Breakthroughs Blog: Child health

Pyramax® Granules (Photo: MMV) After four successful Phase 3 clinical trials enrolling more than 3,500 patients in 18 countries, the European Medicines Agency (EMA) has granted Pyramax® Granules, a pediatric malaria medicine, a positive opinion under Article 58—a mechanism through which the EMA reviews and issues a scientific opinion on products that are not intended for use in Europe. Pyramax® Granules is a combination of two antimalarials and was developed by Medicines for Malaria Venture (MMV), a member of the GHTC, in partnership with Shin Poong Pharmaceutical Co. Ltd. The treatment is designed to be easy for children to consume: its bitter taste is masked and it is taken in liquid form, as children often struggle to swallow pills. Next, MMV and Shin Poong will work to introduce Pyramax® Granules as well as Pyramax®, the tablet version which is suitable for adults, in malaria-endemic countries. A recent article in NPR: Goats & Soda examines Zika virus, a disease transmitted by the same mosquito vector of dengue fever and chikungunya, that has been rapidly spreading throughout South America and the Pacific Islands in recent years. One in five individuals infected with the virus experience Zika fever, which in addition to fever involves rashes, joint pain, conjunctivitis, headaches, vomiting, and muscle pain. Cases of Zika fever are likely underdiagnosed, as awareness of the disease is limited and its symptoms are similar to infections associated with other members of the Flaviviridae virus family, including dengue fever, yellow fever, West Nile, and Japanese encephalitis. There are no reported deaths to date, but there is growing evidence that the virus can be transmitted sexually or from mother to infant during pregnancy. As there are no vaccines or drugs for Zika fever, treatment involves addressing the symptoms, using fever reducers and painkillers. A group of global health advocacy organizations—including GHTC members the Drugs for Neglected Diseases initiative, TB Alliance, Infectious Diseases Society of America Center for Global Health Policy, Sabin Vaccine Institute, and Treatment Action Group—sent an open letter to the US Senate Health, Education, Labor and Pensions (HELP) committee, calling for amendments to the priority review voucher (PRV) program at the US Food and Drug Administration (FDA) to ensure it adequately incentivizes research and development (R&D) for neglected diseases, as intended. Under the program, companies that receive FDA approval for a drug for a neglected disease (see list of eligible diseases) are awarded a voucher for expedited FDA review (six months rather than ten) of a future product. The vouchers are transferable and have been sold at increasing rates, the most recent going for US$350 million. The letter calls for PRVs to only be awarded for products that are "truly new" as two of the six vouchers that have been awarded were for products that had long been in use outside of the United States.[1] The organizations are also calling for recipients of the voucher to be required to develop a strategy to ensure the product is made affordable and accessible to patients in the countries in which the eligible disease is endemic. The United Kingdom (UK) announced last week the creation of the Ross Fund which will provide £1 billion ($1.5 billion) over five years to fight malaria and other infectious diseases. The funding, which will come from the UK overseas aid budget, includes £90 million for malaria eradication; £100 million for infectious disease R&D; £115 million for the development of drugs, diagnostic, and insecticides for malaria, tuberculosis, and other infectious disease resistance; and £188 million for biodefense and rapid response systems for epidemic preparedness. Global Good has developed a cooler that can store and transport vaccines at freezing temperatures for over a month using just ice and no electricity. The Arktek cooler uses vacuum thermal insulation, an approach used to preserve spacecraft entering extreme temperatures. The cooler has been tested in Senegal (with support from GHTC member PATH) and Ethiopia, and last year, the Arktek was modified for use in Ebola vaccine clinical trials, during which the cooler kept the vaccines between -76 and -112 degrees Fahrenheit for three days. [1] There are two separate PRV programs at the FDA, one for neglected tropical diseases and one for rare pediatric diseases. Of the six PRVs that have been awarded, three each have been for neglected tropical diseases and rare pediatric diseases. Since the beginning of the PRV program, six PRVs have been awarded—three for neglected tropical diseases and three for rare pediatric diseases.  

