Research Roundup: genetic protection against malaria, the vaccine pipeline, and counterfeit drugs and the FDA

In this guest post, Dr. Monica Parise—deputy director for program and science—and Dr. Larry Slutsker—director of the Division of Parasitic Disease and Malaria—at the US Centers for Disease Control and Prevention (CDC) Center for Global Health—discuss the role of research in advancing efforts to detect, prevent, and eliminate parasitic diseases. Research is critical to preventing, detecting, and eliminating parasitic diseases. Photo: PATH/Gabe Bienczycki It’s an inspiring time for those of us working on parasitic diseases. Combined, the two of us have spent several decades working to address these infectious diseases that are major causes of death, disability, and suffering for millions of people. Since 2000, we’ve witnessed tremendous successes in reducing the devastating toll from malaria and several of the neglected tropical diseases (NTDs). None of this happened by accident. Sustained commitment from global partners, combined with unrelenting work and attention, has produced results. Massive scale-up of malaria interventions has saved more than 4.2 million lives since 2000, and globally, child deaths have fallen by 47 percent and in sub-Saharan Africa, by 54 percent. There has been similarly impressive progress in eliminating lymphatic filariasis, also known as elephantiasis, with an estimated 97 million cases prevented. We have also seen massive reductions in cases of Guinea worm disease, with only 126 cases from the four remaining endemic countries reported globally in 2014 compared to 3.5 million in 1986. Based on these gains, several NTDs, including lymphatic filariasis, onchocerciasis, and trachoma, have been slated for elimination within the next five years. Equally significant, the newly released Global Technical Strategy for Malaria calls for eliminating malaria in at least 35 new countries by 2030. But this progress is fragile. This is no time to be complacent. While the documented and real successes should be applauded, they’ve also produced a changing epidemiological landscape that has altered such things as the infection levels, where transmission still occurs, and other factors. Increasing resistance of parasites to drugs and mosquitoes to insecticides threatens to unravel progress in malaria elimination. NTD elimination programs are reaching a point where they now require better and different tools for making decisions about when to stop mass drug administration and how best to monitor for disease reoccurrence. To succeed we must adapt so that we keep pace with rapid changes in our foes—the parasites and their vectors. We must identify new tools and approaches to continue to achieve gains. That requires introspection and the willingness to occasionally stop and ask hard but essential questions. As scientists, as well as public health professionals, we constantly ask ourselves: Do we as a community have what it takes to get to the end? Do we have the information, tools, and interventions needed to successfully support a path to elimination? If not, what do we need to do about it? Over the past several months, the two of us, along with colleagues in CDC’s Division of Parasitic Diseases and Malaria, reflected on these challenges and considered possible solutions. The result is a set of strategic priorities to guide our work over the next five years. An important area of focus is research to develop new tools and approaches—to further drive down transmission, overcome technical challenges, and measure progress. We identified specific gaps that need to be addressed: Strengthening the evidence base to support elimination of malaria and NTDs: Additional guidance is needed to help define when a program should stop mass drug administration and transition from control to elimination strategies. Guidelines are also needed to identify which interventions are most appropriate in low transmission settings. Developing and evaluating tools and interventions targeting both the malaria parasite and its mosquito vector: Drug and insecticide resistance are forcing us to think about novel ways to battle those long-time foes, including evaluation of promising vaccines and novel vector control strategies such as spatial repellents—airborne chemicals that prevent human-vector contact with given space—and insecticide-treated durable wall linings. Malaria screening undertaken by community health workers. Photo: PATH/Lynn Heinisch Developing interventions to improve management of malaria cases: Achieving further reductions in malaria burden will require moving diagnosis, treatment, and risk mapping beyond the health facilities and community health workers providing clinical care, to developing strategies for population-based approaches such as focused screening and treatment, mass screening and treatment, and mass drug administration. Optimizing the effectiveness and mix of interventions: Whether it is a promising vaccine or a new method of vector control, no single intervention is