Breakthroughs Blog: Maternal health

There is no doubt that the past decade has brought transformative breakthroughs in global health innovation, from new medicines, to combatting leading child killers like malaria and tuberculosis (TB), to interventions that are making an AIDS-free generation possible. These game changers have saved millions of lives and helped unlock better health and opportunity for people around the world. The Global Health Technologies Coalition (GHTC) spent this past decade standing side-by-side in partnership with scientists and innovators, working to ensure they have the resources and supportive policies needed to advance innovation that truly drives impact. As we close out our tenth anniversary year and mark our first decade of advocacy, we wanted to take a moment to reflect on our shared progress and celebrate the headlines and moments that shaped global health research and development (R&D) over the past decade. Here are ten highlights: Could pills taken daily prevent HIV infection? That was a key question on researchers and activists minds in the early 2000s.By the end of the decade, the evidence pointed to yes. In 2012, the US Food and Drug Administration (FDA) approved the use of the antiretroviral drug Truvada as pre-exposure prophylaxis (PrEP) to prevent HIV infection. While it took several more years for PrEP to begin to be approved and introduced in low- and middle-income countries (LMICs), it has proved a powerful new tool in the global fight against HIV and AIDS. Revolutionary. Simple. Empowering. These are words that have been used to describe Sayana Press, an all-in-one injectable contraceptive developed by GHTC member PATH. Sayana Press combines a long-acting contraceptive with the easy-to-use Uniject injection system that involves minimal training, making it an especially suitable tool for low-resource settings and for women to self-administer. Since its introduction in 2014, more than 1 million doses of Sayana Press have been delivered to women worldwide, giving them greater power and autonomy over their reproductive health. Despite the fact that over 70 percent of all malaria deaths are children, before 2009 there was not a single high-quality malaria drug designed for kids. Instead, parents would crush adult tablets in what amounted to a daily struggle to provide an accurate dose as well as convince their kids to swallow these bitter tasting pills. This changed with the introduction of Coartem Dispersible, the first malaria medicine designed for children. Developed by GHTC member Medicines for Malaria Ventures, the medicine is affordable, easy-to-administer, sweet-tasting, and dosed for children. As of 2016, over 300 million treatments have been distributed worldwide, saving an estimated 750,000 lives. For more than a century, meningitis has ravaged a swath of the African continent known as the “meningitis belt,” killing one in ten people it sickened. But thanks to the efforts of a coalition of partners, including GHTC member PATH, we’ve stopped deadly meningitis A epidemics in their tracks. In 2010, MenAfriVac—a low-cost vaccine against mengingitis A—was introduced in Africa. Since then, more than 270 million people in 26 countries have been vaccinated, and thankfully, meningitis A is becoming a disease of the past. HIV and AIDS remains one of the greatest threats to women’s health globally, yet women and girls still lack the range of tools they need to protect themselves. Thanks to over a decade of effort by a unique partnership led by GHTC member the International Partnership for Microbicides, the future looks different. The partnership has advanced a new woman-center HIV prevention tool: a monthly, vaginal microbicide ring that deliver antiretroviral drugs. The groundbreaking new tool was found to reduce HIV risk in women in late-stage clinical trials in 2016, and it is now under regulatory review and poised for potential introduction worldwide. For parents with kids suffering from TB, getting their child to take multiple pills a day for months was a serious struggle, from trying to split up pills, to achieving the right dosage, to convincing children to swallow bitter tasting medicine. In 2016, this process became easier with the introduction of the first kid-friendly TB drugs. Developed by GHTC member TB Alliance, the drugs are appropriately dosed for children, dissolvable in water, and fruit-flavored to appeal to children. Already close to 80 countries, have adopted this improved treatment, with 700,000 courses ordered. Malaria has plagued humanity for tens of thousands of years. Fortunately, this past decade has brought a number of new and improved tools and approaches to tackle this age-old scourge, including the world’s first approved malaria vaccine, Mosquirix. In 2017, the World Health Organization announced plans to pilot the vaccine—developed by GHTC member PATH—in sub-Saharan Africa. While developing a high-efficacy vaccine against malaria has proved challenging due to the parasite’s complexity, Mosquirix, which reduced the rate of infection in children by 39 percent in clinical trials, is an important scientific breakthrough, and health officials hope it will prove a valuable addition in fighting malaria used alongside existing interventions. In 2014, the world’s deadliest Ebola outbreak caught the global community unaware and unprepared, devastating nations in Western Africa. While health workers went to work in the field to contain the immediate crisis, scientists went to work in their labs to develop a vaccine to prevent future epidemics. Thanks to research on Ebola vaccines that had been undertaken in the early 2000s, researchers were able to accelerate the leading Ebola vaccine candidate—RVSV-ZEBOV—from preclinical testing to phase III trials in less than two years. In 2016, it was announced that the vaccine was found nearly 100 percent effective in these trials. The vaccine could be approved by the FDA as early as 2019. More than two billion people worldwide suffer from hidden hunger—a condition characterized by deficiencies in micronutrients such as zinc, iron, and Vitamin A, which can cause stunted