Breakthroughs Blog: Child health

Researchers at the Durham University in the United Kingdom have received a US$100,000 grant from the Bill & Melinda Gates Foundation to test the feasibility of training dogs to detect malaria. Dogs have been trained to use their keen sense of smell to detect other diseases, including certain cancers, and studies suggest that malaria infection causes a distinct odor, and that unique chemicals can be found on the breath of patients. The team plans to recruit 400 children in the Gambia, including many who are currently infected with malaria. The children will wear nylon socks for 24 hours, which will then be used to train the dogs to identify malaria based on odors in the sweat and skin. If successful, this approach to malaria testing would be quick and cheap, and would not require any equipment or a laboratory setting. A new, commercially-available diagnostic can predict premature births, a critical tool as half of all preterm births occur in women without known risk factors. Between 2011 and 2013, the Utah-based Sera Prognostics enrolled more than 5,500 pregnant women at 11 sites across the United States, and confirmed that the quantity of two proteins in the blood can indicate risk for preterm birth. The test can be administered at 19 or 20 weeks into the pregnancy; pregnancy normally lasts 40 weeks and delivery before 37 weeks is considered preterm. The test—PreTRM®—tells a woman her percentage risk, and currently costs $945, however, Sera Prognostics is working with the Bill & Melinda Gates Foundation to develop tools more suitable for low-income countries. Startup NextGen Jane is developing a “smart tampon” that would collect menstrual blood each month and test for a range of diseases and conditions, including sexually transmitted infections, endometriosis, polycystic ovarian syndrome, uterine fibroids, cervical cancer, and more. Many of these conditions are asymptomatic, and consequently go undetected until significant damage has been done. The team at NextGen Jane has a working prototype—a device that siphons menstrual blood from tampons—and is conducting clinical trials for several of the diagnostics themselves, which identify biomarkers for different conditions in menstrual blood. The tool will connect to a database, allowing women to analyze the data and track their reproductive health over time. The team anticipates having a complete product—combined diagnostics and the delivery mechanism—within the next year, which will be commercially available within three to four years.

Photo: National Institute of Allergy and Infectious Diseases (NIAID) Gavi, the Vaccine Alliance, signed an advanced purchase commitment, pledging to spend US$5 million on an Ebola vaccine currently under development by pharmaceutical company Merck & Co. The vaccine candidate was tested on 4,000 people in Guinea last year, and the results were promising: despite all participants having close contact with at least one Ebola patient, none developed the disease more than ten days after vaccination (several days are required for a vaccine to confer protection). The vaccine candidate—VSV-EBOV—was developed and tested in partnership with the Canadian and US governments, however, without the urgency of an outbreak, public-sector support moving forward is limited. The agreement guarantees that there will be a market for the vaccine, assuring Merck & Co. that they can recover investments in advanced development and manufacturing. This move will also enable Gavi to establish a stockpile of the vaccine so that it can be rapidly deployed in future outbreaks. New research suggests that 2.6 million stillbirths occur each year, 420,000 of which are attributable to malaria or syphilis infections. These results underscore the need for testing and treatment of malaria and syphilis in pregnant women, particularly in endemic regions. Fortunately, there are low-cost interventions that could drastically reduce adverse pregnancy outcomes attributable to malaria and syphilis infections. The malaria parasite is able to reside in the placenta, even when undetectable in the mother’s blood, and thus, preventative treatment for malaria is critical. The antimalarial sulphadoxine-pyrimethamine, which costs a mere $0.20 per patient, is recommended for use in pregnant women in endemic areas. In east and southern Africa, an estimated 5 percent of pregnant women are infected with syphilis and in Tanzania, up to half of stillbirths are caused by syphilis. However, one dose of penicillin can cure both maternal and congenital syphilis and prevent stillbirth—at just $1.40 per person. While malaria- and syphilis-related stillbirths can be prevented with the scale-up of existing medicines, many more could be prevented with interventions that are not appropriate for low-resource settings, which is particularly concerning as 98 percent of stillbirths occur in low- and middle-income countries. Further, the cause of stillbirth is often unknown, according to the Global Alliance to Prevent Prematurity and Stillbirth, and additional research is needed to determine and address these causes. There is little incentive for pharmaceutical companies to invest in antimicrobial research and development (R&D): antibiotics are prescribed for short periods of time and competition among antibiotics keeps prices low. However, with the spread of drug resistance, the “[financial] value assigned to antibiotics and diagnostics often does not reflect the benefits they bring to society,” according to a declaration authored by 80 pharmaceutical and diagnostic companies and released at this year‘s World Economic Forum in Davos, Switzerland. The declaration calls on governments to work with the pharmaceutical industry to spur antimicrobial R&D, identifying innovative financing mechanisms, including prizes (a Market Entry Rewards initiative) and intellectual property–related incentives. In response, the companies pledge to invest in R&D for new antibiotics, as well as improved diagnostics to prevent the unnecessary use of antibiotics (i.e., for viral conditions).

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.