Breakthroughs Blog: Malaria

We have many reasons to be thankful. Photo: Satya Murthy As global health advocates, our work often requires us to focus on unmet needs—such as the number of people worldwide who still die from preventable diseases each year, or the lack of adequate resources and investment to tackle these diseases. Yet with Thanksgiving just around the corner, there is much for which we, as global health advocates, can be grateful in terms of advancements achieved in the development and deployment of lifesaving global health technologies. In the spirit of the holiday, here is my list of ten global health advancements I’m thankful for this Thanksgiving: After years of slow progress in the development of drugs, vaccines, and diagnostic tools to fight Ebola, efforts are now moving at hyper speed. Several experimental treatments and vaccines are now being tested in clinical trials in Ebola-endemic countries. Thanks to the development and widespread implementation of effective vaccines, this year the world moved one step closer to the eradication of polio. Scientists from the US Centers for Disease Control and Prevention believe that the second of three forms of poliovirus has successfully been eradicated. The first vaccine against hookworm has been shown to be safe in early-stage clinical trials. An effective vaccine could protect the more than 600 million people infected with this dangerous parasite worldwide. Widespread access to and use of antiretroviral therapy (ART) is fueling incredible progress in the fight against HIV and AIDS. According to the UNAIDS 2014 report, 2013 saw the lowest level of new HIV infections this century and the lowest number of AIDS-related deaths since 2005. As of this summer, nearly 14 million people are accessing ART. The world could soon have an important new tool in the first against dengue fever. Results from the second Phase III trial of the first vaccine candidate against dengue fever showed the vaccine to decrease incidences of dengue fever by nearly 60 percent. Within a few years, women could have new, user-friendly options to protect themselves against HIV. Several new antimicrobial vaginal gels and antiretroviral-releasing contraceptive vaginal rings are currently undergoing clinical trials. Significant progress has been achieved this year towards the development of new tools to fight malaria. After receiving expedited regulatory approval from the US Food and Drug Administration last year, new malaria drug treatment candidate tafenoquine entered Phase III trials this year. Additionally, the malaria vaccine candidate RTS,S is now under regulatory review by the European Medicines Agency. New pediatric drug formulations to treat tuberculosis (TB) could be available as early as late next year, according to developers. This advancement is critical as there is currently no appropriately dosed, child-friendly TB treatment available. New vaccines, drugs, diagnostics, and other health innovations have led to 4.2 million fewer child deaths globally last year compared to 1990. There are 365 global health products in the research pipeline that have the potential to fuel incredible gains in health for people around the world. With so much accomplished in 2014 and so many promising tools on the cusp of development and delivery, we have much to be thankful for this Thanksgiving. This Thursday, enjoy your Turkey and fixings with family and friends and give thanks for the incredible progress we’ve achieved this year. And then next week, when our turkey hangovers pass, we’ll get back to work.

In this post, Eoghan Walsh—communications officer at Deutsche Stiftung Weltbevoelkerung (DSW)—writes about the need for Europe to increase financial and political support for efforts aimed at creating new ways to tackle diseases such as HIV and AIDS, tuberculosis (TB) and malaria. This post originally appeared on the DSW blog on September 4. Support for global health is at the core of DSW’s advocacy work. One of the four focus areas for the organization is to have global health policies and financing include and support sexual and reproductive health and rights. We recognize at DSW the urgent need to improve the global health situation, and we continue to advocate for health improvements in low- and middle-income countries. As part of this work, we are launching a series of policy briefs on the issue of global health research and development (R&D), outlining why we need to increase financial and political support (in Europe) for efforts aimed at creating new ways to tackle diseases such as HIV and AIDS, TB, and malaria. Download the new infographic on European investment in poverty-related and neglected tropical diseases now!   R&D for PRNDs A crucial element of European investment in global health is support for the development and distribution of innovative new interventions to tackle head-on diseases that affect a huge number of people living in low- and middle-income countries. Poverty-related and neglected tropical diseases (PRNDs), such as HIV and AIDS, TB and malaria—as well as 17 other infectious diseases identified by the World Health Organization (WHO )—affect more than one billion people around the world, causing 6 million deaths annually. 90/10 gap Because these diseases affect people living in some of the world’s poorest countries, for many years there has been insufficient investment in R&D aimed at addressing and eradicating these diseases as the private sector has not seen a market interest in developing new medicines and treatments. It is estimated that, overall, only 10 percent of the world’s resources for health research are directed at diseases that affect the poorest 90 percent of the world’s population. Return on investment for Europe It is because of this “90/10” gap that we work for increased political and financial support to global health R&D, supporting the creation of modern, effective, affordable, and accessible medical interventions to bring an end to the suffering caused by PRNDs. As part of our new series of policy briefs on global health R&D, today we are launching an infographic—developed in collaboration with Policy Cures—outlining the value for the European Union (EU) in investing in global health R&D, and how funding for global health R&D can have positive economic and health benefits for Europe as well as the rest of the world, and have significant return on investment. Read on and support us as we advocate for an end to these terrible diseases! Did you know? PRNDs account for 361 million years of healthy and productive life lost globally There are no vaccines for HIV or malaria The EU invested €2.1 billion in PRNDs research between 2007-2012 Since 2000, 47 new products aimed at PRNDs have been registered, with over 350 more in the pipeline Infographics provided by DSW.

