Marissa Chmiola

  Senate supports global health R&D in defense appropriations bill and report. Photo: Ken Kistler Earlier this month, we reported that both the House and Senate Appropriations Committees included language supporting global health research and development (R&D) in their reports concerning funding for the Department of State, foreign operations and related programs. Last week, we heard even more good news for global health R&D out of the Senate Appropriations Committee—this time related to the Department of Defense (DoD). The fiscal year (FY) 2015 defense appropriations bill—which was approved by the Committee last Thursday—includes a $7 million increase for peer-reviewed medical research—from $200 million in FY 2014 to $207 million this year—despite reducing overall DoD funding from FY 2014 levels. In addition, in the accompanying report, the Appropriations Committee includes very strong language recognizing DoD’s substantial contributions to global health R&D and the need to support sustained US investments in this area. The committee report includes language submitted by GHTC recognizing “the critical contribution that the department’s [R&D] portfolio makes in protecting our troops from infectious and neglected diseases they may encounter on missions around the world” and noting “the need to sustain and support US investment in this area by fully funding those R&D programs that carry out this work.” Committee recognizes role of infectious disease research in improving US security The committee report also recognizes the threat that neglected infectious diseases—such as malaria, dengue fever, and Chikungunya—pose to the effectiveness of US forces deployed overseas and expresses concern over reductions in research funding for these disease areas. In the report, the committee notes that it is “concerned with the department’s decisions over recent years to precipitously decrease funding for malaria research” and that it “encourages the department to address diseases of military importance and invest in research for chemoprophylaxis, surveillance, and other countermeasures.” Photo: PATH/Gabe Bienczycki Report calls for DoD to improve coordination across R&D programming The committee report also includes language—submitted by GHTC—which directs each DoD program involved in infectious disease research to submit a report of its R&D activities to the House and Senate Defense Committees outlining the program’s funding and accomplishments from FY 2011 through 2014. As well, the committee urges DoD to partner with other organizations involved in infectious diseases research—including other federal agencies—to mitigate the duplication of research efforts and maximize the use of DoD resources. It is GHTC’s hope that these reports and activities will lead to improved coordination across DoD global health R&D programs, as well as improved coordination across all US agencies involved in global health R&D, which will in turn help fill current gaps in research programming and assure US investments are used most effectively. GHTC is glad to see the Senate recognizing DoD’s critical role in global health R&D, as well as advocating for sustained funding and improved coordination for global health R&D programming at DoD. We are hopeful that the language included in the Senate defense appropriations report will be included in whatever final legislation is passed.

During the past year, leaders from the US Global Leadership Coalition (USGLC)—an advocacy organization promoting diplomacy and development—have traveled across America seeking out innovators and innovations that best demonstrate how strategic US investments in global development can enhance America’s foreign policy and security interests—an approach USGLC calls “smart power” diplomacy. The VVM is a health innovation that is saving lives and money. Photo: Umit Kartoglu Not surprisingly, USGLC leaders discovered that investments in global health innovation are an essential part of America’s “smart power” toolbox. As USGLC leaders traveled from city to city, they discovered numerous examples of how American businesses and nongovernmental organizations (NGOs) are working with the US government to deliver global health innovations that are not only improving lives worldwide, but also creating jobs here in the United States and enhancing America’s global leadership. In fact, nearly half of the 30 programs USGLC identified as “leading American innovators” in its Innovations in Smart Power report—released today—focused on improving global health and nutrition. The report featured two innovations developed by GHTC members, including the PATH-developed Vaccine Vial Monitor (VVM), which indicates whether vaccines have been damaged from exposure to heat. The VVM not only saves lives, but also produces an estimated $14 million annual savings by preventing undamaged vaccines from being discarded. USGLC also featured the Global Health Fellows Program II—led by the Public Health Institute—which brings private sector experts from America to low- and middle-income countries in Africa and Asia—for up to three months—to share their expertise in research and medical technologies with healthcare workers in local communities. Two interns sponsored by the Global Health Fellow Program help build a house for an HIV expectant mother in Uganda. Photo: Global Health Fellows Program II/PHI Other creative global health innovations featured in the report include low-cost toilets to reduce diarrheal disease, fortified peanut paste to combat malnutrition, and an easy squeeze pouch to help HIV-positive mothers deliver antiretroviral drugs to their newborn babies. All of these projects were supported by the US government, and demonstrate how American ingenuity and investments can tackle some of the world’s greatest global health problems. It’s clear that sustained American investment in global health innovation not only supports domestic and international health improvements and economic growth, but also serves as an important diplomatic tool and a demonstration of America’s character. In other worlds, investing in global health innovation=smart power.

