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.     

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.     

Contribution of the GAVI Alliance to improving health and reducing poverty

The Global Alliance for Vaccines and Immunization (GAVI), now 10 years old, was established as a successful and innovative public-private partnership to deal with a fundamental inequity. The poorest children in the poorest parts of the world were being denied access to life-saving vaccines simply on the basis of cost. GAVI has been successful in mobilizing significant funding from donors and through innovative financing instruments, immunizing large numbers of children. GAVI has been less successful, at least in the time frames first envisaged, at quickly reducing the prices of new and under-used vaccines to levels affordable by the poorest countries. Vaccines remain some of the most cost effective of public health interventions. As GAVI seeks to introduce a new set of vaccines to tackle major killers such as pneumonia and diarrhoea, and emerging threats such as cervical cancer, it needs to raise significant additional funds. There is no single solution. Multiple and new instruments will be required to raise finance both globally and at the country level, and also to incentivize industry and others to provide vaccines at affordable prices to the poorest countries.     

The contribution of vaccination to global health: past,present and future

Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO''s Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer''s disease.     

Global immunization policies and recommendations: objectives and process

The World Health Organization (WHO) has a dual mandate of providing global policies, standards and norms as well as support for member countries in applying such policies and standards to national programmes with the aim to improve health. The vaccine world is changing and with it the demands and expectations of the global and national policy makers, donors, and other interested parties. Changes pertain to : new vaccines and technologies developments, vaccine safety issues, regulation and approval of vaccines, and increased funding flowing through new financing mechanisms. This places a special responsibility on WHO to respond effectively. WHO has recently reviewed and optimized its policy making structure for vaccines and immunization and adjusted it to the new Global Immunization Vision and Strategy, which broadens the scope of immunization efforts to all age groups and vaccines with emphasis on integration of immunization delivery with other health interventions. This includes an extended consultation process to promptly generate evidence base recommendations, ensuring transparency of the decision making process and added communication efforts. This article presents the objectives and impact of the process set to develop global immunization policies, norms, standards and recommendations. The key advisory committees landscape contributing to this process is described. This includes the Strategic Advisory Group of Experts, the Global Advisory Committee on Vaccine Safety and the Expert Committee on Biological Standardization. The elaboration of WHO vaccine position papers is also described.     

Japan's innovation for global health – GHIT's catalytic role

The global fight against infectious diseases, both emerging and re-emerging, endures. Japan's commitments and reputation as a good global citizen and its responsibility to uphold domestic and international human security mean that it is in Japan's best interest to leverage its innovative and technological capabilities for global infectious disease prevention and control. The Global Health Innovative Technology Fund (GHIT Fund), an international non-profit organization based in Tokyo, Japan, was established by the Japanese government, multiple Japanese pharmaceutical companies, and the Bill & Melinda Gates Foundation as the first fund of its kind, with an aim to tackle the global burden of infectious diseases by facilitating and funding global health R&D of drugs, vaccines, and diagnostics. Since its inception in 2013, the GHIT Fund has invested more than 209 million USD in more than 90 projects, which consist of collaborations among Japanese and non-Japanese entities, six of which have already progressed to clinical stage development. Japan will continue to play a major role in the global health arena by further advancing R&D innovations for infectious diseases.     

Oral hepatitis B vaccine candidates produced and delivered in plant material

Hepatitis B is a major global health problem; approximately two billion people are infected with the virus worldwide, despite the fact that safe and efficacious vaccines have been developed and used for nearly 20 years. Prohibitive costs for vaccine purchase and administration restrict uptake in many developing nations. Agencies such as the Global Alliance for Vaccination and Immunization are helping to make current vaccines more available, but reduced costs would greatly aid this effort. Oral delivery is an option to reduce the expense of administering hepatitis B vaccines. It may also improve compliance, and orally delivered vaccines may be more efficacious among poor responders to current vaccines. However, to induce protective efficacy, oral administration may require encapsulation of antigen and delivery of large doses. Plant-based expression systems offer an oral delivery alternative with low production costs, and they also encapsulate the antigen. Some plant-based systems also stabilize antigen and therefore reduce storage and distribution costs. The hepatitis B major surface antigen has been expressed in several plant systems. A variety of regulatory sequences and subcellular targets have been used to achieve expression suitable for early stage clinical trials. However, further increase in expression will be necessary for practical and efficacious products. Appropriate processing can yield palatable products with uniform antigen concentration. The antigen expressed in plant systems shows extensive disulphide cross-linking and oligomerization and forms virus-like particles. Oral delivery of the antigen in plant material can induce a serum antibody response, prime the immune system for a subsequent injection of antigen and give a boosted response to a prior injection. Small scale clinical trials in which the antigen has been delivered orally in edible plant material indicate safety and immunogenicity.     

