Helminth-infected patients with malaria: a low profile transmission hub?

The scale-up of malaria control efforts in recent years, coupled with major investments in malaria research, has produced impressive public health impact in a number of countries and has led to the development of new tools and strategies aimed at further consolidating malaria control goals. As a result, there is a growing need for the malaria policy setting process to rapidly review increasing amounts of evidence. The World Health Organization Global Malaria Programme, in keeping with its mandate to set evidence-informed policies for malaria control, has convened the Malaria Policy Advisory Committee as a mechanism to increase the timeliness, transparency, independence and relevance of its recommendations to World Health Organization member states in relation to malaria control and elimination. The Malaria Policy Advisory Committee, composed of 15 world-renowned malaria experts, will meet in full twice a year, with the inaugural meeting scheduled for 31 January to 2 February 2012 in Geneva. Policy recommendations, and the evidence to support them, will be published within two months of every meeting as part of an open access Malaria Journal thematic series. This article is a prelude to that series and provides the global malaria community with the background and overview of the Committee and its terms of reference.     

Stability evaluation of vaccines: WHO approach

The stability of vaccines has a major impact on the success of immunization programmes worldwide. In line with this, clear definition of the stability characteristics of a vaccine is of critical importance. One of the concerns at country level is whether vaccines will remain potent on its way from the manufacturer, through the distribution channels, to the final users and vaccine recipients. In response to the requests for assistance in defining stability profile of vaccines, the Expert Committee on Biological Standardization (ECBS) in October 2006 agreed that new WHO guidelines be established on stability evaluation of vaccines (http://www.who.int/biologicals/publications/trs/areas/vaccines/stability/en/index.html). This document applies to all vaccines against infectious diseases. The aim of this guideline is to provide the scientific basis and guiding principles for evaluation of vaccine stability for the purpose of clinical trial approval, licensing, and post-licensure monitoring. As part of its initiative to promote use of vaccines of assured quality, WHO emphasizes the role of National Regulatory Authorities (NRAs) and National Control Laboratories (NCLs) in overall vaccine evaluation, including stability assessment. While recognizing that manufacturers are responsible for the quality of the vaccines they produce, compliance with vaccine quality specifications is part of regulatory oversight. This article provides basic information about WHO international standards as well as key definitions and principles for stability evaluation of vaccines that are elaborated in detail in the above mentioned guidance document.     

Accelerating introduction of new vaccines: barriers to introduction and lessons learned from the recent Haemophilus influenzae type B vaccine experience

Adoption of new vaccines in developing countries is critical to reducing child mortality and meeting Millennium Development Goal 4. However, such introduction has historically suffered from significant delays that can be attributed to various factors including (i) lack of recognition of the value of a vaccine, (ii) factors related to weak health systems, and (iii) policy considerations. Recently, the Global Alliance for Vaccines and Immunization (GAVI) supported efforts to accelerate the introduction of Haemophilus influenzae type b (Hib) vaccines in developing countries, which resulted in a significant surge in vaccine adoption by these countries. The experience with Hib vaccines, as well as similar efforts by GAVI to support the introduction of new pneumococcal and rotavirus vaccines, provides a strategy for new vaccine adoption that is reviewed in this paper, providing a useful model to help accelerate the uptake of other life-saving vaccines. This strategy addresses barriers for vaccine adoption by focusing on three major areas: (i) communications to increase awareness about the various factors needed for evidence-based decisions that meet a country's health goals; (ii) research activities to answer key questions that support vaccine introduction and long-term programme sustainability; and (iii) coordination with the various stakeholders at global, regional and country levels to ensure successful programme implementation.     

