Breakthroughs Blog: Guest post

Aedes aegypti mosquitoes which carry Zika. Photo: Dean Calma/IAEAApril showers bring standing pools of water, the onset of mosquito season, and a new wariness of getting bitten. In 1999, we were caught off guard when the West Nile virus first appeared in North America. In 2010, an outbreak of dengue fever spread locally in Florida after an absence of 60 years. In 2014, chikungunya first arrived in the United States after travelling breathtakingly fast through the Western hemisphere. Now, in 2016, Zika virus is the latest mosquito-borne disease to threaten Americans. Yet our collective national response continues to be one of short-term planning rather than long-term preparedness.Since Zika virus arrived in the Americas in May 2015, there has been an alarming spike in reports of birth defects such as microcephaly, particularly in Brazil. Zika infection has also been linked to adverse pregnancy outcomes and Guillain-Barré syndrome—a temporary paralysis that can prove deadly. The World Health Organization has declared Zika a Public Health Emergency.The virus has now spread to 26 countries, including 312 travel-associated cases in the United States. So far, mosquitoes in the United States haven’t infected anyone, but the Centers for Disease Control and Prevention (CDC) just issued a revised map that shows the mosquitoes that carry this virus and others can be found across the Southern tier of the United States all the way up to southern New England on the East Coast.Faced with this chilling situation, we don’t have ready the tools we need to fight Zika. Just like with Ebola, crucial tools did not exist or were still under development when the outbreak began. R&D is urgently needed to understand the Zika virus and its associated health conditions, and develop new diagnostics, vaccines, or other treatments to combat it. A pregnant woman in El Salvador receives an ultrasound as part of the country's response to the Zika outbreak. Photo: Office of the President of El Salvador Today, the Band-aid approach of emergency funding is the only option available to mitigate the crisis. We applaud President Obama’s call for accelerated research efforts, and the need to inform Americans about how to protect themselves, which the CDC has been quick to do. The National Institute of Allergy and Infectious Diseases, led by Dr. Anthony Fauci, has also called for a “full court press” on research.This requires increased funding for those searching for ways to stop this virus. Diverting resources from the Ebola response, however, is short-sighted. Those efforts are just beginning to show the promise of new diagnostics, advanced therapeutics, and more resilient health systems in Ebola-affected countries. Redirecting funding before the job is finished is dangerous, and will most certainly leave the United States and the world unprepared for the next Ebola outbreak.The fact remains that this long-standing patchwork approach to global health R&D funding only degrades our ability to respond to the guaranteed next global health crisis. With more than 500 mosquito-borne diseases across this globally interconnected world, the question is not if but when we see another virus or disease.Just as we need primed and ready firehouses and firefighters, we need a primed and ready research infrastructure. That requires a prioritized agenda and sufficient funding. America’s “firehouses and firefighters” are the National Institutes of Health, CDC, President’s Malaria Initiative and the Army and Navy’s tropical infectious disease programs.Global health means everyone’s health. It’s time US policymakers stop funding by crisis and commit to sustainable, long-term investment in global health R&D so the most effective health solutions are available when they are needed.Stephen Higgs, PhD, FRES, FASTMH is the president of the American Society of Tropical Medicine and Hygiene and a professor at Kansas State University. Erin Will Morton, MA is director of the Global Health Technologies Coalition, a group more than 25 nonprofits that work to save and improve lives by encouraging the research and development of essential health technologies.

