Breakthroughs Blog: Diarrhea

This month marks 35 years since the World Summit for Children, the first time in history when a meeting of heads of state and government was held exclusively to address the well-being of children. At this landmark event in New York City, world leaders adopted a Declaration on the Survival, Protection, and Development of Children and a Plan of Action for its implementation, which made specific recommendations in a variety of areas, including child and maternal health and family planning. We’ve made significant progress in children’s health globally since then—the total number of deaths of children under five worldwide has declined from 12.8 million in 1990 to 4.8 million in 2023. The number of neonatal deaths (deaths in the first 28 days) has also dropped, although more slowly, from 5.2 million in 1990 to 2.3 million in 2023. However, there are still major challenges in children’s health, especially in the Africa region, where children continue to have the highest risk of dying before reaching age five. Infectious diseases, including acute respiratory infections, diarrhea, and malaria, as well as birth complications, remain among the leading causes of death for children under five. More than half of child deaths are due to conditions that could be prevented and treated with adequate access to health care or other quality of life improvements, particularly in that crucial first month: neonatal deaths make up 47 percent of under-five child deaths.Another challenge is the lack of medicines designed specifically for children—only 30 percent of essential medicines are available in child-appropriate formulations. Instead, children are often treated with imprecise partial doses of medicines that were designed and tested in adults, which can lead to toxicity and complications. This gap results from a variety of barriers: it can take up to 25 years to bring a pediatric medicine to market and only one in ten clinical trials registered between 2000 and 2023 included children. Innovative technologies rolled out since 1990 have already saved millions of lives, and new tools in the pipeline designed with the needs of children, and particularly the most vulnerable kids, in mind could bring down child mortality even more. Diarrheal disease vaccines While diarrheal-disease related deaths among children under five have decreased drastically since 1990, down an estimated 79 percent from 1990 to 2021, they still cause a severe burden; 4.8 million children under five died in 2023. Rotavirus, Shigella, and enterotoxigenic Escherichia coli (ETEC) are among the common pathogens that can lead to diarrheal disease.  The first rotavirus vaccines of the generation still in use today become available just under 20 years ago, approved in the United States in 2006 and later recommended by the World Health Organization for all children. Today, these vaccines are used in more than 110 countries around the world and have contributed to a significant drop in child hospitalizations and deaths from diarrhea. Rotavirus vaccines have had a marked impact on child mortality, preventing 139,000 deaths in children under five between 2006 and 2019. However, rotaviruses are still the leading cause of severe diarrhea in children under five in low- and middle-income countries, pointing to the need for increased access to existing vaccines, as well as new and more effective ones.Unfortunately, approved vaccines don’t yet exist for ETEC and Shigella, though promising candidates are in development. PATH is working with partners to advance vaccines against these bacteria, which could help save thousands of additional lives. For Shigella, PATH is working with the US Naval Medical Research Command and the Walter Reed Army Institute of Research to advance a vaccine candidate, which demonstrated strong safety and efficacy in a recent Phase 1 trial. PATH is also working with these US partners, alongside Sanofi Pasteur and the Infectious Disease Research Institute, to advance an ETEC vaccine candidate, which displayed strong potential in a Phase 1 trial in adults, paving the way for the development of a vaccine for infants and young children, who face the highest risk. If they continue to prove successful, these vaccines could have a tremendous public health impact, not only preventing deaths but also reducing the long-term health and economic effects of malnutrition and developmental delays associated with experiencing severe diarrhea, as well as limiting the growth of antimicrobial resistance.  Pediatric products for malaria and more Children under five account for nearly 80 percent of global malaria deaths. Despite this significant burden, for a long time, there was a lack of a suitable malaria medicines for children, who were treated with crushed tablets designed for adults. The first child-friendly, quality-approved malaria treatment, launched in 2009 by Medicines for Malaria Venture (MMV) and Novartis, is sweet-tasting and quickly dissolves in water. 