clark, Simon; Lanni, Faye; Marinova, Dessislava; Rayner, Emma; Martin, Carlos; Williams, Ann

2017-09-01

The need for an effective vaccine against human tuberculosis has driven the development of different candidates and vaccination strategies. Novel live attenuated vaccines are being developed that promise greater safety and efficacy than BCG against tuberculosis. We combined BCG with the vaccine MTBVAC to evaluate whether the efficacy of either vaccine would be affected upon revaccination. In a well-established guinea pig model of aerosol infection with Mycobacterium tuberculosis, BCG and MTBVAC delivered via various prime-boost combinations or alone were compared. Efficacy was determined by a reduction in bacterial load 4 weeks after challenge. Efficacy data suggests MTBVAC-associated immunity is longer lasting than that of BCG when given as a single dose. Long and short intervals between BCG prime and MTBVAC boost resulted in improved efficacy in lungs, compared with BCG given alone. A shorter interval between MTBVAC prime and BCG boost resulted in improved efficacy in lungs, compared with BCG given alone. A longer interval resulted in protection equivalent to that of BCG given alone. These data indicate that, rather than boosting the waning efficacy of BCG, a vaccination schedule involving a combination of the 2 vaccines yielded stronger immunity to M. tuberculosis infection. This work supports development of MTBVAC use as a revaccination strategy to improve on the effects of BCG in vaccinated people living in tuberculosis-endemic countries. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

SIMULTANEOUS BCG AND SMALLPOX VACCINATION ON NEWBORN INFANTS

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Abdul Rivai

2012-09-01

Full Text Available Telah dikemukakan anggapan-anggapan yang terdapat dewasa ini tentang vaksinasi BCG dan cacar secara simultan. Telah dilakukan vaksinasi BCG dan cacar secara simultan pada 729 neonati dengan freeze dried Smallpox vaccine buatan dari Bio Farma dan freeze dried BCG vaccine Tokyo. Pencacaran dilakukan secara multiple puncture dan bifurcated needle dengan suntikan BCG dengan jarum dan spuit khusus intracutan dengan dosis 0,1 ml. Tuberkulin test dilakukan dengan PPD dari Kopenhagen dengan kekuatan 2 TU 9 minggu setelah vaksinasi. Dari 741 bayi yang diikut sertakan dalam survey, 12 menolak, 3 bayi tidak dapat dilakukan pemeriksaan pertama, 35 bayi belum diperiksa, pemeriksaan pertama telah dilakukan pada 691 bayi. Dari 406 bayi yang seharusnya sudah diperiksa untuk pemeriksaan kedua, 23 dapat dilakukan karena tidak dapat dijumpai atau meninggal. Telah dikemukakan bahwa pencatatan alamat yang jelas dan lengkap serta kesungguhan dalam melakukan home visits sangat penting untuk berhasilnya penyelidikan semacam ini. Dari hasil-hasil yang didapatkan sampai sekarang telah dapat diambil kesimpulan sementara, bahwa vaksinasi BCG dan cacar secara simultan memberikan hasil yang memuaskan, juga bila dibandingkan dengan hasil-hasil penyelidikan diluar negeri take pada pencacaran 99.4 percent, test tuberkulin dengan PPD 2 TU 9 minggu setelah vaksinasi memberikan indurasi lebih dari 5 mm pada 99.75 percent dan tidak menimbulkan komplikasi-komplikasi. Pelaksanaan vaksinasi BCG dan cacar dapat dilakukan oleh tenaga paramedis yang telah mendapat latihan khusus dan diawasi oleh dokter yang kompeten. Dianjurkan untuk melakukan follow up pada bayi-bayi yang diikut sertakan dalam survey ini.

Variation of growth in the production of the BCG vaccine and the association with the immune response. An observational study within a randomised trial

DEFF Research Database (Denmark)

Biering-Sørensen, Sofie; Jensen, Kristoffer Jarlov; Aamand, Susanne Havn

2015-01-01

INTRODUCTION: Bacille Calmette-Guérin (BCG) vaccine has beneficial non-specific effects on overall survival. After BCG vaccination, positive PPD response and scar formation are associated with increased survival. During a trial randomising low-birth-weight neonates to BCG at birth or the usual...... randomised to BCG at birth and examined for scar at 12 months; a subgroup was tested for PPD response at 2 and 6 months. The BCG batches from the Slow growth period were compared with the precedent and subsequent Normal growth batches with regard to prevalence and size of BCG scar and PPD response. We also...... batches were associated with larger scar size (5.0mm) than precedent (4.4mm, pPPD responses, and among PPD positive children, a larger PPD...

Features of General Reactive Potential of the Body in Infants with BCG lymphadenitis

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A.I. Bobrovitskaia

2014-11-01

Conclusions. When using BCG vaccine of Russian production, there is far less significant overload of blood flow by products of intoxication and inflammation, more pronounced body’s ability to respond to antigenic stimulus generalization and no risk of infection, especially in infants, compared with Danish BCG vaccine. For vaccination of infants against tuberculosis, it is advisable to use more refined, with high immunogenicity and less reactogenic BCG vaccine of Russian production. Despite the presence of complications when using BCG vaccine, protection of the body from the development of generalized forms of tuberculosis in young children is possible by vaccination in the neonatal period.

BCG protects against tuberculosis irrespective of HIV status

DEFF Research Database (Denmark)

Faurholt-Jepsen, Daniel; Range, Nyagosya; PrayGod, George

2013-01-01

While BCG vaccine protects against severe tuberculosis (TB) in children, its effect against adult TB is questionable. Furthermore, it is not known if HIV co-infection modifies the effect of BCG. Among 352 pairs of Tanzanian TB cases and matched controls, the BCG scar was associated with a reduced...

A booster vaccine expressing a latency-associated antigen augments BCG induced immunity and confers enhanced protection against tuberculosis.

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Bappaditya Dey

Full Text Available BACKGROUND: In spite of a consistent protection against tuberculosis (TB in children, Mycobacterium bovis Bacille Calmette-Guerin (BCG fails to provide adequate protection against the disease in adults as well as against reactivation of latent infections or exogenous reinfections. It has been speculated that failure to generate adequate memory T cell response, elicitation of inadequate immune response against latency-associated antigens and inability to impart long-term immunity against M. tuberculosis infections are some of the key factors responsible for the limited efficiency of BCG in controlling TB. METHODS/PRINCIPAL FINDINGS: In this study, we evaluated the ability of a DNA vaccine expressing α-crystallin--a key latency antigen of M. tuberculosis to boost the BCG induced immunity. 'BCG prime-DNA boost' regimen (B/D confers robust protection in guinea pigs along with a reduced pathology in comparison to BCG vaccination (1.37 log(10 and 1.96 log(10 fewer bacilli in lungs and spleen, respectively; p<0.01. In addition, B/D regimen also confers enhanced protection in mice. Further, we show that B/D immunization in mice results in a heightened frequency of PPD and antigen specific multi-functional CD4 T cells (3(+ simultaneously producing interferon (IFNγ, tumor necrosis factor (TNFα and interleukin (IL2. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of α-crystallin based B/D regimen over BCG. Our study, also demonstrates that protection against TB is predictable by an increased frequency of 3(+ Th1 cells with superior effector functions. We anticipate that this study would significantly contribute towards the development of superior booster vaccines for BCG vaccinated individuals. In addition, this regimen can also be expected to reduce the risk of developing active TB due to reactivation of latent infection.

Another vaccine, another story: BCG vaccination against tuberculosis in India, 1948 to 1960 Outra vacina, outra história: a vacinação de BCG contra tuberculose na Índia, 1948 a 1960

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Niels Brimnes

2011-02-01

Full Text Available Through an examination of mass BCG vaccination against tuberculosis in India between 1948 and 1960 this article draws attention to the diversity of the history of vaccination. The features of vaccination campaigns often differed from those of the celebrated campaign to eradicate smallpox. Due to differences between smallpox and tuberculosis as well as between the vaccines developed against them, an analysis of BCG mass vaccination against tuberculosis seems particularly well suited for this purpose. Three points of difference are identified. First, in non-Western contexts BCG vaccination procedures were modified to a greater extent than vaccination against smallpox. Second, tuberculosis lacked the drama and urgency of smallpox and BCG vaccination campaigns suffered more from recruitment problems than did the more "heroic" smallpox eradication campaign. Third, the BCG vaccine was contested in medical circles and was much better suited than the vaccine against smallpox as a vehicle for the articulation of concerns about post-colonial modernization.Através da observação da vacinação em massa de BCG contra a tuberculose na Índia durante os anos de 1948 a 1960, este artigo chama a atenção para a diversidade da história da vacinação. As características das campanhas de vacinação geralmente diferem daquelas celebradas nas campanhas para erradicação da varíola. Devido às diferenças entre a varíola e a turberculose, assim como entre as vacinas desenvolvidas para combater essas doenças, uma análise da vacinação em massa de BCG contra a turberculose parece especialmente bem situada para essa proposta. Três pontos de diferença foram identificados. O primeiro é que em contextos não ocidentais os procedimentos da vacinação de BCG foram modificados em uma extensão maior do que a vacinação contra a varíola. Em segundo lugar, a tuberculose não tinha o drama e a urgência da varíola, e as campanhas de vacinação de BCG

Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

Science.gov (United States)

Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

2016-02-10

Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible. Copyright © 2016 Elsevier Ltd. All rights reserved.

Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

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JoĂŤl Pestel

2008-06-01

Full Text Available Mycobacterium bovis bacillus Calmette-GuĂŠrin (BCG is a live vaccine that has been used in routine vaccination against tuberculosis for nearly 80 years. However, its efficacy is controversial. The failure of BCG vaccination may be at least partially explained by the induction of poor or inappropriate host responses. Dendritic cells (DCs are likely to play a key role in the induction of immune response to mycobacteria by polarizing the reactivity of T lymphocytes toward a Th1 profile, contributing to the generation of protective cellular immunity against mycobacteria. In this study we aimed to investigate the production of Th1 and Th2 cytokines by naive CD4+ T cells to mycobacterial antigen-pulsed DCs in the group of young, healthy BCG vaccinated volunteers. The response of naive helper T cells was compared with the response of total blood lymphocytes. Our present results clearly showed that circulating naive CD45RA+CD4+ lymphocytes from BCG-vaccinated subjects can become effector helper cells producing IFN-gamma and IL-5 under the stimulation by autologous dendritic cells presenting mycobacterial protein antigen-PPD or infected with live M. bovis BCG bacilli.

Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

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Kowalewicz-Kulbat, Magdalena; Kaźmierczak, Dominik; Donevski, Stefan; Biet, Franck; Pestel, Joël; Rudnicka, Wiesława

2008-01-01

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a live vaccine that has been used in routine vaccination against tuberculosis for nearly 80 years. However, its efficacy is controversial. The failure of BCG vaccination may be at least partially explained by the induction of poor or inappropriate host responses. Dendritic cells (DCs) are likely to play a key role in the induction of immune response to mycobacteria by polarizing the reactivity of T lymphocytes toward a Th1 profile, contributing to the generation of protective cellular immunity against mycobacteria. In this study we aimed to investigate the production of Th1 and Th2 cytokines by naive CD4+ T cells to mycobacterial antigen-pulsed DCs in the group of young, healthy BCG vaccinated volunteers. The response of naive helper T cells was compared with the response of total blood lymphocytes. Our present results clearly showed that circulating naive CD45RA+CD4+ lymphocytes from BCG-vaccinated subjects can become effector helper cells producing IFN-gamma and IL-5 under the stimulation by autologous dendritic cells presenting mycobacterial protein antigen-PPD or infected with live M. bovis BCG bacilli.

Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau.

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Roth, Adam Edvin; Benn, Christine Stabell; Ravn, Henrik; Rodrigues, Amabelia; Lisse, Ida Maria; Yazdanbakhsh, Maria; Whittle, Hilton; Aaby, Peter

2010-03-15

To determine whether BCG revaccination at 19 months of age reduces overall child mortality. Randomised trial, with follow-up to age 5. A health project in Bissau, Guinea-Bissau, which maintains a health and demographic surveillance system in an urban area with 90 000 inhabitants. 2871 children aged 19 months to 5 years with low or no reactivity to tuberculin and who were not severely sick on the day of enrollment. BCG vaccination or no vaccination (control). Hazard ratios for mortality. 77 children died during follow-up. Compared with controls, the BCG revaccinated children had a hazard ratio of 1.20 (95% confidence interval 0.77 to 1.89). Two hundred and fifty children were admitted to hospital for the first time between enrollment and the end of the study, with an incidence rate ratio for BCG revaccinated children versus controls of 1.04 (0.81 to 1.33). The trial was stopped prematurely because of a cluster of deaths in the BCG arm of the study. This increase in mortality occurred at a time when many children had received missing vaccinations or vitamin A or iron supplementation; the hazard ratio for BCG revaccinated children compared with controls was 2.69 (1.05 to 6.88) in the period after these campaigns. Throughout the trial, the effect of BCG revaccination on mortality was significantly different (P=0.006) in children who had received diphtheria-tetanus-pertussis (DTP) booster vaccination before enrollment (hazard ratio 0.36, 0.13 to 0.99) and children who had not received the booster before enrollment (1.78, 1.04 to 3.04). There was no overall beneficial effect of being revaccinated with BCG. The effect of BCG revaccination on mortality might depend on other health interventions. Trial registration Clinical Trials ICA4-CT-2002-10053-REVAC.

Influence of isoniazid on naturally acquired tuberculin allergy and on induction of allergy by BCG vaccination*

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Narain, Raj; Bagga, A. S.; Naganna, K.; Mayurnath, S.

1970-01-01

Previous studies on the influence of isoniazid on the size of the tuberculin reaction have given conflicting results. A controlled study in an area with high prevalence of low-grade allergy has been carried out by the administration of isoniazid or placebo tablets. For those not vaccinated with BCG, isoniazid in a single daily dose of 5 mg/kg body-weight tended to reduce somewhat the size of the tuberculin reaction among those with reactions of 12 mm or more at the initial tuberculin test. In people who were vaccinated with BCG, isoniazid given simultaneously resulted in significantly less increase in the size of post-vaccination tuberculin reactions as compared with controls; the difference was still significant, in tests conducted 4½ months after the discontinuation of isoniazid. However, in spite of isoniazid, the post-vaccination allergy induced by BCG was quite considerable. This considerable increase in post-vaccination allergy suggests that the vaccination was successful in spite of the administration of isoniazid and makes it clear that primary chemoprophylaxis could be combined with BCG vaccination. Administration of isoniazid for 2 months is estimated to have killed about 90% of the bacilli in the BCG vaccine injected intracutaneously. PMID:5312322

Overexpression of a Mycobacterium ulcerans Ag85B-EsxH Fusion Protein in Recombinant BCG Improves Experimental Buruli Ulcer Vaccine Efficacy.

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Bryan E Hart

2016-12-01

Full Text Available Buruli ulcer (BU vaccine design faces similar challenges to those observed during development of prophylactic tuberculosis treatments. Multiple BU vaccine candidates, based upon Mycobacterium bovis BCG, altered Mycobacterium ulcerans (MU cells, recombinant MU DNA, or MU protein prime-boosts, have shown promise by conferring transient protection to mice against the pathology of MU challenge. Recently, we have shown that a recombinant BCG vaccine expressing MU-Ag85A (BCG MU-Ag85A displayed the highest level of protection to date, by significantly extending the survival time of MU challenged mice compared to BCG vaccination alone. Here we describe the generation, immunogenicity testing, and evaluation of protection conferred by a recombinant BCG strain which overexpresses a fusion of two alternative MU antigens, Ag85B and the MU ortholog of tuberculosis TB10.4, EsxH. Vaccination with BCG MU-Ag85B-EsxH induces proliferation of Ag85 specific CD4+ T cells in greater numbers than BCG or BCG MU-Ag85A and produces IFNγ+ splenocytes responsive to whole MU and recombinant antigens. In addition, anti-Ag85A and Ag85B IgG humoral responses are significantly enhanced after administration of the fusion vaccine compared to BCG or BCG MU-Ag85A. Finally, mice challenged with MU following a single subcutaneous vaccination with BCG MU-Ag85B-EsxH display significantly less bacterial burden at 6 and 12 weeks post-infection, reduced histopathological tissue damage, and significantly longer survival times compared to vaccination with either BCG or BCG MU-Ag85A. These results further support the potential of BCG as a foundation for BU vaccine design, whereby discovery and recombinant expression of novel immunogenic antigens could lead to greater anti-MU efficacy using this highly safe and ubiquitous vaccine.

Mycobacterium tuberculosis, but not vaccine BCG, specifically upregulates matrix metalloproteinase-1.

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Elkington, Paul T G; Nuttall, Robert K; Boyle, Joseph J; O'Kane, Cecilia M; Horncastle, Donna E; Edwards, Dylan R; Friedland, Jon S

2005-12-15

Pulmonary cavitation is fundamental to the global success of Mycobacterium tuberculosis. However, the mechanisms of this lung destruction are poorly understood. The biochemistry of lung matrix predicts matrix metalloproteinase (MMP) involvement in immunopathology. We investigated gene expression of all MMPs, proteins with a disintegrin and metalloproteinase domain, and tissue inhibitors of metalloproteinases in M. tuberculosis-infected human macrophages by real-time polymerase chain reaction. MMP secretion was measured by zymography and Western analysis, and expression in patients with pulmonary tuberculosis was localized by immunohistochemistry. MMP-1 and MMP-7 gene expression and secretion are potently upregulated by M. tuberculosis, and no increase in tissue inhibitor of metalloproteinase expression occurs to oppose their activity. Dexamethasone completely suppresses MMP-1 but not MMP-7 gene expression and secretion. In patients with active tuberculosis, macrophages express MMP-1 and MMP-7 adjacent to areas of tissue destruction. MMP-1 but not MMP-7 expression and secretion are relatively M. tuberculosis specific, are not upregulated by tuberculosis-associated cytokines, and are prostaglandin dependent. In contrast, the vaccine M. bovis bacillus Calmette-Guérin (BCG) does not stimulate MMP-1 secretion from human macrophages, although M. tuberculosis and BCG do upregulate MMP-7 equally. BCG-infected macrophages secrete reduced prostaglandin E2 concentrations compared with M. tuberculosis-infected macrophages, and prostaglandin pathway supplementation augments MMP-1 secretion from BCG-infected cells. M. tuberculosis specifically upregulates MMP-1 in a cellular model of human infection and in patients with tuberculosis. In contrast, vaccine BCG, which does not cause lung cavitation, does not upregulate prostaglandin E2-dependent MMP-1 secretion.

The immunological effects of oral polio vaccine provided with BCG vaccine at birth

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Jensen, Kristoffer Jarlov; Karkov, Hanne Sophie; Lund, Najaaraq

2014-01-01

BCG alone at birth, and subsequently randomised to have a blood sample taken at 2, 4 or 6 weeks post-randomisation. Excreted levels of cytokines (IL-2, IL-5, IL-10, TNF-α and IFN-γ) were measured from whole blood in vitro stimulations with a panel of recall vaccine antigens (BCG, PPD, OPV), mitogen...... prevalence of IFN-γ responses to PPD (prevalence ratio (PR): 0.84 (0.72-0.98)) and reduced IL-5 to PPD (PR: 0.78 (0.64-0.96)). No effects were observed for CPR, RBP, white blood cell distribution, or BCG scar prevalence. CONCLUSION: The results corroborate that OPV attenuates the immune response to co...

Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis.

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Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M; Lucas, Megan; Spencer, John S; Amara, Rama Rao; Plikaytis, Bonnie B; Posey, James E; Sable, Suraj B

2016-05-13

Heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32-52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime-Apa-subunit-boost strategy compared to Apa-subunit-prime-BCG-boost approach. However, parenteral BCG-prime-Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime-boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime-boost regimens against tuberculosis in humans.

Sex-differential effects on mortality of BCG and diphtheria-tetanus-pertussis vaccines in a rural area with high vaccination coverage

DEFF Research Database (Denmark)

Aaby, Peter; Nielsen, Jens; Benn, Christine S

2016-01-01

and inactivated polio vaccine (DTP-IPV) with BCG. Subsequent doses of DTP-IPV were administered alone. We analysed mortality according to sex and number of doses of DTP-IPV vaccine. RESULTS: BCG and DTP-IPV1 simultaneously reduced mortality from 60/1000 person-years in unvaccinated girls to 35/1000 person...

Nonspecific effect of BCG vaccination at birth on early childhood infections

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Kjærgaard, Jesper; Birk, Nina Marie; Nissen, Thomas N

2016-01-01

BACKGROUND: Childhood infections are common and Bacillus Calmette-Guérin (BCG) vaccination at birth may prevent these via nonspecific effects. METHODS: A randomized, clinical multicenter trial. All women planning to give birth (n = 16,521) at the three study sites were invited during the recruitm......BACKGROUND: Childhood infections are common and Bacillus Calmette-Guérin (BCG) vaccination at birth may prevent these via nonspecific effects. METHODS: A randomized, clinical multicenter trial. All women planning to give birth (n = 16,521) at the three study sites were invited during...... during the first 3 mo....

BCG vaccination reduces risk of tuberculosis infection in vaccinated badgers and unvaccinated badger cubs.

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Stephen P Carter

Full Text Available Wildlife is a global source of endemic and emerging infectious diseases. The control of tuberculosis (TB in cattle in Britain and Ireland is hindered by persistent infection in wild badgers (Meles meles. Vaccination with Bacillus Calmette-Guérin (BCG has been shown to reduce the severity and progression of experimentally induced TB in captive badgers. Analysis of data from a four-year clinical field study, conducted at the social group level, suggested a similar, direct protective effect of BCG in a wild badger population. Here we present new evidence from the same study identifying both a direct beneficial effect of vaccination in individual badgers and an indirect protective effect in unvaccinated cubs. We show that intramuscular injection of BCG reduced by 76% (Odds ratio = 0.24, 95% confidence interval (CI 0.11-0.52 the risk of free-living vaccinated individuals testing positive to a diagnostic test combination to detect progressive infection. A more sensitive panel of tests for the detection of infection per se identified a reduction of 54% (Odds ratio = 0.46, 95% CI 0.26-0.88 in the risk of a positive result following vaccination. In addition, we show the risk of unvaccinated badger cubs, but not adults, testing positive to an even more sensitive panel of diagnostic tests decreased significantly as the proportion of vaccinated individuals in their social group increased (Odds ratio = 0.08, 95% CI 0.01-0.76; P = 0.03. When more than a third of their social group had been vaccinated, the risk to unvaccinated cubs was reduced by 79% (Odds ratio = 0.21, 95% CI 0.05-0.81; P = 0.02.

Immunological Links to Nonspecific Effects of DTwP and BCG Vaccines on Infant Mortality

DEFF Research Database (Denmark)

Claesson, Mogens Helweg

2011-01-01

females and males may have their lives saved each year by the nonspecific immunological benefits of Bacillus Calmette-Guerin (BCG) vaccination. From an immunological point of view, we hypothesise that the adverse effects of DTwP vaccine may occur because of the Th2-polarising effect of the aluminium...... phosphate adjuvant in the vaccine and because intramuscular administration of the vaccine may cause chronic inflammation at the site of injection. However, the Th1-polarising effect of BCG is likely to be beneficial. Sexual dimorphism affecting immune functions and vitamin A supplementation may influence...

Risk factors for delay in age-appropriate vaccinations among Gambian children.

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Odutola, Aderonke; Afolabi, Muhammed O; Ogundare, Ezra O; Lowe-Jallow, Yamu Ndow; Worwui, Archibald; Okebe, Joseph; Ota, Martin O

2015-08-28

Vaccination has been shown to reduce mortality and morbidity due to vaccine-preventable diseases. However, these diseases are still responsible for majority of childhood deaths worldwide especially in the developing countries. This may be due to low vaccine coverage or delay in receipt of age-appropriate vaccines. We studied the timeliness of routine vaccinations among children aged 12-59 months attending infant welfare clinics in semi-urban areas of The Gambia, a country with high vaccine coverage. A cross-sectional survey was conducted in four health centres in the Western Region of the Gambia. Vaccination dates were obtained from health cards and timeliness assessed based on the recommended age ranges for BCG (birth-8 weeks), Diphtheria-Pertussis-Tetanus (6 weeks-4 months; 10 weeks-5 months; 14 weeks-6 months) and measles vaccines (38 weeks-12 months). Risk factors for delay in age-appropriate vaccinations were determined using logistic regression. Analysis was limited to BCG, third dose of Diphtheria-Pertussis -Tetanus (DPT3) and measles vaccines. Vaccination records of 1154 children were studied. Overall, 63.3% (95 % CI 60.6-66.1%) of the children had a delay in the recommended time to receiving at least one of the studied vaccines. The proportion of children with delayed vaccinations increased from BCG [5.8% (95 % CI 4.5-7.0%)] to DPT3 [60.4% (95 % CI 57.9%-63.0%)] but was comparatively low for the measles vaccine [10.8% (95 % CI 9.1%-12.5%)]. Mothers of affected children gave reasons for the delay, and their profile correlated with type of occupation, place of birth and mode of transportation to the health facilities. Despite high vaccination coverage reported in The Gambia, a significant proportion of the children's vaccines were delayed for reasons related to health services as well as profile of mothers. These findings are likely to obtain in several countries and should be addressed by programme managers in order to improve and optimize the impact of the

Cytochemical and biological properties of Mycobacterium bovis BCG.

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Slosárek, M

1977-01-01

It was the aim of the present communication to find a simple test for a reliable discrimination of Mycobacterium bovis BCG from Mycobacterium tuberculosis. A total of 26 BCG strains, out of them 10 Czechoslovak strains (2 lyophilized cultures of BCG of different batch, 6 strains isolated from abscesses of children after BCG-vaccination and 2 strains from fatal cases after BCG-vaccination) and 16 strains obtained from foreign laboratories, were used. Of the tested characteristics a combination of 3 tests, sensitivity to 1 microgram of 2-thiophene carbonylhydrazide (TCH), activity of 3 acylamidases (urease, nicotinamidase and pyrazinamidase) and a quantitative nitrate test, was found to be most advantageous. The Czechoslovak strains of Mycobacterium bovis BCG were fully sensitive to TCH, of the 3 acylamidases mentioned above only urease was positive and nitrate was reduced only little or not at all. On the other hand, strains of Mycobacterium tuberculosis were always resistant to TCH, had positive urease, nicotinamidase and pyrazinamidase and reduced nitrate very intensively.

Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis.

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Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

2006-08-01

Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary Mycobacterium tuberculosis challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.

Non-clinical efficacy and safety of HyVac4:IC31 vaccine administered in a BCG prime-boost regimen.

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Skeiky, Yasir A W; Dietrich, Jes; Lasco, Todd M; Stagliano, Katherine; Dheenadhayalan, Veerabadran; Goetz, Margaret Ann; Cantarero, Luis; Basaraba, Randall J; Bang, Peter; Kromann, Ingrid; McMclain, J Bruce; Sadoff, Jerald C; Andersen, Peter

2010-01-22

Despite the extensive success with the introduction of M. bovis Bacille Calmette-Guérin (BCG), tuberculosis (TB) remains a major global epidemic infecting between 8 and 9 million people annually with an estimated 1.7 million deaths each year. However, because of its demonstrated effectiveness against some of the most severe forms of childhood TB, it is now realized that BCG vaccination of newborns is unlikely to be replaced. Therefore, BCG or an improved BCG will continue to be used as a prime TB vaccine and there is a need to develop effective boost vaccines that would enhance and prolong the protective immunity induced by BCG prime immunization. We report on a heterologous booster approach using two highly immunogenic TB antigens comprising Ag85B and TB10.4 (HyVac4) delivered as a fusion molecule and formulated in the proprietary adjuvant IC31. This vaccine was found to be immunogenic and demonstrated greater protection in the more stringent guinea pig model of pulmonary tuberculosis than BCG alone when used in a prime/boost regimen. Significant difference in lung involvement was observed for all animals in the HyVac4 boosted group compared to BCG alone regardless of time to death or sacrifice. A vaccine toxicology study of the HyVac4:IC31 regimen was performed and it was judged safe to advance the vaccine into clinical trials. Therefore, all non-clinical data supports the suitability of HyVac4 as a safe, immunogenic, and effective vaccination in a prime-boost regimen with BCG.

Effect of 50,000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial.

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Benn, Christine Stabell; Diness, Birgitte Rode; Roth, Adam; Nante, Ernesto; Fisker, Ane Baerent; Lisse, Ida Maria; Yazdanbakhsh, Maria; Whittle, Hilton; Rodrigues, Amabelia; Aaby, Peter

2008-06-21

To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality. Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering approximately 90,000 inhabitants. Participants 4345 infants due to receive BCG. Infants were randomised to 50,000 IU vitamin A or placebo and followed until age 12 months. Mortality rate ratios. 174 children died during follow-up (mortality=47/1000 person-years). Vitamin A supplementation was not significantly associated with mortality; the mortality rate ratio was 1.07 (95% confidence interval 0.79 to 1.44). The effect was 1.00 (0.65 to 1.56) during the first four months and 1.13 (0.75 to 1.68) from 4 to 12 months of age. The mortality rate ratio in boys was 0.84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration. Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African setting. Although little doubt exists that vitamin A supplementation reduces mortality in older children, a global recommendation of supplementation for all newborn infants may not contribute to better survival. Clinical trials NCT00168597.

Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

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Bacalhau, S; Freitas, C; Valente, R; Barata, D; Neves, C; Schäfer, K; Lubatschofski, A; Schulz, A; Farela Neves, J

2011-01-01

In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID) who developed disseminated BCG disease, highligh...

Lactococcus lactis carrying a DNA vaccine coding for the ESAT-6 antigen increases IL-17 cytokine secretion and boosts the BCG vaccine immune response.

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Pereira, V B; da Cunha, V P; Preisser, T M; Souza, B M; Turk, M Z; De Castro, C P; Azevedo, M S P; Miyoshi, A

2017-06-01

A regimen utilizing Bacille Calmette-Guerin (BCG) and another vaccine system as a booster may represent a promising strategy for the development of an efficient tuberculosis vaccine for adults. In a previous work, we confirmed the ability of Lactococcus lactis fibronectin-binding protein A (FnBPA+) (pValac:ESAT-6), a live mucosal DNA vaccine, to produce a specific immune response in mice after oral immunization. In this study, we examined the immunogenicity of this strain as a booster for the BCG vaccine in mice. After immunization, cytokine and immunoglobulin profiles were measured. The BCG prime L. lactis FnBPA+ (pValac:ESAT-6) boost group was the most responsive group, with a significant increase in splenic pro-inflammatory cytokines IL-17, IFN-γ, IL-6 and TNF-α compared with the negative control. Based on the results obtained here, we demonstrated that L. lactis FnBPA+ (pValac:ESAT-6) was able to increase the BCG vaccine general immune response. This work is of great scientific and social importance because it represents the first step towards the development of a booster to the BCG vaccine using L. lactis as a DNA delivery system. © 2017 The Society for Applied Microbiology.

Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

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Sílvia Bacalhau

2011-01-01

Full Text Available In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID who developed disseminated BCG disease, highlighting the specific strategies adopted.

BCG protects toddlers during a tuberculosis outbreak.

LENUS (Irish Health Repository)

Gaensbauer, J T

2009-05-01

In 2007, an outbreak of tuberculosis occurred in a toddler population attending two child care centres in Cork, Ireland. Of 268 children exposed, 18 were eventually diagnosed with active tuberculosis. We present the initial clinical and radiographic characteristics of the active disease group. Mantoux testing was positive in only 66% of cases. All cases were either pulmonary or involved hilar adenopathy on chest radiograph; there were no cases of disseminated disease or meningitis. 24% of the exposed children had been previously vaccinated with BCG, and no case of active disease was found in this group (p = 0.016), suggesting a profound protective effect of BCG in this population. Our experience provides evidence supporting a protective effect of BCG against pulmonary disease in young children.

Efficacy of oral BCG vaccination in protecting free-ranging cattle from natural infection by Mycobacterium bovis.

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Nugent, Graham; Yockney, Ivor J; Whitford, Jackie; Aldwell, Frank E; Buddle, Bryce M

2017-09-01

Vaccination of cattle against bovine tuberculosis could be a valuable control strategy, particularly in countries faced with intractable ongoing infection from a disease reservoir in wildlife. A field vaccination trial was undertaken in New Zealand. The trial included 1286 effectively free-ranging cattle stocked at low densities in a remote 7600ha area, with 55% of them vaccinated using Mycobacterium bovis BCG (Danish strain 1311). Vaccine was administered orally in all but 34 cases (where it was injected). After inclusion, cattle were exposed to natural sources of M. bovis infection in cattle and wildlife, most notably the brushtail possum (Trichosurus vulpecula). Cattle were slaughtered at 3-5 years of age and were inspected for tuberculous lesions, with mycobacteriological culture of key tissues from almost all animals. The prevalence of M. bovis infection was 4.8% among oral BCG vaccinates, significantly lower than the 11.9% in non-vaccinates. Vaccination appeared to both reduce the incidence of detectable infection, and to slow disease progression. Based on apparent annual incidence, the protective efficacy of oral BCG vaccine was 67.4% for preventing infection, and was higher in cattle slaughtered soon after vaccination. Skin-test reactivity to tuberculin was high in vaccinates re-tested 70days after vaccination but not in non-vaccinates, although reactor animals had minimal response in gamma-interferon blood tests. In re- tests conducted more than 12 months after vaccination, skin-test reactivity among vaccinates was much lower. These results indicate that oral BCG vaccination could be an effective tool for greatly reducing detectable infection in cattle. Copyright © 2017 Elsevier B.V. All rights reserved.

Activity in mice of recombinant BCG-EgG1Y162 vaccine for Echinococcus granulosus infection.

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Ma, Xiumin; Zhao, Hui; Zhang, Fengbo; Zhu, Yuejie; Peng, Shanshan; Ma, Haimei; Cao, Chunbao; Xin, Yan; Yimiti, Delixiati; Wen, Hao; Ding, Jianbing

2016-01-01

Cystic hydatid disease is a zoonotic parasitic disease caused by Echinococcus granulosus which is distributed worldwide. The disease is difficult to treat with surgery removal is the only cure treatment. In the high endemic areas, vaccination of humans is believed a way to protect communities from the disease. In this study we vaccinated BALB/c mice with rBCG-EgG1Y162, and then detected the level of IgG and IgE specifically against the recombinant protein by ELISA, rBCG-EgG1Y162 induced strong and specific cellular and humoral immune responses. In vitro study showed that rBCG-EgG1Y162 vaccine not only promote splenocytes proliferation but also active T cell. In addition, the rBCG-EgG1Y162 induced a protection in the mice against secondary infection of Echinococcus granulosus.

Prime-boost BCG vaccination with DNA vaccines based in β-defensin-2 and mycobacterial antigens ESAT6 or Ag85B improve protection in a tuberculosis experimental model.

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Cervantes-Villagrana, Alberto R; Hernández-Pando, Rogelio; Biragyn, Arya; Castañeda-Delgado, Julio; Bodogai, Monica; Martínez-Fierro, Margarita; Sada, Eduardo; Trujillo, Valentin; Enciso-Moreno, Antonio; Rivas-Santiago, Bruno

2013-01-11

The World Health Organization (WHO) has estimated that there are about 8 million new cases annually of active Tuberculosis (TB). Despite its irregular effectiveness (0-89%), the Bacillus Calmette-Guérin) BCG is the only vaccine available worldwide for prevention of TB; thus, the design is important of novel and more efficient vaccination strategies. Considering that β-defensin-2 is an antimicrobial peptide that induces dendritic cell maturation through the TLR-4 receptor and that both ESAT-6 and Ag85B are immunodominant mycobacterial antigens and efficient activators of the protective immune response, we constructed two DNA vaccines by the fusion of the gene encoding β-defensin-2 and antigens ESAT6 (pDE) and 85B (pDA). After confirming efficient local antigen expression that induced high and stable Interferon gamma (IFN-γ) production in intramuscular (i.m.) vaccinated Balb/c mice, groups of mice were vaccinated with DNA vaccines in a prime-boost regimen with BCG and with BCG alone, and 2 months later were challenged with the mild virulence reference strain H37Rv and the highly virulent clinical isolate LAM 5186. The level of protection was evaluated by survival, lung bacilli burdens, and extension of tissue damage (pneumonia). Vaccination with both DNA vaccines showed similar protection to that of BCG. After the challenge with the highly virulent Mycobacterium tuberculosis strain, animals that were prime-boosted with BCG and then boosted with both DNA vaccines showed significant higher survival and less tissue damage than mice vaccinated only with BCG. These results suggest that improvement of BCG vaccination, such as the prime-boost DNA vaccine, represents a more efficient vaccination scheme against TB. Copyright © 2012 Elsevier Ltd. All rights reserved.

Scar formation and tuberculin conversion following BCG vaccination in infants: A prospective cohort study

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Sara S Dhanawade

2015-01-01

Full Text Available Background: There is considerable variation in BCG scar failure rate on available data and correlation between BCG scar and tuberculin conversion remains controversial. Through this study we aimed to determine the scar failure rate and tuberculin conversion in term infants vaccinated with BCG within the first month. Materials and Methods: A prospective cohort study was conducted among 85 consecutive infants weighing >2 kg attending the immunization clinic of a medical college hospital. Fifteen subjects who could not complete the follow up were excluded. Total of 70 cases were analyzed. All babies were administered 0.1 ml of BCG and examined at 3 months (+1 week for scar. Tuberculin test was done with 5TU PPD. An induration of >5 mm was considered positive. Statistical analysis was done using Microsoft Excel and SPSS-22. Results: Out of the 70 infants, 41 (58.6% were males. Although majority (72.9% of infants were vaccinated within 7 days, only 18 (25.7% received BCG within 48 hours of birth. Sixty-four (91.4% had a visible scar at 12 weeks post vaccination representing a scar failure rate of 8.6%. Tuberculin test was positive in 50 (71.4%. The mean ± s.d. for scar and tuberculin skin test (TST reaction size was 4.93 ± 2.01 mm and 6.01 ± 3.22 mm, respectively. The association between scar formation and tuberculin positivity was highly significant (P < 0.001. There was significant correlation between scar size and TST size (r = 0.401, P = 0.001 Conclusions: Less than 10% of infants fail to develop a scar following BCG vaccination. There is good correlation between scar positivity and tuberculin conversion.

Distribution of 35S-labelled BCG after application to the camera oculi anterior of BCG vaccinated and non-vaccinated rabbits

International Nuclear Information System (INIS)

Luelf, U.

1976-01-01

After application of 35 S-labelled BCG to the camera oculi anterior of the rabbit, the escape pathways of germs and their quantitative and qualitative distribution in eyes and blood has been studied in BCG-vaccinated and non-vaccinated animals while varying the amount of germs applied. As criteria, 35 S concentration and the amount of 35 S in ocular sections and in the blood which can be identified by means of distributing germs under the chosen conditions, have been detected. After only 10 minutes, elimination of germs is to be seen, continuing for a period longer than the 2 hours of post-injection period observed. Relatively high 35 S concentrations indicate a long-term storage in the iris and in the ciliary body. The flow continues regularly but restrained via choroid and sclera into the blood. Flow velocity depends only within specific limits on the amount of germs injected into the anterior chamber. Under study conditions the flow mode via N.opticus and via lymphs is rather unimportant. The rest of the germs are distributed in the organism via blood vessels. A comparison of 35 S concentration in sections of both eyes shows germ enrichment in tissues with sufficient blood supply, particularly in the choroid. Differences in germ distribution in vaccinated and non-vaccinated animals are not to be seen in the 35 S distribution pattern. Neither higher nor lower germ doses indicate a stronger retention in the ocular sections of vaccinated animals. The necessity to complete this study by applying germ doses smaller than 1 mg (humidity weight) is stated pointing out technical difficulties involved while applying a test model. (orig.) [de

A Modified Bacillus Calmette-Guérin (BCG Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

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Douglas S. Kernodle

2013-01-01

Full Text Available Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.

The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles).

Science.gov (United States)

Chambers, Mark A; Aldwell, Frank; Williams, Gareth A; Palmer, Si; Gowtage, Sonya; Ashford, Roland; Dalley, Deanna J; Davé, Dipesh; Weyer, Ute; Salguero, Francisco J; Nunez, Alejandro; Nadian, Allan K; Crawshaw, Timothy; Corner, Leigh A L; Lesellier, Sandrine

2017-01-01

The European badger ( Meles meles ) is a reservoir host of Mycobacterium bovis and responsible for a proportion of the tuberculosis (TB) cases seen in cattle in the United Kingdom and Republic of Ireland. An injectable preparation of the bacillus Calmette-Guérin (BCG) vaccine is licensed for use in badgers in the UK and its use forms part of the bovine TB eradication plans of England and Wales. However, there are practical limitations to the widespread application of an injectable vaccine for badgers and a research priority is the development of an oral vaccine deliverable to badgers in bait. Previous studies reported the successful vaccination of badgers with oral preparations of 10 8 colony forming units (CFU) of both Pasteur and Danish strains of BCG contained within a lipid matrix composed of triglycerides of fatty acids. Protection against TB in these studies was expressed as a reduction in the number and apparent progression of visible lesions, and reductions in the bacterial load and dissemination of infection. To reduce the cost of an oral vaccine and reduce the potential for environmental contamination with BCG, it is necessary to define the minimal efficacious dose of oral BCG for badgers. The objectives of the two studies reported here were to compare the efficacy of BCG Danish strain in a lipid matrix with unformulated BCG given orally, and to evaluate the efficacy of BCG Danish in a lipid matrix at a 10-fold lower dose than previously evaluated in badgers. In the first study, both BCG unformulated and in a lipid matrix reduced the number and apparent progression of visible lesions and the dissemination of infection from the lung. In the second study, vaccination with BCG in the lipid matrix at a 10-fold lower dose produced a similar outcome, but with greater intra-group variability than seen with the higher dose in the first study. Further research is needed before we are able to recommend a final dose of BCG for oral vaccination of badgers against TB

Neonatal BCG has no effect on allergic sensitization and suspected food allergy until 13 months.