In this guest post Tom Harmon, senior policy analyst at the International AIDS Vaccine Initiative (IAVI), highlights a new analysis exploring the critical role of a vaccine in ending AIDS. Photo credit: IAVI When we talk about ending AIDS, what do we mean? The last dozen years have brought tremendous strides in reducing new HIV infections in low- and middle-income countries (LMICs), expanding lifesaving treatment to almost 16 million people living with HIV, and implementing programs to address the epidemic in populations at especially high risk, including women and girls. But we must continue to push for progress in treatment and prevention. The 2 million new infections in 2014 remain far too high, and almost 60 percent of people needing treatment are not getting it. So, when we talk about conclusively and durably ending AIDS and ensuring that it does not bounce back, our experience with other infectious diseases shows that a preventive vaccine will be necessary. The global effort to develop an AIDS vaccine has also recently experienced significant successes and steps forward. For example, we’ve never before seen such a diversity of approaches and partners, with follow-on trials based on the first candidate to show modest efficacy slated to begin later this year in South Africa, exciting new insights toward generating protective antibodies against HIV, and promising approaches toward inducing cellular immune responses that could control HIV infection. Still, there are more far-reaching questions we’re asked today by policymakers, advocates, communities, and even researchers themselves: What would the global response look like if an AIDS vaccine was available? How effective would it need to be? Would it be cost-effective and affordable? A new article, published in PLoS ONE aims to answer some of these crucial questions. The result of a collaboration between IAVI, Avenir Health, and AVAC that builds on work by UNAIDS, this model specifically explores a vaccine’s potential value in terms of preventing HIV infections in LMICs. We analyzed a vaccine’s potential impact depending on how well the world can achieve ambitious HIV and AIDS program objectives, how effectively it can prevent HIV infection, and how it can add to a response that also includes pre-exposure prophylaxis and treatment as prevention. We also looked at cost scenarios to see how a vaccine would stand up to cost-effectiveness criteria used by the World Health Organization to guide the introduction of new health technologies. Despite the potential for today’s tools to have a substantial impact on the epidemic, our results show that a vaccine is a critical piece to ending AIDS. Under our base scenario, a vaccine of 70 percent efficacy with strong uptake would reduce HIV infections in LMICs by 44 percent in its first 10 years and by 65 percent in 25 years, ultimately averting tens of millions of infections and saving millions of lives. Reduction of new annual HIV infections with PrEP, TasP and vaccination added individually and in combination to the Full Scale-up of IFE between 2015 and 2070. A vaccine would be impactful and cost-effective even at lower efficacy levels and costs far higher than many of today’s vaccines. Increasing a vaccine’s efficacy, ensuring it protects for a longer period of time, reducing the number of doses, lowering the cost of a dose, and more effectively rolling it out are all factors that would increase a vaccine’s impact and its value. Such a vaccine could cut the number of people needing treatment in half by the year 2070, and eventually reduce the total cost of fighting AIDS in LMICs even when the additional cost of implementing the vaccination program is included. While these data provide a powerful illustration of a vaccine’s potential value, we acknowledge and welcome discussions of its intrinsic limitations, which reflect the areas the AIDS vaccine field and future program implementers will need to tackle as we research, develop, and ultimately deliver a vaccine to the people who need it most. Such an analysis helps explore the parameters that determine the medical and economic impact and value of a future AIDS vaccine as part of the comprehensive HIV and AIDS response. This data can be a useful guide for research portfolio decisions as new candidates move closer to efficacy trials. In many ways these projections are as much a vaccine development and delivery “to-do list” as they are a crystal ball for what the future holds. A few weeks ago, the US Centers for Disease Control and Prevention organized a Grand Rounds presentation on how models are used to guide pandemic responses. This interesting panel was closed by Dr. Richard Hatchett, chief medical officer and deputy director for strategic sciences at the US Biomedical Advanced Research and Development Authority, who cited modeler Steven Bankes’ use of campfires as an analogy for predictive models, in that their value goes beyond their primary deliverable (be it light, heat, or data), as they just as importantly provide a “gathering place” for discussion between stakeholders. Our new model can perform just such a dual function, adding valuable context for a vaccine’s future role in ending the AIDS epidemic which has ravaged so many communities, while stimulating conversations and new questions on what we need to do in the real world to turn theory to impact.

