Breakthroughs Blog: Diarrhea

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week.Two male health workers on a motorcycle carrying a vaccine carrier and supplies, pulling up in front of a building where women and children are waiting. (PATH/Doune Porter)A breakthrough leprosy vaccine candidate will soon enter a Phase I clinical trial. The vaccine—LepVax—is the first vaccine specifically developed for leprosy, marking a critical step forward in efforts to eradicate the disease. Leprosy is a painful bacterial disease that causes nerve damage, skin disfiguration, and issues with mucous membranes. While treatment options exist, there are many side effects, and these treatments are not capable of reversing the permanent skin and nerve damage. Early results from the trial should be available in 2018. A massive cholera immunization campaign recently launched near the border of Bangladesh in an effort to provide emergency immunizations to host families and displaced Rohingya families and children. Over 200 mobile vaccination teams delivered 900,000 cholera vaccines to the border regions currently affected by both a cholera outbreak and a refugee crisis. A main target of the campaign is children ages one to five, though individuals of all ages will receive vaccines. This immunization campaign follows a recent global pledge to end cholera by 2030. Results from a clinical trial launched in 2015 at the end of Liberia’s Ebola outbreak have demonstrated that two Ebola vaccine candidates are safe and effective in promoting an immune response. The first vaccine—ChAd3—developed by the National Institute of Allergy and Infectious Diseases and GlaxoSmithKline, resulted in an immune response in 64 percent of recipients one year-post vaccination, while the second vaccine—VSV-EBOV—developed by Merck and Canadian scientists resulted in an immune response in 80 percent of recipients at the one-year mark. These results will help inform continued development of both vaccines.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. A new study suggests the Nanopatch vaccine delivery system is more efficacious in protecting against poliovirus than typical syringes or needles. Nanopatch, defined as “a microscopic vaccine delivery platform,” targets immune cells in the outer layers of the skin, as opposed to typical syringes and needles, requiring injection into the muscle. The change from muscle to immune cells results in easier administration of the vaccine as well as a reduction in the required dosage. While initial data on Nanopatch is promising, more research is needed. The World Health Organization has warned that an increase in antibiotic use in livestock will result in increased antibiotic resistance humans, potentially causing one of the biggest threats to human health. The agricultural sectors in both Europe and North America are advancing efforts to curb antibiotic use, but many countries are still lagging behind in efforts to scale back use of antibiotics. While new policies and reform around livestock antibiotic use are needed, experts note there is still a need to treat health complications in livestock, through antibiotic alternatives like animal vaccines, as well as a need for improved diagnostics. The World Health Organization, numerous aid agencies, and relevant stakeholders have announced the first global pledge to end cholera by 2030, following one of the worst outbreaks of cholera in modern history. Cholera is considered a “disease of the poor,” affecting individuals living in areas with poor sanitary and water conditions. The recent outbreak is associated with and exacerbated by weak health systems, poor infrastructure, and a lack of necessary supplies to prevent, diagnose, or treat cholera. The pledge will focus on a multifaceted approach involving improving water and sanitation as a long-term solution and use of an oral, three-year cholera vaccine to provide immediate protection.

Breakthrough ideas are like children—they start small, they need constant nurturing, they don’t always develop according to schedule, but they change lives forever. In honor of Mother’s Day, GHTC is highlighting the stories of five mothers who have given birth to scientific discoveries or bold ideas that have transformed global health. 1. Ruth Bishop (b. 1933), Discoverer of Rotavirus Ruth Bishop at work in her lab. Photo: Stepping Stone Pictures As a young bacteriologist working in the 1970s, Ruth Bishop was on a quest to find the root cause of diarrheal disease—the most common illness among children worldwide. After much research, Bishop concluded that the disease was likely not caused by a bacterial agent, but instead by a virus. To continue her search, Bishop teamed up with two colleagues at the University of Melbourne – virologist Ian Holmes and electron microscopist Brian Ruck. In 1973, using an electron microscope, the team uncovered a previously unidentified virus in the biopsy sample from an intestinal lining. Bishop and her team went on to confirm presence of the virus in other samples. Their published results elicited a global response and confirmation of the virus’s presence in samples around the globe. The virus identified by Bishop and her team would come to be named rotavirus for its wheel-like shape. Rotavirus is the leading cause of severe diarrhea in children worldwide and affects nearly every child in their first three years of life. Bishop and her team went on to develop a diagnostic test for the virus, and their continued research helped pave the way for the development of a rotavirus vaccine which was introduced more than three decades after their initial discovery. Today there are two rotavirus vaccines commercially available with additional candidates in the research pipeline. Gavi, the Vaccine Alliance estimates that by 2030, 2.4 million lives could be saved through rotavirus immunization. Bishop, who is the mother of one son and is now officially retired, has watched these vaccine developments with excitement. “Rotavirus will always be around,” she said, “but we can stop it from being a killer.” For more information on Ruth Bishop, check out this Science in Public article. 