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

PubMed

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

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

PubMed

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.

BCG-SSI(®) vaccine-associated lymphadenitis: Incidence and management.

PubMed

Engelis, Arnis; Kakar, Mohit; Meikšāns, Roberts; Petersons, Aigars

2016-01-01

There is a high incidence of childhood tuberculosis in Latvia, including children aged less than 1 year, while BCG-associated lymphadenitis is one of the most frequent adverse events requiring surgical treatment. The aim of this study was to analyze the incidence of purulent BCG adenitis through-out the population of Latvia after the introduction of BCG-SSI(®) vaccine and to evaluate the treatment results. The study included 194 patients. All patients had received the BCG-SSI(®) vaccine during the first week of life routinely or at a later time according to the indications. The indications for surgical treatment were lymph node destruction also affecting the skin. All patients in this study received surgical treatment - the affected lymph node extirpation. The mean age of the patients was 5.12±0.96 months. A total of 172 patients had purulent axillar lymphadenitis, 14 had purulent supraclavicular lymphadenitis, 8 patients had lymphadenitis at both localizations. During the whole study period the incidence of BCG adenitis varied from 0.02% to 0.36%, while the mean rate was 0.11%±0.08% from 184,068 vaccinated children during the study period. We observed an increasing trend in the incidence of BCG lymphadenitis during the study period. The primary and complete healing rate at the end of period was 99.5% (n=193) following an affected lymph node extirpation. The mean hospitalization time after the operation was 3.71±0.18 days. The incidence of BCG-SSI(®) vaccine associated purulent lymphadenitis varied widely with an increasing trend, followed by the return to the product characteristic limits. Indications for the surgical treatment should not be changed. Extirpation of the purulent BCG adenitis is a safe treatment method and leads to the primary wound healing in the majority of cases. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Engineering new mycobacterial vaccine design for HIV–TB pediatric vaccine vectored by lysine auxotroph of BCG

PubMed Central

Saubi, Narcís; Gea-Mallorquí, Ester; Ferrer, Pau; Hurtado, Carmen; Sánchez-Úbeda, Sara; Eto, Yoshiki; Gatell, Josep M; Hanke, Tomáš; Joseph, Joan

2014-01-01

In this study, we have engineered a new mycobacterial vaccine design by using an antibiotic-free plasmid selection system. We assembled a novel Escherichia coli (E. coli)–mycobacterial shuttle plasmid p2auxo.HIVA, expressing the HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism for plasmid selection and maintenance based on glycine complementation in E. coli and lysine complementation in mycobacteria. This plasmid was first transformed into glycine auxotroph of E. coli strain and subsequently transformed into lysine auxotroph of Mycobacterium bovis BCG strain to generate vaccine BCG.HIVA2auxo. We demonstrated that the episomal plasmid p2auxo.HIVA was stable in vivo over a 7-week period and genetically and phenotypically characterized the BCG.HIVA2auxo vaccine strain. The BCG.HIVA2auxo vaccine in combination with modified vaccinia virus Ankara (MVA). HIVA was safe and induced HIV-1 and Mycobacterium tuberculosis-specific interferon-γ-producing T-cell responses in adult BALB/c mice. Polyfunctional HIV-1-specific CD8+ T cells, which produce interferon-γ and tumor necrosis factor-α and express the degranulation marker CD107a, were induced. Thus, we engineered a novel, safer, good laboratory practice–compatible BCG-vectored vaccine using prototype immunogen HIVA. This antibiotic-free plasmid selection system based on “double” auxotrophic complementation might be a new mycobacterial vaccine platform to develop not only recombinant BCG-based vaccines expressing second generation of HIV-1 immunogens but also other major pediatric pathogens to prime protective response soon after birth. PMID:26015961

Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms

PubMed Central

Zhang, Lu; Ru, Huan-wei; Chen, Fu-zeng; Jin, Chun-yan; Sun, Rui-feng; Fan, Xiao-yong; Guo, Ming; Mai, Jun-tao; Xu, Wen-xi; Lin, Qing-xia; Liu, Jun

2016-01-01

Bacille Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. However, BCG is not an ideal vaccine and has two major limitations: BCG exhibits highly variable effectiveness against the development of TB both in pediatric and adult populations and can cause disseminated BCG disease in immunocompromised individuals. BCG comprises a number of substrains that are genetically distinct. Whether and how these genetic differences affect BCG efficacy remains largely unknown. In this study, we performed comparative analyses of the virulence and efficacy of 13 BCG strains, representing different genetic lineages, in SCID and BALB/c mice. Our results show that BCG strains of the DU2 group IV (BCG-Phipps, BCG-Frappier, BCG-Pasteur, and BCG-Tice) exhibit the highest levels of virulence, and BCG strains of the DU2 group II (BCG-Sweden, BCG-Birkhaug) are among the least virulent group. These distinct levels of virulence may be explained by strain-specific duplications and deletions of genomic DNA. There appears to be a general trend that more virulent BCG strains are also more effective in protection against Mycobacterium tuberculosis challenge. Our findings have important implications for current BCG vaccine programs and for future TB vaccine development. PMID:26643797

Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms.

PubMed

Zhang, Lu; Ru, Huan-Wei; Chen, Fu-Zeng; Jin, Chun-Yan; Sun, Rui-Feng; Fan, Xiao-Yong; Guo, Ming; Mai, Jun-Tao; Xu, Wen-Xi; Lin, Qing-Xia; Liu, Jun

2016-02-01

Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. However, BCG is not an ideal vaccine and has two major limitations: BCG exhibits highly variable effectiveness against the development of TB both in pediatric and adult populations and can cause disseminated BCG disease in immunocompromised individuals. BCG comprises a number of substrains that are genetically distinct. Whether and how these genetic differences affect BCG efficacy remains largely unknown. In this study, we performed comparative analyses of the virulence and efficacy of 13 BCG strains, representing different genetic lineages, in SCID and BALB/c mice. Our results show that BCG strains of the DU2 group IV (BCG-Phipps, BCG-Frappier, BCG-Pasteur, and BCG-Tice) exhibit the highest levels of virulence, and BCG strains of the DU2 group II (BCG-Sweden, BCG-Birkhaug) are among the least virulent group. These distinct levels of virulence may be explained by strain-specific duplications and deletions of genomic DNA. There appears to be a general trend that more virulent BCG strains are also more effective in protection against Mycobacterium tuberculosis challenge. Our findings have important implications for current BCG vaccine programs and for future TB vaccine development.

Ipr1 modified BCG as a novel vaccine induces stronger immunity than BCG against tuberculosis infection in mice.

PubMed

Wang, Yuwei; Yang, Chun; He, Yonglin; Zhan, Xingxing; Xu, Lei

2016-08-01

Tuberculosis is a major challenge to global public health. However, the Bacille Calmette‑Guérin (BCG), the only vaccine available against tuberculosis, has been questioned for the low protective effect. The present study used the mouse gene intracellular pathogen resistance I (Ipr1) gene to alter the current BCG vaccine and evaluated its immunity effect against tuberculosis. This study also investigated the intrinsic relationships of Ipr1 and innate immunity. The reformed BCG (BCGi) carrying the Ipr1 gene was constructed. The mice were intranasally challenged with the M. tuberculosis H37Rv strain after vaccination with BCGi. Protection efficacy of the vaccine was assessed by the organ coefficient, bacterial load and pathological changes in the lung. The differential expression of 113 immune‑related genes between BCGi and BCG groups were detected by an oligo microarray. According to the results of organ coefficient, bacterial load and pathological changes in the organization, BCGi had been shown to have stronger protective effects against M. tuberculosis than BCG. The oligo microarray and reverse transcription‑quantitative polymerase chain reaction further revealed that the Ipr1 gene could upregulate the expression of 13 genes, including a >3‑fold increase in Toll‑like receptor (TLR)4 and 10‑fold increase in surfactant protein D (sftpd). The two genes not only participate in innate immunity against pathogens, but also are closely interrelated. Ipr1 could activate the TLR4 and sftpd signaling pathway and improve the innate immunity against tuberculosis, therefore Ipr1 modified BCG may be a candidate vaccine against M. tuberculosis.

Oral delivery of BCG Moreau Rio de Janeiro gives equivalent protection against tuberculosis but with reduced pathology compared to parenteral BCG Danish vaccination.

PubMed

Clark, Simon O; Kelly, Dominic L F; Badell, Edgar; Castello-Branco, Luiz Roberto; Aldwell, Frank; Winter, Nathalie; Lewis, David J M; Marsh, Philip D

2010-10-08

There is a need for an improved vaccine to better control human tuberculosis (TB), as the only currently available TB vaccine, bacillus Calmette-Guerin (BCG) delivered parenterally, offers variable levels of efficacy. Therefore, recombinant strains expressing additional antigens are being developed alongside alternative routes to parenteral delivery. There is strong evidence that BCG Moreau (RdJ) is a safe and effective vaccine in humans when given by the oral route. This study compared the efficacy of a single oral dose of wild type BCG Moreau Rio de Janeiro (RdJ), or a recombinant RdJ strain expressing Ag85B-ESAT6 fusion protein, formulated with and without lipid to enhance oral delivery, with subcutaneous BCG Danish 1331 and saline control groups in a guinea pig aerosol infection model of pulmonary tuberculosis. Protection was measured as survival at 30 weeks post-challenge and reduced bacterial load and histopathology in lungs and spleen. Results showed that a single oral dose of BCG Moreau (RdJ) or recombinant BCG Moreau (RdJ)-Ag85B-ESAT6, formulated with or without lipid, gave protection equivalent to subcutaneously delivered BCG Danish in the 30 weeks post-challenge survival study. The orally delivered vaccines gave reduced pathology scores in the lungs (three of the four formulations) and spleens (all four formulations) compared to subcutaneously delivered BCG Danish. The oral wild type BCG Moreau (RdJ) in lipid and the unformulated oral wild type BCG Moreau (RdJ) vaccine also gave statistically lower bacterial loads in the lungs and spleens, respectively, compared to subcutaneously delivered BCG Danish. This study provides further evidence to show that lipid formulation does not impair vaccine efficacy and may enhance the delivery and stability of oral vaccines intended for use in countries with poor health infrastructure. Oral delivery also avoids needles (and associated cross-infection risks) and immunisation without the need for specially trained

BCG vaccination-induced suppurative lymphadenitis: four signs to pay attention to.

PubMed

Baek, Sang Oon; Ko, Hyo Sun; Han, Hyun Ho

2017-12-01

Suppurative lymphadenitis is one of the severe complication after BCG vaccination, but its diagnostic criteria and treatment guidelines have not yet been established. In this article, we describe a case of suppurative lymphadenitis caused by BCG vaccination and propose diagnostic criteria and treatment guidelines of the disease. The lymphadenitis was presented as skin involving mass and was completely extirpated. Pathological evaluation revealed a necrotising lymphadenitis, consistent with the diagnosis of BCG lymphadenitis. The patient was administered adjuvant medical treatment with anti-TB medications (Isoniazid and Rifampicin) for 3 months. At 6 months follow-up, the disease was in complete remission without complications. We recommend focus on the following four signs when diagnosing BCG lymphadenitis: (i) previous history of vaccination on the ipsilateral side of the lesion, (ii) absence of any other infection signs, (iii) absence of fever and (iv) isolated axillary or supraclavicular/cervical lymph node enlargement proven by ultrasonography or computed tomography scan. BCG vaccination-induced suppurative lymphadenitis can easily be overlooked, but prompt, accurate diagnosis followed by appropriate surgical resection should result in complete healing as in this case. © 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

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

PubMed Central

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

2017-01-01

Background & objectives: 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. Methods: 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. Results: 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. Interpretation & conclusions: The coverage of

[Relationship between BCG immunization coverage and the immunization delivery system in the Tama area of Tokyo].

PubMed

Sugishita, Yoshiyuki; Hayashi, Kunihiko; Mori, Toru; Horiguchi, Itsuko; Marui, Eiji

2012-03-01

The BCG immunization has long been performed in Japan. Although the BCG immunization service is the responsibility of the municipality, the manner in which the BCG immunization is delivered differs from municipality to municipality. The purpose of this study was to clarify how the different manner of the BCG immunization delivery systems influenced the BCG immunization coverage. The study of BCG immunization coverage was conducted in the Tama area located in the western suburbs of Tokyo in 2004. The birth data and the immunization history by the age of 3 years were collected in the three-year-old health check-up from a total of 2,341 children residing in the Tama area. Based on the age at immunization for each child, the BCG immunization coverage was calculated according to the types of the BCG immunization delivery system. The immunization types were defined as follows; the BCG immunization given on the occasion of the mass health check-up (Group 1); the exclusive mass BCG immunization in a monthly service (Group 2); the exclusive mass BCG immunization in a bimonthly service (Group 3); the exclusive mass BCG immunization in services of fewer than every two months (Group 4); and the immunization given on an individual basis by a general practitioner (Group 5). A univariate analysis was performed to examine the relationship between the BCG immunization coverage by the age of 6 months and the difference among the BCG immunization delivery systems, followed by a multivariate regression analysis to adjust for the factors related to the demography, health care services and the socio-economic status of the municipalities. Unadjusted odds ratios and adjusted odds ratios for BCG unimmunized children under the age of 6 months by the BCG immunization delivery manner groups were OR 1 reference, adj. OR 1 reference in Group 1; OR 1.42 CI 0.87-2.29, adj. OR 4.01 CI 2.24-7.11 in Group 2; OR 4.96 CI 3.66-6.82, adj. OR 15.59 CI 10.10-24.49 in Group 3;OR 18.60 CI 13.77-25.49, adj

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

PubMed

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

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

PubMed

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 < =0.001) to receive Penta3 vaccine compared to children living <30mins from a health post. This effect was not modified by household wealth (p value = 0.240). 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

Causes of variation in BCG vaccine efficacy: examining evidence from the BCG REVAC cluster randomized trial to explore the masking and the blocking hypotheses.

PubMed

Barreto, Mauricio L; Pilger, Daniel; Pereira, Susan M; Genser, Bernd; Cruz, Alvaro A; Cunha, Sergio S; Sant'Anna, Clemax; Hijjar, Miguel A; Ichihara, Maria Y; Rodrigues, Laura C

2014-06-24

BCG protection varies and in some places (nearest the equator) is low or absent. Understanding this variation can inform the efforts to develop new vaccines against tuberculosis. Two main hypotheses are used to explain this variation: under masking, new vaccines are unlikely to increase protection; under blocking new vaccines have a greater potential to be effective when BCG is not. We conducted a cluster randomized trial to explored the masking and blocking hypotheses by studying BCG vaccine efficacy of neonatal vaccination and when administered for the first or a second (revaccination) time at school age in two sites (Manaus close and Salvador further south from the equator). Seven hundred and sixty three state schools were matched on socio economic characteristics of the neighborhood and 239,934 children were randomized to vaccine (BCG vaccination at school age) or control group. Protection by first BCG vaccination at school age was high in Salvador (34%, 95% CI 7-53%, p=0.017) but low in Manaus (8%, 95% CI t0 39-40%, p=0.686). For revaccination at school age, protection was modest in Salvador (19%, 95% CI 3-33%, p=0.022) and absent in Manaus (1%, 95% CI to 27-23%, p=0.932). Vaccine efficacy for neonatal vaccination was similar in Salvador (40%, 95% CI 22-54%, p<0.001) and Manaus (36%, 95% CI 11-53%, p=0.008). Variation in BCG efficacy was marked when vaccine was given at school age but absent at birth, which points towards blocking as the dominant mechanism. New tuberculosis vaccines that overcome or by pass this blocking effect could confer protection in situations where BCG is not protective. Copyright © 2014 Elsevier Ltd. All rights reserved.

Estimation of Nationwide Vaccination Coverage and Comparison of Interview and Telephone Survey Methodology for Estimating Vaccination Status

PubMed Central

Park, Boyoung; Lee, Yeon-Kyeng; Cho, Lisa Y.; Go, Un Yeong; Yang, Jae Jeong; Ma, Seung Hyun; Choi, Bo-Youl; Lee, Moo-Sik; Lee, Jin-Seok; Choi, Eun Hwa; Lee, Hoan Jong

2011-01-01

This study compared interview and telephone surveys to select the better method for regularly estimating nationwide vaccination coverage rates in Korea. Interview surveys using multi-stage cluster sampling and telephone surveys using stratified random sampling were conducted. Nationwide coverage rates were estimated in subjects with vaccination cards in the interview survey. The interview survey relative to the telephone survey showed a higher response rate, lower missing rate, higher validity and a less difference in vaccination coverage rates between card owners and non-owners. Primary vaccination coverage rate was greater than 90% except for the fourth dose of DTaP (diphtheria/tetanus/pertussis), the third dose of polio, and the third dose of Japanese B encephalitis (JBE). The DTaP4: Polio3: MMR1 fully vaccination rate was 62.0% and BCG1:HepB3:DTaP4:Polio3:MMR1 was 59.5%. For age-appropriate vaccination, the coverage rate was 50%-80%. We concluded that the interview survey was better than the telephone survey. These results can be applied to countries with incomplete registry and decreasing rates of landline telephone coverage due to increased cell phone usage and countries. Among mandatory vaccines, efforts to increase vaccination rate for the fourth dose of DTaP, the third dose of polio, JBE and regular vaccinations at recommended periods should be conducted in Korea. PMID:21655054

Oral Vaccination with Lipid-Formulated BCG Induces a Long-lived, Multifunctional CD4+ T Cell Memory Immune Response

PubMed Central

Ancelet, Lindsay R.; Aldwell, Frank E.; Rich, Fenella J.; Kirman, Joanna R.

2012-01-01

Oral delivery of BCG in a lipid formulation (Liporale™-BCG) targets delivery of viable bacilli to the mesenteric lymph nodes and confers protection against an aerosol Mycobacterium tuberculosis challenge. The magnitude, quality and duration of the effector and memory immune response induced by Liporale™-BCG vaccination is unknown. Therefore, we compared the effector and memory CD4+ T cell response in the spleen and lungs of mice vaccinated with Liporale™-BCG to the response induced by subcutaneous BCG vaccination. Liporale™-BCG vaccination induced a long-lived CD4+ T cell response, evident by the detection of effector CD4+ T cells in the lungs and a significant increase in the number of Ag85B tetramer-specific CD4+ T cells in the spleen up to 30 weeks post vaccination. Moreover, following polyclonal stimulation, Liporale™-BCG vaccination, but not s.c. BCG vaccination, induced a significant increase in both the percentage of CD4+ T cells in the lungs capable of producing IFNγ and the number of multifunctional CD4+ T cells in the lungs at 30 weeks post vaccination. These results demonstrate that orally delivered Liporale™-BCG vaccine induces a long-lived multifunctional immune response, and could therefore represent a practical and effective means of delivering novel BCG-based TB vaccines. PMID:23049885

Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis.

PubMed

Perdomo, Carolina; Zedler, Ulrike; Kühl, Anja A; Lozza, Laura; Saikali, Philippe; Sander, Leif E; Vogelzang, Alexis; Kaufmann, Stefan H E; Kupz, Andreas

2016-11-22

Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls for improved vaccination strategies. Mucosal BCG vaccination generates superior protection against TB in animal models; however, the mechanisms of protection remain elusive. Tissue-resident memory T (T RM ) cells have been implicated in protective immune responses against viral infections, but the role of T RM cells following mycobacterial infection is unknown. Using a mouse model of TB, we compared protection and lung cellular infiltrates of parenteral and mucosal BCG vaccination. Adoptive transfer and gene expression analyses of lung airway cells were performed to determine the protective capacities and phenotypes of different memory T cell subsets. In comparison to subcutaneous vaccination, intratracheal and intranasal BCG vaccination generated T effector memory and T RM cells in the lung, as defined by surface marker phenotype. Adoptive mucosal transfer of these airway-resident memory T cells into naive mice mediated protection against TB. Whereas airway-resident memory CD4 + T cells displayed a mixture of effector and regulatory phenotype, airway-resident memory CD8 + T cells displayed prototypical T RM features. Our data demonstrate a key role for mucosal vaccination-induced airway-resident T cells in the host defense against pulmonary TB. These results have direct implications for the design of refined vaccination strategies. BCG remains the only licensed vaccine against TB. Parenterally administered BCG has variable efficacy against pulmonary TB, and thus, improved prevention strategies and a more refined understanding of correlates of vaccine protection are required. Induction of memory T cells has been shown to be essential for protective TB vaccines. Mimicking the natural infection route by mucosal vaccination has been known to generate superior protection against TB in animal models; however, the

Adverse events following immunisation with bacille Calmette-Guérin vaccination: baseline data to inform monitoring in Australia following introduction of new unregistered BCG vaccine.

PubMed

Hendry, Alexandra J; Dey, Aditi; Beard, Frank H; Khandaker, Gulam; Hill, Richard; Macartney, Kristine K

2016-12-24

In recent years there has been a global shortage of bacille Calmette-Guérin (BCG) vaccine and, from September 2012, unregistered vaccines have needed to be used in Australia (a Danish product initially until the end of 2015, and a Polish product used in some jurisdictions from early 2016). We examined rates and types of adverse events following immunisation (AEFI) with BCG vaccine reported to the Therapeutic Goods Administration between 2009 and 2014 in children aged less than 7 years. Reporting rates of AEFI with BCG vaccine increased from 87 per 100,000 doses (registered Sanofi Pasteur product) in 2009 to 201 per 100,000 doses (unregistered Danish Statens Serum Institute product) in 2014, with Victoria having the highest rate each year. Substantial variation between jurisdictions exists, suggesting differential reporting of BCG vaccine doses administered and/or BCG vaccine-related AEFI. The most commonly reported reactions were abscess (31%), injection site reaction (27%) and lymphadenopathy/lymphadenitis (17%). This study provides baseline data on BCG vaccine safety to inform surveillance. Given the current use of unregistered vaccines in the context of vaccine supply issues, improved recording of both administered BCG vaccine doses and the reporting of BCG vaccine-related AEFI are required to facilitate close monitoring of vaccine safety.

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

PubMed

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.

Pros and cons of BCG vaccination in countries with low incidence of tuberculosis.

PubMed

Tala, E O; Tala-Heikkilä, M M

1994-07-01

Preventive bacille Calmette-Guérin (BCG) vaccination, together with case finding and effective chemotherapy, has formed an integral part of the tuberculosis (TB) control program in most countries. In some low-incidence countries the balance of prevention has been more on the side of chemoprophylaxis than of BCG vaccination. The time clearly has come when the strategy of mass BCG vaccination no longer is indicated medically, nor is it cost-effective. The pros and cons of the programs need to be critically evaluated against the present epidemiological background, taking into account the facts that TB, the killer disease, is recovering strength, human immunodeficiency virus infection is on the increase, and multidrug-resistant TB has changed the outcome of this previously fully curable disease. Although no longer appropriate for mass programs, BCG vaccination still should be considered for the protection of selected risk groups in low-incidence countries. The overall efficacy may be of the order 50% to 80%, but the variation is great. Therefore, further research urgently is needed on the effectiveness of BCG as an intervention in local TB programs.

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

PubMed Central

Xie, Jiangan; Codd, Christopher; Mo, Kevin; He, Yongqun

2016-01-01

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-associated death

Vaccination coverage survey in Dhaka District.

PubMed

Khan, M N A; Rahman, M L; Awal Miah, A; Islam, M S; Musa, S A J M; Tofail, F

2005-08-01

A survey was conducted in Dhaka District to measure the level of routine immunization coverage of children (12-23 months), to assess the tetanus toxoid (TT) immunization coverage among mothers of children (12-23 month), to evaluate EPI program continuity (dropout rates) and quality (percent of Invalid doses, vaccination card availability etc.) For this purpose, a thirty cluster cross-sectional survey was conducted in October 2002 to assess the immunization coverage in Dhaka. In this survey 30 clusters were randomly selected from a list of villages in 63 Unions of Dhaka following probability proportion to size (PPS) sampling procedure. A total of 210 children was studied using pre-tested structured questionnaire. Descriptive statistics was employed using software SPSS package for data analysis. The study showed that the routine immunization coverage in Dhaka among children by 12 months of age by card + history was 97% for BCG, 97% for Diphtheria, Pertussis Tetanus (DPT 1) and Oral Polio Vaccine (OPV 1), 75% for DPT3 and OPV3 and 67% for measles. Sixty six percent of all children surveyed had received valid doses of all vaccines by 12 months (fully immunized child). Programme access as measured by crude DPT1 coverage was better in Keranigonj (97%). Vaccination cards retention rate for children was 84%. Invalid DPT (1,2 or 3) doses were given to 25% of vaccinated children; 18% of measles doses were invalid. Surprisingly, major cause for invalid doses were not due to early immunizations or due to card lost but for giving tick in the card, instead of writing a valid date. DPT1 and DPT3 and DPT1- Measles drop out rates were 5% and 13% respectively. Major reason parents gave for never vaccinating their children (zero dose children) was (43%), major reasons for incomplete vaccination was lack of knowledge regarding subsequent doses (46%). TT surveys were also conducted for mothers of the children surveyed for vaccination coverage (mothers between 15-49 year old). Valid TT

BCG vaccination in leprosy: final results of the trial in Karimui, Papua New Guinea, 1963-79.

PubMed Central

Bagshawe, A.; Scott, G. C.; Russell, D. A.; Wigley, S. C.; Merianos, A.; Berry, G.

1989-01-01

The efficacy of BCG vaccine in preventing the clinical manifestations of leprosy in a tuberculosis-free area of Papua New Guinea is reported. Between 1963 and 1966 a total of 5356 subjects, randomized to receive BCG or saline inoculations, were examined for leprosy before the vaccination and surveillance was continued until 1979. BCG afforded 48% protection against clinical leprosy, being most effective against borderline tuberculoid leprosy and in children vaccinated when under 15 years old. Protection was evident within 12 months in those vaccinated between the ages of 10 and 15 years but was delayed in other age groups. There was evidence for accelerated manifestations of tuberculoid leprosy in children vaccinated when under 5 years of age. Tuberculin sensitivity was more likely to be sustained following multiple BCG inoculations; vaccinees with sustained tuberculin sensitivity had the lowest incidence of leprosy, but protection was also evident in tuberculin-negative vaccinees. These results may have implications for ongoing trials of leprosy vaccine incorporating BCG. PMID:2680140

Drug Treatment Combined with BCG Vaccination Reduces Disease Reactivation in Guinea Pigs Infected with Mycobacterium tuberculosis

PubMed Central

Shang, Shaobin; Shanley, Crystal A.; Caraway, Megan L.; Orme, Eileen A.; Henao-Tamayo, Marcela; Hascall-Dove, Laurel; Ackart, David; Orme, Ian M.; Ordway, Diane J.; Basaraba, Randall J.

2012-01-01

Bacillus-Calmette-Guerin (BCG), the only human tuberculosis vaccine, primes a partially protective immune response against M. tuberculosis infection in humans and animals. In guinea pigs, BCG vaccination slows the progression of disease and reduces the severity of necrotic granulomas, which harbor a population of drug-tolerant bacilli. The objective of this study was to determine if reducing disease severity by BCG vaccination of guinea pigs prior to M. tuberculosis challenge enhanced the efficacy of combination drug therapy. At 20 days of infection, treatment of vaccinated and non-vaccinated animals with rifampin, isoniazid, and pyrizinamide (RHZ) was initiated for 4 or 8 weeks. On days 50, 80 and 190 of infection (10 weeks after drug were withdrawn), treatment efficacy was evaluated by quantifying clinical condition, bacterial loads, lesion severity, and dynamic changes in peripheral blood and lung leukocyte numbers by flow cytometry. In a separate, long-term survival study, treatment efficacy was evaluated by determining disease reactivation frequency post-mortem. BCG vaccination alone delayed pulmonary and extra-pulmonary disease progression, but failed to prevent dissemination of bacilli and the formation of necrotic granulomas. Drug therapy either alone or in combination with BCG, was more effective at lessening clinical disease and lesion severity compared to control animals or those receiving BCG alone. Fewer residual lesions in BCG vaccinated and drug treated animals, equated to a reduced frequency of reactivation disease and improvement in survival even out to 500 days of infection. The combining of BCG vaccination and drug therapy was more effective at resolving granulomas such that fewer animals had evidence of residual infection and thus less reactivation disease. PMID:22244979

BCG vaccination of full-term infants with chronic intrauterine malnutrition: influence of immunization age on development of post-vaccination, delayed tuberculin hypersensitivity.

PubMed Central

Mussi-Pinhata, M. M.; Goncalves, A. L.; Foss, N. T.

1993-01-01

To determine the effect of intrauterine growth retardation (IUGR) on the response to BCG vaccination, we evaluated the specific delayed tuberculin hypersensitivity of 57 full-term infants with symmetric IUGR (SGA or small for gestational age) and 52 full-term infants with normal intrauterine growth (AGA or appropriate for gestational age). The infants were evaluated using post-vaccination skin tests to tuberculin purified protein derivative (PPD) and tuberculin lymphocyte transformation tests. Using a positive response to the skin test as an indicator of delayed hypersensitivity, we found that the rate of response to BCG in the SGA and AGA groups was similar. A total of 65% of infants with IUGR responded to BCG vaccination. The response rate among SGA infants who were vaccinated at 5 days of age, about 26 days of age (weight > or = 2500 g), 3 months of age, and 6 months of age was 68%, 47%, 69%, and 88%, respectively. The overall response rate for infants with no IUGR was 71%; the rate response to BCG vaccination among this group was 52% (those vaccinated at 5 days of age), 90% (3 months of age), and 80% (6 months of age). Our data suggest that the immunogenicity of BCG vaccine is similar in term infants who have normal or abnormal intrauterine growth and the presence of IUGR should not be a reason for delaying BCG vaccination. PMID:8440036

Determinants of vaccination coverage in rural Nigeria

PubMed Central

Odusanya, Olumuyiwa O; Alufohai, Ewan F; Meurice, Francois P; Ahonkhai, Vincent I

2008-01-01

Background Childhood immunization is a cost effective public health strategy. Expanded Programme on Immunisation (EPI) services have been provided in a rural Nigerian community (Sabongidda-Ora, Edo State) at no cost to the community since 1998 through a privately financed vaccination project (private public partnership). The objective of this survey was to assess vaccination coverage and its determinants in this rural community in Nigeria Methods A cross-sectional survey was conducted in September 2006, which included the use of interviewer-administered questionnaire to assess knowledge of mothers of children aged 12–23 months and vaccination coverage. Survey participants were selected following the World Health Organization's (WHO) immunization coverage cluster survey design. Vaccination coverage was assessed by vaccination card and maternal history. A child was said to be fully immunized if he or she had received all of the following vaccines: a dose of Bacille Calmette Guerin (BCG), three doses of oral polio (OPV), three doses of diphtheria, pertussis and tetanus (DPT), three doses of hepatitis B (HB) and one dose of measles by the time he or she was enrolled in the survey, i.e. between the ages of 12–23 months. Knowledge of the mothers was graded as satisfactory if mothers had at least a score of 3 out of a maximum of 5 points. Logistic regression was performed to identify determinants of full immunization status. Results Three hundred and thirty-nine mothers and 339 children (each mother had one eligible child) were included in the survey. Most of the mothers (99.1%) had very positive attitudes to immunization and > 55% were generally knowledgeable about symptoms of vaccine preventable diseases except for difficulty in breathing (as symptom of diphtheria). Two hundred and ninety-five mothers (87.0%) had a satisfactory level of knowledge. Vaccination coverage against all the seven childhood vaccine preventable diseases was 61.9% although it was

Determinants of vaccination coverage in rural Nigeria.

PubMed

Odusanya, Olumuyiwa O; Alufohai, Ewan F; Meurice, Francois P; Ahonkhai, Vincent I

2008-11-05

Childhood immunization is a cost effective public health strategy. Expanded Programme on Immunisation (EPI) services have been provided in a rural Nigerian community (Sabongidda-Ora, Edo State) at no cost to the community since 1998 through a privately financed vaccination project (private public partnership). The objective of this survey was to assess vaccination coverage and its determinants in this rural community in Nigeria A cross-sectional survey was conducted in September 2006, which included the use of interviewer-administered questionnaire to assess knowledge of mothers of children aged 12-23 months and vaccination coverage. Survey participants were selected following the World Health Organization's (WHO) immunization coverage cluster survey design. Vaccination coverage was assessed by vaccination card and maternal history. A child was said to be fully immunized if he or she had received all of the following vaccines: a dose of Bacille Calmette Guerin (BCG), three doses of oral polio (OPV), three doses of diphtheria, pertussis and tetanus (DPT), three doses of hepatitis B (HB) and one dose of measles by the time he or she was enrolled in the survey, i.e. between the ages of 12-23 months. Knowledge of the mothers was graded as satisfactory if mothers had at least a score of 3 out of a maximum of 5 points. Logistic regression was performed to identify determinants of full immunization status. Three hundred and thirty-nine mothers and 339 children (each mother had one eligible child) were included in the survey. Most of the mothers (99.1%) had very positive attitudes to immunization and > 55% were generally knowledgeable about symptoms of vaccine preventable diseases except for difficulty in breathing (as symptom of diphtheria). Two hundred and ninety-five mothers (87.0%) had a satisfactory level of knowledge. Vaccination coverage against all the seven childhood vaccine preventable diseases was 61.9% although it was significantly higher (p = 0.002) amongst

Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis

PubMed Central

Perdomo, Carolina; Zedler, Ulrike; Kühl, Anja A.; Lozza, Laura; Saikali, Philippe; Sander, Leif E.; Vogelzang, Alexis; Kupz, Andreas

2016-01-01

ABSTRACT Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls for improved vaccination strategies. Mucosal BCG vaccination generates superior protection against TB in animal models; however, the mechanisms of protection remain elusive. Tissue-resident memory T (TRM) cells have been implicated in protective immune responses against viral infections, but the role of TRM cells following mycobacterial infection is unknown. Using a mouse model of TB, we compared protection and lung cellular infiltrates of parenteral and mucosal BCG vaccination. Adoptive transfer and gene expression analyses of lung airway cells were performed to determine the protective capacities and phenotypes of different memory T cell subsets. In comparison to subcutaneous vaccination, intratracheal and intranasal BCG vaccination generated T effector memory and TRM cells in the lung, as defined by surface marker phenotype. Adoptive mucosal transfer of these airway-resident memory T cells into naive mice mediated protection against TB. Whereas airway-resident memory CD4+ T cells displayed a mixture of effector and regulatory phenotype, airway-resident memory CD8+ T cells displayed prototypical TRM features. Our data demonstrate a key role for mucosal vaccination-induced airway-resident T cells in the host defense against pulmonary TB. These results have direct implications for the design of refined vaccination strategies. PMID:27879332

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

PubMed

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.

Age-related waning of in vitro Interferon-γ levels against r32kDaBCG in BCG vaccinated children

PubMed Central

Anuradha, B; Santosh, CM; Hari Sai Priya, V; Suman Latha, G; Murthy, KJR; Vijaya Lakshmi, Valluri

2007-01-01

Background Mycobacterium bovis BCG vaccine has displayed inconsistent efficacy in different trials conducted in various geographical regions. Nevertheless, it significantly reduces the risk of severe childhood tuberculosis and continues to be used to prevent tuberculosis in many countries. Many studies revealed that efficacy of vaccine wanes with age. Most of the studies were based on in vivo and in vitro responses to tuberculin. With the advent of newer tests such as in vitro interferon-γ assays and identification of potent immunogenic mycobacterial proteins there is a need to corroborate the observations. This study aims at ascertaining the need for a booster at a later age as indicated by in vitro release of IFN-γ while evaluating Ag85A as an antigen. Methods Ninety healthy children who were without any clinical evidence of the disease, 45 with a BCG-scar and the remaining 45 without scar and 25 with tuberculosis were included in the study. The incidence of TB was analyzed in 216 children attending a DOTS clinic during 1996–2005. CD3+, CD4+ and CD8+ cell counts were measured by Flow cytometry. r32kDaBCG (Ag85A-BCG) protein was used to stimulate T cells in in vitro T cell responses and interferon-γ (IFN-γ) cytokine levels in the supernatants were measured by ELISA. Results High incidence of TB was observed in age group 13–14 years followed by children in the age group 10–12 years (Chi-square 242.22; p < 0.000). T cell subsets were within the normal range in all subjects. 79% of vaccinated children showed positive proliferative responses with a mean SI value of 4.98 ± 1.99 while only 39% of the unvaccinated and 58% of the tuberculosis children showed positive responses with mean values of 2.9 ± 1.6 (p < 0.001) and 2.9 ± 1.7(p < 0.057), respectively. The stimulation indices in vaccinated children decreased in the older children concurring with an increase in the incidence of TB. Conclusion Significantly high levels of in vitro IFN-γ demonstrated in

Prospects in Mycobacterium bovis Bacille Calmette et Guérin (BCG) Vaccine Diversity and Delivery: Why does BCG fail to protect against Tuberculosis?

PubMed Central

Moliva, Juan I.; Turner, Joanne; Torrelles, Jordi B.

2015-01-01

Mycobacterium tuberculosis (M.tb) infection leads to active tuberculosis (TB), a disease that kills one human every 18 seconds. Current therapies available to combat TB include chemotherapy and the preventative vaccine Mycobacterium bovis Bacille Calmette et Guérin (BCG). Increased reporting of drug resistant M.tb strains worldwide indicates that drug development cannot be the primary mechanism for eradication. BCG vaccination has been used globally for protection against childhood and disseminated TB, however, its efficacy at protecting against pulmonary TB in adult and aging populations is highly variable. In this regard, the immune response generated by BCG vaccination is incapable of sterilizing the lung post M.tb infection as indicated by the large proportion of individuals with latent TB infection that have received BCG. Although many new TB vaccine candidates have entered the development pipeline, only a few have moved to human clinical trials; where they showed no efficacy and/or were withdrawn due to safety regulations. These trials highlight our limited understanding of protective immunity against the development of active TB. Here, we discuss current vaccination strategies and their impact on the generation and sustainability of protective immunity against TB. PMID:26319069

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

PubMed Central

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.

PubMed

Hart, Bryan E; Lee, Sunhee

2016-12-01

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.

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

PubMed

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.