  In this post, PATH Vice President of Product Development, David Kaslow, writes about the first-ever shipment of semisynthetic artemisinin (ssART)—a new type of malaria treatment that marks a significant milestone in the fight against malaria. This post originally appeared on the PATH blog on August 12. Malaria drugs made with semisynthetic artemisinin make their way to patients This month, after nearly ten years of effort, the first batch of malaria drugs manufactured with a new, semisynthetic form of the key ingredient, artemisinin, will start reaching African countries battling the disease. The lifesaving drugs, manufactured by our partner Sanofi, a French pharmaceutical company, are the first of their kind to use ssART in place of the plant-derived form of artemisinin used in the past. The new shipment marks a milestone in global health, potentially improving access to treatment for the millions of people, mostly African children, sickened by malaria every year. The story of ssART—and the bold partnership that brought it from concept to use—highlights the crucial role international markets play in shaping global health, and the power of collaborative innovation to improve the systems that bring lifesaving products to the people who need them. Soothing a volatile market The first batch of malaria drugs manufactured with a new, semisynthetic form of the key ingredient, artemisinin, will start reaching African countries battling the disease. Photo: PATH In 2004, doctors worldwide were increasingly using a powerful group of drugs called artemisinin-based combination therapies (ACTs), to treat malaria infection. That was good news for children and families everywhere. But as more countries sought ACTs, the supply and price of artemisinin—which was derived only from a slow-growing plant called Artemisia annua, or Asian sweet wormwood—fluctuated wildly. Changes in demand and supply from year to year created a volatile up-and-down cycle of pricing and supply. In 2005, for example, the price of artemisinin was at a high of US$1,100 per kilogram. That price sparked more farmers to plant sweet wormwood, creating an oversupply in 2007 that caused the price to plummet to just $180 per kilogram. That cut the incentive to grow sweet wormwood again, which resulted in a 2009 shortage that drove prices back up over the next two years, to an average of $530 per kilogram in 2011. These fluctuations strained markets, and made it difficult for leaders, manufacturers, and others to stabilize and plan global supply, risking a global shortage. In short, the lifesaving drugs that millions of children, families, and communities relied upon were tied to a supply structure struggling under the push and pull of a volatile market. Worldwide, a market challenge had turned into a crucial global health imperative.   A groundbreaking partnership Solving the challenge took a groundbreaking partnership, led by PATH’s Drug Development program, which brought together experts in research, pharmaceutical product development, and public health. In 2004, the partnership set out to develop a new manufacturing process to produce high-quality, year-round, and affordable artemisinin to supplement the plant-based supply. Over a decade of work, our combined innovation and vision brought a promising concept from small laboratory batches, to large-scale production, and on to global markets. Now, as the first shipment of ssART-based malaria drugs—1.7 million treatments of Sanofi’s gold-standard ACT, Artesunate Amodiaquine Winthrop®—make their way to customers for the first time, we’ve reached the goal we set out to achieve ten years ago. Semisynthetic artemisinin opens a new future for the global artemisinin market. In doing so, it offers new security for the millions of people who rely on ACTs in countries where malaria is a constant threat. By providing a year-round source, ssART helps to manage imbalances in supply and demand, maintain stable and affordable pricing, and keep the market on an even course—ultimately expanding access to ACTs. The future Over a decade of work, PATH's combined innovation and vision brought a promising concept from small laboratory batches, to large-scale production, and on to global markets. Photo: PATH Of course, ssART is only one part of the solution. Eliminating and controlling malaria requires a highly integrated strategy, including new vaccines and diagnostics, expanded surveillance and control, strong partnerships with governments, and much more. I think I can speak for all of our partners when I say that we won’t be satisfied until that very last patient is cured of malaria. Until then, however, the sustained production of ssART, and the careful integration of our product into global markets, has the potential to change the landscape of global health. For the first time in history, artemisinin shouldn’t be a limiting factor in our work to develop and deploy lifesaving treatments. Even more, ssART provides clear evidence that with expertise, hope, and tenacity, it is possible for public and private sector leaders to achieve a bold humanitarian goal. Together, we’re paving the way for a robust, reliable supply of antimalarial drugs. And by continuing to work together, we can create a market where supply chains, farmers, extractors, manufacturers, and funders all align to create a healthier future for women and children worldwide. More Information About the semisynthetic artemisinin project Video: Steve Davis discusses this shared value partnership