2. Rosalyn Sussman Yalow (1921-2011), Unlocked breakthrough diagnostic technique Rosalyn Yalow at Bronx Veterans Administration Hospital in October 1977. Photo: US Information Agency Rosalyn Sussman Yalow knew by the age of eight that she wanted to be a scientist. Despite living in a time when few scientific opportunities were available to women, Yalow remained undeterred in her pursuit. After completing her master’s degree and PhD in physics while working as an electrical engineer and college instructor, Yalow decided she wanted to be a full-time researcher. Unable to find a research position, Yalow decided to volunteer at a Columbia University radiological research laboratory. There she was introduced to the emerging field of radiotherapy. A few years later in 1950 while working at the Bronx Veterans Affairs Hospital, Yalow would meet and begin working with her lifelong research collaborator Solomon Berson. Together the two would develop radio-immunoassay, a technique that used radioactive isotopes as markers to trace and measure concentrations of hormones, viruses, enzymes, and other substances in the body. Their discovery of this technique revolutionized biological and medical research and made possible the development of diagnostic tests for infertility, hypothyroidism, and dwarfism; and screening tests for infectious diseases such as hepatitis and HIV and AIDS in blood donations. In 1977 Yalow became the second woman to earn a Nobel Prize in medicine. A mother of two children, Yalow advocated for the advancement of women in sciences. In her Nobel Prize banquet speech, she said of women, “We must believe in ourselves or no one else will believe in us; we must match our aspirations with the competence, courage, and determination to succeed, and we must feel a personal responsibility to ease the path for those who come afterward.” For more information on Rosalyn Sussman Yalow, check out her bio on the American Chemical Society website or her obituary that appeared in The New York Times. 3. Flossie Wong-Staal (b. 1947), Leading HIV and AIDS researcher Flossie Wong-Staal at the National Cancer Institute. Photo: National Cancer Institute/Bill Branson At the age of 18, Flossie Wong-Staal left Hong Kong to pursue her passion for biology in the United States. After completing her PhD in molecular biology in 1972, Wong-Staal moved to Bethesda, Maryland to study retroviruses with pioneering AIDS researcher Robert Gallo at the National Cancer Institute. Together they searched for the cause of AIDS, which was by then spreading in the United States. In 1983, Wong-Staal, Gallo and their team discovered HIV, the virus that causes AIDS. Two years later, Wong-Staal became the first scientist to clone and produce a genetic map of the virus, both of which were critical steps toward the development of blood tests for HIV. Wong-Stall continued her research on the HIV virus for over a decade, and today she help leads a biopharmaceutical company she co-founded which is working to develop improved drugs for Hepatitis C. Wong-Staal, who is the mother of two daughters, said of her interest in research, “For me, as for most researchers, the main motivation is simply the satisfaction of making discoveries, finding things out that no one knew before.” 4. Dorothy Hodgkin (1910-1994), Mapped the structure of penicillin Dorothy Hodgkin demonstrates the structure of vitamin B12 with a model. Photo: C&EN Archives Born in the early twentieth century, Dorothy Hodgkin was a trailblazer for women interested in the sciences. As a teenager, Hodgkin received as a birthday gift from her mother a book by Nobel Prize–winning physicist William Henry Bragg that discussed using X-rays to “see” the three-dimensional structure of molecules. This present would change the course of her life. Fascinated by the ideas presented in the book, Hodgkin would make the study of this field her life’s work. After graduating from college, Hodgkin found a position in an x-ray crystallography lab where she went to work studying the complex organic molecules that help a living organism function. The technique she used involved crystallizing the substance she was studying, shooting X-rays at it, and then studying the ways the X-rays refract off the structure in order to determine its shape. In 1946, after four years of studying the antibiotic penicillin using this technique, Hodgkin determined its structure, marking an important advancement which would help manufacturers create semisynthetic penicillin. Over the course of her career, Hodgkin also determined the structure of vitamin B12 and insulin. In 1964, she became the third woman to win the Nobel Prize in chemistry. A mother of three children and grandmother of three grandchildren, Hodgkin said of her career, “I was captured for life by chemistry and crystals.” For more information on Dorothy Hodgkin, check out her bio on the Chemical Heritage Foundation website or Nobel Prize website. 5. Margaret Sanger (1879-1966), Birth control pioneer Birth control pioneer Margaret Sanger. Photo: public domain Margaret Sanger devoted her life to expanding the availability of birth control and contraceptive options for women. Sanger’s devotion to this cause was born out of personal tragedy. At age 19, Sanger watched her mother—who gave birth to 11 children and suffered seven miscarriages—die of tuberculosis. Sanger believed that her mother’s repeated pregnancies had weakened her body’s ability to fight the disease. Wishing to build a different life for herself, Sanger became a nurse. Serving the people of New York’s Lower East Side, Sanger tended to the needs of impoverished women who lacked effective options to prevented unwanted pregnancies and often resorted to back-alley abortions in desperation. This experience deepened Sanger’s resolve that women needed access to safe and effective contraceptives so they could stay healthy, limit their family size as desired, and break the cycle of poverty. As a young mother of three children, Sanger switched her focus from nursing to advocating for the legalization of birth control and making it universally available to women. Although Sanger experienced several legal victories over the next three decades which expanded contraceptive access, she remained frustrated by the lack of birth control options available to women and dreamed of a contraceptive pill that would be as easy to take as a vitamin. To make that dream a reality, she recruited reproductive health researcher Gregory Pincus and raised the needed funding from heiress Katharine McCormick. This collaboration would lead to the development and introduction of the first oral contraceptive in 1960. Today Sanger’s vision of a world where all women have the ability to prevent or space their pregnancies remains only partially realized. Although more than 99 percent of American women have used a contraceptive method in their lifetime, an estimated 222 million women in developing countries want to limit or control the timing of their pregnancies but lack access to modern contraceptives. Said Sanger, “No woman can call herself free until she can choose consciously whether she will or will not be a mother.” For more information about Margaret Sanger, check out her bio at the National Women's History Museum website or PBS website.