Delivering vaccines to the people who need them most

Thanks to the Global Alliance for Vaccines and Immunization (GAVI), the Vaccine Fund and the Bill & Melinda Gates Foundation, the global health community has made enormous progress in providing already existing vaccines to developing countries. However, there still exists a gap to develop vaccines for which there is no market in the Western world, owing to low economic incentives for the private sector to justify the investments necessary for vaccine development. In many cases, industry has the technologies, but lacks the impetus to direct resources to develop these vaccine products. The present emergency with the Ebola vaccine provides us an excellent example where a vaccine was feasible several years ago, but the global health community waited for a humanitarian disaster to direct efforts and resources to develop this vaccine. In the beginning of 2015, the first large-scale trials of two experimental vaccines against Ebola virus disease have begun in West Africa. During the past few years, several institutions have dedicated efforts to the development of vaccines against diseases present only in low-income countries. These include the International Vaccine Institute, the Novartis Vaccines Institute for Global Health, the Hilleman Institute, the Sabin Vaccine Institute and the Infectious Disease Research Institute. Nevertheless, solving this problem requires a more significant global effort than that currently invested. These efforts include a clear policy, global coordination of funds dedicated to the development of neglected disease and an agreement on regulatory strategies and incentives for the private sector.     

我国宫颈癌疫苗市场分析及对策研究*

宫颈癌Cervical cancer是最常见的妇科恶性肿瘤,是威胁女性健康的第二大恶性肿瘤。宫颈癌疫苗是预防宫颈癌发病的有效途径。2019年以前葛兰素史克(GSK)和默沙东(MSD)垄断了全球宫颈癌疫苗药物市场。虽然国内宫颈癌疫苗起步较晚,但在国内创新政策驱动下,20种疫苗已进入临床阶段,特别是由厦门万泰联合厦门大学研发的馨可宁于2020年4月获批上市,它是我国首个自主研发、全球第三个的宫颈癌疫苗。相比较欧美等发达国家,我国在宫颈癌疫苗推广力度上还有较大差距,我国9~45岁女性的HPV疫苗接种率不足0.05%。面对HPV疫苗接种覆盖率低,提出了优化HPV疫苗审评审批流程、将HPV疫苗纳入国家免疫规划、提高女性对HPV疫苗的认识等对策建议。     

The WHO network of collaborating centres on standardization and regulatory evaluation of vaccines

WHO Collaborating Centres (CCs) form part of an international collaborative network set up by WHO in support of its mandated programme at the country, intercountry, regional, interregional and global levels, as appropriate. As part of its mandate in the area of biologicals, WHO has broadened the scope of its work and has expanded the range of activities devoted to the establishment of international standards for vaccines. In line with global immunization goals, the need for standards for evaluation of quality, safety and efficacy of new vaccines, as well as those that have been in use for a long time, has significantly increased. Furthermore, complex issues related to new production methodologies, more sophisticated techniques for characterization and laboratory testing, and for nonclinical and clinical evaluation of vaccines have raised a number of regulatory challenges for WHO when requested to assist its Member States. In this context, CCs in the area of standardization of vaccines and biotherapeutics (excluding blood products) have provided technical assistance and have broadened the scope of their work over time. In the area of standardization and regulatory evaluation of vaccines, WHO currently has six CCs as well as one candidate centre for which the designation process has been initiated and a further three candidate centres with great potential. The purpose of the meeting held on 24–26 April 2012 was to improve understanding of WHO's priorities in setting standards, to facilitate their implementation, and to increase transparency of the roles and responsibilities of CCs. The meeting was also an excellent opportunity to explore possibilities for improving collaboration between WHO and CCs, as well as among CCs themselves by working as a CC network. All CCs expressed a wish for increased interaction, information-sharing, collaboration and other ways of working together that may lead to cross-fertilization between the CCs. Synergy was recognized as a significant mechanism for leveraging existing resources in responding to global public health challenges and in addressing WHO's priorities. Agreement was reached for operating as a network of CCs.     