Deletion of nuoG from the Vaccine Candidate Mycobacterium bovis BCG ΔureC::hly Improves Protection against Tuberculosis

PubMed Central

Gengenbacher, Martin; Nieuwenhuizen, Natalie; Vogelzang, Alexis; Liu, Haipeng; Kaiser, Peggy; Schuerer, Stefanie; Lazar, Doris; Wagner, Ina; Mollenkopf, Hans-Joachim

2016-01-01

ABSTRACT The current tuberculosis (TB) vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), provides insufficient protection against pulmonary TB. Previously, we generated a listeriolysin-expressing recombinant BCG strain, which to date has successfully completed phase I and phase IIa clinical trials. In an attempt to further improve efficacy, we deleted the antiapoptotic virulence gene nuoG, encoding NADH dehydrogenase 1 subunit G, from BCG ΔureC::hly. In vitro, deletion of nuoG unexpectedly led to strongly increased recruitment of the autophagosome marker LC3 to the engulfed vaccine, suggesting that nuoG also affects xenophagic pathways. In mice, BCG ΔureC::hly ΔnuoG vaccination was safer than BCG and improved protection over that of parental BCG ΔureC::hly, significantly reducing TB load in murine lungs, ameliorating pulmonary pathology, and enhancing immune responses. Transcriptome analysis of draining lymph nodes after vaccination with either BCG ΔureC::hly or BCG ΔureC::hly ΔnuoG demonstrated earlier and stronger induction of immune responses than that with BCG SSI and suggested upregulation of inflammasome activation and interferon-induced GTPases. In summary, BCG ΔureC::hly ΔnuoG is a promising next-generation TB vaccine candidate with excellent efficacy and safety. PMID:27222470

Monosodium Urate Crystals Promote Innate Anti-Mycobacterial Immunity and Improve BCG Efficacy as a Vaccine against Tuberculosis

PubMed Central

Taus, Francesco; Santucci, Marilina B.; Greco, Emanuela; Morandi, Matteo; Palucci, Ivana; Mariotti, Sabrina; Poerio, Noemi; Nisini, Roberto; Delogu, Giovanni; Fraziano, Maurizio

2015-01-01

A safer and more effective anti-Tuberculosis vaccine is still an urgent need. We probed the effects of monosodium urate crystals (MSU) on innate immunity to improve the Bacille Calmette-Guerin (BCG) vaccination. Results showed that in vitro MSU cause an enduring macrophage stimulation of the anti-mycobacterial response, measured as intracellular killing, ROS production and phagolysosome maturation. The contribution of MSU to anti-mycobacterial activity was also shown in vivo. Mice vaccinated in the presence of MSU showed a lower number of BCG in lymph nodes draining the vaccine inoculation site, in comparison to mice vaccinated without MSU. Lastly, we showed that MSU improved the efficacy of BCG vaccination in mice infected with Mycobacterium tuberculosis (MTB), measured in terms of lung and spleen MTB burden. These results demonstrate that the use of MSU as adjuvant may represent a novel strategy to enhance the efficacy of BCG vaccination. PMID:26023779

[The tuberculin skin test in BCG-vaccinated individualse].

PubMed

Miret Cuadras, P; Pina Gutiérrez, J M

1998-10-01

The aim of this study was to evaluate the tuberculin skin test in individuals vaccinated with bacillus Calmette-Guérin (BCG) using 2 IU of RT-23. One hundred ninety-six individuals aged 22-40 years-old who had been vaccinated with BCG between 1965 and 1974 were enrolled along with 375 non-vaccinated individuals of the same age and with similar level of risk of infection. The positive predictive value of the test was assessed for three levels of response as indicated by areas of thickening in three diameters: 5, 10 and 15 mm. Vaccinated individuals with negative results were given a second skin test 7 days later to detect a booster effect. Positive diameters 5 mm were observed in 66% of the vaccinated individuals and 24% of the non-vaccinated subjects. Positive diameters 10 mm were observed in 51% of the vaccinated individuals and 19% of the non vaccinated ones. Positive diameters 15 mm were observed in 29% of the vaccinated subjects and in 13% of the non vaccinated ones. The differences were significant for all diameters. The positive predictive value of the test was 36.4% for a diameter 5 mm, 37.6% for diameter 10 mm and 44.8% for diameter 15 mm. The booster effect was detected in 25.8% of the vaccinated individuals who had tested negative at first. In vaccinated individuals, no guidelines can be established to guarantee that a positive reaction is due to infection by Mycobacterium tuberculosis infection, although the likelihood of infection (increased positive predictive value) increases with diameter. It is also impossible to fix a time limit. A second skin test is needed to detect a booster effect in all vaccinated individuals whose first test is negative.

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

PubMed

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 < 0.01). This reduction was even higher if only extra-pulmonary infection was considered (17% and 68%, respectively; P < 0.001). This trial demonstrates that BCG vaccination of 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.

Vaccination of cattle with a high dose of BCG vaccine 3 weeks after experimental infection with Mycobacterium bovis increased the inflammatory response, but not tuberculous pathology.

PubMed

Buddle, Bryce M; Shu, Dairu; Parlane, Natalie A; Subharat, Supatsak; Heiser, Axel; Hewinson, R Glyn; Vordermeier, H Martin; Wedlock, D Neil

2016-07-01

A study was undertaken to determine whether BCG vaccination of cattle post-challenge could have an effect on a very early Mycobacterium bovis infection. Three groups of calves (n = 12/group) were challenged endobronchially with M. bovis and slaughtered 13 weeks later to examine for tuberculous lesions. One group had been vaccinated prophylactically with BCG Danish vaccine 21 weeks prior to challenge; a second group was vaccinated with a 4-fold higher dose of BCG Danish 3 weeks post-challenge and the third group, remained non-vaccinated. Vaccination prior to challenge induced only minimal protection with just a significant reduction in the lymph node lesion scores. Compared to the non-vaccinated group, BCG vaccination post-challenge produced no reduction in gross pathology and histopathology, but did result in significant increases in mRNA expression of pro-inflammatory mediators (IFN-γ, IL-12p40, IL-17A, IRF-5, CXCL9, CXCL10, iNOs, and TNF-α) in the pulmonary lymph nodes. Although there was no significant differences in the gross pathology and histopathology between the post-challenge BCG and non-vaccinated groups, the enhanced pro-inflammatory immune responses observed in the post-challenge BCG group suggest caution in the use of high doses of BCG where there is a possibility that cattle may be infected with M. bovis prior to vaccination. Copyright © 2016 Elsevier Ltd. All rights reserved.

Randomised vaccine trial of single dose of killed Leishmania major plus BCG against anthroponotic cutaneous leishmaniasis in Bam, Iran.

PubMed

Sharifi, I; FeKri, A R; Aflatonian, M R; Khamesipour, A; Nadim, A; Mousavi, M R; Momeni, A Z; Dowlati, Y; Godal, T; Zicker, F; Smith, P G; Modabber, F

1998-05-23

A vaccine consisting of a single dose of whole-cell autoclave-killed Leishmania major (ALM) mixed with BCG was assessed in comparison with BCG alone against anthroponotic (human to human transmission) cutaneous leishmaniasis in a randomised double-blind trial in Bam, Iran. 3637 schoolchildren, aged 6-15 years, with no history of cutaneous leishmaniasis and no response to a leishmanin skin test, were randomly assigned to receive 1 mg ALM mixed with BCG (n = 1839), or BCG alone (n = 1798). Safety of the vaccine and the incidence of confirmed cases of cutaneous leishmaniasis were followed up for 2 years. Side-effects were those usually associated with BCG vaccination, but tended to persist longer in the ALM + BCG group. After exclusion of four cases occurring within 80 days of vaccination (one in the ALM + BCG group and three in the BCG group), the 2-year incidence of cutaneous leishmaniasis did not differ significantly between vaccine and BCG groups: 2.8% vs 3.3%, respectively (total cases 112). A sex-stratified analysis showed that in boys the vaccine conferred a protective efficacy of 18% and 78% for the first and second years, respectively--a crude 2-year overall protection of 55% (95% CI 19-75%, p < 0.01). In the first 9 months after vaccination, there was a non-significant excess of cases in the ALM + BCG group (25 vs 16), whereas the incidence of cutaneous leishmaniasis thereafter was significantly reduced in the ALM + BCG group (27 vs 44, p < 0.05). A single dose of ALM + BCG was safe and more immunogenic than BCG alone, as measured by leishmanin skin test. The exact reason for the apparent protective effect of the vaccine in boys is unknown, and may be a chance finding. However, since boys are more exposed to the infection, which is indicated by higher disease prevalence in boys in this study population, the preferential protective effect in boys may have resulted from a greater booster effect produced by repeated exposure to infected sandflies. Booster

Pre-clinical toxicity and immunogenicity evaluation of a MUC1-MBP/BCG anti-tumor vaccine.

PubMed

Hu, Boqi; Wang, Juan; Guo, Yingying; Chen, Tanxiu; Ni, Weihua; Yuan, Hongyan; Zhang, Nannan; Xie, Fei; Tai, Guixiang

2016-04-01

Mucin 1 (MUC1), as an oncogene, plays a key role in the progression and tumorigenesis of many human adenocarcinomas and is an attractive target in tumor immunotherapy. Our previous study showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific Th1-dominant immune response, simulated MUC1-specific cytotoxic T lymphocyte killing activity, and could significantly inhibit MUC1-expression B16 cells' growth in mice. To help move the vaccine into a Phase I clinical trial, in the current study, a pre-clinical toxicity and immunogenicity evaluation of the vaccine was conducted. The evaluation was comprised of a single-dose acute toxicity study in mice, repeat-dose chronic toxicity and immunogenicity studies in rats, and pilot toxicity and immunogenicity studies in cynomolgus monkeys. The results showed that treatment with the MUC1-MBP/BCG anti-tumor vaccine did not cause any organ toxicity, except for arthritis or local nodules induced by BCG in several rats. Furthermore, the vaccine significantly increased the levels of IFN-γ in rats, indicating that Th1 cells were activated. In addition, the results showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific IgG antibody response both in rats and cynomolgus monkeys. Collectively, these data are beneficial to move the MUC1-MBP/BCG anti-tumor vaccine into a Phase I clinical trial. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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.

Early versus late BCG vaccination in HIV-1-exposed infants in Uganda: study protocol for a randomized controlled trial.

PubMed

Nankabirwa, Victoria; Tumwine, James K; Namugga, Olive; Tylleskär, Thorkild; Ndeezi, Grace; Robberstad, Bjarne; Netea, Mihai G; Sommerfelt, Halvor

2017-03-31

Bacillus Calmette-Guérin (BCG) vaccination may have nonspecific effects, i.e., effects on childhood morbidity and mortality that go beyond its effect on the risk of childhood tuberculosis (TB). Though the available scientific literature is mostly from observational studies, and is fraught with controversy, BCG vaccination at birth may protect infants in high-mortality populations against serious infections other than TB. Yet, other studies indicate that giving BCG later in infancy may modify immune responses to non-TB antigens and potentially enhance immunity, potentially also against tuberculosis (TB). It is unclear whether BCG vaccination very early in life offers adequate protection against TB and other infections among HIV-1-exposed children because even those who remain uninfected with HIV-1 show signs of impaired immunocompetence early in infancy. This study will compare BCG vaccination at birth with BCG vaccination at 14 weeks of age in HIV-1-exposed infants. This is an individually randomized controlled trial in 2200 HIV-1-exposed infants. The intervention is BCG vaccination within 24 h of birth while the comparator is BCG given at 14 weeks of age. The study co-primary outcomes are severe illness in the first 14 weeks of life, and production of tumor necrosis factor, interleukin (IL)-1β, IL-6 and interferon-γ in response to mycobacterial and nonmycobacterial antigens. The study is being conducted in three health centers in Uganda. A well-timed BCG vaccination could have important nonspecific effects in HIV-1-exposed infants. This trial could inform the development of appropriate timing of BCG vaccination for HIV-1-exposed infants. ClinicalTrials.gov, identifier: NCT02606526 . Registered on 12 November 2015.

Timeliness and completeness of vaccination and risk factors for low and late vaccine uptake in young children living in rural southern Tanzania.

PubMed

Le Polain de Waroux, Olivier; Schellenberg, Joanna R Armstrong; Manzi, Fatuma; Mrisho, Mwifadhi; Shirima, Kizito; Mshinda, Hassan; Alonso, Pedro; Tanner, Marcel; Schellenberg, David M

2013-06-01

We studied coverage and timeliness of vaccination and risk factors for low and delayed vaccine uptake in children aged <2 years in rural Tanzania. We used data from a cluster survey conducted in 2004, which included 1403 children. Risk factors were analysed by log-binomial regression adjusted for the clustering. The analysis was restricted to BCG, first and third dose of Diphtheria-Tetanus-Pertussis vaccines (DTP-1 and DTP-3) and first dose of measles-containing vaccine (MCV-1). Coverage for BCG, DTP-1, DTP-3 and MCV-1 was 94%, 96%, 90% and 86%, respectively. Delayed vaccination (>1 month after the recommended age) occurred in 398/1205 (33%) children for BCG, 404/1189 (34%) for DTP-1, 683/990 (69%) for DTP-3 and 296/643 (46%) for MCV-1. Coverage was lower for all vaccines except DTP-1 in children living ≥5 km from a healthcare facility. Delayed uptake was associated with poverty. Low and delayed MCV-1 vaccination was associated with low maternal education. Delayed BCG vaccination was associated with ethnicity and rainy season. Despite reasonably high vaccination coverage, we observed substantial vaccination delays, particularly for DTP-3 and MCV-1. We found specific factors associated with low and/or delayed vaccine uptake. These findings can help to improve strategies to reach children who remain inadequately protected.

Intranasal bacille Calmette–Guérin (BCG) vaccine dosage needs balancing between protection and lung pathology

PubMed Central

TREE, J A; WILLIAMS, A; CLARK, S; HALL, G; MARSH, P D; IVANYI, J

2004-01-01

Intranasal vaccination may offer practical benefits and better protection against respiratory infections, including tuberculosis. In this paper, we investigated the persistence of the Mycobacterium bovis-strain bacille Calmette–Guérin (BCG) Pasteur, lung granuloma formation and protection against pathogenic tuberculous challenge in mice. A pronounced BCG dose-dependent granulomatous infiltration of the lungs was observed following intranasal, but not after subcutaneous, vaccination. Corresponding doses of BCG, over a 100-fold range, imparted similar protection against H37Rv challenge when comparing the intranasal and subcutaneous vaccination routes. Interestingly, a BCG dose-dependent reduction of the H37Rv challenge infection was observed in the lungs, but not in the spleens, following both intranasal and subcutaneous vaccination. In the light of the observed concurrence between the extent of granuloma formation and the level of protection of the lungs, we conclude that intranasal vaccination leading to best protective efficacy needs to be balanced with an acceptable safety margin avoiding undue pathology in the lungs. PMID:15544615

Presence of mycobacterial L-forms in human blood: Challenge of BCG vaccination

PubMed Central

Markova, Nadya; Slavchev, Georgi; Michailova, Lilia

2015-01-01

Possible persistence of bacteria in human blood as cell wall deficient forms (L-forms) represents a top research priority for microbiologists. Application of live BCG vaccine and L-form transformation of vaccine strain may display a new intriguing aspect concerning the opportunity for occurrence of unpredictable colonization inside the human body by unusual microbial life forms. L-form cultures were isolated from 141 blood samples of people previously vaccinated with BCG, none with a history of exposure to tuberculosis. Innovative methodology to access the unusual L-form elements derived from human blood was developed. The methodology outlines the path of transformation of non- cultivable L-form element to cultivable bacteria and their adaptation for growth in vitro. All isolates showed typical L-forms growth features (“fried eggs” colonies and biofilm). Electron microscopy revealed morphology evidencing peculiar characteristics of bacterial L-form population (cell wall deficient polymorphic elements of variable shape and size). Regular detection of acid fast bacteria in smears of isolated blood L-form cultures, led us to start their identification by using specific Mycobactrium spp. genetic tests. Forty five of 97 genetically tested blood cultures provided specific positive signals for mycobacteria, confirmed by at least one of the 3 specific assays (16S rRNA PCR; IS6110 Real Time PCR and spoligotyping). In conclusion, the obtained genetic evidence suggests that these L-forms are of mycobacterial origin. As the investigated people had been vaccinated with BCG, we can assume that the identified mycobacterial L-forms may be produced by persisting live BCG vaccine. PMID:25874947

Intranasal mucosal boosting with an adenovirus-vectored vaccine markedly enhances the protection of BCG-primed guinea pigs against pulmonary tuberculosis.

PubMed

Xing, Zhou; McFarland, Christine T; Sallenave, Jean-Michel; Izzo, Angelo; Wang, Jun; McMurray, David N

2009-06-10

Recombinant adenovirus-vectored (Ad) tuberculosis (TB) vaccine platform has demonstrated great potential to be used either as a stand-alone or a boost vaccine in murine models. However, Ad TB vaccine remains to be evaluated in a more relevant and sensitive guinea pig model of pulmonary TB. Many vaccine candidates shown to be effective in murine models have subsequently failed to pass the test in guinea pig models. Specific pathogen-free guinea pigs were immunized with BCG, AdAg85A intranasally (i.n), AdAg85A intramuscularly (i.m), BCG boosted with AdAg85A i.n, BCG boosted with AdAg85A i.m, or treated only with saline. The animals were then infected by a low-dose aerosol of M. tuberculosis (M.tb). At the specified times, the animals were sacrificed and the levels of infection in the lung and spleen were assessed. In separate studies, the long-term disease outcome of infected animals was monitored until the termination of this study. Immunization with Ad vaccine alone had minimal beneficial effects. Immunization with BCG alone and BCG prime-Ad vaccine boost regimens significantly reduced the level of M.tb infection in the tissues to a similar extent. However, while BCG alone prolonged the survival of infected guinea pigs, the majority of BCG-immunized animals succumbed by 53 weeks post-M.tb challenge. In contrast, intranasal or intramuscular Ad vaccine boosting of BCG-primed animals markedly improved the survival rate with 60% of BCG/Ad i.n- and 40% of BCG/Ad i.m-immunized guinea pigs still surviving by 74 weeks post-aerosol challenge. Boosting, particularly via the intranasal mucosal route, with AdAg85A vaccine is able to significantly enhance the long-term survival of BCG-primed guinea pigs following pulmonary M.tb challenge. Our results thus support further evaluation of this viral-vectored TB vaccine in clinical trials.

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

PubMed

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.

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

PubMed

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.

BCG - old workhorse, new skills.

PubMed

Gengenbacher, M; Nieuwenhuizen, N E; Kaufmann, She

2017-08-01

Bacille Calmette-Guérin (BCG), the only tuberculosis (TB) vaccine in clinical practice, has limitations in efficacy, immunogenicity and safety. Much current TB vaccine research focuses on engineering live mycobacteria to interfere with phagosome biology and host intracellular pathways including apoptosis and autophagy, with candidates such as BCG Δzmp1, BCG ΔureC::hly, BCG::ESX-1 Mmar , Mtb ΔphoP ΔfadD26, Mtb ΔRD1 ΔpanCD and M. smegmatis Δesx-3::esx-3(Mtb) in the development pipeline. Correlates of protection in preclinical studies include increased central memory CD4 + T cells and recruitment of antigen-specific T cells to the lungs, with mucosal vaccination found to be superior to parenteral vaccination. Finally, recent studies suggest beneficial non-specific effects of BCG on immunity, which should be taken into account when considering these vaccines for BCG replacement. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Assessment of BCG vaccination in India

PubMed Central

1957-01-01

A second assessment of the mass BCG-vaccination campaign in India is described in this report. Data were collected to corroborate the findings of the first assessment and to study certain aspects of the problems they posed. Sample retesting of children vaccinated in the mass campaign reveals a higher and less variable allergy than that reported from the preliminary assessment work. The results indicate that a uniform and reasonably high level of allergy has been induced in Indian schoolchildren vaccinated in the campaign period assessed and that deficiencies in the tuberculin test by which the allergy was measured rather than defects of vaccine or vaccination technique were responsible for the disappointing variability initially reported. Testing of unvaccinated village populations in Madras and Mysore confirms previous observations that low-grade, non-specific tuberculin sensitivity is widely prevalent in South India, making it virtually impossible to separate the infected from the uninfected with the tuberculin tests in use today. The development of new techniques for use in areas where the low-grade, non-specific sensitivity is widespread is discussed. PMID:13489464

A New Recombinant BCG Vaccine Induces Specific Th17 and Th1 Effector Cells with Higher Protective Efficacy against Tuberculosis

PubMed Central

da Costa, Adeliane Castro; Costa-Júnior, Abadio de Oliveira; de Oliveira, Fábio Muniz; Nogueira, Sarah Veloso; Rosa, Joseane Damaceno; Resende, Danilo Pires; Kipnis, André; Junqueira-Kipnis, Ana Paula

2014-01-01

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials. PMID:25398087

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

PubMed

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.

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

PubMed

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.

Coverage and timing of children's vaccination: an evaluation of the expanded programme on immunisation in The Gambia.

PubMed

Scott, Susana; Odutola, Aderonke; Mackenzie, Grant; Fulford, Tony; Afolabi, Muhammed O; Lowe Jallow, Yamundow; Jasseh, Momodou; Jeffries, David; Dondeh, Bai Lamin; Howie, Stephen R C; D'Alessandro, Umberto

2014-01-01

To evaluate the coverage and timeliness of the Expanded Programme on Immunisation (EPI) in The Gambia. Vaccination data were obtained between January 2005 and December 2012 from the Farafenni Health and Demographic Surveillance System (FHDSS), the Basse Health and Demographic Surveillance System (BHDSS), the Kiang West Demographic surveillance system (KWDSS), a cluster survey in the more urban Western Health Region (WR) and a cross sectional study in four clinics in the semi-urban Greater Banjul area of WR. Kaplan-Meier survival function was used to estimate the proportion vaccinated by age and to assess timeliness to vaccination. BCG vaccine uptake was over 95% in all regions. Coverage of DPT1 ranged from 93.2% in BHDSS to 99.8% in the WR. Coverage decreased with increasing number of DPT doses; DPT3 coverage ranged from 81.7% in BHDSS to 99.0% in WR. Measles vaccination coverage ranged from 83.3% in BHDSS to 97.0% in WR. DPT4 booster coverage was low and ranged from 43.9% in the WR to 82.8% in KWDSS. Across all regions, delaying on previous vaccinations increased the likelihood of being delayed for the subsequent vaccination. The Gambia health system achieves high vaccine coverage in the first year of life. However, there continues to be a delay to vaccination which may impact on the introduction of new vaccines. Examples of effectively functioning EPI programmes such as The Gambia one may well be important models for other low income countries struggling to achieve high routine vaccination coverage.

A live attenuated BCG vaccine overexpressing multistage antigens Ag85B and HspX provides superior protection against Mycobacterium tuberculosis infection.

PubMed

Yuan, Xuefeng; Teng, Xindong; Jing, Yukai; Ma, Jilei; Tian, Maopeng; Yu, Qi; Zhou, Lei; Wang, Ruibo; Wang, Weihua; Li, Li; Fan, Xionglin

2015-12-01

Tuberculosis (TB) remains one of the most menacing infectious diseases, although attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine has been widely used to protect children against primary TB. There are increasing evidences that rapid growing and dormant Mycobacterium tuberculosis (M. tuberculosis) coexist in vivo after infection. However, BCG vaccine only elicits cell-mediated immune responses to secretory antigens expressed by rapid growing pathogen. BCG vaccine is thus unable to thwart the reactivation of latent tuberculosis infection (LTBI), and its protection wanes over age after neonatal immunization. In order to extend its ability for a durable protection, a novel recombinant BCG (rBCG) strain, named rBCG::XB, was constructed by overexpressing immunodominant multistage antigens of Ag85B and HspX, which are expressed by both rapid replicating and dormant M. tuberculosis. Long-term protective effect and immunogenicity of rBCG::XB were compared with the parental BCG in vaccinated C57BL/6 mice. Our results demonstrated that rBCG::XB provided the stronger and long-lasting protection against M. tuberculosis H37Rv intranasal infection than BCG. The rBCG::XB not only elicited the more durable multistage antigen-specific CD4(+)Th1-biased immune responses and specific polyfunctional CD4(+)T cells but also augmented the CD8(+) CTL effects against Ag85B in vivo. In particular, higher levels of CD4(+) TEM and CD8(+) TCM cells, dominated by IL2(+) CD4(+) and CD8(+) TCM cells, were obtained in the spleen of rBCG::XB vaccinated mice. Therefore, our findings indicate that rBCG::XB is a promising candidate to improve the efficacy of BCG.

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

PubMed Central

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

2018-01-01

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. PMID:23196205

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.

PubMed

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.

"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.

PubMed

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

PubMed

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

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

PubMed Central

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 108 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 or

Assessment of BCG and inactivated Mycobacterium bovis vaccines in an experimental tuberculosis infection model in sheep.

PubMed

Balseiro, Ana; Altuzarra, Raúl; Vidal, Enric; Moll, Xavier; Espada, Yvonne; Sevilla, Iker A; Domingo, Mariano; Garrido, Joseba M; Juste, Ramón A; Prieto, Miguel; Pérez de Val, Bernat

2017-01-01

Animal tuberculosis (TB) is a complex animal health problem that causes disruption to trade and significant economic losses. TB involves a multi-host system where sheep, traditionally considered a rare host of this infection, have been recently included. The aims of this study were to develop an experimental TB infection model in sheep with a Mycobacterium caprae field strain isolated from a tuberculous diseased ewe, and to use this to evaluate the safety and efficacy of two vaccines against TB in sheep, the live-attenuated M. bovis BCG vaccine (Danish strain) and a heat-inactivated M. bovis (HIMB) vaccine. Eighteen 2 month-old lambs were experimentally challenged with M. caprae by the endotracheal route (1.5 × 103 CFU). They were separated per treatment group into parenterally vaccinated with a live BCG Danish strain vaccine (n = 6), orally vaccinated with a suspension of HIMB (n = 6) and unvaccinated controls (n = 6). Clinical, immunological, pathological and bacteriological parameters of infection were measured. All lambs were successfully infected and developed gross TB lesions in the respiratory system. The BCG vaccine conferred considerable protection against experimental TB in lambs, as measured by a reduction of the gross lesion volumes and bacterial load. However, HIMB vaccinated animals did not show protection. This study proposes a reliable new experimental model for a better understanding of tuberculosis in sheep. BCG vaccination offers an effective prospect for controlling the disease. Moreover alternative doses and/or routes of administration should be considered to evaluate the efficacy of the HIMB vaccine candidate.

Bacillus Calmette-Guérin (BCG) vaccination patterns in the province of Québec, Canada, 1956-1974.

PubMed

Rousseau, Marie-Claude; Conus, Florence; Kâ, Khady; El-Zein, Mariam; Parent, Marie-Élise; Menzies, Dick

2017-08-24

In the province of Québec, Canada, the Bacillus Calmette-Guérin (BCG) vaccine was offered to newborns and school-age children from the 1950s to mid-1970s in an organized tuberculosis prevention program. We aimed to describe the annual rates of skin test administration, proportion of skin tests that were positive, and rates of BCG vaccination from 1956 to 1974 according to age, sex, and administrative region. For rates, numerators were extracted from the Québec BCG Vaccination Registry whereas population denominators were obtained from the Canadian Census and governmental publications. Time trends were assessed with linear regression. A total of 2,755,336 skin tests and 2,531,366 BCG vaccinations were administered. Yearly rates of skin tests, routinely administered before vaccination among all except newborns, were highest among children aged 5-9 (9.3 per 100) and 10-14years (7.9 per 100). The proportion of positive skin tests varied greatly by age, ranging from 10.2% among children <1year to 67.2% among adults ≥20years. The vast majority of individuals who had a negative skin test were subsequently vaccinated, whereas those with a positive result were not, as per recommended guidelines. The average annual vaccination rate was highest among children aged <1year (43.8 per 100) and 5-9year-olds (6.9 per 100). There were salient differences in immunization rates, including positive skin tests and vaccinations, across administrative regions but no difference by sex. This is the first comprehensive description of the tuberculosis prevention program in Québec which offered free, non-mandatory BCG vaccination. Our results confirm that the targeted groups, newborns and school-age children, were preferentially reached. Socioeconomic, demographic, and organizational factors may explain regional differences in immunization rates. Beyond presenting a historical context for this vaccination campaign, our findings are relevant to contemporary uses of the Québec BCG

Vaccination coverage and immunization timeliness among children aged 12-23 months in Senegal: a Kaplan-Meier and Cox regression analysis approach

PubMed Central

Mbengue, Mouhamed Abdou Salam; Mboup, Aminata; Ly, Indou Deme; Faye, Adama; Camara, Fatou Bintou Niang; Thiam, Moussa; Ndiaye, Birahim Pierre; Dieye, Tandakha Ndiaye; Mboup, Souleymane

2017-01-01

Introduction Expanded programme on immunizations in resource-limited settings currently measure vaccination coverage defined as the proportion of children aged 12-23 months that have completed their vaccination. However, this indicator does not address the important question of when the scheduled vaccines were administered. We assessed the determinants of timely immunization to help the national EPI program manage vaccine-preventable diseases and impact positively on child survival in Senegal. Methods Vaccination data were obtained from the Demographic and Health Survey (DHS) carried out across the 14 regions in the country. Children were aged between 12-23 months. The assessment of vaccination coverage was done with the health card and/or by the mother’s recall of the vaccination act. For each vaccine, an assessment of delay in age-appropriate vaccination was done following WHO recommendations. Additionally, Kaplan-Meier survival function was used to estimate the proportion vaccinated by age and cox-proportional hazards models were used to examine risk factors for delays. Results A total of 2444 living children between 12–23 months of age were included in the analysis. The country vaccination was below the WHO recommended coverage level and, there was a gap in timeliness of children immunization. While BCG vaccine uptake was over 95%, coverage decreased with increasing number of Pentavalent vaccine doses (Penta 1: 95.6%, Penta 2: 93.5%: Penta 3: 89.2%). Median delay for BCG was 1.7 weeks. For polio at birth, the median delay was 5 days; all other vaccine doses had median delays of 2-4 weeks. For Penta 1 and Penta 3, 23.5% and 15.7% were given late respectively. A quarter of measles vaccines were not administered or were scheduled after the recommended age. Vaccinations that were not administered within the recommended age ranges were associated with mothers’ poor education level, multiple siblings, low socio-economic status and living in rural areas

Vaccination coverage and immunization timeliness among children aged 12-23 months in Senegal: a Kaplan-Meier and Cox regression analysis approach.

PubMed

Mbengue, Mouhamed Abdou Salam; Mboup, Aminata; Ly, Indou Deme; Faye, Adama; Camara, Fatou Bintou Niang; Thiam, Moussa; Ndiaye, Birahim Pierre; Dieye, Tandakha Ndiaye; Mboup, Souleymane

2017-01-01

Expanded programme on immunizations in resource-limited settings currently measure vaccination coverage defined as the proportion of children aged 12-23 months that have completed their vaccination. However, this indicator does not address the important question of when the scheduled vaccines were administered. We assessed the determinants of timely immunization to help the national EPI program manage vaccine-preventable diseases and impact positively on child survival in Senegal. Vaccination data were obtained from the Demographic and Health Survey (DHS) carried out across the 14 regions in the country. Children were aged between 12-23 months. The assessment of vaccination coverage was done with the health card and/or by the mother's recall of the vaccination act. For each vaccine, an assessment of delay in age-appropriate vaccination was done following WHO recommendations. Additionally, Kaplan-Meier survival function was used to estimate the proportion vaccinated by age and cox-proportional hazards models were used to examine risk factors for delays. A total of 2444 living children between 12-23 months of age were included in the analysis. The country vaccination was below the WHO recommended coverage level and, there was a gap in timeliness of children immunization. While BCG vaccine uptake was over 95%, coverage decreased with increasing number of Pentavalent vaccine doses (Penta 1: 95.6%, Penta 2: 93.5%: Penta 3: 89.2%). Median delay for BCG was 1.7 weeks. For polio at birth, the median delay was 5 days; all other vaccine doses had median delays of 2-4 weeks. For Penta 1 and Penta 3, 23.5% and 15.7% were given late respectively. A quarter of measles vaccines were not administered or were scheduled after the recommended age. Vaccinations that were not administered within the recommended age ranges were associated with mothers' poor education level, multiple siblings, low socio-economic status and living in rural areas. A significant delay in receipt of infant

The geographic location (latitude) of studies evaluating protective effect of BCG vaccine and it's efficacy/effectiveness against tuberculosis.

PubMed

Zodpey, Sanjay P; Shrikhande, Sunanda N

2007-01-01

To study association between the geographic location (latitude) of studies evaluating protective effect of BCG vaccine and it's efficacy / effectiveness against tuberculosis. A comprehensive literature search was carried out to identify relevant studies. Data extraction from these studies included place of study (geographic latitude), study design and reported point estimate of protective effect of BCG vaccine against tuberculosis. Information on latitude was obtained from Oxford School Atlas for World Geography. A spearman rank correlation coefficient was estimated to study the association between the latitude of studies and protective effect of BCG vaccine. The Spearman's rank correlation coefficient was significant for all studies grouped together & trials and marginally non-significant for other observational studies. However it was not statistically significant for case-control studies and cohort studies. Overall rho (for 80 studies) between latitude and protective effect of BCG was calculated to be 0.3853 (p = 0.0004). The results thus demonstrated that, in general BCG appeared to provide greater protection at higher latitudes. Thus a correlation coefficient of 0.3853 between latitude and protective effect would indicate that (0.3853)(2) or 15% of the variance in protective effect was accounted for by latitude. The study recognized an association between geographic locations of studies and reported protective effects of BCG vaccine against tuberculosis.

Comparison of the Membrane Proteome of Virulent Mycobacterium tuberculosis and the Attenuated Mycobacterium bovis BCG Vaccine Strain by Label-free Quantitative Proteomics

PubMed Central

Gunawardena, Harsha P.; Feltcher, Meghan E.; Wrobel, John A.; Gu, Sheng; Braunstein, Miriam; Chen, Xian

2015-01-01

The Mycobacterium tuberculosis (MTB) membrane is rich in antigens that are potential targets for diagnostics and the development of new vaccines. To better understand the mechanisms underlying MTB virulence and identify new targets for therapeutic intervention we investigated the differential composition of membrane proteomes between virulent M. tuberculosis H37Rv (MTB) and the Mycobacterium bovis BCG vaccine strain. To compare the membrane proteomes, we used LC-MS/MS analysis in combination with label-free quantitative (LFQ) proteomics, utilizing the area-under-curve (AUC) of the extracted ion chromatograms (XIC) of peptides obtained from m/z and retention time alignment of MS1 features. With this approach, we obtained relative abundance ratios for 2,203 identified membrane-associated proteins in high confidence. Of these proteins, 294 showed statistically significant differences of at least 2 fold, in relative abundance between MTB and BCG membrane fractions. Our comparative analysis detected several proteins associated with known genomic regions of difference between MTB and BCG as being absent, which validated the accuracy of our approach. In further support of our label-free quantitative data, we verified select protein differences by immunoblotting. To our knowledge we have generated the first comprehensive and high coverage profile of comparative membrane proteome changes between virulent MTB and its attenuated relative BCG, which helps elucidate the proteomic basis of the intrinsic virulence of the MTB pathogen. PMID:24093440

Delayed BCG vaccination results in minimal alterations in T cell immunogenicity of acellular pertussis and tetanus immunizations in HIV-exposed infants.

PubMed

Blakney, Anna K; Tchakoute, Christophe Toukam; Hesseling, Anneke C; Kidzeru, Elvis B; Jones, Christine E; Passmore, Jo-Ann S; Sodora, Donald L; Gray, Clive M; Jaspan, Heather B

2015-09-11

Bacille Calmette-Guerin (BCG) is effective in preventing disseminated tuberculosis (TB) in children but may also have non-specific benefits, and is thought to improve immunity to unrelated antigens through trained innate immunity. In HIV-infected infants, there is a risk of BCG-associated adverse events. We aimed to explore whether delaying BCG vaccination by 8 weeks, in utero or perinatal HIV infection is excluded, affected T-cell responses to B. pertussis (BP) and tetanus toxoid (TT), in HIV-exposed, uninfected infants. Infants were randomized to receive BCG vaccination at birth or 8 weeks of age. At 8 and 14 weeks, T cell proliferation and intracellular cytokine (IL-2, IL-13, IL-17, and IFN-γ) expression was analyzed in response to BP, TT and Staphylococcal enterotoxin B (SEB) antigens. Delaying BCG vaccination did not alter T-cell proliferation to BP or TT antigens. Infants immunized with BCG at birth had higher CD4+ T cell proliferation to SEB at 14 weeks of age (p=0.018). Birth-vaccinated infants had increased CD8+ IL-2 expression in response to BP, but not TT or SEB, at 8 weeks. Infants vaccinated with BCG at 8 weeks had significantly lower IL-13 expression by BP-specific CD4+ and CD8+ T cells at 14 weeks (p=0.032 and p=0.0035, respectively). There were no observed differences in multifunctional cytokine response to TT, BP or SEB between infants vaccinated with BCG at birth versus 8 weeks of age. Delaying BCG vaccination until 8 weeks of age results in robust T-cellular responses to BP and TT in HIV-exposed infants. NCT02062580. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phenotypic differences between BCG vaccines at the proteome level.

PubMed

Rodríguez-Alvarez, Mauricio; Mendoza-Hernández, Guillermo; Encarnación, Sergio; Calva, Juan José; López-Vidal, Yolanda

2009-03-01

To contribute to Mycobacterium bovis BCG characterization, two substrains were analyzed using two-dimensional gel electrophoresis (2D-PAGE) and mass spectrometry (MS), based on their protective efficacy in a pulmonary-tuberculosis mouse model. Cell-fraction proteins of BCG Denmark and Phipps substrains were separated into approximately 500 spots in 2D-PAGE. The proteomes were similar in protein number, and isoelectric point (pI) and molecular mass (MM) distribution. Statistical analysis, resulted in 72 spots with no change, and 168 and 90 unique for BCG Phipps or Denmark, respectively. Two hundred and fourteen spots showed changes in intensity of >1-fold, 138 of Denmark, and 76 of Phipps. Seventeen spots were selected for MS-based identification (13 from Phipps and 4 from Denmark), including unique, as well as proteins with changes in intensity. The proteins identified participate in virulence, detoxification, adaptation, lipid metabolism, information pathways, cell wall and cell processes, intermediary metabolism and respiration, or still hypotheticals. Our findings contribute to phenotype characterization of BCG substrains and provide new elements to consider for the design of diagnostic tools, drug targets and a new vaccine against tuberculosis based upon protein expression through quantitative statistical analysis.

Using lot quality assurance sampling to improve immunization coverage in Bangladesh.

PubMed Central

Tawfik, Y.; Hoque, S.; Siddiqi, M.

2001-01-01

OBJECTIVE: To determine areas of low vaccination coverage in five cities in Bangladesh (Chittagong, Dhaka, Khulna, Rajshahi, and Syedpur). METHODS: Six studies using lot quality assurance sampling were conducted between 1995 and 1997 by Basic Support for Institutionalizing Child Survival and the Bangladesh National Expanded Programme on Immunization. FINDINGS: BCG vaccination coverage was acceptable in all lots studied; however, the proportion of lots rejected because coverage of measles vaccination was low ranged from 0% of lots in Syedpur to 12% in Chittagong and 20% in Dhaka's zones 7 and 8. The proportion of lots rejected because an inadequate number of children in the sample had been fully vaccinated varied from 11% in Syedpur to 30% in Dhaka. Additionally, analysis of aggregated, weighted immunization coverage showed that there was a high BCG vaccination coverage (the first administered vaccine) and a low measles vaccination coverage (the last administered vaccine) indicating a high drop-out rate, ranging from 14% in Syedpur to 36% in Dhaka's zone 8. CONCLUSION: In Bangladesh, where resources are limited, results from surveys using lot quality assurance sampling enabled managers of the National Expanded Programme on Immunization to identify areas with poor vaccination coverage. Those areas were targeted to receive focused interventions to improve coverage. Since this sampling method requires only a small sample size and was easy for staff to use, it is feasible for routine monitoring of vaccination coverage. PMID:11436470

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

PubMed

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; p<0.001). Most of this difference was driven by for-profit private 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; p<0.001) compared to only 2.4 percentage points for NGOs (95% CI 1.0-3. 8; p<0.01). Moreover, children born at private 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.

Evaluation of the immunogenic capability of the BCG strains BCGΔBCG1419c and BCGΔBCG1416c in a three-dimensional human lung tissue model.