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Thøstesen, Lisbeth Marianne; Kjaer, Henrik Fomsgaard; Pihl, Gitte Thybo; Nissen, Thomas Nørrelykke; Birk, Nina Marie; Kjaergaard, Jesper; Jensen, Aksel Karl Georg; Aaby, Peter; Olesen, Annette Wind; Stensballe, Lone Graff; Jeppesen, Dorthe Lisbeth; Benn, Christine Stabell; Kofoed, Poul-Erik

2017-09-01

Vaccination with Bacillus Calmette-Guérin (BCG) is used in many countries as protection against tuberculosis. Studies have suggested that BCG may also have non-specific effects, reducing non-tuberculosis mortality, morbidity, and atopic manifestations. In this study, we evaluated the effect of neonatal BCG vaccination on allergic sensitization and suspected food allergy at 13 months of age. The Danish Calmette Study was conducted from 2012 to 2015 at three Danish hospitals. Within 7 days of birth, the 4262 newborns of 4184 included mothers were randomized 1:1 to BCG or to a no-intervention control group. Exclusion criteria were gestational age food allergy, resulting in a risk ratio comparing BCG-vaccinated children with control children of 0.91 (95% CI 0.71-1.16). Among 1370 blood samples, sensitization (Phadiatop Infant >0.35 kUA/L) was found in 55 of 743 (7.4%) children in the BCG group and 50 of 627 (8.0%) of the control group (risk ratio 0.94 [0.65-1.36]). In this randomized clinical trial, neonatal BCG had no significant effect on suspected food allergy or on sensitization at 13 months of age. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

BCG and Adverse Events in the Context of Leprosy

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Renate Richardus

2018-04-01

Full Text Available BackgroundNotwithstanding its beneficial immunoprophylactic outcomes regarding leprosy and childhood TB, BCG vaccination may cause adverse events, particularly of the skin. However, this local hyper-immune reactivity cannot be predicted before vaccination, nor is its association with protection against leprosy known. In this study we investigated the occurrence of adverse events after BCG (revaccination in contacts of leprosy patients and analyzed whether the concomitant systemic anti-mycobacterial immunity was associated with these skin manifestations.MethodsWithin a randomized controlled BCG vaccination trial in Bangladesh, 14,828 contacts of newly diagnosed leprosy patients received BCG vaccination between 2012 and 2017 and were examined for adverse events 8 to 12 weeks post-vaccination. From a selection of vaccinated contacts, venous blood was obtained at follow-up examination and stimulated with Mycobacterium leprae (M. leprae antigens in overnight whole-blood assays (WBA. M. leprae phenolic glycolipid-I-specific antibodies and 32 cytokines were determined in WBAs of 13 individuals with and 13 individuals without adverse events after vaccination.ResultsOut of the 14,828 contacts who received BCG vaccination, 50 (0.34% presented with adverse events, mainly (80% consisting of skin ulcers. Based on the presence of BCG scars, 30 of these contacts (60% had received BCG in this study as a booster vaccination. Similar to the pathological T-cell immunity observed for tuberculoid leprosy patients, contacts with adverse events at the site of BCG vaccination showed elevated IFN-γ levels in response to M. leprae-specific proteins in WBA. However, decreased levels of sCD40L in serum and GRO (CXCL1 in response to M. leprae simultaneously indicated less T-cell regulation in these individuals, potentially causing uncontrolled T-cell immunity damaging the skin.ConclusionSkin complications after BCG vaccination present surrogate markers for protective

Effect of 50,000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau

DEFF Research Database (Denmark)

Benn, Christine Stabell; Diness, Birgitte Rode; Roth, Adam

2008-01-01

OBJECTIVE: To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality. DESIGN: Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering...... approximately 90,000 inhabitants. Participants 4345 infants due to receive BCG. INTERVENTION: Infants were randomised to 50,000 IU vitamin A or placebo and followed until age 12 months. MAIN OUTCOME MEASURE: Mortality rate ratios. RESULTS: 174 children died during follow-up (mortality=47/1000 person......-years). Vitamin A supplementation was not significantly associated with mortality; the mortality rate ratio was 1.07 (95% confidence interval 0.79 to 1.44). The effect was 1.00 (0.65 to 1.56) during the first four months and 1.13 (0.75 to 1.68) from 4 to 12 months of age. The mortality rate ratio in boys was 0...

Field evaluation of the efficacy of Mycobacterium bovis BCG vaccine against tuberculosis in goats.

Science.gov (United States)

Vidal, Enric; Arrieta-Villegas, Claudia; Grasa, Miriam; Mercader, Irene; Domingo, Mariano; Pérez de Val, Bernat

2017-08-17

Control of animal tuberculosis (TB) through vaccination has emerged as a long-term strategy to complement test and slaughter control strategy. A pilot trial under field conditions was conducted in a goat herd with high TB prevalence to assess the efficacy of the Mycobacterium bovis BCG vaccine. Twenty-three goat kids vaccinated with BCG and other 22 unvaccinated control kids were euthanized at 18 months post-vaccination. Gross pathological and histopathological examination of target tissues was performed for detection of tuberculous lesions and assessment of vaccine efficacy. Mycobacterial culture and DNA detection were used to confirm Mycobacterium caprae infection. Vaccination significantly reduced the number of animals with TB lesions compared to unvaccinated controls (35% and 77%, respectively; P goats can significantly reduce the TB lesion rates in high disease exposure conditions, indicating that vaccination could contribute to the control of TB in domestic goats.

Neonatal BCG vaccination has no effect on recurrent wheeze in the first year of life

DEFF Research Database (Denmark)

Thøstesen, Lisbeth Marianne; Stensballe, Lone Graff; Pihl, Gitte Thybo

2017-01-01

Background: Recurrent wheeze (RW) is frequent in childhood. Studies have suggested that BCG vaccination can have nonspecific effects, reducing general nontuberculosis morbidity, including respiratory tract infections and atopic diseases. The mechanisms behind these nonspecific effects of BCG...

BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity

NARCIS (Netherlands)

Arts, Rob J W; Moorlag, Simone J C F M; Novakovic, Boris; Li, Yang; Wang, Shuang-Yin; Oosting, Marije; Kumar, Vinod; Xavier, Ramnik J; Wijmenga, Cisca; Joosten, Leo A B; Reusken, Chantal B E M; Benn, Christine S; Aaby, Peter; Koopmans, Marion P; Stunnenberg, Hendrik G; van Crevel, Reinout; Netea, Mihai G

2018-01-01

The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide

BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity

DEFF Research Database (Denmark)

Arts, Rob J W; Moorlag, Simone J C F M; Novakovic, Boris

2018-01-01

The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide ep...

The HyVac4 subunit vaccine efficiently boosts BCG-primed anti-mycobacterial protective immunity.

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Rolf Billeskov

Full Text Available BACKGROUND: The current vaccine against tuberculosis (TB, BCG, has failed to control TB worldwide and the protective efficacy is moreover limited to 10-15 years. A vaccine that could efficiently boost a BCG-induced immune response and thus prolong protective immunity would therefore have a significant impact on the global TB-burden. METHODS/FINDINGS: In the present study we show that the fusion protein HyVac4 (H4, consisting of the mycobacterial antigens Ag85B and TB10.4, given in the adjuvant IC31® or DDA/MPL effectively boosted and prolonged immunity induced by BCG, leading to improved protection against infection with virulent M. tuberculosis (M.tb. Increased protection correlated with an increased percentage of TB10.4 specific IFNγ/TNFα/IL-2 or TNFα/IL-2 producing CD4 T cells at the site of infection. Moreover, this vaccine strategy did not compromise the use of ESAT-6 as an accurate correlate of disease development/vaccine efficacy. Indeed both CD4 and CD8 ESAT-6 specific T cells showed significant correlation with bacterial levels. CONCLUSIONS/SIGNIFICANCE: H4-IC31® can efficiently boost BCG-primed immunity leading to an increased protective anti-M.tb immune response dominated by IFNγ/TNFα/IL-2 or TNFα/IL2 producing CD4 T cells. H4 in the CD4 T cell inducing adjuvant IC31® is presently in clinical trials.

How do parents make their decision about letting their child get a BCG vaccination?

DEFF Research Database (Denmark)

Thybo Pihl, Gitte; Ammentorp, Jette; Schmidt Jensen, Jane

Introduction: In a large prospective randomised clinical trial in Denmark we are testing the hypothesis that compared to non-BCG-vaccinated infants, infants who are BCG vaccinated at birth experience less hospitalisations, use less antibiotics, and develop less atopic disease in early childhood. My...... of illness and atopic diseases in their personal network and family to evaluate risk for their child to develop atopic diseases or get hospitalised. This lay epidemiologi forms the basis for their decision. Davison C, Frankel S, Davey Smith G. Inheriting heart trouble: the relevance of common-sense ideas...

Evolution and Strain Variation in BCG

KAUST Repository

Abdallah, Abdallah

2017-11-07

BCG vaccines were derived by in vitro passage, during the years 1908–1921, at the Pasteur Institute of Lille. Following the distribution of stocks of BCG to vaccine production laboratories around the world, it was only a few decades before different BCG producers recognized that there were variants of BCG, likely due to different passaging conditions in the different laboratories. This ultimately led to the lyophilization of stable BCG products in the 1950s and 1960s, but not before considerable evolution of the different BCG strains had taken place. The application of contemporary research methodologies has now revealed genomic, transcriptomic and proteomic differences between BCG strains. These molecular differences in part account for phenotypic differences in vitro between BCG strains, such as their variable secretion of antigenic proteins. Yet, the relevance of BCG variability for immunization policy remains elusive. In this chapter we present an overview of what is known about BCG evolution and its resulting strain variability, and provide some speculation as to the potential relevance for a vaccine given to over 100 million newborns each year.

Bacillus Calmette-Guérin vaccination at birth

DEFF Research Database (Denmark)

Kjærgaard, Jesper

2016-01-01

to unrelated pathogens. Immune changes have been implicated in changes in both child growth and child development and for that reason we also studied these outcomes. We randomized 4262 children at birth to receive BCG vaccination at birth or to a no-intervention control group. We had pre-specified subgroup...... analyses of child sex, prematurity, and maternal BCG vaccination. The statistical analysis plan was finalized prior to unblinding of the data. Follow-up for the outcomes reported in this thesis consisted of telephone interviews and clinical examination at age 3 and 13 months, as well as online......, there was no effect of BCG on either incidence of infections, growth, body composition or psychomotor development. A subgroup analysis of children of mothers who were BCG vaccinated showed a reduced incidence of infections from 0 to 3 months among BCG vaccinated children (incidence rate ratio = 0.62, CI: 0.39 to 0...

Immunological Links to Nonspecific Effects of DTwP and BCG Vaccines on Infant Mortality

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Mogens Helweg Claesson

2011-01-01

Full Text Available A number of mainly observational studies suggest that many African females below the age of one year die each year from the nonspecific effects of vaccination with diphtheria-tetanus toxoids and killed (whole-cell Bordetella pertussis (DTwP. In contrast, similar studies suggest that many African females and males may have their lives saved each year by the nonspecific immunological benefits of Bacillus Calmette-Guerin (BCG vaccination. From an immunological point of view, we hypothesise that the adverse effects of DTwP vaccine may occur because of the Th2-polarising effect of the aluminium phosphate adjuvant in the vaccine and because intramuscular administration of the vaccine may cause chronic inflammation at the site of injection. However, the Th1-polarising effect of BCG is likely to be beneficial. Sexual dimorphism affecting immune functions and vitamin A supplementation may influence both the deleterious and beneficial nonspecific effects of immunisation.

Effect of 50 000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial

DEFF Research Database (Denmark)

Diness, B.R.; Roth, A.; Nante, E.

2008-01-01

Objective To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality. Design Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering.......84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration. Conclusions Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African...

Neonatal BCG vaccination has no effect on recurrent wheeze in the first year of life

DEFF Research Database (Denmark)

Thøstesen, Lisbeth Marianne; Stensballe, Lone Graff; Pihl, Gitte Thybo

2017-01-01

Background: Recurrent wheeze (RW) is frequent in childhood. Studies have suggested that BCG vaccination can have nonspecific effects, reducing general nontuberculosis morbidity, including respiratory tract infections and atopic diseases. The mechanisms behind these nonspecific effects of BCG...... (relative risk, 1.07; 95% CI, 0.89-1.28). Supplementary analyses were made, including an analysis of baseline risk factors for development of RW. Conclusion: Neonatal BCG had no effect on the development of RW before 13 months of age....

Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

KAUST Repository

Abdallah, Abdallah

2015-10-21

Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains.

Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

KAUST Repository

Abdallah, Abdallah; Hill-Cawthorne, Grant A.; Otto, Thomas D.; Coll, Francesc; Guerra-Assunç ã o, José Afonso; Gao, Ge; Naeem, Raeece; Ansari, Hifzur Rahman; Malas, Tareq Majed Yasin; Adroub, Sabir; Verboom, Theo; Ummels, Roy; Zhang, Huoming; Panigrahi, Aswini Kumar; McNerney, Ruth; Brosch, Roland; Clark, Taane G.; Behr, Marcel A.; Bitter, Wilbert; Pain, Arnab

2015-01-01

Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains.

Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette-Guérin (BCG) vaccination

DEFF Research Database (Denmark)

Elias, D; Wolday, D; Akuffo, H

2001-01-01

The protective efficacy of BCG vaccination against pulmonary tuberculosis (TB) is highly variable in different populations. The reason remains to be elucidated. This study aims to investigate the possible effect of intestinal helminths on the immune response to PPD in naturally immunized or BCG......-vaccinated humans. The study population was assessed for helminthic infection and those found to be positive were randomly assigned to either an albendazole treatment group or a control group who received a placebo. The immune response to PPD was compared between the two groups. In addition, subjects who were...... tuberculin skin test-negative in both groups were BCG vaccinated and later on tested for PPD-specific responses. Albendazole induced elimination/or reduction in intestinal worms resulting in a significant improvement in T cell proliferation and in interferon-gamma production by peripheral blood mononuclear...

A single dose of a DNA vaccine encoding apa coencapsulated with 6,6'-trehalose dimycolate in microspheres confers long-term protection against tuberculosis in Mycobacterium bovis BCG-primed mice.

Science.gov (United States)

Carlétti, Dyego; Morais da Fonseca, Denise; Gembre, Ana Flávia; Masson, Ana Paula; Weijenborg Campos, Lívia; Leite, Luciana C C; Rodrigues Pires, Andréa; Lannes-Vieira, Joseli; Lopes Silva, Célio; Bonato, Vânia Luiza Deperon; Horn, Cynthia

2013-08-01

Mycobacterium bovis BCG prime DNA (Mycobacterium tuberculosis genes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted by M. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratracheal M. tuberculosis challenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carrying apa and 6,6'-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.

Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

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Ting-Yu Angela Liao

Full Text Available Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.

Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

Science.gov (United States)

Liao, Ting-Yu Angela; Lau, Alice; Joseph, Sunil; Hytönen, Vesa; Hmama, Zakaria

2015-01-01

Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb) antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.

Evolution and Strain Variation in BCG

KAUST Repository

Abdallah, Abdallah; Behr, Marcel A.

2017-01-01

BCG vaccines were derived by in vitro passage, during the years 1908–1921, at the Pasteur Institute of Lille. Following the distribution of stocks of BCG to vaccine production laboratories around the world, it was only a few decades before different

Development of Th1 Imprints to rBCG Expressing a Foreign Protein: Implications for Vaccination against HIV-1 and Diverse Influenza Strains

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Carl Power

2010-01-01

Full Text Available We demonstrate here that immunizing naïve mice with low numbers of recombinant Bacille Calmette-Guérin (rBCG expressing β-galactosidase (β-gal generates predominant Th1 responses to both BCG and β-gal whereas infection with high numbers generates a mixed Th1/Th2 response to both BCG and β-gal. Furthermore, the Th1 response to both BCG and β-gal is stable when mice, pre-exposed to low numbers of rBCG, are challenged four months later with high numbers of rBCG. Thus the Th1/Th2 phenotypes of the immune responses to β-gal and to BCG are “coherently” regulated. Such rBCG vectors, encoding antigens of pathogens preferentially susceptible to cell-mediated attack, may be useful in vaccinating against such pathogens. We discuss vaccination strategies employing rBCG vectors that are designed to provide protection against diverse influenza strains or numerous variants of HIV-1 and consider what further experiments are essential to explore the possibility of realizing such strategies.

Newborn Mice Vaccination with BCG.HIVA222 + MVA.HIVA Enhances HIV-1-Specific Immune Responses: Influence of Age and Immunization Routes

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Narcís Saubi

2011-01-01

Full Text Available We have evaluated the influence of age and immunization routes for induction of HIV-1- and M. tuberculosis-specific immune responses after neonatal (7 days old and adult (7 weeks old BALB/c mice immunization with BCG.HIVA222 prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8+ T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA222 compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA222 and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA222 to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine.

Newborn Mice Vaccination with BCG.HIVA222 + MVA.HIVA Enhances HIV-1-Specific Immune Responses: Influence of Age and Immunization Routes

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Saubi, Narcís; Im, Eung-Jun; Fernández-Lloris, Raquel; Gil, Olga; Cardona, Pere-Joan; Gatell, Josep Maria; Hanke, Tomáš; Joseph, Joan

2011-01-01

We have evaluated the influence of age and immunization routes for induction of HIV-1- and M. tuberculosis-specific immune responses after neonatal (7 days old) and adult (7 weeks old) BALB/c mice immunization with BCG.HIVA222 prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8+ T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA222 compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA222 and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA222 to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine. PMID:21603216

BCG: A throwback from the stone age of vaccines opened the path for bladder cancer immunotherapy.

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Morales, Alvaro

2017-06-01

It is 40 years since the initial documentation of the efficacy of bacille Calmette-Guérin (BCG) in the management of non-muscle invasive bladder cancer (NMIBC) and probably an opportune a time as any to retrace the origins of this development and to reflect on the progress that has occurred on the use of immune modifiers in the treatment of NMIBC. A PubMed search for publications on the history of BCG was conducted, and those related to the development of the vaccine for protection against tuberculosis as well as those published in the last 40 years related to its use for treatment for NMIBC were selected for review. A manual search was also carried out for recent articles on immunotherapy for NMIBC failing to respond to BCG. Publications were selected for their usefulness in exemplifying the development of BCG as an antineoplastic agent, elucidating its mechanisms of action of BCG or introducing significant modifications in treatment regimens resulting in enhancement of its efficacy. Alternative innovative immunotherapeutic approaches were chosen to illustrate current trends in the management of this disease. Well thought-out modifications of the original protocol resulted in enhanced efficacy of the vaccine, which currently ranks as the best-known and most-used and investigated agent for high risk NMIBC. Despite its efficacy, a considerable number (30%-40%) of these tumors fail to respond to BCG. In addition, as a live bacterium it carries the potential for serious adverse effects and some patients are unable to tolerate it. These shortcomings have created the need for new agents. These range from other mycobacteria and viruses to monoclonal antibodies alone or in combination with other agents currently at various stages of development. After 4 decades of use, BCG remains the most effective agent against high risk NMIBC, but it still holds substantial drawbacks. The enduring use of immunotherapy for NMIBC has created a propitious environment to search for better

Oral vaccination of white-tailed deer (Odocoileus virginianus with Mycobacterium bovis Bacillus Calmette-Guerin (BCG.

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Mitchell V Palmer

Full Text Available Wildlife reservoirs of Mycobacterium bovis represent serious obstacles to the eradication of tuberculosis from livestock, particularly cattle. In Michigan, USA tuberculous white-tailed deer transmit M. bovis to other deer and cattle. One approach in dealing with this wildlife reservoir is to vaccinate deer, thus interfering with the intraspecies and interspecies transmission cycles. Thirty-three white-tailed deer were assigned to one of two groups; oral vaccination with 1 × 10(8 colony-forming units of M. bovis BCG Danish (n = 17; and non-vaccinated (n = 16. One hundred eleven days after vaccination deer were infected intratonsilarly with 300 colony-forming units of virulent M. bovis. At examination, 150 days after challenge, BCG vaccinated deer had fewer gross and microscopic lesions, fewer tissues from which M. bovis could be isolated, and fewer late stage granulomas with extensive liquefactive necrosis. Fewer lesions, especially those of a highly necrotic nature should decrease the potential for dissemination of M. bovis within the host and transmission to other susceptible hosts.

Comparison of the immunogenicity and protection against bovine tuberculosis following immunization by BCG-priming and boosting with adenovirus or protein based vaccines.

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Dean, G; Whelan, A; Clifford, D; Salguero, F J; Xing, Z; Gilbert, S; McShane, H; Hewinson, R G; Vordermeier, M; Villarreal-Ramos, B

2014-03-05

There is a requirement for vaccines or vaccination strategies that confer better protection against TB than the current live attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine for use in cattle. Boosting with recombinant viral vectors expressing mycobacterial proteins, such as Ag85A, has shown a degree of promise as a strategy for improving on the protection afforded by BCG. Experiments in small animal models have indicated that broadening the immune response to include mycobacterial antigens other than Ag85A, such as Rv0288, induced by boosting with Ad5 constructs has a direct effect on the protection afforded against TB. Here, we compared the immunogenicity and protection against challenge with M. bovis afforded by boosting BCG-vaccinated cattle with a human type 5 (Ad5)-based vaccine expressing the mycobacterial antigens Ag85A (Ad5-85A); or Ag85A, Rv0251, Rv0287 and Rv0288 (Ad5-TBF); or with protein TBF emulsified in adjuvant (Adj-TBF). Boosting with TBF broaden the immune response. The kinetics of Ad5-TBF and Adj-TBF were shown to be different, with effector T cell responses from the latter developing more slowly but being more durable than those induced by Ad5-TBF. No increase in protection compared to BCG alone was afforded by Ad5-TBF or Adj-TBF by gross pathology or bacteriology. Using histopathology, as a novel parameter of protection, we show that boosting BCG vaccinated cattle with Ad5-85A induced significantly better protection than BCG alone. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Lipid-formulated bcg as an oral-bait vaccine for tuberculosis: vaccine stability, efficacy, and palatability to brushtail possums (Trichosurus vulpecula) in New Zealand.

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Cross, Martin L; Henderson, Ray J; Lambeth, Matthew R; Buddle, Bryce M; Aldwell, Frank E

2009-07-01

Bovine tuberculosis (Tb), due to infection with virulent Mycobacterium bovis, represents a threat to New Zealand agriculture due to vectorial transmission from wildlife reservoir species, principally the introduced Australian brushtail possum (Trichosurus vulpecula). An oral-delivery wildlife vaccine has been developed to immunize possums against Tb, based on formulation of the human Tb vaccine (M. bovis BCG) in edible lipid matrices. Here BCG bacilli were shown to be stable in lipid matrix formulation for over 8 mo in freezer storage, for 7 wk under room temperature conditions, and for 3-5 wk under field conditions in a forest/pasture margin habitat (when maintained in weatherproof bait-delivery sachets). Samples of the lipid matrix were flavored and offered to captive possums in a bait-preference study: a combination of 10% chocolate powder with anise oil was identified as the most effective attractant/palatability combination. In a replicated field study, 85-100% of wild possums were shown to access chocolate-flavored lipid pellets, when baits were applied to areas holding approximately 600-800 possums/km(2). Finally, in a controlled vaccination/challenge study, chocolate-flavored lipid vaccine samples containing 10(8) BCG bacilli were fed to captive possums, which were subsequently challenged via aerosol exposure to virulent M. bovis: vaccine immunogenicity was confirmed, and protection was identified by significantly reduced postchallenge weight loss in vaccinated animals compared to nonvaccinated controls. These studies indicate that, appropriately flavored, lipid delivery matrices may form effective bait vaccines for the control of Tb in wildlife.

Enhanced effect of BCG vaccine against pulmonary Mycobacterium tuberculosis infection in mice with lung Th17 response to mycobacterial heparin-binding hemagglutinin adhesin antigen.

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Fukui, Masayuki; Shinjo, Kikuko; Umemura, Masayuki; Shigeno, Satoko; Harakuni, Tetsuya; Arakawa, Takeshi; Matsuzaki, Goro

2015-12-01

Although the BCG vaccine can prevent tuberculosis (TB) in infants, its ability to prevent adult pulmonary TB is reportedly limited. Therefore, development of a novel effective vaccine against pulmonary TB has become an international research priority. We have previously reported that intranasal vaccination of mice with a mycobacterial heparin-binding hemagglutinin adhesin (HBHA) plus mucosal adjuvant cholera toxin (CT) enhances production of IFN-γ and anti-HBHA antibody and suppresses extrapulmonary bacterial dissemination after intranasal infection with BCG. In the present study, the effects of intranasal HBHA + CT vaccine on murine pulmonary Mycobacterium tuberculosis (Mtb) infection were examined. Intranasal HBHA + CT vaccination alone failed to reduce the bacterial burden in the infected lung. However, a combination vaccine consisting of s.c. BCG priming and an intranasal HBHA + CT booster significantly enhanced protective immunity against pulmonary Mtb infection on day 14 compared with BCG vaccine alone. Further, it was found that intranasal HBHA + CT vaccine enhanced not only IFN-γ but also IL-17A production by HBHA-specific T cells in the lung after pulmonary Mtb infection. Therefore, this combination vaccine may be a good candidate for a new vaccine strategy against pulmonary TB. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

The Type of Growth Medium Affects the Presence of a Mycobacterial Capsule and Is Associated With Differences in Protective Efficacy of BCG Vaccination Against Mycobacterium tuberculosis.

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Prados-Rosales, Rafael; Carreño, Leandro J; Weinrick, Brian; Batista-Gonzalez, Ana; Glatman-Freedman, Aarona; Xu, Jiayong; Chan, John; Jacobs, William R; Porcelli, Steven A; Casadevall, Arturo

2016-08-01

Bacillus Calmette-Guerin (BCG) vaccine is widely used for the prevention of tuberculosis, despite limited efficacy. Most immunological studies of BCG or Mycobacterium tuberculosis strains grow bacteria in the presence of detergent, which also strips the mycobacterial capsule. The impact of the capsule on vaccine efficacy has not been explored. We tested the influence of detergent in cultures of BCG and M. tuberculosis strains on the outcome of vaccination experiments on mice and transcriptional responses on M. tuberculosis  Vaccination of mice with encapsulated BCG promoted a more potent immune response relative to vaccination with unencapsulated BCG, including higher polysaccharide-specific capsule antibody titers, higher interferon γ and interleukin 17 splenic responses, and more multifunctional CD4(+) T cells. These differences correlated with variability in the bacterial burden in lung and spleen of mice infected with encapsulated or unencapsulated M. tuberculosis The combination of vaccination and challenge with encapsulated strains resulted in the greatest protection efficacy. The transcriptome of encapsulated M. tuberculosis was similar to that of starvation, hypoxia, stationary phase, or nonreplicating persistence. The presence of detergent in growth media and a capsule on BCG were associated with differences in the outcome of vaccination, implying that these are important variables in immunological studies. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Immunogenic Properties of a BCG Adjuvanted Chitosan Nanoparticle-Based Dengue Vaccine in Human Dendritic Cells.

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Taweewun Hunsawong

2015-09-01

Full Text Available Dengue viruses (DENVs are among the most rapidly and efficiently spreading arboviruses. WHO recently estimated that about half of the world's population is now at risk for DENV infection. There is no specific treatment or vaccine available to treat or prevent DENV infections. Here, we report the development of a novel dengue nanovaccine (DNV composed of UV-inactivated DENV-2 (UVI-DENV and Mycobacterium bovis Bacillus Calmette-Guerin cell wall components (BCG-CWCs loaded into chitosan nanoparticles (CS-NPs. CS-NPs were prepared by an emulsion polymerization method prior to loading of the BCG-CWCs and UVI-DENV components. Using a scanning electron microscope and a zetasizer, DNV was determined to be of spherical shape with a diameter of 372.0 ± 11.2 nm in average and cationic surface properties. The loading efficacies of BCG-CWCs and UVI-DENV into the CS-NPs and BCG-CS-NPs were up to 97.2 and 98.4%, respectively. THP-1 cellular uptake of UVI-DENV present in the DNV was higher than soluble UVI-DENV alone. DNV stimulation of immature dendritic cells (iDCs resulted in a significantly higher expression of DCs maturation markers (CD80, CD86 and HLA-DR and induction of various cytokine and chemokine productions than in UVI-DENV-treated iDCs, suggesting a potential use of BCG- CS-NPs as adjuvant and delivery system for dengue vaccines.

Molecular confirmation of Bacillus Calmette Guerin vaccine related adverse events among Saudi Arabian children.

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Sahal Al-Hajoj

Full Text Available Bacillus Calmette Guerin (BCG is the only available vaccine for tuberculosis (TB. Low grade complications in healthy recipients and disseminated vaccine associated complications among immuno-suppressed individuals were noticed globally after administration. Recently a series of clinically suspected BCG associated suppurative and non-suppurative lymphadenitis cases were reported from different regions of Saudi Arabia. However a molecular confirmative analysis was lacking to prove these claims.During 2009-2010, 42 Mycobacterium bovis BCG suspected clinical isolates from children diagnosed with suppurative lymphadenitis from different provinces of the country were collected and subjected to 24 loci based MIRU-VNTR typing, spoligotyping and first line anti-TB drugs susceptibility testing.Of the total 42 cases, 41 (97.6% were Saudi nationals and particularly male (64.3%. Majority of the cases were aged below 6 months (83.3% with a median of age 4 months. All the enrolled subjects showed left axillary mass which suppurated in a median of 4 months after vaccination. Among the study subjects, 1 (2.4% case was reactive to HIV antigen and 2 (4.8% case had severe combined immunodeficiency. Genotyping results showed that, 41 (97.6% isolates were identical to the vaccine strain Danish 1331 and one to Tokyo 172-1. Phylogenetic analysis revealed all the Danish 1331 isolates in a single cluster.Elevated proportion of suppurative lymphadenitis caused by M. bovis BCG reported in the country recently is majorly related to the vaccine strain Danish 1331. However lack of nationwide data on real magnitude of BCG related adverse events warrants population centric, long term future studies.

A safe and efficient BCG vectored vaccine to prevent the disease caused by the human Respiratory Syncytial Virus.

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Rey-Jurado, Emma; Soto, Jorge; Gálvez, Nicolás; Kalergis, Alexis M

2017-09-02

The human Respiratory Syncytial Virus (hRSV) causes lower respiratory tract infections including pneumonia and bronchiolitis. Such infections also cause a large number of hospitalizations and affects mainly newborns, young children and the elderly worldwide. Symptoms associated with hRSV infection are due to an exacerbated immune response characterized by low levels of IFN-γ, recruitment of neutrophils and eosinophils to the site of infection and lung damage. Although hRSV is a major health problem, no vaccines are currently available. Different immunization approaches have been developed to achieve a vaccine that activates the immune system, without triggering an unbalanced inflammation. These approaches include live attenuated vaccine, DNA or proteins technologies, and the use of vectors to express proteins of the virus. In this review, we discuss the host immune response to hRSV and the immunological mechanisms underlying an effective and safe BCG vectored vaccine against hRSV.

The effect of neonatal BCG vaccination on atopy and asthma at age 7 to 14 years: an historical cohort study in a community with a very low prevalence of tuberculosis infection and a high prevalence of atopic disease.

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Marks, Guy B; Ng, Kitty; Zhou, Jie; Toelle, Brett G; Xuan, Wei; Belousova, Elena G; Britton, Warwick J

2003-03-01

There are conflicting reports on the effect of BCG vaccination on the subsequent development of atopy and asthma. There are no data on the effects of neonatal BCG vaccination on cytokine responses of lymphocytes that are exposed in vitro to allergens. We sought to test the hypothesis that neonatal BCG vaccination or, alternatively, evidence of an immunologic memory of this vaccination is associated with a reduced prevalence of allergic sensitization, asthma, eczema, and hay fever during childhood. An historical cohort study was conducted among 7- to 14-year-old children who were born in 2 districts in Sydney, Australia, and whose mothers were born in southeast Asia. One district had routinely administered BCG vaccination to infants born to overseas-born mothers and the other had not. Eligible subjects were identified from birth registers. Consenting subjects completed questionnaires, performed spirometric and airway hyperresponsiveness testing, and had allergen skin prick testing and tuberculin skin testing. Blood was collected to measure total serum IgE levels and for in vitro lymphocyte culture in the presence of an extract of house dust mite, the dominant allergen in this region, and purified protein derivative of Mycobacterium tuberculosis (tuberculin). IL-4, IL-5, IL-10, and IFN-gamma were measured in the culture supernatant. The cohort included 309 BCG-vaccinated subjects and 442 non-BCG-vaccinated subjects. BCG-vaccinated subjects did not have a lower rate of allergic sensitization than nonvaccinated subjects. However, among the subgroup of subjects with a family history of rhinitis or eczema, BCG vaccination was associated with a lower prevalence of current asthma (defined as recent wheezing plus airway hyperresponsiveness; relative risk, 0.46; 95% CI, 0.22-0.95). BCG vaccination was also associated with lower levels of allergen-stimulated IL-10 production in vitro. Among the BCG-vaccinated subjects, the 44 (14.3%) who had tuberculin skin test reaction

Listeria-vectored vaccine expressing the Mycobacterium tuberculosis 30 kDa major secretory protein via the constitutively active prfA* regulon boosts BCG efficacy against tuberculosis.

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Jia, Qingmei; Dillon, Barbara Jane; Masleša-Galić, Saša; Horwitz, Marcus A

2017-06-19

A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective BCG vaccine. Here we investigate novel live attenuated recombinant Listeria monocytogenes (rLm) vaccines expressing the Mycobacterium tuberculosis (Mtb) 30 kDa major secretory protein (r30/Ag85B) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated Lm vectors, rLm Δ actA (LmI), rLm Δ actA Δ inlB (LmII), and rLm Δ actA Δ inlB prfA * (LmIII), we constructed five rLm30 vaccine candidates expressing the r30 linked in-frame to the Lm Listeriolycin O signal sequence and driven by the hly promoter (h30) or linked in-frame to the ActA N-terminus and driven by the actA promoter (a30). All five rLm30 vaccines secreted r30 in broth and macrophages; while rLm expressing r30 via a constitutively active prfA * regulon (rLmIII/a30) expressed the greatest amount of r30 in broth culture, all five rLm vaccines expressed equivalent amounts of r30 in infected macrophages. In comparative studies, boosting BCG-immunized mice with rLmIII/a30 induced the strongest antigen-specific T-cell responses, including splenic and lung polyfunctional CD4+ T-cells expressing the three cytokines of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) ( P vaccines were generally more potent booster vaccines than r30 in adjuvant and a recombinant adenovirus vaccine expressing r30. In a setting in which BCG alone was highly immunoprotective, boosting mice with rLmIII/a30, the most potent of the vaccines, significantly enhanced protection against aerosolized Mtb ( P <0.01). Copyright © 2017 American Society for Microbiology.

Low birth weight infants and Calmette-Guérin bacillus vaccination at birth

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Roth, Adam Anders Edvin; Jensen, Henrik; Garly, May-Lill

2004-01-01

In developing countries, low birth weight (LBW) children are often not vaccinated with Calmette-Guérin bacillus (BCG) at birth. Recent studies have suggested that BCG may have a nonspecific beneficial effect on infant mortality. We evaluated the consequences of not vaccinating LBW children at birth...

Coverage of childhood vaccination among children aged 12-23 months, Tamil Nadu, 2015, India.

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Murhekar, Manoj V; Kamaraj, P; Kanagasabai, K; Elavarasu, G; Rajasekar, T Daniel; Boopathi, K; Mehendale, Sanjay

2017-03-01

District-Level Household Survey-4 (DLHS-4) indicated that during 2012-2013, only 56 per cent of children aged 12-23 months in Tamil Nadu were fully vaccinated, which were lesser than those reported in earlier national surveys. We, therefore, conducted cluster surveys to estimate coverage of childhood vaccination in the State, and also to identify the factors associated with low coverage. Cross-sectional surveys were conducted in 15 strata [municipal corporation non-slum (n=1), municipal corporation slum (n=1), hilly (n=1), rural (n=6) and urban (n=6)]. From each stratum, 30 clusters were selected using probability proportional to the population size linear systematic sampling; seven children aged 12-23 months were selected from each cluster and their mothers/care-takers were interviewed to collect information about vaccination status of the child. A child was considered fully vaccinated if he/she received bacillus Calmette-Guérin (BCG), three doses of pentavalent, three doses of oral polio vaccine and one dose of measles vaccine, and appropriately vaccinated if all vaccine doses were given at right age and with right interval. Further, coverage of fully vaccinated children (FVC) as per vaccination cards or mothers' recall, validated coverage of FVC (V-FVC) among those having cards, and coverage of appropriately vaccinated children (AVC) were estimated using survey data analysis module with appropriate sampling weights. A total of 3150 children were surveyed, of them 2528 (80.3%) had vaccination card. The weighted coverage of FVC, V-FVC and AVC in the State was 79.9 per cent [95% confidence interval (CI): 78.2-81.5], 78.8 per cent (95% CI: 76.9-80.5) and 69.7 per cent (95% CI: 67.7-71.7), respectively. The coverage of individual vaccine ranged between 84 per cent (measles) and 99.8 per cent (BCG). About 12 per cent V-FVC were not vaccinated as per the vaccination schedule. The coverage of FVC in Tamil Nadu was high, with about 80 per cent children completing

Bacillus Calmette-Guérin (BCG) vaccine: A global assessment of demand and supply balance.

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Cernuschi, Tania; Malvolti, Stefano; Nickels, Emily; Friede, Martin

2018-01-25

Over the past decade, several countries across all regions, income groups and procurement methods have been unable to secure sufficient BCG vaccine supply. While the frequency of stock-outs has remained rather stable, duration increased in 2014-2015 due to manufacturing issues and attracted the attention of national, regional and global immunization stakeholders. This prompted an in-depth analysis of supply and demand dynamics aiming to characterize supply risks. This analysis is unique as it provides a global picture, where previous analyses have focused on a portion of the market procuring through UN entities. Through literature review, supplier interviews, appraisal of shortages, stock-outs and historical procurement data, and through demand forecasting, this analysis shows an important increase in global capacity in 2017: supply is sufficient to meet forecasted BCG vaccine demand and possibly buffer market shocks. Nevertheless, risks remain mainly due to supply concentration and limited investment in production process improvements, as well as inflexibility in demand. Identification of these market risks will allow implementation of risk-mitigating interventions in three areas: (1) enhancing information sharing between major global health actors, countries and suppliers, (2) identifying interests and incentives to expand product registration and investment in the BCG manufacturing process, and (3) working with countries for tighter vaccine management. Copyright © 2017. Published by Elsevier Ltd.

Coley's toxin and BCG vaccine in prevention and treatment of malignant melanoma in humans

Czech Academy of Sciences Publication Activity Database

Kučerová, Petra; Vlasáková, Jitka; Červinková, Monika

2017-01-01

Roč. 28, č. 3 (2017), s. 124-128 ISSN 0954-139X R&D Projects: GA MŠk(CZ) LO1609 Institutional support: RVO:67985904 Keywords : BCG vaccine * Coley´s toxin * cytokines Subject RIV: EC - Immunology OBOR OECD: Immunology

Long-Lasting Effects of BCG Vaccination on Both Heterologous Th1/Th17 Responses and Innate Trained Immunity

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Kleinnijenhuis, Johanneke; Quintin, Jessica; Preijers, Frank

2013-01-01

'. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination. The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months...... in proinflammatory cytokine production after stimulation with the TLR4 ligand lipopolysaccharide. The heterologous production of Th1 (IFN-γ) and Th17 (IL-17 and IL-22) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination. In conclusion, BCG induces sustained...... changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses. © 2013 S. Karger AG, Basel....

Comparison of Tuberculin Skin Test result and interferon gamma response to human PPD in BCG scar positive and negative children.

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Sayyahfar, Shirin; Karimi, Abdollah; Fahimzad, Alireza; Shamshiri, Ahmad Reza

2014-03-01

The aim of this study is to compare Tuberculin Skin Test (TST) result and interferon gamma response to human PPD (purified protein derivative), in scar positive and scar negative BCG-vaccinated children. Between August 2007 and May 2008 a total of 236 children aged 1-168 months (mean 21 months) admitted to Mofid Children's Hospital, Tehran, Iran, were enrolled in a cross-sectional study. Each patient was examined for BCG vaccine scar and tested with TST and human PPD-based Interferon Gamma Release Assay (IGRA). Two hundred and twenty one cases out of 236 (44% female, 1-168 months, mean age 21 months) were scar positive of whom 95% TST result was negative. Human PPD-based IGRA was positive in 110 (49.8%), negative in 85 (38.4 %) and indeterminate in 26 (11.8%) of scar positive patients. Fifteen children (40% female, 1-156 months; mean age 42 months) were scar negative. All the scar negative cases were TST negative. Human PPD-based IGRA was positive in 10 (66.7%), negative in 4 (26.7%) and indeterminate in 1 (6.7%) of scar negative patients. Immune responsiveness to human PPD antigens in scar positive and negative children may not correspond with results of the Tuberculin Skin Test. Copyright © 2013 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

An oral Mycobacterium bovis BCG vaccine for wildlife produced in the absence of animal-derived reagents.

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Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

2009-09-01

Cultures of Mycobacterium bovis BCG, comprising predominantly single-cell bacilli, were prepared in broth without animal-derived reagents. When formulated into a vegetable-derived lipid matrix, the vaccine was stable in vitro and was immunogenic in vivo upon feeding it to mice. This formulation could be useful for oral vaccination of wildlife against tuberculosis, where concern over transmissible prions may preclude the field use of vaccines containing animal products.

The effect of current Schistosoma mansoni infection on the immunogenicity of a candidate TB vaccine, MVA85A, in BCG-vaccinated adolescents: An open-label trial.