Stability testing of vaccines: Developing Countries Vaccine Manufacturers' Network (DCVMN) perspective

Stability testing is an integral part of the vaccine manufacturing process and is crucial for the success of immunization programs. WHO (World Health Organization) has recently published guidelines on the stability testing of vaccines. These guidelines enlist scientific basis and principles for stability testing at various stages like development, pre-clinical, clinical, licensing, lot release and post-licensure monitoring. DCVMN (Developing Countries Vaccine Manufacturers' Network) is an international body of developing countries vaccine manufacturers and has viewpoints on technical and administrative issues in stability testing of vaccines. We here highlight viewpoints, possible roles and global expectations of DCVMN in the area of stability testing of vaccines.     

Effect of expanded US recommendations for seasonal influenza vaccination: comparison of two pediatric emergency departments in the United States and Canada

Background:

Starting in the 2006/2007 influenza season, the US Advisory Committee on Immunization Practices expanded its recommendations for seasonal influenza vaccination to include healthy children aged 24–59 months. The parallel Canadian organization, the National Advisory Committee on Immunization, did not at that time issue a similar recommendation, thereby creating a natural experiment to evaluate the effect of the policy in the United States.

Methods:

We examined data for 2000/2001 through 2008/2009 and estimated relative changes in visits to the emergency department for influenza-like illness at two pediatric hospitals, one in Boston, Massachusetts, and the other in Montréal, Quebec, following the US policy change. Models were adjusted for virologic factors, seasonal trends and all-cause utilization of the emergency department.

Results:

Of 1 043 989 visits to the emergency departments of the two hospitals for any reason during the study period, 114 657 visits were related to influenza-like illness. Adjusted models estimated a 34% decline in rates of influenza-like illness among children two to four years old in the US hospital relative to the Canadian hospital (rate ratio 0.66, 95% confidence interval 0.58–0.75) following the 2006 policy change of the Advisory Committee on Immunization Practices. This was accompanied by more modest declines of 11% to 18% for the other age groups studied.

Interpretation:

The divergence in influenza rates among children in the US and Canadian sample populations after institution of the US policy to vaccinate children two to four years of age is evidence that the recommendation of the US Advisory Committee on Immunization Practices resulted in a reduction in influenza-related morbidity in the target group and may have indirectly affected other pediatric age groups. Provincial adoption of the 2010 recommendation of teh National Advisory Committee on Immunization in Canada to vaccinate childen two to four years of age might positively affect influenza morbidity in Canada.Seasonal influenza is an important cause of visits to the emergency department among children during winter months, and its control and prevention rely on annual vaccination.^1–4 In the United States, the Advisory Committee on Immunization Practices is responsible for guiding immunization practices, and it revises its recommendations annually. Until the 2004/2005 influenza season, vaccination was targeted to primarily older individuals and those with certain medical conditions.⁵ On the basis of evidence that young children are at elevated risk for admission to hospital because of influenza-related complications, the recommendations were expanded for the 2004/2005 season to include healthy children aged 6–23 months.⁶Starting in the 2006/2007 season, the recommendations of the Advisory Committee on Immunization Practices regarding influenza vaccination were expanded again to include healthy children aged 24–59 months, a shift that added 10.6 million children to the target group.⁷ For the 2008/2009 season, recommendations were further expanded to include all persons 6 months to 18 years old,⁸ and for the 2010/2011 season, the influenza vaccine was advised for all individuals over 6 months of age.⁹In Canada, the National Advisory Committee on Immunization is the federal organization responsible for guiding the use of vaccines. Until the 2006/2007 season, the recommendations of this committee for the use of seasonal influenza vaccines were harmonized with those of its US counterpart. However, it was not until the 2010/2011 season that the Canadian committee began recommending that children two to four years old be routinely vaccinated against influenza, and not all Canadian provinces have adopted this recommendation.We aimed to examine the effect of the 2006 recommendation of the Advisory Committee on Immunization Practices to expand influenza vaccination coverage to preschool-aged children. Interannual variation in severity of disease and effectiveness of the vaccine make it difficult to directly estimate the effect of an intervention on the incidence of influenza in any given community. Instead, we compared surveillance data from the emergency departments of two pediatric hospitals, one in Boston, Massachusetts, and the other in Montréal, Quebec, cities with similar epidemiologic dynamics for seasonal influenza.¹⁰ Our specific objective was to estimate the relative effect of the 2006 US recommendation on influenza-related emergency department visits to Children’s Hospital Boston, with the Montreal Children’s Hospital as an untreated control.     