PubMed

Parasa, Venkata Ramanarao; Rose, Jeronimo; Castillo-Diaz, Luis Alberto; Aceves-Sánchez, Michel de Jesús; Vega-Domínguez, Perla Jazmín; Lerm, Maria; Flores-Valdez, Mario Alberto

2018-03-27

Tuberculosis (TB) still remains as an unmet global threat. The current vaccine is not fully effective and novel alternatives are needed. Here, two vaccine candidate strains derived from BCG carrying deletions in the BCG1416c or BCG1419c genes were analysed for their capacity to modulate the cytokine/chemokine profile and granuloma formation in a human lung tissue model (LTM). We show that the clustering of monocytes, reminiscent of early granuloma formation, in LTMs infected with BCG strains was similar for all of them. However, BCGΔBCG1419c, like M. tuberculosis, was capable of inducing the production of IL-6 in contrast to the other BCG strains. This work suggests that LTM could be a useful ex vivo assay to evaluate the potential immunogenicity of novel TB vaccine candidates. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed

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.

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

PubMed

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

Effectiveness of Routine BCG Vaccination on Buruli Ulcer Disease: A Case-Control Study in the Democratic Republic of Congo, Ghana and Togo

PubMed Central

Phillips, Richard Odame; Phanzu, Delphin Mavinga; Beissner, Marcus; Badziklou, Kossi; Luzolo, Elysée Kalundieko; Sarfo, Fred Stephen; Halatoko, Wemboo Afiwa; Amoako, Yaw; Frimpong, Michael; Kabiru, Abass Mohammed; Piten, Ebekalisai; Maman, Issaka; Bidjada, Bawimodom; Koba, Adjaho; Awoussi, Koffi Somenou; Kobara, Basile; Nitschke, Jörg; Wiedemann, Franz Xaver; Kere, Abiba Banla; Adjei, Ohene; Löscher, Thomas; Fleischer, Bernhard; Bretzel, Gisela; Herbinger, Karl-Heinz

2015-01-01

Background The only available vaccine that could be potentially beneficial against mycobacterial diseases contains live attenuated bovine tuberculosis bacillus (Mycobacterium bovis) also called Bacillus Calmette-Guérin (BCG). Even though the BCG vaccine is still widely used, results on its effectiveness in preventing mycobacterial diseases are partially contradictory, especially regarding Buruli Ulcer Disease (BUD). The aim of this case-control study is to evaluate the possible protective effect of BCG vaccination on BUD. Methodology The present study was performed in three different countries and sites where BUD is endemic: in the Democratic Republic of the Congo, Ghana, and Togo from 2010 through 2013. The large study population was comprised of 401 cases with laboratory confirmed BUD and 826 controls, mostly family members or neighbors. Principal Findings After stratification by the three countries, two sexes and four age groups, no significant correlation was found between the presence of BCG scar and BUD status of individuals. Multivariate analysis has shown that the independent variables country (p = 0.31), sex (p = 0.24), age (p = 0.96), and presence of a BCG scar (p = 0.07) did not significantly influence the development of BUD category I or category II/III. Furthermore, the status of BCG vaccination was also not significantly related to duration of BUD or time to healing of lesions. Conclusions In our study, we did not observe significant evidence of a protective effect of routine BCG vaccination on the risk of developing either BUD or severe forms of BUD. Since accurate data on BCG strains used in these three countries were not available, no final conclusion can be drawn on the effectiveness of BCG strain in protecting against BUD. As has been suggested for tuberculosis and leprosy, well-designed prospective studies on different existing BCG vaccine strains are needed also for BUD. PMID:25569674

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

PubMed

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.

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

PubMed

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.

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

PubMed Central

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

2016-01-01

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. PMID:27173443

Mycobacterium indicus pranii as a booster vaccine enhances BCG induced immunity and confers higher protection in animal models of tuberculosis.

PubMed

Saqib, Mohd; Khatri, Rahul; Singh, Bindu; Gupta, Ananya; Kumar, Arvind; Bhaskar, Sangeeta

2016-12-01

BCG, the only approved vaccine protects against severe form of childhood tuberculosis but its protective efficacy wanes in adolescence. BCG has reduced the incidence of infant TB considerably in endemic areas; therefore prime-boost strategy is the most realistic measure for control of tuberculosis in near future. Mycobacterium indicus pranii (MIP) shares significant antigenic repertoire with Mtb and BCG and has been shown to impart significant protection in animal models of tuberculosis. In this study, MIP was given as a booster to BCG vaccine which enhanced the BCG mediated immune response, resulting in higher protection. MIP booster via aerosol route was found to be more effective in protection than subcutaneous route of booster immunization. Pro-inflammatory cytokines like IFN-γ, IL-12 and IL-17 were induced at higher level in infected lungs of 'BCG-MIP' group both at mRNA expression level and in secretory form when compared with 'only BCG' group. BCG-MIP groups had increased frequency of multifunctional T cells with high MFI for IFN-γ and TNF-α in Mtb infected mice. Our data demonstrate for the first time, potential application of MIP as a booster to BCG vaccine for efficient protection against tuberculosis. This could be very cost effective strategy for efficient control of tuberculosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vaccine exemptions and the kindergarten vaccination coverage gap.

PubMed

Smith, Philip J; Shaw, Jana; Seither, Ranee; Lopez, Adriana; Hill, Holly A; Underwood, Mike; Knighton, Cynthia; Zhao, Zhen; Ravanam, Megha Shah; Greby, Stacie; Orenstein, Walter A

2017-09-25

Vaccination requirements for kindergarten entry vary by state, but all states require 2 doses of measles containing vaccine (MCV) at kindergarten entry. To assess (i) national MCV vaccination coverage for children who had attended kindergarten; (ii) the extent to which undervaccination after kindergarten entry is attributable to parents' requests for an exemption; (iii) the extent to which undervaccinated children had missed opportunities to be administered missing vaccine doses among children whose parent did not request an exemption; and (iv) the vaccination coverage gap between the "highest achievable" MCV coverage and actual MCV coverage among children who had attended kindergarten. A national survey of 1465 parents of 5-7year-old children was conducted during October 2013 through March 2014. Vaccination coverage estimates are based provider-reported vaccination histories. Children have a "missed opportunity" for MCV if they were not up-to-date and if there were dates on which other vaccines were administered but not MCV. The "highest achievable" MCV vaccination coverage rate is 100% minus the sum of the percentages of (i) undervaccinated children with parents who requested an exemption; and (ii) undervaccinated children with parents who did not request an exemption and whose vaccination statuses were assessed during a kindergarten grace period or period when they were provisionally enrolled in kindergarten. Among all children undervaccinated for MCV, 2.7% were attributable to having a parent who requested an exemption. Among children who were undervaccinated for MCV and whose parent did not request an exemption, 41.6% had a missed opportunity for MCV. The highest achievable MCV coverage was 98.6%, actual MCV coverage was 90.9%, and the kindergarten vaccination gap was 7.7%. Vaccination coverage may be increased by schools fully implementing state kindergarten vaccination laws, and by providers assessing children's vaccination status at every clinic visit, and

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

PubMed Central

Abdallah, Abdallah M.; Hill-Cawthorne, Grant A.; Otto, Thomas D.; Coll, Francesc; Guerra-Assunção, José Afonso; Gao, Ge; Naeem, Raeece; Ansari, Hifzur; Malas, Tareq B.; Adroub, Sabir A.; 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. PMID:26487098

Blockade of the Kv1.3 K+ Channel Enhances BCG Vaccine Efficacy by Expanding Central Memory T Lymphocytes.

PubMed

Singh, Dhiraj Kumar; Dwivedi, Ved Prakash; Ranganathan, Anand; Bishai, William R; Van Kaer, Luc; Das, Gobardhan

2016-11-01

Tuberculosis is the oldest known infectious disease, yet there is no effective vaccine against adult pulmonary tuberculosis. Emerging evidence indicates that T-helper 1 and T-helper 17 cells play important roles in host protection against tuberculosis. However, tuberculosis vaccine efficacy in mice is critically dependent on the balance between antigen-specific central memory T (Tcm) and effector memory T (Tem) cells. Specifically, a high Tcm/Tem cell ratio is essential for optimal vaccine efficacy. Here, we show that inhibition of Kv1.3, a potassium channel preferentially expressed by Tem cells, by Clofazimine selectively expands Tcm cells during BCG vaccination. Furthermore, mice that received clofazimine after BCG vaccination exhibited significantly enhanced resistance against tuberculosis. This superior activity against tuberculosis could be adoptively transferred to naive, syngeneic mice by CD4 + T cells. Therefore, clofazimine enhances Tcm cell expansion, which in turn provides improved vaccine efficacy. Thus, Kv1.3 blockade is a promising approach for enhancing the efficacy of the BCG vaccine in humans. © 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.

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

PubMed

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

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.

PubMed

Frankel, H; Byberg, S; Bjerregaard-Andersen, M; Martins, C L; Aaby, P; Benn, C S; Fisker, A B

2016-08-31

Different Bacillus Calmette-Guerin (BCG) vaccine strains may have different non-specific effects. We assessed the effect of two BCG strains (Danish and Russian) on childhood morbidity and BCG scarification in Guinea-Bissau. During 2011-2013, infants in the Bandim Health Project'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 models. Scar prevalence and size were compared using binomial regression and ranksum tests. Among 1206 children, 18% received Danish BCG (n=215) and 82% Russian BCG (n=991). The adjusted hazard ratio (aHR) for consultations was 0.94 (95% CI 0.60-1.46) for Danish BCG compared with Russian BCG. Girls vaccinated with Danish BCG tended to have lower consultation rates compared with girls vaccinated with Russian BCG (aHR 0.56 (0.25-1.24)), whereas the effect was opposite for boys (aHR 1.24 (0.74-2.11)), p=0.09. Children vaccinated with Danish BCG were more likely to develop a scar (97%) than children vaccinated with Russian BCG (87%), the relative risk (RR) being 1.11 (1.06-1.16). The effect was stronger in girls, and BCG scar size was larger among infants vaccinated with the Danish strain. BCG strain influences scar prevalence and scar size, and may have sex differential effects on morbidity. BCG strains are currently used interchangeably, but BCG scarring has been linked to subsequent survival. Hence, more research into the health effects of different BCG strains is warranted. Small adjustments of BCG production could potentially lower childhood morbidity and mortality at low cost. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Kinetics of the immune response profile in guinea pigs after vaccination with Mycobacterium bovis BCG and infection with Mycobacterium tuberculosis.

PubMed

Grover, Ajay; Taylor, Jennifer; Troudt, JoLynn; Keyser, Andrew; Arnett, Kimberly; Izzo, Linda; Rholl, Drew; Izzo, Angelo

2009-11-01

The guinea pig model of tuberculosis is used extensively in assessing novel vaccines, since Mycobacterium bovis BCG vaccination effectively prolongs survival after low-dose aerosol infection with virulent M. tuberculosis. To better understand how BCG extends time to death after pulmonary infection with M. tuberculosis, we examined cytokine responses postvaccination and recruitment of activated T cells and cytokine response postinfection. At 10 weeks postvaccination, splenic gamma interferon (IFN-gamma) mRNA was significantly elevated compared to the levels at 5 weeks in ex vivo stimulation assays. At 15, 40, 60, and 120 days postinfection, T-cell activation (CD4+ CD62Llow and CD8+ CD62Llow) and mRNA expression of IFN-gamma, tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-10, IL-12, and eomesodermin were assessed. Our data show that at day 40, BCG-vaccinated guinea pigs had significantly increased levels of IFN-gamma mRNA expression but decreased TNF-alpha mRNA expression in their lungs compared to the levels in nonvaccinated animals. At day 120, a time when nonvaccinated guinea pigs succumbed to infection, low levels of IFN-gamma mRNA were observed even though there were increasing levels of IL-1, IL-12, and IL-10, and the numbers of activated T cells did not differ from those in BCG-vaccinated animals. BCG vaccination conferred the advantage of recruiting greater numbers of CD4+ CD62Llow T cells at day 40, although the numbers of CD8+ CD62Llow T cells were not elevated compared to the numbers in nonvaccinated animals. Our data suggest that day 40 postinfection may be a pivotal time point in determining vaccine efficacy and prolonged survival and that BCG promotes the capacity of T cells in the lungs to respond to infection.

Challenges in Estimating Vaccine Coverage in Refugee and Displaced Populations: Results From Household Surveys in Jordan and Lebanon

PubMed Central

Roberton, Timothy; Weiss, William; Doocy, Shannon

2017-01-01

Ensuring the sustained immunization of displaced persons is a key objective in humanitarian emergencies. Typically, humanitarian actors measure coverage of single vaccines following an immunization campaign; few measure routine coverage of all vaccines. We undertook household surveys of Syrian refugees in Jordan and Lebanon, outside of camps, using a mix of random and respondent-driven sampling, to measure coverage of all vaccinations included in the host country’s vaccine schedule. We analyzed the results with a critical eye to data limitations and implications for similar studies. Among households with a child aged 12–23 months, 55.1% of respondents in Jordan and 46.6% in Lebanon were able to produce the child’s EPI card. Only 24.5% of Syrian refugee children in Jordan and 12.5% in Lebanon were fully immunized through routine vaccination services (having received from non-campaign sources: measles, polio 1–3, and DPT 1–3 in Jordan and Lebanon, and BCG in Jordan). Respondents in Jordan (33.5%) and Lebanon (40.1%) reported difficulties obtaining child vaccinations. Our estimated immunization rates were lower than expected and raise serious concerns about gaps in vaccine coverage among Syrian refugees. Although our estimates likely under-represent true coverage, given the additional benefit of campaigns (not captured in our surveys), there is a clear need to increase awareness, accessibility, and uptake of immunization services. Current methods to measure vaccine coverage in refugee and displaced populations have limitations. To better understand health needs in such groups, we need research on: validity of recall methods, links between campaigns and routine immunization programs, and improved sampling of hard-to-reach populations. PMID:28805672

Heterologous Immunological Effects of Early BCG Vaccination in Low-Birth-Weight Infants in Guinea-Bissau: A Randomized-controlled Trial

PubMed Central

Jensen, Kristoffer Jarlov; Larsen, Nanna; Biering-Sørensen, Sofie; Andersen, Andreas; Eriksen, Helle Brander; Monteiro, Ivan; Hougaard, David; Aaby, Peter; Netea, Mihai G.; Flanagan, Katie L.; Benn, Christine Stabell

2015-01-01

Background. Bacillus Calmette–Guérin (BCG) seems to have beneficial nonspecific effects; early BCG vaccination of low-birth-weight (LBW) newborns reduces neonatal mortality by >40% due to prevention of primarily septicemia and pneumonia. Methods. Within a randomized trial in LBW infants in Guinea-Bissau of early BCG vs the usual postponed BCG, a subgroup was bled 4 weeks after randomization. Levels of interleukin (IL)-1β, IL-5, IL-6, IL-10, IL-17, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured from whole-blood assays stimulated with innate agonists to Toll-like receptor (TLR)-2, -4 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, particularly of the cytokines IL-1β, IL-6, TNF-α, and IFN-γ. Conclusion. Four weeks after immunization, BCG-vaccinated infants have a significantly increased production of cytokines upon heterologous challenge, particularly T helper cell type 1 polarizing and typically monocyte-derived pro-inflammatory cytokines. BCG may accelerate the development of the neonatal immune system, mediating comprehensive protection against infections and mortality. PMID:25210141

An update on vaccines for tuberculosis - there is more to it than just waning of BCG efficacy with time.

PubMed

Romano, Marta; Huygen, Kris

2012-12-01

Apart from better diagnostics and new anti-microbial drugs, an effective vaccine for tuberculosis is urgently needed to halt this poverty-related disease, afflicting millions of people worldwide. After a general introduction on the global threat of tuberculosis, the pros and cons of the existing M. bovis BCG vaccine are discussed. As the correlates of protection against tuberculosis remain largely unknown, new findings in biomarker research are described. Next, an update on the ongoing Phase I and Phase II clinical trials is given. Finally, some of the most promising novel pre-clinical developments using live attenuated vaccines, sub-unit vaccines, prime-boost strategies, and new vaccination routes are discussed. The field has made considerable progress and 12 vaccine candidates have now actually entered Phase I or Phase IIa and IIb clinical trials. It is argued that the variable protection conferred by the existing BCG vaccine against reactivation of latent TB is caused not only by waning of its efficacy with time but also by its weak induction of MHC class I restricted responses. Prime-boost strategies based on the actual BCG vaccine may not be sufficient to overcome this hurdle. The use of plasmid DNA vaccination might offer a solution.

Viral Booster Vaccines Improve Mycobacterium bovis BCG-Induced Protection Against Bovine Tuberculosis

USDA-ARS?s Scientific Manuscript database

Previous work in small animal laboratory models of tuberculosis have shown that vaccination strategies based on heterologous prime-boost protocols using Mycobacterium bovis bacille Calmette-Guerin (BCG) to prime and Modified Vaccinia Ankara strain (MVA85A) or recombinant attenuated adenoviruses (Ad8...

Exposure to human alveolar lining fluid enhances Mycobacterium bovis BCG vaccine efficacy against Mycobacterium tuberculosis infection in a CD8+ T-cell-dependent manner.

PubMed

Moliva, J I; Hossfeld, A P; Canan, C H; Dwivedi, V; Wewers, M D; Beamer, G; Turner, J; Torrelles, J B

2018-05-01

Current tuberculosis (TB) treatments include chemotherapy and preventative vaccination with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). In humans, however, BCG vaccination fails to fully protect against pulmonary TB. Few studies have considered the impact of the human lung mucosa (alveolar lining fluid (ALF)), which modifies the Mycobacterium tuberculosis (M.tb) cell wall, revealing alternate antigenic epitopes on the bacterium surface that alter its pathogenicity. We hypothesized that ALF-induced modification of BCG would induce better protection against aerosol infection with M.tb. Here we vaccinated mice with ALF-exposed BCG, mimicking the mycobacterial cell surface properties that would be present in the lung during M.tb infection. ALF-exposed BCG-vaccinated mice were more effective at reducing M.tb bacterial burden in the lung and spleen, and had reduced lung inflammation at late stages of M.tb infection. Improved BCG efficacy was associated with increased numbers of memory CD8 + T cells, and CD8 + T cells with the potential to produce interferon-γ in the lung in response to M.tb challenge. Depletion studies confirmed an essential role for CD8 + T cells in controlling M.tb bacterial burden. We conclude that ALF modifications to the M.tb cell wall in vivo are relevant in the context of vaccine design.

The Potential for Transmission of BCG from Orally Vaccinated White-Tailed Deer (Odocoileus virginianus) to Cattle (Bos taurus) through a Contaminated Environment: Experimental Findings

PubMed Central

Nol, Pauline; Rhyan, Jack C.; Robbe-Austerman, Suelee; McCollum, Matt P.; Rigg, Tara D.; Saklou, Nadia T.; Salman, Mo D.

2013-01-01

White-tailed deer (Odocoileus virginianus) experimentally infected with a virulent strain of Mycobacterium bovis have been shown to transmit the bacterium to other deer and cattle (Bos taurus) by sharing of pen waste and feed. The risk of transmission of M. bovis bacille Calmette-Guerin (BCG) vaccine from orally vaccinated white-tailed deer to other deer and cattle, however, is not well understood. In order to evaluate this risk, we orally vaccinated 14 white-tailed deer with 1×109 colony forming units BCG in lipid-formulated baits and housed them with nine non-vaccinated deer. Each day we exposed the same seven naïve cattle to pen space utilized by the deer to look for transmission between the two species. Before vaccination and every 60 days until the end of the study, we performed tuberculin skin testing on deer and cattle, as well as interferon-gamma testing in cattle, to detect cellular immune response to BCG exposure. At approximately 27 weeks all cattle and deer were euthanized and necropsied. None of the cattle converted on either caudal fold, comparative cervical tests, or interferon-gamma assay. None of the cattle were culture positive for BCG. Although there was immunological evidence that BCG transmission occurred from deer to deer, we were unable to detect immunological or microbiological evidence of transmission to cattle. This study suggests that the risk is likely to be low that BCG-vaccinated white-tailed deer would cause domestic cattle to react to the tuberculin skin test or interferon-gamma test through exposure to a BCG-contaminated environment. PMID:23565211

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

PubMed Central

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

Bacillus Calmette-Guérin Vaccination Using a Microneedle Patch

PubMed Central

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

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

PubMed

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.

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

PubMed

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.

Evaluating Childhood Vaccination Coverage of NIP Vaccines: Coverage Survey versus Zhejiang Provincial Immunization Information System

PubMed Central

Hu, Yu; Chen, Yaping

2017-01-01

Vaccination coverage in Zhejiang province, east China, is evaluated through repeated coverage surveys. The Zhejiang provincial immunization information system (ZJIIS) was established in 2004 with links to all immunization clinics. ZJIIS has become an alternative to quickly assess the vaccination coverage. To assess the current completeness and accuracy on the vaccination coverage derived from ZJIIS, we compared the estimates from ZJIIS with the estimates from the most recent provincial coverage survey in 2014, which combined interview data with verified data from ZJIIS. Of the enrolled 2772 children in the 2014 provincial survey, the proportions of children with vaccination cards and registered in ZJIIS were 94.0% and 87.4%, respectively. Coverage estimates from ZJIIS were systematically higher than the corresponding estimates obtained through the survey, with a mean difference of 4.5%. Of the vaccination doses registered in ZJIIS, 16.7% differed from the date recorded in the corresponding vaccination cards. Under-registration in ZJIIS significantly influenced the coverage estimates derived from ZJIIS. Therefore, periodic coverage surveys currently provide more complete and reliable results than the estimates based on ZJIIS alone. However, further improvement of completeness and accuracy of ZJIIS will likely allow more reliable and timely estimates in future. PMID:28696387

Evaluating Childhood Vaccination Coverage of NIP Vaccines: Coverage Survey versus Zhejiang Provincial Immunization Information System.

PubMed

Hu, Yu; Chen, Yaping

2017-07-11

Vaccination coverage in Zhejiang province, east China, is evaluated through repeated coverage surveys. The Zhejiang provincial immunization information system (ZJIIS) was established in 2004 with links to all immunization clinics. ZJIIS has become an alternative to quickly assess the vaccination coverage. To assess the current completeness and accuracy on the vaccination coverage derived from ZJIIS, we compared the estimates from ZJIIS with the estimates from the most recent provincial coverage survey in 2014, which combined interview data with verified data from ZJIIS. Of the enrolled 2772 children in the 2014 provincial survey, the proportions of children with vaccination cards and registered in ZJIIS were 94.0% and 87.4%, respectively. Coverage estimates from ZJIIS were systematically higher than the corresponding estimates obtained through the survey, with a mean difference of 4.5%. Of the vaccination doses registered in ZJIIS, 16.7% differed from the date recorded in the corresponding vaccination cards. Under-registration in ZJIIS significantly influenced the coverage estimates derived from ZJIIS. Therefore, periodic coverage surveys currently provide more complete and reliable results than the estimates based on ZJIIS alone. However, further improvement of completeness and accuracy of ZJIIS will likely allow more reliable and timely estimates in future.

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

PubMed

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.

Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review.

PubMed

Higgins, Julian P T; Soares-Weiser, Karla; López-López, José A; Kakourou, Artemisia; Chaplin, Katherine; Christensen, Hannah; Martin, Natasha K; Sterne, Jonathan A C; Reingold, Arthur L

2016-10-13

 To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A.  Systematic review, including assessment of risk of bias, and meta-analyses of similar studies.  Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5.  Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified.  Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies, assessed as being at high risk of bias, have compared sequences

Combined effect of BCG vaccination and enriched environment promote neurogenesis and spatial cognition via a shift in meningeal macrophage M2 polarization.

PubMed

Qi, Fangfang; Zuo, Zejie; Yang, Junhua; Hu, Saisai; Yang, Yang; Yuan, Qunfang; Zou, Juntao; Guo, Kaihua; Yao, Zhibin

2017-02-10

The spatial learning abilities of developing mice benefit from extrinsic cues, such as an enriched environment, with concomitant enhancement in cognitive functions. Interestingly, such enhancements can be further increased through intrinsic Bacillus Calmette-Guérin (BCG) vaccination. Here, we first report that combined neonatal BCG vaccination and exposure to an enriched environment (Enr) induced combined neurobeneficial effects, including hippocampal long-term potentiation, and increased neurogenesis and spatial learning and memory, in mice exposed to the Enr and vaccinated with BCG relative to those in the Enr that did not receive BCG vaccination. Neonatal BCG vaccination markedly induced anti-inflammatory meningeal macrophage polarization both in regular and Enr breeding mice. The meninges are composed of the pia mater, dura mater, and choroid plexus. Alternatively, this anti-inflammatory activity of the meninges occurred simultaneously with increased expression of the neurotrophic factors BDNF/IGF-1 and the M2 microglial phenotype in the hippocampus. Our results reveal a critical role for BCG vaccination in the regulation of neurogenesis and spatial cognition through meningeal macrophage M2 polarization and neurotrophic factor expression; these effects were completely or partially prevented by minocycline or anti-IL-10 antibody treatment, respectively. Together, we first claim that immunological factor and environmental factor induce a combined effect on neurogenesis and cognition via a common pathway-meningeal macrophage M2 polarization. We also present a novel functional association between peripheral T lymphocytes and meningeal macrophages after evoking adaptive immune responses in the periphery whereby T lymphocytes are recruited to the meninges in response to systemic IFN-γ signaling. This leads to meningeal macrophage M2 polarization, subsequent to microglial M2 activation and neurotrophic factor expression, and eventually promotes a positive behavior.

THE EFFECT OF IONIZING RADIATION ON THE REGULARITY OF THE VACCINAL PROCESS FOLLOWING BCG IMMUNIZATION IN EXPERIMENT (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Togunova, A.I.; Kulikova, M.F.

1961-07-01

BS>The influence of x irradiation upon the regularity of the vaccinal process in guinea pigs inoculated subcutaneously with a single dose of the BCG strain in the amount of 1 to 2 mg was studied. It was found that irradiation of guinea pigs at various stages of the BCG vaccinal process in a smaller dose (100 r) does not change essentially the quality and the dynamics of the process. On the other hand, exposition to penetrating radiation of a higher dose (200 r) does. There was, however, no intensification in the specific reactive tissue structures, which might have testified tomore » any changes of the biological properties peculiar to the introduced vaccinal microbacteria. The isolated BCG cultures also showed no sign indicating their alteration. The adaptation of the BCG in the organism of the irradiated animal pursued the course common to the regular dynamics. Certain distinctions in the degrees of tuberculin reactions were evident. Exposure to a dose of 200 r weakened the animals during the first weeks. Some deaths occurred as a result of hemorrhages in the organs and lymph nodes. (auth)« less

Field evaluation of the protective efficacy of Mycobacterium bovis BCG vaccine against bovine tuberculosis.

PubMed

Lopez-Valencia, G; Renteria-Evangelista, T; Williams, J de Jesús; Licea-Navarro, A; Mora-Valle, A De la; Medina-Basulto, G

2010-02-01

The protective efficacy of Mycobacterium bovis BCG (1 x 10(6) single dose) was evaluated under field conditions. A total of 140 male Holstein Friesian calves, one to two week-old were selected. Two groups of 70 each were formed, one group was vaccinated and the other was injected with a placebo during their second week of age and followed until 12 months of age. The study considered a positive case of tuberculosis to be an animal that had a positive reaction to the three following tests in a row: tuberculin, IFNgamma PPD-B and IFNgamma ESAT6-CFP10 during the 12 months of exposure. The results showed a 59.4% efficacy (IC95%: 47.64-71.16). The non-vaccinated calves were 2.4 times more at risk of becoming infected (IC95%: 1.07-5.68) compared to vaccinated animals. As a complementary test a PCR test was performed using nasal exudates in some animals from both groups using a Mycobacterium complex detection kit. All the positive PCR reactions (5/44) were found in the non-vaccinated animals. These findings suggest that the use of the BCG vaccine, even though it is not capable of protecting 100%, does prevent TB vaccinated animals from excreting bacilli in their nasal secretions at their first year of age. Copyright 2009 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Development and Initial Testing of Messages to Encourage Tuberculosis Testing and Treatment Among Bacille Calmette-Guerin (BCG) Vaccinated Persons

PubMed Central

Galindo-Gonzalez, Sebastian; Irani, Tracy A.

2017-01-01

Misperceptions surrounding the Bacille Calmette-Guerin (BCG) vaccine can lead some vaccinated individuals to resist being tested and treated for tuberculosis (TB). Educational messages to best explain the risk of TB to BCG-vaccinated, Hispanic persons were systematically developed and tested. First, TB program staff provided messages they considered effective. These were analyzed and validated by TB experts, and then presented in group interviews initially to foreign-born Hispanic persons with a TB diagnosis, and then persons without a prior TB diagnosis. Based on interviewees’ feedback, preferred statements were used to develop one long and three short comprehensive messages. One-on-one interviews were conducted with Hispanic persons to assess the saliency of the comprehensive educational messages. Participants preferred messages that were gain or positively-framed and explained that BCG does not confer lifelong protection against TB. Participants confirmed the messages would likely have a positive impact on patient decisions to undergo TB testing and treatment. PMID:24141428

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

PubMed

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.

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

PubMed

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

2018-01-10

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 epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was accompanied by functional changes indicative of trained immunity. Reduction of viremia was highly correlated with the upregulation of IL-1β, a heterologous cytokine associated with the induction of trained immunity, but not with the specific IFNγ response. The importance of IL-1β for the induction of trained immunity was validated through genetic, epigenetic, and immunological studies. In conclusion, BCG induces epigenetic reprogramming in human monocytes in vivo, followed by functional reprogramming and protection against non-related viral infections, with a key role for IL-1β as a mediator of trained immunity responses. Copyright © 2017 Elsevier Inc. All rights reserved.

Cultivation of Mycobacterium bovis BCG in bioreactors.

PubMed

Dietrich, Guido; Mollenkopf, Hans-Joachim; Weber, Heinz; Knapp, Bernhard; Diehl, Klaus-Dieter; Hess, Jürgen; Blackkolb, Friedrich; Bröker, Michael; Kaufmann, Stefan H E; Hundt, Erika

2002-07-03

The Mycobacterium bovis BCG vaccine for commercial use is classically produced as surface pellicles by culture on synthetic medium. Under these conditions, reproducibility of the cultures and quality assessment are hampered by slow growth of the bacilli, the formation of bacterial aggregates and a high proportion of dead bacilli after processing and final formulation of the vaccine. Here, we established dispersed cultures of M. bovis BCG in synthetic media in small-scale bioreactors. These cultures allow recording and adjusting of culture parameters and give rise to single bacilli with a high degree of live bacteria. In the murine model, bioreactor-grown M. bovis BCG exhibited slightly stronger replication and persistence than the vaccine produced under the classical conditions. The protective efficacy against challenge with M. tuberculosis was identical for both vaccine preparations.

Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine

PubMed Central

Jensen, Kara; dela Pena-Ponce, Myra Grace; Piatak, Michael; Shoemaker, Rebecca; Oswald, Kelli; Jacobs, William R.; Fennelly, Glenn; Lucero, Carissa; Mollan, Katie R.; Hudgens, Michael G.; Amedee, Angela; Kozlowski, Pamela A.; Estes, Jacob D.; Lifson, Jeffrey D.; Van Rompay, Koen K. A.; Larsen, Michelle

2016-01-01

ABSTRACT Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4+ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants. PMID:27655885

Increased immunization coverage addresses the equity gap in Nepal

PubMed Central

Nelin, Viktoria; Raaijmakers, Hendrikus; Kim, Hyung Joon; Singh, Chahana; Målqvist, Mats

2017-01-01

Abstract Objective To compare immunization coverage and equity distribution of coverage between 2001 and 2014 in Nepal. Methods We used data from the Demographic and Health Surveys carried out in 2001, 2006 and 2011 together with data from the 2014 Multiple Indicator Cluster Survey. We calculated the proportion, in mean percentage, of children who had received bacille Calmette–Guérin (BCG) vaccine, three doses of polio vaccine, three doses of diphtheria–pertussis–tetanus (DPT) vaccine and measles vaccine. To measure inequities between wealth quintiles, we calculated the slope index of inequality (SII) and relative index of inequality (RII) for all surveys. Findings From 2001 to 2014, the proportion of children who received all vaccines at the age of 12 months increased from 68.8% (95% confidence interval, CI: 67.5–70.1) to 82.4% (95% CI: 80.7–84.0). While coverage of BCG, DPT and measles immunization statistically increased during the study period, the proportion of children who received the third dose of polio vaccine decreased from 93.3% (95% CI: 92.7–93.9) to 88.1% (95% CI: 86.8–89.3). The poorest wealth quintile showed the greatest improvement in immunization coverage, from 58% to 77.9%, while the wealthiest quintile only improved from 84.8% to 86.0%. The SII for children who received all vaccines improved from 0.070 (95% CI: 0.061–0.078) to 0.026 (95% CI: 0.013–0.039) and RII improved from 1.13 to 1.03. Conclusion The improvement in immunization coverage between 2001 and 2014 in Nepal can mainly be attributed to the interventions targeting the disadvantaged populations. PMID:28479621

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

PubMed

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.

Clinical and economic impact of a specific BCG vaccination program implemented in Prato, central Italy, involving foreign newborns on hospitalizations.

PubMed

Bellini, Irene; Nastasi, Antonino; Boccalini, Sara

2016-09-01

In Tuscany (Central Italy), the average annual notification rate of tuberculosis (TB) in the years 2007-2012 was 7.5-9.8 per 100,000 people, with the Local Health Unit of Prato (LHU4) showing the highest rate compared to the other regional area. Therefore, in order to reduce the burden of TB, foreign newborns in the LHU4 are being given the Bacillus Calmette-Guérin (BCG) vaccine since 2000. The aim of this study is to assess the impact of BCG vaccination in Prato, in terms of TB-related hospitalizations and costs. The regional archive containing all TB-related discharges and costs in the period 2007-2014 was consulted. Data regarding foreigners living in the LHU4 who have been vaccinated since 2000 were compared with those living in the other Tuscan LHUs and never vaccinated. These populations were then disaggregated by a threshold age of 15 y. After calculating the standardized hospitalization rates, the expected number of hospitalizations for TB among unvaccinated adults (in both populations) was found to be similar in the LHU4 and the other LHUs (165 vs. 156). However, expected number of hospitalizations among children in the other Tuscan LHUs (67) was double that of the LHU4 (34). If the same vaccine had been administrated everywhere, each year 29 hospitalizations could have been avoided and EUR 343,525 saved. Overall, BCG vaccinations cost EUR 14,879 in the LHU4, but 69 hospitalizations were avoided and EUR 107,435 saved. The introduction of the BCG immunization program in the LHU4 of Prato has led to significant reductions in the clinical and economic impact of TB.

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

PubMed

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.

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

PubMed Central

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

2017-01-01

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. PMID:28467415

BCG and New Preventive Tuberculosis Vaccines: Implications for Healthcare Workers

PubMed Central

Hatherill, Mark; Scriba, Thomas J.; Udwadia, Zarir F.; Mullerpattan, Jai B.; Hawkridge, Anthony; Mahomed, Hassan; Dye, Christopher

2016-01-01

Healthcare workers (HCWs) are at high risk of Mycobacterium tuberculosis (Mtb) infection and tuberculosis disease, but also play a crucial role in implementing healthcare. Preexposure tuberculosis vaccination, including revaccination with BCG, might benefit Mtb-uninfected HCWs, but most HCWs in tuberculosis-endemic countries are already sensitized to mycobacteria. A new postexposure tuberculosis vaccine offers greatest potential for protection, in the setting of repeated occupational Mtb exposure. Novel strategies for induction of mycobacteria-specific resident memory T cells in the lung by aerosol administration, or induction of T cells with inherent propensity for residing in mucosal sites, such as CD1-restricted T cells and mucosa-associated innate T cells, should be explored. The need for improved protection of HCWs against tuberculosis disease is clear. However, health systems in tuberculosis-endemic countries would need significantly improved occupational health structures to implement a screening and vaccination strategy for HCWs. PMID:27118856

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

PubMed

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

Vaccination coverage and its determinants among migrant children in Guangdong, China

PubMed Central

2014-01-01

Background Guangdong province attracted more than 31 million migrants in 2010. But few studies were performed to estimate the complete and age-appropriate immunization coverage and determine risk factors of migrant children. Methods 1610 migrant children aged 12–59 months from 70 villages were interviewed in Guangdong. Demographic characteristics, primary caregiver’s knowledge and attitude toward immunization, and child’s immunization history were obtained. UTD and age-appropriate immunization rates for the following five vaccines and the overall series (1:3:3:3:1 immunization series) were assessed: one dose of BCG, three doses of DTP, OPV and HepB, one dose of MCV. Risk factors for not being UTD for the 1:3:3:3:1 immunization series were explored. Results For each antigen, the UTD immunization rate was above 71%, but the age-appropriate immunization rates for BCG, HepB, OPV, DPT and MCV were only 47.8%, 45.1%, 47.1%, 46.8% and 37.2%, respectively. The 1st dose was most likely to be delayed within them. For the 1:3:3:3:1 immunization series, the UTD immunization rate and age-appropriate immunization rate were 64.9% and 12.4% respectively. Several factors as below were significantly associated with UTD immunization. The primary caregiver’s determinants were their occupation, knowledge and attitude toward immunization. The child’s determinants were sex, Hukou, birth place, residential buildings and family income. Conclusions Alarmingly low immunization coverage of migrant children should be closely monitored by NIISS. Primary caregiver and child’s determinants should be considered when taking measures. Strategies to strengthen active out-reach activities and health education for primary caregivers needed to be developed to improve their immunization coverage. PMID:24568184

[Prevention of elderly pneumonia by pneumococcal, influenza and BCG vaccinations].

PubMed

Ohrui, Takashi; Nakayama, Katsutoshi; Fukushima, Takeyasu; Chiba, Hiroshi; Sasaki, Hidetada

2005-01-01

Pneumonia is a major cause of morbidity and mortality in elderly people, especially in those with chronic medical conditions such as chronic heart and lung diseases. We prospectively examined the effect of influenza and pneumococcal vaccinations on the rate of hospitalization for and complications of pneumonia, all respiratory tract conditions and mortality in elderly bedridden patients and found that both febrile days and pneumonia cases decreased. Thus, these results show that it is valuable to vaccinate for influenza elderly people even if they are confined to bed. Furthermore, the tuberculin skin test is an easy method to check the cell-mediated immunity in the elderly people. In the tuberculin skin test, all Japanese over 65 years old should have positive status. A negative result indicates depressed cell-mediated immunity. We undertook a trial to vaccinate tuberculin negative elderly people with BCG vaccine and found that the risk of pneumonia is decreased to a similar degree to that in subjects with positive tuberculin test results. We conclude that vaccination might be an effective strategy for the prevention of pneumonia in elderly people with limited activities of daily living.