Vaccines and future global health needs

Increased international support for both research into new vaccines and their deployment in developing countries has been evident over the past decade. In particular, the GAVI Alliance has had a major impact in increasing uptake of the six common infant vaccines as well as those against hepatitis B and yellow fever. It further aims to introduce pneumococcal and rotavirus vaccines in the near future and several others, including those against human papillomavirus, meningococcal disease, rubella and typhoid not long after that. In addition, there is advanced research into vaccines against malaria, HIV/AIDS and tuberculosis. By 2030, we may have about 20 vaccines that need to be used in the developing world. Finding the requisite funds to achieve this will pose a major problem. A second and urgent question is how to complete the job of global polio eradication. The new strategic plan calls for completion by 2013, but both pre-eradication and post-eradication challenges remain. Vaccines will eventually become available beyond the field of infectious diseases. Much interesting work is being done in both autoimmunity and cancer. Cutting across disease groupings, there are issues in methods of delivery and new adjuvant formulations.     

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     

Adoption of rapid diagnostic tests for the diagnosis of malaria, a preliminary analysis of the global fund program data, 2005 to 2010

Introduction

The World Health Organization Guidelines for the Treatment of Malaria, in 2006 and 2010, recommend parasitological confirmation of malaria before commencing treatment. Although microscopy has been the mainstay of malaria diagnostics, the magnitude of diagnostic scale up required to follow the Guidelines suggests that rapid diagnostic tests (RDTs) will be a large component. This study analyzes the adoption of rapid diagnostic testing in malaria programs supported by the Global Fund to fight AIDS, Tuberculosis and Malaria (Global Fund), the leading international funder of malaria control globally.

Methods and Findings

We analyzed, for the period 2005 to 2010, Global Fund programmatic data for 81 countries on the quantity of RDTs planned; actual quantities of RDTs and artemisinin-based combination treatments (ACTs) procured in 2009 and 2010; RDT-related activities including RDTs distributed, RDTs used, total diagnostic tests including RDTs and microscopy performed, health facilities equipped with RDTs; personnel trained to perform rapid diagnostic malaria test; and grant budgets allocated to malaria diagnosis. In 2010, diagnosis accounted for 5.2% of malaria grant budget. From 2005 to 2010, the procurement plans include148 million RDTs through 96 malaria grants in 81 countries. Around 115 million parasitological tests, including RDTs, had reportedly been performed from 2005 to 2010. Over this period, 123,132 health facilities were equipped with RDTs and 137,140 health personnel had been trained to perform RDT examinations. In 2009 and 2010, 41 million RDTs and 136 million ACTs were purchased. The ratio of procured RDTs to ACTs was 0.26 in 2009 and 0.34 in 2010.

Conclusions/significance

Global Fund financing has enabled 81 malaria-endemic countries to adopt WHO guidelines by investing in RDTs for malaria diagnosis, thereby helping improve case management of acute febrile illness in children. However, roll-out of parasitological diagnosis lags behind the roll-out of ACT-based treatment, and will require prioritization of investments.     

Synthetic biology as a source of global health innovation

Synthetic biology has the potential to contribute breakthrough innovations to the pursuit of new global health solutions. Wishing to harness the emerging tools of synthetic biology for the goals of global health, in 2011 the Bill & Melinda Gates Foundation put out a call for grant applications to “Apply Synthetic Biology to Global Health Challenges” under its “Grand Challenges Explorations” program. A highly diverse pool of over 700 applications was received. Proposed applications of synthetic biology to global health needs included interventions such as therapeutics, vaccines, and diagnostics, as well as strategies for biomanufacturing, and the design of tools and platforms that could further global health research.     

Costs of Eliminating Malaria and the Impact of the Global Fund in 34 Countries

Background

International financing for malaria increased more than 18-fold between 2000 and 2011; the largest source came from The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund). Countries have made substantial progress, but achieving elimination requires sustained finances to interrupt transmission and prevent reintroduction. Since 2011, global financing for malaria has declined, fueling concerns that further progress will be impeded, especially for current malaria-eliminating countries that may face resurgent malaria if programs are disrupted.

