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The US Food and Drug Administration (FDA) approved the first 3D-printed drug last week, paving the way for the technology to be used to customize medical care to individual patients. 3D printing is a manufacturing process that involves using a computer to create an object one layer at a time. In the case of the recently approved Spritam—a treatment for epilepsy—the printing allowed for greater control over formulation of the drugs, resulting in the creation of the first 1,000 milligram tablets that remain easily dissolvable despite their large size. The use of 3D printers could ultimately enable hospitals to produce their own medicines, adjusting the dose for individual patients. Meanwhile, at the University College London School of Pharmacy, researchers are exploring the possibility of using 3D printing to create uniquely shaped drugs. Drugs are absorbed at different rates depending on the surface area and volume of the tablet, and by adjusting the shape of a tablet (i.e., creating a pyramid or doughnut shaped pill) the rate at which a drug’s active ingredients are released could be manipulated. Leaders at the FDA and the US Department of Health and Human Services propose mechanisms and protocol to expedite drug development in public health emergencies in The New England Journal of Medicine, stating “if we are to act on lessons learned [from the Ebola outbreak] there is no time to waste.” The authors note that limited research capacity delayed the testing of experimental treatments, calling for efforts to strengthen clinical trial infrastructure globally. The outbreak also prompted debate about research ethics in emergency settings (i.e., whether it was ethical to administer untested therapies and the ethics of using placebos in an outbreak). Consequently, the authors recommend that processes for ethical review of studies in outbreaks be streamlined. Finally, the authors stress the need for coordination between health and regulatory authorities, researchers, and product developers. In the Ebola outbreak, the US government partnered with West African governments, academic institutions in both regions, and product developers at every stage. Clinical trials of different therapies were conducted concurrently, allowing partners to have a single, shared control group. The authors note that to facilitate collaboration for rapid drug development in outbreaks, there is a need to establish “model agreements” regarding data management and intellectual property rights. BiondVax Pharmaceuticals announced last week that those vaccinated with an experimental flu vaccine in 2012 had stronger immune responses to strands of influenza that didn’t even exist three years ago. The vaccine was developed to provide broad protection against different strands of influenza, in contrast to the seasonal flu vaccine which protects against the three to four strands of influenza predicted to be the most virulent that year. In 2012, the vaccine (M-001) was tested in phase II clinical trials in which 90 participants—all aged 65 or older—received the vaccine and 30 served as the control group. The vaccine successfully triggered an immune response, including the development of antibodies against several different strains of influenza. Earlier this year, BiondVax exposed blood plasma collected from participants in the 2012 trial to a strain of influenza that did not exist in 2012, and discovered protective antibodies against the strain in 50 percent of the plasma samples from those that received the vaccine, compared to just 10 percent of the samples from those in the control group. As BiondVax’s President Ron Babecoff explains, the vaccine “provides a safety net by broadening the immunogenicity [immune response] to existing and future flu strains.” Next, the vaccine will be tested in phase 3 clinical trials. Blood smear revealing Trypanosoma brucei parasites, which cause African sleeping sickness. (Photo: CDC/ Dr. Mae Melvin) A simple innovation—blue cloth and fine netting sprayed with insecticide between two sticks—could wipe out African sleeping sickness in a mere five to six years. African sleeping sickness is transmitted by tsetse flies, which breed along rivers looking for “something that contrasts with the green vegetation,” according to entomologist Steve Torr, “and for some reason they’re especially attracted to bright blue.” The flies are attracted to the blue cloth and the insecticide kills them within three minutes. The contraption is currently being tested in northern Uganda, where more than 17,000 have been installed over 1,500 square miles; in less than two years, the population of tsetse flies has been reduced by 90 percent. Only 1 in 1,000 flies carry the parasite, and the flies only reproduce once every nine days—whereas mosquitoes lay hundreds of eggs each day—bringing Torr’s team to the estimate of five to six years to both reduce the tsetse population, and eliminate the parasite from the remaining population.