Novel Recombinant Mycobacterium bovis BCG, Ovine Atadenovirus, and Modified Vaccinia Virus Ankara Vaccines Combine To Induce Robust Human Immunodeficiency Virus-Specific CD4 and CD8 T-Cell Responses in Rhesus Macaques▿

PubMed Central

Rosario, Maximillian; Hopkins, Richard; Fulkerson, John; Borthwick, Nicola; Quigley, Máire F.; Joseph, Joan; Douek, Daniel C.; Greenaway, Hui Yee; Venturi, Vanessa; Gostick, Emma; Price, David A.; Both, Gerald W.; Sadoff, Jerald C.; Hanke, Tomáš

2010-01-01

Mycobacterium bovis bacillus Calmette-Guérin (BCG), which elicits a degree of protective immunity against tuberculosis, is the most widely used vaccine in the world. Due to its persistence and immunogenicity, BCG has been proposed as a vector for vaccines against other infections, including HIV-1. BCG has a very good safety record, although it can cause disseminated disease in immunocompromised individuals. Here, we constructed a recombinant BCG vector expressing HIV-1 clade A-derived immunogen HIVA using the recently described safer and more immunogenic BCG strain AERAS-401 as the parental mycobacterium. Using routine ex vivo T-cell assays, BCG.HIVA401 as a stand-alone vaccine induced undetectable and weak CD8 T-cell responses in BALB/c mice and rhesus macaques, respectively. However, when BCG.HIVA401 was used as a priming component in heterologous vaccination regimens together with recombinant modified vaccinia virus Ankara-vectored MVA.HIVA and ovine atadenovirus-vectored OAdV.HIVA vaccines, robust HIV-1-specific T-cell responses were elicited. These high-frequency T-cell responses were broadly directed and capable of proliferation in response to recall antigen. Furthermore, multiple antigen-specific T-cell clonotypes were efficiently recruited into the memory pool. These desirable features are thought to be associated with good control of HIV-1 infection. In addition, strong and persistent T-cell responses specific for the BCG-derived purified protein derivative (PPD) antigen were induced. This work is the first demonstration of immunogenicity for two novel vaccine vectors and the corresponding candidate HIV-1 vaccines BCG.HIVA401 and OAdV.HIVA in nonhuman primates. These results strongly support their further exploration. PMID:20375158

The distribution and implications of BCG scars in northern Malawi.

PubMed Central

Fine, P. E.; Ponnighaus, J. M.; Maine, N.

1989-01-01

Reported are data on the BCG scar status of more than 112,000 individuals who were surveyed in Karonga District, northern Malawi, between 1979 and 1984. The age and sex patterns of apparent BCG scars reflect the history of BCG vaccination activities in the district. Repeated independent examinations of large numbers of people revealed that the proportions remaining with the same observed scar status among those initially classified as being scar "positive" or scar "negative" were each approximately 90%. The repeatability of positive scar reading was lower among children and older adults than among young adults aged 15-24 years, and blind follow-up of children known to have been vaccinated as infants in child health clinics indicated that less than 60% had a detectable scar 3 years after receiving the vaccine. "Negative" repeatability increased consistently with age. The implications of these findings for estimating BCG vaccine uptake and for assessing its efficacy in case-control and cohort studies are discussed. The finding that BCG scars may be difficult to read suggests there is a danger of observer bias that could lead to distortion--in particular, to overestimates of vaccine efficacy. PMID:2706726

Vaccination Coverage Cluster Surveys in Middle Dreib – Akkar, Lebanon: Comparison of Vaccination Coverage in Children Aged 12-59 Months Pre- and Post-Vaccination Campaign

PubMed Central

Assaad, Ramia; Rebeschini, Arianna; Hamadeh, Randa

2016-01-01

Introduction With the high proportion of refugee population throughout Lebanon and continuous population movement, it is sensible to believe that, in particular vulnerable areas, vaccination coverage may not be at an optimal level. Therefore, we assessed the vaccination coverage in children under 5 in a district of the Akkar governorate before and after a vaccination campaign. During the vaccination campaign, conducted in August 2015, 2,509 children were vaccinated. Materials and Methods We conducted a pre- and post-vaccination campaign coverage surveys adapting the WHO EPI cluster survey to the Lebanese MoPH vaccination calendar. Percentages of coverage for each dose of each vaccine were calculated for both surveys. Factors associated with complete vaccination were explored. Results Comparing the pre- with the post-campaign surveys, coverage for polio vaccine increased from 51.9% to 84.3%, for Pentavalent from 49.0% to 71.9%, for MMR from 36.2% to 61.0%, while the percentage of children with fully updated vaccination calendar increased from 32.9% to 53.8%. While Lebanese children were found to be better covered for some antigens compared to Syrians at the first survey, this difference disappeared at the post-campaign survey. Awareness and logistic obstacles were the primary reported causes of not complete vaccination in both surveys. Discussion Vaccination campaigns remain a quick and effective approach to increase vaccination coverage in crisis-affected areas. However, campaigns cannot be considered as a replacement of routine vaccination services to maintain a good level of coverage. PMID:27992470

Preclinical development of BCG.HIVA2auxo.int, harboring an integrative expression vector, for a HIV-TB Pediatric vaccine. Enhancement of stability and specific HIV-1 T-cell immunity.

PubMed

Mahant, Aakash; Saubi, Narcís; Eto, Yoshiki; Guitart, Núria; Gatell, Josep Ma; Hanke, Tomáš; Joseph, Joan

2017-08-03

One of the critical issues that should be addressed in the development of a BCG-based HIV vaccine is genetic plasmid stability. Therefore, to address this issue we have considered using integrative vectors and the auxotrophic mutant of BCG complemented with a plasmid carrying a wild-type complementing gene. In this study, we have constructed an integrative E. coli-mycobacterial shuttle plasmid, p2auxo.HIVA int , expressing the HIV-1 clade A immunogen HIVA. This shuttle vector uses an antibiotic resistance-free mechanism for plasmid selection and maintenance. It was first transformed into a glycine auxotrophic E. coli strain and subsequently transformed into a lysine auxotrophic Mycobacterium bovis BCG strain to generate the vaccine BCG.HIVA 2auxo.int . Presence of the HIVA gene sequence and protein expression was confirmed. We demonstrated that the in vitro stability of the integrative plasmid p2auxo.HIVA int was increased 4-fold, as compared with the BCG strain harboring the episomal plasmid, and was genetically and phenotypically characterized. The BCG.HIVA 2auxo.int vaccine in combination with modified vaccinia virus Ankara (MVA).HIVA was found to be safe and induced HIV-1 and Mycobacterium tuberculosis-specific interferon-γ-producing T-cell responses in adult BALB/c mice. We have engineered a more stable and immunogenic BCG-vectored vaccine using the prototype immunogen HIVA. Thus, the use of integrative expression vectors and the antibiotic-free plasmid selection system based on "double" auxotrophic complementation are likely to improve the mycobacterial vaccine stability in vivo and immunogenicity to develop not only recombinant BCG-based vaccines expressing second generation of HIV-1 immunogens but also other major pediatric pathogens to prime protective responses shortly following birth.

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

PubMed Central

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

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

PubMed

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.

Measuring populations to improve vaccination coverage

NASA Astrophysics Data System (ADS)

Bharti, Nita; Djibo, Ali; Tatem, Andrew J.; Grenfell, Bryan T.; Ferrari, Matthew J.

2016-10-01

In low-income settings, vaccination campaigns supplement routine immunization but often fail to achieve coverage goals due to uncertainty about target population size and distribution. Accurate, updated estimates of target populations are rare but critical; short-term fluctuations can greatly impact population size and susceptibility. We use satellite imagery to quantify population fluctuations and the coverage achieved by a measles outbreak response vaccination campaign in urban Niger and compare campaign estimates to measurements from a post-campaign survey. Vaccine coverage was overestimated because the campaign underestimated resident numbers and seasonal migration further increased the target population. We combine satellite-derived measurements of fluctuations in population distribution with high-resolution measles case reports to develop a dynamic model that illustrates the potential improvement in vaccination campaign coverage if planners account for predictable population fluctuations. Satellite imagery can improve retrospective estimates of vaccination campaign impact and future campaign planning by synchronizing interventions with predictable population fluxes.

Measuring populations to improve vaccination coverage

PubMed Central

Bharti, Nita; Djibo, Ali; Tatem, Andrew J.; Grenfell, Bryan T.; Ferrari, Matthew J.

2016-01-01

In low-income settings, vaccination campaigns supplement routine immunization but often fail to achieve coverage goals due to uncertainty about target population size and distribution. Accurate, updated estimates of target populations are rare but critical; short-term fluctuations can greatly impact population size and susceptibility. We use satellite imagery to quantify population fluctuations and the coverage achieved by a measles outbreak response vaccination campaign in urban Niger and compare campaign estimates to measurements from a post-campaign survey. Vaccine coverage was overestimated because the campaign underestimated resident numbers and seasonal migration further increased the target population. We combine satellite-derived measurements of fluctuations in population distribution with high-resolution measles case reports to develop a dynamic model that illustrates the potential improvement in vaccination campaign coverage if planners account for predictable population fluctuations. Satellite imagery can improve retrospective estimates of vaccination campaign impact and future campaign planning by synchronizing interventions with predictable population fluxes. PMID:27703191

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

PubMed

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

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.

PubMed

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.

The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection

PubMed Central

Lin, Philana Ling; Dietrich, Jes; Tan, Esterlina; Abalos, Rodolfo M.; Burgos, Jasmin; Bigbee, Carolyn; Bigbee, Matthew; Milk, Leslie; Gideon, Hannah P.; Rodgers, Mark; Cochran, Catherine; Guinn, Kristi M.; Sherman, David R.; Klein, Edwin; Janssen, Christopher; Flynn, JoAnne L.; Andersen, Peter

2011-01-01

It is estimated that one-third of the world’s population is infected with Mycobacterium tuberculosis. Infection typically remains latent, but it can reactivate to cause clinical disease. The only vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is largely ineffective, and ways to enhance its efficacy are being developed. Of note, the candidate booster vaccines currently under clinical development have been designed to improve BCG efficacy but not prevent reactivation of latent infection. Here, we demonstrate that administering a multistage vaccine that we term H56 in the adjuvant IC31 as a boost to vaccination with BCG delays and reduces clinical disease in cynomolgus macaques challenged with M. tuberculosis and prevents reactivation of latent infection. H56 contains Ag85B and ESAT-6, which are two of the M. tuberculosis antigens secreted in the acute phase of infection, and the nutrient stress–induced antigen Rv2660c. Boosting with H56/IC31 resulted in efficient containment of M. tuberculosis infection and reduced rates of clinical disease, as measured by clinical parameters, inflammatory markers, and improved survival of the animals compared with BCG alone. Boosted animals showed reduced pulmonary pathology and extrapulmonary dissemination, and protection correlated with a strong recall response against ESAT-6 and Rv2660c. Importantly, BCG/H56-vaccinated monkeys did not reactivate latent infection after treatment with anti-TNF antibody. Our results indicate that H56/IC31 boosting is able to control late-stage infection with M. tuberculosis and contain latent tuberculosis, providing a rationale for the clinical development of H56. PMID:22133873

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

PubMed

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

Oral Cholera Vaccine Coverage, Barriers to Vaccination, and Adverse Events following Vaccination, Haiti, 2013.

PubMed

Tohme, Rania A; François, Jeannot; Wannemuehler, Kathleen; Iyengar, Preetha; Dismer, Amber; Adrien, Paul; Hyde, Terri B; Marston, Barbara J; Date, Kashmira; Mintz, Eric; Katz, Mark A

2015-06-01

In 2013, the first government-led oral cholera vaccination (OCV) campaign in Haiti was implemented in Petite Anse and Cerca Carvajal. To evaluate vaccination coverage, barriers to vaccination, and adverse events following vaccination, we conducted a cluster survey. We enrolled 1,121 persons from Petite Anse and 809 persons from Cerca Carvajal, categorized by 3 age groups (1-4, 5-14, >15 years). Two-dose OCV coverage was 62.5% in Petite Anse and 76.8% in Cerca Carvajal. Two-dose coverage was lowest among persons >15 years of age. In Cerca Carvajal, coverage was significantly lower for male than female respondents (69% vs. 85%; p<0.001). No major adverse events were reported. The main reason for nonvaccination was absence during the campaign. Vaccination coverage after this campaign was acceptable and comparable to that resulting from campaigns implemented by nongovernmental organizations. Future campaigns should be tailored to reach adults who are not available during daytime hours.

Variation in rotavirus vaccine coverage by sub-counties in Kenya.

PubMed

Wandera, Ernest Apondi; Mohammad, Shah; Ouko, John Odhiambo; Yatitch, James; Taniguchi, Koki; Ichinose, Yoshio

2017-01-01

Rotavirus gastroenteritis is an important cause of childhood morbidity and mortality in Kenya. In July 2014, Kenya introduced the rotavirus vaccine into her national immunization program. Although immunization coverage is crucial in assessing the real-world impact of this vaccine, variability in the vaccine coverage across the country is likely to occur. In view of this, we estimated the extent of coverage for the rotavirus vaccine at two socio-economically different sub-counties using the administrative data. The findings indicate disparities in vaccine coverage and access between the sub-counties and, thus, underscore the need to strengthen immunization systems to facilitate timely, accessible, and equitable vaccine delivery across the country. Both sub-counties recorded high vaccine dropout, suggestive of poor utilization of the vaccine. In this regard, increased social mobilization is needed to encourage vaccine compliance and to enhance tracking of vaccine defaulters. While efforts to improve the accuracy of the administrative coverage estimates are crucial, vaccination coverage surveys will be needed to verify the administrative coverage data and help identify specific factors relating to rotavirus vaccine coverage in the country.

Vaccination Timeliness in Children Under India's Universal Immunization Program.

PubMed

Shrivastwa, Nijika; Gillespie, Brenda W; Lepkowski, James M; Boulton, Matthew L

2016-09-01

India has the highest number of deaths among children younger than 5 years of age globally; the majority are from vaccine preventable diseases. Untimely vaccination unnecessarily prolongs susceptibility to disease and contributes to the burden of childhood morbidity and mortality, yet there is scarce literature on vaccination delays. The aim of this study is to characterize the timeliness of childhood vaccinations administered under India's routine immunization program using a novel application of an existing statistical methodology. This study utilized the district level household and facility survey data, 2008 from India using vaccination data from children with and without immunization cards. Turnbull estimator of the cumulative distribution function was used to estimate the probability of vaccination at each age. Timeliness of Bacille Calmette-Guerin (BCG), all 3 doses of diphtheria, pertussis and tetanus vaccine (DPT) and measles-containing vaccine (MCV) were considered for this analysis. Vaccination data on 268,553 children who were 0-60 months of age were analyzed; timely administration of BCG, DPT3 and MCV occurred in 31%, 19% and 34% of children, respectively. The estimated vaccination probability plateaued for DPT and BCG around the age of 24 months, whereas MCV uptake increased another 5% after 24 months of age. The 5-year coverage of BCG, DPT3 and MCV in Indian children was 87%, 63% and 76%, respectively. Lack of timely administration of key childhood vaccines, especially DPT3 and MCV, remains a major challenge in India and likely contributes to the significant burden of vaccine preventable disease-related morbidity and mortality in children.

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

PubMed Central

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

2013-01-01

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. PMID:23740922

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

PubMed Central

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

School Entry Requirements and Coverage of Nontargeted Adolescent Vaccines

PubMed Central

Reiter, Paul L.; Truong, Young K.; Rimer, Barbara K.; Brewer, Noel T.

2016-01-01

BACKGROUND: Low human papillomavirus (HPV) vaccination coverage is an urgent public health problem requiring action. To identify policy remedies to suboptimal HPV vaccination, we assessed the relationship between states’ school entry requirements and adolescent vaccination. METHODS: We gathered data on states’ school entry requirements for adolescent vaccination (tetanus, diphtheria, and pertussis [Tdap] booster; meningococcal; and HPV) from 2007 to 2012 from Immunization Action Coalition. The National Immunization Survey–Teen provided medical record–verified vaccination data for 99 921 adolescents. We calculated coverage (among 13- to 17-year-olds) for individual vaccinations and concomitant vaccination. HPV vaccination outcomes were among female adolescents. Analyses used weighted longitudinal multivariable models. RESULTS: States with requirements for Tdap booster and meningococcal vaccination had 22 and 24 percentage point increases in coverage for these vaccines, respectively, compared with other states (both P < .05). States with HPV vaccination requirements had <1 percentage point increase in coverage for this vaccine (P < .05). Tdap booster and meningococcal vaccination requirements, respectively, were associated with 8 and 4 percentage point spillover increases for HPV vaccination coverage (both P < .05) and with increases for concomitant vaccination (all P < .05). CONCLUSIONS: Ensuring all states have meningococcal vaccination requirements could improve the nation’s HPV vaccination coverage, given that many states already require Tdap booster but not meningococcal vaccination for school entry. Vaccination programs and clinicians should capitalize on changes in adolescent vaccination, including concomitant vaccination, that may arise after states adopt vaccination requirements. Additional studies are needed on the effects of HPV vaccination requirements and opt-out provisions. PMID:27940689

School Entry Requirements and Coverage of Nontargeted Adolescent Vaccines.

PubMed

Moss, Jennifer L; Reiter, Paul L; Truong, Young K; Rimer, Barbara K; Brewer, Noel T

2016-12-01

Low human papillomavirus (HPV) vaccination coverage is an urgent public health problem requiring action. To identify policy remedies to suboptimal HPV vaccination, we assessed the relationship between states' school entry requirements and adolescent vaccination. We gathered data on states' school entry requirements for adolescent vaccination (tetanus, diphtheria, and pertussis [Tdap] booster; meningococcal; and HPV) from 2007 to 2012 from Immunization Action Coalition. The National Immunization Survey-Teen provided medical record-verified vaccination data for 99 921 adolescents. We calculated coverage (among 13- to 17-year-olds) for individual vaccinations and concomitant vaccination. HPV vaccination outcomes were among female adolescents. Analyses used weighted longitudinal multivariable models. States with requirements for Tdap booster and meningococcal vaccination had 22 and 24 percentage point increases in coverage for these vaccines, respectively, compared with other states (both P < .05). States with HPV vaccination requirements had <1 percentage point increase in coverage for this vaccine (P < .05). Tdap booster and meningococcal vaccination requirements, respectively, were associated with 8 and 4 percentage point spillover increases for HPV vaccination coverage (both P < .05) and with increases for concomitant vaccination (all P < .05). Ensuring all states have meningococcal vaccination requirements could improve the nation's HPV vaccination coverage, given that many states already require Tdap booster but not meningococcal vaccination for school entry. Vaccination programs and clinicians should capitalize on changes in adolescent vaccination, including concomitant vaccination, that may arise after states adopt vaccination requirements. Additional studies are needed on the effects of HPV vaccination requirements and opt-out provisions. Copyright © 2016 by the American Academy of Pediatrics.

Evaluation of human papilloma virus (HPV) vaccination strategies and vaccination coverage in adolescent girls worldwide.

PubMed

Owsianka, Barbara; Gańczak, Maria

2015-01-01

An analysis of HPV vaccination strategies and vaccination coverage in adolescent girls worldwide for the last eight years with regard to potential improvement of vaccination coverage rates in Poland. Literature search, covering the period 2006-2014, was performed using Medline. Comparative analysis of HPV vaccination strategies and coverage between Poland and other countries worldwide was conducted. In the last eight years, a number of countries introduced HPV vaccination for adolescent girls to their national immunization programmes. Vaccination strategies differ, consequently affecting vaccination coverage, ranging from several percent to more than 90%. Usually, there are also disparities at national level. The highest HPV vaccination coverage rates are observed in countries where vaccines are administered in school settings and funded from the national budget. Poland is one of the eight EU countries where HPV vaccination has not been introduced to mandatory immunization programme and where paid vaccination is only provided in primary health care settings. HPV vaccination coverage in adolescent girls is estimated at 7.5-10%. Disparities in HPV vaccination coverage rates in adolescent girls worldwide may be due to different strategies of vaccination implementation between countries. Having compared to other countries, the low HPV vaccination coverage in Polish adolescent girls may result from the lack of funding at national level and the fact that vaccines are administered in a primary health care setting. A multidimensional approach, involving the engagement of primary health care and school personnel as well as financial assistance of government at national and local level and the implementation of media campaigns, particularly in regions with high incidence of cervical cancer, could result in an increase of HPV vaccination coverage rates in Poland.

Evaluation of a vaccine passport to improve vaccine coverage in people living with HIV.

PubMed

Chadwick, D R; Corbett, K; Mann, S; Teruzzi, B; Horner, S

2018-01-01

An increased risk of vaccine-preventable infections (VPIs) is seen in people living with HIV (PLWH), and current vaccine coverage and immunity is variable. Vaccine passports have the potential to improve vaccine coverage. The objective was to assess how successful a vaccine passport was in improving vaccine coverage in PLWH. Baseline immunity to VPIs was established in PLWH attending a single HIV clinic and vaccinations required were determined based on the BHIVA Vaccination Guidelines (2015). The passport was completed and the PLWH informed about additional vaccines they should obtain from primary care. After 6-9 months the passport was reviewed including confirmation if vaccines were given. PLWH satisfaction with the system was evaluated by a survey. Seventy-three PLWH provided sufficient data for analysis. At baseline significant proportions of PLWH were not immune/unvaccinated to the main VPIs, especially human papillomavirus, pneumococcus and measles. After the passport was applied immunity improved significantly (56% overall, p < 0.01) for most VPIs; however, full coverage was not achieved. The system was popular with PLWH. The passport was successful in increasing vaccination coverage although full or near-full coverage was not achieved. A more successful service would probably be achieved by commissioning English HIV clinics to provide all vaccines.

Surveillance of Vaccination Coverage Among Adult Populations - United States, 2014.

PubMed

Williams, Walter W; Lu, Peng-Jun; O'Halloran, Alissa; Kim, David K; Grohskopf, Lisa A; Pilishvili, Tamara; Skoff, Tami H; Nelson, Noele P; Harpaz, Rafael; Markowitz, Lauri E; Rodriguez-Lainz, Alfonso; Bridges, Carolyn B

2016-02-05

Overall, the prevalence of illness attributable to vaccine-preventable diseases is greater among adults than among children. Adults are recommended to receive vaccinations based on their age, underlying medical conditions, lifestyle, prior vaccinations, and other considerations. Updated vaccination recommendations from CDC are published annually in the U.S. Adult Immunization Schedule. Despite longstanding recommendations for use of many vaccines, vaccination coverage among U.S. adults is low. August 2013-June 2014 (for influenza vaccination) and January-December 2014 (for pneumococcal, tetanus and diphtheria [Td] and tetanus and diphtheria with acellular pertussis [Tdap], hepatitis A, hepatitis B, herpes zoster, and human papillomavirus [HPV] vaccination). The National Health Interview Survey (NHIS) is a continuous, cross-sectional national household survey of the noninstitutionalized U.S. civilian population. In-person interviews are conducted throughout the year in a probability sample of households, and NHIS data are compiled and released annually. The survey objective is to monitor the health of the U.S. population and provide estimates of health indicators, health care use and access, and health-related behaviors. Compared with data from the 2013 NHIS, increases in vaccination coverage occurred for Tdap vaccine among adults aged ≥19 years (a 2.9 percentage point increase to 20.1%) and herpes zoster vaccine among adults aged ≥60 years (a 3.6 percentage point increase to 27.9%). Aside from these modest improvements, vaccination coverage among adults in 2014 was similar to estimates from 2013 (for influenza coverage, similar to the 2012-13 season). Influenza vaccination coverage among adults aged ≥19 years was 43.2%. Pneumococcal vaccination coverage among high-risk persons aged 19-64 years was 20.3% and among adults aged ≥65 years was 61.3%. Td vaccination coverage among adults aged ≥19 years was 62.2%. Hepatitis A vaccination coverage among adults

Non-tuberculous mycobacteria have diverse effects on BCG efficacy against Mycobacterium tuberculosis.

PubMed

Poyntz, Hazel C; Stylianou, Elena; Griffiths, Kristin L; Marsay, Leanne; Checkley, Anna M; McShane, Helen

2014-05-01

The efficacy of Bacillus Calmette-Guerin (BCG) vaccination in protection against pulmonary tuberculosis (TB) is highly variable between populations. One possible explanation for this variability is increased exposure of certain populations to non-tuberculous mycobacteria (NTM). This study used a murine model to determine the effect that exposure to NTM after BCG vaccination had on the efficacy of BCG against aerosol Mycobacterium tuberculosis challenge. The effects of administering live Mycobacterium avium (MA) by an oral route and killed MA by a systemic route on BCG-induced protection were evaluated. CD4+ and CD8+ T cell responses were profiled to define the immunological mechanisms underlying any effect on BCG efficacy. BCG efficacy was enhanced by exposure to killed MA administered by a systemic route; T helper 1 and T helper 17 responses were associated with increased protection. BCG efficacy was reduced by exposure to live MA administered by the oral route; T helper 2 cells were associated with reduced protection. These findings demonstrate that exposure to NTM can induce opposite effects on BCG efficacy depending on route of exposure and viability of NTM. A reproducible model of NTM exposure would be valuable in the evaluation of novel TB vaccine candidates. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

A randomised, double-blind, controlled trial of a killed L. major vaccine plus BCG against zoonotic cutaneous leishmaniasis in Iran.

PubMed

Momeni, A Z; Jalayer, T; Emamjomeh, M; Khamesipour, A; Zicker, F; Ghassemi, R L; Dowlati, Y; Sharifi, I; Aminjavaheri, M; Shafiei, A; Alimohammadian, M H; Hashemi-Fesharki, R; Nasseri, K; Godal, T; Smith, P G; Modabber, F

1999-02-05

Safety and efficacy of killed (autoclaved) L. major promastigotes, ALM, mixed with BCG against zoonotic cutaneous leishmaniasis was tested in healthy volunteers (n = 2453) in a randomized double blind trial vs. BCG as control. Side-effects were similar in both groups but tended to be slightly more frequent and prolonged in the ALM + BCG group. Leishmanin skin test conversion (induration > or =5 mm) was significantly greater in the ALM + BCG than in the BCG group (36.2% vs. 7.9% on day-80 and 33% vs. 19%, after 1 year, respectively). Cumulative incidence rates for 2 years, were similar in both groups (18.0% vs. 18.5%). However, LST responders on day 80 (> or =5 mm) had a significantly lower incidence (35%) of CL during the first year than non-responders. A single dose of ALM + BCG is not sufficiently immunogenic to provide a measurable response when compared to BCG alone. A single dose of this vaccine has been shown to be safe with no evidence of an exacerbating response following natural infection; hence, multiple doses or other adjuvants should be considered to increase its immunogenicity.

Use of Lot Quality Assurance Sampling (LQAS) to estimate vaccination coverage helps guide future vaccination efforts.

PubMed

Alberti, K P; Guthmann, J P; Fermon, F; Nargaye, K D; Grais, R F

2008-03-01

Inadequate evaluation of vaccine coverage after mass vaccination campaigns, such as used in national measles control programmes, can lead to inappropriate public health responses. Overestimation of vaccination coverage may leave populations at risk, whilst underestimation can lead to unnecessary catch-up campaigns. The problem is more complex in large urban areas where vaccination coverage may be heterogeneous and the programme may have to be fine-tuned at the level of geographic subunits. Lack of accurate population figures in many contexts further complicates accurate vaccination coverage estimates. During the evaluation of a mass vaccination campaign carried out in N'Djamena, the capital of Chad, Lot Quality Assurance Sampling was used to estimate vaccination coverage. Using this method, vaccination coverage could be evaluated within smaller geographic areas of the city as well as for the entire city. Despite the lack of accurate population data by neighbourhood, the results of the survey showed heterogeneity of vaccination coverage within the city. These differences would not have been identified using a more traditional method. The results can be used to target areas of low vaccination coverage during follow-up vaccination activities.

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.

PubMed

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

Vaccination coverage and reasons for non-vaccination in a district of Istanbul

PubMed Central

Torun, Sebahat D; Bakırcı, Nadi

2006-01-01

Background In order to control and eliminate the vaccine preventable diseases it is important to know the vaccination coverage and reasons for non-vaccination. The primary objective of this study was to determine the complete vaccination rate; the reasons for non-vaccination and the predictors that influence vaccination of children. The other objective was to determine coverage of measles vaccination of the Measles Immunization Days (MID) 2005 for children aged 9 month to 6 years in a region of Umraniye, Istanbul, Turkey. Methods A '30 × 7' cluster sampling design was used as the sampling method. Thirty streets were selected at random from study area. Survey data were collected by a questionnaire which was applied face to face to parents of 221 children. A Chi-square test and logistic regression was used for the statistical analyses. Content analysis method was used to evaluate the open-ended questions. Results The complete vaccination rate for study population was 84.5% and 3.2% of all children were totally non-vaccinated. The siblings of non-vaccinated children were also non-vaccinated. Reasons for non-vaccination were as follows: being in the village and couldn't reach to health care services; having no knowledge about vaccination; the father of child didn't allow vaccination; intercurrent illness of child during vaccination time; missed opportunities like not to shave off a vial for only one child. In logistic regression analysis, paternal and maternal levels of education and immigration time of both parents to Istanbul were found to influence whether children were completely vaccinated or non-vaccinated. Measles vaccination coverage during MID was 79.3%. Conclusion Efforts to increase vaccination coverage should take reasons for non-vaccination into account. PMID:16677375

Increasing Coverage of Appropriate Vaccinations

PubMed Central

Jacob, Verughese; Chattopadhyay, Sajal K.; Hopkins, David P.; Morgan, Jennifer Murphy; Pitan, Adesola A.; Clymer, John

2016-01-01

Context Population-level coverage for immunization against many vaccine-preventable diseases remains below optimal rates in the U.S. The Community Preventive Services Task Force recently recommended several interventions to increase vaccination coverage based on systematic reviews of the evaluation literature. The present study provides the economic results from those reviews. Evidence acquisition A systematic review was conducted (search period, January 1980 through February 2012) to identify economic evaluations of 12 interventions recommended by the Task Force. Evidence was drawn from included studies; estimates were constructed for the population reach of each strategy, cost of implementation, and cost per additional vaccinated person because of the intervention. Analyses were conducted in 2014. Evidence synthesis Reminder systems, whether for clients or providers, were among the lowest-cost strategies to implement and the most cost effective in terms of additional people vaccinated. Strategies involving home visits and combination strategies in community settings were both costly and less cost effective. Strategies based in settings such as schools and managed care organizations that reached the target population achieved additional vaccinations in the middle range of cost effectiveness. Conclusions The interventions recommended by the Task Force differed in reach, cost, and cost effectiveness. This systematic review presents the economic information for 12 effective strategies to increase vaccination coverage that can guide implementers in their choice of interventions to fit their local needs, available resources, and budget. PMID:26847663

Surveillance of Vaccination Coverage among Adult Populations - United States, 2015.

PubMed

Williams, Walter W; Lu, Peng-Jun; O'Halloran, Alissa; Kim, David K; Grohskopf, Lisa A; Pilishvili, Tamara; Skoff, Tami H; Nelson, Noele P; Harpaz, Rafael; Markowitz, Lauri E; Rodriguez-Lainz, Alfonso; Fiebelkorn, Amy Parker

2017-05-05

Overall, the prevalence of illness attributable to vaccine-preventable diseases is greater among adults than among children. Adults are recommended to receive vaccinations based on their age, underlying medical conditions, lifestyle, prior vaccinations, and other considerations. Updated vaccination recommendations from CDC are published annually in the U.S. Adult Immunization Schedule. Despite longstanding recommendations for use of many vaccines, vaccination coverage among U.S. adults is low. August 2014-June 2015 (for influenza vaccination) and January-December 2015 (for pneumococcal, tetanus and diphtheria [Td] and tetanus and diphtheria with acellular pertussis [Tdap], hepatitis A, hepatitis B, herpes zoster, and human papillomavirus [HPV] vaccination). The National Health Interview Survey (NHIS) is a continuous, cross-sectional national household survey of the noninstitutionalized U.S. civilian population. In-person interviews are conducted throughout the year in a probability sample of households, and NHIS data are compiled and released annually. The survey objective is to monitor the health of the U.S. population and provide estimates of health indicators, health care use and access, and health-related behaviors. Compared with data from the 2014 NHIS, increases in vaccination coverage occurred for influenza vaccine among adults aged ≥19 years (a 1.6 percentage point increase compared with the 2013-14 season to 44.8%), pneumococcal vaccine among adults aged 19-64 years at increased risk for pneumococcal disease (a 2.8 percentage point increase to 23.0%), Tdap vaccine among adults aged ≥19 years and adults aged 19-64 years (a 3.1 percentage point and 3.3 percentage point increase to 23.1% and to 24.7%, respectively), herpes zoster vaccine among adults aged ≥60 years and adults aged ≥65 years (a 2.7 percentage point and 3.2 percentage point increase to 30.6% and to 34.2%, respectively), and hepatitis B vaccine among health care personnel (HCP) aged �

Tuberculosis vaccines in clinical trials

PubMed Central

Rowland, Rosalind; McShane, Helen

2011-01-01

Effective prophylactic and/or therapeutic vaccination is a key strategy for controlling the global TB epidemic. The partial effectiveness of the existing TB vaccine, bacille Calmette–Guérin (BCG), suggests effective vaccination is possible and highlights the need for an improved vaccination strategy. Clinical trials are evaluating both modifications to the existing BCG immunization methods and also novel TB vaccines, designed to replace or boost BCG. Candidate vaccines in clinical development include live mycobacterial vaccines designed to replace BCG, subunit vaccines designed to boost BCG and therapeutic vaccines designed as an adjunct to chemotherapy. There is a great need for validated animal models, identification of immunological biomarkers of protection and field sites with the capacity for large-scale efficacy testing in order to develop and license a novel TB vaccine or regimen. PMID:21604985

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

PubMed

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 < 0.001) and splenic and lung CD8+ T-cells expressing IFN-γ ( P < 0.0001). In mice and guinea pigs, rLmIII/a30 and rLmI/h30 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.

Lactoferrin modulation of BCG-infected dendritic cell functions

PubMed Central

Hwang, Shen-An

2009-01-01

Lactoferrin, an 80-kDa iron-binding protein with immune modulating properties, is a unique adjuvant component able to enhance efficacy of the existing Mycobacterium bovis Bacillus Calmette Guerin (BCG) vaccine to protect against murine model of tuberculosis. Although identified as having effects on macrophage presentation events, lactoferrin's capability to modulate dendritic cells (DCs) function when loaded with BCG antigens has not been previously recognized. In this study, the potential of lactoferrin to modulate surface expression of MHC II, CD80, CD86 and CD40 from bone marrow-derived dendritic cells (BMDCs) was examined. Generally, lactoferrin decreased pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, IL-6 and IL-12p40] and chemokines [macrophage inflammatory protein (MIP)-1α and MIP-2] and increased regulatory cytokine, transforming growth factor-β1 and a T-cell chemotatic factor, monocyte chemotactic protein-1, from uninfected or BCG-infected BMDCs. Culturing BCG-infected BMDCs with lactoferrin also enhanced their ability to respond to IFN-γ activation through up-regulation of maturation markers: MHC I, MHC II and the ratio of CD86:CD80 surface expression. Furthermore, lactoferrin-exposed BCG-infected DCs increased stimulation of BCG-specific CD3+CD4+ splenocytes, as defined by increasing IFN-γ production. Finally, BCG-/lactoferrin-vaccinated mice possessed an increased pool of BCG antigen-specific IFN-γ producing CD3+CD4+CD62L− splenocytes. These studies suggest a mechanism in which lactoferrin may exert adjuvant activity by enhancing DC function to promote generation of antigen-specific T cells. PMID:19692539

Successive Intramuscular Boosting with IFN-Alpha Protects Mycobacterium bovis BCG-Vaccinated Mice against M. lepraemurium Infection

PubMed Central

Guerrero, G. G.; Rangel-Moreno, J.; Islas-Trujillo, S.; Rojas-Espinosa, Ó.

2015-01-01

Leprosy caused by Mycobacterium leprae primarily affects the skin and peripheral nerves. As a human infectious disease, it is still a significant health and economic burden on developing countries. Although multidrug therapy is reducing the number of active cases to approximately 0.5 million, the number of cases per year is not declining. Therefore, alternative host-directed strategies should be addressed to improve treatment efficacy and outcome. In this work, using murine leprosy as a model, a very similar granulomatous skin lesion to human leprosy, we have found that successive IFN-alpha boosting protects BCG-vaccinated mice against M. lepraemurium infection. No difference in the seric isotype and all IgG subclasses measured, neither in the TH1 nor in the TH2 type cytokine production, was seen. However, an enhanced iNOS/NO production in BCG-vaccinated/i.m. IFN-alpha boosted mice was observed. The data provided in this study suggest a promising use for IFN-alpha boosting as a new prophylactic alternative to be explored in human leprosy by targeting host innate cell response. PMID:26484351

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.

PubMed

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

Formulation of a mmaA4 Gene Deletion Mutant of Mycobacterium bovis BCG in Cationic Liposomes Significantly Enhances Protection against Tuberculosis

PubMed Central

Derrick, Steven C.; Dao, Dee; Yang, Amy; Kolibab, Kris; Jacobs, William R.; Morris, Sheldon L.

2012-01-01

A new vaccination strategy is urgently needed for improved control of the global tuberculosis (TB) epidemic. Using a mouse aerosol Mycobacterium tuberculosis challenge model, we investigated the protective efficacy of a mmaA4 gene deletion mutant of Mycobacterium bovis BCG (ΔmmaA4BCG) formulated in dimethyl dioctadecyl ammonium bromide (DDA) – D(+) trehalose 6,6 dibenenate (TDB) (DDA/TDB) adjuvant. In previous studies, deletion of the mmaA4 gene was shown to reduce the suppression of IL-12 production often seen after mycobacterial infections. While the non-adjuvanted ΔmmaA4BCG strain did not protect mice substantially better than conventional BCG against a tuberculous challenge in four protection experiments, the protective responses induced by the ΔmmaA4BCG vaccine formulated in DDA/TDB adjuvant was consistently increased relative to nonadjuvanted BCG controls. Furthermore, the ΔmmaA4BCG-DDA/TDB vaccine induced significantly higher frequencies of multifunctional (MFT) CD4 T cells expressing both IFNγ and TNFα (double positive) or IFNγ, TNFα and IL-2 (triple positive) than CD4 T cells derived from mice vaccinated with BCG. These MFT cells were characterized by having higher IFNγ and TNFα median fluorescence intensity (MFI) values than monofunctional CD4 T cells. Interestingly, both BCG/adjuvant and ΔmmaA4BCG/adjuvant formulations induced significantly higher frequencies of CD4 T cells expressing TNFα and IL-2 than nonadjuvanted BCG or ΔmmaA4BCG vaccines indicating that BCG/adjuvant mixtures may be more effective at inducing central memory T cells. Importantly, when either conventional BCG or the mutant were formulated in adjuvant and administered to SCID mice or immunocompromised mice depleted of IFNγ, significantly lower vaccine-derived mycobacterial CFU were detected relative to immunodeficient mice injected with non-adjuvanted BCG. Overall, these data suggest that immunization with the ΔmmaA4BCG/adjuvant formulation may be an effective, safe

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

PubMed

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.

The impact of new vaccine introduction on the coverage of existing vaccines: a cross-national, multivariable analysis.

PubMed

Shearer, Jessica C; Walker, Damian G; Risko, Nicholas; Levine, Orin S

2012-12-14

A surge of new and underutilized vaccine introductions into national immunization programmes has called into question the effect of new vaccine introduction on immunization and health systems. In particular, countries deciding whether to introduce a new or underutilized vaccine into their routine immunization programme may query possible effects on the delivery and coverage of existing vaccines. Using coverage of diphtheria-tetanus-pertussis (DTP) vaccine as a proxy for immunization system performance, this study aims to test whether new vaccine introduction into national immunization programs was associated with changes in coverage of three doses of DTP vaccine among infants. DTP3 vaccine coverage was analyzed in 187 countries during 1999-2009 using multivariable cross-national mixed-effect longitudinal models. Controlling for other possible determinants of DTP3 coverage at the national level these models found minimal association between the introduction of Hepatitis-, Haemophilus influenzae type b-, and rotavirus-containing vaccines and DTP3 coverage. Instead, frequent and sometimes large fluctuations in coverage are associated with other development and health systems variables, including the presence of armed conflict, coverage of antenatal care services, infant mortality, the percent of health expenditures that are private and total health expenditures per capita. Introductions of new vaccines did not affect national coverage of DTP3 vaccine in the countries studied. Introductions of other new vaccines and multiple vaccine introductions should be monitored for immunization and health systems impacts. Copyright © 2012 Elsevier Ltd. All rights reserved.