In this guest post, Anna Doubell, an analyst at Policy Cures, writes about the findings of this year’s G-FINDER report on neglected disease research and development (R&D). Supporting data from the report was released this week and is now available online through the G-FINDER public search tool. Photo: PATH/Patrick McKern The West African Ebola outbreak featured prominently on the front pages of newspapers globally in 2014, reminding us of the devastating impact that an infectious disease can have on communities when the required vaccines, treatments, and diagnostic tools don’t exist, and the health systems to utilize them are severely lacking. However, Ebola is only one of many infectious diseases for which there are a lack of adequate products. The G-FINDER survey, conducted by Policy Cures, collects data about funding for neglected disease R&D from over two hundred organizations each year. This year’s report, published in December, and the supporting data, released this week, highlight funding trends and gaps for R&D to develop new health technologies for neglected diseases, which can help governments, philanthropic organizations, and industry make informed decisions. Expansion of scope to include Ebola In response to the 2014 outbreak, we included Ebola in the 2015 G-FINDER survey scope for the first time, and the data published this week provides the first detailed picture of global funding for Ebola R&D. In many ways Ebola is a prototypical neglected disease: low-income countries (Sierra Leone, Guinea and Liberia) bore the brunt of the epidemic; no proven vaccines, antiviral drugs, or field-suitable diagnostic tests existed for Ebola when the outbreak began; and despite the existence of some bioterror-related research programmes, there had been insufficient commercial incentives to attract enough R&D investment from industry to develop products through to registration. But the rapid spread and potential global impact of Ebola led to unprecedented levels of attention and new investments in R&D. Grounds for optimism? The response to the outbreak showed that funders can rapidly mobilize money for R&D into neglected diseases in times of crisis. The 2015 G-FINDER survey found that US$165 million was invested in Ebola R&D in 2014, which is remarkable given that the outbreak was only declared a public health emergency in August of that year. This investment made Ebola the fifth best-funded neglected disease, behind only HIV and AIDS, malaria, tuberculosis (TB), and diarrheal diseases. Nearly three quarters of Ebola investment came from the public sector (most of it from the US government), followed by the pharmaceutical industry, providing 21 percent of all funding. The mobilization of resources, both human and financial, resulted in clinical trials for drugs and vaccines being launched in record time,1 showing what might be possible for other neglected diseases, many of which cause more deaths in developing countries every year than did Ebola. Bacterial pneumonia and meningitis, for instance, kill more than 750,000 people in the developing world each year—compared to just over 11,000 deaths in two years from the recent Ebola outbreak—and yet in 2014 these diseases received less than half the R&D funding that went to Ebola. Caution still required This impressive response raises a number of questions. Will investment in Ebola R&D continue as the epidemic comes to an end, and will this funding be sufficient to support the products currently in development through to registration? And was this investment in Ebola R&D from entirely new funding, or was it diverted from other neglected diseases? Declining public funding One of the key findings of the 2015 G-FINDER report was that public funding for non-Ebola neglected disease R&D in 2014 fell to its lowest level since 2007. In this case, the US government again, unfortunately, led the way: US government year-over-year investment in non-Ebola neglected disease R&D fell by just over 2 percent in 2014, following even larger sequester-related cuts the previous year, to be nearly a quarter of a billion dollars lower than its peak in 2009. Public funding from other countries has remained steady, but ongoing cuts from the United States, the world’s biggest funder of neglected disease R&D, are cause for concern. Increasing industry investment In contrast to the decline in public funding, industry investment in neglected disease R&D reached its highest level in the history of the G-FINDER survey. Importantly, this reflected not only the sector’s Ebola R&D activity, but also significantly increased investment in R&D for malaria drugs and vaccines and HIV and AIDS vaccine research. More concerning was the fact that industry funding for TB fell for the fourth year in a row (down $10m or 8.7 percent)—an alarming trend, given the need for new vaccines, drugs, and diagnostics to combat the increasing threat of multidrug-resistant TB and extensively drug-resistant TB. Solidifying funding for PDPs In positive news, funding for product development partnerships (PDPs) rose for the second year in a row, driven by increased funding from the Bill & Melinda Gates Foundation. PDPs are instrumental in the development of new tools to fight neglected diseases, and are involved in the development of 40 percent of products in the neglected disease pipeline, despite accounting for just 16 percent of global funding in neglected disease R&D. The system failures in the global response to the Ebola outbreak have been well documented over the past months. But there should also be recognition of the successes and surprising rapidity with which R&D investment was mobilized. If we could translate this political and financial commitment to other neglected diseases, the impact would be huge. Reference: Moon S, Sridhar D, Pate MA, Jha AK, Clinton C, Delaunay S, et al. Will Ebola change the game? Ten essential reforms before the next pandemic. The report of the Harvard-LSHTM Independent Panel on the Global Response to Ebola. The Lancet. 2015 Dec 4;386(10009):2204–21.