The Global Health Technologies Coalition (GHTC) is pleased to announce that HarvestPlus has joined the coalition as a member. HarvestPlus is an international program that seeks to improve nutrition and public health by developing and promoting biofortified, staple food crops that are rich in vitamins and minerals, and providing global leadership on biofortification evidence and technology. “Micronutrient deficiency is a problem that adversely affects at least 2 billion people in the developing world,” said Dr. Howarth Bouis, director of HarvestPlus. “We believe that biofortification can be a cost-effective approach to tackle this problem on a large scale—making the everyday food staples that people rely on in poor regions more nutritious. To make this mission a reality, HarvestPlus works with diverse partners around the world to breed and promote micronutrient-rich staple food crops in poor countries and build a body of research that support their effectiveness. We look forwarding to partnering with GHTC and its members to educate policymakers about the benefits of biofortification and the important role science and innovation play more broadly in advancing global health.” HarvestPlus was officially launched in 2003 when it became the first recipient of grant funding for biofortification research from the Bill & Melinda Gates Foundation. HarvestPlus is part of the CGIAR Research Program on Agriculture for Nutrition and Health. CGIAR is a global agriculture research partnership for a food secure future. Its science is carried out by its 15 research centers in collaboration with hundreds of partner organizations. The HarvestPlus program is coordinated by two of these centers, the International Center for Tropical Agriculture and the International Food Policy Research Institute. “Biofortification is a novel and promising approach to improve global nutrition and health, and HarvestPlus is the global leader in refining and deploying it globally,” said Erin Will Morton, GHTC’s Coalition Director. “GHTC is committed to advancing groundbreaking research and innovation across global health areas and technology platforms, so we are excited to welcome HarvestPlus’s unique voice to our growing membership.” For more information about HarvestPlus, visit www.harvestplus.org.

Many infants have difficulty breastfeeding and must rely on cup feeding. Photo: PATH/Amy MacIver Breast milk is the perfect first food for newborns; it provides nutrients and energy that infants need and contains substances that strengthen their immune systems. Ideally, newborns are breastfed within their first hour of life with breastfeeding continuing for their first several months of life. However, some babies are not able to breastfeed—preterm babies often do not have the fine motor skills and babies born with facial anomalies like cleft palates cannot breastfeed. And in some cases, babies who are orphaned or have mothers too sick to breastfeed who must be fed with donor milk. In high-resource settings, these infants could have breast milk fed to them through feeding tubes or specially-designed bottles, but in low-resource settings these solutions are impractical and often unsafe in areas where reliable clean water is not available. Tubes must be inserted by a trained medical professional and are often not available in low-resource settings; while bottles are expensive—particularly those that adapted for use by infants with cleft palates— and difficult for mothers to keep free of bacteria due to their crevices. For infants in low-resource settings who cannot breastfeed, the World Health Organization recommends hand expression of breast milk and use of a small cup to feed newborns. Cups are easier to clean so reduce the risk of infection, and cup feeding has been shown in some studies to improve the transition of preterm infants to exclusive breastfeeding. The problem? There is no cup designed specifically for the job, and the household cups many mothers use have some serious drawbacks that can put their baby’s health at risk. A solution? A group of innovators from the University of Washington, Seattle Children’s Hospital Craniofacial Center, and PATH have invented the NIFTY™ cup—a simple-to-use, easy-to-clean, inexpensive cup designed specifically for delivering breast milk to infants. Your average cup won’t do for breastfeeding Because there is no standard cup designed for the purpose, mothers who need to cup feed typically use whatever small cups or devices they have on hand. For example, in India mothers typically use a miniature gravy-boat like device called a paladai—originally used to burn oil during religious ceremonies—that have sharp-edged metal spouts and can cause oral cuts or injuries to an infant. A young infant being cup fed with a mug in Kenya. Photo: PATH/Evelyn Hockstein In other areas of the world, mothers use coffee mugs, shot glasses, medicines cups, or whatever small cups they can find. Unfortunately, the relatively wide rims of these cups can make it difficult for a mother to maintain a consistent flow of milk to her newborn which can be problematic and even dangerous. Too much milk too fast can cause a newborn to aspirate, while too little milk can mean the baby does not get sufficient nutrition. “These infants are getting an erratic, inconsistent, sometimes too rapid flow [of milk] or not enough access to milk while they are feeding,” explained Christy McKinney, PhD, MPH, a clinical assistant professor at the University of Washington who helped design the NIFTY™ cup, “So the infants don’t get enough nutrients within the short amount of time to grow and fight infection.” During lengthy cup