A first-in-human phase 1 trial to evaluate the safety and immunogenicity of the candidate tuberculosis vaccine MVA85A-IMX313, administered to BCG-vaccinated adults

PubMed Central

Minhinnick, Alice; Satti, Iman; Harris, Stephanie; Wilkie, Morven; Sheehan, Sharon; Stockdale, Lisa; Thomas, Zita-Rose Manjaly; Lopez-Ramon, Raquel; Poulton, Ian; Lawrie, Alison; Vermaak, Samantha; Le Vert, Alexandre; Del Campo, Judith; Hill, Fergal; Moss, Paul; McShane, Helen

2016-01-01

Introduction There is an urgent need for a new and effective tuberculosis vaccine because BCG does not sufficiently prevent pulmonary disease. IMX313 is a novel carrier protein designed to improve cellular and humoral immunity. MVA85A-IMX313 is a novel vaccine candidate designed to boost immunity primed by bacillus Calmette-Guérin (BCG) that has been immunogenic in pre-clinical studies. This is the first evaluation of IMX313 delivered as MVA85A-IMX313 in humans. Methods In this phase 1, open-label first-in-human trial, 30 healthy previously BCG-vaccinated adults were enrolled into three treatment groups and vaccinated with low dose MVA85A-IMX313 (group A), standard dose MVA85A-IMX313 (group B), or MVA85A (group C). Volunteers were followed up for 6 months for safety and immunogenicity assessment. Results The majority of adverse events were mild and there were no vaccine-related serious AEs. Both MVA85A-IMX313 and MVA85A induced a significant increase in IFN-γ ELISpot responses. There were no significant differences between the Ag85A ELISpot and intracellular cytokine responses between the two study groups B (MVA85A-IMX313) and C (MVA85A) at any time point post-vaccination. Conclusion MVA85A-IMX313 was well tolerated and immunogenic. There was no significant difference in the number of vaccine-related, local or systemic adverse reactions between MVA85A and MVA85A-IMX313 groups. The mycobacteria-specific cellular immune responses induced by MVA85A-IMX313 were not significantly different to those detected in the MVA85A group. In light of this encouraging safety data, further work to improve the potency of molecular adjuvants like IMX313 is merited. This trial was registered on clinicatrials.gov ref. NCT01879163. PMID:26854906

Timeliness of Childhood Primary Immunization and Risk Factors Related with Delays: Evidence from the 2014 Zhejiang Provincial Vaccination Coverage Survey.

PubMed

Hu, Yu; Li, Qian; Chen, Yaping

2017-09-20

Background: this study aimed to assess both immunization coverage and timeliness, as well as reasons for non-vaccination, and identity the risk factors of delayed immunization, for the vaccines scheduled during the first year of life, in Zhejiang province, east China. Methods: A cluster survey among children aged 24-35 months was conducted. Demographic information and socio-economic characteristics of the selected child, the mother, and the household were collected. Immunization data were transcribed from immunization cards. Timeliness was assessed with Kaplan-Meier analysis for each vaccine given before 12 months of age, based on the time frame stipulated by the expanded program on immunization of China. Cox proportional hazard regression was applied to identify risk factors of delayed immunization. Results: A total of 2772 eligible children were surveyed. The age-appropriate coverage ranged from 25.4% (95% CI: 23.7-27.0%) for Bacillus Calmette-Guerin (BCG) to 91.3% (95% CI: 90.2-92.3%) for the first dose of oral poliomyelitis vaccine (OPV1). The most frequent reason for non-vaccination was parent's fear of adverse events of immunization. Delayed immunizations were associated with mother having a lower education level, mother having a job, delivery at home, increasing number of children per household, and having a lower household income. Conclusions: Although the timeliness of immunization has improved since 2011, necessary steps are still needed to achieve further improvement. Timeliness of immunization should be considered as another important indicator of expanded program on immunization (EPI) performance. Future interventions on vaccination coverage should take into consideration demographic and socio-economic risk factors identified in this study. The importance of adhering to the recommended schedule should be explained to parents.

Timeliness of Childhood Primary Immunization and Risk Factors Related with Delays: Evidence from the 2014 Zhejiang Provincial Vaccination Coverage Survey

PubMed Central

Hu, Yu; Li, Qian; Chen, Yaping

2017-01-01

Background: this study aimed to assess both immunization coverage and timeliness, as well as reasons for non-vaccination, and identity the risk factors of delayed immunization, for the vaccines scheduled during the first year of life, in Zhejiang province, east China. Methods: A cluster survey among children aged 24–35 months was conducted. Demographic information and socio-economic characteristics of the selected child, the mother, and the household were collected. Immunization data were transcribed from immunization cards. Timeliness was assessed with Kaplan–Meier analysis for each vaccine given before 12 months of age, based on the time frame stipulated by the expanded program on immunization of China. Cox proportional hazard regression was applied to identify risk factors of delayed immunization. Results: A total of 2772 eligible children were surveyed. The age-appropriate coverage ranged from 25.4% (95% CI: 23.7–27.0%) for Bacillus Calmette–Guerin (BCG) to 91.3% (95% CI: 90.2–92.3%) for the first dose of oral poliomyelitis vaccine (OPV1). The most frequent reason for non-vaccination was parent’s fear of adverse events of immunization. Delayed immunizations were associated with mother having a lower education level, mother having a job, delivery at home, increasing number of children per household, and having a lower household income. Conclusions: Although the timeliness of immunization has improved since 2011, necessary steps are still needed to achieve further improvement. Timeliness of immunization should be considered as another important indicator of expanded program on immunization (EPI) performance. Future interventions on vaccination coverage should take into consideration demographic and socio-economic risk factors identified in this study. The importance of adhering to the recommended schedule should be explained to parents. PMID:28930165

Effect of intradermal tuberculin tests on BCG-induced allergy

PubMed Central

Magnus, Knut

1957-01-01

Trials are going forward to determine whether intradermal tuberculin testing with 10 TU at yearly intervals after BCG vaccination may prevent waning of BCG-induced allergy in schoolchildren. Meanwhile, two experiments to the same purpose, carried out in guinea-pigs, are described. They show that waning allergy in guinea-pigs can be sustantially enhanced by intradermal injection of either purified tuberculin or Old Tuberculin, the effect lasting for at least 8 weeks, even with so small a dose as 5 TU. It is pointed out that this enhancing effect has been demonstrated only in BCG-vaccinated guinea-pigs and that it is not known whether the same phenomenon would occur in guinea-pigs infected with living human tubercle bacilli. PMID:13489466

Reduction of racial/ethnic disparities in vaccination coverage, 1995-2011.

PubMed

Walker, Allison T; Smith, Philip J; Kolasa, Maureen

2014-04-18

The Presidential Childhood Immunization Initiative was developed in 1993 to address major gaps in childhood vaccination coverage in the United States. Eliminating the cost of vaccines as a barrier to vaccination was one strategy of the Childhood Immunization Initiative; it led to Congressional legislation that authorized creation of the Vaccines for Children program (VFC) in 1994. CDC analyzed National Immunization Survey data for 1995-2011 to evaluate trends in disparities in vaccination coverage rates between non-Hispanic white children and children of other racial/ethnic groups. VFC has been effective in ireducing disparities in vaccination coverage among U.S. children. CDC's Office of Minority Health and Health Equity selected the intervention analysis and discussion that follows to provide an example of a program that has been effective in reducing childhood vaccination coverage-related disparities in the United States. At its inception in 1994, VFC was implemented in 78 Immunization Action Plan areas that covered the entire United States; within each area, concerted efforts were made to improve childhood vaccination coverage. The findings in this report demonstrate that there have been no racial/ethnic disparities in vaccine coverage for measles-mumps-rubella and poliovirus in the United States since 2005. Disparities in coverage for the diphtheria-tetanus-pertussis/diphtheria-tetanus-acellular pertussis vaccine were absent, declining, or inconsistent during this period, depending on the racial/ethnic group examined. The results in this report highlight the effectiveness of VFC.

Socio-economic determinants and inequities in coverage and timeliness of early childhood immunisation in rural Ghana.

PubMed

Gram, Lu; Soremekun, Seyi; ten Asbroek, Augustinus; Manu, Alexander; O'Leary, Maureen; Hill, Zelee; Danso, Samuel; Amenga-Etego, Seeba; Owusu-Agyei, Seth; Kirkwood, Betty R

2014-07-01

To assess the extent of socio-economic inequity in coverage and timeliness of key childhood immunisations in Ghana. Secondary analysis of vaccination card data collected from babies born between January 2008 and January 2010 who were registered in the surveillance system supporting the ObaapaVita and Newhints Trials was carried out. 20 251 babies had 6 weeks' follow-up, 16 652 had 26 weeks' follow-up, and 5568 had 1 year's follow-up. We performed a descriptive analysis of coverage and timeliness of vaccinations by indicators for urban/rural status, wealth and educational attainment. The association of coverage with socio-economic indicators was tested using a chi-square-test and the association with timeliness using Cox regression. Overall coverage at 1 year of age was high (>95%) for Bacillus Calmette-Guérin (BCG), all three pentavalent diphtheria-pertussis-tetanus-haemophilus influenzae B-hepatitis B (DPTHH) doses and all polio doses except polio at birth (63%). Coverage against measles and yellow fever was 85%. Median delay for BCG was 1.7 weeks. For polio at birth, the median delay was 5 days; all other vaccine doses had median delays of 2-4 weeks. We found substantial health inequity across all socio-economic indicators for all vaccines in terms of timeliness, but not coverage at 1 year. For example, for the last DPTHH dose, the proportion of children delayed more than 8 weeks were 27% for urban children and 31% for rural children (P < 0.001), 21% in the wealthiest quintile and 41% in the poorest quintile (P < 0.001), and 9% in the most educated group and 39% in the least educated group (P < 0.001). However, 1-year coverage of the same dose remained above 90% for all levels of all socio-economic indicators. Ghana has substantial health inequity across urban/rural, socio-economic and educational divides. While overall coverage was high, most vaccines suffered from poor timeliness. We suggest that countries achieving high coverage should include timeliness

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

PubMed

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, p<0.001). In addition, a cut-off of 14 and 17mm for TST was defined to identify IGRA positivity in a ROC analysis (AUC: 0.76, p=0.03). TST and/or IGRA positivity was not influenced by medical therapy or disease phenotype. Importantly, smoking was identified as a risk factor for TST but not IGRA positivity (OR: 2.70-5.02, p<0.01, for TSTcut-offs=5-20mm). TST and IGRA tests are partly complimentary methods, and additional testing by TST (with a cut-off of >15mm) 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.

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

PubMed

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.

Childhood vaccination coverage rates among military dependents in the United States.

PubMed

Dunn, Angela C; Black, Carla L; Arnold, John; Brodine, Stephanie; Waalen, Jill; Binkin, Nancy

2015-05-01

The Military Health System provides universal coverage of all recommended childhood vaccinations. Few studies have examined the effect that being insured by the Military Health System has on childhood vaccination coverage. The purpose of this study was to compare the coverage of the universally recommended vaccines among military dependents versus other insured and uninsured children using a nationwide sample of children. The National Immunization Survey is a multistage, random-digit dialing survey designed to measure vaccination coverage estimates of US children aged 19 to 35 months old. Data from 2007 through 2012 were combined to permit comparison of vaccination coverage among military dependent and all other children. Among military dependents, 28.0% of children aged 19 to 35 months were not up to date on the 4:3:1:3:3:1 vaccination series excluding Haemophilus influenzae type b vaccine compared with 21.1% of all other children (odds ratio: 1.4; 95% confidence interval: 1.2-1.6). After controlling for sociodemographic characteristics, compared with all other US children, military dependent children were more likely to be incompletely vaccinated (odds ratio: 1.3; 95% confidence interval: 1.1-1.5). Lower vaccination coverage rates among US military dependent children might be due to this population being highly mobile. However, the lack of a military-wide childhood immunization registry and incomplete documentation of vaccinations could contribute to the lower vaccination coverage rates seen in this study. These results suggest the need for further investigation to evaluate vaccination coverage of children with complete ascertainment of vaccination history, and if lower immunization rates are verified, assessment of reasons for lower vaccination coverage rates among military dependent children. Copyright © 2015 by the American Academy of Pediatrics.

The effect of BCG vaccine at birth on the development of atopy or allergic disease in young children.

PubMed

Townley, R G; Barlan, I B; Patino, C; Vichyanond, P; Minervini, M C; Simasathien, T; Nettagul, R; Bahceciler, N N; Basdemir, D; Akkoc, T; Pongprueksa, S; Hopp, R J

2004-03-01

Exposure to infectious diseases may reduce the development of asthma or allergy. In particular, the role of the BCG vaccine in modulating asthma or allergy has been a source of speculation. To study newborns from 3 international sites to evaluate the prospective effect of BCG vaccine on allergic diseases or atopic development. Infants were enrolled from newborn and well-infant clinics in Thailand, Argentina, and Turkey. The standard BCG vaccine for each country was given at birth. Parents who consented to have their infant included in the protocol completed an allergy family questionnaire. Infants underwent a standard purified protein derivative (PPD) test at 9 to 12 months of age, and the reaction size was measured. At the age of 2 years, the children returned to be studied. Allergy skin tests to common allergens appropriate to location and age were performed, and the parents completed the International Study of Allergy and Asthma in Childhood questionnaire. The PPD reaction size was compared with the presence of atopy and allergy questionnaire responses. A total of 1,704 infants were studied. Statistical significance was found between a negative PPD response vs any positive PPD response and the risk of having an allergic history at the age of 2 years in Turkey (relative risk, 2.11; 95% confidence interval, 1.25-3.55; P = .005) and Thailand (relative risk, 2.16; 95% confidence interval, 1.18-3.94; P = .02) but not Argentina (relative risk, 1.09; 95% confidence interval, 0.70-1.68; P = .70). This study further supports the role of infectious agents in modulating asthma and allergy development.

The BCGΔBCG1419c strain, which produces more pellicle in vitro, improves control of chronic tuberculosis in vivo.

PubMed

Pedroza-Roldán, César; Guapillo, Carolina; Barrios-Payán, Jorge; Mata-Espinosa, Dulce; Aceves-Sánchez, Michel de Jesús; Marquina-Castillo, Brenda; Hernández-Pando, Rogelio; Flores-Valdez, Mario Alberto

2016-09-14

Mycobacterium tuberculosis (Mtb) has been a threat to humans since ancient times, and it is the main causative agent of tuberculosis (TB). Until today, the only licensed vaccine against Mtb is the live attenuated M. bovis Bacillus Calmette-Guérin (BCG), which has variable levels of protection against the pulmonary form of infection. The quest for a new vaccine is a priority given the rise of multidrug-resistant Mtb around the world, as well as the tremendous burden imposed by latent TB. The objective of this study was to evaluate the immunogenicity and capacity of protection of a modified BCG strain (BCGΔBCG1419c) lacking the c-di-GMP phosphodiesterase gene BCG1419c, in diverse mice models. In a previous report, we have shown that BCGΔBCG1419c was capable of increasing biofilm production and after intravenous infection of immunocompetent mice; this strain persisted longer in lungs than parental BCG Pasteur. This led us to hypothesize that BCGΔBCG1419c might therefore possess some advantage as vaccine candidate. Our results in this report indicate that compared to conventional BCG, vaccination with BCGΔBCG1419c induced a better activation of specific T-lymphocytes population, was equally effective in preventing weight loss despite being used at lower dose, reduced tissue damage (pneumonic scores), increased local IFNγ(+) T cells, and diminished bacterial burden in lungs of BALB/c mice infected intratracheally with high dose Mtb H37Rv to induce progressive TB. Moreover, vaccination with BCGΔBCG1419c improved resistance to reactivation after immunosuppression induced by corticosterone in a murine model of chronic infection similar to latent TB. Furthermore, despite showing increased persistence in immunocompetent mice, BCGΔBCG1419c was as attenuated as parental BCG in nude mice. To our knowledge, this is the first demonstration that a modified BCG vaccine candidate with increased pellicle/biofilm production has the capacity to protect against Mtb challenge in

Coincident filarial, intestinal helminth, and mycobacterial infection: helminths fail to influence tuberculin reactivity, but BCG influences hookworm prevalence.

PubMed

Lipner, Ettie M; Gopi, P G; Subramani, R; Kolappan, C; Sadacharam, K; Kumaran, Paul; Prevots, D Rebecca; Narayanan, P R; Nutman, Thomas B; Kumaraswami, V

2006-05-01

The prevalence of helminth and tuberculosis infections is high in South India, whereas Bacille-Calmette-Guerin (BCG) vaccine efficacy is low. Our aim was to determine whether concurrent helminth infection alters the ability to mount a delayed-type hypersensitivity response to tuberculin. In a cross-sectional study in southern India, individuals 6-65 years of age were screened for intestinal helminths, circulating filarial antigenemia, tuberculin reactivity, active tuberculosis, and history of BCG vaccination; 54% were purified protein derivative (PPD) positive, 32% had intestinal helminth infection, 9% were circulating filarial antigen positive, and 0.5% had culture-confirmed active tuberculosis. Only age and BCG vaccination were significantly associated with PPD reactivity; however, BCG vaccination was associated with a lower prevalence of hookworm infection relative to those without prior BCG vaccination. Neither intestinal helminth infection nor filarial infection was associated with diminished frequencies of PPD positivity. Our findings suggest that preceding helminth infection does not influence significantly the delayed-type hypersensitivity response to tuberculin.

Measuring coverage in MNCH: design, implementation, and interpretation challenges associated with tracking vaccination coverage using household surveys.

PubMed

Cutts, Felicity T; Izurieta, Hector S; Rhoda, Dale A

2013-01-01

Vaccination coverage is an important public health indicator that is measured using administrative reports and/or surveys. The measurement of vaccination coverage in low- and middle-income countries using surveys is susceptible to numerous challenges. These challenges include selection bias and information bias, which cannot be solved by increasing the sample size, and the precision of the coverage estimate, which is determined by the survey sample size and sampling method. Selection bias can result from an inaccurate sampling frame or inappropriate field procedures and, since populations likely to be missed in a vaccination coverage survey are also likely to be missed by vaccination teams, most often inflates coverage estimates. Importantly, the large multi-purpose household surveys that are often used to measure vaccination coverage have invested substantial effort to reduce selection bias. Information bias occurs when a child's vaccination status is misclassified due to mistakes on his or her vaccination record, in data transcription, in the way survey questions are presented, or in the guardian's recall of vaccination for children without a written record. There has been substantial reliance on the guardian's recall in recent surveys, and, worryingly, information bias may become more likely in the future as immunization schedules become more complex and variable. Finally, some surveys assess immunity directly using serological assays. Sero-surveys are important for assessing public health risk, but currently are unable to validate coverage estimates directly. To improve vaccination coverage estimates based on surveys, we recommend that recording tools and practices should be improved and that surveys should incorporate best practices for design, implementation, and analysis.

Interventions to increase HPV vaccination coverage: A systematic review

PubMed Central

Smulian, Elizabeth A.; Mitchell, Krista R.; Stokley, Shannon

2016-01-01

ABSTRACT We reviewed intervention studies designed to increase human papillomavirus (HPV) vaccination coverage to further understand the impact interventions can have on HPV vaccination coverage. We searched 5 databases for intervention studies published from June 2006 to May 2015. Studies were included if they quantitatively measured HPV vaccination coverage as an outcome and were conducted in the United States. We abstracted outcomes, methods, and results from each study and classified by type of intervention conducted. Findings from 34 studies suggest many types of intervention strategies can increase HPV vaccination coverage in different settings, and with modest cost. Interventions were effective especially when implemented in combination at both provider and community levels. However, not all interventions showed significant effects on coverage. More research is needed to identify the best methods for widespread implementation of effective strategies. PMID:26838959

[Lupoid syndrome in "BCG-itis." Report of a case].

PubMed

Ramírez, O; Ramírez, R

1986-01-01

It is presented the first case of lupoid syndrome of "BCG-itis" found in El Salvador. Its clinic-pathological study is conclusive for such dermatological entity. The complications of vaccination with BCG are rare. It must be treated as an active tuberculosis, but with a greater control of the patient.

Transport networks and inequities in vaccination: remoteness shapes measles vaccine coverage and prospects for elimination across Africa.

PubMed

Metcalf, C J E; Tatem, A; Bjornstad, O N; Lessler, J; O'Reilly, K; Takahashi, S; Cutts, F; Grenfell, B T

2015-05-01

Measles vaccination is estimated to have averted 13·8 million deaths between 2000 and 2012. Persisting heterogeneity in coverage is a major contributor to continued measles mortality, and a barrier to measles elimination and introduction of rubella-containing vaccine. Our objective is to identify determinants of inequities in coverage, and how vaccine delivery must change to achieve elimination goals, which is a focus of the WHO Decade of Vaccines. We combined estimates of travel time to the nearest urban centre (⩾50 000 people) with vaccination data from Demographic Health Surveys to assess how remoteness affects coverage in 26 African countries. Building on a statistical mapping of coverage against age and geographical isolation, we quantified how modifying the rate and age range of vaccine delivery affects national coverage. Our scenario analysis considers increasing the rate of delivery of routine vaccination, increasing the target age range of routine vaccination, and enhanced delivery to remote areas. Geographical isolation plays a key role in defining vaccine inequity, with greater inequity in countries with lower measles vaccine coverage. Eliminating geographical inequities alone will not achieve thresholds for herd immunity, indicating that changes in delivery rate or age range of routine vaccination will be required. Measles vaccine coverage remains far below targets for herd immunity in many countries on the African continent and is likely to be inadequate for achieving rubella elimination. The impact of strategies such as increasing the upper age range eligible for routine vaccination should be considered.

Surveillance of Vaccination Coverage among Adult Populations — United States, 2015

PubMed Central

Lu, Peng-Jun; O’Halloran, Alissa; Kim, David K.; Grohskopf, Lisa A.; Pilishvili, Tamara; Skoff, Tami H.; Nelson, Noele P.; Harpaz, Rafael; Markowitz, Lauri E.; Rodriguez-Lainz, Alfonso; Fiebelkorn, Amy Parker

2017-01-01

Problem/Condition Overall, the prevalence of illness attributable to vaccine-preventable diseases is greater among adults than among children. Adults are recommended to receive vaccinations based on their age, underlying medical conditions, lifestyle, prior vaccinations, and other considerations. Updated vaccination recommendations from CDC are published annually in the U.S. Adult Immunization Schedule. Despite longstanding recommendations for use of many vaccines, vaccination coverage among U.S. adults is low. Period Covered August 2014–June 2015 (for influenza vaccination) and January–December 2015 (for pneumococcal, tetanus and diphtheria [Td] and tetanus and diphtheria with acellular pertussis [Tdap], hepatitis A, hepatitis B, herpes zoster, and human papillomavirus [HPV] vaccination). Description of System The National Health Interview Survey (NHIS) is a continuous, cross-sectional national household survey of the noninstitutionalized U.S. civilian population. In-person interviews are conducted throughout the year in a probability sample of households, and NHIS data are compiled and released annually. The survey objective is to monitor the health of the U.S. population and provide estimates of health indicators, health care use and access, and health-related behaviors. Results Compared with data from the 2014 NHIS, increases in vaccination coverage occurred for influenza vaccine among adults aged ≥19 years (a 1.6 percentage point increase compared with the 2013–14 season to 44.8%), pneumococcal vaccine among adults aged 19–64 years at increased risk for pneumococcal disease (a 2.8 percentage point increase to 23.0%), Tdap vaccine among adults aged ≥19 years and adults aged 19–64 years (a 3.1 percentage point and 3.3 percentage point increase to 23.1% and to 24.7%, respectively), herpes zoster vaccine among adults aged ≥60 years and adults aged ≥65 years (a 2.7 percentage point and 3.2 percentage point increase to 30.6% and to 34

Vaccination coverage among children in kindergarten - United States, 2013-14 school year.

PubMed

Seither, Ranee; Masalovich, Svetlana; Knighton, Cynthia L; Mellerson, Jenelle; Singleton, James A; Greby, Stacie M

2014-10-17

State and local vaccination requirements for school entry are implemented to maintain high vaccination coverage and protect schoolchildren from vaccine-preventable diseases. Each year, to assess state and national vaccination coverage and exemption levels among kindergartners, CDC analyzes school vaccination data collected by federally funded state, local, and territorial immunization programs. This report describes vaccination coverage in 49 states and the District of Columbia (DC) and vaccination exemption rates in 46 states and DC for children enrolled in kindergarten during the 2013-14 school year. Median vaccination coverage was 94.7% for 2 doses of measles, mumps, and rubella (MMR) vaccine; 95.0% for varying local requirements for diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccine; and 93.3% for 2 doses of varicella vaccine among those states with a 2-dose requirement. The median total exemption rate was 1.8%. High exemption levels and suboptimal vaccination coverage leave children vulnerable to vaccine-preventable diseases. Although vaccination coverage among kindergartners for the majority of reporting states was at or near the 95% national Healthy People 2020 targets for 4 doses of DTaP, 2 doses of MMR, and 2 doses of varicella vaccine, low vaccination coverage and high exemption levels can cluster within communities. Immunization programs might have access to school vaccination coverage and exemption rates at a local level for counties, school districts, or schools that can identify areas where children are more vulnerable to vaccine-preventable diseases. Health promotion efforts in these local areas can be used to help parents understand the risks for vaccine-preventable diseases and the protection that vaccinations provide to their children.

In silico design of Mycobacterium tuberculosis epitope ensemble vaccines.

PubMed

Shah, Preksha; Mistry, Jaymisha; Reche, Pedro A; Gatherer, Derek; Flower, Darren R

2018-05-01

Effective control of Mycobacterium tuberculosis is a global necessity. In 2015, tuberculosis (TB) caused more deaths than HIV. Considering the increasing prevalence of multi-drug resistant forms of M. tuberculosis, the need for effective TB vaccines becomes imperative. Currently, the only licensed TB vaccine is Bacillus Calmette-Guérin (BCG). Yet, BCG has many drawbacks limiting its efficacy and applicability. We applied advanced computational procedures to derive a universal TB vaccine and one targeting East Africa. Our approach selects an optimal set of highly conserved, experimentally validated epitopes, with high projected population coverage (PPC). Through rigorous data analysis, five different potential vaccine combinations were selected each with PPC above 80% for East Africa and above 90% for the World. Two potential vaccines only contained CD8+ epitopes, while the others included both CD4+ and CD8+ epitopes. Our prime vaccine candidate was a putative seven-epitope ensemble comprising: SRGWSLIKSVRLGNA, KPRIITLTMNPALDI, AAHKGLMNIALAISA, FPAGGSTGSL, MLLAVTVSL, QSSFYSDW and KMRCGAPRY, with a 97.4% global PPC and a 92.7% East African PPC. Copyright © 2018 Elsevier Ltd. All rights reserved.

Measuring Coverage in MNCH: Design, Implementation, and Interpretation Challenges Associated with Tracking Vaccination Coverage Using Household Surveys

PubMed Central

Cutts, Felicity T.; Izurieta, Hector S.; Rhoda, Dale A.

2013-01-01

Vaccination coverage is an important public health indicator that is measured using administrative reports and/or surveys. The measurement of vaccination coverage in low- and middle-income countries using surveys is susceptible to numerous challenges. These challenges include selection bias and information bias, which cannot be solved by increasing the sample size, and the precision of the coverage estimate, which is determined by the survey sample size and sampling method. Selection bias can result from an inaccurate sampling frame or inappropriate field procedures and, since populations likely to be missed in a vaccination coverage survey are also likely to be missed by vaccination teams, most often inflates coverage estimates. Importantly, the large multi-purpose household surveys that are often used to measure vaccination coverage have invested substantial effort to reduce selection bias. Information bias occurs when a child's vaccination status is misclassified due to mistakes on his or her vaccination record, in data transcription, in the way survey questions are presented, or in the guardian's recall of vaccination for children without a written record. There has been substantial reliance on the guardian's recall in recent surveys, and, worryingly, information bias may become more likely in the future as immunization schedules become more complex and variable. Finally, some surveys assess immunity directly using serological assays. Sero-surveys are important for assessing public health risk, but currently are unable to validate coverage estimates directly. To improve vaccination coverage estimates based on surveys, we recommend that recording tools and practices should be improved and that surveys should incorporate best practices for design, implementation, and analysis. PMID:23667334

Impact of Coverage-Dependent Marginal Costs on Optimal HPV Vaccination Strategies

PubMed Central

Ryser, Marc D.; McGoff, Kevin; Herzog, David P.; Sivakoff, David J.; Myers, Evan R.

2015-01-01

The effectiveness of vaccinating males against the human papillomavirus (HPV) remains a controversial subject. Many existing studies conclude that increasing female coverage is more effective than diverting resources into male vaccination. Recently, several empirical studies on HPV immunization have been published, providing evidence of the fact that marginal vaccination costs increase with coverage. In this study, we use a stochastic agent-based modeling framework to revisit the male vaccination debate in light of these new findings. Within this framework, we assess the impact of coverage-dependent marginal costs of vaccine distribution on optimal immunization strategies against HPV. Focusing on the two scenarios of ongoing and new vaccination programs, we analyze different resource allocation policies and their effects on overall disease burden. Our results suggest that if the costs associated with vaccinating males are relatively close to those associated with vaccinating females, then coverage-dependent, increasing marginal costs may favor vaccination strategies that entail immunization of both genders. In particular, this study emphasizes the necessity for further empirical research on the nature of coverage-dependent vaccination costs. PMID:25979280

Vaccination against meningococcus C. vaccinal coverage in the French target population.

PubMed

Stahl, J-P; Cohen, R; Denis, F; Gaudelus, J; Lery, T; Lepetit, H; Martinot, A

2013-02-01

Immunization against meningococcus C has been recommended in France since 2009 (infants from 12 to 24 months of age, and catch up vaccination up to 25 years of age). It has been reimbursed since January 2010. We had for aim to assess the vaccine coverage in 2011. The study population included mothers of children targeted by the recommendation. They were recruited using Internet data (quotas based on the French National Institute of Statistics (INSEE) data based on a census made in 2007) based on the Institut des Mamans panel and its partners. The mothers had completed a standardized questionnaire and reported all vaccinations mentioned in their child's health-record. We included 3000 mothers of children, 0 to 35 months of age, (1000 for each of the following age range: 0-11 months, 12-23 months, 24-35 months), and 2250 mothers of teenagers, 14 to 16 years of age. Vaccination was deemed "essential/useful" for respectively 90.2% (CI 95%: 89.2-91.3) and 87.8% (CI 95%: 86.4-89.2) of mothers. Vaccine coverage levels were 32.3% (12-23 months), 57.3% (24-35 months), and 21.3% (14-16 years). Two years after the Ministry of Health's decision to reimburse this vaccine, vaccine coverage levels were much lower than they should have been, to expect effectiveness of the vaccination policy. Only 21.3% of teenagers had been vaccinated, and 32.3% of infants during the second year of life. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Vaccination coverage among children in kindergarten - United States, 2012-13 school year.

PubMed

2013-08-02

State and local school vaccination requirements are implemented to maintain high vaccination coverage and minimize the risk from vaccine preventable diseases. To assess school vaccination coverage and exemptions, CDC annually analyzes school vaccination coverage data from federally funded immunization programs. These awardees include 50 states and the District of Columbia (DC), five cities, and eight U.S.-affiliated jurisdictions. This report summarizes vaccination coverage from 48 states and DC and exemption rates from 49 states and DC for children entering kindergarten for the 2012-13 school year. Forty-eight states and DC reported vaccination coverage, with medians of 94.5% for 2 doses of measles, mumps, and rubella (MMR) vaccine; 95.1% for local requirements for diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccination; and 93.8% for 2 doses of varicella vaccine among awardees with a 2-dose requirement. Forty-nine states and DC reported exemption rates, with the median total of 1.8%. Although school entry coverage for most awardees was at or near national Healthy People 2020 targets of maintaining 95% vaccination coverage levels for 2 doses of MMR vaccine, 4 doses of DTaP† vaccine, and 2 doses of varicella vaccine, low vaccination and high exemption levels can cluster within communities, increasing the risk for disease. Reports to CDC are aggregated at the state level; however, local reporting of school vaccination coverage might be accessible by awardees. These local-level data can be used to create evidence-based health communication strategies to help parents understand the risks for vaccine-preventable diseases and the benefits of vaccinations to the health of their children and other kindergarteners.

Measles seroprevalence, outbreaks, and vaccine coverage in Rwanda.

PubMed

Seruyange, Eric; Gahutu, Jean-Bosco; Mambo Muvunyi, Claude; Uwimana, Zena G; Gatera, Maurice; Twagirumugabe, Theogene; Katare, Swaibu; Karenzi, Ben; Bergström, Tomas

2016-01-01

Measles outbreaks are reported after insufficient vaccine coverage, especially in countries recovering from natural disaster or conflict. We compared seroprevalence to measles in blood donors in Rwanda and Sweden and explored distribution of active cases of measles and vaccine coverage in Rwanda. 516 Rwandan and 215 Swedish blood donors were assayed for measles-specific immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA). Data on vaccine coverage and acute cases in Rwanda from 1980 to 2014 were collected, and IgM on serum samples and polymerase chain reaction (PCR) on nasopharyngeal (NPH) swabs from suspected measles cases during 2010-2011 were analysed. The seroprevalence of measles IgG was significantly higher in Swedish blood donors (92.6%; 95% CI: 89.1-96.1%) compared to Rwandan subjects (71.5%; 95% CI: 67.6-75.4%) and more pronounced <35 years of age. The OD values were significantly lower in the Rwandan blood donors as compared to Swedish subjects (p < 0.00001). However, effective measles vaccine coverage was concomitant with decrease in measles cases in Rwanda, with the exception of an outbreak in 1995 following the 1994 genocide. 76/544 serum samples were IgM positive and 21/31 NPH swabs were PCR positive for measles, determined by sequencing to be of genotype B3. Measles seroprevalence was lower in Rwandan blood donors compared to Swedish subjects. Despite this, the number of reported measles cases in Rwanda rapidly decreased during the study period, concomitant with increased vaccine coverage. Taken together, the circulation of measles was limited in Rwanda and vaccine coverage was favourable, but seroprevalence and IgG levels were low especially in younger age groups.

Human Papillomavirus Vaccine Coverage and Prevalence of Missed Opportunities for Vaccination in an Integrated Healthcare System.

PubMed

Irving, Stephanie A; Groom, Holly C; Stokley, Shannon; McNeil, Michael M; Gee, Julianne; Smith, Ning; Naleway, Allison L

2018-03-01

Human papillomavirus (HPV) vaccination has been recommended in the United States for female and male adolescents since 2006 and 2011, respectively. Coverage rates are lower than those for other adolescent vaccines. The objective of this study was to evaluate an assessment and feedback intervention designed to increase HPV vaccination coverage and quantify missed opportunities for HPV vaccine initiation at preventive care visits. We examined changes in HPV vaccination coverage and missed opportunities within the adolescent (11-17 years) population at 9 Oregon-based Kaiser Permanente Northwest outpatient clinics after an assessment and feedback intervention. Quarterly coverage rates were calculated for the adolescent populations at the clinics, according to age group (11-12 and 13-17 years), sex, and department (Pediatrics and Family Medicine). Comparison coverage assessments were calculated at 3 nonintervention (control) clinics. Missed opportunities for HPV vaccine initiation, defined as preventive care visits in which a patient eligible for HPV dose 1 remained unvaccinated, were examined according to sex and age group. An average of 29,021 adolescents were included in coverage assessments. Before the intervention, 1-dose and 3-dose quarterly coverage rates were increasing at intervention as well as at control clinics in both age groups. Postimplementation quarterly trends in 1-dose or 3-dose coverage did not differ significantly between intervention and control clinics for either age group. One-dose coverage rates among adolescents with Pediatrics providers were significantly higher than those with Family Medicine providers (56% vs 41% for 11- to 12-year-old and 82% vs 69% for 13- to 17-year-old girls; 55% vs 40% for 11- to 12-year-old and 78% vs 62% for 13- to 17-year-old boys). No significant differences in HPV vaccine coverage were identified at intervention clinics. However, coverage rates were increasing before the start of the intervention and might have

Barriers and facilitators to influenza vaccination and vaccine coverage in a cohort of health care personnel.

PubMed

Naleway, Allison L; Henkle, Emily M; Ball, Sarah; Bozeman, Sam; Gaglani, Manjusha J; Kennedy, Erin D; Thompson, Mark G

2014-04-01

Annual influenza vaccination is recommended for health care personnel (HCP). We describe influenza vaccination coverage among HCP during the 2010-2011 season and present reported facilitators of and barriers to vaccination. We enrolled HCP 18 to 65 years of age, working full time, with direct patient contact. Participants completed an Internet-based survey at enrollment and the end of influenza season. In addition to self-reported data, we collected information about the 2010-2011 influenza vaccine from electronic employee health and medical records. Vaccination coverage was 77% (1,307/1,701). Factors associated with higher vaccination coverage include older age, being married or partnered, working as a physician or dentist, prior history of influenza vaccination, more years in patient care, and higher job satisfaction. Personal protection was reported as the most important reason for vaccination followed closely by convenience, protection of patients, and protection of family and friends. Concerns about perceived vaccine safety and effectiveness and low perceived susceptibility to influenza were the most commonly reported barriers to vaccination. About half of the unvaccinated HCP said they would have been vaccinated if required by their employer. Influenza vaccination in this cohort was relatively high but still fell short of the recommended target of 90% coverage for HCP. Addressing concerns about vaccine safety and effectiveness are possible areas for future education or intervention to improve coverage among HCP. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

A single, low dose of a cGMP recombinant BCG vaccine elicits protective T cell immunity against the human respiratory syncytial virus infection and prevents lung pathology in mice.

PubMed

Céspedes, Pablo F; Rey-Jurado, Emma; Espinoza, Janyra A; Rivera, Claudia A; Canedo-Marroquín, Gisela; Bueno, Susan M; Kalergis, Alexis M

2017-02-01

Human respiratory syncytial virus (hRSV) is a major health burden worldwide, causing the majority of hospitalizations in children under two years old due to bronchiolitis and pneumonia. HRSV causes year-to-year outbreaks of disease, which also affects the elderly and immunocompromised adults. Furthermore, both hRSV morbidity and epidemics are explained by a consistently high rate of re-infections that take place throughout the patient life. Although significant efforts have been invested worldwide, currently there are no licensed vaccines to prevent hRSV infection. Here, we describe that a recombinant Bacillus Calmette-Guerin (BCG) vaccine expressing the nucleoprotein (N) of hRSV formulated under current good manufacture practices (cGMP rBCG-N-hRSV) confers protective immunity to the virus in mice. Our results show that a single dose of the GMP rBCG-N-hRSV vaccine retains its capacity to protect mice against a challenge with a disease-causing infection of 1×10 7 plaque-forming units (PFUs) of the hRSV A2 clinical strain 13018-8. Compared to unimmunized infected controls, vaccinated mice displayed reduced weight loss and less infiltration of neutrophils within the airways, as well as reduced viral loads in bronchoalveolar lavages, parameters that are characteristic of hRSV infection in mice. Also, ex vivo re-stimulation of splenic T cells at 28days post-immunization activated a repertoire of T cells secreting IFN-γ and IL-17, which further suggest that the rBCG-N-hRSV vaccine induced a mixed, CD8 + and CD4 + T cell response capable of both restraining viral spread and preventing damage of the lungs. All these features support the notion that rBCG-N-hRSV is a promising candidate vaccine to be used in humans to prevent the disease caused by hRSV in the susceptible population. Copyright © 2016 Elsevier Ltd. All rights reserved.