Interactive learning and action: realizing the promise of synthetic biology for global health

The emerging field of synthetic biology has the potential to improve global health. For example, synthetic biology could contribute to efforts at vaccine development in a context in which vaccines and immunization have been identified by the international community as being crucial to international development efforts and, in particular, the millennium development goals. However, past experience with innovations shows that realizing a technology’s potential can be difficult and complex. To achieve better societal embedding of synthetic biology and to make sure it reaches its potential, science and technology development should be made more inclusive and interactive. Responsible research and innovation is based on the premise that a broad range of stakeholders with different views, needs and ideas should have a voice in the technological development and deployment process. The interactive learning and action (ILA) approach has been developed as a methodology to bring societal stakeholders into a science and technology development process. This paper proposes an ILA in five phases for an international effort, with national case studies, to develop socially robust applications of synthetic biology for global health, based on the example of vaccine development. The design is based on results of a recently initiated ILA project on synthetic biology; results from other interactive initiatives described in the literature; and examples of possible applications of synthetic biology for global health that are currently being developed.     

Rabies control and management.

Since the 1950s rabies has become a familiar threat in southern Canada. Periodic outbreaks remind us how slight our control over it is. Although new vaccines such as human diploid-cell rabies vaccine have greatly improved the management of rabies in humans, true control must be sought through knowledge of the disease in or wildlife. A guide to rabies prophylaxis in humans is presented, courtesy of the National Advisory Committee on Immunization.     

Accelerating Policy Decisions to Adopt Haemophilus influenzae Type b Vaccine: A Global,Multivariable Analysis

Background

Adoption of new and underutilized vaccines by national immunization programs is an essential step towards reducing child mortality. Policy decisions to adopt new vaccines in high mortality countries often lag behind decisions in high-income countries. Using the case of Haemophilus influenzae type b (Hib) vaccine, this paper endeavors to explain these delays through the analysis of country-level economic, epidemiological, programmatic and policy-related factors, as well as the role of the Global Alliance for Vaccines and Immunisation (GAVI Alliance).

Methods and Findings

Data for 147 countries from 1990 to 2007 were analyzed in accelerated failure time models to identify factors that are associated with the time to decision to adopt Hib vaccine. In multivariable models that control for Gross National Income, region, and burden of Hib disease, the receipt of GAVI support speeded the time to decision by a factor of 0.37 (95% CI 0.18–0.76), or 63%. The presence of two or more neighboring country adopters accelerated decisions to adopt by a factor of 0.50 (95% CI 0.33–0.75). For each 1% increase in vaccine price, decisions to adopt are delayed by a factor of 1.02 (95% CI 1.00–1.04). Global recommendations and local studies were not associated with time to decision.

Conclusions

This study substantiates previous findings related to vaccine price and presents new evidence to suggest that GAVI eligibility is associated with accelerated decisions to adopt Hib vaccine. The influence of neighboring country decisions was also highly significant, suggesting that approaches to support the adoption of new vaccines should consider supply- and demand-side factors. Please see later in the article for the Editors'' Summary     

Proteomics for development of vaccine

The success of genome projects has provided us with a vast amount of information on genes of many pathogenic species and has raised hopes for rapid progress in combating infectious diseases, both by construction of new effective vaccines and by creating a new generation of therapeutic drugs. Proteomics, a strategy complementary to the genomic-based approach, when combined with immunomics (looking for immunogenic proteins) and vaccinomics (characterization of host response to immunization), delivers valuable information on pathogen-host cell interaction. It also speeds the identification and detailed characterization of new antigens, which are potential candidates for vaccine development. This review begins with an overview of the global status of vaccinology based on WHO data. The main part of this review describes the impact of proteomic strategies on advancements in constructing effective antibacterial, antiviral and anticancer vaccines. Diverse aspects of disease mechanisms and disease preventions have been investigated by proteomics.     