feedings, an infant can actually expend more energy trying to feed than it takes in, which can lead to a rapid decline in health. Another problem with standard cups is spillage. “About a third of milk is spilled at each feeding, said McKinney, “If you are trying to feed and hand expressing your breast milk, it’s a pretty painful experience to have a third of that spilled and wasted every time you are feeding, which can be 12 times a day for a newborn.” The NIFTY™ cup: a game changer for cup feeding A demonstration of feeding using the NIFTY cup. Photo: Marissa Chmiola/GHTC McKinney and her collaborators kept these drawbacks in mind as they set out to create the perfect cup for cup feeding. The NIFTY™ cup was designed with a unique reservoir that can hold a bolus of milk at its end. McKinney called this reservoir a “game changer.” It reduces spillage and allows the milk to be constantly available to the infant. McKinney explained that unlike a spout which only allows milk to be poured into an infant’s mouth, the unique reservoir of the NIFTY™ cup enables cup feeding to become a two-way street just like traditional breastfeeding or bottle feeding. “The mother is making sure that the reservoir is filled and then the infant gets to help pace the feed,” said McKinney, “That pacing results in a much calmer infant. They don’t run the risk of aspirating from too much milk poured into their mouth; instead, they can get the milk they need at the rate they want it, which allows for a calmer, integrated feeding experience between mother and infant.” The NIFTY™ cup inventors also made the cup out of silicone, which offers several advantages: The cup is soft and easy to squeeze, it prevents mouth injuries, it’s durable, and it can be boiled, which makes it easy to sterilize. Because the NIFTY™ has a reservoir that controls the flow of milk, the cup can be sized much larger than other cups used for cup feeding. This allow mothers to directly hand express the milk into the NIFTY™ cup rather than using multiple cups which in turn reduces spillage and opportunities for contamination. In addition, the NIFTY™ cup contains tracking markers on the side to monitor milk intake, it’s ergonomically designed for comfort, and it can be affordably produced at less than $1.00 per cup. In short, the NIFTY™ cup offers more advantages for mothers and infants than any other available cup. The long road to innovation For McKinney it has been over a five-year odyssey to turn the NIFTY™ cup from idea to reality. Inspired by her time as a Peace Corp volunteer in Ethiopia and having just completed her PhD studying craniofacial anomalies and beginning her new post-doctoral position, McKinney was looking for ways she could help children in low-resource settings with oral clefts. She saw feeding as the most problematic area and an area most in need of innovation. “So I just thought it would be nice to come up with an idea to feed these infants with,” said McKinney. With this concept in mind, McKinney began searching for a partner who could help make such an idea possible. She discussed the idea with Dr. Michael Cunningham, the director of the Seattle Children’s Hospital Craniofacial Center, where she completed her PhD, and they approached GHTC member PATH, based in Seattle. “We reached out to PATH…and there was sufficient interest to say let’s try and make this work,” said McKinney. Together they developed a design team which included McKinney (an epidemiologist); Dr. Cunningham (a craniofacial pediatrician); a social scientist, engineer, and commercialization officer from PATH; and an occupational therapist/lactation consultant from Seattle Children’s Hospital. Together, with funding from PATH and the Seattle Children’s Hospital Craniofacial Center, the team designed their first prototype cup. A product can only have impact if it meets end-user needs and people are actually interested in obtaining it. To make sure both applied to the NIFTY™ cup prototype, the team set out to test drive the cup in low-resource settings. With support from a nonprofit Transforming Faces—which supports care for children with oral clefts in South India—and additional funding from the University of Washington CoMotion, McKinney and the team took the NIFTY™ cup to Sri Ramachandra University in South India to do formative design work in both the cleft center and the Neonatal Intensive Care Unit. They introduced the cup to mothers and health providers including lactation consultants, watched the product in use, and conducted surveys to gauge interest in the product and to inform design. The NIFTY™ cup was a big hit. “I was really excited that they liked it more than what they were using,” said McKinney, “I didn’t quite know what to expect on that, but they are really excited to get it commercialized.” Armed with valuable feedback from South India, McKinney and the team regrouped and are doing a minor redesign of the product which will be complete this summer. Last month, the team won a grant from the Saving Lives at Birth Challenge. With this funding, the NIFTY™ cup developers plan to conduct a clinical study in Ethiopia to evaluate the product’s effectiveness compared to standard cups being used, and also develop a market shaping strategy for introducing the product. While it could still be some time before the product is widely available to those who need it, McKinney and the rest of the team are energized by the NIFTY™ cup’s lifesaving potential and the support they are receiving to continue development and introduction. “I’m so excited. This little idea has percolated so long, and people have finally seen the value it can bring,” said McKinney.

