Breakthroughs Blog: Diarrhea

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.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Last week, the Center for Strategic and International Studies hosted a 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 tuberculosis (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 create robust, long-term research partnerships with key institutions in select emerging economies to promote the discovery and development of new TB tools. GHTC member PATH has been awarded a three-year, US$15.6 million grant from the Bill & Melinda Gates Foundation to develop effective treatments for severe acute secretory diarrhea (ASD). The new grant will support a portfolio approach to drug development in an effort to maximize the chances of successful drug candidates to treat ASD, as well as support new engagement with the public and private sectors. Last week, the US House of Representatives introduced the End Neglected Tropical Diseases Act in an effort to turn the tide in the fight against neglected tropical diseases. The bill was introduced by Rep. Chris Smith (R-NJ) and already has bipartisan support from Reps. Matt Salmon (R-AZ), Hank Johnson (D-GA), and Greg Meeks (D-NY).   Osman Sankoh, executive director of INDEPTH, emphasized the important role of research and innovation for development in low- and middle-income countries (LMICs) in The Lancet Global Health Blog. Sankoh writes that “stronger international commitment to investing in research, development, and innovation in LMICs” is crucial in the post-2015 development agenda. He added that “research into health threats not only saves lives—it also helps governments and donors to save money.” Scientists at Imperial College London have created genetically-modified mosquitoes that produce 95 percent male offspring with the goal of helping control malaria. They believe introducing these mosquitoes into the normal mosquito population could lead to a shortage of females and a crash in overall population, thus reducing malaria incidences. GHTC member Aeras has released a new film exploring the TB crisis in the mines of South Africa. The film—called Undermined—looks at “the river of TB flowing out from the mines, and why a vaccine is critical to the global fight against this disease.”

In this post—which originally appeared on the DefeatDD.org blog and PATH’s Drug Development Program blog on June 4—Geno de Hostos—director of research and preclinical development at PATH’s Drug Development Program—reflects on themes in the organization’s new video “Defeat diarrheal disease? Together, we’ve got it covered” . He discusses how an integrated approach to tackling diarrheal disease can save thousands of children’s lives each year. The uneasy reality When you walk into a diarrheal disease health clinic in a place like Bangladesh, the reality of the disease strikes you immediately. It’s the rows of bright orange bed covers drying in the sun, long lines of women with children waiting to be seen, and the patients—most of them too young and vulnerable to be already fighting for their lives. Diarrhea takes the lives of more than 1,600 children every day before they can grow to see their fifth birthday. Photo: Jonathan Torgovnik © The onslaught of diarrhea is sudden and loss of fluids is copious. Mere inconvenience quickly turns to a daily struggle for life as you fight off dehydration that diarrhea causes. A child is rushed to a hospital where lifesaving oral rehydration solution (ORS) is administered, usually by a mother or a care provider. Spoon by spoon, lost fluids are slowly restored, though weakness can persist for several weeks, and repeated bouts of diarrhea are common. The reality is that despite rapid progress in reducing child deaths from diarrhea over the last decade—a decrease by more than 50 percent, from almost 1.3 million in 2000 to approximately 600,000 in 2012—there is a lot more to be done. And as long as diarrhea continues to take the lives of more than 1,600 children every day before they can grow to see their fifth birthday, there is no time we can allow ourselves to waste. Power of an integrated approach Another reality is that it doesn’t have to be this way. Effective, proven solutions for tackling diarrhea— safe drinking water and improved sanitation, adequate nutrition, rotavirus vaccines, ORS, and supplemental zinc, combined with continued feeding—are already in our hands. We need to work harder to scale them up and find new methods to deliver them to those who need them. Research and development (R&D) efforts focused on new drugs and vaccines hold tremendous potential, and we need to sustain appropriate funding and efforts on that front to continue with our progress forward. Together, these critical solutions form a network of approaches to diarrheal disease that reinforce one another and form a solid foundation for a healthy life. That’s why at PATH, we work to address diarrhea on multiple fronts. Our drug development team is developing new treatments to shorten the severity and duration of diarrhea before it becomes fatal, while also working to improve the effectiveness of proven diarrhea therapies like ORS. PATH is also working to develop new vaccines against the leading causes of diarrheal disease, partnering with countries to increase access to existing vaccines for rotavirus, developing and delivering safe water treatment and storage products, advancing health devices, and strengthening behaviors like breastfeeding education. R&D efforts focused on new drugs and vaccines for diarrheal diseases hold tremendous potential, and we need to sustain appropriate funding and efforts on to further progress. Let’s keep going! Having worked in nonprofit drug development for nearly seven years, I am more heartened than ever before by the impressive gains being made in R&D of innovative health technologies to fight the leading causes of child death like diarrhea. I am also reminded of the critical value of sustained commitment to our children and the need to accelerate progress. A multipronged approach can help us get there—among other factors, development of innovative health technologies, opening access to needed vaccines, drugs, clean water and sanitation, adequate nutrition, and education will continue to push us forward. It’s time we change the reality of diarrheal disease. More information Defeat diarrheal disease? Together, we’ve got it covered Defeat DD: Simple solutions to fight a common killer Targeting diarrheal diseases