Tomorrow US policymakers and global health advocates will come together to talk progress made on preventing maternal and child deaths. During the day, the US Agency for International Development (USAID) will host a high-level forum called Acting on the Call: Ending Preventable Child and Maternal Deaths to both celebrate progress and assess the challenges that remain. That evening, the 5th Birthday and Beyond coalition will celebrate America’s leadership and investments worldwide to help children reach their fifth birthday. US investment in R&D has led to new innovations that are saving the lives of mothers and children. Photo: PATH/Teresa Guillien While you’ll probably hear a lot of different facts and figures, one message will be clear—the world has made remarkable progress in preventing the deaths of millions of women and children. In fact, maternal and child deaths have been cut in half in just over two decades. That means that every day this year, 17,000 more children will live and 700 more mothers will survive childbirth than did two decades ago. Central to this progress has been US investment in research and development (R&D) that has led to new medicines and innovative health products that are saving the lives of mothers and children. Globally new vaccines, drugs, diagnostics, and other health innovations have led to 4.2 million fewer child deaths in 2013 compared to 1990, according to a report by the Institute for Health Metrics and Evaluation. Innovations like the polio vaccine, oral rehydration solution to treat diarrhea, and antiretroviral therapies that prevent maternal to child HIV transfer, and others treatments have resulted in incredible gains for maternal and child health.   No country has done more than the United States to help save the lives of the world’s poorest mothers and children. A critical part of the US approach has been our world-leading investment in global health R&D. In fact, the US government is the largest funder of global heath R&D in the world—contributing over 45 percent of total investment. US government investment in global health R&D has led to breakthroughs that have transformed or are poised to transform efforts to reduce maternal and child mortality. Some examples include: The Oxytocin-Uniject™ This is a device filled with oxytocin that helps contract the uterus to reduce post-partum hemorrhage—or excessive bleeding—the leading cause of maternal death worldwide. It is easy to inject and requires little training to administer, so it’s made a dramatic difference in the ability of health workers to administer oxytocin in emergencies or in remote locations outside of traditional hospital facilities. USAID played a crucial role in funding research towards the development of this product. RTS,S malaria vaccine candidate RTS,S is the most clinically-advanced vaccine candidate for malaria—a disease which kills a child every 40 seconds. A recent study showed that infants who receive the RTS, S vaccine had one third fewer cases of both clinical and severe malaria. A vaccine could be an important tool in reducing child sickness and death from malaria. The Department of Defense provided critical funding for the early development and clinical testing of RTS,S. Rotavirus vaccines Rotavirus-induced diarrheal disease kills roughly 435,000 children younger than five each year. Two currently available rotavirus vaccines were introduced in the past two decades, with other vaccines under development showing tremendous progress. The National Institutes of Health developed the first available rotavirus vaccine and has been a financial partner in the development of subsequent vaccines. In addition, the Centers for Disease Control and Prevention also monitors efficacy and safety, and supports clinical trials of rotavirus vaccines. New contraceptive technologies Family planning technologies allow women to space their pregnancies—making it more likely for both the mother and child to survive childbirth. An analysis of 172 countries found that family planning prevented 272,000 maternal deaths in just one year. However, the contraceptive options that exist today don’t always meet the needs of women in developing countries. New vaginal rings are being developed that will be long-lasting and easy for the user to insert and remove without a doctor’s assistance, while new multipurpose prevention technologies combine the delivery of contraceptives with microbicides which reduce the transmission of HIV and other sexually transmitted infections. USAID provides funding towards the development of many of these new contraceptive technologies. While tremendous progress has been made in decreasing maternal and child deaths worldwide thanks in part to new health innovations, each year 6.6 million children still die before their first birthday and 289,000 women still die from pregnancy-related causes. That translates to 18,000 children under the age of five and 800 pregnant women or women in childbirth dying every single day. The United States can and must do more. While the United States should increase access to proven and existing drugs, vaccines, and other health tools for maternal and child health, it is just as critical to develop the next generation of tools to prevent and treat existing and emerging diseases. Sustained and continued investment by the US government in global health R&D is critical to ending maternal and child deaths.