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In this guest post, Mandy Goldberg from Research!America writes about an event today in Washington, DC, that focuses on research and development (R&D) for new malaria tools. The event is sponsored by Research!America, the Global Health Technologies Coalition (GHTC), and several other partners. In the United States, the bite of a mosquito is uncomfortable and irritating. For 3.3 billion people abroad, a mosquito bite can be deadly. Almost half of the global population is at risk of contracting malaria from the bite of an infected mosquito. Although malaria is preventable and curable, an estimated 655,000 people, mostly children in Africa, died from the disease in 2010. On April 25, the global health community commemorates the fifth annual World Malaria Day by recognizing the progress that has been made in the fight against malaria and calling for increased investment to sustain this momentum and achieve malaria control worldwide. The current basis of malaria control efforts are mosquito control strategies and treatment. Studies have shown that bednets can reduce malaria transmission by 90 percent in areas with high coverage rates. In addition, indoor residual spraying with insecticides can also reduce malaria transmission in areas with at least 80 percent coverage. In the past decade, malaria deaths have decreased by one-third in Africa. In countries with improved access to malaria control interventions, child mortality rates have fallen by 20 percent. More research is needed, however, to develop new, longer-lasting tools to bring eradication within reach. Photo credit: PATH/Evelyn Hockstein The tide is turning against malaria, thanks in part to remarkable achievements in R&D. In the past decade, malaria deaths have decreased by one-third in Africa. In countries with improved access to malaria control interventions, child mortality rates have fallen by 20 percent. More research is needed, however, to develop new, longer-lasting tools to bring eradication within reach. Hope on the way: the malaria product pipeline Anti-malarial medicines are used for curative and preventive purposes, but the increasing threat of drug resistance is making R&D for new, more effective drugs even more essential. Widespread resistance to the drug chloroquine in the 1970s and 1980s necessitated the use of artemisinin-based combination therapies (ACT), currently the best available treatment. The plant from which artemisinin is derived is in short supply in nature, threatening future availability of ACT. OneWorld Health, a drug development affiliate of PATH, in collaboration with private-sector partners, is working to solve this problem through the development and production of semi-synthetic artemisinin at an affordable price that can sustain the supply of ACT for years to come. In addition, the product development partnership Medicines for Malaria Venture (MMV) has several promising drug candidates in its R&D pipeline. MMV is developing a one-dose cure to replace current three-day regimens, eliminating the need for treatment follow-up and reducing the likelihood of drug resistance. MMV is also working on the development of non-artemisinin-based treatments. Considering recent reports of increasing resistance to ACTs in Southeast Asia, increased investment is needed to support the development of new therapies that may be necessary to control malaria in the future. The greatest hope for malaria eradication is the development of a safe, effective vaccine to prevent infection. RTS,S, the most advanced malaria vaccine candidate, has been shown to reduce the risk of infection by 50 percent among children age 5-17 months in a recent late-stage clinical trial. Developed through collaboration between the Walter Reed Army Institute of Research, GlaxoSmithKline, and the PATH Malaria Vaccine Initiative, this vaccine could be recommended for widespread use by the World Health Organization as early as 2015. Research has played an essential role in the progress already made against malaria, and additional scientific breakthroughs may be around the corner due to the robust R&D pipeline. Malaria R&D has the potential to save hundreds of thousands of lives, including American troops stationed abroad, and also has important economic benefits here at home by creating jobs and stimulating economic growth. In order to fully realize these health and economic benefits, increased investment in malaria R&D is required.

Mark Alderson, PhD, is the director of the pneumococcal vaccine project at PATH , a nonprofit international organization based in Seattle, Washington, specializing in global health. In this guest post, he writes about PATH’s efforts to develop new vaccines to fight pneumonia among children. In honor of World Immunization Week, the global health community is coming together to engage in immunization campaigns, advocacy, and awareness activities to bring the power of vaccines into the spotlight. Vaccines are one of the most successful and cost-effective technologies that prevent childhood mortality. According to the World Health Organization, immunization prevents between two and three million deaths per year. Regardless, many vaccine-preventable diseases continue to take lives unnecessarily because of gaps in vaccine research and development (R&D) that neglect developing-world needs. Barriers to vaccine access also prevent low- and middle-income populations from receiving the protection they need. Pneumonia—the number one killer of children under five years of age worldwide—is one such disease for which vaccines and treatments could save millions of lives. However, achieving sustainable global health impact over the long-term requires further investment in new vaccines that cater specifically to the developing world, where pneumonia hits hardest. To this end, public-private sector partnerships are essential to maximizing resources and speeding development. In the fight against pneumonia, we have reason to celebrate. Overall, investments in combating pneumonia have helped contribute to a 35 percent reduction in child mortality since 1990—no small feat. We have vaccines for several top causes of the disease, including the pneumococcus bacterium, which is the most common cause of severe childhood pneumonia and takes the lives of an estimated 800,000 children annually. Pneumococcal vaccines, having been accessible in the industrialized world for over a decade, are now rolling out in low-resource countries with the help of the GAVI Alliance and other groups. This month, Ghana is making history by becoming the first GAVI-eligible country to introduce two vaccines simultaneously—pneumococcal and rotavirus vaccines. The power of vaccines is evident, but unless we continue to invest in new vaccine tools that can provide better, more affordable protection, our ability to protect our children will be incomplete. Photo credit: PATH Despite these great strides, we must not forget that there is still a long way to go. The pneumococcal vaccines in use today are effective against certain