growth, blindness, and learning disabilities. In the 1990s, a young economist Howarth Bouis had a kernel of an idea: What if we could create better crops to provide better nutrition? His answer was biofortification, a process of naturally breeding sustenance crops so they are rich in micronutrients. After years of proof of concept research, in 2009, the nonprofit he founded—GHTC member HarvestPlus—introduced its first wave of crops in LMICs, providing nutrient-rich food for people in need. For decades, diagnosing multi-drug resistant TB (MDR-B) meant using older testing methods that took weeks to deliver results and required expensive laboratory equipment. In 2010, this began to change with the introduction of the Xpert MTB/RIF test, an automated diagnostic test developed by GHTC member FIND, which does not require microscopes or a laboratory, involves very little training to operate, and can deliver results in less than two hours, start to finish. FIND and partners will soon introduce a next-generation version—the Genexpert Omni—that is smaller, more portable, and battery-operated, which should further expand access to improved TB diagnosis. View a slideshow of more moments and milestones in global health R&D over the past decade. Here’s to ten more years of progress! At GHTC, we are proud to work with so many believers, innovators, and changemakers who are driving progress in global health. As we embark on 2018 and beyond, we recommit to continuing this momentum and look forward to another decade of advancing innovation to save lives.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past we. A quick and inexpensive test may make it easier to diagnose and distinguish betweenZika and dengue. Both viruses produce the same NS1 protein, making it is impossible for current NS1 protein-based diagnostic tests to discern between the two. To overcome this problem, scientists developed a set of antibodies produced from immune cells that can distinguish between an NS1 protein produced by the Zika virus and an NS1 protein produced by the dengue virus. In a study, the diagnostic test was able to discern between the two viruses, even when there was a lowNS1 protein count in the body. While further studies are required, this tool could become an essential diagnostic tool in areas of the world where both Zika and dengue are endemic. A series of papers exploring the impact of group B streptococcus (GBS) was published in Clinical Infectious Diseases. GBS is an infection a mother can pass to her fetus that can cause septicemia, meningitis, and even death. The papers argue that there are 410,000 cases of GBS every year with 147,000 associated stillbirths and infant deaths. There is also a major disparity of GBS cases between developed and developing countries: Many at-risk women in developed countries receive prophylactic antibiotics during labor, but those resources are often not available to women in developing countries. Scientists believe the solution to this problem is a GBS-specific vaccine, which could save over 100,000 infant lives.This vaccine may be critically important as scientists believe “immunizing expecting mothers is a potentially groundbreaking approach that could dramatically reduce the number of maternal and child deaths.”There is currently no GBS vaccine available, but there are candidates in development. The US Environmental Protection Agency approved the release of lab-reared “killer mosquitoes” to help reduce the population of disease-carrying mosquitoes in certain American states. A biotechnology start-up based in Kentucky—MosquitoMate—will rear these mosquitoes with a lethal bacterium that impedes reproduction and release the infected males into the wild. When the infected males mate with wild females, the offspring will not be viable due to malformed chromosomes. Over time, disease-carrying mosquito populations will dwindle. Other countries, including Brazil, have tried this method and found it successful, suggesting this could be a solution for countries severely affected by mosquito-borne illnesses. This method is also a “non-chemical way of dealing with mosquitoes,” so offers an alternative to pesticide-based vector control.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Sanofi Pasteur’s announcement that it will cease work on its Zika vaccine candidate has raised concerns about the future of Zika vaccine development. While the World Health Organization has reported 40 Zika vaccine candidates in development, with six candidates in phase 1 clinical trials, Sanofi was the only major pharmaceutical company working on a vaccine against the virus. Its exit from this space raises questions about who will fund clinical development if these candidates show further promise. Additionally, many unanswered questions remain about the virus’s epidemiology and the target population for a vaccine. While the number of Zika cases is now falling, Zika epidemics will likely reoccur in the future. Because of this risk, developing an effective and low-cost Zika vaccine must remain a priority. Johnson & Johnson and the Biomedical Advanced Research and Development Authority (BARDA) have formed a partnership to develop vaccines and drugs to protect against pandemic influenza. Among its projects, the partnership is seeking to develop a “universal” flu vaccine that protects against all or most influenza strains. This collaborative effort highlights a larger trend in partnerships between the private sector, the US government, and nonprofits to develop vaccines and technologies against emerging health threats for which there is currently limited commercial market. Pakistan has launched its first nationwide vaccination drive for polio, aiming to immunize over 37 million children. Pakistan is one of just three countries where polio cases remain, so this nationwide drive is an important step toward eradication. While polio still remains endemic in Pakistan, the number of cases has reduced dramatically in recent years from 306 cases in 2014 to just 4 today. Pakistan has experienced obstacles in its attempts to eradicate the virus, which include efforts by extremists to target immunization campaigns.