A brief review of vaccination coverage in immunization registries.

PubMed

Goldstein, Neal D; Maiese, Brett A

2011-01-01

Immunization registries are effective electronic tools for assessing vaccination coverage, but are only as good as the information reported to them. This review summarizes studies through August 2010 on vaccination coverage in registries and identifies key characteristics of successful registries. Based on the current state of registries, paper-based charts combined with electronic registry reporting provide the most cohesive picture of coverage. To ultimately supplant paper charts, registries must exhibit increased coverage and participation.

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

PubMed Central

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

[Strategies to improve influenza vaccination coverage in Primary Health Care].

PubMed

Antón, F; Richart, M J; Serrano, S; Martínez, A M; Pruteanu, D F

2016-04-01

Vaccination coverage reached in adults is insufficient, and there is a real need for new strategies. To compare strategies for improving influenza vaccination coverage in persons older than 64 years. New strategies were introduced in our health care centre during 2013-2014 influenza vaccination campaign, which included vaccinating patients in homes for the aged as well as in the health care centre. A comparison was made on vaccination coverage over the last 4 years in 3 practices of our health care centre: P1, the general physician vaccinated patients older than 64 that came to the practice; P2, the general physician systematically insisted in vaccination in elderly patients, strongly advising to book appointments, and P3, the general physician did not insist. These practices looked after P1: 278; P2: 320; P3: 294 patients older than 64 years. Overall/P1/P2/P3 coverages in 2010: 51.2/51.4/55/46.9% (P=NS), in 2011: 52.4/52.9/53.8/50.3% (P=NS), in 2012: 51.9/52.5/55.3/47.6% (P=NS), and in 2013: 63.5/79.1/59.7/52.7 (P=.000, P1 versus P2 and P3; P=NS between P2 and P3). Comparing the coverages in 2012-2013 within each practice P1 (P=.000); P2 (P=.045); P3 (P=.018). In P2 and P3 all vaccinations were given by the nurses as previously scheduled. In P3, 55% of the vaccinations were given by the nurses, 24.1% by the GP, 9.7% rejected vaccination, and the remainder did not come to the practice during the vaccination period (October 2013-February 2014). The strategy of vaccinating in the homes for the aged improved the vaccination coverage by 5% in each practice. The strategy of "I've got you here, I jab you here" in P1 improved the vaccination coverage by 22%. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Evaluation of Immunogenicity and Protective Efficacy Elicited by Mycobacterium bovis BCG Overexpressing Ag85A Protein against Mycobacterium tuberculosis Aerosol Infection.

PubMed

Xu, Zheng Zhong; Chen, Xiang; Hu, Ting; Meng, Chuang; Wang, Xiao Bo; Rao, Yan; Zhang, Xiao Ming; Yin, Yue Lan; Pan, Zhi Ming; Jiao, Xin An

2016-01-01

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is currently the only vaccine available for preventing tuberculosis (TB), however, BCG has varying success in preventing pulmonary TB. In this study, a recombinant BCG (rBCG::Ag85A) strain overexpressing the immunodominant Ag85A antigen was constructed, and its immunogenicity and protective efficacy were evaluated. Our results indicated that the Ag85A protein was successfully overexpressed in rBCG::Ag85A, and the Ag85A peptide-MHC complexes on draining lymph node dendritic cells of C57BL/6 mice infected with rBCG::Ag85A were detectable 4 h post-infection. The C57BL/6 mice infected with this strain had stronger antigen-specific interferon-gamma (IFN-γ) responses and higher antibody titers than those immunized with BCG, and the protective experiments showed that rBCG::Ag85A can enhance protection against Mycobacterium tuberculosis (M. tuberculosis) H37Rv infection compared to the BCG vaccine alone. Our results demonstrate the potential of rBCG::Ag85A as a candidate vaccine against TB.

Vaccination coverage among children in kindergarten--United States, 2009-10 school year.

PubMed

2011-06-03

Healthy People 2020 objectives include maintaining vaccination coverage among children in kindergarten (IID-10) (1). The target is ≥95% vaccination coverage for the following vaccines: poliovirus; diphtheria and tetanus toxoids and acellular pertussis (DTP/DTaP/DT); measles, mumps, and rubella (MMR); hepatitis B (HepB); and varicella (1). Data from school assessment surveys are used to monitor vaccination coverage and vaccination exemption levels among children enrolled in kindergarten. This report summarizes data from school assessment surveys submitted to CDC by 48 federal immunization program grantees (including 47 states and the District of Columbia) for the 2009-10 school year to describe vaccination coverage and exemption rates (2). For that period, 17 grantees reported coverage of ?95% for four vaccines (poliovirus, DTP/DTaP/DT, MMR, and HepB) and four grantees reported coverage of ≥95% for 2 doses of varicella vaccine. Total exemption rates, including medical, religious, and philosophical exemptions, ranged from <1% to 6.2% across grantees, and 15 grantees reported exemption rates<1%. Survey methods for vaccination coverage and exemption rates varied among grantees, making comparisons difficult and limiting the use of school assessment surveys to report aggregate national rates. Further standardization of school assessment survey methods will generate comparable data between grantees to monitor and track progress in reaching national objectives, and allow development of best practice guidelines for grantees to more effectively use and report school coverage and exemption data. CDC will continue to monitor vaccination coverage and exemption levels and assist grantees in identification of local areas with low vaccination coverage or high exemption rates for further evaluation or intervention.

Correlates of human papillomavirus vaccine coverage: a state-level analysis.

PubMed

Moss, Jennifer L; Reiter, Paul L; Brewer, Noel T

2015-02-01

We tested the hypothesis that states with higher rates of cancers associated with human papillomavirus (HPV) would have lower HPV vaccine coverage. We gathered state-level data on HPV-related cancer rates and HPV vaccine initiation coverage for girls and boys, separately, and HPV vaccine follow-through (i.e., receipt of 3 doses among those initiating the series) for girls only. In addition, we gathered state-level data on demographic composition and contact with the health care system. We calculated Pearson correlations for these ecological relationships. Human papillomavirus vaccine initiation among girls was lower in states with higher levels of cervical cancer incidence and mortality (r = -0.29 and -0.46, respectively). In addition, vaccine follow-through among girls was lower in states with higher levels of cervical cancer mortality (r = -0.30). Other cancer rates were associated with HPV vaccine initiation and follow-through among girls, but not among boys. Human papillomavirus vaccine initiation among girls was lower in states with higher proportions of non-Hispanic black residents and lower proportions of higher-income residents. Human papillomavirus vaccine follow-through was higher in states with greater levels of adolescents' contact with the health care system. Human papillomavirus vaccine coverage for girls was lower in states with higher HPV-related cancer rates. Public health efforts should concentrate on geographic areas with higher cancer rates. Strengthening adolescent preventive health care use may be particularly important to increase vaccine follow-through. Cost-effectiveness analyses may overestimate the benefits of current vaccination coverage and underestimate the benefits of increasing coverage.

rBCG30-Induced Immunity and Cross-Protection against Mycobacterium leprae Challenge Are Enhanced by Boosting with the Mycobacterium tuberculosis 30-Kilodalton Antigen 85B

PubMed Central

Gillis, Thomas P.; Tullius, Michael V.

2014-01-01

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. PMID:25001602

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

PubMed

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.

Effectiveness of interventions that apply new media to improve vaccine uptake and vaccine coverage.

PubMed

Odone, Anna; Ferrari, Antonio; Spagnoli, Francesca; Visciarelli, Sara; Shefer, Abigail; Pasquarella, Cesira; Signorelli, Carlo

2015-01-01

Vaccine-preventable diseases (VPD) are still a major cause of morbidity and mortality worldwide. In high and middle-income settings, immunization coverage is relatively high. However, in many countries coverage rates of routinely recommended vaccines are still below the targets established by international and national advisory committees. Progress in the field of communication technology might provide useful tools to enhance immunization strategies. To systematically collect and summarize the available evidence on the effectiveness of interventions that apply new media to promote vaccination uptake and increase vaccination coverage. We conducted a systematic literature review. Studies published from January 1999 to September 2013 were identified by searching electronic resources (Pubmed, Embase), manual searches of references and expert consultation. Study setting We focused on interventions that targeted recommended vaccinations for children, adolescents and adults and: (1) aimed at increasing community demand for immunizations, or (2) were provider-based interventions. We limited the study setting to countries that are members of the Organisation for Economic Co-operation and Development (OECD). The primary outcome was a measure of vaccination (vaccine uptake or vaccine coverage). Considered secondary outcomes included willingness to receive immunization, attitudes and perceptions toward vaccination, and perceived helpfulness of the intervention. Nineteen studies were included in the systematic review. The majority of the studies were conducted in the US (74%, n = 14); 68% (n = 13) of the studies were experimental, the rest having an observational study design. Eleven (58%) reported results on the primary outcome. Retrieved studies explored the role of: text messaging (n.7, 37%), smartphone applications (n.1, 5%), Youtube videos (n.1, 5%), Facebook (n.1, 5%), targeted websites and portals (n.4, 21%), software for physicians and health professionals (n.4, 21

Effectiveness of interventions that apply new media to improve vaccine uptake and vaccine coverage

PubMed Central

Odone, Anna; Ferrari, Antonio; Spagnoli, Francesca; Visciarelli, Sara; Shefer, Abigail; Pasquarella, Cesira; Signorelli, Carlo

2014-01-01

Background Vaccine-preventable diseases (VPD) are still a major cause of morbidity and mortality worldwide. In high and middle-income settings, immunization coverage is relatively high. However, in many countries coverage rates of routinely recommended vaccines are still below the targets established by international and national advisory committees. Progress in the field of communication technology might provide useful tools to enhance immunization strategies. Objective To systematically collect and summarize the available evidence on the effectiveness of interventions that apply new media to promote vaccination uptake and increase vaccination coverage. Design We conducted a systematic literature review. Studies published from January 1999 to September 2013 were identified by searching electronic resources (Pubmed, Embase), manual searches of references and expert consultation. Study setting We focused on interventions that targeted recommended vaccinations for children, adolescents and adults and: (1) aimed at increasing community demand for immunizations, or (2) were provider-based interventions. We limited the study setting to countries that are members of the Organisation for Economic Co-operation and Development (OECD). Main outcome measures The primary outcome was a measure of vaccination (vaccine uptake or vaccine coverage). Considered secondary outcomes included willingness to receive immunization, attitudes and perceptions toward vaccination, and perceived helpfulness of the intervention. Results Nineteen studies were included in the systematic review. The majority of the studies were conducted in the US (74%, n = 14); 68% (n = 13) of the studies were experimental, the rest having an observational study design. Eleven (58%) reported results on the primary outcome. Retrieved studies explored the role of: text messaging (n.7, 37%), smartphone applications (n.1, 5%), Youtube videos (n.1, 5%), Facebook (n.1, 5%), targeted websites and portals (n.4, 21

Do selective immunisation against tuberculosis and hepatitis B reach the targeted populations? A nationwide register-based study evaluating the recommendations in the Norwegian Childhood Immunisation Programme.

PubMed

Feiring, Berit; Laake, Ida; Molden, Tor; Håberg, Siri E; Nøkleby, Hanne; Seterelv, Siri Schøyen; Magnus, Per; Trogstad, Lill

2016-04-12

Selective immunisation is an alternative to universal vaccination if children at increased risk of disease can be identified. Within the Norwegian Childhood Immunisation Programme, BCG vaccine against tuberculosis and vaccine against hepatitis B virus (HBV) are offered only to children with parents from countries with high burden of the respective disease. We wanted to study whether this selective immunisation policy reaches the targeted groups. The study population was identified through the Norwegian Central Population Registry and consisted of all children born in Norway 2007-2010 and residing in Norway until their second birthday, in total 240,484 children. Information on vaccinations from the Norwegian Immunisation Registry, and on parental country of birth from Statistics Norway, was linked to the population registry by personal identifiers. The coverage of BCG and HBV vaccine was compared with the coverage of vaccines in the universal programme. Among the study population, 16.1% and 15.9% belonged to the target groups for BCG and HBV vaccine, respectively. Among children in the BCG target group the BCG vaccine coverage was lower than the coverage of pertussis and measles vaccine (83.6% vs. 98.6% and 92.3%, respectively). Likewise, the HBV vaccine coverage was lower than the coverage of pertussis and measles vaccine in the HBV target group (90.0% vs. 98.6% and 92.3%, respectively). The coverage of the targeted vaccines was highest among children with parents from South Asia and Sub-Saharan Africa. The coverage of vaccines in the universal programme was similar in targeted and non-targeted groups. Children targeted by selective vaccination had lower coverage of the target vaccines than of vaccines in the universal programme, indicating that selective vaccination is challenging. Improved routines for identifying eligible children and delivering the target vaccines are needed. Universal vaccination of all children with these vaccines could be considered

Influenza vaccination coverage among US children from 2004/2005 to 2015/2016.

PubMed

Tian, Changwei; Wang, Hua; Wang, Wenming; Luo, Xiaoming

2018-05-15

Quantify the influenza vaccine coverage is essential to identify emerging concerns and to immunization programs for targeting interventions. Data from National Health Interview Survey were used to estimate receipt of at least one dose of influenza vaccination among children 6 months to 17 years of age. Influenza vaccination coverage increased from 16.70% during 2004/2005 to 49.43% during 2015/2016 (3.18% per year, P < 0.001); however, the coverage increased slightly after 2010/2011. Children at high risk of influenza complications had higher influenza vaccination coverage than non at-risk children. Boys and girls had similar coverage each year. While the coverage increased from 2004/2005 to 2015/2016 for all age groups, the coverage decreased with age each year (-0.64 to -1.58% per age group). There was a higher and rapid increase of coverage in Northeast than Midwest, South and West. American Indian or Alaskan Native and Asian showed higher coverage than other race groups (White, Black/African American, Multiple race). Multivariable analysis showed that high-risk status and region had the greatest associations with levels of vaccine coverage. Although the influenza vaccination coverage among children had increased remarkably since 2004/2005, establishing more effective immunization programs are warranted to achieve the Healthy People 2020 target.

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

PubMed

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.

Increasing Coverage of Hepatitis B Vaccination in China

PubMed Central

Wang, Shengnan; Smith, Helen; Peng, Zhuoxin; Xu, Biao; Wang, Weibing

2016-01-01

Abstract This study used a system evaluation method to summarize China's experience on improving the coverage of hepatitis B vaccine, especially the strategies employed to improve the uptake of timely birth dosage. Identifying successful methods and strategies will provide strong evidence for policy makers and health workers in other countries with high hepatitis B prevalence. We conducted a literature review included English or Chinese literature carried out in mainland China, using PubMed, the Cochrane databases, Web of Knowledge, China National Knowledge Infrastructure, Wanfang data, and other relevant databases. Nineteen articles about the effectiveness and impact of interventions on improving the coverage of hepatitis B vaccine were included. Strong or moderate evidence showed that reinforcing health education, training and supervision, providing subsidies for facility birth, strengthening the coordination among health care providers, and using out-of-cold-chain storage for vaccines were all important to improving vaccination coverage. We found evidence that community education was the most commonly used intervention, and out-reach programs such as out-of-cold chain strategy were more effective in increasing the coverage of vaccination in remote areas where the facility birth rate was respectively low. The essential impact factors were found to be strong government commitment and the cooperation of the different government departments. Public interventions relying on basic health care systems combined with outreach care services were critical elements in improving the hepatitis B vaccination rate in China. This success could not have occurred without exceptional national commitment. PMID:27175710

Demonstration of increased anti-mycobacterial activity in peripheral blood monocytes after BCG vaccination in British school children.

PubMed Central

Cheng, S H; Walker, L; Poole, J; Aber, V R; Walker, K B; Mitchison, D A; Lowrie, D B

1988-01-01

A blood sample was taken from children aged 13-15 years immediately before BCG vaccination and 8 weeks after. The children were tuberculin skin-test negative to PPD-S before vaccination and positive after. Mononuclear cells were separated from the blood, infected with Mycobacterium microti at a low bacterium/monocyte ratio and allowed to form monolayers in microtitre wells. The infected monolayers were rinsed daily and the change in number of live bacteria in monolayers and supernatants was monitored by colony counts on agar. The cells were bacteriostatic during the first day, thereafter growth accelerated in pre-vaccination monolayers. When monolayers received pulsed exposures to autologous lymphocytes that had been incubated with whole dead tubercle bacilli the growth rates of M. microti were increased. However, growth rates in lymphocyte-pulsed monolayers were significantly lower after vaccination than before. It is proposed that this difference reflects the protective effect of vaccination. PMID:3219800

Optimal control on bladder cancer growth model with BCG immunotherapy and chemotherapy

NASA Astrophysics Data System (ADS)

Dewi, C.; Trisilowati

2015-03-01

In this paper, an optimal control model of the growth of bladder cancer with BCG (Basil Calmate Guerin) immunotherapy and chemotherapy is discussed. The purpose of this optimal control is to determine the number of BCG vaccine and drug should be given during treatment such that the growth of bladder cancer cells can be suppressed. Optimal control is obtained by applying Pontryagin principle. Furthermore, the optimal control problem is solved numerically using Forward-Backward Sweep method. Numerical simulations show the effectiveness of the vaccine and drug in controlling the growth of cancer cells. Hence, it can reduce the number of cancer cells that is not infected with BCG as well as minimize the cost of the treatment.

Patterns of in vitro cell-death, metaloproteinase-9 and pro-inflammatory cytokines in human monocytes induced by the BCG vaccine, Moreau strain.

PubMed

Simas, C J A; Silva, D P H; Ponte, C G G; Castello-Branco, L R R; Antas, P R Z

2011-09-02

Mononuclear cells have been implicated in the primary inflammatory response against mycobacteria. Yet, little is known about the interaction of Mycobacterium bovis bacillus Calmette-Guerin (BCG) with human monocytes. Here, we investigated the potential of BCG Moreau strain to induce in vitro specific cell-death utilizing a flow cytometry approach that revealed an increase in apoptosis events in BCG-stimulated monocytes from healthy adults. We also detected a concomitant release of interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), but not metalloproteinase (MMP)-9. In addition, annexin V-propidium iodide double staining demonstrated an enhancement of monocytes necrosis, but not apoptosis, following BCG Moreau strain stimulation of umbilical vein cells from naïve, neonate. This pattern was paralleled by different pro-inflammatory cytokine levels, as well as MMP-9 induction when compared to the adults. Our findings support the hypothesis that BCG induces distinct cell-death patterns during the maturation of the immune system and that this pattern might set the stage for a subsequent antimycobacterial immune response that might have profound effects during vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.

Robust immunity to an auxotrophic Mycobacterium bovis BCG-VLP prime-boost HIV vaccine candidate in a nonhuman primate model.

PubMed

Chege, Gerald K; Burgers, Wendy A; Stutz, Helen; Meyers, Ann E; Chapman, Rosamund; Kiravu, Agano; Bunjun, Rubina; Shephard, Enid G; Jacobs, William R; Rybicki, Edward P; Williamson, Anna-Lise

2013-05-01

We previously reported that a recombinant pantothenate auxotroph of Mycobacterium bovis BCG expressing human immunodeficiency virus type 1 (HIV-1) subtype C Gag (rBCGpan-Gag) efficiently primes the mouse immune system for a boost with a recombinant modified vaccinia virus Ankara (rMVA) vaccine. In this study, we further evaluated the immunogenicity of rBCGpan-Gag in a nonhuman primate model. Two groups of chacma baboons were primed or mock primed twice with either rBCGpan-Gag or a control BCG. Both groups were boosted with HIV-1 Pr55(gag) virus-like particles (Gag VLPs). The magnitude and breadth of HIV-specific cellular responses were measured using a gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay, and the cytokine profiles and memory phenotypes of T cells were evaluated by polychromatic flow cytometry. Gag-specific responses were detected in all animals after the second inoculation with rBCGpan-Gag. Boosting with Gag VLPs significantly increased the magnitude and breadth of the responses in the baboons that were primed with rBCGpan-Gag. These responses targeted an average of 12 Gag peptides per animal, compared to an average of 3 peptides per animal for the mock-primed controls. Robust responses of Gag-specific polyfunctional T cells capable of simultaneously producing IFN-γ, tumor necrosis alpha (TNF-α), and interleukin-2 (IL-2) were detected in the rBCGpan-Gag-primed animals. Gag-specific memory T cells were skewed toward a central memory phenotype in both CD4(+) and CD8(+) T cell populations. These data show that the rBCGpan-Gag prime and Gag VLP boost vaccine regimen is highly immunogenic, inducing a broad and polyfunctional central memory T cell response. This report further indicates the feasibility of developing a BCG-based HIV vaccine that is safe for childhood HIV immunization.

Protective efficacy of recombinant BCG Tokyo (Ag85A) in rhesus monkeys (Macaca mulatta) infected intratracheally with H37Rv Mycobacterium tuberculosis.

PubMed

Sugawara, I; Sun, L; Mizuno, S; Taniyama, T

2009-01-01

We have reported previously that recombinant BCG Tokyo (Ag85A) (rBCG-Ag85A[Tokyo]) shows promise as a tuberculosis vaccine, demonstrating protective efficacy in cynomolgus monkeys. As a next step, rhesus monkeys were utilized because they are also susceptible to Mycobacterium tuberculosis and show a continuous course of infection resembling human tuberculosis. The recombinant BCG vaccine (5x10(5) CFU per monkey) was administered once intradermally into the back skin to three groups of rhesus monkeys, and its protective efficacy was compared for 4months with that of its parental BCG Tokyo strain. Eight week vaccination of the monkeys with rBCG-Ag85A[Tokyo] resulted in a reduction of tubercle bacilli CFU (p<0.01) and lung pathology in animals infected intratracheally with 3000 CFU H37Rv M. tuberculosis. Vaccination prevented an increase in the old tuberculin test after challenge with M. tuberculosis and reaction of M. tuberculosis-derived antigen. Thus, it was shown that even in rhesus monkeys rBCG-Ag85A[Tokyo] induced higher protective efficacy than BCG Tokyo.

Two Birds With One Stone: Estimating Population Vaccination Coverage From a Test-negative Vaccine Effectiveness Case-control Study.

PubMed

Doll, Margaret K; Morrison, Kathryn T; Buckeridge, David L; Quach, Caroline

2016-10-15

Vaccination program evaluation includes assessment of vaccine uptake and direct vaccine effectiveness (VE). Often examined separately, we propose a design to estimate rotavirus vaccination coverage using controls from a rotavirus VE test-negative case-control study and to examine coverage following implementation of the Quebec, Canada, rotavirus vaccination program. We present our assumptions for using these data as a proxy for coverage in the general population, explore effects of diagnostic accuracy on coverage estimates via simulations, and validate estimates with an external source. We found 79.0% (95% confidence interval, 74.3%, 83.0%) ≥2-dose rotavirus coverage among participants eligible for publicly funded vaccination. No differences were detected between study and external coverage estimates. Simulations revealed minimal bias in estimates with high diagnostic sensitivity and specificity. We conclude that controls from a VE case-control study may be a valuable resource of coverage information when reasonable assumptions can be made for estimate generalizability; high rotavirus coverage demonstrates success of the Quebec program. © 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.

Crude childhood vaccination coverage in West Africa: Trends and predictors of completeness.

PubMed

Kazungu, Jacob S; Adetifa, Ifedayo M O

2017-02-15

Background : Africa has the lowest childhood vaccination coverage worldwide. If the full benefits of childhood vaccination programmes are to be enjoyed in sub-Saharan Africa, all countries need to improve on vaccine delivery to achieve and sustain high coverage. In this paper, we review trends in vaccination coverage, dropouts between vaccine doses and explored the country-specific predictors of complete vaccination in West Africa.  Methods : We utilized datasets from the Demographic and Health Surveys Program, available for Benin, Burkina Faso, The Gambia, Ghana, Guinea, Cote d'Ivoire, Liberia, Mali, Niger, Nigeria, Senegal, Sierra Leone and Togo, to obtain coverage for Bacillus Calmette-Guerin, polio, measles, and diphtheria, pertussis and tetanus (DPT) vaccines in children aged 12 - 23 months. We also calculated the DPT1-to-DPT3 and DPT1-to-measles dropouts, and proportions of the fully immunised child (FIC). Factors predictive of FIC were explored using Chi-squared tests and multivariable logistic regression.  Results : Overall, there was a trend of increasing vaccination coverage. The proportion of FIC varied significantly by country (range 24.1-81.4%, mean 49%). DPT1-to-DPT3 dropout was high (range 5.1% -33.9%, mean 16.3%). Similarly, DPT1-measles dropout exceeded 10% in all but four countries. Although no single risk factor was consistently associated with FIC across these countries, maternal education, delivery in a health facility, possessing a vaccine card and a recent post delivery visit to a health facility were the key predictors of complete vaccination.  Conclusions : The low numbers of fully immunised children and high dropout between vaccine doses highlights weaknesses and the need to strengthen the healthcare and routine immunization delivery systems in this region. Country-specific correlates of complete vaccination should be explored further to identify interventions required to increase vaccination coverage. Despite the promise of an

Influenza vaccination coverage among adults in Korea: 2008-2009 to 2011-2012 seasons.

PubMed

Yang, Hye Jung; Cho, Sung-Il

2014-11-25

The aim of this study was to examine seasonal and pandemic influenza vaccination coverage in adults from the 2008-2009 season to the 2011-2012 season, including pandemic and post-pandemic seasons in Korea. We collected data of self-reported vaccine use from the Korean Community Health Survey. We also collected information on socioeconomic status and health behaviors in subpopulations. We tested for linear trends among the data to investigate vaccine coverage before and after the pandemic; and multiple logistic regression analyses were performed to identify predictors of obtaining the influenza vaccination. The results revealed a steady increase in vaccination coverage in every subgroup during four consecutive seasons. The highest rate of vaccine coverage (43.6%) occurred two years after the pandemic. Factors associated with vaccine receipt were: older age; lower education level; lower income; and health behaviors such as regular walking and receiving a health check-up. Smoking and drinking alcohol were inversely associated with vaccination. Having a chronic health condition was also a strong predictor of vaccine receipt. Though vaccination coverage rates were high in high-risk groups; disparities in coverage rates were substantial; particularly in young adults. Interventions are needed to minimize the coverage gaps among subgroups and to improve overall vaccination rates.

Routine Vaccination Coverage in Northern Nigeria: Results from 40 District-Level Cluster Surveys, 2014-2015.

PubMed

Gunnala, Rajni; Ogbuanu, Ikechukwu U; Adegoke, Oluwasegun J; Scobie, Heather M; Uba, Belinda V; Wannemuehler, Kathleen A; Ruiz, Alicia; Elmousaad, Hashim; Ohuabunwo, Chima J; Mustafa, Mahmud; Nguku, Patrick; Waziri, Ndadilnasiya Endie; Vertefeuille, John F

2016-01-01

Despite recent success towards controlling poliovirus transmission, Nigeria has struggled to achieve uniformly high routine vaccination coverage. A lack of reliable vaccination coverage data at the operational level makes it challenging to target program improvement. To reliably estimate vaccination coverage, we conducted district-level vaccine coverage surveys using a pre-existing infrastructure of polio technical staff in northern Nigeria. Household-level cluster surveys were conducted in 40 polio high risk districts of Nigeria during 2014-2015. Global positioning system technology and intensive supervision by a pool of qualified technical staff were used to ensure high survey quality. Vaccination status of children aged 12-23 months was documented based on vaccination card or caretaker's recall. District-level coverage estimates were calculated using survey methods. Data from 7,815 children across 40 districts were analyzed. District-level coverage with the third dose of diphtheria-pertussis-tetanus vaccine (DPT3) ranged widely from 1-63%, with all districts having DPT3 coverage below the target of 80%. Median coverage across all districts for each of eight vaccine doses (1 Bacille Calmette-Guérin dose, 3 DPT doses, 3 oral poliovirus vaccine doses, and 1 measles vaccine dose) was <50%. DPT3 coverage by survey was substantially lower (range: 28%-139%) than the 2013 administrative coverage reported among children aged <12 months. Common reported reasons for non-vaccination included lack of knowledge about vaccines and vaccination services (50%) and factors related to access to routine immunization services (15%). Survey results highlighted vaccine coverage gaps that were systematically underestimated by administrative reporting across 40 polio high risk districts in northern Nigeria. Given the limitations of administrative coverage data, our approach to conducting quality district-level coverage surveys and providing data to assess and remediate issues

The effectiveness of vaccine day and educational interventions on influenza vaccine coverage among health care workers at long-term care facilities.

PubMed

Kimura, Akiko C; Nguyen, Christine N; Higa, Jeffrey I; Hurwitz, Eric L; Vugia, Duc J

2007-04-01

We examined barriers to influenza vaccination among long-term care facility (LTCF) health care workers in Southern California and developed simple, effective interventions to improve influenza vaccine coverage of these workers. In 2002, health care workers at LTCFs were surveyed regarding their knowledge and attitudes about influenza and the influenza vaccine. Results were used to develop 2 interventions, an educational campaign and Vaccine Day (a well-publicized day for free influenza vaccination of all employees at the worksite). Seventy facilities were recruited to participate in an intervention trial and randomly assigned to 4 study groups. The combination of Vaccine Day and an educational campaign was most effective in increasing vaccine coverage (53% coverage; prevalence ratio [PR]=1.45; 95% confidence interval [CI]=1.24, 1.71, compared with 27% coverage in the control group). Vaccine Day alone was also effective (46% coverage; PR= 1.41; 95% CI=1.17, 1.71). The educational campaign alone was not effective in improving coverage levels (34% coverage; PR=1.18; 95% CI=0.93, 1.50). Influenza vaccine coverage of LTCF health care workers can be improved by providing free vaccinations at the worksite with a well-publicized Vaccine Day.

Multiple Consecutive Infections Might Explain the Lack of Protection by BCG

PubMed Central

Cardona, Pere-Joan; Vilaplana, Cristina

2014-01-01

Although contacts between tuberculosis patients may result in multiple consecutive infections (MCI), no experimental animal models consider this fact when used in basic studies. Moreover, the current TB vaccine (BCG) has demonstrated a limited protection in humans. In this study we evaluate the effect of tuberculosis MCI by way of a simple mathematical analysis using data from the low dose aerosol murine experimental model. The results show that a higher number of, or shorter intervals between, multiple consecutive infections reduce the protective effect of BCG. This is due to both the increase in bacillary load at the stationary level of the infection, and the protective immune response induced by the infection itself. This factor must therefore be taken into account when designing new prophylactic strategies as candidate vaccines for the replacement of BCG. PMID:24740286

Multiple consecutive infections might explain the lack of protection by BCG.

PubMed

Cardona, Pere-Joan; Vilaplana, Cristina

2014-01-01

Although contacts between tuberculosis patients may result in multiple consecutive infections (MCI), no experimental animal models consider this fact when used in basic studies. Moreover, the current TB vaccine (BCG) has demonstrated a limited protection in humans. In this study we evaluate the effect of tuberculosis MCI by way of a simple mathematical analysis using data from the low dose aerosol murine experimental model. The results show that a higher number of, or shorter intervals between, multiple consecutive infections reduce the protective effect of BCG. This is due to both the increase in bacillary load at the stationary level of the infection, and the protective immune response induced by the infection itself. This factor must therefore be taken into account when designing new prophylactic strategies as candidate vaccines for the replacement of BCG.

BCG protects toddlers during a tuberculosis outbreak.

PubMed

Gaensbauer, J T; Vandaleur, M; O'Neil, M; Altaf, A; Ní Chróinín, M

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.

The free vaccination policy of influenza in Beijing, China: The vaccine coverage and its associated factors.

PubMed

Lv, Min; Fang, Renfei; Wu, Jiang; Pang, Xinghuo; Deng, Ying; Lei, Trudy; Xie, Zheng

2016-04-19

In order to improve influenza vaccination coverage, the coverage rate and reasons for non-vaccination need to be determined. In 2007, the Beijing Government published a policy providing free influenza vaccinations to elderly people living in Beijing who are older than 60. This study examines the vaccination coverage after the policy was carried out and factors influencing vaccination among the elderly in Beijing. A cross-sectional survey was conducted through the use of questionnaires in 2013. A total of 1673 eligible participants were selected by multistage stratified random sampling in Beijing using anonymous questionnaires in-person. They were surveyed to determine vaccination status and social demographic information. The influenza vaccination coverage was 38.7% among elderly people in Beijing in 2012. The most common reason for not being vaccinated was people thinking they did not need to have a flu shot. After controlling for age, gender, income, self-reported health status, and the acceptance of health promotion, the rate in rural areas was 2.566 (95% confidence interval [CI], 1.801-3.655, P<0.010) times greater than that in urban areas. Different mechanisms of health education and health promotion have different influences on vaccination uptake. Those whom received information through television, community boards, or doctors were more likely to get vaccinated compared to those who did not (Odds Ratio [OR]=1.403, P<0.010; OR=1.812, P<0.010; OR=2.647, P<0.010). The influenza vaccine coverage in Beijing is much lower than that of developed countries with similar policies. The rural-urban disparity in coverage rate (64.1% versus 33.5%), may be explained by differing health provision systems and personal attitudes toward free services due to socioeconomic factors. Methods for increasing vaccination levels include increasing the focus on primary care and health education programs, particularly recommendations from doctors, to the distinct target populations

Effects of the introduction of new vaccines in Guinea-Bissau on vaccine coverage, vaccine timeliness, and child survival: an observational study.

PubMed

Fisker, Ane B; Hornshøj, Linda; Rodrigues, Amabelia; Balde, Ibraima; Fernandes, Manuel; Benn, Christine S; Aaby, Peter

2014-08-01

In 2008, the GAVI Alliance funded the introduction of new vaccines (including pentavalent diphtheria-tetanus-pertussis [DTP] plus hepatitis B and Haemophilus influenzae type b antigens) in Guinea-Bissau. The introduction was accompanied by increased vaccination outreach services and a more restrictive wastage policy, including only vaccinating children younger than 12 months. We assessed coverage of all vaccines in the Expanded Program on Immunizations before and after the new vaccines' introduction, and the implications on child survival. This observational cohort study used data from the Bandim Health Project, which has monitored vaccination status and mortality in randomly selected village clusters in Guinea-Bissau since 1990. We assessed the change in vaccination coverage using cohort data from children born in 2007 and 2009; analysed the proportion of children who received measles vaccine after 12 months of age using data from 1999-2006; and compared child mortality after age 12 months in children who had received measles vaccine and those who had not using data from 1999 to 2006. The proportion of children who were fully vaccinated by 12 months of age was 53% (468 of 878) in the 2007 cohort and 53% (467 of 879) in the 2009 cohort (relative risk [RR] 1·00, 95% CI 0·89-1·11). Coverage of DTP-3 and pentavalent-3 increased from 73% (644 of 878) in 2007 to 81% (712 of 879) in 2009 (RR 1·10, 95% CI 1·04 -1·17); by contrast, the coverage of measles vaccination declined from 71% (620 of 878) to 66% (577 of 879; RR 0·93, 0·85-1·01). The effect of the changes was significantly different for DTP-3 coverage compared with measles vaccine coverage (p=0·002). After 12 months of age, the adjusted mortality rate ratio was 0·71 (95% CI 0·56-0·90) for children who had received measles vaccine compared with those who had not (0·59 [0·43-0·80] for girls and 0·87 [0·62-1·23] for boys). The introduction of the new vaccination programme in 2008 was associated with

Comparative assessment of immunization coverage of migrant children between national immunization program vaccines and non-national immunization program vaccines in East China.

PubMed

Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing

2015-01-01

This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%- vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage.

Validity of vaccination cards and parental recall to estimate vaccination coverage: a systematic review of the literature.

PubMed

Miles, Melody; Ryman, Tove K; Dietz, Vance; Zell, Elizabeth; Luman, Elizabeth T

2013-03-15

Immunization programs frequently rely on household vaccination cards, parental recall, or both to calculate vaccination coverage. This information is used at both the global and national level for planning and allocating performance-based funds. However, the validity of household-derived coverage sources has not yet been widely assessed or discussed. To advance knowledge on the validity of different sources of immunization coverage, we undertook a global review of literature. We assessed concordance, sensitivity, specificity, positive and negative predictive value, and coverage percentage point difference when subtracting household vaccination source from a medical provider source. Median coverage difference per paper ranged from -61 to +1 percentage points between card versus provider sources and -58 to +45 percentage points between recall versus provider source. When card and recall sources were combined, median coverage difference ranged from -40 to +56 percentage points. Overall, concordance, sensitivity, specificity, positive and negative predictive value showed poor agreement, providing evidence that household vaccination information may not be reliable, and should be interpreted with care. While only 5 papers (11%) included in this review were from low-middle income countries, low-middle income countries often rely more heavily on household vaccination information for decision making. Recommended actions include strengthening quality of child-level data and increasing investments to improve vaccination card availability and card marking. There is also an urgent need for additional validation studies of vaccine coverage in low and middle income countries. Copyright © 2013. Published by Elsevier Ltd.

Estimation of child vaccination coverage at state and national levels in India

PubMed Central

Gupta, Satish; Kumar, Rakesh; Haldar, Pradeep; Sethi, Raman; Bahl, Sunil

2016-01-01

Abstract Objective To review the data, for 1999–2013, on state-level child vaccination coverage in India and provide estimates of coverage at state and national levels. Methods We collated data from administrative reports, population-based surveys and other sources and used them to produce annual estimates of vaccination coverage. We investigated bacille Calmette–Guérin vaccine, the first and third doses of vaccine against diphtheria, tetanus and pertussis, the third dose of oral polio vaccine and the first dose of vaccine against measles. We obtained relevant data covering the period 1999–2013 for each of 16 states and territories and the period 2001–2013 for the state of Jharkhand – which was only created in 2000. We aggregated the resultant state-level estimates, using a population-weighted approach, to give national values. Findings For each of the vaccinations we investigated, about half of the 253 estimates of annual coverage at state level that we produced were based on survey results. The rest were based on interpolation between – or extrapolation from – so-called anchor points or, more rarely, on administrative data. Our national estimates indicated that, for each of the vaccines we investigated, coverage gradually increased between 1999 and 2010 but then levelled off. Conclusion The delivery of routine vaccination services to Indian children appears to have improved between 1999 and 2013. There remains considerable scope to improve the recording and reporting of childhood vaccination coverage in India and regular systematic reviews of the coverage data are recommended. PMID:27843162

Global Rotavirus Vaccine Introductions and Coverage: 2006 - 2016.