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Anne Wajja

2017-05-01

Full Text Available Helminth infection may affect vaccine immunogenicity and efficacy. Adolescents, a target population for tuberculosis booster vaccines, often have a high helminth burden. We investigated effects of Schistosoma mansoni (Sm on the immunogenicity and safety of MVA85A, a model candidate tuberculosis vaccine, in BCG-vaccinated Ugandan adolescents.In this phase II open label trial we enrolled 36 healthy, previously BCG-vaccinated adolescents, 18 with no helminth infection detected, 18 with Sm only. The primary outcome was immunogenicity measured by Ag85A-specific interferon gamma ELISpot assay. Tuberculosis and schistosome-specific responses were also assessed by whole-blood stimulation and multiplex cytokine assay, and by antibody ELISAs.Ag85A-specific cellular responses increased significantly following immunisation but with no differences between the two groups. Sm infection was associated with higher pre-immunisation Ag85A-specific IgG4 but with no change in antibody levels following immunisation. There were no serious adverse events. Most reactogenicity events were of mild or moderate severity and resolved quickly.The significant Ag85A-specific T cell responses and lack of difference between Sm-infected and uninfected participants is encouraging for tuberculosis vaccine development. The implications of pre-existing Ag85A-specific IgG4 antibodies for protective immunity against tuberculosis among those infected with Sm are not known. MVA85A was safe in this population.ClinicalTrials.gov NCT02178748.

Vaccination status and sequence of vaccinations as risk factors for hospitalisation among outpatients in a high mortality country.

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Biai, Sidu; Rodrigues, Amabelia; Nielsen, Jens; Sodemann, Morten; Aaby, Peter

2011-05-09

Most developing countries are implementing the WHO immunisation programme. Although vaccines reach most children, many modifications of the recommended schedule are observed in practice. We investigated the association between vaccination status and risk of hospitalisation in Guinea-Bissau. From May 2003 to May 2004, all consultations of children less than five years of age at the outpatient clinic of the paediatric ward at the national hospital in Bissau were registered. For each consultation, information was collected about the child's name, sex, age and socio-cultural conditions, as well as diagnosis and whether the child was hospitalised. Information about vaccinations was also registered from the child's vaccination card. We analysed the association between vaccination status and risk of hospitalisation in age intervals according to the pre-dominant vaccines. We particularly emphasised the comparison of those who had received the recommended vaccination for the age groups and those who were delayed and only had the previous vaccinations. We also examined those who had received the vaccines out of sequence. Information about vaccinations was available for 11,949 outpatient children of whom 2219 (19%) were hospitalised. Among children less than 3 months of age, unvaccinated children compared to BCG children had as expected a higher risk of hospitalisation; controlled for important determinants of hospitalisation, the hospitalisation risk ratio (HRR) was 1.99 (95% CI 1.37-2.89). In contrast, there was no difference in the HRR for children aged 1½-8 months who were delayed and had only received BCG compared to those who as recommended had received diphtheria-tetanus-pertussis (DTP) vaccine after BCG (HRR=1.10 (0.77-1.59)). In the age interval 9-17 months of age, children who were delayed and had only received DTP had significantly higher risk of hospitalisation compared with children who as recommended had measles vaccine (MV) as the most recent vaccination (HRR

Interruption of persistent exposure to leprosy combined or not with recent BCG vaccination enhances the response to Mycobacterium leprae specific antigens.

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de Carvalho, Fernanda Marques; Rodrigues, Luciana Silva; Duppre, Nádia Cristina; Alvim, Iris Maria Peixoto; Ribeiro-Alves, Marcelo; Pinheiro, Roberta Olmo; Sarno, Euzenir Nunes; Pessolani, Maria Cristina Vidal; Pereira, Geraldo Moura Batista

2017-05-01

Household contacts of multibacillary leprosy patients (HCMB) constitute the group of individuals at the highest risk of developing leprosy. Early diagnosis and treatment of their index cases combined with Bacille Calmette-Guerin (BCG) immunization remain important strategies adopted in Brazil to prevent HCMB from evolving into active disease. In the present study, we assessed the impact of these measures on the immune response to Mycobacterium leprae in HCMB. Peripheral blood mononuclear cells (PBMC) from HCMB (n = 16) were obtained at the beginning of leprosy index case treatment (T0). At this time point, contacts were vaccinated (n = 13) or not (n = 3) in accordance with their infancy history of BCG vaccination and PBMCs were recollected at least 6 months later (T1). As expected, a significant increase in memory CD4 and CD8 T cell frequencies responsive to M. leprae whole-cell sonicate was observed in most contacts. Of note, higher frequencies of CD4+ T cells that recognize M. leprae specific epitopes were also detected. Moreover, increased production of the inflammatory mediators IL1-β, IL-6, IL-17, TNF, IFN-γ, MIP1-β, and MCP-1 was found at T1. Interestingly, the increment in these parameters was observed even in those contacts that were not BCG vaccinated at T0. This result reinforces the hypothesis that the continuous exposure of HCMB to live M. leprae down regulates the specific cellular immune response against the pathogen. Moreover, our data suggest that BCG vaccination of HCMB induces activation of T cell clones, likely through "trained immunity", that recognize M. leprae specific antigens not shared with BCG as an additional protective mechanism besides the expected boost in cell-mediated immunity by BCG homologues of M. leprae antigens.

Reducing the activity and secretion of microbial antioxidants enhances the immunogenicity of BCG.

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Shanmugalakshmi Sadagopal

Full Text Available In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB. Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production.To determine whether microbial antioxidants influence vaccine immunogenicity, we eliminated duplicated alleles encoding the oxidative stress sigma factor SigH in BCG Tice and reduced the activity and secretion of iron co-factored superoxide dismutase. We then used assays of gene expression and flow cytometry with intracellular cytokine staining to compare BCG-specific immune responses in mice after vaccination with BCG Tice or the modified BCG vaccine. Compared to BCG, the modified vaccine induced greater IL-12p40, RANTES, and IL-21 mRNA in the spleens of mice at three days post-immunization, more cytokine-producing CD8+ lymphocytes at the peak of the primary immune response, and more IL-2-producing CD4+ lymphocytes during the memory phase. The modified vaccine also induced stronger secondary CD4+ lymphocyte responses and greater clearance of challenge bacilli.We conclude that antioxidants produced by BCG suppress host immune responses. These findings challenge the hypothesis that the failure of extensively cultivated BCG vaccines to prevent pulmonary tuberculosis is due to over-attenuation and suggest instead a new model in which BCG evolved to produce more immunity-suppressing antioxidants. By targeting these antioxidants it may be possible to restore BCG's ability to protect against pulmonary TB.

BCG-vaccination of newborns – a descriptive study about shared decision making and decisional conflicts

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Thybo Pihl, Gitte

BCG-vaccination of newborns – a descriptive study about shared decision making and decisional conflicts Objective: To evaluate the use of shared decision making to support the parent in a low-evidence decision about a vaccine when using telephone consultations. The present study was conducted........ The principles included promoting trust through transparency and creating “shared minds” regarding uncertainties about the evidence. O’Connor’s Decisional Conflict Scale was used to identify decisional conflicts after the process of shared decision making. Findings: A decisional conflict score was obtained...... on the phone based on their need and wishes, this uncertainty about the best choice might reflect the principle of letting parents make an autonomous decision in combination with low evidence for the benefits of BCG. The process of sharing responsibility and the impact of the health care providers’ attitude...

Tuberculin Skin Test and Quantiferon in BCG Vaccinated, Immunosuppressed Patients with Moderate-to-Severe Inflammatory Bowel Disease.

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Kurti, Zsuzsanna; Lovasz, Barbara Dorottya; Gecse, Krisztina Barbara; Balint, Anita; Farkas, Klaudia; Morocza-Szabo, Agnes; Gyurcsanyi, Andras; Kristof, Katalin; Vegh, Zsuzsanna; Gonczi, Lorant; Kiss, Lajos Sandor; Golovics, Petra Anna; Lakatos, Laszlo; Molnar, Tamas; Lakatos, Peter Laszlo

2015-12-01

There are few data available on the effect of immunomodulator/biological therapy on the accuracy of the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in BCG-vaccinated immunosuppressed patients with inflammatory bowel disease (IBD). Our aim was to define the accuracy, predictors and agreement of TST and IGRA in a BCG-vaccinated immunosuppressed referral IBD cohort. 166 consecutive moderate-to-severe IBD patients (122 Crohn's disease, CD and 44 ulcerative colitis, UC) were enrolled in a prospective study from three centers. Patients were treated with immunosuppressives and/or biologicals. IGRA and TST were performed on the same day. Both in- and outpatient records were collected and comprehensively reviewed. TST positivity rate was 23.5%, 21.1%,14.5% and 13.9% when cut-off values of 5, 10, 15 and 20mm were used. IGRA positivity rate was 8.4% with indeterminate result in 0.6%. Chest X-ray was suggestive of latent tuberculosis in 2 patients. Correlation between TST and IGRA was moderate (kappa: 0.39-0.41, p15mm) should be considered to identify patients at risk for latent TB. Accuracy is satisfactory in BCG-vaccinated, immunosuppressed IBD patients. Smoking is a risk factor for TST positivity.

The immunological effect of revaccination with Bacille Calmette-Guérin vaccine at 19 months of age

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Andersen, Andreas; Roth, Adam; Jensen, Kristoffer Jarlov

2013-01-01

Bacille Calmette-Guérin (BCG) vaccination has important non-specific immune effects. In a randomized trial in Guinea-Bissau, BCG revaccination was associated with significantly increased survival in children who received diphtheria-tetanus-pertussis (DTP)-booster vaccine before enrolment and in c...... and in children who did not receive micronutrient supplementation (MN). Within the trial we assessed the immunological effects of BCG revaccination....

Characterization of immune response to killed leishmania major promastigotes plus BCG vaccine in Sudanese volunteers: a double-blind placebo controlled study

International Nuclear Information System (INIS)

Sati, Iman Nasr Eldin

1996-12-01

This work was examined whether intradermal immunization of healthy adult Sudanese volunteers with killed leishmania major (KLM) promastigotes plus BCG would induce antigen-specific T cell responses. Only healthy Sudanese volunteers with negative reactivity to leishmania skin test and with ≤20 mm induration of reactivity to purified protein derivative (PPD) were included in the trial. Group (A) (n=3): received a single dose (0.1ml) at a concentration of 10 mg protein of a whole cell component of KLM promastigotes/ml BCG, group (B) (n=12): received as a single dose of viable attenuated BCG alone (0.1 ml) at a concentration of 1 mg protein/ml diluent, group (C) (n=11): received the vaccine diluent only (Placebo) (o.1 ml). Study subjects were tested for their immunological and clinical responses before intervention, . Following vaccination 65% of group (A) subjects converted in their reactivity to leishmanin skin testing,non of the BCG vaccinated subjects converted in leishmanin skin test and only one subject of group (C) became leishmanin positive. Levels of Interferon-gamma (IFN-γ), interleukin-5 (IL-5) and interleukin-10 (IL-10) were measured by a double sandwich enzyme-linked immunosorbent assay (ELISA). A vaccine was considered as a positive responder in terms of cytokine production when the level of the produced cytokine was equal to the 80th percentile of the levels produced by the volunteers in the placebo group. 92% of the group vaccinated with KLM=BCG had circulating T cells. No significant of IL-5 or Il-10 was reported in any of the volunteers in the three group. Levels of anti l eishmania specific IgG were measured by ELISA in optical densities. Volunteers with mean antibody titre above the cut-off point (mean=3X standard deviation) were considered to have positive scores. Accordingly after vaccination 7.69% one volunteers in group (A) had a positive antibody response corresponding to 0% in the other two groups. No serious side effects were reported

Bacillus Calmette-Guérin vaccination at birth: Effects on early childhood infections, growth, and development.

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Kjærgaard, Jesper

2016-11-01

The Bacillus Calmette-Guérin vaccine (BCG), which is used to protect against tuberculosis, has been associated with a variety of other effects since it was developed almost 100 years ago. Most notably, observational studies and randomized clinical trials from low-income countries indicate that it protects against unrelated infections, i.e. a so-called non-specific effect. The Danish Calmette Study was conducted to study these effects in a high-income population. The immune response to BCG is not fully understood but involves a pro-inflammatory profiling of the immune system, also when exposed to unrelated pathogens. Immune changes have been implicated in changes in both child growth and child development and for that reason we also studied these outcomes. We randomized 4262 children at birth to receive BCG vaccination at birth or to a no-intervention control group. We had pre-specified subgroup analyses of child sex, prematurity, and maternal BCG vaccination. The statistical analysis plan was finalized prior to unblinding of the data. Follow-up for the outcomes reported in this thesis consisted of telephone interviews and clinical examination at age 3 and 13 months, as well as online developmental questionnaires distributed to the parents at 12 months and additionally to the parents of premature children at age 6 and 22 months. The outcomes of this thesis were number of parent reported infections, child growth and body composition, and child psychomotor development. Overall, there was no effect of BCG on either incidence of infections, growth, body composition or psychomotor development. A subgroup analysis of children of mothers who were BCG vaccinated showed a reduced incidence of infections from 0 to 3 months among BCG vaccinated children (incidence rate ratio = 0.62, CI: 0.39 to 0.98), but there was no effect from 3 to 13 months. Previous research has shown that maternal exposure to BCG or mycobacteria can alter the effect of BCG in the offspring, and thus the

Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis

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Bhowmick Sudipta

2010-06-01

Full Text Available Abstract Background The development of an effective vaccine against visceral leishmaniasis (VL caused by Leishmania donovani is an essential aim for controlling the disease. Use of the right adjuvant is of fundamental importance in vaccine formulations for generation of effective cell-mediated immune response. Earlier we reported the protective efficacy of cationic liposome-associated L. donovani promastigote antigens (LAg against experimental VL. The aim of the present study was to compare the effectiveness of two very promising adjuvants, Bacille Calmette-Guerin (BCG and Monophosphoryl lipid A (MPL plus trehalose dicorynomycolate (TDM with cationic liposomes, in combination with LAg, to confer protection against murine VL. Results All the three formulations afforded significant protection against L. donovani in both the visceral organs, liver and spleen. Although comparable level of protection was observed in BCG+LAg and MPL-TDM+LAg immunized mice, highest level of protection was exhibited by the liposomal LAg immunized group. Significant increase in anti-LAg IgG levels were detected in both MPL-TDM+LAg and liposomal LAg immunized animals with higher levels of IgG2a than IgG1. But BCG+LAg failed to induce any antibody response. As an index of cell-mediated immunity DTH responses were measured and significant response was observed in mice vaccinated with all the three different formulations. However, highest responses were observed with liposomal vaccine immunization. Comparative evaluation of IFN-γ and IL-4 responses in immunized mice revealed that MPL-TDM+LAg group produced the highest level of IFN-γ but lowest IL-4 level, while BCG+LAg demonstrated generation of suboptimum levels of both IFN-γ and IL-4 response. Elicitation of moderate levels of prechallenge IFN-γ along with optimum IL-4 corresponds with successful vaccination with liposomal LAg. Conclusion This comparative study reveals greater effectiveness of the liposomal vaccine for

The effect of high-dose vitamin A supplementation administered with BCG vaccine at birth may be modified by subsequent DTP vaccination

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Benn, Christine Stabell; Rodrigues, Amabelia; Yazdanbakhsh, Maria

2009-01-01

Unexpectedly, we found no overall beneficial effect on mortality in a randomised trial of vitamin A supplementation (VAS) or placebo administered with BCG vaccine at birth in Guinea-Bissau. We conducted an explorative analysis to examine whether subsequent diphtheria-tetanus-pertussis (DTP) vacci...

Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development: Results from the Danish Calmette Study - A Randomised Clinical Trial.

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Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie; Nissen, Thomas Nørrelykke; Foss, Kim Thestrup; Thøstesen, Lisbeth Marianne; Pihl, Gitte Thybo; Andersen, Andreas; Kofoed, Poul-Erik; Pryds, Ole; Greisen, Gorm

2016-01-01

To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development. This is a pre-specified secondary outcome from a randomised, clinical trial. Maternity units and paediatric wards at three university hospitals in Denmark. Children born at gestational age (GA) 32 weeks and above. All women planning to give birth at the three sites were invited during the recruitment period. Out of 4262 randomised children, 144 were premature (GA Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age psychomotor development was excluded in term children. ClinicalTrials.gov NCT01694108.

A review of the literature on the economics of vaccination against TB.

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Tu, Hong-Anh T; Vu, Hoa D; Rozenbaum, Mark H; Woerdenbag, Herman J; Postma, Maarten J

2012-03-01

The BCG vaccine was introduced in 1921 and remains the only licensed vaccine for the prevention of TB worldwide. Despite its extensive use, the BCG vaccine lacks the ability to fully control the TB-endemic and -pandemic situations. The BCG vaccine is most effective in preventing pediatric TB, in particular, miliary TB and tuberculous meningitis. However, it has a limited effect in preventing pulmonary TB, which occurs more frequently in adults. BCG vaccination has now been implemented in more than 157 countries worldwide. For various countries, the benefits of vaccination are only limited and potentially not cost effective. The International Union Against Tuberculosis and Lung Diseases had set the criteria for discontinuation of BCG vaccination in 1994. This decision, however, was not based on economic considerations. Many developed countries have met the criteria set by the International Union Against Tuberculosis and Lung Disease and stopped universal BCG vaccination. For developing countries, the BCG vaccine is still an effective intervention in protecting young children from TB infection. A lot of effort has been spent on R&D of new TB vaccines, the first of which are expected to be available within 5-7 years from now. Novel TB vaccines are expected to be better and more effective than the current BCG vaccine and should provide a viable strategy in controlling TB morbidity and mortality. In this review, the aim is to explore economic evaluations that have been carried out for vaccination against TB worldwide. In addition to epidemiological evidence, economic evidence can play a crucial role in supporting the governments of countries in making proper public health decisions on BCG vaccination policies, in particular, to implement, continue, or discontinue.

The Type of Growth Medium Affects the Presence of a Mycobacterial Capsule and Is Associated With Differences in Protective Efficacy of BCG Vaccination Against Mycobacterium tuberculosis

OpenAIRE

Prados-Rosales, Rafael; Carreño, Leandro J.; Weinrick, Brian; Batista-Gonzalez, Ana; Glatman-Freedman, Aarona; Xu, Jiayong; Chan, John; Jacobs, William R.; Porcelli, Steven A.; Casadevall, Arturo

2016-01-01

Background. Bacillus Calmette-Guerin (BCG) vaccine is widely used for the prevention of tuberculosis, despite limited efficacy. Most immunological studies of BCG or Mycobacterium tuberculosis strains grow bacteria in the presence of detergent, which also strips the mycobacterial capsule. The impact of the capsule on vaccine efficacy has not been explored.

Impact of PGL-I seropositivity on the protective effect of BCG vaccination among leprosy contacts: a cohort study.

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Nádia C Düppre

Full Text Available BACKGROUND: Contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. Seropositivity to the phenolic glycolipid I (PGL-I antigen of Mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. In the present study, we studied the effect of seropositivity in patient contacts, on the risk of developing leprosy, stratified by Bacille Calmette Guerin (BCG vaccination after index case diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: Leprosy contacts were examined as part of the surveillance programme of the Oswaldo Cruz Institute Leprosy Outpatient Clinic in Rio de Janeiro. Demographic, social, epidemiological and clinical data were collected. The presence of IgM antibodies to PGL-I in sera and BCG vaccination status at the time of index case diagnosis were evaluated in 2,135 contacts. During follow-up, 60 (2.8%; 60/2,135 leprosy cases were diagnosed: 41 among the 1,793 PGL-I-negative contacts and 19 among the 342 PGL-I-positive contacts. Among PGL-I-positive contacts, BCG vaccination after index case diagnosis increased the adjusted rate of developing clinical manifestations of leprosy (Adjusted Rate Ratio (aRR = 4.1; 95% CI: 1.8-8.2 compared with the PGL-I-positive unvaccinated contacts (aRR = 3.2; 95% CI: 1.2-8.1. The incidence density was highest during the first year of follow-up for the PGL-I-positive vaccinated contacts. However, all of those contacts developed PB leprosy, whereas most MB cases (4/6 occurred in PGL-I-positive unvaccinated contacts. CONCLUSION: Contact examination combined with PGL-I testing and BCG vaccination remain important strategies for leprosy control. The finding that rates of leprosy cases were highest among seropositive contacts justifies targeting this specific group for close monitoring. Furthermore, it is recommended that PGL-I-positive contacts and contacts with a high familial bacteriological index

Impact of PGL-I Seropositivity on the Protective Effect of BCG Vaccination among Leprosy Contacts: A Cohort Study

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Düppre, Nádia C.; Camacho, Luiz Antonio B.; Sales, Anna M.; Illarramendi, Ximena; Nery, José Augusto C.; Sampaio, Elizabeth P.; Sarno, Euzenir N.; Bührer-Sékula, Samira

2012-01-01

Background Contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. Seropositivity to the phenolic glycolipid I (PGL-I) antigen of Mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. In the present study, we studied the effect of seropositivity in patient contacts, on the risk of developing leprosy, stratified by Bacille Calmette Guerin (BCG) vaccination after index case diagnosis. Methodology/Principal Findings Leprosy contacts were examined as part of the surveillance programme of the Oswaldo Cruz Institute Leprosy Outpatient Clinic in Rio de Janeiro. Demographic, social, epidemiological and clinical data were collected. The presence of IgM antibodies to PGL-I in sera and BCG vaccination status at the time of index case diagnosis were evaluated in 2,135 contacts. During follow-up, 60 (2.8%; 60/2,135) leprosy cases were diagnosed: 41 among the 1,793 PGL-I-negative contacts and 19 among the 342 PGL-I-positive contacts. Among PGL-I-positive contacts, BCG vaccination after index case diagnosis increased the adjusted rate of developing clinical manifestations of leprosy (Adjusted Rate Ratio (aRR) = 4.1; 95% CI: 1.8–8.2) compared with the PGL-I-positive unvaccinated contacts (aRR = 3.2; 95% CI: 1.2–8.1). The incidence density was highest during the first year of follow-up for the PGL-I-positive vaccinated contacts. However, all of those contacts developed PB leprosy, whereas most MB cases (4/6) occurred in PGL-I-positive unvaccinated contacts. Conclusion Contact examination combined with PGL-I testing and BCG vaccination remain important strategies for leprosy control. The finding that rates of leprosy cases were highest among seropositive contacts justifies targeting this specific group for close monitoring. Furthermore, it is recommended that PGL-I-positive contacts and contacts with a high familial bacteriological index, regardless of

Non-specific Effects of Vaccines and Stunting: Timing May Be Essential

NARCIS (Netherlands)

Berendsen, M.L.T.; Smits, J.P.J.M.; Netea, M.G.; Ven, A.J.A.M. van der

2016-01-01

BACKGROUND - Bacillus Calmette-Guérin (BCG) vaccination possesses effects on health beyond its target disease, the so called “non-specific effects”. We evaluate these effects, as well as the effect of timing of BCG and other vaccinations, on stunting in Sub-Saharan African (SSA) children under

Stimulation of alveolar macrophages by BCG vaccine enhances the process of lung fibrosis induced by bleomycin.

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Chyczewska, E; Chyczewski, L; Bańkowski, E; Sułkowski, S; Nikliński, J

1993-01-01

It was found that the BCG vaccine injected subcutaneously to the rats enhances the process of lung fibrosis induced by bleomycin. Pretreatment of rats with this vaccine results in accumulation of activated macrophages in lung interstitium and in the bronchoalveolar spaces. It may be suggested that the activated macrophages release various cytokines which may stimulate the proliferation of fibroblasts and biosynthesis of extracellular matrix components.

Effects of low birth weight on time to BCG vaccination in an urban poor settlement in Nairobi, Kenya: an observational cohort study.

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Mutua, Martin Kavao; Ochako, Rhoune; Ettarh, Remare; Ravn, Henrik; Echoka, Elizabeth; Mwaniki, Peter

2015-04-18

The World Health Organization recommends Bacillus Calmette-Guérin (BCG) vaccination against tuberculosis be given at birth. However, in many developing countries, pre-term and low birth weight infants get vaccinated only after they gain the desired weight. In Kenya, the ministry of health recommends pre-term and low birth weight infants to be immunized at the time of discharge from hospital irrespective of their weight. This paper seeks to understand the effects of birth weight on timing of BCG vaccine. The study was conducted in two Nairobi urban informal settlements, Korogocho and Viwandani which hosts the Nairobi Urban Health and Demographic Surveillance system. All infants born in the study area since September 2006 were included in the study. Data on immunization history and birth weight of the infant were recorded from child's clinic card. Follow up visits were done every four months to update immunization status of the child. A total of 3,602 infants were included in this analysis. Log normal accelerated failure time parametric model was used to assess the association between low birth weight infants and time to BCG immunization. In total, 229 (6.4%) infants were low birth weight. About 16.6% of the low birth weight infants weighed less than 2000 grams and 83.4% weighed between 2000 and 2490 grams. Results showed that, 60% of the low birth weight infants received BCG vaccine after more than five weeks of life. Private health facilities were less likely to administer a BCG vaccine on time compared to public health facilities. The effects of low birth weight on females was 0.60 and 0.97-times that of males for infants weighing 2000-2499 grams and for infants weighing <2000 grams respectively. The effect of low birth weight among infants born in public health facilities was 1.52 and 3.94-times that of infants delivered in private health facilities for infants weighing 2000-2499 grams and those weighing < 2000 grams respectively. Low birth weight infants

The immunological effect of revaccination with Bacille Calmette-Guérin vaccine at 19 months of age.

Science.gov (United States)

Andersen, Andreas; Roth, Adam; Jensen, Kristoffer Jarlov; Erikstrup, Christian; Lisse, Ida Marie; Whittle, Hilton; Sartono, Erliyani; Yazdanbakhsh, Maria; Aaby, Peter; Benn, Christine Stabell

2013-04-19

Bacille Calmette-Guérin (BCG) vaccination has important non-specific immune effects. In a randomized trial in Guinea-Bissau, BCG revaccination was associated with significantly increased survival in children who received diphtheria-tetanus-pertussis (DTP)-booster vaccine before enrolment and in children who did not receive micronutrient supplementation (MN). Within the trial we assessed the immunological effects of BCG revaccination. Children were randomized to BCG or nothing. Blood was sampled 6-11 weeks after randomization (early sample group) or 5-9 months later (late sample group). In vitro cytokine responses (interferon (IFN)-γ, interleukin (IL)-13, tumor-necrosis-factor (TNF)-α, and IL-10) were assessed in whole blood cultures stimulated with lipopolysaccharide (LPS), purified protein derivative (PPD) or phytohaemagglutinin (PHA). Effect-modification by sex, DTP-booster vaccination and MN was studied. Cytokines were measured in 345 infants. BCG was associated with significantly increased IFN-γ (geometric mean ratio (GMR)=4.54 (95% confidence interval: 3.13-6.58)) and IL-13 (GMR=1.43 (1.00-2.05)) PPD responses, the effect being strongest in the early sample group. Across all three conditions BCG tended to increase IL-10 (LPS, PHA, PPD: GMR=1.20, 1.12, 1.20), most pronounced in the late sample group. BCG reduced the TNF-α/IL-10 ratio in boys with DTP-booster at bleeding and increased it in those without (interaction test: p=0.03). In children without MN, BCG was associated with reduced TNF-α response in the early sample group (p=0.006), and increased IL-10 in the late sample group (p=0.03). BCG revaccination resulted in a strong IFN-γ response to PPD, which waned slightly over time. BCG also affected the pro-/anti-inflammatory balance, with reduced TNF-α and increased IL-10 responses to LPS, PHA and PPD. This effect depended on sex, DTP-booster vaccination and micronutrient supplementation, being most pronounced in children who had received DTP

Factors determining whether the parents accept BCG immunization of the new-born child in a high-income country

DEFF Research Database (Denmark)

Thybo Pihl, Gitte; Ammentorp, Jette; Kofoed, Poul-Erik

Introduction: A large prospective randomised clinical trial in Denmark is planned to test the hypothesis that compared to non-BCG-vaccinated infants, infants who are BCG vaccinated at birth experience less hospitalisations, use less antibiotics, and develop less atopic disease in early childhood......' Connors 'Decisional Conflict scale' to compare decisional conflicts for the parents that accept BCG vaccination and parents who do not accept the BCG vaccination of their newborn child....

Molecular Characterization of Heterologous HIV-1gp120 Gene Expression Disruption in Mycobacterium bovis BCG Host Strain: A Critical Issue for Engineering Mycobacterial Based-Vaccine Vectors

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Joseph, Joan; Fernández-Lloris, Raquel; Pezzat, Elías; Saubi, Narcís; Cardona, Pere-Joan; Mothe, Beatriz; Gatell, Josep Maria

2010-01-01

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) as a live vector of recombinant bacterial vaccine is a promising system to be used. In this study, we evaluate the disrupted expression of heterologous HIV-1gp120 gene in BCG Pasteur host strain using replicative vectors pMV261 and pJH222. pJH222 carries a lysine complementing gene in BCG lysine auxotrophs. The HIV-1 gp120 gene expression was regulated by BCG hsp60 promoter (in plasmid pMV261) and Mycobacteria spp. α-antigen promoter (in plasmid pJH222). Among 14 rBCG:HIV-1gp120 (pMV261) colonies screened, 12 showed a partial deletion and two showed a complete deletion. However, deletion was not observed in all 10 rBCG:HIV-1gp120 (pJH222) colonies screened. In this study, we demonstrated that E. coli/Mycobacterial expression vectors bearing a weak promoter and lysine complementing gene in a recombinant lysine auxotroph of BCG could prevent genetic rearrangements and disruption of HIV 1gp120 gene expression, a key issue for engineering Mycobacterial based vaccine vectors. PMID:20617151

Molecular Characterization of Heterologous HIV-1gp120 Gene Expression Disruption in Mycobacterium bovis BCG Host Strain: A Critical Issue for Engineering Mycobacterial Based-Vaccine Vectors

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Joan Joseph

2010-01-01

Full Text Available Mycobacterium bovis Bacillus Calmette-Guérin (BCG as a live vector of recombinant bacterial vaccine is a promising system to be used. In this study, we evaluate the disrupted expression of heterologous HIV-1gp120 gene in BCG Pasteur host strain using replicative vectors pMV261 and pJH222. pJH222 carries a lysine complementing gene in BCG lysine auxotrophs. The HIV-1 gp120 gene expression was regulated by BCG hsp60 promoter (in plasmid pMV261 and Mycobacteria spp. α-antigen promoter (in plasmid pJH222. Among 14 rBCG:HIV-1gp120 (pMV261 colonies screened, 12 showed a partial deletion and two showed a complete deletion. However, deletion was not observed in all 10 rBCG:HIV-1gp120 (pJH222 colonies screened. In this study, we demonstrated that E. coli/Mycobacterial expression vectors bearing a weak promoter and lysine complementing gene in a recombinant lysine auxotroph of BCG could prevent genetic rearrangements and disruption of HIV 1gp120 gene expression, a key issue for engineering Mycobacterial based vaccine vectors.

Effect of vaccine dose on the safety and immunogenicity of a candidate TB vaccine, MVA85A, in BCG vaccinated UK adults.

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Pathan, Ansar A; Minassian, Angela M; Sander, Clare R; Rowland, Rosalind; Porter, David W; Poulton, Ian D; Hill, Adrian V S; Fletcher, Helen A; McShane, Helen

2012-08-17

A non-randomised, open-label, Phase I safety and immunogenicity dose-finding study to assess the safety and immunogenicity of the candidate TB vaccine Modified Vaccinia virus Ankara expressing Antigen 85A (MVA85A) from Mycobacterium tuberculosis (MTB) in healthy adult volunteers previously vaccinated with BCG. Healthy BCG-vaccinated volunteers were vaccinated with either 1×10(7) or 1×10(8)PFU of MVA85A. All adverse events were documented and antigen specific T cell responses were measured using an ex vivo IFN-γ ELISPOT assay. Safety and immunogenicity were compared between the 2 dose groups and with a previous trial in which a dose of 5×10(7)PFU MVA85A had been administered. There were no serious adverse events recorded following administration of either 1×10(7) or 1×10(8)PFU of MVA85A. Systemic adverse events were more frequently reported following administration of 1×10(8)PFU of MVA85A when compared to either 5×10(7) or 1×10(7)PFU of MVA85A but were mild or moderate in severity and resolved completely within 7 days of immunisation. Antigen specific T cell responses as measured by the IFN-γ ELISPOT were significantly higher following immunisation in adults receiving 1×10(8)PFU compared to the 5×10(7) and 1×10(7) doses. Additionally, a broader range of Ag85A epitopes are detected following 1×10(8)PFU of MVA85A. A higher dose of 1×10(8)PFU of MVA85A is well-tolerated, increases the frequency of IFN-γ secreting T cells detected following immunisation and broadens the range of Ag85A epitopes detected. Copyright © 2012 Elsevier Ltd. All rights reserved.

Tuberculin skin reactivity after neonatal BCG vaccination in preterm infants in Minas Gerais, Brazil, 2001-2002 Reactividad cutánea a la tuberculina tras la vacunación con BCG de neonatos prematuros en Minas Gerais, Brasil, 2001-2002

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Paulo Camargos

2006-06-01

Full Text Available OBJECTIVES: The efficacy of BCG vaccination in preterm babies is unknown, and available data on conversion rates to tuberculin in this age group are scarce and controversial. This study assessed the tuberculin response in preterm infants after BCG vaccination. METHODS: This randomized cohort study was carried out at the Neonatal Department, University Hospital, Federal University of Minas Gerais in Brazil during 2001 and 2002. The BCG vaccine was administered at birth to 65 full-term (control and 40 preterm newborns. All of them were tested with 5 tuberculin units of purified protein derivative-S approximately 3 months after vaccination. RESULTS: A typical BCG scar was verified in 96.9% of the control group and in 90.0% of the preterm infants (P = 0.19. Indurations > 5 mm in diameter were recorded in 87.7% of the full-term and 67.5% of the preterm infants (P = 0.02. Indurations > 10 mm were recorded in 70.8% of the full-term and 42.5% of the preterm infants (P = 0.007. For indurations > 5 mm the upper and the lower limits of the 95% confidence interval for the difference between proportions were 8.5% to 31.8%, and for indurations > 10 mm these limits were 18.0% to 38.4%. No adverse reactions were observed in the study population. CONCLUSION: BCG vaccination could be recommended for preterm infants upon discharge from the neonatal unit to reduce morbidity and mortality in infants at risk for tuberculous infection, and to increase BCG vaccination coverage rates, especially in countries with high prevalence rates of tuberculosis.OBJETIVOS: Se desconoce la eficacia de la vacunación con Bacilo de Calmette-Guérin (BCG en neonatos prematuros, y los datos que existen acerca de la proporción de casos de conversión tuberculínica en este grupo de edad son pocos y cuestionables. En este estudio se evaluó la respuesta a la prueba de tuberculina de neonatos prematuros tras la vacunación con BCG. MÉTODOS: Este estudio de cohorte aleatorizado se llev

"Lay epidemiology": an important factor in Danish parents' decision of whether to allow their child to receive a BCG vaccination. A qualitative exploration of parental perspective.

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Pihl, Gitte Thybo; Johannessen, Helle; Ammentorp, Jette; Jensen, Jane Schmidt; Kofoed, Poul-Erik

2017-11-21

Vaccination is used worldwide to prevent infectious diseases. However, vaccination programmes in western countries face challenges in sustaining high coverage rates. The aim of this study was to explore how parents in Denmark make a decision about whether to allow their child to receive a Bacille Calmette Guerin vaccine at birth for the purpose of achieving non-specific effects on the immune system. A total of five focus groups were conducted with expectant mothers and fathers. Written information about the vaccine and information about the hypothesis of non-specific effects of the vaccine were delivered in order to discuss considerations and determinants of parents' decisions. Heritable factors and the possibility of stimulating the immune system of the child to achieve less atopic diseases and fewer infections were identified as arguments in favour of receiving the BCG vaccine. Arguments against receiving BCG mainly focused on concerns about its described and non-described side effects. Both arguments for and arguments against the vaccine were seen as parents attempt to make an individual risk evaluation for their child. Attitudes and beliefs in the local network were identified as important for parents' decisions. It is discussed how "lay epidemiology" characterizes parents' risk evaluation as an individual addition to the population-based risk declaration. It is furthermore discussed how health professionals should engage with both the empirical element and the value element of "Lay epidemiology". "Lay epidemiology" forms the basis for the parental decision of whether to allow their child to receive a BCG vaccination. Attitudes and beliefs about the causes and distribution of illnesses in the family or local network influence parents' risk evaluations. It would be ideal for parents if health professionals focused their communication about the BCG vaccine on individual risk evaluations.

The expression of ferritin, lactoferrin, transferrin receptor and solute carrier family 11A1 in the host response to BCG-vaccination and Mycobacterium tuberculosis challenge.

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Thom, R E; Elmore, M J; Williams, A; Andrews, S C; Drobniewski, F; Marsh, P D; Tree, J A

2012-05-02

Iron is an essential cofactor for both mycobacterial growth during infection and for a successful protective immune response by the host. The immune response partly depends on the regulation of iron by the host, including the tight control of expression of the iron-storage protein, ferritin. BCG vaccination can protect against disease following Mycobacterium tuberculosis infection, but the mechanisms of protection remain unclear. To further explore these mechanisms, splenocytes from BCG-vaccinated guinea pigs were stimulated ex vivo with purified protein derivative from M. tuberculosis and a significant down-regulation of ferritin light- and heavy-chain was measured by reverse-transcription quantitative-PCR (P≤0.05 and ≤0.01, respectively). The mechanisms of this down-regulation were shown to involve TNFα and nitric oxide. A more in depth analysis of the mRNA expression profiles, including genes involved in iron metabolism, was performed using a guinea pig specific immunological microarray following ex vivo infection with M. tuberculosis of splenocytes from BCG-vaccinated and naïve guinea pigs. M. tuberculosis infection induced a pro-inflammatory response in splenocytes from both groups, resulting in down-regulation of ferritin (P≤0.05). In addition, lactoferrin (P≤0.002), transferrin receptor (P≤0.05) and solute carrier family 11A1 (P≤0.05), were only significantly down-regulated after infection of the splenocytes from BCG-vaccinated animals. The results show that expression of iron-metabolism genes is tightly regulated as part of the host response to M. tuberculosis infection and that BCG-vaccination enhances the ability of the host to mount an iron-restriction response which may in turn help to combat invasion by mycobacteria. Copyright © 2012 Elsevier Ltd. All rights reserved.

Estimativa do risco de infecção tuberculosa em populações vacinadas pelo BCG Determining the risk of tuberculosis infection in BCG-vaccinated populations

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Gilberto Ribeiro Arantes

1992-04-01

Full Text Available A revacinação de escolares com BCG, capaz de restaurar a alergia remanescente de vacinação realizada nos primeiros meses de vida, porém incapaz de modificar a alergia devida à infecção pelo M. tuberculosis, possibilitaria a quantificação da parcela dessa população infectada pelo bacilo de Koch. Foi desenvolvida pesquisa com o objetivo de avaliar a aplicabilidade desses pressupostos na estimativa do risco de infecção tuberculosa em áreas sob elevada cobertura com BCG. A população de estudo foi constituída por escolares com 6 a 9 anos de idade freqüentando escolas municipais da zona leste da cidade de São Paulo, durante o primeiro semestre letivo de 1988. De 11.455 vacinados, apenas 7.470 foram submetidos ao teste tuberculínico, revacinados em seguida e retestados dez semanas depois. Destes, 3.314 tinham sido vacinados no primeiro trimestre de vida com meia dose e os demais 4.156 receberam dose plena acima dessa idade (75% no primeiro ano de vida, 20% no segundo e 5% no terceiro. A contagem dos infectados, pelo confronto dos resultados pré e pós vacinais em tabelas de correlação, foi realizada segundo os critérios do método original e modificação introduzida pelos autores, separadamente para os vacinados no primeiro trimestre de vida e após essa idade. O risco de infecção foi, respectivamente, 0,35% e 0,37% com o critério original e 0,45% e 0,49% com o modificado. O referencial médio disponível para a área estudada, estimado por outros métodos, foi 0,55%. As diferenças entre critérios e idades e destes com o referencial não foram significantes (P > 0,05. Os resultados sugerem que o método é aplicável para a estimativa do risco de infecção tuberculosa na idade escolar, em vacinados com BCG no primeiro ano de vida, com dose plena de vacina.The revaccination of schoolchildren can restore the residual allergy induced by vaccination in the first years of life but can not modify the allergy resulting from a

Assessment of different formulations of oral Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine in rodent models for immunogenicity and protection against aerosol challenge with M. bovis.

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Clark, Simon; Cross, Martin L; Smith, Alan; Court, Pinar; Vipond, Julia; Nadian, Allan; Hewinson, R Glyn; Batchelor, Hannah K; Perrie, Yvonne; Williams, Ann; Aldwell, Frank E; Chambers, Mark A

2008-10-29

Bovine tuberculosis (bTB) caused by infection with Mycobacterium bovis is causing considerable economic loss to farmers and Government in the United Kingdom as its incidence is increasing. Efforts to control bTB in the UK are hampered by the infection in Eurasian badgers (Meles meles) that represent a wildlife reservoir and source of recurrent M. bovis exposure to cattle. Vaccination of badgers with the human TB vaccine, M. bovis Bacille Calmette-Guérin (BCG), in oral bait represents a possible disease control tool and holds the best prospect for reaching badger populations over a wide geographical area. Using mouse and guinea pig models, we evaluated the immunogenicity and protective efficacy, respectively, of candidate badger oral vaccines based on formulation of BCG in lipid matrix, alginate beads, or a novel microcapsular hybrid of both lipid and alginate. Two different oral doses of BCG were evaluated in each formulation for their protective efficacy in guinea pigs, while a single dose was evaluated in mice. In mice, significant immune responses (based on lymphocyte proliferation and expression of IFN-gamma) were only seen with the lipid matrix and the lipid in alginate microcapsular formulation, corresponding to the isolation of viable BCG from alimentary tract lymph nodes. In guinea pigs, only BCG formulated in lipid matrix conferred protection to the spleen and lungs following aerosol route challenge with M. bovis. Protection was seen with delivery doses in the range 10(6)-10(7) CFU, although this was more consistent in the spleen at the higher dose. No protection in terms of organ CFU was seen with BCG administered in alginate beads or in lipid in alginate microcapsules, although 10(7) in the latter formulation conferred protection in terms of increasing body weight after challenge and a smaller lung to body weight ratio at necropsy. These results highlight the potential for lipid, rather than alginate, -based vaccine formulations as suitable delivery

Characteristics of children with positive tuberculin skin test.