Tomorrow US policymakers and global health advocates will come together to talk progress made on preventing maternal and child deaths. During the day, the US Agency for International Development (USAID) will host a high-level forum called Acting on the Call: Ending Preventable Child and Maternal Deaths to both celebrate progress and assess the challenges that remain. That evening, the 5th Birthday and Beyond coalition will celebrate America’s leadership and investments worldwide to help children reach their fifth birthday. US investment in R&D has led to new innovations that are saving the lives of mothers and children. Photo: PATH/Teresa Guillien While you’ll probably hear a lot of different facts and figures, one message will be clear—the world has made remarkable progress in preventing the deaths of millions of women and children. In fact, maternal and child deaths have been cut in half in just over two decades. That means that every day this year, 17,000 more children will live and 700 more mothers will survive childbirth than did two decades ago. Central to this progress has been US investment in research and development (R&D) that has led to new medicines and innovative health products that are saving the lives of mothers and children. Globally new vaccines, drugs, diagnostics, and other health innovations have led to 4.2 million fewer child deaths in 2013 compared to 1990, according to a report by the Institute for Health Metrics and Evaluation. Innovations like the polio vaccine, oral rehydration solution to treat diarrhea, and antiretroviral therapies that prevent maternal to child HIV transfer, and others treatments have resulted in incredible gains for maternal and child health.   No country has done more than the United States to help save the lives of the world’s poorest mothers and children. A critical part of the US approach has been our world-leading investment in global health R&D. In fact, the US government is the largest funder of global heath R&D in the world—contributing over 45 percent of total investment. US government investment in global health R&D has led to breakthroughs that have transformed or are poised to transform efforts to reduce maternal and child mortality. Some examples include: The Oxytocin-Uniject™ This is a device filled with oxytocin that helps contract the uterus to reduce post-partum hemorrhage—or excessive bleeding—the leading cause of maternal death worldwide. It is easy to inject and requires little training to administer, so it’s made a dramatic difference in the ability of health workers to administer oxytocin in emergencies or in remote locations outside of traditional hospital facilities. USAID played a crucial role in funding research towards the development of this product. RTS,S malaria vaccine candidate RTS,S is the most clinically-advanced vaccine candidate for malaria—a disease which kills a child every 40 seconds. A recent study showed that infants who receive the RTS, S vaccine had one third fewer cases of both clinical and severe malaria. A vaccine could be an important tool in reducing child sickness and death from malaria. The Department of Defense provided critical funding for the early development and clinical testing of RTS,S. Rotavirus vaccines Rotavirus-induced diarrheal disease kills roughly 435,000 children younger than five each year. Two currently available rotavirus vaccines were introduced in the past two decades, with other vaccines under development showing tremendous progress. The National Institutes of Health developed the first available rotavirus vaccine and has been a financial partner in the development of subsequent vaccines. In addition, the Centers for Disease Control and Prevention also monitors efficacy and safety, and supports clinical trials of rotavirus vaccines. New contraceptive technologies Family planning technologies allow women to space their pregnancies—making it more likely for both the mother and child to survive childbirth. An analysis of 172 countries found that family planning prevented 272,000 maternal deaths in just one year. However, the contraceptive options that exist today don’t always meet the needs of women in developing countries. New vaginal rings are being developed that will be long-lasting and easy for the user to insert and remove without a doctor’s assistance, while new multipurpose prevention technologies combine the delivery of contraceptives with microbicides which reduce the transmission of HIV and other sexually transmitted infections. USAID provides funding towards the development of many of these new contraceptive technologies. While tremendous progress has been made in decreasing maternal and child deaths worldwide thanks in part to new health innovations, each year 6.6 million children still die before their first birthday and 289,000 women still die from pregnancy-related causes. That translates to 18,000 children under the age of five and 800 pregnant women or women in childbirth dying every single day. The United States can and must do more. While the United States should increase access to proven and existing drugs, vaccines, and other health tools for maternal and child health, it is just as critical to develop the next generation of tools to prevent and treat existing and emerging diseases. Sustained and continued investment by the US government in global health R&D is critical to ending maternal and child deaths.

