Breakthroughs Blog: Child health

Last week, Moderna announced that it has received an award from the Coalition for Epidemic Preparedness Innovations (CEPI) for up to $54.3 million to support ongoing development of its bird flu mRNA vaccine candidate, after US government backing was cancelled earlier this year. There are currently no vaccines available specifically for bird flu, as the virus continues its worrying spread among animal populations in the United States and globally. A vaccine, especially one using the mRNA platform known for its speed and adaptability, could play a crucial role in curbing a future outbreak in humans with pandemic potential.  A research team led by the Australian Peter Doherty Institute for Infection and Immunity has identified a tool that can detect emerging hotspots for Buruli ulcer years before human infections occur, as the serious bacterial skin infection continues to spread across Australia and endures in other regions around the world. The infection has a long and variable incubation period, making it hard to identify when and where patients were exposed. The researchers tracked the excreta of possums, who have small ranges, making the presence of the bacterium that cause the infection in their excreta a likely sign that it is present locally. Then, they used DNA sequencing to compare the bacterial genomes of possum-derived and human-derived infections, finding where they overlapped to identify areas where human infections could occur. The method aims to allow public health authorities to implement targeted interventions early on, far before human cases occur. Two new studies looking at preventive RSV vaccines and drugs found that that their effectiveness waned over time, suggesting that boosters may be needed to ensure long-lasting protection, as RSV continues to pose a growing seasonal challenge, especially for older adults and infants. The first study found that one dose of the Abrysvo RSV vaccine was highly effective at preventing infections and reducing hospital, emergency department, and intensive care unit admissions in US veterans 60 and older, but this protection decreased over time, with the reductions most notable for immunocompromised individuals. A second study found that the long-acting monoclonal antibody nirsevimab was highly effective in hospitalized European children two years or younger for one season, but after that, protection waned. Both studies demonstrate the real-world impact of these crucial tools and suggest that boosters could be implemented to ensure long-lasting protection, especially for higher-risk individuals. 

An international research team, led by scientists at the University of Maryland School of Medicine, shared the results of the Phase 1 trial of a novel vaccine designed to protect against typhoid fever and non-typhoidal Salmonella infections, reporting that the vaccine produced a strong immune response and was safe and well-tolerated in a small group of healthy US adults. These encouraging findings pave the way for the next step of evaluating the vaccine in children. A single vaccine that targets Typhoid fever and non-typhoid Salmonella, both leading causes of illness and death in children in Africa, could be a game-changer for pediatric health. The vaccine could also help protect people in the United States and other high-income countries, where some types of Salmonella are common causes of foodborne illness. Following the example of the US military, who often wear uniforms treated with insecticide to repel mosquitoes in malaria-endemic regions, a research team has tested a similar approach to try to protect young children, who face a significant burden of malaria in sub-Saharan Africa. While existing vector control tools, such as insecticide-treated bednets, only protect children while they’re sleeping, a large randomized controlled trial in Uganda tested the efficacy of insecticide-treated baby wraps, used in conjunction with bednets. The trial found that the baby wraps were highly effective at preventing malaria infections. The dramatic scale of the reduction of new infections also suggests that malaria-carrying mosquitoes were biting during the daytime more often than previously thought, which could help guide the development of new vector control tools and approaches. Last week, The Safety of Antimalarials in the FIRst trimEster (SAFIRE) consortium announced that it had enrolled its first patient in Mali, marking the official start of the first-ever Phase 3 adaptive platform trial evaluating the efficacy and safety of antimalarial drugs in the first trimester of pregnancy. The trial is a landmark achievement that could not only help fill the crucial gap of safe and effective options for pregnant women at risk of malaria, but it is also a step toward equity and inclusion for clinical research and drug development in general, which have long excluded pregnant women, fueling the gap in the first place. SAFIRE partners have shared that early formative research in the communities where the trial will take place was a crucial step in ensuring that the design and process were appropriate and acceptable to the communities. The study will continue to progress in Mali, Burkina Faso, and Kenya. 

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. 

Last week, Monod Bio, a spinout company from the University of Washington, announced that it has received a $1.5 million Gates Foundation grant to develop a urine-based rapid diagnostic test for tuberculosis (TB). The company aims to help fill the gap of non-sputum-based, rapid, point-of-care TB diagnostics that are suitable for low-resource settings. Most World Health Organization-recommended TB diagnostics rely on sputum, which not all patients can provide and can be logistically difficult for health care providers to collect, but current alternatives using urine and stool samples have low specificity, and current TB tests are also not available at the point of care in communities. The test will utilize the company’s NovoBodies, novel proteins designed to be highly specific and sensitive—diagnostics have primarily used natural proteins that are adapted for use in tests.  The Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) last week announced that it is awarding $1 million to Zeteo Tech to further work on a rapid, non-invasive diagnostic test that can diagnose lower respiratory tract infections, like pneumonia, using breath samples. Lower respiratory tract infections kill 700,000 children under five annually. A less invasive, rapid test could help speed up diagnosis and guide more effective treatment, particularly of drug-resistant infections, helping reduce the prescribing of unnecessary antibiotics that can fuel the rise of antibiotic resistance. Zeteo’s platform analyzes the tiny particles and droplets in breath samples to distinguish between viral and bacterial infections and assess antibiotic susceptibility.  The results of a clinical trial released last week found that a common over-the-counter nasal spray that is used for seasonal allergies could work as an antiviral against a range of respiratory infections, including influenza, RSV, and the virus that causes COVID-19. The researchers suggest that the nasal spray, Azelastine, could help block COVID-19 infections by inhibiting a key enzyme that the virus uses to replicate or by preventing the virus from latching on to the point at which the virus enters human cells. If proven safe and effective in further studies, Azelastine could serve as an easily scalable, over-the-counter prevention method complementary to vaccines and other tools, especially when a virus is spreading among a community or in high-risk situations, like when traveling or attending crowded events. The research also provides another potential target for future vaccines.