Gene/Protein Disease Symptom Drug Enzyme Compound
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Literature on genetic screening in the community suggests that people having specific genotypes may either get or protect from infection, for example, malaria, human papilloma virus, and haemophilic influenza, for which vaccines are either already developed or being targeted. In such a situation, the evaluation of the efficacy of vaccine in the community needs to be examined with caution. In this paper, I present a method for the estimation of vaccine efficacy (VE) in the presence of genetic traits/component (theta) and the sample size required to estimate the 95 per cent CI with a given relative width for the estimated vaccine efficacy. Considering true efficacy ranging from 40 to 80 per cent and the possible values of the genetic component (theta) ranging from 0 to 60 per cent, the VE was estimated. The 95 per cent confidence intervals (CI) for the estimated VE for relative widths (R) 1.0 and 0.1 were computed. The sample sizes required for each of the unvaccinated and vaccinated cohorts were computed for estimating the 95 per cent CI for given incidence rates in the unvaccinated (Iu) cohort. In the presence of genetic traits I found that the VE was consistently overestimated. There existed change in the location as well as the asymmetry of the 95 per cent CIs over the point estimate of VE. The sample size required for estimating 95 per cent CI of VE was substantially reduced, resulting in savings. The more the genetic component (theta) affecting disease in the community, the more the savings in sample size. I examined the above estimators for (i) VE, (ii) 95 per cent CI for VE and (iii) sample size required for estimating 95 per cent CI of VE using the real-life data from the Haemophilus influenzae type b vaccine trial conducted in Finland and the global genetic structure of encapsulated H. influenza. Because of escalated VE and large savings in sample size for estimating the 95 per cent CI for VE, I recommend that the design should consider the genetic component that causes/protects from infection/disease for the evaluation of efficacy of vaccine in the field.
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PMID:Implications of genetic traits on vaccine efficacy. 1280 17

Vaccines are a key contributor to public health, especially in developing countries. Despite numerous demonstrations of the cost-effectiveness of immunisation, vaccines spending accounted for only 1.7% of the total pharmaceutical market in 2002, when UNICEF estimated that 34 million children were not reached by routine immunisation, most of them in developing countries. Several international organizations or initiatives, like the Global Alliance for Vaccines and Immunisation (GAVI), have defined a long-term goal of universal immunisation in developing countries. There is an urgent need to estimate the financial resources required to meet this goal. The objective of this study was to anticipate the funding needs for childhood immunisation in developing countries over the 2004-2014 period. The study scope includes all the 75 countries eligible for support from GAVI, and covers existing vaccines that are considered as a priority for GAVI (DTP (diphtheria, tetanus, pertussis), hepatitis B, Haemophilus influenzae type b (as a stand alone presentation or in combination with DTP) and yellow fever) as well as future vaccines (meningitis A and C, rotavirus, human papilloma virus (HPV), malaria, Streptococcus pneumoniae and tuberculosis) likely to be available within the 10-year period. We developed a methodology to estimate the number of doses required, based on disease prevalence and incidence, target populations, introduction dates of new vaccines, coverage dynamics and dosing regimen. The introduction price and price evolution of vaccines over time were modelled, taking into account the type of vaccine, the expected return on investment from vaccine manufacturers and the competitive landscape. Non-vaccine costs (capital costs and non-vaccine recurrent costs) were estimated based on the number of people immunised and number of doses dispensed, using available case studies as a reference. According to the optimal scenario that would consider the provision of all vaccines to all relevant developing countries as soon as they are available, funding requirements to cover the associated total costs over the 10-year period were estimated to be about US$ 30 billion. Vaccines-related costs represent the largest share, with estimated costs of US$ 21 billion (among which 18 billion for new vaccines), the remaining needs being split between capital costs and other recurrent costs. Accounting for the main imponderables (such as delay in vaccines launch compared to industry plans) as well as probable phasing of vaccine introduction in countries, the total costs of immunisation would be reduced to US$ 14-17 billion over the same period. Vaccines-related costs represent the largest share (US$ 7.1-9.3 billion, among which 4.3-6.5 billion for new vaccines). This study advocates for the anticipation of the substantial financial resources needed to (a) purchase and introduce these vaccines in the developing countries in order to reduce the time lag between availability in industrialised and developing countries; and (b) stimulate vaccine researchers and manufacturers to continue research and development of much needed vaccines for the developing world.
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PMID:Financial requirements of immunisation programmes in developing countries: a 2004-2014 perspective. 1597 69