The answer is yes according to a group of 35 leading scientists who have come together to explore new strategies to accelerate vaccine development for deadly diseases such as malaria, HIV, tuberculosis (TB), and cancer. These scientists—who are part of planning a new initiative called the Human Vaccines Project (HVP)—hope that just as the Human Genome Project successfully mapped the building blocks of human life and led to numerous drug development and medical breakthroughs, a Human Vaccines Project could decipher the “human immunome”—providing a road map of the human immune system that would help scientists accelerate the development of vaccines for existing and emerging diseases. On Wednesday, Nature Immunology released a paper by researchers exploring the HVP that outlined the challenges to vaccine development, the opportunities presented by recent technological advances, and a broad vision for HVP’s future work. Could mapping the “human immunome” lead to the next generation of vaccines? Scientists hope yes. Photo: PATH/Aaron Joel Santos “A Human Vaccines Project focused on solving the major scientific problems impeding vaccine development could be transformative for efforts to help prevent these devastating infectious diseases as well as certain cancers,” said Wayne C. Koff, Chief Scientific Officer of the International AIDS Vaccine Initiative (IAVI) and lead author of the report. Vaccines are among the most effective interventions in the history of public health, having led to the eradication or near eradication of diseases like smallpox and polio and the collective prevention of 2-3 million deaths per year. However, scientists have not yet been able to develop broadly effective vaccines against a number of common and deadly diseases like malaria, AIDS, TB and cancer.   Why do vaccines for some diseases elude us? One of the reasons is because the viruses that cause these diseases are so complex and clever. Take for example variable viruses like influenza and HIV. These viruses behave sort of like characters from the Transformer movie. Like Optimus Prime, they constantly mutate, evolve, and change their form—making it difficult for scientists to develop a vaccine against them. Other viruses are just tough nuts for scientists to crack. For example, the respiratory syncytial virus (RSV)—which causes respiratory infection in infants—has mechanisms that not only block the immune system’s ability to signal to certain cells that it has been compromised, but also alters the immune system’s “memory” processes which typically allows it to react more quickly to subsequent exposure to the same pathogen. As a result, RSV re-infects people throughout their lives. Another challenge impeding vaccine development is the fact that different individuals’ immune systems respond differently to the same virus. In particular, the immune systems of infants and the elderly behave differently than those of adults, so a vaccine that works for adults may not work for either of these populations. In addition, our immune system can react haphazardly when it is assaulted from multiple fronts. For example, rotavirus vaccines are more effective in the developed world than in developing countries where people’s immune systems—as a result of poor sanitation, water and hygiene—are often already fighting off other infections. The opportunity and vision for a Human Vaccines Project Despite these challenges, the paper notes that scientific and technological breakthroughs over the last decade have introduced news tools and technologies that provide an opportunity to revolutionize vaccine development. An HVP would hope to exploit these technologies to change how vaccine development is undertaken. Drawing a parallel to the success of the Human Genome Project, HVP envisions a large-scale, highly collaborative effort—estimated at $1 billion over the next decade—that would bring together industry, government, academia, and nongovernmental organizations to work together to tackle the challenges outlined above. Part of the project’s approach will be a major effort to map the “human immunome.” What does it mean to map the “human immunome”? The human immune system is a series of cells with receptors that recognize and respond to the introduction of foreign substances into the body. It’s a complicated system with an enormous diversity of cells working together to weed out and attack viruses and infections. Traditionally vaccine research has focused more on results coming from experimentation for a specific disease, rather than on understanding the underlying principles of the immune system. Relatively little is known about the interaction of immune responses and cellular processes that provide immunity in response to a vaccination. In the past it would have been inconceivable to try to map the immune system because of the sheer number of genetically different cells involved, but due to improvements in genetic sequencing technologies and computer tools to manage and analyze large data sets, the paper’s authors now believe it could be possible to figure out the sequence of all those receptor cells in the human adaptive immune system. Like the Human Genome Project, such an initiative could take many years, but it would create an essential public tool with the potential to transform the science of vaccine development.