In this guest post, Dr. John Boslego, director of PATH’s Vaccine Development Global Program, writes about an innovative partnership between the United States and India to develop an oral vaccine against rotavirus diarrhea. I recently had the pleasure of attending an international symposium on rotavirus vaccines where the government of India’s Department of Biotechnology (DBT) and the Indian vaccine manufacturer Bharat Biotech announced positive results from a Phase III clinical trial of an oral rotavirus vaccine that was developed and manufactured in India. Data from the trial showed the vaccine, ROTAVAC®, to be safe and effective in protecting infants against severe rotavirus diarrhea, the most lethal cause of childhood diarrhea. ROTAVAC® represents an important scientific breakthrough against severe rotavirus diarrhea, responsible for approximately 100,000 deaths of small children in India each year. Credit: PATH. However, what’s most extraordinary about this announcement actually may not be the results themselves, but the long and unique road that ROTAVAC® traveled to reach this point. This vaccine is the product of an innovative partnership between the United States and India, involving renowned experts from a range of agencies and sectors across the two countries. The vaccine originated from an attenuated (weakened) strain of rotavirus that was isolated from an Indian child at the All India Institute of Medical Sciences in New Delhi in the mid-1980s. Since then, partners in the vaccine’s development have included DBT, Bharat Biotech, the US National Institutes of Health (NIH), the US Centers for Disease Control and Prevention (CDC), Stanford University School of Medicine, and PATH. Each group has provided its own contribution to the project, ranging from technical assistance on vaccine development and manufacturing the vaccine batches used in clinical trials, to guidance on designing and implementing clinical trials that meet international standards. With the development costs shared by several partners, Bharat Biotech was able to commit to a price of US$1.00 per dose for ROTAVAC®. As such, Bharat Biotech plans to register the vaccine for use in India first. If licensed by the Indian regulatory authority, the vaccine will be a more affordable alternative to the rotavirus vaccines already on the market. This represents an important scientific breakthrough against severe rotavirus diarrhea, responsible for approximately 100,000 deaths of small children in India each year. If licensed, this vaccine could save the lives of thousands of children each year in the country. Bharat Biotech also plans to submit ROTAVAC® for prequalification by the World Health Organization, so it may be procured for subsidized use in the developing world, giving it the potential to have an enormous impact on global public health by reducing rotavirus-related illness and deaths worldwide. I’m proud of the role that PATH has played in reaching this incredible milestone, and I am particularly impressed with how this truly innovative approach to a vaccine development partnership has resulted in the production of a safe and efficacious new rotavirus vaccine, ROTAVAC®.