Sabin Vaccine Institute—a member of GHTC—and Texas Children’s Hospital Center for Vaccine Development received a US$1.8 million grant to expedite the research and development of the first therapeutic vaccine for Chagas disease, which is currently undergoing preclinical research by the same team. Chagas is caused by the parasite Trypanosoma cruzi, which attacks and feeds on human tissue, resulting in heart or digestive disorders in nearly one-third of those infected. The disease is endemic throughout Latin America and in recent years has moved into the United States. The grant comes from the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation, which works to improve the quality of life in southern Texas, where investigators estimate there are anywhere from tens to hundreds of thousands of Chagas cases in humans. The Critical Path Institute (C-Path)—a nonprofit that facilitates cross-sector partnerships to expedite drug development and regulatory approval—has formed a Pre-Launch Consortium tasked with establishing and operating a Global Pediatric Clinical Trials Network. The Consortium will be comprised of representatives from academia, the public and private sectors, the pharmaceutical industry, foundations, and child health advocacy groups and will determine the structure and leadership of the Network, which will be nonprofit and independent from C-Path. The Network is intended to be a resource, providing technical expertise and using its global infrastructure to advance the development and approval of pediatric treatments across diseases and conditions, phases of trials, and types of studies. The Network’s resources will be available to all product developers, both for- and not-for-profit. Photo: CDC Dr. Rebecca Richards-Kortum and Dr. Maria Oden, professors of Bioengineering at Rice University, are working to create a “Nursery of the Future” to save the lives of babies born prematurely in low-resource settings. Prematurity is the leading cause of death for children under five years old. In hospitals in high-income countries, expensive computer monitors are used to alert staff when a baby stops breathing, so that they can wake the infant and trigger him or her to keep breathing. As a low-cost, innovative alternative, the team has successfully tested a band that wraps around an infant’s belly and vibrates—using motors similar to those in cell phones—when the baby stops breathing, waking it directly. Next, Richards-Kortum and Oden want to develop low-cost alternatives for infant warmers, oxygen concentrators, and serum bilirubin tests—all expensive equipment used in hospitals in high-income countries. Their eventual goal is to create an entire nursery that costs less than US$10,000. A new study suggests that “leaky” vaccines, which decrease the severity of an infection rather than prevent it entirely, could lead to the evolution of more virulent pathogens. The basic premise is that when a pathogen is able to survive in a vaccinated person, it grows stronger, and the vaccinated person can then become an asymptomatic carrier of the more deadly version of the pathogen. The study, led by Dr. Andrew Read, a professor of Biology and Entomology and Pennsylvania State University, applied the theory to Marek’s disease, a poultry disease against which farmers regularly vaccinate their chickens. Read’s team demonstrated that, when infected with different strains of Marek’s disease virus, vaccinated chickens were effective carriers, and that those infected with highly virulent strains were able to spread the disease to a greater number of unvaccinated chickens. Read believes that “we are entering the era of leaky vaccines in humans,” as researchers develop partially effective vaccines for complicated viruses such as malaria or HIV and AIDS. However, vaccine researcher Dr. Adrian Hill of Oxford University argues that the theory is plausible but unlikely, referring to Marek’s disease as “the only example of this happening” and noting that the development of natural immunity in a population could have the same effect.