In this guest post, S. Patrick Kachur, MD, MPH, FACPM—chief of the Malaria Branch in the Division of Parasitic Diseases and Malaria at the Center for Disease Control and Prevention’s (CDC) Center for Global Health—and Larry Slutsker, MD, MPH—director of the Division of Parasitic Diseases and Malaria at CDC’s Center for Global Health—write about the emerging global security threat of anti-malaria drug resistance and CDC’s efforts to prevent, detect, and respond to this growing threat. Emerging resistance to antimalarial drugs is of growing concern to the CDC. Photo: CDC Malaria starts with a small bite from a mosquito and can quickly turn into a life threatening illness. The President’s Malaria Initiative (PMI), Global Fund to Fight AIDS, Tuberculosis, and Malaria, and other global efforts have made remarkable progress to help control malaria, saving an estimated 3.3 million lives since 2000 according to the World Health Organization’s (WHO) 2013 World Malaria Report. Key interventions that contributed to this success include insecticide treated bed nets (ITNs), indoor residual spraying (IRS), rapid diagnosis and treatment with artemisinin-containing combination therapies (ACTs), and intermittent preventative treatment during pregnancy (IPTp). However, to sustain momentum and move toward elimination of malaria, new tools and technologies will be required. While ITNs remain a highly effective tool and should continue to be used, we must acknowledge that ITNs are not perfect given the challenges of adequate coverage, personal use, durability, daytime biting, and insecticide resistance. Of additional concern, there is evidence in Southeast Asia that the malaria parasite may be developing resistance to artemisinin drugs—the last remaining class of antimalarial drugs and the basis for treatment around the world. Reasons for this resistance are multifactorial, including poor treatment practices, inadequate patient adherence to treatment, and widespread availability of monotherapies, counterfeits, and substandard forms of the drug. Given the mobility of human populations, this resistance could easily spread. We have witnessed the spread of resistance to antimalarial drugs (chloroquine) before, beginning in Southeast Asia and then quickly spreading globally; it would be a devastating setback for child survival and a threat to global health security if artemisinin drug resistance followed this same pattern and reached Africa, where most malaria occurs. Understanding this resistance phenomenon, containing its current focus of transmission, and remaining vigilant for resistance in other parts of the world align well with the Global Health Security Agenda to prevent, detect, and respond to potential threats. Prevent Limiting inappropriate use of antimalarial drugs is important to preventing resistance. New rapid diagnostic tests help. Photo: PATH/Gena Morgan One way to actively prevent or mitigate resistance is to limit the inappropriate use of antimalarial drugs. For generations, health workers and consumers used malaria drugs without confirming the diagnosis of malaria. In the last decade, new rapid diagnostic tests made it possible to detect the parasites before giving treatment. Used consistently, this approach could reduce the unnecessary use of antimalarial drugs and improve the detection and treatment of other illnesses. Another approach to prevent drug resistance relies on identifying and removing counterfeit and substandard antimalarials from the market. These medications, similar to substandard doses of antibiotics, can contribute to increased resistance. The US government—CDC, the Food and Drug Administration, the US Agency for International Development, and PMI—are using novel technologies to easily detect counterfeit and substandard drugs with the touch of a button, outside of a specially equipped laboratory. Additional efforts will be needed to ensure these medications are removed from the market. Another way to help prevent resistance from worsening is to ensure a wide spectrum of tools exist to prevent and control malaria, especially where drug-resistant parasites are present. CDC, as part of PMI, is working with partners to develop and evaluate newer interventions and approaches such as durable wall linings or spatial repellants to aid in mosquito control, and promising vaccines which have been shown to reduce the number of malaria cases in vaccinated children and young infants. Detect Enhanced surveillance is critical to track how, where, and how fast the resistance is spreading. Through PMI, the US government supports and provides financial and technical assistance to countries for antimalarial drug resistance monitoring. Furthermore, rapid and accurate detection of resistant malaria parasites are critical for the prevention, treatment, and containment or elimination of infections, and will drive reduction of unnecessary antimicrobial use. As part of its efforts to monitor malaria domestically, CDC is working to characterize the drug resistance profile of malaria infections diagnosed in the U.S. This provides an early warning of spreading resistance and helps to monitor the situation more accurately. The use of genetic sequencing can also help quickly determine when a person is infected with drug resistant malaria parasites, so that clinicians can provide the best treatment. This information also guides CDC’s recommendation for medications taken for malaria prevention for people traveling to an area where resistance is detected. Respond Containment efforts are underway in all areas with suspected or confirmed artemisinin resistance in affected countries. PMI supports containment of artemisinin-resistant malaria in the Greater Mekong sub-region in Southeast Asia. In higher transmission areas, efforts focus on limiting the risk of spread by lowering the malaria burden through intensified malaria control, by increasing access to diagnosis and appropriate treatment, and by scaling up provision of health care services to migrant and mobile populations. In addition to containment efforts, CDC and partners actively contribute to global policy discussions on antimalarial drug resistance, helping provide recommendations for action that are based on the best available data. The ability to respond quickly and accurately also requires building global capacity and developing a cadre of trained and experienced staff. The call under the Global Health Security Agenda is to create and strengthen real-time networks of information systems to detect outbreaks and up-to-date rapid diagnostic tests enabling in-country laboratories to conduct at least five of 10 core tests for high-risk and high-priority diseases—malaria being one of them. The public health investments made through the Global Health Security Agenda will not just benefit a few target diseases. Instead, the increased capacity to prevent, detect, and respond through current and newly developed evidence based interventions, improved surveillance systems, accurate real-time rapid diagnostic testing, and an available cadre of trained people will benefit all known and emerging infectious disease threats, including resistant malaria parasites.