  The development of new diagnostic, treatment, and prevention products is fundamental to accelerating the decline of the global tuberculosis (TB) burden, panelists from the World Health Organization (WHO), the National Institutes of Health (NIH), and the Bill & Melinda Gates Foundation agreed on during a panel discussion hosted by the Center for Strategic and International Studies (CSIS) on Monday. CSIS panelists say R&D is fundamental to meeting new global TB targets. Photo: PATH/Satvir Malhotra CSIS hosted the panel on the occasion of the release of its summary report Strategic US Leadership – Essential to Address the Global Tuberculosis Pandemic—which examines US approaches to tackling TB both in the United States and abroad. The report concludes that the United States needs to better lead, coordinate, and prioritize its TB efforts, as well as increase fiscal and other resources devoted to the issue. Among its recommendations, the report encourages the United States to create robust, long-term research partnerships with key institutions in select emerging economies to promote the discovery and development of new TB tools. During the panel discussion, Dr. Mario Raviglione—director of the global TB program at WHO—discussed the ambitious TB targets put forward in a World Health Assembly resolution including the goal of achieving 95 percent reduction in TB deaths by 2035. He noted that the model for achieving this target assumes the introduction of new TB diagnostics, medicines, or vaccines and said achieving this target will not be possible without investments in research and development (R&D) that result in the introduction of new interventions. The panelists agreed that while the United States will continue to drive efforts toward the development of new TB tools, middle-income countries and rising economies also have an important role to play as well. Dr. Peter Small—deputy director of the TB program at the Gates Foundation—noted that many of these emerging economies also have high TB disease burdens so they are uniquely positioned to contribute. Dr. Small said he believes that it is important for these nations to increase their R&D capacity and investments in science and that US leadership in fostering R&D capacity within these nations will prove key to the long-term development of more frugal and locally-viable TB products. Dr. Tony Fauci—director of the National Institute of Allergy and Infectious Diseases at NIH—agreed with Dr. Small’s statements regarding the need to forge TB partnerships and collaborations with our emerging economy partners. As an example of successful collaborations, he mentioned the increased use of co-principal investigator projects, where a researcher form the United States and a researcher from a different country collaborate on a research project with each of their home countries providing part of the funding. The panelists discussed not only the need for improved collaboration and coordination with other nations, but also the need for enhanced coordination within the United States. Dr. Fauci said while he believes there should be a concerted, coordinated R&D effort by the US government, it needs to be approached carefully. He said he believes fundamental research at the early stages needs to remain somewhat spontaneous, but that he sees a need for greater coordination downstream. A common theme throughout the discussion was the lack of adequate financial resources to meet the demands of a growing and complicated pandemic. Dr. Fauci mentioned the decreasing purchasing power NIH now as a result of stagnated federal funding over the last few years. He noted that as a result, NIH has less flexibility to jump on promising TB research. Dr. Fauci said he believes our country needs to reevaluate how we think about biomedical innovation and research funding—arguing that the US research budget should not be thought of as discretionary funding, but rather an item that needs to be automatically increased each year like cost of living increases. Panelists were also asked to consider the best arguments to convince US policymakers to increase investment in R&D for TB. Dr. Fauci said advocates should talk about how we live in a global community in which we can’t think of it as “our disease versus their disease”—that the United States has an economic and security interest in tackling TB. He also said the TB community should not see HIV as a source of competition for funding, but rather hold it up as an example of the impact that can be realized as a result of robust investments throughout the development process. Dr. Raviglione agreed, noting that within just a few years of the emergence of the AIDS epidemic, the world had already developed diagnostic tests and a few years later developed antiretroviral treatments. Dr. Raviglione said this is a very visible example of the results that can be achieved for a disease through strong investment in R&D.  

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Sarah Alexander—director of external relations for the Global Alliance to Prevent Prematurity and Stillbirth—writes about the recent groundswell of momentum surrounding maternal and child health and the role research and development (R&D) can play in helping more babies have a healthy start to life. Researchers at the University of Tokyo are bioengineering rice to transform it into a low-cost storage and delivery mechanism for drugs to combat cholera, rotavirus, and other infectious diseases and contagious illnesses. The researchers say that bioengineering the vaccines or antibodies into rice would allow them to be stockpiled and stored at room temperature, avoiding cold chain issues that exist with existing vaccines. Geno de Hostos—director of research and preclinical development at PATH’s Drug Development Program—writes about how an integrated approach to tackling diarrheal disease can save thousands of children’s lives each year. He argues that R&D efforts focused on new drugs and vaccines hold tremendous potential, and there is a need to sustain appropriate funding to achieve more progress. The Bill & Melinda Gates Foundation announced funding for 55 projects through its Grand Challenges Explorations initiative program which funds innovative ideas to address global health and development problems. Grant recipients include several projects to improve condom design, “cologne” for cows that alters their smell to mimic humans in order to divert disease-carrying insects from people, and two projects to improve the vaccine cold chain, among others. Dr. Margaret Hamburg—commissioner of the US Food and Drug Administration (FDA)—writes on the FDA Voice blog about the World Health Organization’s passage of a resolution to strengthen regulatory systems. She notes the unique challenges and opportunities faced by regulators because of globalization and the extraordinary increase in the global supply of medical products, and she discusses the increasing efforts by nations to collaborate to share information and reduce system inefficiencies.