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Hocaoğlu, Arzu Babayiğit; Erge, Duygu Olmez; Anal, Ozden; Makay, Balahan; Uzuner, Nevin; Karaman, Ozkan

2011-01-01

The aim of the study was to define the characteristics of children with latent tuberculosis diagnosed with positive tuberculin skin test (TST) and evaluate potential risk factors in children with positive TST. Children followed with the diagnosis of latent tuberculosis infection were included in the study retrospectively. Demographic characteristics of patients including history of atopy, respiratory infections, family history of tuberculosis and atopy, number of BCG vaccinations, findings of physical examination and laboratory data were extracted from patient's file. Eighty-one children (51 male, 30 female) who had positive TST were retrospectively evaluated in the study. Mean age of the patients was 8.00 ± 4.00 years. Only 13 (16%) of the children had contact with a case who had active tuberculosis. It was shown that the age of the patients, number of BCG scars and BCG vaccination significantly affected TST reaction size. TST size was not affected with time passed after last dose of BCG vaccination, family history of tuberculosis, presence of TST positive case in the family, exposure to cigarette smoke, number of household family members and presence of respiratory allergic disease. The patient's age, numbers of BCG vaccination and BCG scars significantly affect TST results in childhood. This may cause difficulty in diagnosing latent tuberculosis infection and in decision of initiating prophylactic treatment. The results of this study may show that recently developed, more accurate and convenient in vitro tests that they have higher costs and require sophisticated laboratory, can be used to diagnose latent tuberculosis.

Deletion of zmp1 improves Mycobacterium bovis BCG-mediated protection in a guinea pig model of tuberculosis.

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Sander, Peter; Clark, Simon; Petrera, Agnese; Vilaplana, Cristina; Meuli, Michael; Selchow, Petra; Zelmer, Andrea; Mohanan, Deepa; Andreu, Nuria; Rayner, Emma; Dal Molin, Michael; Bancroft, Gregory J; Johansen, Pål; Cardona, Pere-Joan; Williams, Ann; Böttger, Erik C

2015-03-10

Having demonstrated previously that deletion of zinc metalloprotease zmp1 in Mycobacterium bovis BCG increased immunogenicity of BCG vaccines, we here investigated the protective efficacy of BCG zmp1 deletion mutants in a guinea pig model of tuberculosis infection. zmp1 deletion mutants of BCG provided enhanced protection by reducing the bacterial load of tubercle bacilli in the lungs of infected guinea pigs. The increased efficacy of BCG due to zmp1 deletion was demonstrated in both BCG Pasteur and BCG Denmark indicating that the improved protection by zmp1 deletion is independent from the BCG sub-strain. In addition, unmarked BCG Δzmp1 mutant strains showed a better safety profile in a CB-17 SCID mouse survival model than the parental BCG strains. Together, these results support the further development of BCG Δzmp1 for use in clinical trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sex-differential and non-specific effects of routine vaccinations in a rural area with low vaccination coverage

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Aaby, Peter; Nielsen, Jens; Benn, Christine Stabell

2015-01-01

.53-0.89) compared with unvaccinated children. There was no benefit for children receiving BCG-first or DTP1-first. The female-male MRR was 0.79 (0.64-0.96) among unvaccinated children, but was significantly inversed with 1.45 (1.00-2.10) for children receiving DTP vaccination (test of homogeneity, p=0.......006). Children who had received DTP simultaneously with MV or DTP after MV had significantly higher mortality (MRR=2.59 [1.32-5.07]) compared with children having MV-only as their most recent vaccination. After 9 months, the female-male MRR was 0.61 (0.31-1.19) for measles-vaccinated children but remained 1...

Role of fibronectin in intravesical BCG therapy for superficial bladder cancer.

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Ratliff, T L; Kavoussi, L R; Catalona, W J

1988-02-01

Intravesical bacillus Calmette-Guerin (BCG) has been demonstrated to be effective both for prophylaxis and treatment of superficial bladder cancer. In order to identify the progression of events that result in BCG-mediated antitumor activity, studies were performed to evaluate the mechanism of binding of BCG within the bladder. Histological and quantitative studies in a mouse model revealed that BCG attached to the bladder wall only in areas of urothelial damage. Preliminary in vitro data showed that BCG attached to surfaces coated with extracellular matrix proteins. Further studies were then performed using purified extracellular matrix proteins to identify the proteins responsible for attachment. BCG were observed to attach to surfaces coated only with purified fibronectin (FN) but not to other purified proteins including laminin, collagen or fibrinogen. The attachment of BCG to purified FN in vitro was dose dependent and was inhibited by anti-FN antibodies. Moreover, BCG attachment in vivo to bladders with damaged urothelial surfaces was inhibited more than 95% by anti-FN antibodies, but binding was not affected by anti-laminin antibodies or preimmune serum. A survey of commercially available BCG vaccines (Pasteur, Tice, Glaxo, Connaught) showed that only Glaxo BCG did not attach to FN-coated surfaces. Glaxo BCG also was shown to express inferior antitumor activity suggesting that the absence of FN binding by Glaxo may have been associated with the absence of antitumor activity of the vaccine.

SIMULTANEOUS SMALLPOX AND B.C.G. VACCINATION IN INDONESIA

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Nyoman Kumara Rai

2012-09-01

Full Text Available Vaksinasi cacar dan BCG mulai diberikan secara simultan di Jawa dan Bali pada bulan April 1972 vaksinasi cacar diberikan pada lengan kiri dan BCG pada lengan kanan. Secara berangsur-angsur prograi ini kemudian diperluas kedaerah luar Jawa-Bali, sehingga pada akhir tahun 1973 sudah mencakup seluruh Indonesia. Tenaga yang digunakan adalah para juru cacar yang sudah ada dalam rangka proyek pembasmian penyakit cacar yang dimulai tahun 1968, dan terdapat hampir disemua kecamatan diseluru Indonesia. Ide untuk menggabungkan kedua jenis vaksinasi ini yang kebetulan mempunyai target sam (anak2 0 - 14 thn  timbul setelah penderita cacar tidak dilaporkan lagi dibulan September 1971 (ternyata kemudian letusan cacar terakhir adalah dibulan Desember 1971. Sampai saat itu vaksina BCG dilakukan oleh petugas Puskesmas dan tenaga part timer. Ternyata target tidak pernah tercapa hal ini mungkin disebabkan oleh terbatasnya waktu yang tersedia untuk melakukan vaksinasi BCC sehingga para tenaga part timer tsb. hanya mampu mencakup daerah disekitar Puskesmas dan sekolah dasar. Sebelumnya telah diadakan dua trial; yang pertama diadakan di Bandung untuk melihat at tidaknya saling pengaruh mempengaruhi antara kedua jenis vaksin cacar dan BCG bila diberikan pat saat yang bersamaan, sedangkain trial kedua dilakukan untuk menilai kemampuan juru cacar dala melaksanakan vaksinasi BCG serta kesukaran! yang dijumpai dilapangan (masing2 didua kabupaten (Jawa Tengah, Timur dan Yogyakarta. Disamping keuntungan yang diperoleh dari penggabungan kedua jenis vaksinasi ini yakni penghematan tenaga, biaya dan waktu, dijumpai juga beberapa kesukaran antara lain pengumpulan anak2, supply vaksin BCG yang tidak teratur dll. Walaupun demikian, di Jawa dan Bali hasil vaksinasi BCG antara April 1972 sampai dengan April 1973 menunjukkan kenaikan out-put leb dari 4 kali lipat bila dibandingkan dengan out-put sebelum penggabungan, meskipun out-put prin vaksinasi cacar mempunyai tendensi menurun

Optimizing HIV-1-specific CD8+ T-cell induction by recombinant BCG in prime-boost regimens with heterologous viral vectors.

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Hopkins, Richard; Bridgeman, Anne; Bourne, Charles; Mbewe-Mvula, Alice; Sadoff, Jerald C; Both, Gerald W; Joseph, Joan; Fulkerson, John; Hanke, Tomáš

2011-12-01

The desire to induce HIV-1-specific responses soon after birth to prevent breast milk transmission of HIV-1 led us to propose a vaccine regimen which primes HIV-1-specific T cells using a recombinant Mycobacterium bovis bacillus Calmette-Guérin (rBCG) vaccine. Because attenuated live bacterial vaccines are typically not sufficiently immunogenic as stand-alone vaccines, rBCG-primed T cells will likely require boost immunization(s). Here, we compared modified Danish (AERAS-401) and Pasteur lysine auxotroph (222) strains of BCG expressing the immunogen HIVA for their potency to prime HIV-1-specific responses in adult BALB/c mice and examined four heterologous boosting HIVA vaccines for their immunogenic synergy. We found that both BCG.HIVA(401) and BCG.HIVA(222) primed HIV-1-specific CD8(+) T-cell-mediated responses. The strongest boosts were delivered by human adenovirus-vectored HAdV5.HIVA and sheep atadenovirus-vectored OAdV7.HIVA vaccines, followed by poxvirus MVA.HIVA; the weakest was plasmid pTH.HIVA DNA. The prime-boost regimens induced T cells capable of efficient in vivo killing of sensitized target cells. We also observed that the BCG.HIVA(401) and BCG.HIVA(222) vaccines have broadly similar immunologic properties, but display a number of differences mainly detected through distinct profiles of soluble intercellular signaling molecules produced by immune splenocytes in response to both HIV-1- and BCG-specific stimuli. These results encourage further development of the rBCG prime-boost regimen. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Long-term in vitro and in vivo effects of γ-irradiated BCG on innate and adaptive immunity

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Arts, Rob J W; Blok, Bastiaan A; Aaby, Peter

2015-01-01

were less strong than those induced by live BCG. γBCG vaccination in volunteers had only minimal effects on innate immunity, whereas a significant increase in heterologous Th1/Th17 immunity was observed. Our results indicate that γBCG induces long-term training of innate immunity in vitro. In vivo, γ......BCG vaccination is associated with a reduced mortality from nonmycobacterial infections. This is likely to be mediated by a combination of innate-immune memory ("trained immunity") and heterologous effects on adaptive immunity. As such, BCG could be used to boost host immunity...

Increased TNF-alpha/IFN-gamma/IL-2 and decreased TNF-alpha/IFN-gamma production by central memory T cells are associated with protective responses against bovine tuberculosis following BCG vaccination

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Mayara Fernanda Maggioli

2016-10-01

Full Text Available Central memory T cells (Tcm and polyfunctional CD4 T cell responses contribute to vaccine-elicited protection with both human and bovine tuberculosis (TB; however, their combined role in protective immunity to TB is unclear. To address this question, we evaluated polyfunctional cytokine responses by CD4 T cell effector / memory populations from bacille Calmette Guerin (BCG vaccinated and non-vaccinated calves prior to and after aerosol challenge with virulent Mycobacterium bovis. Polyfunctional cytokine expression patterns in the response by Tcm, effector memory, and effector T cell subsets were similar between BCG-vaccinated and M. bovis-infected calves; only differing in magnitude (i.e., infected > vaccinated. BCG vaccination, however, did alter the kinetics of the ensuing response to virulent M. bovis infection. Early after challenge (three weeks post-infection, non-vaccinates had greater antigen-specific IFN-γ/TNF-α and lesser IFN-γ/TNF-α/IL-2 responses by Tcm cells than did vaccinated animals. Importantly, these differences were also associated with mycobacterial burden upon necropsy. Polyfunctional responses to ESAT-6:CFP10 (antigens not synthesized by BCG strains were detected in memory subsets, as well as in effector cells, as early as three weeks after challenge. These findings suggest that cell fate divergence may occur early after antigen priming in the response to bovine TB and that memory and effector T cells may expand concurrently during the initial phase of the immune response. In summary, robust IFN-γ/TNF-α response by Tcm cells is associated with greater mycobacterial burden while IFN-γ/TNF-α/IL-2 response by Tcm cells are indicative of a protective response to bovine TB.

[Immunization for children travelling to the tropics: neglected vaccines].

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Imbert, P; Guérin, N; Sorge, F

2008-06-01

Each year hundreds of thousands of children leave France to travel to developing countries where they are exposed to infectious agents that can be prevented by vaccination. During the child's pre-travel check-up, practitioners should check that all mandatory immunizations are up-to-date and provide advice on relevant vaccines in function of the epidemiological situation at the chosen destination. However various factors hinder full compliance with this approach and some vaccines are underused. Underused vaccines are referred to as neglected vaccines. In the French vaccination schedule three vaccinations can be considered as neglected. The first is the hepatitis B vaccine that has a low coverage level in France due to strong reluctance to its use despite the fact that the virus is widespread in tropical areas. The second is pneumococcal vaccine that should be administered to all infants less than 2 years of age, especially for travel to areas where pneumonia and meningitis are frequent. The third is BCG vaccine that is now at greater risk of being neglected in child travellers because its use has been downgraded from a general requirement to a recommendation only for children at risk. A serious limitation on the use of travel vaccinations is cost that can lead families to neglect some infectious risk such as hepatitis A that is a major risk for child travellers as well as for their relatives during or after the trip and typhoid fever that is essentially an imported disease. Rabies vaccine is also underused due to its cost and to poor understanding of the risk by many practitioners and families. The purpose of this article is to underline the need to improve information and access to vaccines that are all too often neglected in child travellers.

Vaccination against tuberculosis.

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Martin, Carlos; Aguilo, Nacho; Gonzalo-Asensio, Jesús

2018-04-04

BCG (Bacille Calmette-Guérin) vaccination is included in the immunization schedule for tuberculosis endemic countries with a global coverage at birth close to 90% worldwide. BCG was attenuated from Mycobacterium bovis almost a century ago, and provides a strong protection against disseminated forms of the disease, though very limited against pulmonary forms of tuberculosis, responsible for transmission. Novel prophylactic tuberculosis vaccines are in clinical development either to replace BCG or to improve its protection against respiratory forms of the disease. There are limitations understanding the immunological responses involved and the precise type of long-lived immunity that new vaccines need to induce. MTBVAC is the first and only tuberculosis vaccine candidate based on live-attenuated Mycobacterium tuberculosis in clinical evaluation. MTBVAC clinical development plans to target tuberculosis prevention in newborns, as a BCG replacement strategy, and as secondary objective to be tested in adolescents and adults previous vaccinated with BCG. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

The value of counting BCG scars for interpretation of tuberculin skin tests in a tuberculosis hyperendemic shanty-town, Peru

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Saito, M.; Bautista, C. T.; Gilman, R. H.; Bowering, A.; Levy, M. Z.; Evans, C. A.

2010-01-01

SUMMARY SETTING The tuberculin skin test (TST) is widely used as a diagnostic or screening test for Mycobacterium tuberculosis infection and disease. A peri-urban shanty-town in the desert hills of south Lima, Peru, highly endemic for tuberculosis, and where bacille Calmette-Guérin (BCG) vaccine had been given in multiple doses until 1995. OBJECTIVE To analyze the effect of multiple BCG vaccines on TST in a community-based setting. DESIGN Point-prevalence survey of TST reactions of 572 people aged 6–26 years from 255 households. TST reactions were compared to the observed number of BCG scars and other potential risk factors (age, living with a TST-positive person, and contact with active tuberculosis). RESULT People with two or more scars had significantly larger reactions, even after adjusting for potential risk factors. The adjusted population attributable fraction of being TST-positive and having two or more BCG scars was 26%. CONCLUSION There is no demonstrated benefit of repeat BCG vaccination. We therefore recommend that physicians take into consideration the number of BCG scars when interpreting the TST and that programs give no more than one BCG vaccination. PMID:15260275

The association between travel time to health facilities and childhood vaccine coverage in rural Ethiopia. A community based cross sectional study.

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Okwaraji, Yemisrach B; Mulholland, Kim; Schellenberg, Joanna R M Armstrong; Andarge, Gashaw; Admassu, Mengesha; Edmond, Karen M

2012-06-22

Few studies have examined associations between access to health care and childhood vaccine coverage in remote communities that lack motorised transport. This study assessed whether travel time to health facilities was associated with childhood vaccine coverage in a remote area of Ethiopia. This was a cross-sectional study using data from 775 children aged 12-59 months who participated in a household survey between January -July 2010 in Dabat district, north-western Ethiopia. 208 households were randomly selected from each kebele. All children in a household were eligible for inclusion if they were aged between 12-59 months at the time of data collection. Travel time to vaccine providers was collected using a geographical information system (GIS). The primary outcome was the percentage of children in the study population who were vaccinated with the third infant Pentavalent vaccine ([Diphtheria, Tetanus,-Pertussis Hepatitis B, Haemophilus influenza type b] Penta3) in the five years before the survey. We also assessed effects on BCG, Penta1, Penta2 and Measles vaccines. Analysis was conducted using Poisson regression models with robust standard error estimation and the Wald test. Missing vaccination data ranged from 4.6% (36/775) for BCG to 16.4% (127/775) for Penta3 vaccine. In children with complete vaccination records, BCG vaccine had the highest coverage (97.3% [719/739]), Penta3 coverage was (92.9% [602/648]) and Measles vaccine had the lowest coverage (81.7% [564/690]). Children living ≥60mins from a health post were significantly less likely (adjRR = 0.85 [0.79-0.92] p value Travel time also had a highly significant association with BCG (adjRR = 0.95 [0.93-0.98] p value =0.002) and Measles (adjRR = 0.88 [0.79-0.97] p value =0.027) vaccine coverage. Travel time to vaccine providers in health posts appeared to be a barrier to the delivery of infant vaccines in this remote Ethiopian community. New vaccine delivery strategies are needed for the

Enhanced and enduring protection against tuberculosis by recombinant BCG-Ag85C and its association with modulation of cytokine profile in lung.

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Ruchi Jain

Full Text Available BACKGROUND: The variable efficacy (0-80% of Mycobacterium bovis Bacille Calmette Guréin (BCG vaccine against adult tuberculosis (TB necessitates development of alternative vaccine candidates. Development of recombinant BCG (rBCG over-expressing promising immunodominant antigens of M. tuberculosis represents one of the potential approaches for the development of vaccines against TB. METHODS/PRINCIPAL FINDINGS: A recombinant strain of BCG - rBCG85C, over expressing the antigen 85C, a secretory immuno-dominant protein of M. tuberculosis, was evaluated for its protective efficacy in guinea pigs against M. tuberculosis challenge by aerosol route. Immunization with rBCG85C resulted in a substantial reduction in the lung (1.87 log(10, p<0.01 and spleen (2.36 log(10, p<0.001 bacillary load with a commensurate reduction in pathological damage, when compared to the animals immunized with the parent BCG strain at 10 weeks post-infection. rBCG85C continued to provide superior protection over BCG even when post-challenge period was prolonged to 16 weeks. The cytokine profile of pulmonary granulomas revealed that the superior protection imparted by rBCG85C was associated with the reduced levels of pro-inflammatory cytokines - interleukin (IL-12, interferon (IFN-gamma, tumor necrosis factor (TNF-alpha, moderate levels of anti-inflammatory cytokine - transforming growth factor (TGF-beta along with up-regulation of inducible nitric oxide synthase (iNOS. In addition, the rBCG85C vaccine induced modulation of the cytokine levels was found to be associated with reduced fibrosis and antigen load accompanied by the restoration of normal lung architecture. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of rBCG85C over BCG as a promising prophylactic vaccine against TB. The enduring protection observed in this study gives enough reason to postulate that if an open-ended study is carried out with low dose of infection, rBCG85C vaccine in all

Estudo sobre a evolução do risco de infecção tuberculosa em área com elevada cobertura por BCG The trend in the risk of tuberculous infection in an area with wide coverage with BCG vaccination

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Gilberto Ribeiro Arantes

1985-04-01

Full Text Available A partir da prevalência de infecção tuberculosa em escolares com 7 anos de idade, calculou-se a taxa de redução do risco anual de infecção na cidade de São Paulo (Brasil, entre 1974 e 1982. Nesse período o declínio médio foi de 5% ao ano. Nas 59 escolas municipais pesquisadas não houve correlação entre a cobertura de vacinação BCG e a prevalência de infecção natural em não-vacinados, à idade estudada. A alergia tuberculínica no grupo de crianças vacinadas, que recebeu a vacina em alguma idade anterior entre o 1° e o 6° ano de vida, revelou-se 2,5 vezes mais intensa do que a alergia no grupo de mesma idade (7 anos, não vacinado previamente. Foram feitos comentários quanto à impropriedade do material utilizado com vistas ao cálculo do verdadeiro valor do risco de infecção tuberculosa na área em questão.The estimation of the risk of tuberculous infection from prevalence data obtained at school-age, in 1974 and in 1982, permitted the determination of the relevant trend in the city of S. Paulo, Brazil, between those years. The risk of infection decreased, on average, by 5% annually during the period. There was no evidence of any association between the proportions of vaccinated children and that of infected children among those unvaccinated, in the 59 schools studied. Tuberculin sensitivity in 7 years old school-children, vaccinated with BCG at any age between the 1st and the 6th year of life was 2.5 times more intense than that in unvaccinaetd children of the same age. With regard to the calculation of the true value of the risk of tuberculous infection, commentaries about the unrealiability of the available data were made.

Ag85A-specific CD4+ T cell lines derived after boosting BCG-vaccinated cattle with Ad5-85A possess both mycobacterial growth inhibition and anti-inflammatory properties.

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Metcalfe, Hannah J; Biffar, Lucia; Steinbach, Sabine; Guzman, Efrain; Connelley, Tim; Morrison, Ivan; Vordermeier, H Martin; Villarreal-Ramos, Bernardo

2018-05-11

There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4 + T cells post-boosting. Here, the capacity of Ag85A-specific CD4 + T cell lines - derived before and after viral boosting - to interact with BCG-infected macrophages was evaluated. No difference before and after boosting was found in the capacity of these Ag85A-specific CD4 + T cell lines to restrict mycobacterial growth, but the secretion of IL-10 in vitro post-boost increased significantly. Furthermore, cell lines derived post-boost had no statistically significant difference in the secretion of pro-inflammatory cytokines (IL-1β, IL-12, IFNγ or TNFα) compared to pre-boost lines. In conclusion, the protection associated with the increased number of Ag85A-specific CD4 + T cells restricting mycobacterial growth may be associated with anti-inflammatory properties to limit immune-pathology. Copyright © 2018 Department for Environment Food and Rural Affairs. Published by Elsevier Ltd.. All rights reserved.

rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B.

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Gillis, Thomas P; Tullius, Michael V; Horwitz, Marcus A

2014-09-01

Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Mycobacterium tuberculosis PPD-induced immune biomarkers measurable in vitro following BCG vaccination of UK adolescents by multiplex bead array and intracellular cytokine staining

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Worth Andrew

2010-07-01

Full Text Available Abstract Background The vaccine efficacy reported following Mycobacterium bovis Bacillus Calmette Guerin (BCG administration to UK adolescents is 77% and defining the cellular immune response in this group can inform us as to the nature of effective immunity against tuberculosis. The aim of this study was to identify which cytokines and lymphocyte populations characterise the peripheral blood cellular immune response following BCG vaccination. Results Diluted blood from before and after vaccination was stimulated with Mycobacterium tuberculosis purified protein derivative for 6 days, after which soluble biomarkers in supernatants were assayed by multiplex bead array. Ten out of twenty biomarkers measured were significantly increased (p Mycobacterium tuberculosis purified protein derivative stimulation of PBMC samples from the 12 month group revealed that IFNγ expression was detectable in CD4 and CD8 T-cells and natural killer cells. Polyfunctional flow cytometry analysis demonstrated that cells expressing IFNγ alone formed the majority in each subpopulation of cells. Only in CD4 T-cells and NK cells were there a notable proportion of responding cells of a different phenotype and these were single positive, TNFα producers. No significant expression of the cytokines IL-2, IL-17 or IL-10 was seen in any population of cells. Conclusions The broad array of biomarker responses detected by multiplex bead array suggests that BCG vaccination is capable, in this setting, of inducing a complex immune phenotype. Although polyfunctional T-cells have been proposed to play a role in protective immunity, they were not present in vaccinated adolescents who, based on earlier epidemiological studies, should have developed protection against pulmonary tuberculosis. This may be due to the later sampling time point available for testing or on the kinetics of the assays used.

Packaging BCG: standardizing an anti-tuberculosis vaccine in interwar Europe.

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Bonah, Christian

2008-06-01

Using the example of the anti-tuberculosis vaccine BCG during the 1920s and 1930s, this article asks how a labile laboratory-modified bacteria was transformed into a genuine standard vaccine packaged and commercialized as a pharmaceutical product. At the center of the analysis lies the notion of standardization inquiring why and how a local laboratory process with standard operating procedures (SOPs) reached its limits and was transformed when the product faced international distribution. Moving from Paul Ehrlich's initial technological notion of Wertbestimmung referring to a practice physiologically testing the effects of ill-defined antitoxins, the concept of standardization is extended to pharmaceutical and economical meanings implying quality control for biological therapeutic agents produced by a variety of industrial entrepreneurs. Following the request for product uniformity, two ways to maintain levels of compatibility and commonality are depicted opposing SOPs and end-product control. Furthermore, standardization is understood as a spiral, never ending process where progressive transformation of the vaccine in its production and medical uses periodically recreated the necessity of standardization. Developments analyzed are thus understood as a stabilization process aligning laboratory settings, products, and practices with medical theories and practices through technical, bureaucratic, and organizational systems. A paradox of the analysis is that standardization as a historical phenomenon and moment in the history of drug development was initially linked to a problem of under-determination of what was to be standardized and to a knowledge gap before it could become a central concept for quality control.

The effect of oral vaccination with Mycobacterium bovis BCG on the development of tuberculosis in captive European badgers (Meles meles)

OpenAIRE

Chambers, MA; Aldwell, F; Williams, GA; Palmer, S; Gowtage, S; Ashford, R; Dalley, D; Davé, D; Weyer, U; Salguero Bodes, FJ; Nunez, A; Nadian, A; Crawshaw, T; Corner, LAL; Lesellier, S

2017-01-01

The European badger (Meles meles) is a reservoir host of Mycobacterium bovis and responsible for a proportion of the tuberculosis (TB) cases seen in cattle in the United Kingdom and Republic of Ireland. An injectable preparation of the bacillus Calmette-Guérin (BCG) vaccine is licensed for use in badgers in the UK and its use forms part of the bovine TB eradication plans of England and Wales. However, there are practical limitations to the widespread application of an injectable vaccine for b...

Vacuna contra la tuberculosis BCG: Eficacia y efectos adversos

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Quezada-Andrade, Steven

2015-12-01

Full Text Available TB is the second leading cause of death from an infectious agent, disease caused by Mycobacterium tuberculosis. It allowed the creation of a vaccine officially launched in 1924 and known as Bacillus Calmette-Guerin (BCG used since then. However, there has been extensive research on its effectiveness and other related factors have shown an imbalance. Several countries recommend the use of this vaccine in infants, but in the case of Ecuador has failed to suggest its application, although there are no data regarding the efficacy of the vaccine in that country. Other studies show that the knowledge of people about the disease is destitute, thus allowing this could spread more quickly because the infected person does not know the type of symptoms that generates Tuberculosis. This article aims to identify the current status of the efficiency and safety of BCG through review and analysis of collected items related to the use of the vaccine and its effectiveness in the research population.

Adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in new-born infants-an evaluation of the Danish strain 1331 SSI in a randomized clinical trial

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Nissen, Thomas Nørrelykke; Birk, Nina Marie; Kjærgaard, Jesper

2016-01-01

or no intervention. Follow-up until 13 months of age. SETTING: Pediatric and maternity wards at three Danish university hospitals. PARTICIPANTS: All women planning to give birth at the three study sites (n=16,521) during the recruitment period were invited to participate in the study. Four thousand one hundred...... lymphadenitis were hospitalized and thus classified as serious adverse reactions related to BCG. The most severe adverse reactions were 10 cases of suppurative lymphadenitis. This was nearly a fivefold increase compared to what was expected based on the summary of product characteristics of the vaccine. All...... cases were treated conservatively and recovered. Six of 10 (60%) families of children experiencing suppurative lymphadenitis compared to 117/2071 (6%) of those with no lymphadenitis indicated that the vaccine had more adverse effects than expected (p-value

MicroRNA expression profiling of PPD-B stimulated PBMC from M. bovis-challenged unvaccinated and BCG vaccinated cattle.

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Golby, P; Villarreal-Ramos, B; Dean, G; Jones, G J; Vordermeier, M

2014-10-07

There is an urgent need to identify additional diagnostic biomarkers for bovine TB to complement existing read-out systems such as interferon-gamma and for predictive markers of vaccine efficacy to accelerate vaccine development. To evaluate the potential of miRNAs as such biomarkers, we have analysed their expression in bovine PPD stimulated PBMC isolated from unvaccinated and BCG vaccinated cattle before and following Mycobacterium bovis (M. bovis) infection. Using a bovine microRNA microarray, miR-155 was found to show a significant up-regulation in expression in early (week 2) and late (week 11) M. bovis post-infection samples from unvaccinated cattle, while in BCG vaccinated cattle up-regulation was observed only in late post-infection samples. No differential expression of miR-155 was observed in pre-infection samples from unvaccinated and vaccinated cattle. These observations suggest that miR-155 could be exploited as a marker distinguishing vaccinated from infected animals (DIVA). Analysis by TaqMan RT-PCR, verified the up-regulation of miR-155 in unvaccinated cattle post-infection. Significant correlation was found between the degree of pathology and miR-155 induction in the experimentally infected cattle, suggesting miR-155 is a biomarker of disease development and/or severity. Induction of miR155 expression in cattle sourced from farms with confirmed bTB that tested positive in the tuberculin skin or interferon-gamma blood test was found to be significantly higher in cattle presenting with more advanced pathology (defined by the presence of visible TB lesions) compared to infected cattle without visible pathology and thus likely to be of lower infectivity than those with more advanced disease. In conclusion, our data indicate that miR-155 has potential both as a diagnostic and prognostic biomarker that could be used to identify animals with advanced pathology and as a DIVA test read-out. Its role in the immune biology of bovine TB will also be discussed

Early BCG-Denmark and Neonatal Mortality Among Infants Weighing <2500 g: A Randomized Controlled Trial

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Biering-Sørensen, Sofie; Aaby, Peter; Lund, Najaaraq

2017-01-01

ratios (MRRs). We had prespecified an analysis censoring follow-up at oral poliovirus vaccine campaigns. Results. Early administration of BCG-Denmark was associated with a nonsignificant reduction in neonatal mortality rate (MRR, 0.70; 95% confidence interval [CI], .47–1.04) and a 34% reduction (0.......66; .44–1.00) when censoring for oral poliovirus vaccine campaigns. There was no reduction in mortality rate for noninfectious diseases, but a 43% reduction in infectious disease mortality rate (MRR, 0.57; 95% CI, .35–.93). A meta-analysis of 3 BCG trials showed that early BCG-Denmark reduced mortality...

Bacillus Calmette-Guérin vaccination at birth

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Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie

2016-01-01

BACKGROUND: Bacillus Calmette-Guérin vaccine (BCG) induces a complex, pro-inflammatory immune response. Obesity is associated with low-grade inflammation. AIMS: The purpose of the study was to test whether BCG at birth has effects on infant growth and body composition. STUDY DESIGN, SUBJECTS......, AND OUTCOME MEASURES: The Danish Calmette Study is a randomized, clinical trial. The study was conducted at three university hospitals and randomized 4262 children of gestational age ≥32weeks to receive BCG within seven days of birth or to a no-intervention control group. Follow-up consisted of clinical......-up was 94% complete at 3 and 13months after birth. The children were bigger than the WHO reference population. There was no effect of BCG on weight z-score at 13months (-0.028 [95% confidence interval: -0.085 to 0.029], p=0.34). There was no effect on weight and length at 3months, or length, mid...

Immunization coverage among children in Al-Taizyah district, Taiz Governorate, Yemen

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Nabil Ahmed Al-Rabeei

2014-12-01

Full Text Available Introduction: At least 2 million people die every year from diseases preventable by vaccines recommended by the World Health Organization. Objective: To assess the routine immunization coverage among children aged 12-23 month and to determine the reasons for unvaccinated. Methods: We conducted a community-based survey in Al-Taizyah district, Taiz governorate, Yemen. Information about vaccination status and related barriers was collected for 420 children from 1st March to 31st March 2012. Results: 49.8% of the children had vaccination cards. About 69.5% of the children were fully vaccinated by cards and by history, 15.5% were partially vaccinated and 15% not vaccinated. As a regards to crude vaccination coverage, 82.9% of children were received BCG vaccine. OPV1 vaccine was 82.6%. Pentavalent1 was 82.6%. Measles 1 represented for 71.7% and vitamin A1 was 46.4%. 91% was valid doses for OPV1 and 93% for pentavalent1. Only 76% of measles1 dose was valid. The high scores14% of drop-out rate was recorded between BCG and Measles. The main reasons for partially vaccinated and unvaccinated of children were the lack of information 61.7%. Conclusion: There is low vaccination coverage among children aged 12-23 months. There is a need to raise the awareness of community about vaccination and EPI services in Al-Taizyah district.

The association between travel time to health facilities and childhood vaccine coverage in rural Ethiopia. A community based cross sectional study

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Okwaraji Yemisrach B

2012-06-01

Full Text Available Abstract Background Few studies have examined associations between access to health care and childhood vaccine coverage in remote communities that lack motorised transport. This study assessed whether travel time to health facilities was associated with childhood vaccine coverage in a remote area of Ethiopia. Methods This was a cross-sectional study using data from 775 children aged 12–59 months who participated in a household survey between January –July 2010 in Dabat district, north-western Ethiopia. 208 households were randomly selected from each kebele. All children in a household were eligible for inclusion if they were aged between 12–59 months at the time of data collection. Travel time to vaccine providers was collected using a geographical information system (GIS. The primary outcome was the percentage of children in the study population who were vaccinated with the third infant Pentavalent vaccine ([Diphtheria, Tetanus,-Pertussis Hepatitis B, Haemophilus influenza type b] Penta3 in the five years before the survey. We also assessed effects on BCG, Penta1, Penta2 and Measles vaccines. Analysis was conducted using Poisson regression models with robust standard error estimation and the Wald test. Results Missing vaccination data ranged from 4.6% (36/775 for BCG to 16.4% (127/775 for Penta3 vaccine. In children with complete vaccination records, BCG vaccine had the highest coverage (97.3% [719/739], Penta3 coverage was (92.9% [602/648] and Measles vaccine had the lowest coverage (81.7% [564/690]. Children living ≥60mins from a health post were significantly less likely (adjRR = 0.85 [0.79-0.92] p value  Conclusions Travel time to vaccine providers in health posts appeared to be a barrier to the delivery of infant vaccines in this remote Ethiopian community. New vaccine delivery strategies are needed for the hardest to reach children in the African region.

Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM cells which expand following virulent mycobacterial challenge.

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Daryan A Kaveh

Full Text Available To more closely understand the mechanisms of how BCG vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. Given the established central role of CD4 T cells in BCG induced immunity, we sought to characterise the generation of memory CD4 T cell responses to BCG vaccination and M. bovis infection in a murine challenge model. We demonstrate that a single systemic BCG vaccination induces distinct systemic and mucosal populations of T effector memory (T(EM cells in vaccinated mice. These CD4+CD44(hiCD62L(loCD27⁻ T cells concomitantly produce IFN-γ and TNF-α, or IFN-γ, IL-2 and TNF-α and have a higher cytokine median fluorescence intensity MFI or 'quality of response' than single cytokine producing cells. These cells are maintained for long periods (>16 months in BCG protected mice, maintaining a vaccine-specific functionality. Following virulent mycobacterial challenge, these cells underwent significant expansion in the lungs and are, therefore, strongly associated with protection against M. bovis challenge. Our data demonstrate that a persistent mucosal population of T(EM cells can be induced by parenteral immunization, a feature only previously associated with mucosal immunization routes; and that these multifunctional T(EM cells are strongly associated with protection. We propose that these cells mediate protective immunity, and that vaccines designed to increase the number of relevant antigen-specific T(EM in the lung may represent a new generation of TB vaccines.

The candidate TB vaccine, MVA85A, induces highly durable Th1 responses.

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Michele Tameris

Full Text Available Vaccination against tuberculosis (TB should provide long-term protective immunity against Mycobacterium tuberculosis (M.tb. The current TB vaccine, Bacille Calmette-Guerin (BCG, protects against disseminated childhood TB, but protection against lung TB in adolescents and adults is variable and mostly poor. One potential reason for the limited durability of protection may be waning of immunity through gradual attrition of BCG-induced T cells. We determined if a MVA85A viral-vector boost could enhance the durability of mycobacteria-specific T cell responses above those induced by BCG alone.We describe a long-term follow-up study of persons previously vaccinated with MVA85A. We performed a medical history and clinical examination, a tuberculin skin test and measured vaccine-specific T cell responses in persons previously enrolled as adults, adolescents, children or infants into three different Phase II trials, between 2005 and 2011.Of 252 potential participants, 183 (72.6% consented and completed the study visit. Vaccine-induced Ag85A-specific CD4+ T cell responses were remarkably persistent in healthy, HIV-uninfected adults, adolescents, children and infants, up to 6 years after MVA85A vaccination. Specific CD4+ T cells expressed surface markers consistent with either CD45RA-CCR7+ central memory or CD45RA-CCR7- effector memory T cells. Similarly durable Ag85A-specific CD4+ T cell responses were detected in HIV-infected persons who were on successful antiretroviral therapy when MVA85A was administered. By contrast, Ag85A-specific CD4+ T cell frequencies in untreated MVA85A-vaccinated HIV-infected persons were mostly undetectable 3-5 years after vaccination.MVA85A induces remarkably durable T cell responses in immunocompetent persons. However, results from a recent phase IIb trial of MVA85A, conducted in infants from the same geographic area and study population, showed no vaccine efficacy, suggesting that these durable T cell responses do not

Duas epidemias de tuberculose em crianças menores de três anos de idade, vacinadas com BCG oral, numa creche do município de São Paulo, Brasil Two epidemics of tuberculosis in children under three years of age vaccinated with oral BCG in a day-nursery in S. Paulo county, Brazil

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Roberto Brólio

1974-09-01

Full Text Available São descritas duas epidemias de tuberculose em crianças menores de 3 anos de idade vacinadas com BCG oral, ocorridas numa creche para crianças menores de 5 anos de idade, no município de São Paulo, nos anos de 1967 e 1969. Em 1967 havia no estabelecimento 96 crianças, inicialmente não reatoras ao teste tuberculínico padronizado (PPD, Rt-23, 2 UT. Foram encontrados 19 reatores, sendo 12 reatores fortes (63,2% e 7 reatores fracos (36,8% e imagens radiológicas indicativas de anormalidade pulmonar em 15 crianças ou 78,9% dos reatores. Em 1969 havia no estabelecimento mais 62 crianças não reatoras, que foram acompanhadas separadamente em relação ao grupo de 1967, embora convivessem no mesmo ambiente. Foram encontrados 36 reatores à tuberculina, sendo 29 reatores fortes (80,5% e 7 reatores fracos (19,5% e imagens radiológicas indicativas de anormalidade pulmonar em 11 crianças, ou 30,5% dos reatores. Nesse mesmo ano houve viragem tuberculínica em mais 7 crianças pertencentes ao grupo de não reatores de 1967, sendo 5 reatores fortes e 2 reatores fracos. Nas duas epidemias, as viragens tuberculínicas e as alterações radiológicas pulmonares foram constatadas apenas nas crianças menores de 3 anos de idade, em sua maioria vacinadas previamente com 3 doses de BCG oral, com intervalo de uma semana entre uma dose e outra. A fonte de infecção foi um operário que trabalhou no estabelecimento durante aproximadamente dois meses em 1967 e um mês em 1969, nos locais onde eram mantidas as crianças menores de 3 anos de idade. A vacina administrada por esse método não parece ter influenciado nas conversões tuberculínicas e no desenvolvimento de imunidade específica.Two epidemics of tuberculosis in children under three years of age vaccinated with oral BCG, in the year of 1967 and 1969, in a day-nursery in S. Paulo borough, are here described. In 1967 there were 96 children in the place, at first non-reactors, to the standard

Immunometabolic Pathways in BCG-Induced Trained Immunity

NARCIS (Netherlands)

Arts, R.J.; Carvalho, A.; Rocca, C. La; Palma, C.; Rodrigues, F.; Silvestre, R.; Kleinnijenhuis, J.; Lachmandas, E.; Goncalves, L.G.; Belinha, A.; Cunha, C.; Oosting, M.; Joosten, L.A.; Matarese, G.; Crevel, R. van; Netea, M.G.

2016-01-01

The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity.

A review of the literature on the economics of vaccination against TB

NARCIS (Netherlands)

Tu, H.A.; Vu, H.D.; Rozenbaum, M.H.; Woerdenbag, H.J.; Postma, M.J.

The BCG vaccine was introduced in 1921 and remains the only licensed vaccine for the prevention of TB worldwide. Despite its extensive use, the BCG vaccine lacks the ability to fully control the TB-endemic and -pandemic situations. The BCG vaccine is most effective in preventing pediatric TB, in

The benefits and risks of bacille Calmette-Guérin vaccination among infants at high risk for both tuberculosis and severe combined immunodeficiency: assessment by Markov model

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Cameron D William

2006-03-01

Full Text Available Abstract Background Bacille Calmette-Guérin (BCG vaccine is given to Canadian Aboriginal neonates in selected communities. Severe reactions and deaths associated with BCG have been reported among infants born with immunodeficiency syndromes. The main objective of this study was to estimate threshold values for severe combined immunodeficiency (SCID incidence, above which BCG is associated with greater risk than benefit. Methods A Markov model was developed to simulate the natural histories of tuberculosis (TB and SCID in children from birth to 14 years. The annual risk of tuberculous infection (ARI and SCID incidence were varied in analyses. The model compared a scenario of no vaccination to intervention with BCG. Appropriate variability and uncertainty analyses were conducted. Outcomes included TB incidence and quality-adjusted life years (QALYs. Results In sensitivity analyses, QALYs were lower among vaccinated infants if the ARI was 0.1% and the rate of SCID was higher than 4.2 per 100,000. Assuming an ARI of 1%, this threshold increased to 41 per 100,000. In uncertainty analyses (Monte Carlo simulations which assumed an ARI of 0.1%, QALYs were not significantly increased by BCG unless SCID incidence is 0. With this ARI, QALYs were significantly decreased among vaccinated children if SCID incidence exceeds 23 per 100,000. BCG is associated with a significant increase in QALYs if the ARI is 1%, and SCID incidence is below 5 per 100,000. Conclusion The possibility that Canadian Aboriginal children are at increased risk for SCID has serious implications for continued BCG use in this population. In this context, enhanced TB Control – including early detection and treatment of infection – may be a safer, more effective alternative.