500 million courses of Coartem® Dispersible have been delivered worldwide as of this April, saving more than 1.8 million lives. MMV also delivered the first malaria treatment for newborn babies and young infants, which is an adapted version of Coartem® that was approved earlier this year. The two first-ever malaria vaccines, approved in the last five years, have been another major game changer for children with malaria, with 21 countries in Africa having introduced them so far, alongside other complementary prevention methods like chemoprevention and vector controlMMV is also working with partner Eyam Health to develop next-generation monoclonal antibody-based approaches to create affordable, long-acting malaria preventative therapies and treatments. Eyam’s technology has the potential to deliver future durable therapies without the need for cold storage and at an extremely low cost, projecting that a single long-acting therapeutic injection could provide protection for more than 50 million children and pregnant women for the months-long rainy season, which is peak time for malaria transmission. This would significantly simplify seasonal malaria chemoprevention, which today involves taking a course of oral drugs monthly for up to five months. Alongside these innovations for malaria, child-friendly medicines for HIV and neglected tropical diseases are also helping address the gap of suitable medicines for children and reduce the burden of treatment for children and their caregivers.  Diagnostics for pre- and postnatal complications and infections Premature birth, birth complications, and neonatal infections are among the leading causes of neonatal deaths, often resulting from limited access to timely screening, particularly in low-resource settings that face a lack of health care services, poor laboratory infrastructure and insufficiently skilled health care workers. Low-cost, easy-to-use diagnostics that can be deployed at the point of care are helping ensure that mothers and babies everywhere have access to routine screening in the pre- and postnatal periods, helping catch and address complications and infections earlier. One innovation is a portable, user-friendly ultrasound developed by Philips that connects to a mobile app on a phone or tablet, helping bring high-quality diagnostics to the point of care. The technology is being rolled out in low- and middle-income countries with the support of the Gates Foundation and has already demonstrated its ability to improve informed decision-making when triaging pregnant women in rural underserved communities.Bacterial infections caused by pneumonia, sepsis, and meningitis are the primary cause of neonatal infections, and most could be averted with adequate access to preventive interventions, early diagnosis, and care. Almost half of sepsis cases occur in children under five. The Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator has awarded funding to Melio, AstraDx, and QuantaMatrix to demonstrate feasibility of their rapid diagnostics for neonatal sepsis, all of which aim to provide results in mere hours, down from days. Early diagnosis is particularly important because the risk of death from neonatal sepsis increases about 7.6 percent every hour treatment is delayed. These innovations have the potential to help greatly reduce the risk of babies and mothers dying from complications and infections during the critical periods before and after birth.  Thirty-five years since the World Summit for Children, we’ve made tremendous progress in children’s health. Investing in innovative technologies specifically designed for children and striving to ensure children and their needs are considered and included in research across health areas will set up future generations for an even healthier future. 

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. A study published last week tested a promising new malaria vaccination strategy that aims to boost immunity through bites from mosquitoes carrying a genetically engineered version of the malaria parasite, which could pave the way for improved malaria vaccines. There are two approved vaccines for malaria, but they are only about 75 percent effective and require booster shots. In a trial, researchers exposed participants to bites from mosquitoes that had a version of the malaria parasite that was genetically modified to stop developing after delivery into a human, finding that nearly 90 percent of participants exposed to the modified parasites avoided contracting the disease after being bitten. The next step will be a larger trial to confirm this strategy as a viable candidate to advance malaria control efforts.A new study found that vaccines for diarrhea could reduce bacteria-associated diarrhea and antibiotic use among young children in low- and middle-income countries, which could also help reduce the emergence of antimicrobial resistance due to antibiotic overuse in low-resource settings where cases of diarrheal disease are most common. The research team used data from a previously published study exploring enteric infections and diarrheal illness in children in low- and middle-income countries and generated simulations to estimate the hypothetical impact of nine vaccine scenarios, including six single-pathogen vaccines and three combination vaccines. They found that, compared to the other single-pathogen vaccines, a vaccine against Shigella could cause the greatest reduction in antibiotic courses, and an adenovirus-norovirus-rotavirus vaccine could cause the greatest reductions in antibiotic use compared to the other combination vaccines.Last week, the Coalition for Epidemic Preparedness Innovations (CEPI) announced $1.46 million in funding for PATH to develop antibody reagents for developing vaccines against Severe Acute Respiratory Syndrome, or SARS. Antibody reagents are critical for measuring and analyzing a vaccine’s potency and ability to induce an immune response. PATH will lead efforts to develop and test reagents, as well as collaborate with the Texas Children’s Center for Vaccine Development to select and scale up a SARS-CoV-1-specific antibody to ensure these reagents are available globally, particularly in low and middle-income countries. The project aims to strengthen global health security by allowing researchers and manufacturers the tools to develop and scale up vaccines quickly in the face of an outbreak or new variant.

