scholarly journals A systematic approach to simultaneously evaluate safety, immunogenicity, and efficacy of novel tuberculosis vaccination strategies

2020 ◽  
Vol 6 (10) ◽  
pp. eaaz1767 ◽  
Author(s):  
Visai Muruganandah ◽  
Harindra D. Sathkumara ◽  
Saparna Pai ◽  
Catherine M. Rush ◽  
Roland Brosch ◽  
...  
Keyword(s):  
Systematic Approach ◽  
Booster Vaccination ◽  
Adverse Outcomes ◽  
Bacille Calmette Guerin ◽  
Preclinical Evaluation ◽  
Routes Of Administration ◽  
Vaccination Strategies ◽  
Multiple Measurements ◽  
Human Use ◽  
Simple Empirical Model

Tuberculosis (TB) is the deadliest infectious disease worldwide. Bacille-Calmette-Guérin (BCG), the only licensed TB vaccine, affords variable protection against TB but remains the gold standard. BCG improvement is focused around three strategies: recombinant BCG strains, heterologous routes of administration, and booster vaccination. It is currently unknown whether combining these strategies is beneficial. The preclinical evaluation for new TB vaccines is heavily skewed toward immunogenicity and efficacy; however, safety and efficacy are the dominant considerations in human use. To facilitate stage gating of TB vaccines, we developed a simple empirical model to systematically rank vaccination strategies by integrating multiple measurements of safety, immunogenicity, and efficacy. We assessed 24 vaccination regimens, composed of three BCG strains and eight combinations of delivery. The model presented here highlights that mucosal booster vaccination may cause adverse outcomes and provides a much needed strategy to evaluate and rank data obtained from TB vaccine studies using different routes, strains, or animal models.

scholarly journals Combating pertussis resurgence: One booster vaccination schedule does not fit all

2015 ◽  
Vol 112 (5) ◽  
pp. E472-E477 ◽  
Author(s):  
Maria A. Riolo ◽  
Pejman Rohani
Keyword(s):  
Booster Vaccination ◽  
Cost Effective ◽  
Vaccination Schedule ◽  
Health Concern ◽  
Transmission Model ◽  
Public Health Concern ◽  
Vaccine Failure ◽  
Vaccination Strategies ◽  
Vaccine Booster ◽  
Pertussis Epidemiology

Pertussis has reemerged as a major public health concern in many countries where it was once considered well controlled. Although the mechanisms responsible for continued pertussis circulation and resurgence remain elusive and contentious, many countries have nevertheless recommended booster vaccinations, the timing and number of which vary widely. Here, using a stochastic, age-stratified transmission model, we searched for cost-effective booster vaccination strategies using a genetic algorithm. We did so assuming four hypothesized mechanisms underpinning contemporary pertussis epidemiology: (I) insufficient coverage, (II) frequent primary vaccine failure, (III) waning of vaccine-derived protection, and (IV) vaccine “leakiness.” For scenarios I–IV, successful booster strategies were identified and varied considerably by mechanism. Especially notable is the inability of booster schedules to alleviate resurgence when vaccines are leaky. Critically, our findings argue that the ultimate effectiveness of vaccine booster schedules will likely depend on correctly pinpointing the causes of resurgence, with misdiagnosis of the problem epidemiologically ineffective and economically costly.

Prescribing in the elderly

2016 ◽  
Vol 10 (2) ◽  
pp. 96-104
Author(s):  
Lucy Webber
Keyword(s):  
Functional Ability ◽  
Older Patients ◽  
Systematic Approach ◽  
Cumulative Effect ◽  
The Elderly ◽  
Adverse Outcomes ◽  
Healthcare Team ◽  
Ageing Population ◽  
Slow Disease Progression ◽  
Unique Challenge

Prescribing in the elderly is a unique challenge faced by every GP. As the ageing population grows, more patients are presenting to GPs with an array of co-morbidities. The cumulative effect of this growth in morbidity is an increase in the prescribing of multiple medications. Although the use of appropriate medication can improve functional ability, slow disease progression and improve symptoms; medication can also cause adverse outcomes. Older patients are at particularly high risk of adverse outcomes, necessitating a rational and systematic approach to prescribing in the elderly. This article focuses on the challenges and pitfalls of prescribing in the elderly, and the ways in which GPs and the wider primary healthcare team can improve their practices for this group of patients.

scholarly journals Routes of Administration of Illicit Drugs among Young Swiss Men: Their Prevalence and Associated Socio-Demographic Characteristics and Adverse Outcomes

2021 ◽  
Vol 18 (21) ◽  
pp. 11158
Author(s):  
Natalia Estévez-Lamorte ◽  
Simon Foster ◽  
Gerhard Gmel ◽  
Meichun Mohler-Kuo
Keyword(s):  
Alcohol Use Disorder ◽  
Illicit Drugs ◽  
Demographic Characteristics ◽  
Adverse Outcomes ◽  
Social Consequences ◽  
Routes Of Administration ◽  
Financial Autonomy ◽  
Prevalence Estimates ◽  
Civil Status ◽  
Single Versus