Early BCG-Denmark and Neonatal Mortality Among Infants Weighing <2500 g: A Randomized Controlled Trial

DEFF Research Database (Denmark)

Biering-Sørensen, Sofie; Aaby, Peter; Lund, Najaaraq

2017-01-01

-Denmark” (intervention group; n = 2083) or “control” (local policy for LW and no BCG-Denmark; n = 2089) at discharge from the maternity ward or at first contact with the health center. The infants were randomized (1:1) without blinding in blocks of 24. Data was analyzed in Cox hazards models providing mortality rate...... ratios (MRRs). We had prespecified an analysis censoring follow-up at oral poliovirus vaccine campaigns. Results. Early administration of BCG-Denmark was associated with a nonsignificant reduction in neonatal mortality rate (MRR, 0.70; 95% confidence interval [CI], .47–1.04) and a 34% reduction (0......Background. BCG vaccine may reduce overall mortality by increasing resistance to nontuberculosis infections. In 2 randomized trials in Guinea-Bissau of early BCG-Denmark (Statens Serum Institut) given to low-weight (LW) neonates (mortality rates, we observed...

Immune reconstitution inflammatory syndrome in children | Rabie ...

African Journals Online (AJOL)

IRIS) occurs in up to 21% of children initiating antiretroviral therapy. Mycobacterial diseases are the most common, with BCG-vaccine adenitis predominating in infants and Mycobacterium tuberculosis (TB) in older children. The difficulty of ...

Neonatal BCG has no effect on allergic sensitization and suspected food allergy until 13 months

DEFF Research Database (Denmark)

Thøstesen, Lisbeth Marianne; Kjaer, Henrik Fomsgaard; Pihl, Gitte Thybo

2017-01-01

BACKGROUND: Vaccination with Bacillus Calmette-Guérin (BCG) is used in many countries as protection against tuberculosis. Studies have suggested that BCG may also have non-specific effects, reducing non-tuberculosis mortality, morbidity, and atopic manifestations. In this study we evaluated...

The relationship between nutritional and sociodemographic factors and the likelihood of children in the Dominican Republic having a BCG scar Relación entre los factores nutricionales y sociodemográficos y la probabilidad de que los niños de la República Dominicana tengan cicatriz de BCG

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Eddy Pérez-Then

2007-06-01

Full Text Available OBJECTIVES: To critically assess the prevalence among schoolchildren 6 to 9 years of age throughout the Dominican Republic of a bacille Calmette-Guérin (BCG vaccination scar, and to examine the relationship between nutritional and sociodemographic factors and the likelihood of having a BCG scar. METHODS: This correlational study used the database of the Second National Census on Height and Weight of Elementary School First Grade Students, which was conducted in the Dominican Republic August 2001-May 2002, to provide a critical assessment of BCG coverage nationwide. The Census information for the children included the presence of BCG scar, their nutritional status, and basic demographic data. We developed a new sociodemographic indicator, the "Rosa Index," to examine the potential influence of poverty and other environmental characteristics on scar presence. We used logistic regression models to predict the presence of a BCG scar. RESULTS: An overall BCG scar prevalence of 55.3% (85 644/154 887 was found. Malnourished children were less likely to have a BCG scar than were children with adequate nutritional status (odds ratio = 0.91; 95% confidence interval: 0.87, 0.95, P OBJETIVOS: Evaluar críticamente la prevalencia de cicatrices por la vacunación con el bacilo de Calmette-Guérin (BCG en niños de 6 a 9 años de la República Dominicana y examinar la relación entre los factores nutricionales y socioeconómicos y la probabilidad de tener cicatriz de BCG. MÉTODOS: Para este estudio correlacional se empleó la base de datos del II Censo Nacional de Talla y Peso en Escolares de Primer Grado de Básica, realizado en la República Dominicana entre agosto de 2001 y mayo de 2002, para evaluar críticamente el nivel de cobertura nacional de la vacunación con BCG. Entre la información censal de los niños estaban si tenían cicatriz de BCG, su estado nutricional y sus datos demográficos básicos. Se desarrolló un nuevo indicador sociodemogr

Clinical features and outcome of eleven patients with disseminated Bacille Calmette-Guerin (BCG) infection

International Nuclear Information System (INIS)

Al-Arishi, Haider M.; Frayha, Husn H.; Qari, Hussni Y.; Al-Rayes, H.; Tufenkeji, Haysam T.; Harfi, H.

1996-01-01

Disseminated BCG infection is a very rare complication of BCG vaccination. This study presents 11 patients with such complication. The underlying disease in eight of the 11 patients was primary immunodeficiency. Seven of these had severe combined immune deficiency (SCID) and one had isolated T-cell defect. Of the three remaining patients, one was healthy, one was diagnosed with mucocutaneous candidiasis and the third was diagnosed with leukocytoclastic vasculitis. Cutaneous nodular lesion, persistent fever, hepatosplenomegaly and pulmonary symptoms were common presenting features. All but one patient received antituberculous treatment. Four of 11 patients died because of extensive BCG disease. Three of these had SCID and one had T-cell deficiency. Patients with SCID who survived had bone marrow transplantation in addition to antituberculous chemotherapy. We conclude that a family history of immunodeficiency should be sought and if suggestive, BCG vaccine should be deferred until the immune status of the baby is clarified. In addition, early diagnosis is important for successful outcome. Bone marrow transplant on an emergency basis is the treatment of choice in patients with SCID and disseminated BCG infection, as immune reconstitution is essential to control infection in these patients. (author)

Testing the hypothesis that diphtheria-tetanus-pertussis vaccine has negative non-specific and sex-differential effects on child survival in high-mortality countries.

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Aaby, Peter; Benn, Christine; Nielsen, Jens; Lisse, Ida Maria; Rodrigues, Amabelia; Ravn, Henrik

2012-01-01

Measles vaccines (MV) have sex-differential effects on mortality not explained by protection against measles infection. The authors examined whether whole-cell diphtheria-tetanus-pertussis (DTP) vaccine has sex-differential and non-specific effects. Following previous reviews and a new search, the effect of DTP on mortality up to the next vaccination was assessed in all studies where DTP was given after BCG or DTP was given after MV and there was prospective follow-up after ascertainment of vaccination status. High-mortality countries in Africa and Asia. The initial observation of negative effect of DTP generated six hypotheses, which were examined in all available studies and two randomised trials reducing the time of exposure to DTP. Consistency between studies. In the first study, DTP had negative effects on survival in contrast to the beneficial effects of BCG and MV. This pattern was repeated in the six other studies available. Second, the two 'natural experiments' found significantly higher mortality for DTP-vaccinated compared with DTP-unvaccinated children. Third, the female-male mortality ratio was increased after DTP in all nine studies; in contrast, the ratio was decreased after BCG and MV in all studies. Fourth, the increased female mortality associated with high-titre measles vaccine was found only among children who had received DTP after high-titre measles vaccine. Fifth, in six randomised trials of early MV, female but not male mortality was increased if DTP was likely to be given after MV. Sixth, the mortality rate declined markedly for girls but not for boys when DTP-vaccinated children received MV. The authors reduced exposure to DTP as most recent vaccination by administering a live vaccine (MV and BCG) shortly after DTP. Both trials reduced child mortality. These observations are incompatible with DTP merely protecting against the targeted diseases. With herd immunity to whooping cough, DTP is associated with higher mortality for girls

The 3H-thymidine incorporation into the DNA of different tissues of the guinea pip after BCG-vaccination and the radiation insultus

International Nuclear Information System (INIS)

Langbein, U.

1976-01-01

The radioprotective effects of BCG vaccines have been examined. The 3 H-thymidine incorporation into the DNA of different tissues of the guinea-pig after solitary whole-body irradiation by the doses of 160, 400, and 700 R have been used as a parameter for radiation injuries and radioprotection. The specific activity of DNA has been detected by means of liquid scintillation counting and by indirect photomeric determination of the amount at 7 h p.r. It has been revealed that independent of the chosen irradiation dose, there was no significant difference in the rate of DNA synthesis in the duodenal, testicular, bone marrow, liver, and lymphatic ganglion tissues of animals vaccinated 30 days before irradiation insultus and the rate of DNA synthesis in normal animals. Based on medical evidence, effect principles which can be observed on other antigenous radioprotective substances can be excluded this time. The dose effect curve has qualitatively the same features as the curves of cell cultures and synchronized cell systems in mammals. Furthermore, the process of DNA synthesis was observed for 56 days. During this observation period there was no significant difference to be seen in the rate of duodenal, testicular, bone marrow, and liver tissues in vaccinated and in normal animals. Only in lymphatic tissues the synthesis rate of vaccinated animals has shown a significantly more decreasing tendency than that of normal animals. A relation concerning radioprotective substances containing SH-groups and 'short-term' protectors (endotoxines) could be excluded because of medical evidence. It is suggested to carry out further tests with parameters affecting the RES in order to comprehend radioprotection after BCG vaccination. (orig./MG) [de

BCGitis and BCGosis in children with primary immunodeficiency - imaging characteristics

Energy Technology Data Exchange (ETDEWEB)

Shrot, Shai; Soudack, Michalle [Sheba Medical Center, Department of Diagnostic Imaging, Ramat-Gan (Israel); Tel Aviv University, Sackler School of Medicine, Tel Aviv (Israel); Barkai, Galia [Sheba Medical Center, Pediatric Infectious Diseases Unit, Safra Children' s Hospital, Tel-Hashomer (Israel); Ben-Shlush, Aviva [Sheba Medical Center, Department of Diagnostic Imaging, Ramat-Gan (Israel)

2016-02-15

When administered to an immune-compromised patient, BCG (Bacille Calmette-Guerin) can cause disseminated and life-threatening infections. To describe the imaging findings in children with primary immunodeficiency and BCG-related infections. We reviewed the imaging findings of children with primary immunodeficiency treated at a children's hospital during 2012-2014 with localized or disseminated BCG infection. Imaging modalities included US, CT and radiography. Nine children with primary immunodeficiency had clinical signs of post-vaccination BCGitis; seven of these children showed disseminated disease and two showed only regional lesions with characteristic ipsilateral lymphadenopathy. Overall, lymphadenopathy was the most prevalent feature (n = 8) and characteristically appeared as a ring-enhancing hypodense (CT) or hypoechoic (US) lesion. Visceral involvement with multiple abscesses appeared in the spleen (n = 2), liver (n = 1) and bones (n = 1). All lesions regressed following appropriate anti-tuberculosis treatment. BCG infection needs to be considered in children with typical findings and with suspected primary immunodeficiency. (orig.)

Bacillus Calmette-Guérin Vaccination Using a Microneedle Patch

Science.gov (United States)

Hiraishi, Yasuhiro; Nandakumar, Subhadra; Choi, Seong-O; Lee, Jeong Woo; Kim, Yeu-Chun; Posey, James E.; Sable, Suraj B.; Prausnitz, Mark R.

2011-01-01

Tuberculosis (TB) caused by Mycobacterium tuberculosis continues to be a leading cause of mortality among bacterial diseases, and the bacillus Calmette-Guerin (BCG) is the only licensed vaccine for human use against this disease. TB prevention and control would benefit from an improved method of BCG vaccination that simplifies logistics and eliminates dangers posed by hypodermic needles without compromising immunogenicity. Here, we report the design and engineering of a BCG-coated microneedle vaccine patch for a simple and improved intradermal delivery of the vaccine. The microneedle vaccine patch induced a robust cell-mediated immune response in both the lungs and spleen of guinea pigs. The response was comparable to the traditional hypodermic needle based intradermal BCG vaccination and was characterized by a strong antigen specific lymphocyte proliferation and IFN-γ levels with high frequencies of CD4+IFN-γ+, CD4+TNF-α+ and CD4+IFN-γ+TNF-α+ T cells. The BCG-coated microneedle vaccine patch was highly immunogenic in guinea pigs and supports further exploration of this new technology as a simpler, safer, and compliant vaccination that could facilitate increased coverage, especially in developing countries that lack adequate healthcare infrastructure. PMID:21277407

Strategy to better select HIV-infected individuals for latent TB treatment in BCG-vaccinated population.

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Chin-Hui Yang

Full Text Available OBJECTIVE: To evaluate the T-SPOT.TB interferon-γ releasing assay and the tuberculin skin test (TST, for the diagnosis of latent tuberculosis infection(LTBI and the development of subsequent active tuberculosis, in BCG-vaccinated HIV-infected individuals. METHODS: HIV-infected individuals without clinical suspicion of active TB or a past history of TB were enrolled from 1 January 2008 to 30 November 2010. Both T-SPOT.TB test and TST were offered to the participants whom were followed up prospectively until April 30, 2012 for development of TB. RESULTS: Among the 909 participants, 25% had positive TST reactions with cut-off point of 5 mm and 15% had positive T-SPOT.TB results. After a median follow-up of 2.97 years, there were 5 cases developed culture-confirmed active TB (all had dual positive TST and T-SPOT.TB results, and the incidence was 0.17 per 100 person-years. The relative risks (RRs for subsequent active TB in HIV-infected individuals with positive TST results, positive T-SPOT.TB results and dual positive results compared with the risk for individuals with negative results were 40.6 (95% CI 2.1-767.9, 73.9 (95% CI 3.9-1397.7 and 226.5 (95% CI 12.0-4284, respectively. The number needed to treat to prevent one subsequent TB case among patients with a positive TST, a positive T-SPOT.TB and dual positive results was 35, 22 and 8 respectively. CONCLUSIONS: Adopting positive results of the TST and T-SPOT.TB to screen LTBI among BCG-vaccinated HIV-infected individuals might be feasible. Number needed to treat for isoniazid preventive therapy could be reduced significantly by using dual positive strategy.

Rational design of diagnostic and vaccination strategies for tuberculosis

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Sibele Borsuk

Full Text Available The development of diagnostic tests which can readily differentiate between vaccinated and tuberculosis-infected individuals is crucial for the wider utilization of bacillus Calmette-Guérin (BCG as vaccine in humans and animals. BCG_0092 is an antigen that elicits specific delayed type hypersensitivity reactions similar in size and morphological aspects to that elicited by purified protein derivative, in both animals and humans infected with the tubercle bacilli. We carried out bioinformatics analyses of the BCG_0092 and designed a diagnostic test by using the predicted MHC class I epitopes. In addition, we performed a knockout of this gene by homologous recombination in the BCG vaccine strain to allow differentiation of vaccinated from infected individuals. For that, the flanking sequences of the target gene (BCG_0092were cloned into a suicide vector. Spontaneous double crossovers, which result in wild type revertants or knockouts were selected using SacB. BCG_0092 is present only in members of the Mycobacterium tuberculosis complex. Eight predicted MHC class I epitopes with potential for immunological diagnosis were defined, allowing the design of a specific diagnostic test. The strategy used to delete the (BCG_0092 gene from BCG was successful. The knockout genotype was confirmed by PCR and by Southern blot. The mutant BCG strain has the potential of inducing protection against tuberculosis without interfering with the diagnostic test based on the use of selected epitopes from BCG_0092.

High-sensitive and rapid detection of Mycobacterium tuberculosis infection by IFN-γ release assay among HIV-infected individuals in BCG-vaccinated area

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Jiang Weimin

2009-05-01

Full Text Available Abstract Background An accurate test for Mycobacterium tuberculosis infection is urgently needed in immunosuppressed populations. The aim of this study was to investigate the diagnostic power of enzyme-linked immunospot (ELISPOT-based IFN-γ release assay in detecting active and latent tuberculosis in HIV-infected population in bacillus Calmette-Guerin (BCG-vaccinated area. A total of 100 HIV-infected individuals including 32 active tuberculosis patients were recruited. An ELISPOT-based IFN-γ release assay, T-SPOT.TB, was used to evaluate the M. tuberculosis ESAT-6 and CFP-10 specific IFN-γ response. Tuberculin skin test (TST was performed for all recruited subjects. Results The subjects were divided into group HIV+ATB (HIV-infected individuals with active tuberculosis, n = 32, group HIV+LTB (HIV-infected individuals with positive results of T-SPOT.TB assay, n = 46 and group HIV only (HIV-infected individuals with negative results of T-SPOT.TB assay and without evidence of tuberculosis infection, n = 22. In group HIV+ATB and HIV+LTB, T-SPOT.TB positive rate in subjects with TST P 85% in patients with TB treatment for less than 1 month and CD4+ T cells ≥200/μl, while for patients treated for more than 3 months and CD4+ T cells Conclusion ELISPOT-based IFN-γ release assay is more sensitive and rapid for the diagnosis of TB infection in Chinese HIV-infected individuals with history of BCG vaccination, and could be an effective tool for guiding preventive treatment with isoniazid in latently infected people and for TB control in China.

Digestive juices action on the absorption and the oral BCG destination

International Nuclear Information System (INIS)

Mortatti, R.C.; Fonseca, L.

1986-01-01

The absorption and the biological routing of Mycobacterium bovis BCG vaccine following intragastric administration to mice was studied. A harmful action of gastric (GJ) and duodenal juices (DJ) on BCG cells in vitro was found. Treatment with GJ induced a significant decrease of the oxygen uptake and a moderate loss of viability as expressed by the number of colony-forming units (CFU) of BCG. Severe decreases of bacilli respiration and a notable fall of CFU counts were detected during DJ treatment. The biorouting of BCG cells was determined using carbon-14 labelled bacilli. The labelling was accomplished through a metabolic precursor of mycobacterial lipids, sup(14)C-glycerol. The levels of radioactivity recovered at the first day in the organs of mice receiving either gastric instillation of sup(14)C-BCG, sonically disrupted sup(14)-BCG or sup(14)C glycerol were very similar. Subsequently, sonicated sup(14)C-BCG and sup(14)C-glycerol were involved in a biological decay process, while the level of sup(14)C-BCG associated radioactivity remained stable in the organs from 6 to 24 days. Data on the biodecay from the small intestine and liver showed that absorptive events were fast enough to reach the highest level at 24 hours, dropping thereafter according to the complexity of the material given to the mice. In all instances, however, living BCG was not cultured from organs of mice given unlabelled BCG. The preceding data suggest that the great majority of BCG cells that passed the gut barriers were absorbed intact but not alive. (author)

Sex-differential effects of diphtheria-tetanus-pertussis vaccine for the outcome of paediatric admissions? A hospital based observational study from Guinea-Bissau

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Andersen, Annemette; Bjerregaard-Andersen, Morten; Rodrigues, Amabelia

2017-01-01

study using data from Bandim Health Project's continuous registration of all admissions to the paediatric ward at the National Hospital Simão Mendes in Bissau, we investigated whether DTP was associated with higher female than male in-hospital mortality (female/male case fatality ratio (F/M CFR......Background: In spite of protection against the targeted infections, a large volume of observational data indicates that diphtheria-tetanus-pertussis (DTP) vaccine may have a negative impact on overall childhood mortality in low-income countries, especially in girls. Methods: In an observational......-vaccinated children was 1.23 (1.03-1.46); while it was 0.95 (0.66-1.38) among the 506 children who had not received DTP. DTP-vaccinated children were older and had better socioeconomic status. Adjusted for age, BCG-vaccination, residence, and maternal education the CFR comparing DTP-vaccinated boys with DTP...

Review: New Vaccine Against Tuberculosis: Current Developments and Future Challenges

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Liu, Jun

2009-04-01

Tuberculosis (TB) continues to be a global health threat. BCG was developed as an attenuated live vaccine for tuberculosis control nearly a century ago. Despite being the most widely used vaccine in human history, BCG is not an ideal vaccine and has two major limitations: its poor efficacy against adult pulmonary TB and its disconcerting safety in immunocompromised individuals. A safer and more effective TB vaccine is urgently needed. This review article discusses current strategies to develop the next generation of TB vaccines to replace BCG. While some progresses have been made in the past decade, significant challenges lie ahead.

PPD-induced monocyte mitochondrial damage is associated with a protective effect to develop tuberculosis in BCG vaccinated individuals: A cohort study.

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Marín, Diana; Marín, Nancy; Del Corral, Helena; López, Lucelly; Ramirez-Agudelo, María Elena; Rojas, Carlos A; Arbeláez, María P; García, Luis F; Rojas, Mauricio

2017-01-01

The mechanisms of mononuclear phagocyte death have been associated with the permissiveness and resistance to mycobacterial replication, but it remains unknown whether or not they help predict the risk of developing TB. To describe the factors associated with the induction of monocyte mitochondrial and membrane damage in response to PPD as well as determine if this type of damage might predict the susceptibility of developing active tuberculosis in a cohort of household contacts (HHCs) from Medellin, Colombia from 2005 to 2008. The prospective cohort study contains 2060 HHCs patients with pulmonary tuberculosis who were meticulously followed for two years. A survey of the socio-demographic, clinical, epidemiological factors and blood samples were collected. Mononuclear cell cultures were stimulated with or without PPD and the type of monocyte death was determined by the flow of cytometry, an indicator was also used for its analysis. Logistic regression was adjusted by the Generalized Estimations Equations and the survival was estimated with the Kaplan-Meier and Cox regression. Confidence intervals were used for estimating the association. 1,859 out of 2,060 blood samples of the HHCs patients analyzed showed monocyte death. In response to PPD, 83.4% underwent mitochondrial damage while 50.9% had membrane damage. The membrane damage in response to PPD was higher in children under 4 years (OR: 1.57; (95% CI: 1.1 to 2.4) and the HHCs who slept regularly in the same household has an index case of (OR: 1.54; 95% CI: 1.0 to 2.3). After adjustment by age, comorbidities, nutritional status, proximity to index case and overcrowding, the risk of developing active TB among BCG vaccinated HHCs individuals with induction of mitochondrial damage was HR = 0.19 (95% CI: 0.1 to 0.5). The induction of monocytes mitochondrial damage by PPD stimulation correlates with protection of TB disease development in BCG-vaccinated HHCs. This represents a potential tool to predict susceptibility

Surgical management of BCG vaccine-induced regional axillary ...

African Journals Online (AJOL)

The age of the patient and mode of presentation, imaging findings, and results of tuberculin skin testing (Mantoux test) ... Primary surgical treatment (incisional drainage or biopsy) is therefore not considered an ideal form of management in BCG lymphadenitis because of the high fistulisation and poor wound healing, ...

Difference in TB10.4 T-cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis

DEFF Research Database (Denmark)

Billeskov, Rolf; Grandal, Michael V; Poulsen, Christian

2010-01-01

vaccine Ag, TB10.4, in a recombinant form, or when expressed by the pathogen Mycobacterium tuberculosis (M.tb), or by the current anti-tuberculosis vaccine, Mycobacterium bovis BCG. We showed that BCG and M.tb induced a similar CD4(+) T-cell specific TB10.4 epitope-pattern, which differed completely from...... that induced by recombinant TB10.4. This difference was not due to post-translational modifications of TB10.4 or because TB10.4 is secreted from BCG and M.tb as a complex with Rv0287. In addition, BCG and TB10.4/CAF01 were both taken up by DC and macrophages in vivo, and in vitro uptake experiments revealed...... that both TB10.4 and BCG were transported to Lamp(+)-compartments. BCG and TB10.4 however, were directed to different types of Lamp(+)-compartments in the same APC, which may lead to different epitope recognition patterns. In conclusion, we show that different vectors can induce completely different...

[Complete genome sequencing and sequence analysis of BCG Tice].

Science.gov (United States)

Wang, Zhiming; Pan, Yuanlong; Wu, Jun; Zhu, Baoli

2012-10-04

The objective of this study is to obtain the complete genome sequence of Bacillus Calmette-Guerin Tice (BCG Tice), in order to provide more information about the molecular biology of BCG Tice and design more reasonable vaccines to prevent tuberculosis. We assembled the data from high-throughput sequencing with SOAPdenovo software, with many contigs and scaffolds obtained. There are many sequence gaps and physical gaps remained as a result of regional low coverage and low quality. We designed primers at the end of contigs and performed PCR amplification in order to link these contigs and scaffolds. With various enzymes to perform PCR amplification, adjustment of PCR reaction conditions, and combined with clone construction to sequence, all the gaps were finished. We obtained the complete genome sequence of BCG Tice and submitted it to GenBank of National Center for Biotechnology Information (NCBI). The genome of BCG Tice is 4334064 base pairs in length, with GC content 65.65%. The problems and strategies during the finishing step of BCG Tice sequencing are illuminated here, with the hope of affording some experience to those who are involved in the finishing step of genome sequencing. The microarray data were verified by our results.

Efficacy of a vaccine formula against tuberculosis in cattle.

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Germinal J Canto Alarcon

Full Text Available "Test-and-slaughter" has been successful in industrialized countries to control and eradicate tuberculosis from cattle; however, this strategy is too expensive for developing nations, where the prevalence is especially high. Vaccination with the Calmette-Guérin (BCG strain has been shown to protect against the development of lesions in vaccinated animals: mouse, cattle and wildlife species. In this study, the immune response and the pathology of vaccinated (BCG-prime and BCG prime-CFP-boosted and unvaccinated (controls calves were evaluated under experimental settings. A 10(6 CFU dose of the BCG strain was inoculated subcutaneously on the neck to two groups of ten animas each. Thirty days after vaccination, one of the vaccinated groups was boosted with an M. bovis culture filtrate protein (CFP. Three months after vaccination, the three groups of animals were challenged with 5×10(5 CFU via intranasal by aerosol with a field strain of M. bovis. The immune response was monitored throughout the study. Protection was assessed based on immune response (IFN-g release prechallenge, presence of visible lesions in lymph nodes and lungs at slaughter, and presence of bacilli in lymph nodes and lung samples in histological analysis. Vaccinated cattle, either with the BCG alone or with BCG and boosted with CFP showed higher IFN-g response, fewer lesions, and fewer bacilli per lesion than unvaccinated controls after challenge. Animals with low levels of IFN-g postvaccine-prechallenge showed more lesions than animals with high levels. Results from this study support the argument that vaccination could be incorporated into control programs to reduce the incidence of TB in cattle in countries with high prevalence.

HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice.

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Tsungai Ivai Jongwe

Full Text Available Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG ΔpanCD auxotroph and modified vaccinia Ankara (MVA vaccines expressing HIV-1C mosaic Gag (GagM were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study. The BCG-GagM vaccine was stable and persisted 11.5 weeks post vaccination in BALB/c mice. Priming with BCG-GagM and boosting with MVA-GagM elicited higher Gag-specific IFN-γ ELISPOT responses than the BCG-GagM only and MVA-GagM only homologous vaccination regimens. The heterologous vaccination also generated a more balanced and persistent CD4+ and CD8+ T cell Gag-specific IFN-γ ELISPOT response with a predominant effector memory phenotype. A Th1 bias was induced by the vaccines as determined by the predominant secretion of IFN-γ, TNF-α, and IL-2. This study shows that a low dose of MVA (104 pfu can effectively boost a BCG prime expressing the same mosaic immunogen, generating strong, cellular immune responses against Gag in mice. Our data warrants further evaluation in non-human primates. A low dose vaccine would be an advantage in the resource limited countries of sub-Saharan Africa and India (where the predominating virus is HIV-1 subtype C.

Joint effect of MCP-1 genotype GG and MMP-1 genotype 2G/2G increases the likelihood of developing pulmonary tuberculosis in BCG-vaccinated individuals.

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Malathesha Ganachari

2010-01-01

Full Text Available We previously reported that the -2518 MCP-1 genotype GG increases the likelihood of developing tuberculosis (TB in non-BCG-vaccinated Mexicans and Koreans. Here, we tested the hypothesis that this genotype, alone or together with the -1607 MMP-1 functional polymorphism, increases the likelihood of developing TB in BCG-vaccinated individuals. We conducted population-based case-control studies of BCG-vaccinated individuals in Mexico and Peru that included 193 TB cases and 243 healthy tuberculin-positive controls from Mexico and 701 TB cases and 796 controls from Peru. We also performed immunohistochemistry (IHC analysis of lymph nodes from carriers of relevant two-locus genotypes and in vitro studies to determine how these variants may operate to increase the risk of developing active disease. We report that a joint effect between the -2518 MCP-1 genotype GG and the -1607 MMP-1 genotype 2G/2G consistently increases the odds of developing TB 3.59-fold in Mexicans and 3.9-fold in Peruvians. IHC analysis of lymph nodes indicated that carriers of the two-locus genotype MCP-1 GG MMP-1 2G/2G express the highest levels of both MCP-1 and MMP-1. Carriers of these susceptibility genotypes might be at increased risk of developing TB because they produce high levels of MCP-1, which enhances the induction of MMP-1 production by M. tuberculosis-sonicate antigens to higher levels than in carriers of the other two-locus MCP-1 MMP-1 genotypes studied. This notion was supported by in vitro experiments and luciferase based promoter activity assay. MMP-1 may destabilize granuloma formation and promote tissue damage and disease progression early in the infection. Our findings may foster the development of new and personalized therapeutic approaches targeting MCP-1 and/or MMP-1.

Joint effect of MCP-1 genotype GG and MMP-1 genotype 2G/2G increases the likelihood of developing pulmonary tuberculosis in BCG-vaccinated individuals.

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Ganachari, Malathesha; Ruiz-Morales, Jorge A; Gomez de la Torre Pretell, Juan C; Dinh, Jeffrey; Granados, Julio; Flores-Villanueva, Pedro O

2010-01-25

We previously reported that the -2518 MCP-1 genotype GG increases the likelihood of developing tuberculosis (TB) in non-BCG-vaccinated Mexicans and Koreans. Here, we tested the hypothesis that this genotype, alone or together with the -1607 MMP-1 functional polymorphism, increases the likelihood of developing TB in BCG-vaccinated individuals. We conducted population-based case-control studies of BCG-vaccinated individuals in Mexico and Peru that included 193 TB cases and 243 healthy tuberculin-positive controls from Mexico and 701 TB cases and 796 controls from Peru. We also performed immunohistochemistry (IHC) analysis of lymph nodes from carriers of relevant two-locus genotypes and in vitro studies to determine how these variants may operate to increase the risk of developing active disease. We report that a joint effect between the -2518 MCP-1 genotype GG and the -1607 MMP-1 genotype 2G/2G consistently increases the odds of developing TB 3.59-fold in Mexicans and 3.9-fold in Peruvians. IHC analysis of lymph nodes indicated that carriers of the two-locus genotype MCP-1 GG MMP-1 2G/2G express the highest levels of both MCP-1 and MMP-1. Carriers of these susceptibility genotypes might be at increased risk of developing TB because they produce high levels of MCP-1, which enhances the induction of MMP-1 production by M. tuberculosis-sonicate antigens to higher levels than in carriers of the other two-locus MCP-1 MMP-1 genotypes studied. This notion was supported by in vitro experiments and luciferase based promoter activity assay. MMP-1 may destabilize granuloma formation and promote tissue damage and disease progression early in the infection. Our findings may foster the development of new and personalized therapeutic approaches targeting MCP-1 and/or MMP-1.

Vaccination coverage and out-of-sequence vaccinations in rural Guinea-Bissau

DEFF Research Database (Denmark)

Hornshøj, Linda; Benn, Christine Stabell; Fernandes, Manuel

2012-01-01

OBJECTIVE: The WHO aims for 90% coverage of the Expanded Program on Immunization (EPI), which in Guinea-Bissau included BCG vaccine at birth, three doses of diphtheria-tetanus-pertussis vaccine (DTP) and oral polio vaccine (OPV) at 6, 10 and 14 weeks and measles vaccine (MV) at 9 months when...

The association between Bacillus Calmette-Guérin vaccination (1331 SSI) skin reaction and subsequent scar development in infants

DEFF Research Database (Denmark)

Birk, Nina Marie; Nissen, Thomas Nørrelykke; Ladekarl, Monica

2017-01-01

BACKGROUND: The Bacillus Calmette-Guérin vaccine (BCG) against tuberculosis is administered intradermally, and vaccination is often followed by a scar at the injection site. Among BCG-vaccinated individuals, having a scar has been associated with lower mortality. We aimed to examine the impact...... of vaccination technique for scarring in a high income setting, by assessing the associations between the post injection reaction, the wheal size, and the probability of developing a scar, and scar size. METHODS: This study was nested within a clinical multicenter study randomizing 4262 infants to either BCG...... vaccination (BCG 1331 SSI) or no intervention. In this substudy, including 492 vaccinated infants, the immediate post BCG vaccination reaction was registered as either wheal (a raised, blanched papule at the injection site), bulge (a palpable element at the injection site), or no reaction. The presence...

[Mycobacterial bovis BCG cutaneous infections following mesotherapy: 2 cases].

Science.gov (United States)

Marco-Bonnet, J; Beylot-Barry, M; Texier-Maugein, J; Barucq, J P; Supply, P; Doutre, M S; Beylot, C

2002-05-01

Infectious complications following mesotherapy are usually due to ordinary bacteria or atypical mycobacteria. We report two new cases of mycobacterial bovis BCG infections following mesotherapy. To our knowledge only one case has already been reported. A 52 year-old woman developed vaccinal MERIEUX BCG cutaneous abscesses following mesotherapy. Identification was made by a novel class of repeated sequences: Mycobacterial interspersed repetitive units. Despite prolonged anti-tuberculous therapy, complete remission was not obtained and surgical excision was performed. The second case was a 49 year-old man who developed a mycobacterial bovis BCG cutaneous abscess (Connaught) after mesotherapy, the regression of which was obtained with anti-tuberculous therapy. The severity of these two mycobacterial infections following mesotherapy illustrate the potential risks of mesotherapy. Identification is possible by molecular biology techniques (PCR and sequencing). The origin of this infection is unclear and therapeutic decision is difficult. Some authors recommend anti-tuberculous therapy but surgical excision may be necessary as in our cases.

Combined immunomodulating effects of BCG and Lentinan after intranasal application in guinea pigs.

Science.gov (United States)

Drandarska, Ivanka; Kussovski, Vesselin; Nikolaeva, Sascha; Markova, Nadya

2005-04-01

The ability of a Shiitake (Lentinus edodes) medical mushroom-derived bioactive polymer Lentinan (Ajinomoto, Japan) to modulate the immune response makes it a potential candidate for combination therapy with BCG, or as adjunct for BCG vaccination, especially in high-risk individuals. We studied the combined immune-potential effectiveness of intranasal application of Lentinan (at a dose of 1 mg/kg, three times at 2-day intervals), followed by administration of BCG (strain Sofia SL-222 at a dose of 1 x 10(8) CFU, once) in guinea pigs. Samples of broncho-alveolar lavage fluid, as well as tissue fragments of lungs, spleens and lymph nodes were obtained from four groups (combined treatment with Lentinan and BCG; only with Lentinan; only with BCG; control with saline) of animals at different intervals--1, 14 and 45 days after last treatment and were evaluated by several parameters (establishing the number, H2O2 and nitrite production, and killing ability against Mycobacterium tuberculosis and Staphylococcus aureus of alveolar macrophages; spleen index, BCG CFU in spleens and histomorphological observations). Our attention was focused both on local effects in lungs, and systematical effects in reticuloendothelial system. The results indicate that intranasal application of BCG alone, or in combination with Lentinan induced high level of alveolar macrophage activation. Pre-treatment with Lentinan enhanced the local immunohistological response to BCG in lung and reduced the generalized side effects.

Effects of MVA85A vaccine on tuberculosis challenge in animals: systematic review

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Kashangura, Rufaro; Sena, Emily S; Young, Taryn; Garner, Paul

2015-01-01

Background: The existing Bacillus Calmette–Guérin (BCG) vaccination provides partial protection against tuberculosis (TB). The modified vaccinia ankara virus-expressing antigen 85A (MVA85A) aims to boost BCG immunity. We evaluated the animal evidence supporting the testing of MVA85A in humans. Methods: Our protocol included in vivo preclinical studies of the MVA85A booster with BCG compared with BCG alone, followed by a TB challenge. We used standard methods for systematic review of animal studies, and summarized mortality, measures of pathology and lung bacterial load. The comprehensive literature search was to September 2014. Two independent investigators assessed eligibility and performed data extraction. We assessed study quality and pooled bacteria load using random effect meta-analysis. Findings: We included eight studies in 192 animals. Three experiments were in mice, two in guinea pigs, two in macaques and one in calves. Overall, study quality was low with no randomization, baseline comparability not described and blinding not reported. For animal death (including euthanasia due to severe morbidity), studies were underpowered, and overall no benefit demonstrated. No difference was shown for lung pathology measured on an ordinal scale or bacterial load. The largest mortality trial carried out in macaques had more deaths in the MVA85A vaccine group, and was published after a trial in South Africa had started recruiting children. Conclusions: This independent assessment of the animal data does not provide evidence to support efficacy of MVA85A as a BCG booster. More rigorous conduct and reporting of preclinical research are warranted, and we believe the results of studies should be publicly available before embarking on trials in humans, irrespective of the findings. PMID:26351306

Compliance with the vaccination schedule in children hospitalized with pneumonia and associated factors

Science.gov (United States)

da Silva, Amanda Tabosa Pereira; Lima, Eduardo Jorge da Fonseca; Caminha, Maria de Fátima Costa; da Silva, Andresa Tabosa Pereira; Rodrigues, Edil de Albuquerque; dos Santos, Carmina Silva

2018-01-01

ABSTRACT OBJECTIVE: To verify the adequacy and factors associated with compliance with the immunization schedule (BCG, DTP-Hib, MMR, PCV-10) in children hospitalized with pneumonia at a pediatric referral hospital in Northeast Brazil. METHODS: This is a cross-sectional, descriptive study with an analytical component, with a sample of 452 children hospitalized with pneumonia at the Instituto de Medicina Integral Prof. Fernando Figueira, between 2010 and 2013. The inclusion criterion was children aged from one month to less than five years of age with proof in the immunization record. The exclusion criterion was the presence of hospital-acquired pneumonia or concomitant disease. We have evaluated the adequacy of the immunization schedule for the BCG, tetravalent, MMR, and 10-valent pneumococcal conjugate (PCV-10) vaccines. We used the chi-square test and Fisher's exact test followed by multivariate Poisson regression, estimating the crude and adjusted prevalence ratios and respective 95% confidence intervals. The variables with p < 0.20 in the univariate analysis were included in the multivariate analysis. RESULTS: There was good adequacy in the immunization schedule, except for PCV-10, which presented a percentage lower than 85%. We have observed an association between adequate compliance with the immunization schedule and education level of the mother (89.9% complete high school), sex of the child (87.2% female), age of the child (94.2% younger than six months), and breastfeeding (84.3% breastfed). CONCLUSIONS: Given the high rate of education level of the mother and the high percentage of breastfeeding, we can understand that there is a better understanding of the health of the child by the mothers studied in this study, showing the effectiveness of public policies for infant feeding. However, children did not have good adequacy of the immunization schedule of PCV-10, one of the main vaccines against pneumonia, which can be one of the main factors in the causes of

Risk of Inflammatory Bowel Disease following Bacille Calmette-Guérin and Smallpox Vaccination

DEFF Research Database (Denmark)

Villumsen, Anne Marie; Jess, Tine; Sørup, Signe

2013-01-01

Childhood immunology has been suggested to play a role in development of inflammatory bowel disease (IBD) based on the studies of childhood vaccinations, infections, and treatment with antibiotics. Bacille Calmette-Guérin (BCG) and smallpox vaccinations were gradually phased-out in Denmark...... for children born between 1965 and 1976, hence allowing the study of subsequent risk of Crohn's disease and ulcerative colitis in a unique prospective design....

Tuberculin reaction and BCG scar

DEFF Research Database (Denmark)

Timmermann, Clara Amalie Gade; Biering-Sørensen, Sofie; Aaby, Peter

2015-01-01

rate ratio (MRR) comparing children with a BCG scar with those without was 0.42 (95% CI = 0.19; 0.93). There was a similar tendency for TST positivity: MRR = 0.47 (95% CI = 0.14; 1.54). For LBW children who had both a positive TST reaction and a scar, the MRR was 0.22 (95% CI = 0.05; 0.87). For NBW...

Risk of lymphoma and leukaemia after bacille Calmette-Guérin and smallpox vaccination: a Danish case-cohort study

DEFF Research Database (Denmark)

Villumsen, Marie; Sørup, Signe; Jess, Tine

2009-01-01

Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines...... cohort and analysed in a case-cohort design. BCG vaccination reduced the risk of lymphomas (HR=0.49 (95% CI: 0.26-0.93)), whereas smallpox vaccination did not (HR=1.32 (0.56-3.08)). With the small number of leukaemia cases, the analysis of leukaemia had limited power (BCG vaccination HR=0.81 (0.......31-2.16); smallpox vaccination HR=1.32 (0.49-3.53)). The present study with very reliable vaccine history information indicates a beneficial effect of BCG vaccination on the risk of lymphomas....

Vaccination of School Children With Live Mumps Virus Vaccine

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Furesz, J.; Nagler, F. P.

1970-01-01

Live, attenuated mumps virus vaccine (Mumpsvax) was administered to 146 school children 6 to 9 years of age. One child developed clinical mumps nine days after vaccination; epidemiological and serological data strongly suggest that this child had become infected before vaccination. Apart from this single instance there were no apparent clinical reactions that could be ascribed to the administration of the vaccine. Sixty-three of the 146 children with no clinical history of mumps had an initial serum neutralizing antibody titre of less than 1:2. Specific antibodies to mumps virus were detected in 93.5% of the sera of the susceptible children 28 days after vaccination, and the geometric mean antibody titre of these sera was low (1:6). Of the 80 initially seropositive children 21 (26.2%) showed a significant antibody response to the vaccine and this was influenced by the pre-existing antibody level. These data have further demonstrated the safety and efficacy of the live mumps vaccine in children. PMID:5420994

Sex differences in the effect of vaccines on the risk of hospitalization due to measles in Guinea-bissau.