Photo: PATH/Gabe Bienczycki Preterm birth complications are the leading cause of death for children under five years of age. Survival rates, particularly for babies born extremely premature (three months early), can vary drastically from 10 percent in low-resource settings to 90 percent in high-resource settings. While many babies are born in low-resource settings, outside of hospitals, and without access to high-tech interventions, it is still possible to provide the basic care many preemies need to survive. For example, a number of low-cost innovations and interventions, such as breathing support and clean cord care, have the potential to slash newborn mortality. GHTC member, The Global Alliance to Prevent Prematurity and Stillbirth (GAPPS), in partnership with Project Concern International and the American College of Nurse Midwives, has received a five-year, US$9 million grant from the US Agency for International Development for the Every Preemie—SCALE initiative to identify lifesaving interventions for the prevention and treatment of preterm birth and low birthweight and to support the scale-up of these interventions in 23 countries across Asia and Africa. To learn more about GAPPS’ work on the Every Preemie—SCALE initiative, we’re joined by Dr. Jim Litch, director of the Perinatal Interventions Program at GAPPS. Q: Central to the Every Preemie—SCALE initiative is research to identify evidence-based solutions for the treatment and management of preterm birth and low birthweight. What’s been done so far and what key findings are emerging? A: Ideally, pregnant women should have access to prenatal care, which is particularly important for women at risk of preterm birth who need particular prevention services and care interventions. Far too often, however, prenatal care is out of reach for families, of poor quality, or does not include the special needs for preterm births and preterm newborn care. Preterm birth has only recently received attention from the global health community, and there are many emerging opportunities to learn from current efforts to expand maternal and newborn health programs to include preterm birth prevention and care content. Preterm babies have different needs than full-term babies, and recognizing this helps us develop tools and interventions across the continuum of care. Just this month, accurate growth curves for weight, length, and head circumference for healthy preterm babies born as a single birth were published to complement existing growth standards for full-term infants and provide new, accurate standards for fetal growth. Through Every Preemie, GAPPS is supporting implementation research with local partners in Bangladesh, Ethiopia, India, and Malawi. In Bangladesh, we are testing a simple method of estimating gestational age during pregnancy using a tape measure and weight scale. In Ethiopia, we are evaluating implementation of preterm birth services within multi-partner maternal and newborn health programs across the continuum from the community to district hospital level in different living contexts (settled, semi-settled and urban). In India we are preparing to assess the safe use of antenatal corticosteroids (ACS)—which have been shown to reduce preterm birth complications—among women in imminent preterm labor, including pre-referral first dose of ACS administered by auxiliary nurse midwives. And in Malawi we are investigating the effectiveness of a comprehensive community mobilization approach designed to better link communities to preterm-related health services from the household to the facility level. A recurring finding from the implementation and research communities is that context is critical. What works well in one setting may not work well in another. This is a lesson that returns to us time and again. Standardized outcomes and robust descriptions of the settings from which evidence is obtained create a greater burden on research, evaluation, and program resources. Q: Can you talk a bit about some of the technologies identified as potential solutions under Every Preemie? And what characteristics make a product or intervention realistically scalable in low-resource settings? A: Infant death and morbidity following preterm birth can be reduced through interventions provided to the mother before and during pregnancy, including the period around delivery, and to the preterm infant after birth. The most beneficial set of maternal interventions are those that could improve survival chances and health outcomes of preterm infants when preterm birth is inevitable. In August 2015, the first World Health Organization recommendations on the Interventions to Improve Preterm Birth Outcomes were issued. These recommendations provide important guidance on interventions and related technologies that could be provided during pregnancy, labor, and the newborn period with the aim of improving outcomes for preterm infants. Understanding the demand for services is of critical importance when working to realistically reach scale in low-resource settings. This includes a need to better understand the knowledge, attitudes, and perceptions of families around preterm birth and preterm newborns in individual communities and settings, as well as the demand created by care providers within existing maternal, newborn, and reproductive health service delivery systems. Now more than ever, improvement in preterm outcomes requires a truly integrated approach. Q: What role will advocacy—whether at the global, national, and local level—play in advancing the innovations and interventions identified through Every Preemie? A: Advocacy is fundamental at all levels for real, lasting change. Moving a community to success can be accelerated by advocacy. When professional organizations, parent groups, economists, and others all demonstrate the effects of quality prenatal and newborn care, governments will institute policies to provide not just for the wealthy but also for the most vulnerable. The best interventions, products, and services can have impact on preterm survival only when the required attention and ongoing needs are continuously met for these highly vulnerable developing fetuses and preterm newborns. Ultimately a chain of basic newborn care, combined with special basic care for preterm newborns (thermal care, adequate feeding, hygiene, and counseling) is essential for more sophisticated clinical interventions and products to be successful in saving lives and limiting morbidity. Doing basic care well, for all pregnant women and newborns, will go a long way in supporting preterm survival and the effectiveness of clinical interventions directed at preterm complications. The numbers support this approach. Infants born before 34 weeks gestation, for which more advanced clinical interventions target, comprise roughly 3 percent of all births and about 30 percent of all preterm births. Also, the majority of newborns who die as a result of intrapartum complications, birth asphyxia, and severe newborn infection (also among the leading causes on newborn mortality) are preterm. Success depends on the right care, in the right place, at the right time—every time.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. This month at the Saving Lives at Birth: A Grand Challenge for Development’s DevelopmentXChange event in Washington, DC, bright minds from all over the world came together to display groundbreaking prevention and treatment approaches for pregnant women and newborns in low- and middle-income countries. The event also offered an opportunity for policymakers and decision makers to talk about the importance of science, research, and innovation for global health. During last week’s US-Africa Leaders Summit, the White House released a fact sheet on American and African cooperation for global health. As the world’s largest donor to global health, the United States is committed to working with African governments to improve the health of its citizens—including achieving an AIDS-free generation, ending preventable maternal and child deaths, enhancing global health security, and supporting African countries invest in the health of its own citizens. The World Health Organization said it thinks an Ebola vaccine should be ready for public use by 2015. There is currently no vaccine or cure for Ebola, which is currently widespread in parts of West Africa and has killed over 900 people since March of this year. This year’s outbreak is the biggest ever reported since Ebola was discovered over 40 years ago. In the Huffington Post’s blog, Dr. Jonathan Mermin—director of the Center for Disease Control and Prevention’s National Center for HIV and AIDS, Viral Hepatitis, Sexually Transmitted Diseases, and Tuberculosis (TB) Prevention—writes about the desperate need for new tools to prevent, detect, and treat TB and that “until we have better ways of detecting and treating TB, thousands of Americans and millions of people worldwide will continue to suffer from an illness that should have been consigned to history long ago.” An experimental vaccine to prevent dengue could be commercially available by July 2015, according to the vaccine’s makers—pharmaceutical company Sanofi Pasteur. There is currently no vaccine to prevent this mosquito-borne disease that affects thousands of people—mainly in low- and middle-income countries—every year.