The prevalence of different routes of administration (ROAs) of illicit drugs other than cannabis was examined in young Swiss men, in addition to the association between socio-demographics and adverse outcomes and particular ROAs. Our sample consisted of 754 men (mean age = 25.4 ± 1.2 years) who participated in the Cohort Study on Substance Use Risk Factors and reported using any of 18 illicit drugs over the last 12 months. Prevalence estimates were calculated for oral use, nasal use, smoking, injecting, and other ROAs. Associations between ROAs and socio-demographics and adverse outcomes (i.e., alcohol use disorder (AUD), suicidal ideations, and health and social consequences) were calculated for using single versus multiple ROAs. The most prevalent ROA was oral use (71.8%), followed by nasal use (59.2%), smoking (22.1%), injecting (1.1%), and other ROAs (1.7%). Subjects’ education, financial autonomy, and civil status were associated with specific ROAs. Smoking was associated with suicidal ideations and adverse health consequences and multiple ROAs with AUD, suicidal ideations, and health and social consequences. The most problematic pattern of drug use among young adults appears to be using multiple ROAs, followed by smoking. Strategies to prevent and reduce the use of such practices are needed to avoid adverse outcomes at this young age.

scholarly journals Integrating fish models in tuberculosis vaccine development

2020 ◽  
Vol 13 (8) ◽  
pp. dmm045716
Author(s):  
Anni K. Saralahti ◽  
Meri I. E. Uusi-Mäkelä ◽  
Mirja T. Niskanen ◽  
Mika Rämet
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Bacillus Calmette Guerin ◽  
Antibiotic Resistant ◽  
Vaccine Candidates ◽  
Preclinical Evaluation ◽  
Vaccination Strategies ◽  
Resistant Strains ◽  
New Vaccines

ABSTRACTTuberculosis is a chronic infection by Mycobacterium tuberculosis that results in over 1.5 million deaths worldwide each year. Currently, there is only one vaccine against tuberculosis, the Bacillus Calmette–Guérin (BCG) vaccine. Despite widespread vaccination programmes, over 10 million new M. tuberculosis infections are diagnosed yearly, with almost half a million cases caused by antibiotic-resistant strains. Novel vaccination strategies concentrate mainly on replacing BCG or boosting its efficacy and depend on animal models that accurately recapitulate the human disease. However, efforts to produce new vaccines against an M. tuberculosis infection have encountered several challenges, including the complexity of M. tuberculosis pathogenesis and limited knowledge of the protective immune responses. The preclinical evaluation of novel tuberculosis vaccine candidates is also hampered by the lack of an appropriate animal model that could accurately predict the protective effect of vaccines in humans. Here, we review the role of zebrafish (Danio rerio) and other fish models in the development of novel vaccines against tuberculosis and discuss how these models complement the more traditional mammalian models of tuberculosis.

scholarly journals Pertussis diagnosis in Belgium: results of the National Reference Centre for Bordetella anno 2015

2017 ◽  
Vol 145 (11) ◽  
pp. 2366-2373 ◽  
Author(s):  
H. MARTINI ◽  
C. RODEGHIERO ◽  
C. VAN DEN POEL ◽  
M. VINCENT ◽  
D. PIERARD ◽  
...  
Keyword(s):  
Acute Infection ◽  
Booster Vaccination ◽  
Infants And Children ◽  
Age Group ◽  
Limited Data ◽  
Serum Samples ◽  
Pertussis Infection ◽  
Vaccination Strategies ◽  
National Reference ◽  
Reference Centre

SUMMARYIn 2015, the Belgian National Reference Centre for Bordetella analyzed 4110 respiratory samples by qPCR and 4877 serum samples by serology. Whereas about 50% of respiratory samples were from infants and children below the age of five, serum samples were distributed among all age categories. A total of 394 (9·6%) cases was diagnosed as positive for Bordetella pertussis by qPCR and 844 (17·3%) cases were diagnosed as acute infection by serology (anti-pertussis toxin (PT) IgG > 125 IU/ml). Another 1042 (21·4%) sera had anti-PT IgG between 55 and 125 IU/ml reflecting a vaccination or pertussis infection during the last 1–2 years. Seventy per cent of the pertussis cases diagnosed by qPRC were in infants and children younger than 14 years old, whereas the highest number of sera with anti-PT levels >125 IU/ml was in the age group of 10–14 years old. Based on the limited data of the last vaccination (reported for only 15% of the samples), recent booster vaccination in the teenager group may have contributed only minimally to these elevated anti-PT levels. The highest number of sera with anti-PT titers between 55 and 125 IU/ml was found in the age category 50–59 years old. It is clear that pertussis continues to be a problem in Belgium and that other vaccination strategies (maternal vaccination, cocoon vaccination) and ultimately better vaccines will be needed to control this highly infectious respiratory disease.