Objectives

This study aims to 1) assess past total and Global Fund funding to the 34 current malaria-eliminating countries, and 2) estimate their future funding needs to achieve malaria elimination and prevent reintroduction through 2030.

Methods

Historical funding is assessed against trends in country-level malaria annual parasite incidences (APIs) and income per capita. Following Kizewski et al. (2007), program costs to eliminate malaria and prevent reintroduction through 2030 are estimated using a deterministic model. The cost parameters are tailored to a package of interventions aimed at malaria elimination and prevention of reintroduction.

Results

The majority of Global Fund-supported countries experiencing increases in total funding from 2005 to 2010 coincided with reductions in malaria APIs and also overall GNI per capita average annual growth. The total amount of projected funding needed for the current malaria-eliminating countries to achieve elimination and prevent reintroduction through 2030 is approximately US$8.5 billion, or about $1.84 per person at risk per year (PPY) (ranging from $2.51 PPY in 2014 to $1.43 PPY in 2030).

Conclusions

Although external donor funding, particularly from the Global Fund, has been key for many malaria-eliminating countries, sustained and sufficient financing is critical for furthering global malaria elimination. Projected cost estimates for elimination provide policymakers with an indication of the level of financial resources that should be mobilized to achieve malaria elimination goals.     

Biodiversität und Klima: Wandel in vollem Gange!

Global change is in full progress! Global change is in full progress and includes world‐wide climatic and biodiversity changes. Alterations of land and water use in many areas as well as passive and active spreading of exotic species are further drivers of change. Mankind is impacted in many respects. Global change will lead in many countries to increasing poverty and will result in political instability. The research about causes and consequences of biological and climatic changes and the discussion within the society is therefore a crucial challenge.     

Scaling up towards international targets for AIDS, tuberculosis, and malaria: contribution of global fund-supported programs in 2011-2015

Objective

The paper projects the contribution to 2011–2015 international targets of three major pandemics by programs in 140 countries funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria, the largest external financier of tuberculosis and malaria programs and a major external funder of HIV programs in low and middle income countries.

Design

Estimates, using past trends, for the period 2011–2015 of the number of persons receiving antiretroviral (ARV) treatment, tuberculosis case detection using the internationally approved DOTS strategy, and insecticide-treated nets (ITNs) to be delivered by programs in low and middle income countries supported by the Global Fund compared to international targets established by UNAIDS, Stop TB Partnership, Roll Back Malaria Partnership and the World Health Organisation.

Results

Global Fund-supported programs are projected to provide ARV treatment to 5.5–5.8 million people, providing 30%–31% of the 2015 international target. Investments in tuberculosis and malaria control will enable reaching in 2015 60%–63% of the international target for tuberculosis case detection and 30%–35% of the ITN distribution target in sub-Saharan Africa.

Conclusion

Global Fund investments will substantially contribute to the achievement by 2015 of international targets for HIV, TB and malaria. However, additional large scale international and domestic financing is needed if these targets are to be reached by 2015.     

Integration of hepatitis B vaccination into national immunisation programmes. Viral Hepatitis Prevention Board.

Hepatitis B is a major public health problem even though safe and effective vaccines have been available for over 10 years. Because hepatitis B infection is largely asymptomatic with long term complications occurring after many years it has not received the attention it deserves. Strategies to immunise those at high risk have failed to control the disease. Delegates to the World Health Assembly of the World Health Organisation recommended in May 1992 that all countries should integrate hepatitis B vaccination into their national immunisation programmes by 1997. Some western European countries remain unconvinced that the burden of disease warrants the expense of universal vaccination. However, epidemiological data and economic evaluation show that universal hepatitis B vaccination is cost effective in countries with low endemicity and that it will control hepatitis B, reinforcing the necessity for action.     

Vaccine preventable viral diseases in developing countries

There are several viral infectious diseases with a high impact on developing countries which can be prevented by immunization with existing vaccines. The most important are poliomyelitis, measles, hepatitis B and yellow fever. Vaccines against poliomyelitis and measles used within the framework of the WHO/Expanded Programme on Immunization prevent about 1.4 million deaths from measles and 360,000 cases of paralytic polio per year in developing countries, but about 1.5 million measles' deaths and 200,000 cases of paralytic polio still occur. Hepatitis B infection and its sequelae are responsible for over 50 million infections and one million deaths annually. Highly effective hepatitis B vaccines are now available and the price of these vaccines for the developing world has fallen dramatically. Despite the availability of a safe and efficacious yellow fever vaccine since 1937, 5400 cases of this disease with 3200 deaths were reported in Africa and South America from 1986 to 1988. Because of the efficacy of existing vaccines and the lack of animal reservoirs or vectors, systematic vaccination programmes within the framework of the Expanded Programme on Immunization (EPI) could theoretically eliminate and even eradicate poliomyelltis, measles and hepatitis B. Many different obstacles need to be overcome before these goals are realized.This paper was presented at the IUMS Symposium on New Developments in Diagnosis and Control of Infectious Diseases held in conjunction with the Eighth International Congress of Virology, Berlin, Germany, 24–31 August 1990.     