The aim of this paper is to review the use of genetics in palaeomicrobiology, and to highlight the importance of understanding past diseases. Palaeomicrobiology is the study of disease pathogens in skeletal and mummified remains from archaeological contexts. It has revolutionarised our understanding of health in the past by enabling a deeper knowledge of the origins and evolution of many diseases that have shaped us as a species. Bacterial diseases explored include tuberculosis, leprosy, bubonic plague, typhoid, syphilis, endemic and epidemic typhus, trench fever, and Helicobacter pylori. Viral diseases discussed include influenza, hepatitis B, human papilloma virus (HPV), human T-cell lymphotrophic virus (HTLV-1) and human immunodeficiency virus (HIV). Parasitic diseases investigated include malaria, leishmaniasis, Chagas' disease, roundworm, whipworm, pinworm, Chinese liver fluke, fleas and lice. Through a better understanding of disease origins and their evolution, we can place into context how many infectious diseases are changing over time, and so help us estimate how they may change in the future.
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PMID:Palaeopathology and genes: investigating the genetics of infectious diseases in excavated human skeletal remains and mummies from past populations. 2379 62

Viral structural proteins share a common nature of homotypic interactions that drive viral capsid formation. This natural process has been mimicked in vitro through recombinant technology to generate various virus-like particles (VLPs) and small subviral particles that exhibit similar structural and antigenic properties of their authentic viruses. Therefore, such self-assembled, polyvalent, and highly immunogenic VLPs and small subviral particles are excellent subunit vaccines against individual viruses, such as the VLP vaccines against the hepatitis B virus, human papilloma virus, and hepatitis E virus, which have already been in the markets. In addition, various antigens and epitopes can be fused with VLPs, small subviral particles, or protein polymers, forming chimeric mono-, bi-, or trivalent vaccines. Owing to their easy-production, un-infectiousness, and polyvalence, the recombinant, chimeric vaccines offer a new approach for development of safe, low-cost, and high efficient subunit vaccines against a single or more pathogens or diseases. While the first VLP-based combination vaccine against malaria has been approved for human use, many others are under development with promising future, which are summarized in this commentary.
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PMID:Recent advancements in combination subunit vaccine development. 2764 19

Global immunization efforts to date have heavily focused on infants and children, with noted success on public health. Healthy adolescents and adults contribute to the economic growth and development of countries but efforts to ensure vaccine coverage for these groups receive inadequate global attention and resources. Emerging epidemics for a number of infectious diseases including Ebola, Zika, dengue, malaria and the continuing epidemics of tuberculosis and several sexually transmitted infections, including HIV, HPV and Hepatitis B, have high incidence and prevalence in adolescents and adults. New vaccines under development for these diseases and under-used vaccines such as for human papilloma virus will have the greatest health and economic impact in these populations. Global consensus, political will, policies, global and country infrastructure, and financing mechanisms are needed to accelerate access for the billions of adolescents and adults living under the threat of devastating infectious disease outbreaks and epidemics, especially in lower income countries. The global health community and countries cannot afford to delay planning for implementation of adolescent and adult vaccine programs that will potentially save millions of lives and strengthen global and national economies. The article examines this next challenge and suggests a research agenda and a framework for action to galvanize global and national policy decision-makers to begin preparations for future immunization challenges.
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PMID:Strengthening global vaccine access for adolescents and adults. 2912 84

Background: While the rise of antimicrobial resistance (AMR) has been recognised as a major public health problem, the value of vaccines to control AMR is poorly defined. This expert survey was launched with the aim of informing the 2018 Vaccine Investment Strategy through which Gavi, the Vaccine Alliance prioritises future vaccine funding. This exercise focused on both vaccines currently supported by Gavi and under consideration for future funding. Methods: The relative importance of pre-defined criteria as drivers of overall value of vaccines as a tool/ intervention to control AMR was assessed by 18 experts: prevention of mortality and morbidity due to resistant pathogens, antibiotic use prevented, societal impact, ethical importance and sense of urgency. For each vaccine, experts attributed scores reflecting the estimated value for each criterion, and overall value relative to AMR was derived from the value assigned to each criterion and their relative importance for each vaccine. Results: Mortality, morbidity due to targeted resistant pathogens, and antibiotic use prevented were considered the most important determinants of overall value. Pneumococcal, typhoid and malaria vaccines were assigned highest value relative to antimicrobial resistance. Intermediate value was estimated for specific rotavirus, cholera, respiratory syncytial virus (RSV), influenza, dengue, measles, meningitis and Haemophilus influenza type b- (Hib-) containing pentavalent vaccines. Lowest value relative to AMR was estimated for Japanese encephalitis, hepatitis A, yellow fever, rabies and human papilloma virus vaccine. Conclusions: In the future, more evidence-based, data-driven, robust methodologies should be developed to guide coordinated, rational decision making on priority actions aimed at strengthening the use of vaccines against AMR.
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PMID:Vaccine impact on antimicrobial resistance to inform Gavi, the Vaccine Alliance's 2018 Vaccine Investment Strategy: report from an expert survey. 3173 60