What do an onsite chlorine generator, fingerprint scanning technology for newborns, and temperature-monitoring wristband all have in common? The potential to save the lives of mothers and newborns in some of the poorest, hardest-to-reach communities around the world. These were among the many innovations pitched on July 27 at the DevelopmentXChange—the final stage of competition in the seventh annual Saving Lives at Birth: A Grand Challenge for Development, a prize program sponsored by the US Agency of International Development and other partners to identify and advance transformative, cost-effective solutions to improve maternal and newborn health, particularly during the first 48 hours after birth. Through the challenge, innovators compete for grants to develop, test, and bring their ideas to scale. This year, the challenge received more than 550 applications from across the world, with 53 teams chosen as finalists to compete at this year’s DevelopmentXChange. At the conclusion of the event, 15 winners were selected, with additional grant recipients to be announced later this year in the transition-to-scale category. GHTC members featured among finalists Among the 53 finalists were five promising innovations from GHTC member organizations, profiled below: Validation of an innovative, onsite, easy-to-use chlorine generator for infection prevention and control in labor wards* PATH The chlorine generator for infection prevention and control in labor wards. (Photo: GHTC/Marissa Chmiola)With just salt, water, and a power source, a hospital or clinic can create chlorinated water onsite to disinfect equipment and surfaces to keep mothers and babies healthy. That’s the idea behind the SE Flow Chlorinator—an easy-to-use, cost-effective chlorine generator designed for low-resource settings.  Infections are a leading cause of death for mothers and newborns during childbirth. While chlorine is one of the most widely-used and accepted methods for disinfecting surfaces, getting chlorine to remote health care facilities can be a challenge due to combination of weak supply chains, inconsistent transportation networks, and bureaucratic hurdles. The result: Close to one-third of facilities in low-income countries recently surveyed by the World Health Organization (WHO) did not have chlorine available. PATH and its partner MSR Global Health hope the SE flow will address chlorine supply chain hurdles by enabling facilities to produce consistently chlorinated water on the spot, at the quantity needed. The device also produces an additional benefit: cost savings. Over five years, the SE flow is estimated to save a facility 50 percent over the cost of purchasing chlorine on the market. PATH and MSR Global Health plan to test 50 of the devices next summary to collective evidence, refine the design, and support a broader roll out. Validation of an innovative newborn respiratory package of equipment and training* PATH Respiratory infections are a leading cause of infant mortality, particularly in premature infants whose lungs are not fully formed. Without strong lungs and appropriate oxygen intake, newborns face significant challenges in healthy development, including lifelong neurological damage or blindness. Continuous positive airway pressure (CPAP) therapy helps mitigate these challenges; however, the tools used in high-income nations to administer this therapy have traditionally been too costly to use in low-resource settings overseas.  A low-cost  bCPAP device for newborn health. (Photo: GHTC/Taylor Capizola) PATH and other partners developed a low-cost bubble CPAP (bCPAP) device, combined with an oxygen blender, that is appropriate for low-resource settings and has proven effective in controlling the flow of air to support breathing. To support further uptake and effective use of this intervention, PATH is now partnering with the Massachusetts General Hospital Division of Global Health and Human Rights to package the bCPAP, oxygen blender, nasal prongs, and a pulse oximeter with training and educational materials, including checklists, manuals, and wall charts. The training materials will be essential to expanding newborn access to respiratory therapy, particularly in facilities where no prior intervention existed and medical staff may be uncertain of how to best use these new tools. The team has also partnered with Sinapi biomedical, a South African biomedical manufacturer, to manufacture the package of tools and training materials to greatly expand the number of medical facilities using these interventions by bring the toolkit to scale. They expect that with Saving Lives at Birth support, mortality will drop 25 percent among newborns treated in facilities introducing bCPAP therapy for the first time. Building social accountability structures for respectful maternity care in Kenya: “RMC Virtual Space” Population Council Population Council's virtual space photos. (Photo: GHTC/Marissa Chmiola)The birth of a child can be one of the most moving experiences of a mother’s life, but in many low-income countries, it can also expose a woman to abuse and disrespect. Women who visit a health care facility during childbirth often face mistreatment, whether in the form of physical abuse, non-consent for physical examinations, neglect, or disrespectful comments. Often women are hesitant to report these incidents due to fear of reprisal or distrust that their feedback will be heard. Population Council has designed a low-cost mobile text message reporting platform