varieties of the bacterium, but no vaccine yet exists that can protect against all of the more than 90 pneumococcal strains, leaving children susceptible to strains not covered by these vaccines. Also, current pneumococcal vaccines are relatively expensive, making them difficult for low- and middle-income countries to afford without substantial assistance from international donors. To fight pneumonia, which takes the life of one child every 20 seconds, we must waste no time in striving for broadly effective and affordable vaccines that can be sustainably accessible in even the most impoverished regions of the world. Because market forces alone are not always strong enough to drive the development of vaccines most urgently needed in lower-income countries, PATH is stepping in to help fill the gap. Our pneumococcal vaccine project is advancing R&D for new, low-cost pneumococcal vaccines that are tailored to meet the needs of children in the developing world. We collaborate with an array of public- and private-sector partners on vaccine R&D projects, including universities, research institutions, vaccine manufacturers, and biotechnology companies. We also work with US and foreign government agencies on epidemiology, vaccine research, and regulatory issues. Several of the vaccine candidates we support could provide broad protection against pneumococcus by using proteins that could help the body’s immune system recognize and defend against virtually all pneumococcal varieties. If successful, these vaccines could change the face of pneumococcal disease by providing universal protection at low cost. For candidates ready to enter clinical trials, we coordinate closely with the US Food and Drug Administration (FDA) to ensure compliance with regulatory requirements. We are also partnering in India to develop a vaccine candidate using technologies similar to current pneumococcal vaccines, but at significantly lower inherent cost. This vaccine candidate targets only pneumococcal varieties common in the developing world. If successful, India could become a global manufacturer of pneumococcal vaccines, blazing the trail for endemic country vaccine producers in a market previously occupied solely by European and US manufacturers. Recognizing that successful vaccine development requires access to a full spectrum of scientific resources, we also support research that advances the vaccine field at large. Among our various research partnerships are several with the US Government, including FDA and the US Centers for Disease Control and Prevention. Collaborations of this nature are essential to helping lay the scientific groundwork for new pneumococcal vaccines to come to fruition. The power of vaccines is evident, but unless we continue to invest in new vaccine tools that can provide better, more affordable protection, our ability to protect our children will be incomplete. Tackling prolific killers like pneumonia in the developing world is a critical step toward truly making an impact on the global burden of disease. Working in partnership here in the United States and abroad can help get us there sooner rather than later.

In this guest post, Dick Walker—director of the Enteric Vaccine Initiative at PATH’s Vaccine Development Program—writes about how the double-mutant heat-labile toxin is a potential booster for much-needed new vaccines against diarrhea. The leading bacterial causes of diarrhea are enterotoxigenic Escherichia coli (ETEC) and Shigella, and vaccines against these pathogens could save the lives of up to a half-million children each year. PATH’s enteric vaccine project is working to accelerate the development of several promising vaccine candidates. We are also looking at innovative ways to make these vaccines as effective, practical, and affordable as possible so they can be easily implemented in the developing world. Adjuvants, ingredients that may enhance the effectiveness of some vaccines, are one important area of focus. PATH is currently involved in research on a highly promising new adjuvant, the double-mutant heat-labile toxin (dmLT), which could open more doors to achieving immunity in the intestine. The dmLT is actually an ETEC antigen (a substance that causes the immune system to produce antibodies against it), so it may offer protection against both diarrhea and intestinal infection when used in conjunction with vaccines that are targeted to mucosal surfaces like the intestine. We aren’t exactly sure why, but children in resource-poor countries often have a lower response rate to mucosal vaccines. A wide range of factors may contribute to this issue, such as the influence of breastfeeding and maternal antibodies, poor nutrition, or increased exposure to intestinal pathogens. An adjuvant like the dmLT may help to bridge this gap in effectiveness. Dick Walker with children in Cambodia. Promising vaccine technologies can help expand and improve the arsenal of tools to use in the fight against diarrhea among children. Right now, we’re working with the National Institutes of Health’s (NIH) Division of Microbiology and Infectious Diseases on a Phase 1 clinical trial using oral doses of dmLT (not in conjunction with a vaccine) in healthy adults. We will have complete results later this year, but the preliminary data are quite promising. Meanwhile, we are about to launch our first Phase 1 trial of the dmLT combined with one of our oral ETEC vaccine candidates. In addition, we plan to start another Phase 1 trial to test the dmLT intradermally (through the skin), and we would also like to study its use sublingually (under the tongue), to see if these alternative delivery routes can achieve an immune response in the intestine. If preclinical studies accurately predict what will be seen in humans, delivering dmLT in these ways could open up a whole range of possibilities for developing more effective and practical vaccines. This type of innovative research is critical to moving forward the field of vaccines to address diarrheal disease, and support from the NIH and other partners is critical to this effort. As the dmLT and other promising vaccine technologies progress in their development, we know we are getting ever closer to expanding and improving the arsenal of tools to use in the fight against this major killer of children.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. The White House Office of Science and Technology Policy and the Results for Development Institute have released new reports that examine incentives for global health research and development. Pharmaceutical company AstraZeneca and the Drugs for Neglected Diseases initiative have announced an agreement to collaborate on drug-compound screening for the neglected tropical diseases leishmaniasis, Chagas disease, and sleeping sickness. Todd Park, US chief technology officer, discusses innovation efforts undertaken by the US Government, including the Entrepreneurs in Residence Program at the US Food and Drug Administration. The Institute of Medicine has released a report on how to make clinical trials more efficient and effective.