Meeting of the Strategic Advisory Group of Experts on immunization,October 2009 – Conclusions and recommendations

The conclusions and recommendations from the October 2009 meeting of the Strategic Advisory Group of Experts (SAGE) on immunization have been published in the WHO weekly epidemiological record (December 11, 2009) and are reproduced with the permission.     

WHO Study Group on cell substrates for production of biologicals, Geneva, Switzerland, 11–12 June 2007

For many years, the World Health Organization (WHO) has provided global leadership in defining technical specifications for quality assurance and safety of biological medicines produced in cell substrates. Current WHO requirements for the use of animal cells as substrates for production of vaccines and other biologicals were adopted by the WHO Expert Committee on Biological Standardization in 1996 (WHO TRS 878). Since then, significant progress especially in the development of vaccines in novel continuous cell lines of mammalian origin as well as in insect cells has been made and consequently there is an increasing need for the re-evaluation of existing criteria for the acceptability of such cell lines. In addition there is also a need to consider new issues in cell substrate safety arising from these new cell types and developments in technology and scientific knowledge. In response to these demands, the WHO Study Group on Cell Substrates was formed in 2006 to initiate revision of WHO requirements and to address the need for further research in this area. At its second meeting on 11-12 June 2007, the Study Group reviewed scientific data that would form the basis for new recommendations and made a number of proposals for further investigations. The Study Group is working on the preparation of a revised WHO document, and a broad consultation with regulators, manufacturers, and other relevant parties is planned for 2008.     

Vaccination of children born from HIV-infected mothers against Haemophilus influenzae type b infection

Course of postvaccinal period after injection of vaccine against Haemophilus influenzae type b administered simultaneously with vaccines of Russian national immunization schedule was studied in children born from HIV-infected mothers. Good tolerability of the vaccine administered concomitantly with diphtheria-tetanus-whole cell pertussis and inactivated polio vaccines (Imovax Polio), which is comparable with tolerability in healthy children, was demonstrated. Prevaccination titers of antibodies and their dynamics during immunization process were described. Increase of levels of antibodies was detected both in the group of children with perinatal contact with HIV infection and in the group of HIV-infected children.     

A vision of a world without polio: the OPV cessation strategy.

Once the eradication of wild poliovirus has been confirmed, the public health benefits of routine immunization with OPV will no longer outweigh the burden of disease either due to paralysis caused by OPV (vaccine associated paralytic polio), or by outbreaks caused by circulating vaccine-derived polioviruses. The eventual cessation of OPV use in routine immunization programmes worldwide will become necessary to assure a lasting eradication of polio. As the world moves towards polio eradication and its certification, preparations are therefore being intensified for OPV cessation, and the risk management framework for safe OPV cessation is being put in place. The framework includes bio-containment of all known poliovirus and potentially infected substances, development of an international stockpile of oral polio vaccine, ensuring a mechanism for continued global surveillance and response for polio after eradication has been certified, and national policies if countries decide to continue vaccinating with inactivated polio vaccine (IPV). It is ironic that the vaccine on which the world has depended for polio eradication will itself become a risk to eradication once the transmission of wild poliovirus has been interrupted. Final preparations for the eventual global and simultaneous cessation of OPV will require the same level of international cooperation and coordination that has brought the world to the verge of polio eradication.     