that they believe will empower women to report their experiences and help providers comprehend the scope of the problem and develop solutions. This intervention works by enrolling women in the platform when they visit a facility for care. Following a visit, the patient is prompted through text message with a series of simple questions to collect information about her experience. The data is then aggregated and presented to the provider or facility in an easy-to-understand, dashboard-style system. Population Council chose to design the platform using text messaging as the basis for collecting feedback because it is ubiquitous across the African continent and provides a level of anonymity that encourages women to report their experience. The project team is at the concept stage and is currently testing the intervention in health facilities in Kenya to solicit feedback and refine its approach. Innovative packaging and pasteurization for donor human milk to improve health outcomes for preterm infants PATH Human milk banks play a critical role in ensuring that safe, high-quality human milk can be made available to infants whose mothers are unable to directly provide their own milk. Current guidelines for human milk pasteurization require temperature control of 62.5 degrees Celsius for 30 minutes to ensure all pathogens and bacteria are killed. Unfortunately, while this temperature kills microorganisms that can make infants sick, it also kills vital nutrients for an infant’s growth and development. No further international guidelines have been established, leaving engineers and scientists with the challenge of delivering safe, yet properly nutritious donor milk to milk banks. To solve this issue, PATH is seeking to improve the two processes involved in transporting human milk to milk banks: Pasteurization and packaging. PATH plans to research and narrow in on the optimal temperature range and timing capable of keeping human milk safe to drink and properly nutritious for infants. As part of this, PATH is also exploring the most effective packaging that help in achieving this temperature range and timing. Currently, the most common packaging for human milk is plastic or glass jars, but PATH researchers have found these jars do not transfer heat well or consistently. PATH plans to test a number of packaging options from stainless steel jars, which are commonly used in countries like India, to sterile plastic bags coated in aluminum—which in early testing have shown to distribute heat evenly and are easy to transport. Once the optimal temperature rage and optimal packaging are discovered, PATH plans to distribute this information widely to milk banks, donor human milk pasteurization equipment manufacturers, and human milk packagers to improve health and survival outcomes for all infants who receive heat-treated donor human milk globally. Advancing a simple, low-cost rapid diagnostic test for urinary adipsin: A promising new biomarker-based test for improving preclampsia screening in low-resource settings* PATH The preeclampsia (PE) test. (Photo: GHTC/Matt Robinson) Preeclampsia (PE) is a dangerous condition that causes organ failure and seizures, and it is one of the leading causes of maternal and newborn deaths worldwide. While diagnostic tests already exist that can provide early warning of risk factors, accurate tests require samples collected over 24 hours, and rapid tests were able to identify only 51 percent to 68 percent of risk cases. Thanks to a Saving Lives at Birth Round 4 Seed Award, PATH has developed an early prototype of a rapid diagnostic test (RDT) that is just as fast as existing RDTs, but is capable of catching 85 percent of risk cases early in the third trimester of pregnancy in plenty of time to take action. It is also temperature stable at 37 to 45 degrees Celsius and can be produced for pennies on the dollar of the cost of previous tests.  With its round seven award, the PATH team will undertake additional activities to bring the new RDT closer to broad scale use. First, the team will further optimize the test to expand its shelf life and determine the feasibility of increasing the test’s accuracy. Second, the team will explore whether the test—which currently requires a strip be dipped into urine in a separate container—can be incorporated into a form similar to at home pregnancy tests, making it easier to use and allowing women to take the test in the comfort of their own homes. Finally, the team will begin negotiations with commercial partners to scale up the product so it becomes widely available worldwide. The transformative power of innovation GHTC congratulates both our members and the other teams who were selected as finalists and award winners. This year’s prize winners will join the growing community of over 100 innovators supported by the Saving Lives at Birth partnership. Many of these innovations are beginning to have an impact as they are brought to scale. To date, the program has supported 1.5 million women and newborns and saved nearly 10,000 lives. The Saving Lives at Birth program proves that through creative partnerships and innovative ideas and interventions, we can create dramatic improvements in the health and well-being of people around the world. *indicates this intervention was among the 15 winners. GHTC staff including Taylor Capizola, program assistant; Matthew Robinson, MA, multilateral advocacy and policy officer; and Courtney Carson; US advocacy and policy officer, contributed to this article.