To celebrate Valentine’s Day, GHTC staff embraced our health policy wonkiness by participating in the time-honored beltway tradition: #HealthPolicyValentines.For those who are unfamiliar, this tradition started in 2012 when a former staffer and Twitter aficionado at the US Department of Health and Human Services, Emma Sandoe, became inspired to “tweet one ‘health policy valentine’ every day until Valentine’s Day.” Other health policy experts soon joined in with their own poems and puns related to health care, and an annual tradition was born.Now every February, health policy wonks tweet out their most creative #HealthPolicyValentines. This year, GHTC staff joined in on the fun to share our passion for global health research and development (R&D). Here are our favorites: Please be my valentine 💕Be “mon amour” 💑To defeat diseases like #AIDS, #TB & #malaria 🦠We need R&D for #vaccines, #diagnostics & cures. 💉 🔬 💊#HealthPolicyValentines #innovate4health @GHTCoalition— Jamie Bay Nishi (@JBayNishi) February 13, 2020 I love your guts ❤️Yet diarrheal diseases impact many worldwide 🌍Thankfully, with ORS, Zinc & #vaccines 💉 💊We’re helping more children survive. 🧒🏽 🧒🏼 🧒🏿#HealthPolicyValentines— Marissa Chmiola (@MarissaChmiola) February 13, 2020 Roses are red 🌹Violets are blue 💙With a universal vaccine 💉 We can take on the #flu 🦠#HealthPolicyValentine— Julien Rashid (@Julien_Rashid) February 13, 2020 Hey girl. My love for you is like biomedical research 🔬: complex, lengthy, & life-altering. #HealthPolicyValentines— Ansley Kahn (@ansleykahn) February 13, 2020 Roses are red 🌹Please be my honey 💑If we proactively develop vaccines to #outsmartepidemics 💉We’ll save lives & money 👩‍👩‍👧‍👧💰#HealthPolicyValentines— Philip Kenol (@Phil_kenol88) February 13, 2020 Getting in the #Valentines spirit a day early...Hey girl. Someone should alert @CDCgov because what you're doing to my heart is a health emergency. #HealthPolicyValentines pic.twitter.com/R8udCacb4d— Emily Conron (@thatNTDgirl) February 13, 2020 Hey girl, my love for you is like antimicrobial resistance.🦠🧫 Constantly evolving and growing every day (because we lack the right tools to stem its rise.)#HealthPolicyValentines #globalhealth #AMR pic.twitter.com/jstQXWIzFk— Marissa Chmiola (@MarissaChmiola) February 14, 2020 I’ve been bitten by your love 🥰You make my temperature rise 🌡️Is it #malaria or #dengue fever? 🦟We need diagnostic tests to surmise. ⁉️#HealthPolicyValentines— Ansley Kahn (@ansleykahn) February 14, 2020 Find yourself someone as committed to you as @NIAIDNews Director Tony Fauci is to infectious disease & #globalhealth R&D 😍🔬 His 36 years of leadership have earned him a spot in the Hall of Fame of my heart 💕 #HealthPolicyValentines pic.twitter.com/4ONP15XhNS— Emily Conron (@thatNTDgirl) February 14, 2020 I love you. You love me.Thanks to new technologies, we are reducing child mortality. #HealthPolicyValentines #Innovate4health pic.twitter.com/BRcv7G3Wh0— Jamie Bay Nishi (@JBayNishi) February 14, 2020 Roses are red 🌹Violets are blue 💙We can’t achieve #HealthForAll 🌍⚕️👩‍👩‍👧‍👦Without investing in R&D too! 🔬#HealthPolicyValentines pic.twitter.com/araErSTv2N— Philip Kenol (@Phil_kenol88) February 14, 2020 Feeling passionate about sexual & reproductive health (#SHRH) with my #HealthPolicyValentines:A woman deserves love 💕 She deserves gratification 🥰But she also deserves a healthy & bright future 👩‍🔬👩‍🎓‍Which is why we need more contraceptive innovation. 🤰🏽— Marissa Chmiola (@MarissaChmiola) February 14, 2020 Find someone that loves you the way @DrTedros loves #UHC.#HealthPolicyValentines pic.twitter.com/AFNBvOc42r— Julien Rashid (@Julien_Rashid) February 14, 2020