PubMed

Abou-Nader, Alice; Sauer, Molly; Steele, A Duncan; Tate, Jacqueline E; Atherly, Deborah; Parashar, Umesh D; Santosham, Mathuram; Nelson, E Anthony S

2018-05-22

An estimated 215,000 children died of rotavirus infections in 2013, accounting for 37% of diarrhea-related deaths worldwide, 92% of which occurred in low and lower-middle income countries. Since 2009 the World Health Organization (WHO) recommends the use of rotavirus vaccines in all national immunization programs. This review compares rotavirus vaccine (RV) introductions and vaccine coverage by region, country income status and Gavi-eligibility from 2006-2016. Gross National Income data from the World Bank and surviving infant population from United Nations Population Division was obtained for 2016. Data from WHO were collected on rotavirus vaccine coverage, national immunization schedules, and new vaccine introductions for 2016 while estimated rotavirus deaths were collected for 2013, the last year of available WHO data. As of December 2016, the majority of countries (57%, 110/194) had not introduced universal rotavirus vaccine despite WHO's 2009 recommendation to do so. Countries in the WHO African region had the greatest proportion of introductions (37%, 31/84) by December 2016 and a great majority of these (77%, 24/31) were supported by new vaccine introduction (NVI) grants from Gavi. Almost half (48%) of global introductions were in low and lower-middle income Gavi-eligible and Gavi-graduating countries. Conversely, countries in the Southeast Asia WHO region and those not eligible for Gavi NVI support have been slow to introduce rotavirus vaccine. High-income countries, on average, had poorer rotavirus vaccine coverage compared to low and lower-middle income countries. The over-representation of African countries within the Gavi subset and high estimated rotavirus deaths in these African countries, likely explains why introduction efforts have been focused in this region. While much progress has been made with the integration and implementation of rotavirus vaccine into national immunization programs, 110 countries representing 69% of the global birth cohort

Seasonal influenza vaccine coverage among high-risk populations in Thailand, 2010-2012.

PubMed

Owusu, Jocelynn T; Prapasiri, Prabda; Ditsungnoen, Darunee; Leetongin, Grit; Yoocharoen, Pornsak; Rattanayot, Jarowee; Olsen, Sonja J; Muangchana, Charung

2015-01-29

The Advisory Committee on Immunization Practice of Thailand prioritizes seasonal influenza vaccinations for populations who are at highest risk for serious complications (pregnant women, children 6 months-2 years, persons ≥65 years, persons with chronic diseases, obese persons), and healthcare personnel and poultry cullers. The Thailand government purchases seasonal influenza vaccine for these groups. We assessed vaccination coverage among high-risk groups in Thailand from 2010 to 2012. National records on persons who received publicly purchased vaccines from 2010 to 2012 were analyzed by high-risk category. Denominator data from multiple sources were compared to calculate coverage. Vaccine coverage was defined as the proportion of individuals in each category who received the vaccine. Vaccine wastage was defined as the proportion of publicly purchased vaccines that were not used. From 2010 to 2012, 8.18 million influenza vaccines were publicly purchased (range, 2.37-3.29 million doses/year), and vaccine purchases increased 39% over these years. Vaccine wastage was 9.5%. Approximately 5.7 million (77%) vaccine doses were administered to persons ≥65 years and persons with chronic diseases, 1.4 million (19%) to healthcare personnel/poultry cullers, 82,570 (1.1%) to children 6 months-2 years, 78,885 (1.1%) to obese persons, 26,481 (0.4%) to mentally disabled persons, and 17,787 (0.2%) to pregnant women. Between 2010 and 2012, coverage increased among persons with chronic diseases (8.6% versus 14%; p<0.01) and persons ≥65 years (12%, versus 20%; p<0.01); however, coverage decreased for mentally disabled persons (6.1% versus 4.9%; p<0.01), children 6 months-2 years (2.3% versus 0.9%; p<0.01), pregnant women (1.1% versus 0.9%; p<0.01), and obese persons (0.2% versus 0.1%; p<0.01). From 2010 to 2012, the availability of publicly purchased vaccines increased. While coverage remained low for all target groups, coverage was highest among persons ≥65 years and persons

Human papillomavirus vaccination coverage using two-dose or three-dose schedule criteria.

PubMed

Lin, Xia; Rodgers, Loren; Zhu, Liping; Stokley, Shannon; Meites, Elissa; Markowitz, Lauri E

2017-10-13

In October 2016, the Advisory Committee on Immunization Practices (ACIP) updated the human papillomavirus (HPV) vaccination recommendation to include a 2-dose schedule for U.S. adolescents initiating the vaccine series before their 15th birthday. We analyzed records for >4million persons aged 9-17years receiving any HPV vaccine by the end of each quarter during January 1, 2014-September 30, 2016 from six Immunization Information Systems Sentinel Sites, and reclassified HPV vaccination up-to-date coverage according to the updated recommendations. Compared with HPV vaccination up-to-date coverage by the 3-dose schedule only, including criteria for either a 2-dose or 3-dose schedule increased up-to-date coverage in 11-12, 13-14, and 15-17 year-olds by 4.5-8.5 percentage points. The difference between 3-dose up-to-date coverage and 2- or 3-dose up-to-date coverage was greatest in late 2016. These data provide baseline HPV vaccination coverage using current ACIP recommendations. Published by Elsevier Ltd.

Routine Vaccination Coverage in Northern Nigeria: Results from 40 District-Level Cluster Surveys, 2014-2015

PubMed Central

Ogbuanu, Ikechukwu U.; Adegoke, Oluwasegun J.; Scobie, Heather M.; Uba, Belinda V.; Wannemuehler, Kathleen A.; Ruiz, Alicia; Elmousaad, Hashim; Ohuabunwo, Chima J.; Mustafa, Mahmud; Nguku, Patrick; Waziri, Ndadilnasiya Endie; Vertefeuille, John F.

2016-01-01

Background Despite recent success towards controlling poliovirus transmission, Nigeria has struggled to achieve uniformly high routine vaccination coverage. A lack of reliable vaccination coverage data at the operational level makes it challenging to target program improvement. To reliably estimate vaccination coverage, we conducted district-level vaccine coverage surveys using a pre-existing infrastructure of polio technical staff in northern Nigeria. Methods Household-level cluster surveys were conducted in 40 polio high risk districts of Nigeria during 2014–2015. Global positioning system technology and intensive supervision by a pool of qualified technical staff were used to ensure high survey quality. Vaccination status of children aged 12–23 months was documented based on vaccination card or caretaker’s recall. District-level coverage estimates were calculated using survey methods. Results Data from 7,815 children across 40 districts were analyzed. District-level coverage with the third dose of diphtheria-pertussis-tetanus vaccine (DPT3) ranged widely from 1–63%, with all districts having DPT3 coverage below the target of 80%. Median coverage across all districts for each of eight vaccine doses (1 Bacille Calmette-Guérin dose, 3 DPT doses, 3 oral poliovirus vaccine doses, and 1 measles vaccine dose) was <50%. DPT3 coverage by survey was substantially lower (range: 28%–139%) than the 2013 administrative coverage reported among children aged <12 months. Common reported reasons for non-vaccination included lack of knowledge about vaccines and vaccination services (50%) and factors related to access to routine immunization services (15%). Conclusions Survey results highlighted vaccine coverage gaps that were systematically underestimated by administrative reporting across 40 polio high risk districts in northern Nigeria. Given the limitations of administrative coverage data, our approach to conducting quality district-level coverage surveys and

Use of the 1 tuberculin unit (TU) Mantoux test in the assessment of tuberculous infection in children following neonatal BCG vaccination.

PubMed

Hoskyns, E W; Simpson, H; Monk, P

1994-10-01

BCG vaccination alters the response to tuberculin testing and influences the potential validity of the Heaf test in the diagnosis of tuberculosis. This study used a purified protein derivative 1 tuberculin unit (TU) Mantoux test with a cut off of 5 mm induration as an indicator of tuberculous infection in high risk children to determine whether this would distinguish infection from previous neonatal BCG vaccination. Children at high risk of tuberculosis on chest radiography, Heaf test, or contact history who had been screened in the contact tracing clinic and referred for further assessment were included in the study. After clinical examination, chest radiography, and Mantoux testing they were assigned to three groups (tuberculous disease, chemoprophylaxis, or no treatment) and followed up for 6-24 months in the outpatient clinic and subsequently by postal questionnaire. Comparison of the Heaf and Mantoux tests showed a difference in the results with 82% of cases positive by the Heaf test and 59% positive by the Mantoux test. Using the Mantoux test result in combination with clinical and radiographic findings 194 children were allocated to the three groups as follows: primary tuberculosis (5), chemoprophylaxis (101), no treatment (88). During follow up for a mean (range) time of 46 (11-102) months four additional cases received treatment for primary tuberculosis, two in the chemoprophylaxis group and two in the untreated group. The use of the 1 TU Mantoux test after neonatal BCG vaccination reduced the number of children receiving treatment from 129 to 93-that is, by 36%. Although the numbers are small, there was no increase in the later development of tuberculosis.

Health newscasts for increasing influenza vaccination coverage: an inductive reasoning game approach.

PubMed

Breban, Romulus

2011-01-01

Both pandemic and seasonal influenza are receiving more attention from mass media than ever before. Topics such as epidemic severity and vaccination are changing the way in which we perceive the utility of disease prevention. Voluntary influenza vaccination has been recently modeled using inductive reasoning games. It has thus been found that severe epidemics may occur because individuals do not vaccinate and, instead, attempt to benefit from the immunity of their peers. Such epidemics could be prevented by voluntary vaccination if incentives were offered. However, a key assumption has been that individuals make vaccination decisions based on whether there was an epidemic each influenza season; no other epidemiological information is available to them. In this work, we relax this assumption and investigate the consequences of making more informed vaccination decisions while no incentives are offered. We obtain three major results. First, individuals will not cooperate enough to constantly prevent influenza epidemics through voluntary vaccination no matter how much they learned about influenza epidemiology. Second, broadcasting epidemiological information richer than whether an epidemic occurred may stabilize the vaccination coverage and suppress severe influenza epidemics. Third, the stable vaccination coverage follows the trend of the perceived benefit of vaccination. However, increasing the amount of epidemiological information released to the public may either increase or decrease the perceived benefit of vaccination. We discuss three scenarios where individuals know, in addition to whether there was an epidemic, (i) the incidence, (ii) the vaccination coverage and (iii) both the incidence and the vaccination coverage, every influenza season. We show that broadcasting both the incidence and the vaccination coverage could yield either better or worse vaccination coverage than broadcasting each piece of information on its own.

Health Newscasts for Increasing Influenza Vaccination Coverage: An Inductive Reasoning Game Approach

PubMed Central

Breban, Romulus

2011-01-01

Both pandemic and seasonal influenza are receiving more attention from mass media than ever before. Topics such as epidemic severity and vaccination are changing the way in which we perceive the utility of disease prevention. Voluntary influenza vaccination has been recently modeled using inductive reasoning games. It has thus been found that severe epidemics may occur because individuals do not vaccinate and, instead, attempt to benefit from the immunity of their peers. Such epidemics could be prevented by voluntary vaccination if incentives were offered. However, a key assumption has been that individuals make vaccination decisions based on whether there was an epidemic each influenza season; no other epidemiological information is available to them. In this work, we relax this assumption and investigate the consequences of making more informed vaccination decisions while no incentives are offered. We obtain three major results. First, individuals will not cooperate enough to constantly prevent influenza epidemics through voluntary vaccination no matter how much they learned about influenza epidemiology. Second, broadcasting epidemiological information richer than whether an epidemic occurred may stabilize the vaccination coverage and suppress severe influenza epidemics. Third, the stable vaccination coverage follows the trend of the perceived benefit of vaccination. However, increasing the amount of epidemiological information released to the public may either increase or decrease the perceived benefit of vaccination. We discuss three scenarios where individuals know, in addition to whether there was an epidemic, (i) the incidence, (ii) the vaccination coverage and (iii) both the incidence and the vaccination coverage, every influenza season. We show that broadcasting both the incidence and the vaccination coverage could yield either better or worse vaccination coverage than broadcasting each piece of information on its own. PMID:22205944

Vaccination coverage of children with rare genetic diseases and attitudes of their parents toward vaccines

PubMed Central

Esposito, Susanna; Cerutti, Marta; Milani, Donatella; Menni, Francesca; Principi, Nicola

2016-01-01

Abstract Despite the fact that the achievement of appropriate immunization coverage for routine vaccines is a priority for health authorities worldwide, vaccination delays or missed opportunities for immunization are common in children with chronic diseases. The main aim of this cross-sectional study was to evaluate immunization coverage and the timeliness of vaccination in children suffering from 3 different rare genetic diseases: Rubinstein-Taybi syndrome (RSTS), Sotos syndrome (SS), and Beckwith-Wiedemann syndrome (BWS). A total of 57 children with genetic diseases (15 with RSTS, 14 children with SS, and 28 with BWS) and 57 healthy controls with similar characteristics were enrolled. The coverage of all the recommended vaccines in children with genetic syndromes was significantly lower than that observed in healthy controls (p < 0.05 for all the comparisons). However, when vaccinated, all of the patients, independent of the genetic syndrome from which they suffer, were administered the primary series and the booster doses at a similar time to healthy controls. In comparison with parents of healthy controls, parents of children with genetic diseases were found to more frequently have negative attitudes toward vaccination (p < 0.05 for all the comparisons), mainly for fear of the emergence of adverse events or deterioration of the underlying disease. This study shows that vaccination coverage is poor in pediatric patients with RSTS, BWS, and SS and significantly lower than that observed in healthy children. These results highlight the need for educational programs specifically aimed at both parents and pediatricians to increase immunization coverage in children with these rare genetic diseases. PMID:26337545

Vaccination coverage in the US Commonwealth of the Northern Mariana Islands, 2005.

PubMed

Luman, Elizabeth T; Sablan, Mariana; Anaya, Gabriel; Stokley, Shannon; McCauley, Mary Mason; Shaw, Kate M; Salazar, Angela; Balajadia, Ron; Chaine, Jean Paul; Duncan, Richard

2007-01-01

In July 2005, a house-to-house survey was conducted to determine vaccination coverage achieved through routine health services on the three inhabited islands (Saipan, Rota, and Tinian) of the US Commonwealth of the Northern Mariana Islands (CNMI). A population-based cluster survey was conducted on Saipan; clusters and households were selected by systematic random sampling. On the smaller islands of Rota and Tinian, all households were visited. Vaccination histories and demographic information were obtained during household interview for all children aged 19-35 months, children aged 6 years, and adults aged 65 years and older. Vaccination histories for children were supplemented by hospital/clinic records and an electronic vaccination registry. Among 295 children aged 19-35 months, estimated coverage with the primary vaccination series was 80 percent; coverage with individual vaccines was generally higher. Among 193 children aged 6 years, coverage for vaccines required at school-aged was 83 percent. Among 226 adults aged 65 years and older, 52 percent received influenza vaccine during the previous season while 21 percent had ever received pneumococcal vaccine. The CNMI has achieved the US Healthy People 2010 objective of 80 percent coverage for the standard vaccination series among children aged 19-35 months. High coverage levels among 6-year-old children may reflect the benefit of school entry requirements. Influenza and pneumococcal vaccination among older adults remains low. Efforts to ensure that children and older adults throughout the CNMI are equally well-protected should continue. Strategies to address parental awareness of vaccinations that are due should be explored and may be facilitated by upgrading the electronic vaccination registry.

Comparative assessment of immunization coverage of migrant children between national immunization program vaccines and non-national immunization program vaccines in East China

PubMed Central

Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing

2015-01-01

This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%– vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage. PMID:25760670

Protective efficacy of BCG against leprosy in São Paulo.

PubMed

Lombardi, C; Pedrazzani, E S; Pedrazzani, J C; Filho, P F; Zicker, F

1996-03-01

The case-control study reported here evaluated the protective effect of BCG vaccine against leprosy in São Paulo, Brazil. Seventy-eight patients under age 16 who had been diagnosed as having leprosy (cases) and 385 healthy individuals (controls) were selected and matched by sex, age, place of residence, and type of exposure to leprosy (intradomiciliary or extradomiciliary). The cases were drawn from an active patient registry and from a group of new leprosy cases treated at 50 health centers in the cities of Bauru and Ribeirão Preto in the state of São Paulo. In order to estimate the protective effect of BCG, the prevalences of BCG scars in cases and controls were compared. The presence of one or more scars was associated with an estimated protective efficacy of 90% (95% confidence interval: 78% to 96%). Stratified analysis by age group, sex, socioeconomic level, and clinical form of the disease revealed no significant differences in the protection provided by the vaccine. However, it seems clear that more data will be needed in order to accurately assess the true relevance of BCG for leprosy control programs.

Effect of Experimental Parameters on Alginate/Chitosan Microparticles for BCG Encapsulation

PubMed Central

Caetano, Liliana A.; Almeida, António J.; Gonçalves, Lídia M.D.

2016-01-01

The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal route. BCG was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. For comparison purposes, similar formulations were prepared with high shear homogenization and sonication. Additional optimization studies were conducted with polymers of different quality specifications in a wide range of pH values, and with three different cryoprotectors. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. Chitosan addition to BCG shifted the bacilli surface charge from negative zeta potential values to strongly positive ones. Chitosan of low molecular weight produced particle suspensions of lower size distribution and higher stability, allowing efficient BCG encapsulation and biocompatibility. Particle formulation consistency was improved when the availability of functional groups from alginate and chitosan was close to stoichiometric proportion. Thus, the herein described microparticulate system constitutes a promising strategy to deliver BCG vaccine by the intranasal route. PMID:27187418

Immunisation coverage of adults: a vaccination counselling campaign in the pharmacies in Switzerland.

PubMed

Valeri, Fabio; Hatz, Christoph; Jordan, Dominique; Leuthold, Claudine; Czock, Astrid; Lang, Phung

2014-01-01

To assess vaccination coverage for adults living in Switzerland. Through a media campaign, the general population was invited during 1 month to bring their vaccination certificates to the pharmacies to have their immunisation status evaluated with the software viavac©, and to complete a questionnaire. A total of 496 pharmacies in Switzerland participated in the campaign, of which 284 (57%) submitted valid vaccination information. From a total of 3,634 participants in the campaign, there were 3,291 valid cases (participants born ≤ 1992) and 1,011 questionnaires completed. Vaccination coverage for the participants was 45.9% and 34.6% for five and six doses of diphtheria, 56.4% and 44.0% for tetanus and 66.3% and 48.0% for polio, respectively. Coverage estimates for one and two doses of measles vaccine were 76.5% and 49.4%, respectively, for the birth cohort 1967-1992 and 4.0% and 0.8%, respectively, for the cohort ≤ 1966. There was a significant difference in coverage for most vaccinations between the two aforementioned birth cohorts. A plot of the measles vaccine coverage over time shows that the increase in coverage correlated with policy changes in the Swiss Immunisation Schedule. Despite selection bias and low participation, this study indicates that vaccination coverage for the basic recommended immunisations in the adult population in Switzerland is suboptimal. More efforts using various means and methods are needed to increase immunisation coverage in adolescents before they leave school. An established method to determine vaccination coverage for the general population could provide invaluable insights into the effects of changes in vaccination policies and disease outbreaks.

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

PubMed

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.

Country-level predictors of vaccination coverage and inequalities in Gavi-supported countries.

PubMed

Arsenault, Catherine; Johri, Mira; Nandi, Arijit; Mendoza Rodríguez, José M; Hansen, Peter M; Harper, Sam

2017-04-25

Important inequalities in childhood vaccination coverage persist between countries and population groups. Understanding why some countries achieve higher and more equitable levels of coverage is crucial to redress these inequalities. In this study, we explored the country-level determinants of (1) coverage of the third dose of diphtheria-tetanus-pertussis- (DTP3) containing vaccine and (2) within-country inequalities in DTP3 coverage in 45 countries supported by Gavi, the Vaccine Alliance. We used data from the most recent Demographic and Health Surveys (DHS) conducted between 2005 and 2014. We measured national DTP3 coverage and the slope index of inequality in DTP3 coverage with respect to household wealth, maternal education, and multidimensional poverty. We collated data on country health systems, health financing, governance and geographic and sociocultural contexts from published sources. We used meta-regressions to assess the relationship between these country-level factors and variations in DTP3 coverage and inequalities. To validate our findings, we repeated these analyses for coverage with measles-containing vaccine (MCV). We found considerable heterogeneity in DTP3 coverage and in the magnitude of inequalities across countries. Results for MCV were consistent with those from DTP3. Political stability, gender equality and smaller land surface were important predictors of higher and more equitable levels of DTP3 coverage. Inequalities in DTP3 coverage were also lower in countries receiving more external resources for health, with lower rates of out-of-pocket spending and with higher national coverage. Greater government spending on heath and lower linguistic fractionalization were also consistent with better vaccination outcomes. Improving vaccination coverage and reducing inequalities requires that policies and programs address critical social determinants of health including geographic and social exclusion, gender inequality and the availability of

From non school-based, co-payment to school-based, free Human Papillomavirus vaccination in Flanders (Belgium): a retrospective cohort study describing vaccination coverage, age-specific coverage and socio-economic inequalities.

PubMed

Lefevere, Eva; Theeten, Heidi; Hens, Niel; De Smet, Frank; Top, Geert; Van Damme, Pierre

2015-09-22

School-based, free HPV vaccination for girls in the first year of secondary school was introduced in Flanders (Belgium) in 2010. Before that, non school-based, co-payment vaccination for girls aged 12-18 was in place. We compared vaccination coverage, age-specific coverage and socio-economic inequalities in coverage - 3 important parameters contributing to the effectiveness of the vaccination programs - under both vaccination systems. We used retrospective administrative data from different sources. Our sample consisted of all female members of the National Alliance of Christian Mutualities born in 1995, 1996, 1998 or 1999 (N=66,664). For each vaccination system we described the cumulative proportion HPV vaccination initiation and completion over time. We used life table analysis to calculate age-specific rates of HPV vaccination initiation and completion. Analyses were done separately for higher income and low income groups. Under non school-based, co-payment vaccination the proportions HPV vaccination initiation and completion slowly rose over time. By age 17, the proportion HPV vaccination initiation/completion was 0.75 (95% CI 0.74-076)/0.66 (95% CI 0.65-0.67). The median age at vaccination initiation/completion was 14.4 years (95% CI 14.4-14.5)/15.4 years (95% CI 15.3-15.4). Socio-economic inequalities in coverage widened over time and with age. Under school-based, free vaccination rates of HPV vaccination initiation were substantially higher. By age 14,the proportion HPV vaccination initiation/completion was 0.90 (95% CI 0.90-0.90)/0.87 (95% CI 0.87-0.88). The median age at vaccination initiation/completion was 12.7 years (95% CI 12.7-12.7)/13.3 years (95% CI 13.3-13.3). Socio-economic inequalities in coverage and in age-specific coverage were substantially smaller. Copyright © 2015. Published by Elsevier Ltd.

Low coverage of central point vaccination against dog rabies in Bamako, Mali.

PubMed

Muthiani, Yvonne; Traoré, Abdallah; Mauti, Stephanie; Zinsstag, Jakob; Hattendorf, Jan

2015-06-15

Canine rabies remains an important public-health problem in Africa. Dog mass vaccination is the recommended method for rabies control and elimination. We report on the first small-scale mass dog vaccination campaign trial in Bamako, Mali. Our objective was to estimate coverage of the vaccination campaign and to quantify determinants of intervention effectiveness. In September 2013, a central point vaccination campaign--free of cost for dog owners--was carried out in 17 posts on three consecutive days within Bamako's Commune 1. Vaccination coverage and the proportion of ownerless dogs were estimated by combining mark-recapture household and transect surveys using Bayesian modeling. The estimated vaccination coverage was 17.6% (95% Credibility Interval, CI: 14.4-22.1%) which is far below the World Health Organization (WHO) recommended vaccination coverage of 70%. The Bayesian estimate for the owned dog population of Commune 1 was 3459 dogs (95% CI: 2786-4131) and the proportion of ownerless dogs was about 8%. The low coverage observed is primarily attributed to low participation by dog owners. Dog owners reported several reasons for not bringing their dogs to the vaccination posts. The most frequently reported reasons for non-attendance were lack of information (25%) and the inability to handle the dog (16%). For 37% of respondents, no clear reason was given for non-vaccination. Despite low coverage, the vaccination campaign in Bamako was relatively easy to implement, both in terms of logistics and organization. Almost half of the participating dog owners brought their pets on the first day of the campaign. Participatory stakeholder processes involving communities and local authorities are needed to identify effective communication channels and locally adapted vaccination strategies, which could include both central-point and door-to-door vaccination. Copyright © 2015 Elsevier B.V. All rights reserved.

Immune systems in developed and developing countries; implications for the design of vaccines that will work where BCG does not.

PubMed

Rook, Graham A W; Dheda, Keertan; Zumla, Alimuddin

2006-01-01

New vaccine candidates for tuberculosis are beginning to enter clinical trials. In this review we discuss issues surrounding the design of these candidates, and the way they were screened in animal models. First, screening vaccines for their ability to attenuate inevitably fatal tuberculosis in immunologically naïve mice might be leading to the selection of inappropriate candidates. We need to screen vaccines for their ability to stop the development of progressive disease, since this is what they must achieve in man. A solution to this problem is proposed. Secondly, we point out that some mouse models of tuberculosis in laboratories in developing countries, where exposure to environmental mycobacteria is large, mimic neglected aspects of human disease more closely than do low-dose infections in hyper-susceptible immunologically naïve mice in the USA or Europe. We need to think more about geographical differences in immunological experience, and these mouse models can help us. Thirdly, we conclude that in developing countries where BCG fails this is not because there is too little Th1 response, but rather because the Th1 response is rendered ineffective and immunopathological by other subversive mechanisms, including IL-4 responses and inappropriate regulatory T cell function. Therefore, we suggest that vaccines that will work in those countries might need to have immunoregulatory properties that can switch off pre-existing subversive mechanisms, and block their development in the future. The development of such vaccines, that might work where BCG does not, will require a greater understanding of the roles of the many types of regulatory T cell in tuberculosis.

Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis.

PubMed

Williams, Ann; Hatch, Graham J; Clark, Simon O; Gooch, Karen E; Hatch, Kim A; Hall, Graham A; Huygen, Kris; Ottenhoff, Tom H M; Franken, Kees L M C; Andersen, Peter; Doherty, T Mark; Kaufmann, Stefan H E; Grode, Leander; Seiler, Peter; Martin, Carlos; Gicquel, Brigitte; Cole, Stewart T; Brodin, Priscille; Pym, Alexander S; Dalemans, Wilfried; Cohen, Joe; Lobet, Yves; Goonetilleke, Nilu; McShane, Helen; Hill, Adrian; Parish, Tanya; Smith, Debbie; Stoker, Neil G; Lowrie, Douglas B; Källenius, Gunilla; Svenson, Stefan; Pawlowski, Andrzej; Blake, Karen; Marsh, Philip D

2005-01-01

The TB Vaccine Cluster project funded by the EU Fifth Framework programme aims to provide novel vaccines against tuberculosis that are suitable for evaluation in humans. This paper describes the studies of the protective efficacy of vaccines in a guinea pig aerosol-infection model of primary tuberculosis. The objective was to conduct comparative evaluations of vaccines that had previously demonstrated efficacy in other animal models. Groups of 6 guinea pigs were immunized with vaccines provided by the relevant EU Vaccine Cluster partners. Survival over 17 or 26 weeks was used as the principal measure of vaccine efficacy following aerosol challenge with H37Rv. Counts of mycobacteria in lungs and spleens, and histopathological changes in the lungs, were also used to provide evidence of protection. A total of 24 vaccines were evaluated in 4 experiments each of a different design. A heterologous prime-boost strategy of DNA and MVA, each expressing Ag85A and a fusion protein of ESAT-6 and Ag85B in adjuvant, protected the guinea pigs to the same extent as BCG. Genetically modified BCG vaccines and boosted BCG strategies also protected guinea pigs to the same extent as BCG but not statistically significantly better. A relatively high aerosol-challenge dose and evaluation over a protracted time post-challenge allowed superior protection over BCG to be demonstrated by BCG boosted with MVA and fowl pox vectors expressing Ag85A.

Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection

PubMed Central

2011-01-01

Background Studies of Mycobacterium bovis BCG strains used in different countries and vaccination programs show clear variations in the genomes and immune protective properties of BCG strains. The aim of this study was to characterise the genomic and immune proteomic profile of the BCG 1931 strain used in Mexico. Results BCG Mexico 1931 has a circular chromosome of 4,350,386 bp with a G+C content and numbers of genes and pseudogenes similar to those of BCG Tokyo and BCG Pasteur. BCG Mexico 1931 lacks Region of Difference 1 (RD1), RD2 and N-RD18 and one copy of IS6110, indicating that BCG Mexico 1931 belongs to DU2 group IV within the BCG vaccine genealogy. In addition, this strain contains three new RDs, which are 53 (RDMex01), 655 (RDMex02) and 2,847 bp (REDMex03) long, and 55 single-nucleotide polymorphisms representing non-synonymous mutations compared to BCG Pasteur and BCG Tokyo. In a comparative proteomic analysis, the BCG Mexico 1931, Danish, Phipps and Tokyo strains showed 812, 794, 791 and 701 protein spots, respectively. The same analysis showed that BCG Mexico 1931 shares 62% of its protein spots with the BCG Danish strain, 61% with the BCG Phipps strain and only 48% with the BCG Tokyo strain. Thirty-nine reactive spots were detected in BCG Mexico 1931 using sera from subjects with active tuberculosis infections and positive tuberculin skin tests. Conclusions BCG Mexico 1931 has a smaller genome than the BCG Pasteur and BCG Tokyo strains. Two specific deletions in BCG Mexico 1931 are described (RDMex02 and RDMex03). The loss of RDMex02 (fadD23) is associated with enhanced macrophage binding and RDMex03 contains genes that may be involved in regulatory pathways. We also describe new antigenic proteins for the first time. PMID:21981907

[The protective efficacy of BCG against leprosy in São Paulo, Brazil].

PubMed

Lombardi, C; Pedrazzani, E S; Pedrazzani, J C; Ferreira Filho, P; Zicker, F

1995-11-01

The protection against leprosy conferred by BCG vaccination was evaluated in a case-control study. Selected for the study were 97 patients under 16 years of age who had been diagnosed with leprosy (cases) and 385 healthy persons (controls), who were matched according to sex, age, place of residence, and type of contact (intra- or extradomicilliary). The cases were selected from a register of active cases as well as a series of new leprosy patients treated in 50 centers in the city of São Paulo, Brasil. To estimate the protective effect of BCG, the prevalences of BCG scars among cases and controls were compared. The presence of one or more scars was associated with a protective efficacy of 90% (95% confidence interval: 78%-96%). Stratified analysis by age group, sex, socioeconomic level, and clinical form of leprosy did not reveal any important differences in the protection conferred by the vaccine. The significance of these findings and the appropriateness of using BCG in leprosy control programs is discussed.

Biochemical characteristics among Mycobacterium bovis BCG substrains.

PubMed

Hayashi, Daisuke; Takii, Takemasa; Mukai, Tetsu; Makino, Masahiko; Yasuda, Emi; Horita, Yasuhiro; Yamamoto, Ryuji; Fujiwara, Akiko; Kanai, Keita; Kondo, Maki; Kawarazaki, Aya; Yano, Ikuya; Yamamoto, Saburo; Onozaki, Kikuo

2010-05-01

In order to evaluate the biochemical characteristics of 14 substrains of Mycobacterium bovis bacillus Calmette Guérin (BCG) - Russia, Moreau, Japan, Sweden, Birkhaug, Danish, Glaxo, Mexico, Tice, Connaught, Montreal, Phipps, Australia and Pasteur - we performed eight different biochemical tests, including those for nitrate reduction, catalase, niacin accumulation, urease, Tween 80 hydrolysis, pyrazinamidase, p-amino salicylate degradation and resistance to thiophene 2-carboxylic acid hydrazide. Catalase activities of the substrains were all low. Data for nitrate reduction, niacin accumulation, Tween 80 hydrolysis, susceptibility to hydrogen peroxide and nitrate, and optimal pH for growth were all variable among these substrains. These findings suggest that the heterogeneities of biochemical characteristics are relevant to the differences in resistance of BCG substrains to environmental stress. The study also contributes to the re-evaluation of BCG substrains for use as vaccines.

Seasonal influenza vaccine coverage among high-risk populations in Thailand, 2010–2012

PubMed Central

Owusu, Jocelynn T.; Prapasiri, Prabda; Ditsungnoen, Darunee; Leetongin, Grit; Yoocharoen, Pornsak; Rattanayot, Jarowee; Olsen, Sonja J.; Muangchana, Charung

2015-01-01

Background The Advisory Committee on Immunization Practice of Thailand prioritizes seasonal influenza vaccinations for populations who are at highest risk for serious complications (pregnant women, children 6 months–2 years, persons ≥65 years, persons with chronic diseases, obese persons), and health-care personnel and poultry cullers. The Thailand government purchases seasonal influenza vaccine for these groups. We assessed vaccination coverage among high-risk groups in Thailand from 2010 to 2012. Methods National records on persons who received publicly purchased vaccines from 2010 to 2012 were analyzed by high-risk category. Denominator data from multiple sources were compared to calculate coverage. Vaccine coverage was defined as the proportion of individuals in each category who received the vaccine. Vaccine wastage was defined as the proportion of publicly purchased vaccines that were not used. Results From 2010 to 2012, 8.18 million influenza vaccines were publicly purchased (range, 2.37–3.29 million doses/year), and vaccine purchases increased 39% over these years. Vaccine wastage was 9.5%. Approximately 5.7 million (77%) vaccine doses were administered to persons ≥65 years and persons with chronic diseases, 1.4 million (19%) to healthcare personnel/poultry cullers, 82,570 (1.1%) to children 6 months–2 years, 78,885 (1.1%) to obese persons, 26,481 (0.4%) to mentally disabled persons, and 17,787 (0.2%) to pregnant women. Between 2010 and 2012, coverage increased among persons with chronic diseases (8.6% versus 14%; p < 0.01) and persons ≥65 years (12%, versus 20%; p < 0.01); however, coverage decreased for mentally disabled persons (6.1% versus 4.9%; p < 0.01), children 6 months–2 years (2.3% versus 0.9%; p < 0.01), pregnant women (1.1% versus 0.9%; p < 0.01), and obese persons (0.2% versus 0.1%; p < 0.01). Conclusions From 2010 to 2012, the availability of publicly purchased vaccines increased. While coverage remained low for all target groups

Vaccination Coverage Among Children Aged 2 Years - U.S. Affiliated Pacific Islands, April-October, 2016.

PubMed

Tippins, Ashley; Murthy, Neil; Meghani, Mehreen; Solsman, Amy; Apaisam, Carter; Basilius, Merlyn; Eckert, Maribeth; Judicpa, Peter; Masunu, Yolanda; Pistotnik, Kelsey; Pedro, Daisy; Sasamoto, Jeremy; Underwood, J Michael

2018-05-25

Vaccine-preventable diseases (VPDs) cause substantial morbidity and mortality in the United States Affiliated Pacific Islands (USAPI).* CDC collaborates with USAPI immunization programs to monitor vaccination coverage. In 2016, † USAPI immunization programs and CDC piloted a method for estimating up-to-date status among children aged 2 years using medical record abstraction to ascertain regional vaccination coverage. This was the first concurrent assessment of childhood vaccination coverage across five USAPI jurisdictions (American Samoa; Chuuk State, Federated States of Micronesia [FSM]; Commonwealth of the Northern Mariana Islands [CNMI]; Republic of the Marshall Islands [RMI]; and Republic of Palau). § Differences in vaccination coverage between main and outer islands ¶ were assessed for two jurisdictions where data were adequate.** Series coverage in this report includes the following doses of vaccines: ≥4 doses of diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP); ≥3 doses of inactivated poliovirus vaccine (IPV); ≥1 dose of measles, mumps, and rubella vaccine (MMR); ≥3 doses of Haemophilus influenzae type B (Hib) vaccine; ≥3 doses of hepatitis B (HepB) vaccine; and ≥4 doses of pneumococcal conjugate vaccine (PCV); i.e., 4:3:1:3:3:4. Coverage with ≥3 doses of rotavirus vaccine was also assessed. Completion of the recommended series of each of these vaccines †† was <90% in all jurisdictions except Palau. Coverage with the full recommended six-vaccine series (4:3:1:3:3:4) ranged from 19.5% (Chuuk) to 69.1% (Palau). In RMI and Chuuk, coverage was lower in the outer islands than in the main islands for most vaccines, with differences ranging from 0.9 to 66.8 percentage points. Medical record abstraction enabled rapid vaccination coverage assessment and timely dissemination of results to guide programmatic decision-making. Effectively monitoring vaccination coverage, coupled with implementation of data-driven interventions

Cost-effectiveness of novel vaccines for tuberculosis control: a decision analysis study

PubMed Central

2011-01-01

Background The development of a successful new tuberculosis (TB) vaccine would circumvent many limitations of current diagnostic and treatment practices. However, vaccine development is complex and costly. We aimed to assess the potential cost effectiveness of novel vaccines for TB control in a sub-Saharan African country - Zambia - relative to the existing strategy of directly observed treatment, short course (DOTS) and current level of bacille Calmette-Guérin (BCG) vaccination coverage. Methods We conducted a decision analysis model-based simulation from the societal perspective, with a 3% discount rate and all costs expressed in 2007 US dollars. Health outcomes and costs were projected over a 30-year period, for persons born in Zambia (population 11,478,000 in 2005) in year 1. Initial development costs for single vaccination and prime-boost strategies were prorated to the Zambian share (0.398%) of global BCG vaccine coverage for newborns. Main outcome measures were TB-related morbidity, mortality, and costs over a range of potential scenarios for vaccine efficacy. Results Relative to the status quo strategy, a BCG replacement vaccine administered at birth, with 70% efficacy in preventing rapid progression to TB disease after initial infection, is estimated to avert 932 TB cases and 422 TB-related deaths (prevention of 199 cases/100,000 vaccinated, and 90 deaths/100,000 vaccinated). This would result in estimated net savings of $3.6 million over 30 years for 468,073 Zambians born in year 1 of the simulation. The addition of a booster at age 10 results in estimated savings of $5.6 million compared to the status quo, averting 1,863 TB cases and 1,011 TB-related deaths (prevention of 398 cases/100,000 vaccinated, and of 216 deaths/100,000 vaccinated). With vaccination at birth alone, net savings would be realized within 1 year, whereas the prime-boost strategy would require an additional 5 years to realize savings, reflecting a greater initial development cost

Vaccination coverage for measles, mumps and rubella in anthroposophical schools in Gelderland, The Netherlands.

PubMed

Klomp, Judith H E; van Lier, Alies; Ruijs, Wilhelmina L M

2015-06-01

Social clustering of unvaccinated children in anthroposophical schools occurs, as inferred from various measles outbreaks that can be traced to these schools. However, accurate vaccination coverage data of anthroposophical schools are not widely available. In 2012, we performed a survey to estimate the vaccination coverage in three different grades of 11 anthroposophical schools in Gelderland, The Netherlands. We also gauged the opinion on childhood vaccination of the parents and compared these with the results of a national survey. In 2014, we were also able to obtain the registered total vaccination coverage per school from the national vaccination register to compare this with our survey data. The self-reported MMR vaccination coverage (2012) in the three grades of the schools in our study was 83% (range 45-100% per school). The registered total vaccination coverage (2014) was 78% (range 59-88% per school). The 95% confidence intervals of the two different vaccination coverages overlap for all schools. The parents in this study were less convinced about the beneficial effect of vaccinations and more worried about the possible side effects of vaccination compared with parents in general. Despite high overall vaccination coverage, the WHO goal to eliminate measles and rubella will not easily be achieved when social clustering of unvaccinated children in anthroposophical schools remains. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Coverage with Tetanus, Diphtheria, and Acellular Pertussis Vaccine and Influenza Vaccine Among Pregnant Women - Minnesota, March 2013-December 2014.