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Aaby, Peter; Martins, Cesario; Bale, Carlito; Garly, May-Lill; Rodrigues, Amabelia; Biai, Sidu; Lisse, Ida M; Whittle, Hilton; Benn, Christine S

2010-04-01

Routine immunizations have non-specific and sex-differential effects on childhood mortality and morbidity in low-income countries; BCG and measles vaccine (MV) may reduce and diphtheria-tetanus-pertussis vaccine (DTP) may increase the mortality of girls relative to boys. Urban area in Guinea-Bissau, with a demographic surveillance system and registration of all pediatric hospitalizations. Guinea-Bissau experienced a large outbreak of measles infection in 2003-2004. We used hospital and community data to examine the impact of other vaccines on the risk of hospitalizations for measles infection. Vaccine efficacy (VE) against hospitalization for children aged 6 to 59 months of age was examined. We assessed whether VE depended on vaccination status for other vaccines and whether the pattern differed for boys and girls. Sex-specific vaccine efficacy against hospitalization for children aged 6 to 59 months of age. The VE depended on sex and the sequence of vaccinations. The VE of MV against hospitalization for measles was better for girls than for boys. Among children who had received MV as the most recent vaccine VE against hospitalization was as high as 96% for girls, but only 81% for boys (P = 0.002). Among children who had received DTP simultaneously with MV or DTP after MV, VE declined for girls (91%) and increased for boys (90%). Compared with having received MV as most recent vaccination, DTP simultaneously with MV or DTP after MV improved the efficacy significantly for boys and the effect was significantly different for boys and girls (P = 0.023). The female-male risk ratio of hospitalization varied significantly, depending on the most recent vaccination (P = 0.014); it was 0.28 (0.11-0.68) for MV alone, but 1.21 (0.82-1.77) for DTP but no MV, and 1.13 (0.58-2.18) for DTP simultaneously with MV or after MV. Among MV-unvaccinated children, BCG-vaccinated girls had a lower risk of measles hospitalization than DTP-vaccinated girls (RR=0.0 (0.0-0.99), exact test).

Adverse Events Following Immunization in Brazil: Age of Child and Vaccine-Associated Risk Analysis Using Logistic Regression

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Sílvia R.C. Lopes

2018-06-01

Full Text Available Objective: Vaccines are effective in controlling and eradicating infectious diseases. However, adverse events following immunization (AEFI can occur in susceptible individuals. The objective of this study was to analyze the Brazilian AEFI database and compare eight vaccines in order to profile risks of AEFIs related to the mandated pediatric schedule of immunization, considering the age and sex of the child, type of vaccine, and reported adverse events. Methods: We analyzed the Brazilian AEFI database integrating reports between 2005 and 2010 for children less than 10-years old immunized with eight mandated vaccines: diphtheria, pertussis, tetanus, Haemophilus influenzae type b (TETRA; diphtheria, tetanus, and pertussis (DTP; Bacillus Calmette–Guerin (BCG; oral poliovirus vaccine (OPV; measles, mumps, and rubella (MMR; oral rotavirus vaccine (ORV; hepatitis B (HB; and yellow fever (YF. We compared the children’s age regarding types of AEFI, evaluated AEFI factors associated with the chance of hospitalization of the child, and estimated the chance of notification of an AEFI as a function of the type of vaccine. In total, 47,105 AEFIs were observed for the mandated vaccines. Results: The highest AEFI rate was for the TETRA vaccine and the lowest was for the OPV vaccine, with 60.1 and 2.3 events per 100,000 inoculations, respectively. The TETRA vaccine showed the highest rate of hypotonic hyporesponsive episode, followed by convulsion and fever. The MMR and YF vaccines were associated with generalized rash. BCG was associated with enlarged lymph glands but showed the largest negative (protective association with hyporesponsive events and seizures. Compared with children aged 5–9-years old, young children (<1 year showed significantly higher odds of hospitalization. Conclusions: The Brazilian AEFI registry is useful to compare the magnitude and certain characteristics of adverse events associated with mandated pediatric vaccines.

Challenges and solutions for a rational vaccine design for TB-endemic regions.

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Gowthaman, Uthaman; Mushtaq, Khurram; Tan, Amabel C; Rai, Pradeep K; Jackson, David C; Agrewala, Javed N

2015-01-01

Vaccines have been successful for global eradication or control of dreaded diseases such as smallpox, diphtheria, tetanus, yellow fever, whooping cough, polio, and measles. Unfortunately, this success has not been achieved for controlling tuberculosis (TB) worldwide. Bacillus Calmette Guérin (BCG) is the only available vaccine against TB. Paradoxically, BCG has deciphered success in the Western world but has failed in TB-endemic areas. In this article, we highlight and discuss the aspects of immunity responsible for controlling Mycobacterium tuberculosis infection and factors responsible for the failure of BCG in TB-endemic countries. In addition, we also suggest strategies that contribute toward the development of successful vaccine in protecting populations where BCG has failed.

Varicella Vaccination of Children With Leukemia Without Interruption of Maintenance Therapy

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Smedegaard, Lotte Møller; Poulsen, Anja; Kristensen, Ines Ackerl

2016-01-01

Background: Varicella-zoster virus (VZV) can be fatal or cause severe complications in children with acute lymphoblastic leukemia (ALL). This analysis set out to investigate the morbidity and mortality of VZV vaccination without interruption of maintenance therapy in children with ALL. Methods......: Files of 73 seronegative children with ALL were examined for data regarding VZV vaccination and infection, and long-term seroconversion was measured. Criteria before VZV vaccination were (1) seronegative, (2) in complete remission, (3) age >= 1.0 year, (4) lymphocyte count >= 0.6 × 109/L at time...... of vaccination and (5) receiving maintenance therapy. Results: Forty-five children were vaccinated. No child died or experienced serious adverse events due to VZV vaccination. Nine children developed late chickenpox despite vaccination. Long-term protection was found in 86% of children not receiving acyclovir...

Lipoproteins of slow-growing Mycobacteria carry three fatty acids and are N-acylated by apolipoprotein N-acyltransferase BCG_2070c.

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Brülle, Juliane K; Tschumi, Andreas; Sander, Peter

2013-10-05

Lipoproteins are virulence factors of Mycobacterium tuberculosis. Bacterial lipoproteins are modified by the consecutive action of preprolipoprotein diacylglyceryl transferase (Lgt), prolipoprotein signal peptidase (LspA) and apolipoprotein N- acyltransferase (Lnt) leading to the formation of mature triacylated lipoproteins. Lnt homologues are found in Gram-negative and high GC-rich Gram-positive, but not in low GC-rich Gram-positive bacteria, although N-acylation is observed. In fast-growing Mycobacterium smegmatis, the molecular structure of the lipid modification of lipoproteins was resolved recently as a diacylglyceryl residue carrying ester-bound palmitic acid and ester-bound tuberculostearic acid and an additional amide-bound palmitic acid. We exploit the vaccine strain Mycobacterium bovis BCG as model organism to investigate lipoprotein modifications in slow-growing mycobacteria. Using Escherichia coli Lnt as a query in BLASTp search, we identified BCG_2070c and BCG_2279c as putative lnt genes in M. bovis BCG. Lipoproteins LprF, LpqH, LpqL and LppX were expressed in M. bovis BCG and BCG_2070c lnt knock-out mutant and lipid modifications were analyzed at molecular level by matrix-assisted laser desorption ionization time-of-flight/time-of-flight analysis. Lipoprotein N-acylation was observed in wildtype but not in BCG_2070c mutants. Lipoprotein N- acylation with palmitoyl and tuberculostearyl residues was observed. Lipoproteins are triacylated in slow-growing mycobacteria. BCG_2070c encodes a functional Lnt in M. bovis BCG. We identified mycobacteria-specific tuberculostearic acid as further substrate for N-acylation in slow-growing mycobacteria.

Nutritional and immunisation status, weaning practices and socio-economic conditions of under five children in three villages of Bangladesh.

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Iqbal Hossain, M; Yasmin, R; Kabir, I

1999-01-01

A total of 479 children aged 6-60 months (male/female, 240/239) were studies during 1991 to 1992. Weight for age, height for age (mean +/- SD) were 72 +/- 11%, 90 +/- 7 and 87 +/- 10% of NCHS median respectively. According to Gomez classification, 96% of children had varying degrees of protein energy malnutrition (PEM) (28.4% mild, 58.2% moderate and 9.2% severe). According to Waterlow classification 84% were stunted(36% mild, 33% moderate and 15% severe) and 67% were wasted (47% mild, 18% moderate and 2% severe). Of all children 368 (77%) received BCG and 439 (82%) received partial or full dose of DPT and Polio vaccines. Among children aged 13-60 months 75% received Measles vaccine. Weaning food was started at (mean +/- SD) 8 +/- 4 months. Low household income, parental illiteracy, small family size (< or = 6), early or late weaning and absence of BCG vaccination were significantly associated with severe PEM. Timely weaning, education and promotion of essential vaccination may reduce childhood malnutrition especially severe PEM.

Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau

DEFF Research Database (Denmark)

Roth, A.E.; Benn, Christine Stabell; Ravn, H.

2010-01-01

-up. Compared with controls, the BCG revaccinated children had a hazard ratio of 1.20 (95% confidence interval 0.77 to 1.89). Two hundred and fifty children were admitted to hospital for the first time between enrolment and the end of the study, with an incidence rate ratio for BCG revaccinated children versus...

Financing children's vaccines.

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Nelson, E Anthony S; Sack, David; Wolfson, Lara; Walker, Damian G; Seng, Lim Fong; Steele, Duncan

2009-11-20

A 2006 Commonwealth Association of Paediatric Gastroenterology and Nutrition workshop on financing children's vaccines highlighted the potential for vaccines to control diarrhoea and other diseases as well as spur economic development through better health. Clear communication of vaccination value to decision-makers is required, together with sustainable funding mechanisms. GAVI and partners have made great progress providing funding for vaccines for children in the poorest countries but other solutions may be required to achieve the same gains in middle- and high-income countries. World Health Organization has a wealth of freely available country-level data on immunisation that academics and advocates can use to communicate the economic and health benefits of vaccines to decision-makers.

Active Mycobacterium Infection Due to Intramuscular BCG Administration Following Multi-Steps Medication Errors

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MohammadReza Rafati

2015-10-01

Full Text Available Bacillus Calmette-Guérin (BCG is indicated for treatment of primary or relapsing flat urothelial cell carcinoma in situ (CIS of the urinary bladder. Disseminated infectious complications occasionally occur due to BCG as a vaccine and intravesical therapy.  Intramuscular (IM or Intravenous (IV administrations of BCG are rare medication errors which are more probable to produce systemic infections. This report presents 13 years old case that several steps medication errors occurred consequently from physician handwriting, pharmacy dispensing, nursing administration and patient family. The physician wrote βHCG instead of HCG in the prescription. βHCG was read as BCG by the pharmacy staff and 6 vials of intravesical BCG were administered IM twice a week for 3 consecutive weeks. The patient experienced fever and chills after each injection, but he was admitted 2 months after first IM administration of BCG with fever and pancytopenia. Unfortunately four month after using drug, during second admission duo to cellulitis at the sites of BCG injection the physicians diagnosed the medication error. Using handwritten prescription and inappropriate abbreviations, spending inadequate time for taking a brief medical history in pharmacy, lack of verifying name, dose and wrote before medication administration and lack of considering medication error as an important differential diagnosis had roles to occur this multi-steps medication error.

Vaccination of dogs with six different candidate leishmaniasis vaccines composed of a chimerical recombinant protein containing ribosomal and histone protein epitopes in combination with different adjuvants.

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Poot, J; Janssen, L H M; van Kasteren-Westerneng, T J; van der Heijden-Liefkens, K H A; Schijns, V E J C; Heckeroth, A

2009-07-16

Chimerical protein "Q", composed of antigenic ribosomal and histone sequences, in combination with live BCG is a promising canine leishmaniasis vaccine candidate; one of the few vaccine candidates that have been tested successfully in dogs. Unfortunately, live BCG is not an appropriate adjuvant for commercial application due to safety problems in dogs. In order to find a safe adjuvant with similar efficacy to live BCG, muramyl dipeptide, aluminium hydroxide, Matrix C and killed Propionibacterium acnes in combination with either E. coli- or baculovirus-produced recombinant JPCM5_Q protein were tested. Groups of five or seven dogs were vaccinated with six different adjuvant-antigen combinations and challenged with a high dose intravenous injection of Leishmania infantum JPC strain promastigotes. All candidate vaccines proved to be safe, and both humoral and cellular responses to the recombinant proteins were detected at the end of the prime-boost vaccination scheme. However, clinical and parasitological data obtained during the 10 month follow-up period indicated that protection was not induced by either of the six candidate vaccines. Although no direct evidence was obtained, our data suggest that live BCG may have a significant protective effect against challenge with L. infantum in dogs.

Inhibitory effect of BCG cell-wall skeletons (BCG-CWS) emulsified in squalane on tumor growth and metastasis in mice.

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Yoo, Yung Choon; Hata, Katsusuke; Lee, Kyung Bok; Azuma, Ichiro

2002-08-01

The antimetastatic effect of BCG-CWS, which was emulsified in an oil-in-water form with either Drakeol 6VR mineral oil (BCG-CWS/DK) or squalane (BCG-CWS/SQA), on lung metastasis produced by highly metastatic murine tumor cells, Colon26-M3.1 carcinoma cells and B16-BL6 melanoma cells, was investigated in syngeneic mice. An intravenous (i.v.) administration of BCG-CWS (100 mg/mouse) 1 day after tumor inoculation significantly inhibited tumor metastasis of both Colon26-M3.1 carcinoma and B16-BL6 melanoma cells in experimental lung metastasis models. No differences in the antitumor activity of the two oil-based formulations (BCG-CWS/DK and BCG-CWS/SQA) were obverved. However, BCG-CWS/SQA administered through subcutaneous (s.c.) route was shown to be effective only when it was consecutively injected (3 times) after tumor inoculation. An in vivo analysis for tumor-induced angiogenesis showed that a single i.v. administration of BCG-CWS/SQA inhibited the number of tumor-induced blood vessels and suppressed tumor growth. Furthermore, the multiple administration of BCG-CWS/SQA given at on week intervals led to a significant reduction in spontaneous lung metastasis of B16-BL6 melanoma cells in a spontaneous metastasis model. These results suggest that BCG-CWS emulsified with squalane is a potent inhibitory agent of lung metastasis, and that the antimetastatic effect of BCG-CWS is related to the suppression of tumor growth and the inhibition of tumor-induced angiogenesis.

Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations.

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Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta

2014-06-16

Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed.

Public awareness regarding children vaccination in Jordan

OpenAIRE

Masadeh, Majed M; Alzoubi, Karem H; Al-Azzam, Sayer I; Al-Agedi, Hassan S; Abu Rashid, Baraa E; Mukattash, Tariq L

2014-01-01

Immunization can contribute to a dramatic reduction in number of vaccine-preventable diseases among children. The aim of this study is to investigate mothers? awareness about child vaccines and vaccination in Jordan. This study was a community-based, cross-sectional study that was performed at public places in Irbid City. Data was collected from 506 mothers. After verbal approval, mothers were interviewed to assess their knowledge, attitudes, and practice toward vaccination. Results show that...

Surgical Complications of Bacille Calmette-Guérin (BCG) Infection in ...

African Journals Online (AJOL)

Surgical Complications of Bacille Calmette-Guérin (BCG) Infection in HIV infected children. J Karpelowsky, A Alexander, SD Peek, A Millar, H Rode. Abstract. Aim. Bacille Calmette-Guérin (BCG) immunisation is well established as part of the South African national expanded programme for immunisation (EPI). The World ...

Mitsuda's reactions: induced by BCG in the normal Rhesus ("Macacca mulatta"

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M. J. Pereira Filho

1955-12-01

Full Text Available The reversals of Mitsuda's reactions induced by BCG have been objected to based on the possiblem interference of other determination causes of the phenomenon: tuberculous primo-infections, communicants of unsuspected leprosy, revearsals due to other causes, such as anti-diphteric and anti-tetanic vaccination, etc. In order to study the problem, we have used Rhesus monkeys (Macaca mulatta, which were reared in isolation, in an attempt to avoid the referred to interferences. Prior to the experiments, all animals were tested and found negative to radiograph, tuberculin and lepromin tests and were then submitted to the application of BCG vaccine (from 1 to 3 days old, in different doses and by different via. At different times, after the application of BCG, they were again submitted to the radiographic, tuberculin and lepromin tests. In the tables I to IV the experiences were summarised. From the experiments, the following conclusions were reached: 1 - From 12 Rhesus that received BCG 11 showed reversals of the Mitsuda reaction (91.7%. 2 - These reverseals took place both in tests effected shortly after BCG (from 6 days to 2 months, and tests effected much later (from 7 to 12 months after BCG. 3 - Some differences were found in the results, according to the dosis and the application via of the BCG. a - The testicular and peritonela via (0,02g were the only that determined strong positive Mitsuda's reactions (+++. b - By oral via, animals that received high dosis (0.6g and 1.2 g, there resulted uniform and regular reversals, even though of low intensity (+; but from those who got small doses (0.2 g. one showed no reversals in all tests, and the other presented reversals in the 2nd and 3rd tests only, also with low positivity (+. 4 In the 2nd and 3rd Mitsuda's reactions in the same animals, positivity was always precocious (generally within 48 hours, one getting the impression that there occurs a sensibilization of the animal body by the antigen with

Heterologous Immunological Effects of Early BCG Vaccination in Low-Birth-Weight Infants in Guinea-Bissau

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Jensen, Kristoffer Jarlov; Larsen, Nanna; Biering-Sørensen, Sofie

2015-01-01

or -7/8, or purified protein derivative (PPD). RESULTS:  Among 467 infants, BCG significantly increased the in vitro cytokine responses to purified protein derivative of Mycobacterium tuberculosis (PPD), as expected. BCG was also associated with increased responses to heterologous innate stimulation...

Varicella vaccination coverage of children under two years of age in Germany

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Reuss Annicka M

2010-08-01

Full Text Available Abstract Background Since July 2004, routine varicella vaccination is recommended by the German Standing Vaccination Committee in Germany. Health Insurance Funds started to cover vaccination costs at different time points between 2004 and 2006 in the Federal States. Nationwide representative data on vaccination coverage against varicella of children under two years of age are not available. We aimed to determine varicella vaccination coverage in statutory health insured children under two years of age in twelve German Federal States using data from associations of statutory health insurance physicians (ASHIPs, in order to investigate the acceptance of the recommended routine varicella vaccination programme. Methods We analysed data on varicella vaccination from 13 of 17 ASHIPs of the years 2004 to 2007. The study population consisted of all statutory health insured children under two years of age born in 2004 (cohort 2004 or 2005 (cohort 2005 in one of the studied regions. Vaccination coverage was determined by the number of children vaccinated under 2 years of age within the study population. Results Varicella vaccination coverage of children under two years of age with either one dose of the monovalent varicella vaccine or two doses of the measles, mumps, rubella, and varicella vaccine increased from 34% (cohort 2004 to 51% (cohort 2005 in the studied regions (p Conclusions Our study shows increasing varicella vaccination coverage of young children, indicating a growing acceptance of the routine varicella vaccination programme by the parents and physicians. We recommend further monitoring of vaccination coverage using data from ASHIPs to investigate acceptance of the routine vaccination programmes over time.

Drying a tuberculosis vaccine without freezing.

Science.gov (United States)

Wong, Yun-Ling; Sampson, Samantha; Germishuizen, Willem Andreas; Goonesekera, Sunali; Caponetti, Giovanni; Sadoff, Jerry; Bloom, Barry R; Edwards, David

2007-02-20

With the increasing incidence of tuberculosis and drug resistant disease in developing countries due to HIV/AIDS, there is a need for vaccines that are more effective than the present bacillus Calmette-Guérin (BCG) vaccine. We demonstrate that BCG vaccine can be dried without traditional freezing and maintained with remarkable refrigerated and room-temperature stability for months through spray drying. Studies with a model Mycobacterium (Mycobacterium smegmatis) revealed that by removing salts and cryoprotectant (e.g., glycerol) from bacterial suspensions, the significant osmotic pressures that are normally produced on bacterial membranes through droplet drying can be reduced sufficiently to minimize loss of viability on drying by up to 2 orders of magnitude. By placing the bacteria in a matrix of leucine, high-yield, free-flowing, "vial-fillable" powders of bacteria (including M. smegmatis and M. bovis BCG) can be produced. These powders show relatively minor losses of activity after maintenance at 4 degrees C and 25 degrees C up to and beyond 4 months. Comparisons with lyophilized material prepared both with the same formulation and with a commercial formulation reveal that the spray-dried BCG has better overall viability on drying.

Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations

Science.gov (United States)

Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta

2014-01-01

Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed. PMID:26344627

Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations

Directory of Open Access Journals (Sweden)

Amaya Leunda

2014-06-01

Full Text Available Novel efficient vaccines are needed to control tuberculosis (TB, a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine. In this review we provide up to date information on novel tuberculosis (TB vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed.

Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children: an observational study within a randomised trial.

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Aaby, Peter; Ravn, Henrik; Roth, Adam; Rodrigues, Amabelia; Lisse, Ida Maria; Diness, Birgitte Rode; Lausch, Karen Rokkedal; Lund, Najaaraq; Rasmussen, Julie; Biering-Sørensen, Sofie; Whittle, Hilton; Benn, Christine Stabell

2012-08-01

Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants. 2320 LBW newborns were visited at 2, 6 and 12 months of age to assess nutritional and vaccination status. The authors examined survival until the 6-month visit for children who were DTP vaccinated and DTP unvaccinated at the 2-month visit. Two-thirds of the children had received DTP at 2 months and 50 deaths occurred between the 2-month and 6-month visits. DTP vaccinated children had a better anthropometric status for all indices than DTP unvaccinated children. Small mid-upper arm circumference (MUAC) was the strongest predictor of mortality. The death rate ratio (DRR) for DTP vaccinated versus DTP unvaccinated children differed significantly for girls (DRR 2.45; 95% CI 0.93 to 6.45) and boys (DRR 0.53; 95% CI 0.23 to 1.20) (p=0.018, homogeneity test). Adjusting for MUAC, the overall effect for DTP vaccinated children was 2.62 (95% CI 1.34 to 5.09); DRR was 5.68 (95% CI 1.83 to 17.7) for girls and 1.29 (95% CI 0.56 to 2.97) for boys (p=0.023, homogeneity test). While anthropometric indices were a strong predictor of mortality among boys, there was little or no association for girls. Surprisingly, even though the children with the best nutritional status were vaccinated early, early DTP vaccination was associated with increased mortality for girls.

[Implementation of vaccinations in Chechen refugees' children in Poland].

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Hartmann, Piotr; Jackowska, Teresa

2010-01-01

Poland is a destination country or temporary living place for many refugees from Chechnya. Refugees are provided with full, free of charge, health care including the vaccination programme according to the present National Vaccination Programme (NVP). To assess the implementation of vaccinations in Chechen refugees' children in Poland. The group comprised 310 children from the Centre for Foreigners in Warsaw-Bielany. The mean age of the examined children was 7.5 years. The investigations were performed three times during the study--the first was conducted in a group of 220 children in June, the second one in 303 children in August and the third in 310 children in October 2008 (the differences in the numbers resulted from the changes in the size of the Chechen population living in the Centre). The vaccination records were assessed paying special attention to the implementation of vaccinations. During the consecutive two examinations the implementation of vaccination recommendations was analyzed as well as the availability of this information in the records. At every visit the history was obtained on the reasons for not having the vaccination programme implemented. The information on vaccination programme implementation was available in 19, 30 and 45%, of analyzed records from the Centre at the first, second and third visit, respectively. The majority of the obtained data regarded the implementation of vaccinations in children in the first year of life (85%), while the least data was on vaccinations in children over 12 years of age (30%). Similar results were obtained when analyzing a group of 168 children at the all three visits (18, 32 and 48%, respectively). The reasons for non-implementation of vaccinations were as follows: (a) low parents' awareness of the necessity of vaccinations; (b) lack of self-discipline (every other child did not report for a scheduled appointment); (c) relocation of refugees to other Centres; (d) exceedingly frequent postponing of

Different effects of BCG strains - A natural experiment evaluating the impact of the Danish and the Russian BCG strains on morbidity and scar formation in Guinea-Bissau

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Frankel, H; Byberg, S; Andersen, Morten Bjerregaard

2016-01-01

's urban study area received the Danish or Russian BCG in a natural experiment. Health center consultations were registered at point of care and scar status and size at age 4½ months. We assessed the effect of strain on consultation rates between vaccination and age 45days in Cox proportional hazards...

Effective influenza vaccines for children

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Banzhoff, Angelika; Stoddard, Jeffrey J.

2012-01-01

Seasonal influenza causes clinical illness and hospitalization in all age groups; however, conventional inactivated vaccines have only limited efficacy in young children. MF59®, an oil-in-water emulsion adjuvant, has been used since the 1990s to enhance the immunogenicity of influenza vaccines in the elderly, a population with waning immune function due to immunosenescence.   Clinical trials now provide information to support a favorable immunogenicity and safety profile of MF59-adjuvanted influenza vaccine in young children. Published data indicate that Fluad®, a trivalent seasonal influenza vaccine with MF59, was immunogenic and well tolerated in young children, with a benefit/risk ratio that supports routine clinical use. A recent clinical trial also shows that Fluad provides high efficacy against PCR-confirmed influenza. Based on the results of clinical studies in children, the use of MF59-adjuvanted vaccine offers the potential to enhance efficacy and make vaccination a viable prevention and control strategy in this population. PMID:22327501

Recombinant M. bovis BCG expressing the PLD protein promotes survival in mice challenged with a C. pseudotuberculosis virulent strain.

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Leal, Karen Silva; de Oliveira Silva, Mara Thais; de Fátima Silva Rezende, Andréa; Bezerra, Francisco Silvestre Brilhante; Begnini, Karine; Seixas, Fabiana; Collares, Tiago; Dellagostin, Odir; Portela, Ricardo Wagner; de Carvalho Azevedo, Vasco Ariston; Borsuk, Sibele

2018-06-14

The aim of this study was to evaluate the survival of mice inoculated with M. bovis BCG Pasteur recombinant expressing the PLD protein and challenged with a C. pseudotuberculosis virulent strain. Four groups were immunized with a sterile 0.9% saline solution (G1), 10 6  CFU of M. bovis BCG Pasteur (G2), 10 6  CFU of M. bovis BCG/pld (G3) or 10 6  CFU of M. bovis BCG/pld with a booster with rPLD (G4) and challenged with 10 4 CFU of C. pseudotuberculosis MIC-6 strain. The highest survival rate of 88% was observed in G4, followed by 77% in G3 and 66% in G2. A significant statistical difference was observed in the levels of cytokines IFN-γ and IL-10 in vaccinated groups (G3 and G4) when compared with the control group (G1) (p < 0.05). The results seem promising as the recombinant vaccine elicited a cellular immune response and provided significant survival after a high virulent challenge. Copyright © 2018 Elsevier Ltd. All rights reserved.

Bacillus Calmette-Guérin (BCG) Treatment Failures with Non-Muscle Invasive Bladder Cancer: A Data-Driven Definition for BCG Unresponsive Disease.

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Steinberg, Ryan L; Thomas, Lewis J; Mott, Sarah L; O'Donnell, Michael A

2016-04-27

Objective: To create the first data-driven definition for those unlikely to benefit from further BCG treatment. Materials and Methods: The database created for the Phase 2 BCG-Interferon- α 2B (IFN) study was queried and BCG failure patients were identified ( n  = 334). Full study protocols have previously been published. Separate models were constructed for analysis of patients with any CIS (pure or concomitant) and pure papillary disease. Variables considered included age, gender, stage, grade, tumor size and focality (for papillary only), number of prior BCG courses, and prior BCG failure interval. Results: Patients with recurrent CIS within 6 months of their most recent prior BCG course (HR 2.56, p  disease within 6 months (HR 1.82, p  = 0.02), ≥2 BCG failures (HR 1.54, p  = 0.03), and multifocal disease (HR 2.05, p  disease remained disease free in 38% of cases (24-51% 95% CI) at 2 years with low rates of progression. Conclusions: Patients who fail two courses of BCG with either persistent or recurrent multifocal papillary disease within 6 months or CIS within 12 months of their prior BCG should be considered BCG unresponsive. Recurrent T1 disease respond reasonably well to another course with low progression rates but further investigation is warranted.

VACCINATION OF CHILDREN WITH MALIGNANCIES

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D.Yu. Kachanov

2010-01-01

Full Text Available Children suffering from oncological diseases fall into the group of immunocompromised patients. They are more at risk of severe children’s banal infections. Development of safe and efficient methods for immunological prevention of preventable infections diseases in this group of children is one of priorities for modern medicine. It is also important to properly organise the process of vaccinating the persons surrounding the patient to eliminate the risk of postvaccinal complications in the sick (non-vaccinated child. The article provides a detailed overview of the global experience in vaccinating children with malignant neoplasms. It describes modern principles of immunological prevention in children both being administered the standard anticancer therapy and those have undergone transplantation of hemopoietic stem cells. Key words: children, malignancy, vaccination.(Pediatric Pharmacology. – 2010; 7(3:28-34

Childhood vaccination in informal urban settlements in Nairobi, Kenya: Who gets vaccinated?

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Ettarh Remare R

2011-01-01

Full Text Available Abstract Background Recent trends in global vaccination coverage have shown increases with most countries reaching 90% DTP3 coverage in 2008, although pockets of undervaccination continue to persist in parts of sub-Saharan Africa particularly in the urban slums. The objectives of this study were to determine the vaccination status of children aged between 12-23 months living in two slums of Nairobi and to identify the risk factors associated with incomplete vaccination. Methods The study was carried out as part of a longitudinal Maternal and Child Health study undertaken in Korogocho and Viwandani slums of Nairobi. These slums host the Nairobi Urban Health and Demographic Surveillance System (NUHDSS run by the African Population and Health Research Centre (APHRC. All women from the NUHDSS area who gave birth since September 2006 were enrolled in the project and administered a questionnaire which asked about the vaccination history of their children. For the purpose of this study, we used data from 1848 children aged 12-23 months who were expected to have received all the WHO-recommended vaccinations. The vaccination details were collected during the first visit about four months after birth with follow-up visits repeated thereafter at four month intervals. Full vaccination was defined as receiving all the basic childhood vaccinations by the end of 24 months of life, whereas up-to-date (UTD vaccination referred to receipt of BCG, OPV 1-3, DTP 1-3, and measles vaccinations within the first 12 months of life. All vaccination data were obtained from vaccination cards which were sighted during the household visit as well as by recall from mothers. Multivariate models were used to identify the risk factors associated with incomplete vaccination. Results Measles coverage was substantially lower than that for the other vaccines when determined using only vaccination cards or in addition to maternal recall. Up-to-date (UTD coverage with all vaccinations

A human type 5 adenovirus-based tuberculosis vaccine induces robust T cell responses in humans despite preexisting anti-adenovirus immunity.

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Smaill, Fiona; Jeyanathan, Mangalakumari; Smieja, Marek; Medina, Maria Fe; Thanthrige-Don, Niroshan; Zganiacz, Anna; Yin, Cindy; Heriazon, Armando; Damjanovic, Daniela; Puri, Laura; Hamid, Jemila; Xie, Feng; Foley, Ronan; Bramson, Jonathan; Gauldie, Jack; Xing, Zhou

2013-10-02

There is an urgent need to develop new tuberculosis (TB) vaccines to safely and effectively boost Bacille Calmette-Guérin (BCG)-triggered T cell immunity in humans. AdHu5Ag85A is a recombinant human type 5 adenovirus (AdHu5)-based TB vaccine with demonstrated efficacy in a number of animal species, yet it remains to be translated to human applications. In this phase 1 study, we evaluated the safety and immunogenicity of AdHu5Ag85A in both BCG-naïve and previously BCG-immunized healthy adults. Intramuscular immunization of AdHu5Ag85A was safe and well tolerated in both trial volunteer groups. Moreover, although AdHu5Ag85A was immunogenic in both trial volunteer groups, it much more potently boosted polyfunctional CD4(+) and CD8(+) T cell immunity in previously BCG-vaccinated volunteers. Furthermore, despite prevalent preexisting anti-AdHu5 humoral immunity in most of the trial volunteers, we found little evidence that such preexisting anti-AdHu5 immunity significantly dampened the potency of AdHu5Ag85A vaccine. This study supports further clinical investigations of the AdHu5Ag85A vaccine for human applications. It also suggests that the widely perceived negative effect of preexisting anti-AdHu5 immunity may not be universally applied to all AdHu5-based vaccines against different types of human pathogens.

Timeliness vaccination of measles containing vaccine and barriers to vaccination among migrant children in East China.

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Yu Hu

Full Text Available BACKGROUND: The reported coverage rates of first and second doses of measles containing vaccine (MCV are almost 95% in China, while measles cases are constantly being reported. This study evaluated the vaccine coverage, timeliness, and barriers to immunization of MCV1 and MCV2 in children aged from 8-48 months. METHODS: We assessed 718 children aged 8-48 months, of which 499 children aged 18-48 months in September 2011. Face to face interviews were administered with children's mothers to estimate MCV1 and MCV2 coverage rate, its timeliness and barriers to vaccine uptake. RESULTS: The coverage rates were 76.9% for MCV1 and 44.7% for MCV2 in average. Only 47.5% of surveyed children received the MCV1 timely, which postpone vaccination by up to one month beyond the stipulated age of 8 months. Even if coverage thus improves with time, postponed vaccination adds to the pool of unprotected children in the population. Being unaware of the necessity for vaccination and its schedule, misunderstanding of side-effect of vaccine, and child being sick during the recommended vaccination period were significant preventive factors for both MCV1 and MCV2 vaccination. Having multiple children, mother's education level, household income and children with working mothers were significantly associated with delayed or missing MCV1 immunization. CONCLUSIONS: To avoid future outbreaks, it is crucial to attain high coverage levels by timely vaccination, thus, accurate information should be delivered and a systematic approach should be targeted to high-risk groups.

The safety of influenza vaccines in children: An Institute for Vaccine Safety white paper.

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Halsey, Neal A; Talaat, Kawsar R; Greenbaum, Adena; Mensah, Eric; Dudley, Matthew Z; Proveaux, Tina; Salmon, Daniel A

2015-12-30

Most influenza vaccines are generally safe, but influenza vaccines can cause rare serious adverse events. Some adverse events, such as fever and febrile seizures, are more common in children than adults. There can be differences in the safety of vaccines in different populations due to underlying differences in genetic predisposition to the adverse event. Live attenuated vaccines have not been studied adequately in children under 2 years of age to determine the risks of adverse events; more studies are needed to address this and several other priority safety issues with all influenza vaccines in children. All vaccines intended for use in children require safety testing in the target age group, especially in young children. Safety of one influenza vaccine in children should not be extrapolated to assumed safety of all influenza vaccines in children. The low rates of adverse events from influenza vaccines should not be a deterrent to the use of influenza vaccines because of the overwhelming evidence of the burden of disease due to influenza in children. Copyright © 2016. Published by Elsevier Ltd.

Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children

DEFF Research Database (Denmark)

Aaby, Peter; Ravn, Henrik; Roth, Adam Anders Edvin

2012-01-01

Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants....

Parental perspectives on vaccinating children against sexually transmitted infections.

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Mays, Rose M; Sturm, Lynne A; Zimet, Gregory D

2004-04-01

Several vaccines for sexually transmitted infections (STI) are presently in development and the eventual availability of such vaccines is expected to result in the prevention of a significant number of burdensome conditions. Young adolescents are presumed to be likely targets for these vaccines since adolescents' risk for STI increases as they age and become sexually active. It is unclear, however, to what extent parents will agree to having adolescents receive STI vaccines. Inasmuch as acceptance is the foundation for effective immunization programs, an understanding of parental perspectives about this issue is required to inform future STI vaccine program strategies. This paper presents findings from a qualitative study that used in-depth interviews to elicit attitudes from 34 parents about accepting vaccines for genital herpes, human immunodeficiency virus, human papillomavirus and gonorrhea for their children (aged 8-17). Data were collected from parents bringing their children for care at an urban clinic and a suburban private office. Content analysis of the responses revealed that most parents (>70%) approved the administration of all four of the STI vaccines proposed. Parents' reasons for acceptance included wanting to protect their children, being concerned about specific disease characteristics, and previous experience with the infections. Parents who declined the vaccines did so primarily because they perceived their children to be at low risk for the infections or they had low concern about features of the diseases. Most parents thought they should be the decision-maker regarding children receiving an STI vaccine. Results from this study will be used to plan subsequent investigations of the determinants of STI vaccine acceptance by parents.

Economics of influenza vaccine administration timing for children.

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Lee, Bruce Y; Tai, Julie H Y; Bailey, Rachel R; Smith, Kenneth J; Nowalk, Andrew J

2010-03-01

To determine how much should be invested each year to encourage and operationalize the administration of influenza vaccine to children before November and how late the vaccine should be offered each year. Monte Carlo decision analytic computer simulation models. The children's influenza vaccination timing model quantified the incremental economic value of vaccinating a child earlier in the influenza season and the incremental cost of delaying vaccination. The children's monthly influenza vaccination decision model evaluated the cost-effectiveness of vaccinating versus not vaccinating for every month of the influenza season. Getting children vaccinated by the end of October rather than when they are currently getting vaccinated could save society between $6.4 million and $9.2 million plus 653 and 926 quality-adjusted life-years (QALYs) and third-party payers between $4.1 million and $6.1 million plus 647 to 942 QALYs each year. Decision makers may want to continue offering influenza vaccination to children at least through the end of December. Vaccinating with trivalent inactivated virus vaccine was more cost-effective than vaccinating with live attenuated influenza vaccine for every month. Policymakers could invest up to $6 million to $9 million a year to get children vaccinated in September or October without expending any net costs.

Measles vaccination in children with neurological disorders

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S. P. Kaplina

2012-01-01

Full Text Available The data on the current vaccination process and specific antibody in 212 children with pathology of nervous systems in age from 1 year to 6 years old, vaccinated against measles. The comparison group consisted of 36 children without neurological disease. 86 children (40,6% were vaccinated measles – mumps vaccine, and 126 children (59,4% only measles vaccine. Post-vaccination period in 77,8% immunized against measles, was uneventful, layering intercurrent infections was noted in 22,2% of vaccine’s, and demonstrated the development of viral respiratory infections, bronchitis, otitis media and exacerbation of underlying disease. It is shown that the level of specific antibody to measles in children with pathology of nervous systems at 30 days after vaccination was 5,04±0,16 log 2, which did not differ from the comparison group (5,88±0,31 log 2. No significant differences in the level of antibody in a smooth and complicated course of vaccination period were found. Immunization of children with disorders of the nervous system of live vaccines is quite effective and leads to the formation of protective antibody titers in all vaccinated.

Adenovirus type 35-vectored tuberculosis vaccine has an acceptable safety and tolerability profile in healthy, BCG-vaccinated, QuantiFERON(®)-TB Gold (+) Kenyan adults without evidence of tuberculosis.

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Walsh, Douglas S; Owira, Victorine; Polhemus, Mark; Otieno, Lucas; Andagalu, Ben; Ogutu, Bernhards; Waitumbi, John; Hawkridge, Anthony; Shepherd, Barbara; Pau, Maria Grazia; Sadoff, Jerald; Douoguih, Macaya; McClain, J Bruce

2016-05-05

In a Phase 1 trial, we evaluated the safety of AERAS-402, an adenovirus 35-vectored TB vaccine candidate expressing 3 Mycobacterium tuberculosis (Mtb) immunodominant antigens, in subjects with and without latent Mtb infection. HIV-negative, BCG-vaccinated Kenyan adults without evidence of tuberculosis, 10 QuantiFERON(®)-TB Gold In-Tube test (QFT-G)(-) and 10 QFT-G(+), were randomized 4:1 to receive AERAS-402 or placebo as two doses, on Days 0 and 56, with follow up to Day 182. There were no deaths, serious adverse events or withdrawals. For 1 AERAS-402 QFT-G(-) and 1 AERAS-402 QFT-G(+) subject, there were 3 self-limiting severe AEs of injection site pain: 1 after the first vaccination and 1 after each vaccination, respectively. Two additional severe AEs considered vaccine-related were reported after the first vaccination in AERAS-402 QFT-G(+) subjects: elevated blood creatine phosphokinase and neutropenia, the latter slowly improving but remaining abnormal until study end. AERAS-402 was not detected in urine or throat cultures for any subject. In intracellular cytokine staining studies, curtailed by technical issues, we saw modest CD4+ and CD8+ T cell responses to Mtb Ag85A/b peptide pools among both QFT-G(-) and (+) subjects, with trends in the CD4+ T cells suggestive of boosting after the second vaccine dose, slightly more so in QFT-G(+) subjects. CD4+ and CD8+ responses to Mtb antigen TB10.4 were minimal. Increases in Adenovirus 35 neutralizing antibodies from screening to end of study, seen in 50% of AERAS-402 recipients, were mostly minimal. This small study confirms acceptable safety and tolerability profiles for AERAS-402, in line with other Phase 1 studies of AERAS-402, now to include QFT-G(+) subjects. Published by Elsevier Ltd.

SAFETY AND EFFICIENCY OF INACTIVATED OF SUBUNIT INFLUENZA VACCINE AT MASS VACCINATION OF CHILDREN

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Yu.Z. Gendon

2007-01-01

Full Text Available The article considers the results of infantile mass vaccination with inactivated subunit influenza vaccine (Influvac. It shows that vaccination of 57–72% of children aged 3–17 from organized collectives residing in Mytishchi and Orekhovoczuevo districts of Moscow region was accompanied with nearly triple reduce of flu rates vs. Narofominsk and Odintsovo districts where vaccination was occasional (< 1% of children. The efficiency of the vaccination made 63,7%. Low reactogenicity of the influenza vaccine was recorded. Its convenient packing allows vaccination of large number of children in a short time. The article justifies the necessity of yearly vaccinations even in case of similarity of flu virus strain.Key words: children, mass vaccination, subunit flu vaccine, safety.