Faces of Innovation—a new GHTC project that features scientists on the front lines of research and development on new global health tools and technologies—profiles Dr. Rohit Ramchandani, who we met at the American Society of Tropical Medicine and Hygiene Annual Conferenc. Dr. Ramchandani does research to innovate global treatment options for childhood diarrhea at the Johns Hopkins School of Public Health in Baltimore, Maryland and the University of Waterloo. My name: Rohit Ramchandani, DrPHWhere I work: Johns Hopkins School of Public Health in Baltimore, Maryland and the University of WaterlooI’m funded by: US Agency for International DevelopmentMy research: My research focuses on diarrhea in children…the second-leading cause of death in children under five globally…These are close to 500,000 deaths that are happening every year, most of which are preventable, and treatable. They’re treatable with medicines, oral rehydration salts [ORS] and zinc. That’s the globally recommended treatment for diarrhea. But the problem is, in many low- and middle-income countries, access to these medicines is not where it should be, particularly in rural communities. So we looked at that issue of access. We did it by leveraging human-centered design approach. And we really focused on the details and the challenges that mothers face treating their children with diarrhea…Our research showed that 40% of the time, mothers are preparing ORS in the wrong concentration: either too diluted, or too concentrated. That can lead to hypernatremia, that can make the diarrhea even worse, or the efficacy gets reduced if it’s too diluted. So we actually worked with a local pharmaceutical company in Zambia to shrink down then size of the ORS sachets—the standard all over the world is a one-liter sachet—we shrunk those down to make 200-mililiter sachets, and then we made the packaging double as a measurement vessel for the right amount of water…One of our key funders during our scale-up phase was USAID—their Discover Health Program. They played a fundamental role in some of the social marketing we were doing as we were scaling up the development of our diarrhea treatment kit.Motivation: There’s just a fundamental issue of justice in the world…We often think of innovation being new product development, high technology, but things like ORS and zinc—innovation can happen really in the delivery side of things. And that’s really where our innovation focused.Why federal support is critical: I think this is low-hanging fruit. Diarrhea, as one of the leading causes of death in the world for children—we have the solutions, we know what to do, and these kinds of innovations can really make a huge difference in saving lives.…[And] there’s a health security argument [to do this work]. The world is getting smaller and smaller every day. We are inextricably linked to one another. When I’m not in the lab: I’m a dad! I’m a dad of two amazing young girls. They inspire me every day. It makes my work in child health that much more meaningful—the inspiration I get from them. I want all parents to have that.