PubMed

Barber, Alexandra; Muscoplat, Miriam Halstead; Fedorowicz, Anna

2017-01-20

Pertussis and influenza infections can result in severe disease in infants. The diphtheria, tetanus, acellular pertussis (DTaP) vaccine is recommended for infants beginning at age 2 months, and influenza vaccine is recommended for infants aged ≥6 months. Vaccination of pregnant women induces the production of antibodies that are transferred across the placenta to the fetus and provide passive protection until infants are old enough to receive DTaP and influenza vaccines (1-3). To protect young infants before they are age-eligible for vaccination, the Advisory Committee on Immunization Practices (ACIP) has recommended since 2004 that all women who are or will be pregnant during influenza season receive inactivated influenza vaccine (1), and since 2013 that all pregnant women receive the tetanus, diphtheria, acellular pertussis (Tdap) vaccine (3). Tdap and influenza vaccination coverage was assessed among pregnant women in Minnesota. Vital records data containing maternal demographic characteristics, prenatal care data, and delivery payment methods were matched with vaccination data from the Minnesota Immunization Information Connection (MIIC) to assess vaccination coverage. MIIC stores vaccination records for Minnesota residents. Overall, coverage with Tdap vaccine was 58.2% and with influenza vaccine was 45.9%. Coverage was higher for each vaccine among women who received adequate prenatal care compared with those who received inadequate or intermediate care, based on the initiation of prenatal care and the number of recommended prenatal visits attended. Coverage also varied based on mother's race, country of birth or region, and other demographic characteristics. Further study is needed to better understand the maternal vaccination disparities found in this study and to inform future public health initiatives.

Determinants of Vaccination Coverage and Consequences for Rabies Control in Bali, Indonesia.

PubMed

Arief, Riana A; Hampson, Katie; Jatikusumah, Andri; Widyastuti, Maria D W; Sunandar; Basri, Chaerul; Putra, Anak A G; Willyanto, Iwan; Estoepangestie, Agnes T S; Mardiana, I W; Kesuma, I K G N; Sumantra, I P; Doherty, Paul F; Salman, M D; Gilbert, Jeff; Unger, Fred

2016-01-01

Maintaining high vaccination coverage is key to successful rabies control, but mass dog vaccination can be challenging and population turnover erodes coverage. Declines in rabies incidence following successive island-wide vaccination campaigns in Bali suggest that prospects for controlling and ultimately eliminating rabies are good. Rabies, however, has continued to circulate at low levels. In the push to eliminate rabies from Bali, high coverage needs to be maintained across all areas of the island. We carried out door-to-door (DTD) questionnaire surveys ( n  = 10,352 dog-owning households) and photographic mark-recapture surveys (536 line transects, 2,597 observations of free-roaming dogs) in 2011-2012 to estimate dog population sizes and assess rabies vaccination coverage and dog demographic characteristics in Bali, Indonesia. The median number of dogs per subvillage unit ( banjar ) was 43 (range 0-307) for owned dogs estimated from the DTD survey and 17 (range 0-83) for unconfined dogs (including both owned and unowned) from transects. Vaccination coverage of owned dogs was significantly higher in adults (91.4%) compared to juveniles (<1 year, 43.9%), likely due to insufficient targeting of pups and from puppies born subsequent to vaccination campaigns. Juveniles had a 10-70 times greater risk of not being vaccinated in urban, suburban, and rural areas [combined odds ratios (ORs): 9.9-71.1, 95% CI: 8.6-96.0]. Free-roaming owned dogs were also 2-3 times more likely to be not vaccinated compared to those confined (combined Ors: 1.9-3.6, 95% CI: 1.4-5.4), with more dogs being confined in urban (71.2%) than in suburban (16.1%) and rural areas (8.0%). Vaccination coverage estimates from transects were also much lower (30.9%) than household surveys (83.6%), possibly due to loss of collars used to identify the vaccination status of free-roaming dogs, but these unconfined dogs may also include dogs that were unowned or more difficult to vaccinate. Overall

Determinants of Vaccination Coverage and Consequences for Rabies Control in Bali, Indonesia

PubMed Central

Arief, Riana A.; Hampson, Katie; Jatikusumah, Andri; Widyastuti, Maria D. W.; Sunandar; Basri, Chaerul; Putra, Anak A. G.; Willyanto, Iwan; Estoepangestie, Agnes T. S.; Mardiana, I. W.; Kesuma, I. K. G. N.; Sumantra, I. P.; Doherty, Paul F.; Salman, M. D.; Gilbert, Jeff; Unger, Fred

2017-01-01

Maintaining high vaccination coverage is key to successful rabies control, but mass dog vaccination can be challenging and population turnover erodes coverage. Declines in rabies incidence following successive island-wide vaccination campaigns in Bali suggest that prospects for controlling and ultimately eliminating rabies are good. Rabies, however, has continued to circulate at low levels. In the push to eliminate rabies from Bali, high coverage needs to be maintained across all areas of the island. We carried out door-to-door (DTD) questionnaire surveys (n = 10,352 dog-owning households) and photographic mark–recapture surveys (536 line transects, 2,597 observations of free-roaming dogs) in 2011–2012 to estimate dog population sizes and assess rabies vaccination coverage and dog demographic characteristics in Bali, Indonesia. The median number of dogs per subvillage unit (banjar) was 43 (range 0–307) for owned dogs estimated from the DTD survey and 17 (range 0–83) for unconfined dogs (including both owned and unowned) from transects. Vaccination coverage of owned dogs was significantly higher in adults (91.4%) compared to juveniles (<1 year, 43.9%), likely due to insufficient targeting of pups and from puppies born subsequent to vaccination campaigns. Juveniles had a 10–70 times greater risk of not being vaccinated in urban, suburban, and rural areas [combined odds ratios (ORs): 9.9–71.1, 95% CI: 8.6–96.0]. Free-roaming owned dogs were also 2–3 times more likely to be not vaccinated compared to those confined (combined Ors: 1.9–3.6, 95% CI: 1.4–5.4), with more dogs being confined in urban (71.2%) than in suburban (16.1%) and rural areas (8.0%). Vaccination coverage estimates from transects were also much lower (30.9%) than household surveys (83.6%), possibly due to loss of collars used to identify the vaccination status of free-roaming dogs, but these unconfined dogs may also include dogs that were unowned or more difficult to vaccinate

Strengthening routine immunization systems to improve global vaccination coverage.

PubMed

Sodha, S V; Dietz, V

2015-03-01

Global coverage with the third dose of diphtheria-tetanus-pertussis vaccine among children under 1 year of age stagnated at ∼ 83-84% during 2008-13. Annual World Health Organization and UNICEF-derived national vaccination coverage estimates. Incomplete vaccination is associated with poor socioeconomic status, lower education, non-use of maternal-child health services, living in conflict-affected areas, missed immunization opportunities and cancelled vaccination sessions. Vaccination platforms must expand to include older ages including the second year of life. Immunization programmes, including eradication and elimination initiatives such as those for polio and measles, must integrate within the broader health system. The Global Vaccine Action Plan (GVAP) 2011-20 is a framework for strengthening immunization systems, emphasizing country ownership, shared responsibility, equity, integration, sustainability and innovation. Immunization programmes should identify, monitor and evaluate gaps and interventions within the GVAP framework. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Impact of the CDC's Section 317 Immunization Grants Program funding on childhood vaccination coverage.

PubMed

Rein, David B; Honeycutt, Amanda A; Rojas-Smith, Lucia; Hersey, James C

2006-09-01

The Centers for Disease Control and Prevention's Section 317 Grants Program is the main source of funding for state and jurisdictional immunization programs, yet no study has evaluated its direct impact on vaccination coverage rates. Therefore, we used a fixed-effects model and data collected from 56 US jurisdictions to estimate the impact of Section 317 financial assistance immunization grants on childhood vaccination coverage rates from 1997 to 2003. Our results showed that increases in Section 317 funding were significantly and meaningfully associated with higher rates of vaccination coverage; a 10 dollars increase in per capita funding corresponded with a 1.6-percentage-point increase in vaccination coverage. Policymakers charged with funding public health programs should consider this study's findings, which indicate that money allocated to vaccine activities translates directly into higher vaccine coverage rates.

Influenza Vaccination Coverage among Adults in Korea: 2008–2009 to 2011–2012 Seasons

PubMed Central

Yang, Hye Jung; Cho, Sung-il

2014-01-01

The aim of this study was to examine seasonal and pandemic influenza vaccination coverage in adults from the 2008–2009 season to the 2011–2012 season, including pandemic and post-pandemic seasons in Korea. We collected data of self-reported vaccine use from the Korean Community Health Survey. We also collected information on socioeconomic status and health behaviors in subpopulations. We tested for linear trends among the data to investigate vaccine coverage before and after the pandemic; and multiple logistic regression analyses were performed to identify predictors of obtaining the influenza vaccination. The results revealed a steady increase in vaccination coverage in every subgroup during four consecutive seasons. The highest rate of vaccine coverage (43.6%) occurred two years after the pandemic. Factors associated with vaccine receipt were: older age; lower education level; lower income; and health behaviors such as regular walking and receiving a health check-up. Smoking and drinking alcohol were inversely associated with vaccination. Having a chronic health condition was also a strong predictor of vaccine receipt. Though vaccination coverage rates were high in high-risk groups; disparities in coverage rates were substantial; particularly in young adults. Interventions are needed to minimize the coverage gaps among subgroups and to improve overall vaccination rates. PMID:25429683

Cellular Immune Responses to Nine Mycobacterium tuberculosis Vaccine Candidates following Intranasal Vaccination

PubMed Central

Sable, Suraj B.; Cheruvu, Mani; Nandakumar, Subhadra; Sharma, Sunita; Bandyopadhyay, Kakali; Kellar, Kathryn L.; Posey, James E.; Plikaytis, Bonnie B.; Amara, Rama Rao; Shinnick, Thomas M.

2011-01-01

Background The identification of Mycobacterium tuberculosis vaccines that elicit a protective immune response in the lungs is important for the development of an effective vaccine against tuberculosis. Methods and Principal Findings In this study, a comparison of intranasal (i.n.) and subcutaneous (s.c.) vaccination with the BCG vaccine demonstrated that a single moderate dose delivered intranasally induced a stronger and sustained M. tuberculosis-specific T-cell response in lung parenchyma and cervical lymph nodes of BALB/c mice than vaccine delivered subcutaneously. Both BCG and a multicomponent subunit vaccine composed of nine M. tuberculosis recombinant proteins induced strong antigen-specific T-cell responses in various local and peripheral immune compartments. Among the nine recombinant proteins evaluated, the alanine proline rich antigen (Apa, Rv1860) was highly antigenic following i.n. BCG and immunogenic after vaccination with a combination of the nine recombinant antigens. The Apa-induced responses included induction of both type 1 and type 2 cytokines in the lungs as evaluated by ELISPOT and a multiplexed microsphere-based cytokine immunoassay. Of importance, i.n. subunit vaccination with Apa imparted significant protection in the lungs and spleen of mice against M. tuberculosis challenge. Despite observed differences in the frequencies and location of specific cytokine secreting T cells both BCG vaccination routes afforded comparable levels of protection in our study. Conclusion and Significance Overall, our findings support consideration and further evaluation of an intranasally targeted Apa-based vaccine to prevent tuberculosis. PMID:21799939

Association of Health Insurance Status and Vaccination Coverage among Adolescents 13-17 Years of Age.

PubMed

Lu, Peng-Jun; Yankey, David; Jeyarajah, Jenny; O'Halloran, Alissa; Fredua, Benjamin; Elam-Evans, Laurie D; Reagan-Steiner, Sarah

2018-04-01

To assess selected vaccination coverage among adolescents by health insurance status and other access-to-care characteristics. The 2015 National Immunization Survey-Teen data were used to assess vaccination coverage disparities among adolescents by health insurance status and other access-to-care variables. Multivariable logistic regression analysis and a predictive marginal modeling were conducted to evaluate associations between health insurance status and vaccination coverage. Overall, vaccination coverage was significantly lower among uninsured compared with insured adolescents for all vaccines assessed for except ≥3 doses of human papillomavirus vaccine (HPV) among male adolescents. Among adolescents 13-17 years of age, vaccination of uninsured compared with insured adolescents, respectively, for tetanus toxoid, reduced content diphtheria toxoid, and acellular pertussis vaccine was 77.4% vs 86.8%; for ≥1 dose of meningococcal conjugate vaccine was 72.9% vs 81.7%; for ≥1 dose of HPV was 38.8% vs 50.2% among male and 42.9% vs 63.8% among female adolescents; for 3 doses of HPV was 24.9% vs 42.8% among female adolescents. In addition, vaccination coverage differed by the following: type of insurance among insured adolescents, having a well-child visit at 11-12 years of age, and number of healthcare provider contacts in the past year. Uninsured were less likely than insured adolescents to be vaccinated for HPV (female: ≥1 dose and 3 doses; and male: ≥1 doses) after adjusting for confounding variables. Overall, vaccination coverage was lower among uninsured adolescents. HPV vaccination coverage was lower than tetanus toxoid, reduced content diphtheria toxoid, and acellular pertussis vaccine Tdap and meningococcal conjugate vaccine in both insured and uninsured adolescents. Wider implementation of effective evidence-based strategies is needed to help improve vaccination coverage among adolescents, particularly for those who are uninsured. Limitation of

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

PubMed

Mutua, Martin K; Kimani-Murage, Elizabeth; Ettarh, Remare R

2011-01-04

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. 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. 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 at 12 months was 41.3% and 51.8% with and without

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

PubMed Central

2011-01-01

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 at 12 months was 41

Measles vaccine coverage and factors related to uncompleted vaccination among 18-month-old and 36-month-old children in Kyoto, Japan.

PubMed

Matsumura, Takayo; Nakayama, Takeo; Okamoto, Shigeru; Ito, Hideko

2005-06-04

Due to low vaccine coverage, Japan has not only experienced outbreaks of measles but has also been exporting it overseas. This study aims to survey measles vaccine coverage and the factors uncompleted vaccination among community-living children. Subjects were the parents whose children had undergone either an 18-month or a 36-month checkup publicly provided by Kyoto City during November 2001 to January 2002. An anonymous self-administered questionnaire survey was conducted. The coverage was 73.2% among the 18-month-old children (n = 2707) and 88.9% among the 36-month-old children (n = 2340), respectively. The following characteristics of mothers were related to uncompleted measles vaccination: aged below 30, working, concerned about the adverse events of the vaccine, and had insufficient knowledge. Similarly, the following characteristics among children were related to uncompleted measles vaccination: not the first-born child, interacting with other children in group settings. The coverage was the lowest among the children whose mothers were concerned about the adverse events of the vaccine without proper knowledge of measles and its vaccination. To increase vaccine coverage among children, parents' awareness about measles and vaccination against it should be promoted, especially for working mothers. Efforts to enhance access to vaccination services and to communicate with parents about changing vaccination schedules are necessary.

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

PubMed

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 <32 weeks, birth weight <1000 g, known immunodeficiency, or no Danish-speaking parent. Follow-up information was collected through telephone interviews at 3 and 13 months of age. Subgroups of participants were offered blood sampling at 13 months of age. By 13 months of age, the parents and/or general practitioners of 5.6% (117/2089) of the children in the BCG group and 6.1% (126/2061) of the control group suspected 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.

Vaccine coverage estimation using a computerized vaccination registry with potential underreporting and a seroprevalence study.

PubMed

Breva, Lina Pérez; Domingo, Javier Díez; Martínez Beneito, Miguel Ángel; Barberà, Joan Puig

2015-04-27

To develop a method to estimate vaccination coverage using both a computerized vaccine registry with an unknown underreporting rate and a seroprevalence study. A real example of a meningococcal C conjugate vaccine (MCCV) coverage estimation is studied to illustrate the proposed methodology. We reviewed the Vaccine Information System of Valencia (Sistema de Información Vacunal, SIV) for the MCCV status of 1430 subjects aged 3-29 years as part of a seroprevalence study. When MCCV was not registered in SIV, subjects were classified into three groups (MCCV non-registered, no vaccination records and missing information) depending on the registry of other vaccines. A Bayesian model was developed to ascertain the percentage of MCCV-vaccinated subjects based on the meningococcal C seroprotection levels from the seroprevalence study. The seroprotection levels in subjects with no MCCV registered in SIV (358) were similar to those in subjects with MCCV registered (1072). This indicated a large proportion of vaccinated subjects with no MCCV registered. The estimated vaccine coverage was over 80% in all age groups, except >22 years, where it was 67.6% (95% CI: [54.0-80.4]), which corresponded to those aged over 13 years at the time of the catch-up campaign. An underreporting rate of 23.5-73.4%, depending on the age group, was estimated in those vaccinated in the 2002 catch-up campaign. The Bayesian model allowed for a more realistic estimation of MCCV uptake. In this example, we quantified the underreporting of a vaccine registry, especially occurring during a catch-up campaign that occurred at the establishment of the registry. Copyright © 2015. Published by Elsevier Ltd.

Global yellow fever vaccination coverage from 1970 to 2016: an adjusted retrospective analysis.

PubMed

Shearer, Freya M; Moyes, Catherine L; Pigott, David M; Brady, Oliver J; Marinho, Fatima; Deshpande, Aniruddha; Longbottom, Joshua; Browne, Annie J; Kraemer, Moritz U G; O'Reilly, Kathleen M; Hombach, Joachim; Yactayo, Sergio; de Araújo, Valdelaine E M; da Nóbrega, Aglaêr A; Mosser, Jonathan F; Stanaway, Jeffrey D; Lim, Stephen S; Hay, Simon I; Golding, Nick; Reiner, Robert C

2017-11-01

Substantial outbreaks of yellow fever in Angola and Brazil in the past 2 years, combined with global shortages in vaccine stockpiles, highlight a pressing need to assess present control strategies. The aims of this study were to estimate global yellow fever vaccination coverage from 1970 through to 2016 at high spatial resolution and to calculate the number of individuals still requiring vaccination to reach population coverage thresholds for outbreak prevention. For this adjusted retrospective analysis, we compiled data from a range of sources (eg, WHO reports and health-service-provider registeries) reporting on yellow fever vaccination activities between May 1, 1939, and Oct 29, 2016. To account for uncertainty in how vaccine campaigns were targeted, we calculated three population coverage values to encompass alternative scenarios. We combined these data with demographic information and tracked vaccination coverage through time to estimate the proportion of the population who had ever received a yellow fever vaccine for each second level administrative division across countries at risk of yellow fever virus transmission from 1970 to 2016. Overall, substantial increases in vaccine coverage have occurred since 1970, but notable gaps still exist in contemporary coverage within yellow fever risk zones. We estimate that between 393·7 million and 472·9 million people still require vaccination in areas at risk of yellow fever virus transmission to achieve the 80% population coverage threshold recommended by WHO; this represents between 43% and 52% of the population within yellow fever risk zones, compared with between 66% and 76% of the population who would have required vaccination in 1970. Our results highlight important gaps in yellow fever vaccination coverage, can contribute to improved quantification of outbreak risk, and help to guide planning of future vaccination efforts and emergency stockpiling. The Rhodes Trust, Bill & Melinda Gates Foundation, the

Socioeconomic inequalities and vaccination coverage: results of an immunisation coverage survey in 27 Brazilian capitals, 2007-2008.

PubMed

Barata, Rita Barradas; Ribeiro, Manoel Carlos Sampaio de Almeida; de Moraes, José Cássio; Flannery, Brendan

2012-10-01

Since 1988, Brazil's Unified Health System has sought to provide universal and equal access to immunisations. Inequalities in immunisation may be examined by contrasting vaccination coverage among children in the highest versus the lowest socioeconomic strata. The authors examined coverage with routine infant immunisations from a survey of Brazilian children according to socioeconomic stratum of residence census tract. The authors conducted a household cluster survey in census tracts systematically selected from five socioeconomic strata, according to average household income and head of household education, in 26 Brazilian capitals and the federal district. The authors calculated coverage with recommended vaccinations among children until 18 months of age, according to socioeconomic quintile of residence census tract, and examined factors associated with incomplete vaccination. Among 17,295 children with immunisation cards, 14,538 (82.6%) had received all recommended vaccinations by 18 months of age. Among children residing in census tracts in the highest socioeconomic stratum, 77.2% were completely immunised by 18 months of age versus 81.2%-86.2% of children residing in the four census tract quintiles with lower socioeconomic indicators (p<0.01). Census tracts in the highest socioeconomic quintile had significantly lower coverage for bacille Calmette-Guérin, oral polio and hepatitis B vaccines than those with lower socioeconomic indicators. In multivariable analysis, higher birth order and residing in the highest socioeconomic quintile were associated with incomplete vaccination. After adjusting for interaction between socioeconomic strata of residence census tract and household wealth index, only birth order remained significant. Evidence from Brazilian capitals shows success in achieving high immunisation coverage among poorer children. Strategies are needed to reach children in wealthier areas.

Pertussis vaccination coverage among French parents of infants after 10years of cocoon strategy.

PubMed

Cohen, R; Gaudelus, J; Denis, F; Stahl, J-P; Chevaillier, O; Pujol, P; Martinot, A

2016-06-01

The cocoon strategy against pertussis has been recommended in France since 2004 to indirectly protect young infants who are not yet vaccinated. We aimed to measure vaccination coverage among French parents of infants. A representative sample of 300 mothers and 200 fathers of infants aged <12 months completed a self-administered online questionnaire. They all provided their own vaccination records. Overall, 87% of mothers believed vaccination against pertussis to be important; 83% reported being immunized against pertussis but their vaccination records showed that a third of them was wrong (34%). On the basis of our sample, the 2009-2014 vaccination coverage against pertussis among mothers increased from 22 to 61% (P<0.005); over the same period of time, vaccination coverage against diphtheria, tetanus, and polio remained stable (80%). Vaccination coverage against pertussis among fathers increased from 21 to 42% between 2010 and 2013 (P=0.009). In 2013, one couple out of four (26%) was adequately immunized against pertussis. The cocoon strategy was implemented 10years ago in France but vaccination coverage remains suboptimal among parents of young infants. Healthcare professionals must recommend vaccination against pertussis to young adults and check that their vaccination status is up to date. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

HPV Vaccination Coverage of Male Adolescents in the United States

PubMed Central

Lu, Peng-jun; Yankey, David; Jeyarajah, Jenny; O’Halloran, Alissa; Elam-Evans, Laurie D.; Smith, Philip J.; Stokley, Shannon; Singleton, James A.; Dunne, Eileen F.

2018-01-01

Background In 2011, the Advisory Committee for Immunization Practices (ACIP) recommended routine use HPV vaccine for male adolescents. Methods We used the 2013 National Immunization Survey-Teen (NIS-Teen) data to assess HPV vaccine uptake (≥1 dose) and series completion (≥3 doses). Multivariable logistic regression analysis and a predictive marginal model were conducted to identify independent predictors of vaccination among adolescent males aged 13–17 years. Results HPV vaccination coverage with ≥1 dose was 34.6% while series completion (≥3 doses) was 13.9%. Coverage was significantly higher among non-Hispanic blacks and Hispanics compared with non-Hispanic white males. Multivariable logistic regression showed that characteristics independently associated with a higher likelihood of HPV vaccination (≥1 dose) included: being non-Hispanic black race or Hispanic ethnicity, having mothers who were widowed, divorced, or separated, having 1–3 physician contacts in the past 12 months, a well-child visit at age 11–12 years, having one or two vaccination providers, living in urban or suburban areas, and receiving vaccinations from more than one type of facility (p<0.05). Having mothers with some college or college education, having a higher family income to poverty ratio, living in South or Midwest, and receiving vaccinations from all STD/school/teen clinics or other facilities were independently associated with a lower likelihood of HPV vaccination (p<0.05). Conclusions Following recommendations for routine HPV vaccination among male adolescents, uptake in 2013 was low in males. Increased efforts are needed to improve vaccination coverage, especially for those who are least likely to be vaccinated. PMID:26504124

Improving birth dose coverage of hepatitis B vaccine.

PubMed Central

Hipgrave, David B.; Maynard, James E.; Biggs, Beverley-Ann

2006-01-01

Administration of a birth dose of hepatitis B vaccine (HepB vaccine) to neonates is recommended to prevent mother-to-infant transmission and chronic infection with the hepatitis B virus (HBV). Although manufacturers recommend HepB vaccine distribution and storage at 2-8 degrees C, recognition of the heat stability of hepatitis B surface antigen stimulated research into its use after storage at, or exposure to, ambient or high temperatures. Storage of HepB vaccine at ambient temperatures would enable birth dosing for neonates delivered at home in remote areas or at health posts lacking refrigeration. This article reviews the current evidence on the thermostability of HepB vaccine when stored outside the cold chain (OCC). The reports reviewed show that the vaccines studied were safe and effective whether stored cold or OCC. Field and laboratory data also verifies the retained potency of the vaccine after exposure to heat. The attachment of a highly stable variety of a vaccine vial monitor (measuring cumulative exposure to heat) on many HepB vaccines strongly supports policies allowing their storage OCC, when this will benefit birth dose coverage. We recommend that this strategy be introduced to improve birth dose coverage, especially in rural and remote areas. Concurrent monitoring and evaluation should be undertaken to affirm the safe implementation of this strategy, and assess its cost, feasibility and effect on reducing HBV infection rates. Meanwhile, release of manufacturer data verifying the potency of currently available HepB vaccines after exposure to heat will increase confidence in the use of vaccine vial monitors as a managerial tool during storage of HepB vaccine OCC. PMID:16501717

Tuberculosis vaccine development at a divide.

PubMed

Kaufmann, Stefan H E

2014-05-01

Tuberculosis (TB) remains a major health threat that will only be defeated by a combination of better drugs, diagnostics and vaccines. The only licensed TB vaccine, bacille Calmette-Guérin (BCG), protects against extrapulmonary TB in infants. Novel vaccine candidates that could protect against pulmonary TB either in TB naïve or in latent TB-infected healthy individuals have been developed and are currently being assessed in clinical trials. Subunit booster vaccines are either based on viral vectors expressing TB-specific antigens or on TB-protein antigens in adjuvants. Subunit vaccines are administered on top of BCG. Replacement vaccines for BCG are recombinant viable BCG or Mycobacterium tuberculosis. Several candidates are undergoing, or will soon start, phase IIb assessment for efficacy. The first vaccine candidate, MVA85A, to complete a phase IIb trial, unfortunately failed to show protection against TB in infants. Therapeutic vaccines composed of killed mycobacterial preparations target patients with complicated TB in adjunct to drug treatment. With increasing numbers of TB vaccine candidates in clinical trials, financial, regulatory and infrastructural issues arise, which would be best tackled by a global strategy. In addition, selection of the most promising vaccine candidates for further clinical development gains increasing importance.

Coverage and predictors of vaccination against 2012/13 seasonal influenza in Madrid, Spain

PubMed Central

Jiménez-García, Rodrigo; Esteban-Vasallo, María D; Rodríguez-Rieiro, Cristina; Hernandez-Barrera, Valentín; Domínguez-Berjón, MA Felicitas; Carrasco Garrido, Pilar; Lopez de Andres, Ana; Cameno Heras, Moises; Iniesta Fornies, Domingo; Astray-Mochales, Jenaro

2014-01-01

We aim to determine 2012–13 seasonal influenza vaccination coverage. Data were analyzed by age group and by coexistence of concomitant chronic conditions. Factors associated with vaccine uptake were identified. We also analyze a possible trend in vaccine uptake in post pandemic seasons. We used computerized immunization registries and clinical records of the entire population of the Autonomous Community of Madrid, Spain (6 284 128 persons) as data source. A total of 871 631 individuals were vaccinated (13.87%). Coverage for people aged ≥ 65 years was 56.57%. Global coverage in people with a chronic condition was 15.7% in children and 18.69% in adults aged 15–59 years. The variables significantly associated with a higher likelihood of being vaccinated in the 2012–13 campaign for the age groups studied were higher age, being Spanish-born, higher number of doses of seasonal vaccine received in previous campaigns, uptake of pandemic vaccination, and having a chronic condition. We conclude that vaccination coverage in persons aged <60 years with chronic conditions is less than acceptable. The very low coverage among children with chronic conditions calls for urgent interventions. Among those aged ≥60 years, uptake is higher but still far from optimal and seems to be descending in post-pandemic campaigns. For those aged ≥65 years the mean percentage of decrease from the 2009/10 to the actual campaign has been 12%. Computerized clinical and immunization registers are useful tools for providing rapid and detailed information about influenza vaccination coverage in the population. PMID:24280728

Achieving high coverage in Rwanda's national human papillomavirus vaccination programme.

PubMed

Binagwaho, Agnes; Wagner, Claire M; Gatera, Maurice; Karema, Corine; Nutt, Cameron T; Ngabo, Fidele

2012-08-01

Virtually all women who have cervical cancer are infected with the human papillomavirus (HPV). Of the 275,000 women who die from cervical cancer every year, 88% live in developing countries. Two vaccines against the HPV have been approved. However, vaccine implementation in low-income countries tends to lag behind implementation in high-income countries by 15 to 20 years. In 2011, Rwanda's Ministry of Health partnered with Merck to offer the Gardasil HPV vaccine to all girls of appropriate age. The Ministry formed a "public-private community partnership" to ensure effective and equitable delivery. Thanks to a strong national focus on health systems strengthening, more than 90% of all Rwandan infants aged 12-23 months receive all basic immunizations recommended by the World Health Organization. In 2011, Rwanda's HPV vaccination programme achieved 93.23% coverage after the first three-dose course of vaccination among girls in grade six. This was made possible through school-based vaccination and community involvement in identifying girls absent from or not enrolled in school. A nationwide sensitization campaign preceded delivery of the first dose. Through a series of innovative partnerships, Rwanda reduced the historical two-decade gap in vaccine introduction between high- and low-income countries to just five years. High coverage rates were achieved due to a delivery strategy that built on Rwanda's strong vaccination system and human resources framework. Following the GAVI Alliance's decision to begin financing HPV vaccination, Rwanda's example should motivate other countries to explore universal HPV vaccine coverage, although implementation must be tailored to the local context.

Human papillomavirus (HPV) vaccine coverage achievements in low and middle-income countries 2007-2016.

PubMed

Gallagher, Katherine E; Howard, Natasha; Kabakama, Severin; Mounier-Jack, Sandra; Burchett, Helen E D; LaMontagne, D Scott; Watson-Jones, Deborah

2017-12-01

Since 2007, HPV vaccine has been available to low and middle income countries (LAMIC) for small-scale 'demonstration projects', or national programmes. We analysed coverage achieved in HPV vaccine demonstration projects and national programmes that had completed at least 6 months of implementation between January 2007-2016. A mapping exercise identified 45 LAMICs with HPV vaccine delivery experience. Estimates of coverage and factors influencing coverage were obtained from 56 key informant interviews, a systematic published literature search of 5 databases that identified 61 relevant full texts and 188 solicited unpublished documents, including coverage surveys. Coverage achievements were analysed descriptively against country or project/programme characteristics. Heterogeneity in data, funder requirements, and project/programme design precluded multivariate analysis. Estimates of uptake, schedule completion rates and/or final dose coverage were available from 41 of 45 LAMICs included in the study. Only 17 estimates from 13 countries were from coverage surveys, most were administrative data. Final dose coverage estimates were all over 50% with most between 70% and 90%, and showed no trend over time. The majority of delivery strategies included schools as a vaccination venue. In countries with school enrolment rates below 90%, inclusion of strategies to reach out-of-school girls contributed to obtaining high coverage compared to school-only strategies. There was no correlation between final dose coverage and estimated recurrent financial costs of delivery from cost analyses. Coverage achieved during joint delivery of HPV vaccine combined with another intervention was variable with little/no evaluation of the correlates of success. This is the most comprehensive descriptive analysis of HPV vaccine coverage in LAMICs to date. It is possible to deliver HPV vaccine with excellent coverage in LAMICs. Further good quality data are needed from health facility based

An equity dashboard to monitor vaccination coverage.

PubMed

Arsenault, Catherine; Harper, Sam; Nandi, Arijit; Rodríguez, José M Mendoza; Hansen, Peter M; Johri, Mira

2017-02-01

Equity monitoring is a priority for Gavi, the Vaccine Alliance, and for those implementing The 2030 agenda for sustainable development . For its new phase of operations, Gavi reassessed its approach to monitoring equity in vaccination coverage. To help inform this effort, we made a systematic analysis of inequalities in vaccination coverage across 45 Gavi-supported countries and compared results from different measurement approaches. Based on our findings, we formulated recommendations for Gavi's equity monitoring approach. The approach involved defining the vulnerable populations, choosing appropriate measures to quantify inequalities, and defining equity benchmarks that reflect the ambitions of the sustainable development agenda. In this article, we explain the rationale for the recommendations and for the development of an improved equity monitoring tool. Gavi's previous approach to measuring equity was the difference in vaccination coverage between a country's richest and poorest wealth quintiles. In addition to the wealth index, we recommend monitoring other dimensions of vulnerability (maternal education, place of residence, child sex and the multidimensional poverty index). For dimensions with multiple subgroups, measures of inequality that consider information on all subgroups should be used. We also recommend that both absolute and relative measures of inequality be tracked over time. Finally, we propose that equity benchmarks target complete elimination of inequalities. To facilitate equity monitoring, we recommend the use of a data display tool - the equity dashboard - to support decision-making in the sustainable development period. We highlight its key advantages using data from Côte d'Ivoire and Haiti.

An equity dashboard to monitor vaccination coverage

PubMed Central

Harper, Sam; Nandi, Arijit; Rodríguez, José M Mendoza; Hansen, Peter M; Johri, Mira

2017-01-01

Abstract Equity monitoring is a priority for Gavi, the Vaccine Alliance, and for those implementing The 2030 agenda for sustainable development. For its new phase of operations, Gavi reassessed its approach to monitoring equity in vaccination coverage. To help inform this effort, we made a systematic analysis of inequalities in vaccination coverage across 45 Gavi-supported countries and compared results from different measurement approaches. Based on our findings, we formulated recommendations for Gavi’s equity monitoring approach. The approach involved defining the vulnerable populations, choosing appropriate measures to quantify inequalities, and defining equity benchmarks that reflect the ambitions of the sustainable development agenda. In this article, we explain the rationale for the recommendations and for the development of an improved equity monitoring tool. Gavi’s previous approach to measuring equity was the difference in vaccination coverage between a country’s richest and poorest wealth quintiles. In addition to the wealth index, we recommend monitoring other dimensions of vulnerability (maternal education, place of residence, child sex and the multidimensional poverty index). For dimensions with multiple subgroups, measures of inequality that consider information on all subgroups should be used. We also recommend that both absolute and relative measures of inequality be tracked over time. Finally, we propose that equity benchmarks target complete elimination of inequalities. To facilitate equity monitoring, we recommend the use of a data display tool – the equity dashboard – to support decision-making in the sustainable development period. We highlight its key advantages using data from Côte d’Ivoire and Haiti. PMID:28250513

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

PubMed

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.

Trends in influenza vaccination coverage rates in South Korea from 2005 to 2014: Effect of public health policies on vaccination behavior.

PubMed

Seo, Jeongmin; Lim, Juwon

2018-05-05

Influenza is a major cause of morbidity and mortality worldwide. Annual vaccination is effective in its prevention and is recommended especially in susceptible populations such as the elderly over 65 years, children younger than 5, pregnant women, and people with chronic diseases. Overall, South Korea has a high vaccination rate owing to its National Immunization Program, although the method and extent of its coverage varies among the target subgroups. The aim of this study is to assess the trend of influenza vaccination coverage between 2005 and 2014 in South Korea to address the influence of sociodemographic and disease factors on vaccination behavior. Also, we aim to compare the vaccination coverage of target subgroups and evaluate the effect of relevant policies to provide suggestions for their improvement. A total of 61,036 respondents from the Korea National Health and Nutrition Examination Surveys III to VI were included. The total influenza vaccination coverage increased from 38.0% in 2005 to 44.1% in 2014. Vaccination coverage was higher among the elderly aged ≥65 years (range, 70.0-79.8%; p-for-trend <0.001) and children under 5 (range, 64.6-78.9%; p-for-trend < 0.001) than among pregnant women (range, 9.4-37.8%; p-for-trend = 0.122) and people with chronic diseases (range, 29.6-42.6%; p-for-trend = 0.068) from 2005 to 2014. High vaccination coverage was associated with female gender, rural residence, low education level, high income, and increasing number of chronic diseases. But the effect of high income on high vaccination coverage was absent in the elderly aged ≥65 years and children under 5. Influenza vaccination rates have steadily increased from 2005 to 2014 in South Korea. Disparities between target groups correspond to their financial coverage under the National Immunization Program, and financial aids remove the influence of high income on higher vaccination rates. Future vaccination policies should focus on pregnant women

Children on the move and vaccination coverage in a low-income, urban Latino population.

PubMed

Findley, S E; Irigoyen, M; Schulman, A

1999-11-01

The purpose of this study was to determine the impact of childhood moves and foreign birth on vaccination coverage among Latino children in New York City. Vaccination coverage was assessed in a survey of 314 children younger than 5 years at 2 immunization clinics. Forty-seven percent of the study children had moved abroad. After adjustment for health insurance, regular source of care, and country of birth, child moves had no independent effect on vaccination coverage. Foreign-born children had diphtheria-pertussis-tetanus, oral polio vaccine, and measles-mumps-rubella vaccination coverage rates similar to those of US-born children, but they were underimmunized in regard to Haemophilus influenzae type b and hepatitis B. Foreign birth, but not childhood moves, is a barrier to vaccinations among low-income, urban Latino children.

A PRELIMINARY assessment of BCG vacination in India.

PubMed

1955-01-01

A NEW ASSESSMENT ACTIVITY IN RELATION TO THE WHO/UNICEF BCG VACCINATION PROGRAMME IS DESCRIBED IN THIS REPORT: according to a detailed plan special field teams collect data on tuberculin sensitivity to determine how efficiently children are being selected for vaccination and to appraise the allergy produced by the mass vaccinations. Results of nine months' work in India have important implications for the practical BCG work.Testing of unvaccinated groups of schoolchildren shows that the pattern of tuberculin sensitivity differs in different parts of India. Specific tuberculin sensitivity is found in all areas, as evidenced by strong reactions to the 5 TU test. Many children had a low-grade non-specific sensitivity, evidenced by small reactions to 5 TU and large reactions to 100 TU. This non-specific tuberculin sensitivity was less frequent at high altitudes, and most common in low-lying humid areas: in all areas it was more prevalent than specific sensitivity.In some areas non-specific tuberculin sensitivity is so strong that it cannot be effectively distinguished from specific sensitivity: consequently, many children not infected with tuberculosis are undoubtedly being excluded from vaccination.Sample retesting of children vaccinated in the mass campaign revealed variable levels of allergy, in many instances much lower than had been expected. These results cannot be explained by a native incapacity of the Indian children to develop strong allergy-nor presumably by the vaccine used. Impairment of the vaccine by exposure to light could be no more than a contributory factor. The marked variability of the campaign results suggests that some factor connected with the handling or application of the vaccine (or possibly of the tuberculin) is involved.

Highlights of Historical Events Leading to National Surveillance of Vaccination Coverage in the United States

PubMed Central

Smith, Philip J.; Wood, David; Darden, Paul M.

2011-01-01

The articles published in this special supplement of Public Health Reports provide examples of only some of the current efforts in the United States for evaluating vaccination coverage. So, how did we get here? The history of vaccination and assessment of vaccination coverage in the U.S. has its roots in the pre-Revolutionary War era. In many cases, development of vaccines, and attention devoted to the assessment of vaccination coverage, has grown from the impact of infectious disease on major world events such as wars. The purpose of this commentary is to provide a brief overview of the key historical events in the U.S. that influenced the development of vaccines and the efforts to track vaccination coverage, which laid the foundation for contemporary vaccination assessment efforts. PMID:21815302

The current situation of voluntary vaccination and the factors influencing its coverage among children in Takatsuki, Japan: focus on Hib and pneumococcal vaccines.