The Innovative Vector Control Consortium: improved control of mosquito-borne diseases

Few new insecticides have been produced for control of disease vectors for public health in developing countries over the past three decades, owing to market constraints, and the available insecticides are often poorly deployed. The Innovative Vector Control Consortium will address these market failures by developing a portfolio of chemical and technological tools that will be directly and immediately accessible to populations in the developing world. The Bill and Melinda Gates Foundation has supported this new initiative to enable industry and academia to change the vector control paradigm for malaria and dengue and to ensure that vector control, alongside drugs, case management and vaccines, can be better used to reduce disease.     

Oral vaccines: new needs, new possibilities

Vaccination is an important tool for handling healthcare programs both in developed and developing countries. The current global scenario calls for a more-efficacious, acceptable, cost-effective and reliable method of immunization for many fatal diseases. It is hoped that the adoption of oral vaccines will help to provide an effective vaccination strategy, especially in developing countries. Mucosal immunity generated by oral vaccines can serve as a strong first line of defense against most of the pathogens infecting through the mucosal lining. Advances in elucidating the mechanism of action of oral vaccines will facilitate the design of more effective, new generation vaccines. There are promising developments in the use of different agents to effectively deliver the vaccine candidate. It is hoped that ongoing research may be able to set another cardinal point, after polio vaccine, in eradicating infectious diseases.     

Human papillomavirus (HPV) infection in Southern Africa: prevalence,immunity, and vaccine prospects

Human papillomavirus (HPV) associated cancers are more prevalent in developing countries compared to developed countries. The major cancer caused by HPV is cervical cancer. The humoral immune response to HPV can be a marker of past infection but may also reflect persistent infection and cervical disease. IgA antibodies to HPV in oral fluid were also found to be markers of cervical disease. Cell mediated immunity is important in clearing HPV infection and for regression of the associated lesions: this means that women infected with HIV have a high prevalence of co-infection with HPV. Good cervical screening programmes can control HPV associated cervical neoplasia. However, in countries such as South Africa, where these programmes are inadequate, there is a need for an HPV vaccine. The development of HPV vaccines is reviewed. There is a call for an inexpensive vaccine that will be accessible to the women that do not have access to adequate screening programmes and are therefore at the greatest risk of cervical cancer.     

Estimating the Development Assistance for Health Provided to Faith-Based Organizations, 1990–2013

Background

Faith-based organizations (FBOs) have been active in the health sector for decades. Recently, the role of FBOs in global health has been of increased interest. However, little is known about the magnitude and trends in development assistance for health (DAH) channeled through these organizations.

Material and Methods

Data were collected from the 21 most recent editions of the Report of Voluntary Agencies. These reports provide information on the revenue and expenditure of organizations. Project-level data were also collected and reviewed from the Bill & Melinda Gates Foundation and the Global Fund to Fight AIDS, Tuberculosis and Malaria. More than 1,900 non-governmental organizations received funds from at least one of these three organizations. Background information on these organizations was examined by two independent reviewers to identify the amount of funding channeled through FBOs.

Results

In 2013, total spending by the FBOs identified in the VolAg amounted to US$1.53 billion. In 1990, FB0s spent 34.1% of total DAH provided by private voluntary organizations reported in the VolAg. In 2013, FBOs expended 31.0%. Funds provided by the Global Fund to FBOs have grown since 2002, amounting to $80.9 million in 2011, or 16.7% of the Global Fund’s contributions to NGOs. In 2011, the Gates Foundation’s contributions to FBOs amounted to $7.1 million, or 1.1% of the total provided to NGOs.

Conclusion

Development assistance partners exhibit a range of preferences with respect to the amount of funds provided to FBOs. Overall, estimates show that FBOS have maintained a substantial and consistent share over time, in line with overall spending in global health on NGOs. These estimates provide the foundation for further research on the spending trends and effectiveness of FBOs in global health.