Global diversity of dietary intakes and standards for zinc,iron, and copper

BackgroundThe essentiality of trace elements in human diets is well recognized and adequate levels are a critical component of optimal health. To date, public health efforts have focused primarily on macronutrients or trace minerals that are easily analyzed. The goal of this research is to provide assessment of the dietary standards developed for Zn, Fe, and Cu in 100+ developed, marginal, and developing countries. We summarize the current recommendations and changes from the last decade, categorize and provide scientific basis for values established, factors that affect requirements, and current global challenges.MethodsThe electronic databases of Google Scholar, PubMed, Embase, Web of Science and Cochrane Library were searched using the keywords “trace minerals,” “micronutrients, ““zinc,” “iron,” “copper,” “dietary standards” and “recommendations.” A total of 123 studies published from 1965 to 2019 were included.ResultsThe World Health Organization (WHO) has established dietary standards to address nutrient deficiencies, prevent infections and ensure basic metabolic functions; these are utilized by most developing countries. Developed countries or their alliances have established values similar to or higher than the WHO, primarily for promotion of optimal health and well-being. Transitional countries are more concerned with issues of bioavailability, food security and undernutrition. Globally, Zn and Cu recommendations are lower in women than in men; Fe requirements are higher to compensate for menstrual losses. Important considerations in establishing guidelines for these minerals include bioaccessibility, dietary practices and restrictions, food processing, interactions, and chemical forms. The global challenges of the triple burden of malnutrition, hidden hunger, increased consumption of ultra-processed foods and obesity have been associated with Zn, Fe, and Cu deficiencies.ConclusionThis research provides public policy and health professionals evidenced-based information useful for the establishment of dietary standards world-wide.     

Technology transfer of Sabin-IPV to new developing country markets.

The Netherlands Vaccine Institute (NVI) developed the micro-carrier technology for large-scale production of IPV in the late 1960s and has used this technology successfully to produce IPV as well as DTP-IPV for the national immunization program in the Netherlands. As a public sector organization, and as one of the Millennium Development Goals, NVI has supported over the years access to vaccine technology like DTP and Hib for vaccine manufacturers in developing countries. In line with this role as a resource institute, NVI has recently been approached by a number of vaccine manufacturers, predominantly from developing countries, for transfer of IPV technology to meet the anticipated increase in demand for IPV following OPV cessation. Since WHO encourages new manufacturers to use the attenuated Sabin virus instead of wild polio strains in the production of IPV, NVI decided to respond positively to this WHO policy. The existing NVI experience in large-scale production of IPV and OPV using Vero cell based micro-carrier technology and its experience with experimental Sabin-IPV is an attractive start for the development of Sabin-IPV. This paper discusses the approach followed and the experience already gained in the project, as well as factors critical to its success.     

A conceptual framework for the revision of the ICD-10 classification of mental and behavioural disorders

The World Health Organization (WHO) is revising the ICD-10 classification of mental and behavioural disorders, under the leadership of the Department of Mental Health and Substance Abuse and within the framework of the overall revision framework as directed by the World Health Assembly. This article describes WHO’s perspective and priorities for mental and behavioural disorders classification in ICD-11, based on the recommendations of the International Advisory Group for the Revision of ICD-10 Mental and Behavioural Disorders. The WHO considers that the classification should be developed in consultation with stakeholders, which include WHO member countries, multidisciplinary health professionals, and users of mental health services and their families. Attention to the cultural framework must be a key element in defining future classification concepts. Uses of the ICD that must be considered include clinical applications, research, teaching and training, health statistics, and public health. The Advisory Group has determined that the current revision represents a particular opportunity to improve the classification’s clinical utility, particularly in global primary care settings where there is the greatest opportunity to identify people who need mental health treatment. Based on WHO’s mission and constitution, the usefulness of the classification in helping WHO member countries, particularly low- and middle-income countries, to reduce the disease burden associated with mental disorders is among the highest priorities for the revision. This article describes the foundation provided by the recommendations of the Advisory Group for the current phase of work.