Oral vaccination of guinea pigs with a Mycobacterium bovis bacillus Calmette-Guerin vaccine in a lipid matrix protects against aerosol infection with virulent M. bovis.

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Clark, Simon; Cross, Martin L; Nadian, Allan; Vipond, Julia; Court, Pinar; Williams, Ann; Hewinson, R Glyn; Aldwell, Frank E; Chambers, Mark A

2008-08-01

Increased incidence of bovine tuberculosis (TB) in the United Kingdom caused by infection with Mycobacterium bovis is a cause of considerable economic loss to farmers and the government. The Eurasian badger (Meles meles) represents a wildlife source of recurrent M. bovis infections of cattle in the United Kingdom, and its vaccination against TB with M. bovis bacillus Calmette-Guérin (BCG) is an attractive disease control option. Delivery of BCG in oral bait holds the best prospect for vaccinating badgers over a wide geographical area. Using a guinea pig pulmonary challenge model, we evaluated the protective efficacy of candidate badger oral vaccines, based on broth-grown or ball-milled BCG, delivered either as aqueous suspensions or formulated in two lipids with differing fatty acid profiles (one being animal derived and the other being vegetable derived). Protection was determined in terms of increasing body weight after aerosol challenge with virulent M. bovis, reduced dissemination of M. bovis to the spleen, and, in the case of one oral formulation, restricted growth of M. bovis in the lungs. Only oral BCG formulated in lipid gave significant protection. These data point to the potential of the BCG-lipid formulation for further development as a tool for controlling tuberculosis in badgers.

[Active search for leprosy and other skin diseases in school children from Agua de Dios, Colombia].

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Rodríguez, Gerzaín; González, Rosalba; Gonzalez, Deysy; Granados, Carolina; Pinto, Rafael; Herrera, Hilda; Gutiérrez, Luisa F; Hernández, Elkin; López, Fernando; Gómez, Yenny

2007-01-01

Actively searching for leprosy, other skin diseases and BCG vaccination scars amongst school children from Agua de Dios, the municipality having the highest prevalence of leprosy in Colombia. A clinical examination of the children was carried out by nurses, interns, general practitioners and experts on leprosy. Skin smear tests and skin biopsies were performed when the clinical findings suggested leprosy. Anti-phenolic glycolipid antibodies in blood were determined in special cases. 86 % of the 2 844 school children were examined; 833 had skin diseases and 16 % of these required evaluation by specialists. Four new cases of paucibacillary leprosy, two indeterminate and two primary polyneuritic cases were found. Pediculosis capitis, pityriasis alba, tinea versicolor, hypopigmented nevus, insect bites and miliaria were frequently detected. BCG vaccination scars were absent in 387 children; following several logistical problems, they were vaccinated. Four children had signs of childhood abuse. An 11-year-old girl presented hypopigmented mycosis fungoides. All diseases and conditions found were treated. The community received information regarding the results, emphasising the importance of an early diagnosis of leprosy. The incidence of leprosy found (16/10,000) was 123 times higher than the rest of the country's incidence. It is advisable to continue clinical examinations in Agua de Dios and research into risk factors for acquiring leprosy.

Vaccination Patterns in Children After Autism Spectrum Disorder Diagnosis and in Their Younger Siblings.

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Zerbo, Ousseny; Modaressi, Sharareh; Goddard, Kristin; Lewis, Edwin; Fireman, Bruce H; Daley, Matthew F; Irving, Stephanie A; Jackson, Lisa A; Donahue, James G; Qian, Lei; Getahun, Darios; DeStefano, Frank; McNeil, Michael M; Klein, Nicola P

2018-05-01

In recent years, rates of vaccination have been declining. Whether this phenomenon disproportionately affects children with autism spectrum disorder (ASD) or their younger siblings is unknown. To investigate if children after receiving an ASD diagnosis obtain their remaining scheduled vaccines according to the Advisory Committee on Immunization Practices (ACIP) recommendations and to compare the vaccination patterns of younger siblings of children with ASD with the vaccination patterns of younger siblings of children without ASD. This investigation was a retrospective matched cohort study. The setting was 6 integrated health care delivery systems across the United States within the Vaccine Safety Datalink. Participants were children born between January 1, 1995, and September 30, 2010, and their younger siblings born between January 1, 1997, and September 30, 2014. The end of follow-up was September 30, 2015. Recommended childhood vaccines between ages 1 month and 12 years. The proportion of children who received all of their vaccine doses according to ACIP recommendations. The study included 3729 children with ASD (676 [18.1%] female), 592 907 children without ASD, and their respective younger siblings. Among children without ASD, 250 193 (42.2%) were female. For vaccines recommended between ages 4 and 6 years, children with ASD were significantly less likely to be fully vaccinated compared with children without ASD (adjusted rate ratio, 0.87; 95% CI, 0.85-0.88). Within each age category, vaccination rates were significantly lower among younger siblings of children with ASD compared with younger siblings of children without ASD. The adjusted rate ratios varied from 0.86 for siblings younger than 1 year to 0.96 for those 11 to 12 years old. Parents who had a child with ASD were more likely to refuse at least 1 recommended vaccine for that child's younger sibling and to limit the number of vaccines administered during the younger sibling's first year of life

Experimental animal modelling for TB vaccine development

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Pere-Joan Cardona

2017-03-01

Full Text Available Research for a novel vaccine to prevent tuberculosis is an urgent medical need. The current vaccine, BCG, has demonstrated a non-homogenous efficacy in humans, but still is the gold standard to be improved upon. In general, the main indicator for testing the potency of new candidates in animal models is the reduction of the bacillary load in the lungs at the acute phase of the infection. Usually, this reduction is similar to that induced by BCG, although in some cases a weak but significant improvement can be detected, but none of candidates are able to prevent establishment of infection. The main characteristics of several laboratory animals are reviewed, reflecting that none are able to simulate the whole characteristics of human tuberculosis. As, so far, no surrogate of protection has been found, it is important to test new candidates in several models in order to generate convincing evidence of efficacy that might be better than that of BCG in humans. It is also important to investigate the use of “in silico” and “ex vivo” models to better understand experimental data and also to try to replace, or at least reduce and refine experimental models in animals.

Vaccinations against smallpox and tuberculosis are associated with better long-term survival

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Rieckmann, Andreas; Villumsen, Marie; Sørup, Signe

2017-01-01

to natural causes of death; those who only received BCG had an aHR of 0.58 (95% CI: 0.39-0.85). Vaccinia and BCG were not associated with any protection against deaths by accidents, suicide or murder, the combined aHR being 0.94 (95% CI: 0.62-1.42). CONCLUSIONS: Vaccinia and BCG vaccinations were associated...

Factors associated with seasonal influenza vaccine uptake among children in Japan.

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Shono, Aiko; Kondo, Masahide

2015-02-18

Seasonal influenza vaccine was once part of the routine immunization schedule that is routinely offered to all children in Japan, but it is now excluded from the schedule. This study aimed to investigate factors influential to parents' decision to have their children receive seasonal influenza vaccine, as well as types of seasonal influenza vaccine information that is given to parents. We conducted a cross-sectional online survey of 555 participants who have at least one child younger than 13 years of age. Respondents were asked to categorize the history of influenza vaccination of their youngest child as either 'annual' , 'sometimes' , or 'never'. Participants were also asked about potentially influential factors in their decision to have their children receive a seasonal influenza vaccine. A total of 75% of respondents answered that their youngest child had received a seasonal influenza vaccine, and 57% of respondents answered that their child receives the vaccine every year. The higher income group was more likely than the lowest income group to have a history of influenza vaccine uptake. A recommendation from a pediatrician or school/nursery to have their child vaccinated was also positively associated with a history of influenza vaccine uptake. The most common reason for a pediatrician's recommendation was 'it leads to milder symptoms if infected'. The main finding of the study is a significant association between household income and influenza vaccination of the youngest child in the household. We also found that cost could be a barrier to vaccinating children in low income households and that information from pediatricians and schools/nurseries could motivate parents to have their children vaccinated.

The safety and immunogenicity of influenza vaccine in children with asthma in Mexico.

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Pedroza, Alvaro; Huerta, José G; Garcia, Maria de la Luz; Rojas, Arsheli; López-Martínez, Irma; Penagos, Martín; Franco-Paredes, Carlos; Deroche, Christele; Mascareñas, Cesar

2009-07-01

The morbidity and mortality associated with influenza is substantial in children with asthma. There are no available data on the safety and immunogenicity of influenza vaccine in children with asthma in Latin America. Furthermore, it is unclear if influenza vaccination may cause asthma exacerbations. We conducted a placebo-controlled trial to investigate the safety and immunogenicity of an inactivated trivalent split virus influenza vaccine in children with asthma in Mexico. We also measured the impact of influenza vaccination on pulmonary function tests in this population. The inactivated influenza vaccine was immunogenic and safe in terms of local and systemic side effects compared to placebo. We observed no significant impact on pulmonary function tests among vaccine recipients. Given the significant morbidity associated with influenza in children, strategies to promote increased influenza vaccination coverage in this high-risk group in Latin America and elsewhere are urgently needed.

Bacillus Calmette-Guérin vaccination, thymic size, and thymic output in healthy newborns

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Birk, Nina Marie; Nissen, Thomas Nørrelykke; Zingmark, Vera

2017-01-01

BACKGROUND: The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial nonspecific effects on infant health. We aimed to examine the effect of BCG at birth on thymic size and the associations between thymic output, circulating lymphocytes, risk of infection, and thymic size...... to age 3 mo were parent-reported. RESULTS: BCG vaccination did not affect thymic size at age 3 mo, measured as TI. At birth, the number of lymphocytes, CD4+ T cells, CD8+ T cells, and RTEs were positively associated with TI and TWI. Furthermore, a reduced risk of infections up to age 3 mo was associated...... with a large thymic size at birth. CONCLUSION: We found no effect of BCG vaccination on thymic size. The positive association between thymic output, lymphocytes, reduced risk of infections, and TI/TWI suggests that assessment of TI/TWI by ultrasound may be a predictor of the immunological capacity...

Vaccine Adverse Events Reported during the First Ten Years (1998–2008 after Introduction in the State of Rondonia, Brazil

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Mônica P. L. Cunha

2013-01-01

Full Text Available Despite good safety records, vaccines given to young children can cause adverse events. We investigated the reported adverse events following immunization (AEFI of vaccines given to children of less than seven years of age during the first ten years (1998 to 2008 in the state of Rondonia, Brazil. We worked with the events related to BCG (Bacillus Calmett-Guérin, HB (hepatitis B, DTwP/Hib (diphtheria-tetanus-pertussis+Hemophillus influenza b, DTP (diphtheria-tetanus-pertussis, MMR (mumps, measles, rubella, and YF (yellow fever vaccines because they were part of the recommended scheme. The number of doses of vaccines given was 3,231,567 with an average of AEFI of 57.2/year during the studied period. DTwP/Hib was responsible for 298 (57.8%, DTP 114 (22.9%, HB 31 (6%, MMR 28 (5.4%, BCG 24 (4.7%, and YF 20 (3.9% of the reported AEFI. The combination of the AEFI for DTwP/Hib vaccines showed the highest number of systemic (61.4% and local events (33.8%. Young children (≤1-year old were more susceptible to AEFI occurring in the 6 hours (54.2% following vaccine uptake. This study suggests significant differences in reactogenicity of vaccines and that despite limitations of the AEFI Brazilian registry system we cannot ignore underreporting and should use the system to expand our understanding of adverse events and effects.

Maternal characteristics associated with vaccination of young children.

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Luman, Elizabeth T; McCauley, Mary Mason; Shefer, Abigail; Chu, Susan Y

2003-05-01

Mothers can be instrumental in gaining access to vaccination services for their children. This study examines maternal characteristics associated with vaccination in US preschool children. We analyzed data from 21 212 children aged 19 to 35 months in the National Immunization Survey. Bivariate and multivariate analyses were used to identify maternal characteristics associated with completion of all recommended vaccinations in these children. Factors most strongly associated with undervaccination included having mothers who were black; had less than a high school education; were divorced, separated, or widowed; had multiple children; were eligible for the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) but not participating; or had incomes below 50% of the federal poverty level. Because most mothers play an important role in their children's vaccination, it is important to address maternal concerns and barriers when developing public health interventions for promoting childhood vaccinations. Encouraging eligible women and their children to participate in the WIC program and providing support and encouragement for immunization to mothers with multiple children may improve early childhood vaccination coverage.

When parents won't vaccinate their children: a qualitative investigation of australian primary care providers' experiences.

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Berry, Nina J; Henry, Alexandra; Danchin, Margie; Trevena, Lyndal J; Willaby, Harold W; Leask, Julie

2017-01-17

Increasingly, the experiences and perceptions of parents who decline vaccination are the subject of investigation. However, the experiences of clinicians who encounter these parents in the course of their work has received little academic attention to date. This study aimed to understand the challenges faced and strategies used when general practitioners and immunising nurses encounter parents who choose not to vaccinate their children. Primary care providers were recruited from regions identified through the Australian Childhood Immunisation Register (ACIR) as having higher than national average rates of registered objection to childhood vaccination. Interviews began with an exploration of provider experiences with parents who accept, are hesitant towards, and who decline vaccination. Participants were asked specifically about how they addressed any difficulties they encountered in their interactions. Thematic analysis focused on encounters with parents - challenges and strategies. Twenty-six general practitioners (GPs), community and practice nurses (PNs) were interviewed across two regions in NSW, Australia. Providers' sense of professional identity as health advocates and experts became conflicted in their encounters with vaccine objecting parents. Providers were dissatisfied when such consultations resulted in a 'therapeutic roadblock' whereby provider-parent communication came to a standstill. There were mixed views about being asked to sign forms exempting parents from vaccinating their children. These ranged from a belief that completing the forms rewarded parents for non-conformity to seeing it as a positive opportunity for engagement. Three common strategies were employed by providers to navigate through these challenges; 1) to explore and inform, 2) to mobilise clinical rapport and 3) to adopt a general principle to first do no harm to the therapeutic relationship. Many healthcare providers find consultations with vaccine objecting parents challenging

Bacillus Calmette-Guérin vaccination, thymic size, and thymic output in healthy newborns

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Birk, Nina Marie; Nissen, Thomas Nørrelykke; Zingmark, Vera

2017-01-01

Background: The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial nonspecific effects on infant health. We aimed to examine the effect of BCG at birth on thymic size and the associations between thymic output, circulating lymphocytes, risk of infection, and thymic size...... with a large thymic size at birth. Conclusion: We found no effect of BCG vaccination on thymic size. The positive association between thymic output, lymphocytes, reduced risk of infections, and TI/TWI suggests that assessment of TI/TWI by ultrasound may be a predictor of the immunological capacity...... in the newborn....

Vaccines for preventing influenza in healthy children.

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Jefferson, Tom; Rivetti, Alessandro; Di Pietrantonj, Carlo; Demicheli, Vittorio

2018-02-01

The consequences of influenza in children and adults are mainly absenteeism from school and work. However, the risk of complications is greatest in children and people over 65 years of age. This is an update of a review published in 2011. Future updates of this review will be made only when new trials or vaccines become available. Observational data included in previous versions of the review have been retained for historical reasons but have not been updated because of their lack of influence on the review conclusions. To assess the effects (efficacy, effectiveness, and harm) of vaccines against influenza in healthy children. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 12), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE (1966 to 31 December 2016), Embase (1974 to 31 December 2016), WHO International Clinical Trials Registry Platform (ICTRP; 1 July 2017), and ClinicalTrials.gov (1 July 2017). Randomised controlled trials comparing influenza vaccines with placebo or no intervention in naturally occurring influenza in healthy children under 16 years. Previous versions of this review included 19 cohort and 11 case-control studies. We are no longer updating the searches for these study designs but have retained the observational studies for historical purposes. Review authors independently assessed risk of bias and extracted data. We used GRADE to rate the certainty of evidence for the key outcomes of influenza, influenza-like illness (ILI), complications (hospitalisation, ear infection), and adverse events. Due to variation in control group risks for influenza and ILI, absolute effects are reported as the median control group risk, and numbers needed to vaccinate (NNVs) are reported accordingly. For other outcomes aggregate control group risks are used. We included 41 clinical trials (> 200,000 children). Most of the studies were conducted in children over the

Targeted vaccination in healthy school children - Can primary school vaccination alone control influenza?

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Thorrington, Dominic; Jit, Mark; Eames, Ken

2015-10-05

The UK commenced an extension to the seasonal influenza vaccination policy in autumn 2014 that will eventually see all healthy children between the ages of 2-16 years offered annual influenza vaccination. Models suggest that the new policy will be both highly effective at reducing the burden of influenza as well as cost-effective. We explore whether targeting vaccination at either primary or secondary schools would be more effective and/or cost-effective than the current strategy. An age-structured deterministic transmission dynamic SEIR-type mathematical model was used to simulate a national influenza outbreak in England. Costs including GP consultations, hospitalisations due to influenza and vaccinations were compared to potential gains in quality-adjusted life years achieved through vaccinating healthy children. Costs and benefits of the new JCVI vaccination policy were estimated over a single season, and compared to the hypothesised new policies of targeted and heterogeneous vaccination. All potential vaccination policies were highly cost-effective. Influenza transmission can be eliminated for a particular season by vaccinating both primary and secondary school children, but not by vaccinating only one group. The most cost-effective policy overall is heterogeneous vaccination coverage with 48% uptake in primary schools and 34% in secondary schools. The Joint Committee on Vaccination and Immunisation can consider a modification to their policy of offering seasonal influenza vaccinations to all healthy children of ages 2-16 years. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sex differences in the effect of vaccines on the risk of hospitalization due to measles in Guinea-bissau

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Aaby, Peter; Martins, Cesario; Bale, Carlito

2010-01-01

Routine immunizations have non-specific and sex-differential effects on childhood mortality and morbidity in low-income countries; BCG and measles vaccine (MV) may reduce and diphtheria-tetanus-pertussis vaccine (DTP) may increase the mortality of girls relative to boys.......Routine immunizations have non-specific and sex-differential effects on childhood mortality and morbidity in low-income countries; BCG and measles vaccine (MV) may reduce and diphtheria-tetanus-pertussis vaccine (DTP) may increase the mortality of girls relative to boys....

Human T cell responses induced by vaccination with Mycobacterium bovis bacillus Calmette-Guérin

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Ravn, P; Boesen, H; Pedersen, B K

1997-01-01

have studied in vitro cell-mediated immune responses primed by BCG vaccination in 22 healthy Danish donors with different levels of in vitro purified protein derivative (PPD) reactivity before vaccination. The study demonstrated a markedly different development of reactivity to mycobacterial Ags...... depending on the prevaccination sensitivity to PPD. Previously sensitized donors mounted a potent and highly accelerated recall response within the first week of BCG vaccination. Nonsensitized donors, in contrast, exhibited a gradually increasing responsiveness to mycobacterial Ags, reaching maximal levels...

Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for influenza vaccination in children

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2010-01-01

Background Influenza vaccination in infants and children with existing health complications is current practice in many countries, but healthy children are also susceptible to influenza, sometimes with complications. The under-recognised burden of disease in young children is greater than in elderly populations and the number of paediatric influenza cases reported does not reflect the actual frequency of influenza. Discussion Vaccination of healthy children is not widespread in Europe despite clear demonstration of the benefits of vaccination in reducing the large health and economic burden of influenza. Universal vaccination of infants and children also provides indirect protection in other high-risk groups in the community. This paper contains the Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for the vaccination of infants and children against influenza. The aim of CEVAG is to encourage the efficient and safe use of vaccines to prevent and control infectious diseases. Summary CEVAG recommends the introduction of universal influenza vaccination for all children from the age of 6 months. Special attention is needed for children up to 60 months of age as they are at greatest risk. Individual countries should decide on how best to implement this recommendation based on their circumstances. PMID:20546586

VACCINATION OF CHILDREN AGAINST MEASLES, PAROTIDITIS AND VITAMINOTHERAPY

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S.M. Kharit

2007-01-01

Full Text Available The researchers observed 45 children inoculated with the Russian divalent vaccine (measles–parotiditis. 25 children received mineral and vitamin complex «jungle» for a month since the date of vaccination. The application of «jungle» medication was efficient and conduced to prophylaxis of the complication of the vaccination, prevention of the inter current diseases among the vaccinated, as well as positively affected the intensity of the special antibody formation because of activation of cellular and antiviral mechanisms.Key words: vaccination, measles, parotiditis, prevention, mineral and vitamin complex, children.

Vaccinating high-risk children with the intranasal live-attenuated influenza vaccine: the Quebec experience.

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Quach, Caroline

2014-12-01

Given the burden of illness associated with influenza, vaccination is recommended for individuals at high risk of complications. The live-attenuated influenza vaccine (LAIV) is administered by intranasal spray, thus directly stimulating mucosal immunity. In this review, we aimed to provide evidence for its efficacy and safety in different paediatric populations. We also share the Quebec experience of LAIV use through a publicly funded vaccination program for children with chronic, high-risk conditions. from randomized controlled trials in healthy children and in asthmatics have demonstrated superior efficacy of LAIV over the injectable vaccine (IIV). LAIV is well tolerated: its administration is associated with runny nose and nasal congestion, but not with asthma exacerbations and is well tolerated in children with cystic fibrosis, when compared to IIV. The vaccine is well accepted by children and parents and can easily be part of vaccination clinics in paediatric tertiary care centres targeting children with chronic, high-risk conditions, not leading to immunosuppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

SEROLOGICAL RESPONSE TO VACCINES IN CHILDREN WITH DIABETES.

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Dashti, Anahita Sanaei; Alaei, Mohammad Reza; Musavi, Zahra; Faramarzi, Raheleh; Mansouri, Farhad; Nasimfar, Amir

2015-01-01

Patients with diabetes mellitus (DM) are more susceptible to infections. Deficiency in some domains of immune system could be one of the main reasons, which increases the risk of infections. The aim of this study was to assess antibody responses to vaccines in a group of children with diabetes and in the controls. A cross-sectional study was performed among 90 children under 15 years of age with a history of type 1 DM, referred to endocrinology clinics of university hospitals; Mofid Children Hospital and Loghman Hospital. Also, we enrolled ninety healthy children as the control group. Antibody levels against diphtheria, tetanus, pertussis, measles, mumps, rubella and hepatitis B (HB) were measured by enzyme-linked immunosorbent assay (ELISA). Among 90 patients with diabetes, 48% were male and 52% were female and in the control group 49% were male and 51% were female. Regarding IgG antibody levels against measles, there was not any significant difference between the two groups, but according to the applied kit, IgG levels against measles vaccine were positive in 62% of the diabetic and 84% of the controls. Also, there was a significant difference between the two groups in terms of IgG antibody level against rubella, but consistent with the applied kit, there was not any significant difference between the two the groups. Given the results of the study, no difference was found between patients with diabetes and controls who were vaccinated with pertussis, diphtheria, tetanus, mumps and HB vaccines. But there are some concerns about measles and rubella vaccinations that need further investigation.

Immunization dropout rate and data quality among children 12-23 months of age in Ghana.

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Baguune, Benjamin; Ndago, Joyce Aputere; Adokiya, Martin Nyaaba

2017-01-01

Immunization against diseases is one of the most important public health interventions with cost effective means to preventing childhood morbidity, mortality and disability. However, a proportion of children particularly in Africa are not fully immunized with the recommended vaccines. Thus, many children are still susceptible to the Expanded Program on Immunization (EPI) targeted diseases. The objective of this study was to determine the immunization dropout rate and data quality among children aged 12-23 months in Techiman Municipality, Ghana. A cross-sectional cluster survey was conducted among 600 children. Data was collected using semi-structured questionnaire through face-to-face interviews. Before the main data collection, the tools were pre-tested in three different communities in the Municipality. The mothers/caregivers were interviewed, extracted information from the child immunization cards and observation employed to confirm the presence of Bacillus Calmette-Guerin (BCG) scar on each child. Routine immunization data was also extracted from immunization registers and annual reports in the Municipality. I mmunization coverage for each of the fifteen vaccines doses is above 90.0% while full childhood immunized status is 89.5%. Immunization dropout rate was 5.6% (using BCG and Measles as proxy vaccines). This is lower than the 10.0% cutoff point by World Health Organization. However, routine administrative data was characterized by some discrepancies (e.g. > 100.0% immunization coverage for each of the vaccines) and high dropout rate (BCG - Measles = 31.5%). Binary regression was performed to determine predictors of dropout rate. The following were statistically significant: married (OR = 0.31; 95% = CI 0.15-0.62; and p  = 0.001), Christianity (OR = 0.27; 95% CI = 0.13-0.91; and p  dropout. Childhood full immunized status (89.5%) and immunization coverages (>90%) are high while dropout rate is lower than the recommended cutoff point by WHO

BCG strain S4-Jena: An early BCG strain is capable to reduce the proliferation of bladder cancer cells by induction of apoptosis

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Hermann Inge-Marie

2010-06-01

Full Text Available Abstract Background Intravesical immunotherapy with Mycobacterium bovis bacillus Calmette-Guérin has been established as the most effective adjuvant treatment for high risk non-muscle-invasive bladder cancer (NMIBC. We investigated the differences between the S4-Jena BCG strain and commercially available BCG strains. We tested the genotypic varieties between S4-Jena and other BCG strains and analysed the effect of the BCG strains TICE and S4-Jena on two bladder cancer cell lines. Results In contrast to commercially available BCG strains the S4-Jena strain shows genotypic differences. Spoligotyping verifies the S4-Jena strain as a BCG strain. Infection with viable S4-Jena or TICE decreased proliferation in the T24 cell line. Additionally, hallmarks of apoptosis were detectable. In contrast, Cal29 cells showed only a slightly decreased proliferation with TICE. Cal29 cells infected with S4-Jena, though, showed a significantly decreased proliferation in contrast to TICE. Concordantly with these results, infection with TICE had no effect on the morphology and hallmarks of apoptosis of Cal29 cells. However, S4-Jena strain led to clearly visible morphological changes and caspases 3/7 activation and PS flip. Conclusions S4-Jena strain has a direct influence on bladder cancer cell lines as shown by inhibition of cell proliferation and induction of apoptosis. The data implicate that the T24 cells are responder for S4-Jena and TICE BCG. However, the Cal29 cells are only responder for S4-Jena and they are non-responder for TICE BCG. S4-Jena strain may represent an effective therapeutic agent for NMIBC.

Mycobacterium leprae Activates Toll-Like Receptor-4 Signaling and Expression on Macrophages Depending on Previous Bacillus Calmette-Guerin Vaccination.

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Polycarpou, Anastasia; Holland, Martin J; Karageorgiou, Ioannis; Eddaoudi, Ayad; Walker, Stephen L; Willcocks, Sam; Lockwood, Diana N J

2016-01-01

Toll-like receptor (TLR)-1 and TLR2 have been shown to be receptors for Mycobacterium leprae (M. leprae), yet it is unclear whether M. leprae can signal through alternative TLRs. Other mycobacterial species possess ligands for TLR4 and genetic association studies in human populations suggest that people with TLR4 polymorphisms may be protected against leprosy. Using human embryonic kidney (HEK)-293 cells co-transfected with TLR4, we demonstrate that M. leprae activates TLR4. We used human macrophages to show that M. leprae stimulation of cytokine production is diminished if pre-treated with TLR4 neutralizing antibody. TLR4 protein expression was up-regulated on macrophages derived from non-bacillus Calmette-Guerin (BCG) vaccinated healthy volunteers after incubation with M. leprae, whereas it was down-regulated in macrophages derived from BCG-vaccinated donors. Finally, pre-treatment of macrophages derived from BCG-naive donors with BCG reversed the effect of M. leprae on TLR4 expression. This may be a newly described phenomenon by which BCG vaccination stimulates "non-specific" protection to the human immune system.

Immune responses after fractional doses of inactivated poliovirus vaccine using newly developed intradermal jet injectors: a randomized controlled trial in Cuba.

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Resik, Sonia; Tejeda, Alina; Mach, Ondrej; Fonseca, Magile; Diaz, Manuel; Alemany, Nilda; Garcia, Gloria; Hung, Lai Heng; Martinez, Yenisleydis; Sutter, Roland

2015-01-03

The World Health Organization recommends that, as part of the new polio endgame, a dose of inactivated poliovirus vaccine (IPV) be introduced by the end of 2015 in all countries using only oral poliovirus vaccine (OPV). Administration of fractional dose (1/5th of full dose) IPV (fIPV) intradermally may reduce costs, but its administration is cumbersome with BCG needle and syringe. We evaluated performance of two newly developed intradermal-only jet injectors and compared the immune response induced by fIPV with that induced by full-dose IPV. Children between 12 and 20 months of age, who had previously received two doses of OPV, were enrolled in Camaguey, Cuba. Subjects received a single dose of IPV (either full-dose IPV intramuscularly with needle and syringe or fIPV intradermally administered with one of two new injectors or with BCG needle or a conventional needle-free injector). Serum was tested for presence of poliovirus neutralizing antibodies on day 0 (pre-IPV) and on days 3, 7 and 21 (post-vaccination). Complete data were available from 74.2% (728/981) subjects. Baseline median antibody titers were 713, 284, and 113 for poliovirus types 1, 2, and 3, respectively. Seroprevalence at study end were similar across the intervention groups (≥ 94.8%). The immune response induced with one new injector was similar to BCG needle and to the conventional injector; and superior to the other new injector. fIPV induced significantly lower boosting response compared to full-dose IPV. No safety concerns were identified. One of the two new injectors demonstrated its ability to streamline intradermal fIPV administration, however, further investigations are needed to assess the potential contribution of fIPV in the polio endgame plan. Copyright © 2014 Elsevier Ltd. All rights reserved.

Serological response to influenza vaccination among children vaccinated for multiple influenza seasons.

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Sajjad Rafiq

Full Text Available To evaluate if, among children aged 3 to 15 years, influenza vaccination for multiple seasons affects the proportion sero-protected.Participants were 131 healthy children aged 3-15 years. Participants were vaccinated with trivalent inactivated seasonal influenza vaccine (TIV over the 2005-06, 2006-07 and 2007-8 seasons. Number of seasons vaccinated were categorized as one (2007-08; two (2007-08 and 2006-07 or 2007-08 and 2005-06 or three (2005-06, 2006-07, and 2007-08. Pre- and post-vaccination sera were collected four weeks apart. Antibody titres were determined by hemagglutination inhibition (HAI assay using antigens to A/Solomon Islands/03/06 (H1N1, A/Wisconsin/67/05 (H3N2 and B/Malaysia/2506/04. The proportions sero-protected were compared by number of seasons vaccinated using cut-points for seroprotection of 1:40 vs. 1:320. The proportions of children sero-protected against H1N1 and H3N2 was high (>85% regardless of number of seasons vaccinated and regardless of cut-point for seroprotection. For B Malaysia there was no change in proportions sero-protected by number of seasons vaccinated; however the proportions protected were lower than for H1N1 and H3N2, and there was a lower proportion sero-protected when the higher, compared to lower, cut-point was used for sero-protection.The proportion of children sero-protected is not affected by number of seasons vaccinated.

Cost Effectiveness of Influenza Vaccine for U.S. Children: Live Attenuated and Inactivated Influenza Vaccine.

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Shim, Eunha; Brown, Shawn T; DePasse, Jay; Nowalk, Mary Patricia; Raviotta, Jonathan M; Smith, Kenneth J; Zimmerman, Richard K

2016-09-01

Prior studies showed that live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, supporting the Centers for Disease Control and Prevention (CDC) recommendations in 2014 for preferential LAIV use in this age group. However, 2014-2015 U.S. effectiveness data indicated relatively poor effectiveness of both vaccines, leading CDC in 2015 to no longer prefer LAIV. An age-structured model of influenza transmission and vaccination was developed, which incorporated both direct and indirect protection induced by vaccination. Based on this model, the cost effectiveness of influenza vaccination strategies in children aged 2-8 years in the U.S. was estimated. The base case assumed a mixed vaccination strategy where 33.3% and 66.7% of vaccinated children aged 2-8 years receive LAIV and IIV, respectively. Analyses were performed in 2014-2015. Using published meta-analysis vaccine effectiveness data (83% LAIV and 64% IIV), exclusive LAIV use would be a cost-effective strategy when vaccinating children aged 2-8 years, whereas IIV would not be preferred. However, when 2014-2015 U.S. effectiveness data (0% LAIV and 15% IIV) were used, IIV was likely to be preferred. The cost effectiveness of influenza vaccination in children aged 2-8 years is highly dependent on vaccine effectiveness; the vaccine type with higher effectiveness is preferred. In general, exclusive IIV use is preferred over LAIV use, as long as vaccine effectiveness is higher for IIV than for LAIV. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Are we there yet? Travel vaccinations for Australian children.

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Slonim, Marnie; Starr, Mike; Blashki, Grant

2014-06-01

Australians travel overseas frequently and general practitioners (GPs) are often asked to provide detailed advice on travel vaccinations for children. Planning a safe and effective vaccination schedule is dependent on the context: where and when the family is travelling, the individual child's medical needs and past vaccination history, and if they are visiting family and friends. In this paper we provide an overview of the issues to consider when vaccinating Australian children for overseas travel. We also list the suite of common travel vaccinations and discuss some clinical scenarios that are likely to present in Australian general practice. Australians love to travel overseas and, increasingly, GPs are asked by patients to provide detailed advice on travel vaccinations for their children. Decisions regarding vaccinations for travelling children can be complex and the advice often differs from that provided for adults. Children differ from adults in their vulnerability to illnesses and side effects of medications. These differences, as well as their status regarding routine childhood vaccinations, all need to be taken into account. As with adults, it is important to consider the location and duration of travel and time until departure. The age of the child is also important and there may be a case for accelerating the routine childhood vaccinations in some children. The aim of this paper is to provide a clear and simple outline of the vaccination recommendations for children travelling overseas from Australia.

Was there a disparity in age appropriate infant immunization uptake in the theatre of war in the North of Sri Lanka at the height of the hostilities?: a cross-sectional study in resettled areas in the Kilinochchi district

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Parameswaran Ananthan

2012-10-01

Full Text Available Abstract Background It was long speculated that there could be under-immunized pockets in the war affected Northern part of Sri Lanka relative to other areas. With the cessation of hostilities following the military suppression of the rebellion, opportunities have arisen to appraise the immunization status of children in areas of re-settlement in former war ravaged districts. Methods We conducted a cross-sectional study to describe the coverage and age appropriateness of infant vaccinations in a former conflict district during the phase of re-settlement. The target population comprised all children of re-settled families in the age group of 12 – 23 months in the district. We selected a study sample of 300 children from among the target population using the WHO’s 30 cluster EPI survey method. Trained surveyors collected data using a structured checklist. The infant vaccination status was ascertained by reviewing vaccination records in the Child Health Development Record or any other alternative documentary evidence. Results The survey revealed that the proportion of fully vaccinated children in the district was 91%. For individual vaccines, it ranged from 92% (measles to 100% (BCG, DPT/OPV1. However, the age appropriateness of vaccination was less than 50% for all antigens except for BCG (94%. The maximum number of days of delay of vaccinations ranged from 21 days for BCG to 253 days for measles. Age appropriate vaccination rates significantly differed for DPT/OPV1-3 and measles during the conflict and post-conflict stages while it did not for the BCG. Age appropriate vaccination rates were significantly higher for DPT/OPV1-3 during the conflict while for the measles it was higher in the post conflict stage. Conclusions Though the vaccination coverage for infant vaccines in the war affected Kilinochchi district was similar to other districts in the country, it masked a disparity in terms of low age-appropriateness of infant immunizations

Tuberculous meningitis in children: a review of clinical, laboratory, epidemiological, and therapeutic aspects and of the usefulness of BCG vaccination Meningitis tuberculosa en niños: una revisión de aspectos clínicos, de laboratorio, epidemiológicos y terapéuticos y de la utilidad de la vacunación con BCG

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José William Cornejo Ochoa

2010-08-01

Full Text Available

Tuberculous meningitis is the most frequent extrapulmonary form of tuberculosis in underdeveloped countries, among them Colombia. It is associated with high rates of morbidity and mortality. In this article a review is presented of the following aspects of the disease: clinical, epidemiological, therapeutic, prophylactic by means of BCG vaccination, laboratory diagnosis, and tomographic findings.

La tuberculosis meníngea (MTB es la enfermedad tuberculosa extrapulmonar más frecuente en los países del tercer mundo, incluida Colombia, y tiene tasas altas de morbilidad y mortalidad. En este artículo se presenta una revisión de la literatura sobre los siguientes aspectos de la enfermedad: clínicos, epidemiológicos, de laboratorio, tomográficos, terapéuticos y de prevención con la vacuna BCG.

Public awareness regarding children vaccination in Jordan.

Science.gov (United States)

Masadeh, Majed M; Alzoubi, Karem H; Al-Azzam, Sayer I; Al-Agedi, Hassan S; Abu Rashid, Baraa E; Mukattash, Tariq L

2014-01-01

Immunization can contribute to a dramatic reduction in number of vaccine-preventable diseases among children. The aim of this study is to investigate mothers' awareness about child vaccines and vaccination in Jordan. This study was a community-based, cross-sectional study that was performed at public places in Irbid City. Data was collected from 506 mothers. After verbal approval, mothers were interviewed to assess their knowledge, attitudes, and practice toward vaccination. Results show that majority of mothers had acceptable knowledge and positive attitude toward vaccination. Most of mothers (94.7-86.8%) were able to identify vaccines that are mandatory as per the national vaccination program. Lower knowledge was observed among mothers (71.6%) for HIB vaccination being mandatory. Most mothers (97.2%) had vaccination card for their baby form the national vaccination programs. Vaccination delay was reported by about 36.6% of mothers and was shown to be associated with significantly (P = 0.001) lower vaccination knowledge/attitude score. Additionally, mothers who reported to be regularly offered information about vaccination during visits and those who identified medical staff members as their major information source had significantly higher vaccination knowledge/attitude score (P = 0.002). In conclusion, vaccination coverage rate is high; however, some aspects of knowledge, attitudes, and practice of vaccination need to be improved. Knowledge and attitudes of mothers were directly associated with their practice of vaccination. Medical staff education about vaccination during each visit seems to be the most effective tool that directly reflects on better practice of vaccination such as reducing the possibility for vaccination delay.

Does oral polio vaccine have non-specific effects on all-cause mortality?

DEFF Research Database (Denmark)

Aaby, Peter; Andersen, Andreas; Martins, Cesário L

2016-01-01

BACKGROUND: BCG and measles vaccine (MV) may have beneficial non-specific effects (NSEs). If an unplanned intervention with a vaccine (a natural experiment) modifies the estimated effect in a randomised controlled trial (RCT), this suggests NSEs. We used this approach to test NSEs of triple oral...... was 1.04 (0.53 to 2.04) when OPV at birth (OPV0) was not given, suggesting that early priming with OPV was important for the effect of 2-dose MV. The effect of OPV0 depended on age of administration; the MRR (2-dose/1-dose MV) was 0.45 (0.29 to 0.71) for children receiving OPV0 in the first week of life...

Associations between health communication behaviors, neighborhood social capital, vaccine knowledge, and parents' H1N1 vaccination of their children.

Science.gov (United States)

Jung, Minsoo; Lin, Leesa; Viswanath, K

2013-10-01

During the H1N1 pandemic in 2009-10, the vaccination behavior of parents played a critical role in preventing and containing the spread of the disease and the subsequent health outcomes among children. Several studies have examined the relationship between parents' health communication behaviors and vaccinations for children in general. Little is known, however, about the link between parents' health communication behaviors and the vaccination of their children against the H1N1 virus, and their level of vaccine-related knowledge. We drew on a national survey among parents with at least one child less than 18 years of age (n=639) to investigate Parents' H1N1-related health communication behaviors including sources of information, media exposure, information-seeking behaviors, H1N1-related knowledge, and neighborhood social capital, as well as the H1N1 vaccination rates of their children. Findings showed that there is a significant association between the degree at which parents obtained H1N1 vaccination for their children and health communication variables: watching the national television news and actively seeking H1N1 information. And this association was moderated by the extent of the parents' H1N1-related knowledge. In addition, the parents' degree of neighborhood social capital mediated the association between H1N1 knowledge of the parents and H1N1 vaccination acceptance for their children. We found, compared to those with a low-level of neighborhood social capital, parents who have a high-level of neighborhood social capital are more likely to vaccinate their children. These findings suggest that it is necessary to design a strategic health communication campaign segmented by parent health communication behaviors. Copyright © 2013 Elsevier Ltd. All rights reserved.

MMR vaccination of children with egg allergy is safe

DEFF Research Database (Denmark)

Andersen, Dorthe Vestergård; Jørgensen, Inger Merete

2013-01-01

Measles, mumps and rubella (MMR) vaccination is part of the Danish Childhood Vaccination Programme. It is known that children may react with anaphylaxis to MMR vaccines containing traces of egg protein. In Denmark, national clinical guidelines recommend that children with egg allergy be referred...... to vaccination at a paediatric ward despite changed recommendations in other countries. The purpose of this study was to determine whether children with egg allergy presented with anaphylactic/allergic reactions to MMR vaccination and to discuss whether Danish recommendations should be upheld....

Correlates of complete childhood vaccination in East African countries.

Directory of Open Access Journals (Sweden)

Maureen E Canavan

Full Text Available BACKGROUND: Despite the benefits of childhood vaccinations, vaccination rates in low-income countries (LICs vary widely. Increasing coverage of vaccines to 90% in the poorest countries over the next 10 years has been estimated to prevent 426 million cases of illness and avert nearly 6.4 million childhood deaths worldwide. Consequently, we sought to provide a comprehensive examination of contemporary vaccination patterns in East Africa and to identify common and country-specific barriers to complete childhood vaccination. METHODS: Using data from the Demographic and Health Surveys (DHS for Burundi, Ethiopia, Kenya, Rwanda, Tanzania, and Uganda, we looked at the prevalence of complete vaccination for polio, measles, Bacillus Calmette-Guérin (BCG and DTwPHibHep (DTP as recommended by the WHO among children ages 12 to 23 months. We conducted multivariable logistic regression within each country to estimate associations between complete vaccination status and health care access and sociodemographic variables using backwards stepwise regression. RESULTS: Vaccination varied significantly by country. In all countries, the majority of children received at least one dose of a WHO recommended vaccine; however, in Ethiopia, Tanzania, and Uganda less than 50% of children received a complete schedule of recommended vaccines. Being delivered in a public or private institution compared with being delivered at home was associated with increased odds of complete vaccination status. Sociodemographic covariates were not consistently associated with complete vaccination status across countries. CONCLUSIONS: Although no consistent set of predictors accounted for complete vaccination status, we observed differences based on region and the location of delivery. These differences point to the need to examine the historical, political, and economic context of each country in order to maximize vaccination coverage. Vaccination against these childhood diseases is a

Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival

DEFF Research Database (Denmark)

Benn, Christine S; Fisker, Ane B; Whittle, Hilton C

2016-01-01

BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore hypothesi......BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore...