scholarly journals Advances in Toxoplasma gondii Vaccines: Current Strategies and Challenges for Vaccine Development

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 413
Author(s):  
Ki-Back Chu ◽  
Fu-Shi Quan
Keyword(s):  
Toxoplasma Gondii ◽  
Clinical Studies ◽  
Vaccine Development ◽  
Apicomplexan Parasite ◽  
Zoonotic Diseases ◽  
Effective Vaccine ◽  
Protein Subunits ◽  
Vaccination Strategies ◽  
Human Use

Toxoplasmosis, caused by the apicomplexan parasite Toxoplasma gondii, is one of the most damaging parasite-borne zoonotic diseases of global importance. While approximately one-third of the entire world’s population is estimated to be infected with T. gondii, an effective vaccine for human use remains unavailable. Global efforts in pursuit of developing a T. gondii vaccine have been ongoing for decades, and novel innovative approaches have been introduced to aid this process. A wide array of vaccination strategies have been conducted to date including, but not limited to, nucleic acids, protein subunits, attenuated vaccines, and nanoparticles, which have been assessed in rodents with promising results. Yet, translation of these in vivo results into clinical studies remains a major obstacle that needs to be overcome. In this review, we will aim to summarize the current advances in T. gondii vaccine strategies and address the challenges hindering vaccine development.

scholarly journals THE SHORELINE RESPONSE DECISION-MAKING PROCESS

2008 ◽  
Vol 2008 (1) ◽  
pp. 443-449
Author(s):  
Edward H. Owens ◽  
Gary A. Sergy
Keyword(s):  
Decision Making ◽  
Decision Process ◽  
Systematic Approach ◽  
Oil Spills ◽  
Physical Processes ◽  
Coastal Marine ◽  
Oil Spill Response ◽  
Human Use ◽  
Monitoring Response ◽  
Selection Of

ABSTRACT The decision process that generates oil spill response objectives, strategies and tactics at regional and site-specific scales is a form of risk management. Typically this decision process involves an analysis of the probabilities and consequences of events and the selection of actions to achieve the defined objective(s). Coastal marine, lake and river oil spills frequently are the more difficult ones to manage due to the dynamics and complexity of the environment in terms of physical processes, ecosystem variability and sensitivity, and human use activities. The development of a systematic approach to decision-making is intended to address and reduce the complexity of these issues. This can be achieved by the identification of the elemental components of a response operation in terms of four phases: preplanning; reactive response; planned response; and the completion and monitoring response phase. The framework of the decision process within each of the three response phases is a logical and systematic sequence of nine integrated steps. This discussion explains the purpose and actions that are involved in each step and the manner in which the different components relate to each other.

scholarly journals Immunogenicity of convalescent and vaccinated sera against clinical isolates of ancestral SARS-CoV-2, beta, delta, and omicron variants

2022 ◽  
Author(s):  
Arinjay Banerjee ◽  
Jocelyne Lew ◽  
Andrea Kroeker ◽  
Kaushal Baid ◽  
Patryk Aftanas ◽  
...  
Keyword(s):  
Clinical Specimen ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Clinical Isolates ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Vaccination Strategies ◽  
Antibody Titers ◽  
Ancestral Virus ◽  
Antibody Levels

The omicron variant of concern (VOC) of SARS-CoV-2 was first reported in November 2021 in Botswana and South Africa. Omicron variant has evolved multiple mutations within the spike protein and the receptor binding domain (RBD), raising concerns of increased antibody evasion. Here, we isolated infectious omicron from a clinical specimen obtained in Canada. The neutralizing activity of sera from 65 coronavirus disease (COVID-19) vaccine recipients and convalescent individuals against clinical isolates of ancestral SARS-CoV-2, beta, delta, and omicron VOCs was assessed. Convalescent sera from unvaccinated individuals infected by the ancestral virus during the first wave of COVID-19 in Canada (July, 2020) demonstrated reduced neutralization against beta, delta and omicron VOCs. Convalescent sera from unvaccinated individuals infected by the delta variant (May-June, 2021) neutralized omicron to significantly lower levels compared to the delta variant. Sera from individuals that received three doses of the Pfizer or Moderna vaccines demonstrated reduced neutralization of both delta and omicron variants relative to ancestral SARS-CoV-2. Sera from individuals that were naturally infected with ancestral SARS-CoV-2 and subsequently received two doses of the Pfizer vaccine induced significantly higher neutralizing antibody levels against ancestral virus and all VOCs. Importantly, infection alone, either with ancestral SARS-CoV-2 or the delta variant was not sufficient to induce high neutralizing antibody titers against omicron. This data will inform current booster vaccination strategies and we highlight the need for additional studies to identify longevity of immunity against SARS-CoV-2 and optimal neutralizing antibody levels that are necessary to prevent infection and/or severe COVID-19.

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