“Innovation can’t take place if people say we don’t need new tools,” said Partners in Health Co-founder Paul Farmer at an event sponsored by the Saving Lives at Birth: A Grand Challenge for Development program last week in Washington, DC. And new tools were certainly on display at DevelopmentXChange 2014—a key component of the Saving Lives at Birth program. The DevelopmentXChange is an opportunity for hundreds of bright minds to come together and display groundbreaking prevention and treatment approaches for pregnant women and newborns in low- and middle-income countries. The event is also a time for key policymakers and decision makers to talk about the importance of science, research, and innovation for global health. Saving Lives at Birth—a partnership between the US Agency for International Development (USAID), the Bill & Melinda Gates Foundation, the Government of Norway, Grand Challenges Canada, and the UK Department for International Development—provides funding for a select group of finalists that offer the most innovative new tools. Large crowds were spotted at the DevelopmentXChange Marketplace the morning of the event. The DevelopmentXChange opened up with a marketplace where finalists of the Saving Lives at Birth challenge could display their innovations and demonstrate how these new tools could make a difference in the lives of mothers and children in low-resourced settings. Imagine a giant science fair where, instead of competing for a blue ribbon, the participants are competing for funding to make their innovation a reality. On display were several proposed innovations from GHTC members FHI 360, Jhpiego, and PATH. FHI 360 proposed a synchronized schedule for postpartum women to receive family planning services and for their newborns to receive immunizations and growth monitoring all at the same time. One of the innovations Jhpiego developed was the E-Partogram—an affordable, easy-to-use handheld electronic decision-making tool for preventing and managing complications during labor. PATH was one of many other organizations to address postpartum hemorrhage by developing heat-stabilized oxytocin—a common treatment for hemorrhaging women after childbirth—in a fast-dissolving oral tablet that would treat postpartum hemorrhage.   USAID Administrator Raj Shah addresses the crowd at the DevelopmentXChange Forum After the marketplace, policymakers, scientists, members of the global health community, and the Saving Lives at Birth finalists gathered together for the DevelopmentXChange Forum, which included opening remarks from USAID Deputy Assistant Administrator for Global Health Katie Taylor, USAID Administrator Raj Shah, and Paul Farmer. Administrator Shah commended many of the past year’s innovations for making a real difference in the lives of women and children, and commented on how the Saving Lives at Birth program influenced the creation of USAID’s new Global Development Lab. The rest of the forum featured innovators from all over the world, including past Saving Lives at Birth challenge winners. One of the innovations featured at the forum was a new, low-cost device that assists in delivering babies when complications occur in the second stage of labor. The device—called the Odon Device—was originally thought of by an Argentine mechanic named Jorge Odon when he was thinking about how to get a cork out of a bottle one night. The Odon device is made of a film-like polyethylene material and could be a safer and easier way to deliver complicated births rather than using than forceps or a vacuum extractor. After Mr. Odon partnered with Becton, Dickinson and Company, and received funding from Saving Lives at Birth at last year’s DevelopmentXChange, the Odon Device was finally ready for full development. Now the device is being tested in clinical trials and—if approved—has the potential for wide application in resource poor settings. If there was one thing very apparent during the day, it was that great, life-saving ideas can come from anyone—no matter what they do or where they live. Saving Lives at Birth is a good example of a mechanism that brings governments, foundations, and for-profit companies together to encourage creativity and innovation to tackle some of the world’s most pressing problems. The day concluded with Wendy Taylor—director of USAID’s Center for Accelerating Innovation and Impact—announcing the winners of the Saving Lives at Birth challenge. GHTC members PATH and FHI 360 both won seed grants to get their ideas up and running so that one day they could have the potential to protect and improve the lives of mothers and children all over the world. GHTC congratulates all of the challenge winners and is inspired by every single one of the innovators who were at this year’s DevelopmentXChange.