BCG-induced interleukin-6 upregulation and BCG internalization in well and poorly differentiated human bladder cancer cell lines

NARCIS (Netherlands)

Bevers, R. F.; de Boer, E. C.; Kurth, K. H.; Schamhart, D. H.

1998-01-01

Intravesical bacillus Calmette-Guerin (BCG) is a successful therapy for superficial bladder cancer. However, the working mechanism of BCG after intravesical instillation is not completely understood. A functional role of urothelial (tumor) cells in the initiation of the BCG-induced immune reaction

Rotavirus specific plasma secretory immunoglobulin in children with acute gastroenteritis and children vaccinated with an attenuated human rotavirus vaccine

Science.gov (United States)

Herrera, Daniel; Vásquez, Camilo; Corthésy, Blaise; Franco, Manuel A; Angel, Juana

2013-01-01

Rotavirus (RV)–specific secretory immunoglobulin (RV-SIg) has been previously detected in serum of naturally RV infected children and shown to reflect the intestinal Ig immune response. Total plasma SIgA and plasma RV-SIg were evaluated by ELISA in children with gastroenteritis due or not due to RV infection and in 50 children vaccinated with the attenuated RIX4414 human RV vaccine and 62 placebo recipients. RV-SIg was only detected in children with evidence of previous RV infection or with acute RV gastroenteritis. Vaccinees had higher RV-SIg titers than placebo recipients and RV-SIg titers increased after the second vaccine dose. RV-SIg measured after the second dose correlated with protection when vaccinees and placebo recipients were analyzed jointly. RV-SIg may serve as a valuable correlate of protection for RV vaccines. PMID:23839157

Successes and failures in human tuberculosis vaccine development.

Science.gov (United States)

Zenteno-Cuevas, Roberto

2017-12-01

Tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium tuberculosis. In 2016, the WHO estimated 10.5 million new cases and 1.8 million deaths, making this disease the leading cause of death by an infectious agent. The current and projected TB situation necessitates the development of new vaccines with improved attributes compared to the traditional BCG method. Areas covered: In this review, the authors describe the most promising candidate vaccines against TB and discuss additional key elements in vaccine development, such as animal models, new adjuvants and immunization routes and new strategies for the identification of candidate vaccines. Expert opinion: At present, around 13 candidate vaccines for TB are in the clinical phase of evaluation; however, there is still no substitute for the BCG vaccine. One major impediment to developing an effective vaccine is our lack of understanding of several of the mechanisms associated with infection and the immune response against TB. However, the recent implementation of an entirely new set of technological advances will facilitate the proposal of new candidates. Finally, development of a new vaccine will require a major coordination of effort in order to achieve its effective administration to the people most in need of it.

Safety of influenza vaccination in children with allergic diseases

OpenAIRE

Yang, Hyeon-Jong

2015-01-01

Global guidelines strongly recommend annual influenza vaccination in people age 6 months and older, particularly in asthmatic children. There is no doubt about the benefit of influenza vaccination in asthmatic children. However, some of the vaccine's components may elicit an IgE mediated hypersensitivity or disease exacerbation, including life-threatening events, in children with allergic diseases. As a result, concerns regarding the safety of the vaccine still continue today. The influenza v...

The impact of a novel franchise clinic network on access to medicines and vaccinations in Kenya: a cross-sectional study

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Adhvaryu, Achyuta

2012-01-01

Objectives To study the impact of a new franchise health clinic model (The HealthStore Foundation's CFWShops) on access to vaccinations and treatment for acute illnesses in a nationally representative sample of children in Kenya. Design The authors used multivariate linear and count regressions to examine associations between receipt of vaccinations or treatment and proximity to a franchise health clinic, adjusting for individual, household and clinic attributes as well as region fixed effects. Setting Demographic and Health Survey data from Kenya, 2008–2009. Participants 6079 Kenyan children younger than 5 years, of whom 2310 reported recent acute illness. Main outcome measures Outcomes for all children were number of polio doses received, number of DPT doses received, receipt of BCG vaccine, receipt of measles vaccine and number of total vaccinations received. Outcomes for acutely ill children were receipt of any medical treatment, treatment for fever, treatment for malaria and treatments specifically stocked by CFWShops. Results Children living within 30 km of a CFWShop received 0.129 (p=0.017) and 0.113 (p=0.025) more DPT and polio doses, respectively; and 0.285 more total vaccinations (p=0.023). Among acutely ill children, CFWShop proximity was associated with significant increases in the probabilities of receiving any medical treatment (0.142; pfranchise health clinic model could substantially increase access to essential vaccinations and treatments in low-income countries. Moreover, the model's benefits may accrue to lesser- and higher-income households alike. PMID:22786948

The impact of a novel franchise clinic network on access to medicines and vaccinations in Kenya: a cross-sectional study.

Science.gov (United States)

Berk, Justin; Adhvaryu, Achyuta

2012-01-01

To study the impact of a new franchise health clinic model (The HealthStore Foundation's CFWShops) on access to vaccinations and treatment for acute illnesses in a nationally representative sample of children in Kenya. The authors used multivariate linear and count regressions to examine associations between receipt of vaccinations or treatment and proximity to a franchise health clinic, adjusting for individual, household and clinic attributes as well as region fixed effects. Demographic and Health Survey data from Kenya, 2008-2009. 6079 Kenyan children younger than 5 years, of whom 2310 reported recent acute illness. Outcomes for all children were number of polio doses received, number of DPT doses received, receipt of BCG vaccine, receipt of measles vaccine and number of total vaccinations received. Outcomes for acutely ill children were receipt of any medical treatment, treatment for fever, treatment for malaria and treatments specifically stocked by CFWShops. Children living within 30 km of a CFWShop received 0.129 (p=0.017) and 0.113 (p=0.025) more DPT and polio doses, respectively; and 0.285 more total vaccinations (p=0.023). Among acutely ill children, CFWShop proximity was associated with significant increases in the probabilities of receiving any medical treatment (0.142; pfranchise health clinic model could substantially increase access to essential vaccinations and treatments in low-income countries. Moreover, the model's benefits may accrue to lesser- and higher-income households alike.

Delayed-type hypersensitivity skin test responses to PPD and other antigens among BCG-vaccinated HIV-1-infected and healthy children and adolescents.

Science.gov (United States)

Costa, Natalia Moriya Xavierda; Albuquerque, Maly de; Lins, Janaína Bacelar Acioli; Alvares-Junior, João Teixeira; Stefani, Mariane Martins de Araújo

2011-10-01

Among HIV-1-infected patients, CD4+ T cell counts are well-established markers of cell-mediated immunity. Delayed-type hypersensitivity (DTH) skin tests can be used to evaluate in vivo cell-mediated immunity to common antigens. DTH responses to tuberculin purified protein derivative (PPD), sporotrichin, trichophytin, candidin and streptokinase/streptodornase antigens were assessed. Thirty-six HIV-1-infected children/adolescents and 56 age- and sex-matched HIV-1/HIV-2-seronegative participants were tested. All participants had a BCG scar. Fisher's exact test was used to evaluate significant differences between groups (pPPD positivity prevailed among healthy participants (40/56, 71.4%). PPD reactivity in the HIV-1-positive group was 8.3% (pPPD induration was 2.5mm (range: 2-5mm) in the HIV-1 group and 6.0 mm among healthy participants (range: 3-15 mm). There was no correlation between PPD positivity and age. No correlation between CD4+ T cell counts and DTH reactivity was observed among HIV-1-infected patients. DTH skin test responses, including PPD reactivity, were significantly lower among HIV-1-infected participants compared to healthy controls, which likely reflects advanced disease and T cell depletion.

Factors that affect voluntary vaccination of children in Japan.

Science.gov (United States)

Shono, Aiko; Kondo, Masahide

2015-03-10

Some important vaccinations are not included in the routine childhood immunization schedule in Japan. Voluntary vaccinations are usually paid as an out-of-pocket expense. Low voluntary vaccination coverage rates and high target disease incidence are assumed to be a consequence of voluntary vaccination. Therefore, this study aimed to explore factors associated with voluntary vaccination patterns in children. We conducted an online survey of 1243 mothers from a registered survey panel who had at least one child 2 months to <3 years of age. The voluntary vaccination mainly correlated positively with annual household income and mothers' positive opinions about voluntary vaccinations, but negatively with number of children. Financial support, especially for low income households and households with more than one child, may motivate parents to vaccinate their children. Communication is also an important issue. More opportunities for education and information about voluntary vaccinations should be provided to mothers without distinguishing between voluntary and routine vaccination. Copyright © 2014 Elsevier Ltd. All rights reserved.

A tuberculin skin test survey among Ghanaian school children.

Science.gov (United States)

Addo, Kennedy Kwasi; van den Hof, Susan; Mensah, Gloria Ivy; Hesse, Adukwei; Bonsu, Christian; Koram, Kwadwo Ansah; Afutu, Felix Kwami; Bonsu, Frank Adae

2010-01-26

Ghana has not conducted a national tuberculin survey or tuberculosis prevalence survey since the establishment of the National Tuberculosis Control Programme. The primary objective of this study was therefore to determine the prevalence of tuberculin skin sensitivity in Ghanaian school children aged 6-10 years in 8 out of 10 regions of Ghana between 2004 and 2006. Tuberculin survey was conducted in 179 primary schools from 21 districts in 8 regions. Schools were purposively selected so as to reflect the proportion of affluent private and free tuition public schools as well as the proportion of small and large schools. Of the 24,778 children registered for the survey, 23,600 (95.2%) were tested of which 21,861 (92.6%) were available for reading. The age distribution showed an increase in numbers of children towards older age: 11% of the children were 6 years and 25%, 10 years. Females were 52.5% and males 47.5%. The proportion of girls was higher in all age groups (range 51.4% to 54.0%, p < 0.001). BCG scar was visible in 89.3% of the children. The percentage of children with a BCG scar differed by district and by age. The percentage of children with a BCG scar decreased with increasing age in all districts, reflecting increasing BCG vaccination coverage in Ghana in the last ten years. The risk of tuberculosis infection was low in the northern savannah zones compared to the southern coastal zones. Using a cut-off of 15 mm, the prevalence of infection ranged from 0.0% to 5.4% and the Annual Risks of Tuberculosis Infection 0.0% to 0.6%. There was an increase in the proportion of infected children after the age of 7 years. Children attending low and middle-class schools had a higher risk of infection than children attending upper-class schools. Tuberculosis infection is still a public health problem in Ghana and to monitor the trend, the survey needs to be repeated at 5 years interval.

Internationally adopted children: what vaccines should they receive?

Science.gov (United States)

Cilleruelo, M J; de Ory, F; Ruiz-Contreras, J; González-González, R; Mellado, M J; García-Hortelano, M; Villota, J; García-Ascaso, M; Piñeiro, R; Martín-Fontelos, P; Herruzo, R

2008-10-29

It is of paramount importance to know the vaccination status in internationally adopted children, so that they can be correctly immunized. This study ascertains the seroprotection rate for vaccine-preventable diseases and the validity of the immunization cards in 637 adopted children. The absence of the immunization card (13% of children) correlated with a poor global vaccine protection. Children with immunization records (87%) had a better global seroprotection but the information obtained from the card did not accurately predict seroprotection for each particular antigen. The best variable to predict the status of seroprotection was the country of origin. The highest rate of protection was found in children from Eastern Europe and, in descending order, India, Latin America, China and Africa. General recommendations for immunization of internationally adopted children are difficult to establish. Actions for vaccination have to be mainly implemented on the basis of the existence of the immunization card and of the country of origin.

VACCINATION IN CHILDREN WITH DIFFERENT MANIFESTATIONS OF TUBERCULOSIS INFECTION

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T.S. Drozdenko

2011-01-01

Full Text Available The paper presents the experience of childhood immunization with the various manifestations of tuberculosis infection inanimate (ADC-M, Pneumo 23 and live vaccines (domestic divaccine «measles–parotitis», combined vaccine Priorix. The safety and efficacy of vaccination in this group of children with positive clinical and laboratory dynamics of tuberculosis on the background of a specific treatment have been demonstrated, as well as the vaccination tactics of children registered at the TB clinic based on the results of the study have been elaborated.Key words: various manifestations of tuberculosis infection, vaccination tactics, safety, efficiency, children.

Safety of pandemic H1N1 vaccines in children and adolescents.

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Wijnans, Leonoor; de Bie, Sandra; Dieleman, Jeanne; Bonhoeffer, Jan; Sturkenboom, Miriam

2011-10-06

During the 2009 influenza A (H1N1) pandemic several pandemic H1N1 vaccines were licensed using fast track procedures, with relatively limited data on the safety in children and adolescents. Different extensive safety monitoring efforts were put in place to ensure timely detection of adverse events following immunization. These combined efforts have generated large amounts of data on the safety of the different pandemic H1N1 vaccines, also in children and adolescents. In this overview we shortly summarize the safety experience with seasonal influenza vaccines as a background and focus on the clinical and post marketing safety data of the pandemic H1N1 vaccines in children. We identified 25 different clinical studies including 10,505 children and adolescents, both healthy and with underlying medical conditions, between the ages of 6 months and 23 years. In addition, large monitoring efforts have resulted in large amounts of data, with almost 13,000 individual case reports in children and adolescents to the WHO. However, the diversity in methods and data presentation in clinical study publications and publications of spontaneous reports hampered the analysis of safety of the different vaccines. As a result, relatively little has been learned on the comparative safety of these pandemic H1N1 vaccines - particularly in children. It should be a collective effort to give added value to the enormous work going into the individual studies by adhering to available guidelines for the collection, analysis, and presentation of vaccine safety data in clinical studies and to guidance for the clinical investigation of medicinal products in the pediatric population. Importantly the pandemic has brought us the beginning of an infrastructure for collaborative vaccine safety studies in the EU, USA and globally. Copyright © 2011 Elsevier Ltd. All rights reserved.

VACCINATION OF PREMATURE INFANTS AND CHILDREN WITH CONGENITAL HEART DISEASE IN IRKUTSK USING CONJUGATED PNEUMOCOCCAL VACCINES

Directory of Open Access Journals (Sweden)

S. V. Il'ina

2013-01-01

Full Text Available Study aim: analyzing the results of pneumococcal infection vaccination conducted to reduce infantile morbidity and mortality in 2011-2012 at the expenses of the Irkutsk municipal budget. Patients and methods. Vaccination using the 7- and 13-valent pneumococcal conjugated vaccine was conducted for more than 700 risk group children: premature infants, children with congenital heart diseases or bronchopulmonary dysplasia from 2 months to 2 years of age. 193 vaccinated children had been observed for 1.5 years. 30% of premature infants and 46% of children with congenital heart diseases were vaccinated using the PCV7/PCV13 vaccine at the age of 2-6 months, 52 and 40% - at the age of 7-11 months, accordingly. The PCV7/PCV13 vaccine was administered together with other vaccines of the national preventive vaccination calendar in 65% of cases. Results. Rate of general post-vaccinal reactions (body temperature increase from 37.6 to 38.0oC – 4%; no local reactions were registered. No other unfavorable phenomena were noted in the post-vaccinal period. No cases of pneumonia, meningitis, acute otitis media and bronchoobstructive syndrome were registered within the observation period. Conclusions: pneumococcal infection vaccination of premature infants with congenital heart diseases and bronchopulmonary dysplasia conducted in Irkutsk proved high efficacy and safety of the used vaccine – PCV7/PCV13. 

Influenza vaccination of Michigan children by provider type, 2010-2011.

Science.gov (United States)

Clayton, Joshua L; Potter, Rachel C; Wells, Eden V; Carlton, Cristi A; Boulton, Matthew L

2014-07-01

Influenza vaccination for all children aged 6 months to 18 years has been recommended since 2008 to prevent flu-related morbidity and mortality. However, 2010-2011 influenza vaccine coverage estimates show under-vaccination in children of all ages. We examined predictors of influenza vaccination in Michigan during the 2010-2011 influenza season. To determine whether immunization provider type was associated with a child's influenza vaccination in Michigan and assess whether county-level factors were confounders of the association. Influenza vaccinations reported to the Michigan Care Improvement Registry from the 2010-2011 influenza season were analyzed in 2012 to estimate ORs for the association between immunization provider type and influenza vaccination. Among 2,373,826 Michigan children aged 6 months through 17 years, 17% were vaccinated against influenza and lower vaccination rates were observed for public compared to private providers (13% vs 18%). In the unadjusted model, public providers had lower odds of vaccinating children compared to private providers (OR=0.60, 95% CI=0.60, 0.61). County-level factors, including percentage of families living below the poverty line, median household income, and percentage black race, were not shown to confound the association. In the adjusted models, public providers had lower odds of vaccinating children compared to private providers (OR=0.87, 95% CI=0.86, 0.88). Although a child's likelihood of influenza vaccination in Michigan varies by provider type, more effective strategies to improve influenza vaccination rates for all Michigan children are needed. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

VACCINATION OF CHILDREN AGAINST MEASLES, PAROTIDITIS AND VITAMINOTHERAPY

OpenAIRE

S.M. Kharit; T.V. Chernyaeva; E.P. Nacharova; O.V. Goleva

2007-01-01

The researchers observed 45 children inoculated with the Russian divalent vaccine (measles–parotiditis). 25 children received mineral and vitamin complex «jungle» for a month since the date of vaccination. The application of «jungle» medication was efficient and conduced to prophylaxis of the complication of the vaccination, prevention of the inter current diseases among the vaccinated, as well as positively affected the intensity of the special antibody formation because of activation of cel...

Rodent malaria: BCG-induced protection and immunosuppression

International Nuclear Information System (INIS)

Smrkovski, L.L.; Strickland, G.T.

1978-01-01

One dose of 10 7 viable units of Mycobacterium bovis, strain BCG, protected a significant number of Swiss mice from a primary challenge with 10 4 thoracic sporozoites of Plasmodium berghei. Immunization with irradiated sporozoites induced greater protection than that observed in BCG-treated animals. Mice treated with BCG and surviving a primary sporozoite challenge were not protected from rechallenge, whereas mice immunized with irradiated sporozoites and surviving initial challenge of sporozoites were solidly immune to further challenge. Immunizing mice with BCG and irradiated sporozoites simulataneously resulted in a synergistic effect of increased protection against a primary challenge of sporozoites only if the two immunogens were administered on the same day and if the mice were challenged 1 to 3 days later. Mice given BCG and irradiated sporozoites and surviving a primary challenge of sporozoites were unable to survive rechallenge. BCG given to mice previously immunized with irradiated sporozoites suppressed their protective immunity against sporozoite challenge

[Lack of association between MMR vaccination and the incidence of autism in children: a case-control study].

Science.gov (United States)

Mrozek-Budzyn, Dorota; Kiełtyka, Agnieszka; Majewska, Renata

2009-01-01

The matched case-control study has been undertook to investigate whether measles, mumps, and rubella (MMR) vaccine may be casually associated with autism in children. Cases were children to 14-year old with diagnosis of core autism or atypical autism. Controls were matched on age, sex and general practice. The 96 cases and 192 controls were included. The study provides strong evidence against association of autism with both MMR and a single measles individual vaccine. Additionally children vaccinated with MMR, regardless of age of vaccination (to 18th, 24th and 36th month of life), had risk equal half of that of single measles vaccinated (for vaccinated to 18th month OR=0.41 95%PU: 0.20-0.85). Our findings confirm that MMR vaccination is not associated with an increased risk of autism in children.

The Effect of Smallpox and Bacillus Calmette-Guérin Vaccination on the Risk of Human Immunodeficiency Virus-1 Infection in Guinea-Bissau and Denmark

DEFF Research Database (Denmark)

Rieckmann, Andreas; Villumsen, Marie; Jensen, Mette Lundsby

2017-01-01

: The studies from Guinea-Bissau and Denmark, 2 very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search......BACKGROUND: The live smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with better adult survival in both Guinea-Bissau and Denmark. In Guinea-Bissau, human immunodeficiency virus (HIV)-1 became an important cause of death after smallpox vaccination was phased out...... globally in 1980. We hypothesised that smallpox and BCG vaccinations were associated with a lower prevalence of HIV-1 infection, and we tested this hypothesis in both Guinea-Bissau and Denmark. METHODS: We conducted 2 studies: (1) a cross-sectional study of HIV infection and vaccination scars in Guinea...

Systemic BCG-Osis as a Rare Side Effect of Intravesical BCG Treatment for Superficial Bladder Cancer

Directory of Open Access Journals (Sweden)

S. Lukacs

2013-01-01

Full Text Available Intravesical Bacilli Calmette-Guérin (BCG immunotherapy is a commonly used treatment for superficial bladder cancer. Although the treatment is well tolerated in 95% of cases, life-threatening side effects including BCG sepsis can occur. This report describes the case of an 82-year-old man with a background of lung disease. He developed septic shock and type two respiratory failure after receiving the sixth installation of intravesical BCG (TICE strain immunotherapy for recurrent bladder Transitional Cell Carcinoma in situ. Despite the early initiation of broad spectrum antibiotics (tazocin and gentamicin, he remained pyrexial. There was a rapid deterioration, and on the second day of his admission, he developed type two respiratory failure secondary to Acute Respiratory Distress Syndrome (ARDS prompting transfer to Intensive Care for Bilevel Positive Airway Pressure (BiPAP Ventilation. The blood cultures taken before the induction of antibiotics results were negative. Increasing clinical suspicion of systemic BCG-osis prompted the initiation of antituberculosis therapy (ethambutol, isoniazid rifampicin and steroids. Following six days of BiPAP and anti-tuberculosis therapy in ITU, his condition started to improve. Following a prolonged hospital stay he was discharged on long term ethambutol therapy. BCG-osis is a well-known though rare side effect of intravesical BCG therapy. We would like to highlight the importance of having a low threshold for starting anti-TB treatment.

Vaccines and multiple sclerosis

DEFF Research Database (Denmark)

Mailand, Mia Topsøe; Frederiksen, Jette Lautrup

2017-01-01

on the database PubMed. The study found no change in risk of developing multiple sclerosis (MS) after vaccination against hepatitis B virus, human papillomavirus, seasonal influenza, measles–mumps–rubella, variola, tetanus, Bacillus Calmette-Guérin (BCG), polio, or diphtheria. No change in risk of relapse...

Factors associated with routine immunization coverage of children under one year old in Lao People's Democratic Republic.

Science.gov (United States)

Phoummalaysith, Bounfeng; Yamamoto, Eiko; Xeuatvongsa, Anonh; Louangpradith, Viengsakhone; Keohavong, Bounxou; Saw, Yu Mon; Hamajima, Nobuyuki

2018-05-03

Routine vaccination is administered free of charge to all children under one year old in Lao People's Democratic Republic (Lao PDR) and the national goal is to achieve at least 95% coverage with all vaccines included in the national immunization program by 2025. In this study, factors related to the immunization system and characteristics of provinces and districts in Lao PDR were examined to evaluate the association with routine immunization coverage. Coverage rates for Bacillus Calmette-Guerin (BCG), Diphtheria-Tetanus-Pertussis-Hepatitis B (DTP-HepB), DTP-HepB-Hib (Haemophilus influenzae type B), polio (OPV), and measles (MCV1) vaccines from 2002 to 2014 collected through regular reporting system, were used to identify the immunization coverage trends in Lao PDR. Correlation analysis was performed using immunization coverage, characteristics of provinces or districts (population, population density, and proportion of poor villages and high-risk villages), and factors related to immunization service (including the proportions of the following: villages served by health facility levels, vaccine session types, and presence of well-functioning cold chain equipment). To determine factors associated with low coverage, provinces were categorized based on 80% of DTP-HepB-Hib3 coverage (<80% = low group; ≥80% = high group). Coverages of BCG, DTP-HepB3, OPV3 and MCV1 increased gradually from 2007 to 2014 (82.2-88.3% in 2014). However, BCG coverage showed the least improvement from 2002 to 2014. The coverage of each vaccine correlated with the coverage of the other vaccines and DTP-HepB-Hib dropout rate in provinces as well as districts. The provinces with low immunization coverage were correlated with higher proportions of poor villages. Routine immunization coverage has been improving in the last 13 years, but the national goal is not yet reached in Lao PDR. The results of this study suggest that BCG coverage and poor villages should be targeted to improve

Priming-boosting vaccination with recombinant Mycobacterium bovis bacillus Calmette-Guérin and a nonreplicating vaccinia virus recombinant leads to long-lasting and effective immunity.

Science.gov (United States)

Ami, Yasushi; Izumi, Yasuyuki; Matsuo, Kazuhiro; Someya, Kenji; Kanekiyo, Masaru; Horibata, Shigeo; Yoshino, Naoto; Sakai, Koji; Shinohara, Katsuaki; Matsumoto, Sohkichi; Yamada, Takeshi; Yamazaki, Shudo; Yamamoto, Naoki; Honda, Mitsuo

2005-10-01

Virus-specific T-cell responses can limit immunodeficiency virus type 1 (HIV-1) transmission and prevent disease progression and so could serve as the basis for an affordable, safe, and effective vaccine in humans. To assess their potential for a vaccine, we used Mycobacterium bovis bacillus Calmette-Guérin (BCG)-Tokyo and a replication-deficient vaccinia virus strain (DIs) as vectors to express full-length gag from simian immunodeficiency viruses (SIVs) (rBCG-SIVgag and rDIsSIVgag). Cynomolgus macaques were vaccinated with either rBCG-SIVgag dermally as a single modality or in combination with rDIsSIVgag intravenously. When cynomologus macaques were primed with rBCG-SIVgag and then boosted with rDIsSIVgag, high levels of gamma interferon (IFN-gamma) spot-forming cells specific for SIV Gag were induced. This combination regimen elicited effective protective immunity against mucosal challenge with pathogenic simian-human immunodeficiency virus for the 1 year the macaques were under observation. Antigen-specific intracellular IFN-gamma activity was similarly induced in each of the macaques with the priming-boosting regimen. Other groups receiving the opposite combination or the single-modality vaccines were not effectively protected. These results suggest that a recombinant M. bovis BCG-based vector may have potential as an HIV/AIDS vaccine when administered in combination with a replication-deficient vaccinia virus DIs vector in a priming-boosting strategy.

Effect of milk fermentation by kefir grains and selected single strains of lactic acid bacteria on the survival of Mycobacterium bovis BCG.

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Macuamule, C L S; Wiid, I J; van Helden, P D; Tanner, M; Witthuhn, R C

2016-01-18

Mycobacterium bovis that causes Bovine tuberculosis (BTB) can be transmitted to humans thought consumption of raw and raw fermented milk products from diseased animals. Lactic acid bacteria (LAB) used in popular traditional milk products in Africa produce anti-microbial compounds that inhibit some pathogenic and spoilage bacteria. M. bovis BCG is an attenuated non-pathogenic vaccine strain of M. bovis and the aim of the study was to determine the effect of the fermentation process on the survival of M. bovis BCG in milk. M. bovis BCG at concentrations of 6 log CFU/ml was added to products of kefir fermentation. The survival of M. bovis BCG was monitored at 12-h intervals for 72 h by enumerating viable cells on Middlebrook 7H10 agar plates enriched with 2% BD BACTEC PANTA™. M. bovis BCG was increasingly reduced in sterile kefir that was fermented for a period of 24h and longer. In the milk fermented with kefir grains, Lactobacillus paracasei subsp. paracasei or Lactobacillus casei, the viability of M. bovis BCG was reduced by 0.4 logs after 24h and by 2 logs after 48 h of fermentation. No viable M. bovis BCG was detected after 60 h of fermentation. Results from this study show that long term fermentation under certain conditions may have the potential to inactivate M. bovis BCG present in the milk. However, to ensure safety of fermented milk in Africa, fermentation should be combined with other hurdle technologies such as boiling and milk pasteurisation. Copyright © 2015 Elsevier B.V. All rights reserved.

Gaps in vaccine financing for underinsured children in the United States.

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Lee, Grace M; Santoli, Jeanne M; Hannan, Claire; Messonnier, Mark L; Sabin, James E; Rusinak, Donna; Gay, Charlene; Lett, Susan M; Lieu, Tracy A

2007-08-08

The number of new vaccines recommended for children and adolescents has nearly doubled during the past 5 years, and the cost of fully vaccinating a child has increased dramatically in the past decade. Anecdotal reports from state policy makers and clinicians suggest that new gaps have arisen in financial coverage of vaccines for children who are underinsured (ie, have private insurance that does not cover all recommended vaccines). In 2000, approximately 14% of children were underinsured for vaccines in the United States. To describe variation among states in the provision of new vaccines to underinsured children and to identify barriers to state purchase and distribution of new vaccines. A 2-phase mixed-methods study of state immunization program managers in the United States. The first phase included 1-hour qualitative telephone interviews conducted from November to December 2005 with 9 program managers chosen to represent different state vaccine financing policies. The second phase incorporated findings from phase 1 to develop a national telephone and paper-based survey of state immunization program managers that was conducted from January to June 2006. Percentage of states in which underinsured children are unable to receive publicly purchased vaccines in the private or public sectors. Immunization program managers from 48 states (96%) participated in the study. Underinsured children were not eligible to receive publicly purchased meningococcal conjugate or pneumococcal conjugate vaccines in the private sector in 70% and 50% of states, respectively, or in the public sector in 40% and 17% of states, respectively. Due to limited financing for new vaccines, 10 states changed their policies for provision of publicly purchased vaccines between 2004 and early 2006 to restrict access to selected new vaccines for underinsured children. The most commonly cited barriers to implementation in underinsured children were lack of sufficient federal and state funding to

Role of the private sector in vaccination service delivery in India: evidence from private-sector vaccine sales data, 2009-12.

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Sharma, Abhishek; Kaplan, Warren A; Chokshi, Maulik; Zodpey, Sanjay P

2016-09-01

India's Universal Immunization Programme (UIP) provides basic vaccines free-of-cost in the public sector, yet national vaccination coverage is poor. The Government of India has urged an expanded role for the private sector to help achieve universal immunization coverage. We conducted a state-by-state analysis of the role of the private sector in vaccinating Indian children against each of the six primary childhood diseases covered under India's UIP. We analyzed IMS Health data on Indian private-sector vaccine sales, 2011 Indian Census data and national household surveys (DHS/NFHS 2005-06 and UNICEF CES 2009) to estimate the percentage of vaccinated children among the 2009-12 birth cohort who received a given vaccine in the private sector in 16 Indian states. We also analyzed the estimated private-sector vaccine shares as function of state-specific socio-economic status. Overall in 16 states, the private sector contributed 4.7% towards tuberculosis (Bacillus Calmette-Guérin (BCG)), 3.5% towards measles, 2.3% towards diphtheria-pertussis-tetanus (DPT3) and 7.6% towards polio (OPV3) overall (both public and private sectors) vaccination coverage. Certain low income states (Uttar Pradesh, Rajasthan, Madhya Pradesh, Orissa, Assam and Bihar) have low private as well as public sector vaccination coverage. The private sector's role has been limited primarily to the high income states as opposed to these low income states where the majority of Indian children live. Urban areas with good access to the private sector and the ability to pay increases the Indian population's willingness to access private-sector vaccination services. In India, the public sector offers vaccination services to the majority of the population but the private sector should not be neglected as it could potentially improve overall vaccination coverage. The government could train and incentivize a wider range of private-sector health professionals to help deliver the vaccines, especially in the low

The biography of the immune system and the control of cancer: from St Peregrine to contemporary vaccination strategies.

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Krone, Bernd; Kölmel, Klaus F; Grange, John M

2014-08-16

The historical basis and contemporary evidence for the use of immune strategies for prevention of malignancies are reviewed. Emphasis is focussed on the Febrile Infections and Melanoma (FEBIM) study on melanoma and on malignancies that seem to be related to an overexpression of human endogenous retrovirus K (HERV-K). It is claimed that, as a result of recent observational studies, measures for prevention of some malignancies such as melanoma and certain forms of leukaemia are already at hand: vaccination with Bacille Calmette-Guérin (BCG) of new-borns and vaccination with the yellow fever 17D (YFV) vaccine of adults. While the evidence of their benefit for prevention of malignancies requires substantiation, the observations that vaccinations with BCG and/or vaccinia early in life improved the outcome of patients after surgical therapy of melanoma are of practical relevance as the survival advantage conferred by prior vaccination is greater than any contemporary adjuvant therapy. The reviewed findings open a debate as to whether controlled vaccination studies should be conducted in patients and/or regions for whom/where they are needed most urgently. A study proposal is made and discussed. If protection is confirmed, the development of novel recombinant vaccines with wider ranges of protection based, most likely, on BCG, YFV or vaccinia, could be attempted.

Fc-based delivery system enhances immunogenicity of a tuberculosis subunit vaccine candidate consisting of the ESAT-6:CFP-10 complex.

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Farsiani, Hadi; Mosavat, Arman; Soleimanpour, Saman; Sadeghian, Hamid; Akbari Eydgahi, Mohammad Reza; Ghazvini, Kiarash; Sankian, Mojtaba; Aryan, Ehsan; Jamehdar, Saeid Amel; Rezaee, Seyed Abdolrahim

2016-06-21

Tuberculosis (TB) remains a major global health threat despite chemotherapy and Bacilli Calmette-Guérin (BCG) vaccination. Therefore, a safer and more effective vaccine against TB is urgently needed. This study evaluated the immunogenicity of a recombinant fusion protein consisting of early secreted antigenic target protein 6 kDa (ESAT-6), culture filtrate protein 10 kDa (CFP-10) and the Fc-domain of mouse IgG2a as a novel subunit vaccine. The recombinant expression vectors (pPICZαA-ESAT-6:CFP-10:Fcγ2a and pPICZαA-ESAT-6:CFP-10:His) were transferred into Pichia pastoris. After SDS-PAGE and immunoblotting, the immunogenicity of the recombinant proteins was evaluated in mice. When both recombinant proteins (ESAT-6:CFP-10:Fcγ2a and ESAT-6:CFP-10:His) were used for vaccination, Th1-type cellular responses were induced producing high levels of IFN-γ and IL-12. However, the Fc-tagged recombinant protein induced more effective Th1-type cellular responses with a small increase in IL-4 as compared to the BCG and ESAT-6:CFP-10:His groups. Moreover, mice primed with BCG and then supplemented with ESAT-6:CFP-10:Fcγ2a produced the highest levels of IFN-γ and IL-12 in immunized groups. The findings indicate that when Fcγ2a is fused to the ESAT-6:CFP-10 complex, as a delivery vehicle, there could be an increase in the immunogenicity of this type of subunit vaccine. Therefore, additional investigations are necessary for the development of appropriate Fc-based tuberculosis vaccines.

Field Trial of an Aerially-Distributed Tuberculosis Vaccine in a Low-Density Wildlife Population of Brushtail Possums (Trichosurus vulpecula).

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Nugent, Graham; Yockney, Ivor J; Whitford, E Jackie; Cross, Martin L; Aldwell, Frank E; Buddle, Bryce M

2016-01-01

Oral-delivery Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine in a lipid matrix has been shown to confer protection against M. bovis infection and reduce the severity of tuberculosis (TB) when fed to brushtail possums (Trichosurus vulpecula), the major wildlife vector of bovine TB in New Zealand. Here we demonstrate the feasibility of aerial delivery of this live vaccine in bait form to an M. bovis-infected wild possum population, and subsequently assess vaccine uptake and field efficacy. Pre-trial studies indicated a resident possum population at very low density (matrix baits in weather-proof sachets could be successfully sown aerially via helicopter and were palatable to, and likely to be consumed by, a majority of wild possums under free-choice conditions. Subsequently, sachet-held lipid baits containing live BCG vaccine were sown at 3 baits/ha over a 1360 ha area, equating to >5 baits available per possum. Blood sampling conducted two months later provided some evidence of vaccine uptake. A necropsy survey conducted one year later identified a lower prevalence of culture-confirmed M. bovis infection and/or gross TB lesions among adult possums in vaccinated areas (1.1% prevalence; 95% CI, 0-3.3%, n = 92) than in unvaccinated areas (5.6%; 0.7-10.5%, n = 89); P = 0.098. Although not statistically different, the 81% efficacy in protecting possums against natural infection calculated from these data is within the range of previous estimates of vaccine efficacy in trials where BCG vaccine was delivered manually. We conclude that, with further straightforward refinement to improve free-choice uptake, aerial delivery of oral BCG vaccine is likely to be effective in controlling TB in wild possums. We briefly discuss contexts in which this could potentially become an important complementary tool in achieving national eradication of TB from New Zealand wildlife.

A Birth Cohort Study of Maternal and Infant Serum PCB-153 and DDE Concentrations and Responses to Infant Tuberculosis Vaccination

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Jusko, Todd A.; De Roos, Anneclaire J.; Lee, Sue Y.; Thevenet-Morrison, Kelly; Schwartz, Stephen M.; Verner, Marc-André; Murinova, Lubica Palkovicova; Drobná, Beata; Kočan, Anton; Fabišiková, Anna; Čonka, Kamil; Trnovec, Tomas; Hertz-Picciotto, Irva; Lawrence, B. Paige

2015-01-01

Background: Reasons for the highly variable and often poor protection conferred by the Mycobacterium bovis bacille Calmette–Guérin (BCG) vaccine are multifaceted and poorly understood. Objectives: We aimed to determine whether early-life exposure to PCBs (polychlorinated biphenyls) and DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] reduces 6-month infant BCG vaccine response. Methods: Data came from families participating in a prospective birth cohort in eastern Slovakia. At birth, maternal and cord blood were collected for chemical analyses, and infants were immunized with BCG. Blood was collected from infants for chemical analyses and to determine 6-month BCG-specific immunoglobulin (Ig) G and IgA levels. Multivariable linear regression models were fit to examine chemical–BCG associations among approximately 500 mother–infant pairs, with adjustment for confounders. Results: The median 6-month infant concentration of the prevalent congener PCB-153 was 113 ng/g lipid [interquartile range (IQR): 37–248], and 388 ng/g lipid (IQR: 115–847) for DDE. Higher 6-month infant concentrations of PCB-153 and DDE were strongly associated with lower 6-month BCG-specific antibody levels. For instance, BCG-specific IgG levels were 37% lower for infants with PCB-153 concentrations at the 75th percentile compared to the 25th percentile (95% CI: –42, –32; p PCB–DDE additivity, where exposure to both compounds reduced anti-BCG levels more than exposure to either compound alone. Conclusions: The associations observed in this study indicate that environmental exposures may be overlooked contributors to poorer responses to BCG vaccine. The overall association between these exposures and tuberculosis incidence is unknown. Citation: Jusko TA, De Roos AJ, Lee SY, Thevenet-Morrison K, Schwartz SM, Verner MA, Palkovicova Murinova L, Drobná B, Kočan A, Fabišiková A, Čonka K, Trnovec T, Hertz-Picciotto I, Lawrence BP. 2016. A birth cohort study of maternal and infant

STUDY ON FEASIBILITY AND LOGISTICS OF VACCINATION WITH TYPHOID VI-VACCINE ON SCHOOL CHILDREN IN NORTH JAKARTA INDONESIA: ANALYSIS OF THE VACCINATION COST

Directory of Open Access Journals (Sweden)

Roy G.A. Massie

2012-11-01

Full Text Available Background: In recent years, Indonesia government has become increasingly concerned with the issues of financing childhood vaccines and immunization programs including vaccine for typhoid  fever. The objective of the analysis is to provide alternative resources and to provide understandable data generated from the Study on Feasibility and Logistics of Vaccination School Age Children With Typhoid Vi-Vaccine in North Jakarta Indonesia. Methods: The analysis was focus on measurement of the cost for vaccinating school children with Typhoid Vi-vaccine from 18 selected primary schools in North Jakarta. The primary source of data was generated from the actual expenditures that were used in the vaccine delivery program in Indonesia. Results: The Vaccination Cost from the Study on Feasibility and Logistics of Vaccination School Age Children with Typhoid Vi-Vaccine conducted by DOMI project is not applicable for public vaccination program. The program might be feasible to be delivered only in private health sector settings.   Key words: Immunization expenditure, vaccine for typhoid fever, North Jakarta Indonesia

Seasonal influenza vaccination rates and reasons for non-vaccination in children with gastrointestinal disorders.

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Peleg, Noam; Zevit, Noam; Shamir, Raanan; Chodick, Gabriel; Levy, Itzhak

2015-01-01

Despite advances in the treatment and prevention of influenza, it is still considered an important cause of morbidity and mortality worldwide. Annual vaccination is the safest and most effective mean of prevention. Our study aims were to explore the uptake of influenza vaccination among children with gastrointestinal disorders, and to characterize non-adherent patients. The present cross-sectional study included parents of pediatric patients attending the Gastroenterology Institute at Schneider Children's Medical Center of Israel between September and October 2011. Parents were asked to complete a questionnaire concerning demographic and clinical parameters, influenza vaccination of the child, and reasons for not vaccinating the child, when appropriate. The study population included 273 patients (50% female), with a median age of 10 years (range, 2-18 years). Overall, the rate of seasonal influenza vaccination was 30.8%. Higher rates were found among immunosuppressed patients (46.1%), and in patients with inflammatory bowel disease (50%). There was no significant effect of patient age, gender, ethnic origin or parental level of education on the vaccination rate. Vaccination rates were significantly associated with parents' information and knowledge of, as well as their personal beliefs regarding the vaccine (Pvaccination rates are relatively low in the pediatric population attending gastroenterology clinics, in both high- and low-risk groups. The importance of parental knowledge in compliance with influenza vaccination of children should prompt general pediatricians and gastroenterologists to discuss and address the common misconceptions regarding the vaccine. Copyright © 2014 Elsevier Ltd. All rights reserved.