In this guest post, Dara Erck, vice president of external affairs at Aeras, discusses the new White House National Action Plan for Combating Multidrug-Resistant Tuberculosis and how it could accelerate research and development (R&D) of new technologies to combat multidrug-resistant TB (MDR-TB). When the World Health Organization (WHO) unveiled its Global Tuberculosis Report 2015 last October, the most striking revelation was that tuberculosis (TB) is now the world’s leading single infectious disease killer, accounting for 9.6 million illnesses and 1.5 million deaths in 2014. And the report’s findings about MDR-TB were also alarming, noting 480,000 cases of MDR-TB globally in 2014, with nearly 10 percent of these being extensively drug resistant (XDR-TB). Considering this high human toll in context of the estimated annual US$1.3 billion funding gap for TB R&D, it is clear we must achieve a sea change in the global approach to TB R&D funding. This is why there was much hopeful anticipation for the release of the White House’s recent plan to address MDR-TB, as a follow up to its 2014 National Action Plan for Combating Antibiotic Resistant Bacteria. Released in late December 2015, the National Action Plan for Combating Multidrug-Resistant Tuberculosis is a product of countless hours of collaboration between the Obama Administration and its partners in government, including the White House Office of Science and Technology Policy which convened an interagency working group including the US Agency for International Development, the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), the State Department, and others. During the course of the plan’s development, TB advocates vigorously urged the Administration to broaden the goals related to MDR-TB. And the White House listened. The goals of the action plan are to strengthen domestic capacity, improve international capacity and collaboration, and accelerate basic and applied research to combat MDR-TB. I am especially pleased to see this acknowledgment of the critical role of TB R&D. Accelerating basic and applied research to combat MDR-TB is absolutely necessary if we are to conquer the TB epidemic. The plan recognizes that “ultimately, an effective vaccine to prevent all forms of TB will be required to eliminate TB globally.” This acknowledgment is an important step, indeed. But we must not ignore that funding this critical work is a necessary next step. We simply cannot discover and develop the new tools required to end this deadly epidemic without urgently needed additional resources. I urge President Obama to include robust funding for implementing agencies in his fiscal year 2017 budget. TB vaccine research. Photo: Aeras The plan outlines a significant focus on R&D. In the coming year, NIH is directed to expand its TB dialogue among basic scientists, funders, and vaccine developers to identify novel strategies for vaccine development, encourage research related to vaccine design, and educate partners about resources available to contribute to vaccine development, as well as continue to support studies to map the diversity of immune responses required for vaccine efficacy. Within three to five years, NIH is tasked with continuing its support for TB research, preclinical studies, and clinical trials and studies for the evaluation of new vaccines, adjuvants, and preventive drugs. NIH and CDC will also intensify collaborations with domestic and international vaccine developers to leverage preclinical and clinical resources for vaccine development. These directives are an important move in the right direction—but without significant new strategies and resources, the scientific community will struggle to advance new vaccine candidates that can prove effective in providing protection against TB. I am particularly encouraged to see the call for collaboration with private-sector organizations including nonprofit product developers. At Aeras, we partner with a wide range of academic and pharmaceutical organizations dedicated to TB vaccine research. And we aren’t alone—other nonprofit product developers such as TB Alliance and FIND lead their fields in new drug and diagnostic development, respectively. The release of this plan was an exciting moment for all TB advocates and researchers, as it attracts new and much needed attention to the threat of MDR-TB. It provides the opportunity to create renewed accountability for ending this deadly epidemic. It also validates and supports other initiatives, including the WHO’s aim to end the TB epidemic by 2035, and the United Nations’ new Sustainable Development Goals which target ending the TB epidemic by 2030. But for the plan to be successful, Congress will need to dedicate the resources necessary to achieve its ambitious treatment, diagnostic, and vaccine development targets. The US government is a key partner in this critical work. I deeply appreciate the Administration’s efforts to create this plan and hope that the US Congress will provide the funding that is so urgently needed to realize a TB-free world.