likely to be a “magic bullet” for malaria control and elimination. Adding new tools and interventions into the mix of ones currently in use will require an understanding of which tools—used when and how—are needed. Evaluating the impact of parasitic disease control programs on other endemic diseases: Because individuals are commonly infected with more than one parasite or other disease-causing organism, opportunities and efficiencies exist for integrating interventions. Evaluating how parasitic disease control programs impact other endemic diseases can provide additional information on how to maximize resources and further integrate programs. Improving global research capacity for parasitic disease prevention and control through technical assistance and training: Ultimately, the goal is for governments and their academic partners in endemic countries to develop the capacity to lead research efforts to advance disease control and elimination within their own setting. The advancement of parasitic disease research is dependent upon strong research collaborations both with ministries of health and their partners in endemic countries and here in the United States. While adequate research infrastructure exists in some areas, there is a need to strengthen capacity through technical assistance and training that will facilitate collaborative research. We should celebrate the successes of the work so far that has saved millions of lives and eased suffering worldwide. But there is more—much more—to do. We must continue to scale-up existing technologies to sustain progress while at the same time advancing scientific research that will inform the way forward. With a strong base in science to support effective programs and policies, we are in a far stronger position to meet the challenges we face on the path towards elimination.

The US Department of Health and Human Services (HHS) is partnering with New York–based Regeneron Pharmaceuticals, Inc. for the development of an Ebola treatment. The treatment, developed by Regeneron, is comprised of three monoclonal antibodies that help the human immune system identify and bind to the Ebola virus, and thus prevent the virus from entering human cells and reproducing. Through the Biomedical Advanced Research and Development Authority, HHS will contribute up to US$38 million over two years, which will support both the advanced development of the treatment, as well as manufacturing enough doses of the treatment to be used in clinical trials. Swiss pharmaceutical company Novartis announced a new program last week to expand access to 15 of its medicines by offering them to health care providers in low- and middle-income countries for just $1 per drug per month. The program will initially be launched in Kenya, Ethiopia, and Vietnam, but could be expanded to as many as 30 countries. The 15 medicines included in the Novartis Access portfolio treat chronic diseases including cardiovascular and respiratory illnesses, diabetes, and breast cancer. Novartis will partner with governments and nongovernmental organizations to implement the program. Photo credit: CDC/ Melissa Dankel Researchers at Stanford University may have discovered a way to combat Clostridium difficile (C. diff)—a deadly bacteria that affects the intestines—without using antibiotics. C. diff’s virulence relies on a specific toxin—Toxin B—it releases that is responsible for the diarrhea, abdominal pain, and damage to the intestinal wall associated with the bacteria. While broad-spectrum antibiotics combat C. diff and other bacteria by attacking all bacteria—including safe, healthy bacteria—this new approach uses a molecule called ebselen that targets and deactivates Toxin B. The team at Stanford gave mice multiple rounds of antibiotics followed by a multidrug-resistant strand of C. diff; in other words, they made the mice particularly susceptible to infection and then introduced a particularly virulent bacteria. However, the use of ebselen to treat the infection almost completely protected the mice from symptoms. Ebselen is currently being tested for use in humans to treat other conditions, and initial results suggest that it is safe and well-tolerated. The US Food and Drug Administration (FDA) gives breakthrough designation to drugs that treat serious conditions and that have the potential to be significantly better than anything on the market. The FDA expedites the development and review of drugs deemed to be breakthroughs, but the designation is not a guarantee of safety, efficacy, or ultimate approval of the drug. However, a new study suggests that use of the word “breakthrough” could give patients “unwarranted confidence […] which could prevent them from making a fully informed decision about whether to take the drug or not,” according to the study’s coauthor Tamar Krishnamurti. The team recruited 600 online participants, each of whom were given one of five descriptions of a drug that has received breakthrough designation. The first description included just the facts, while the second and third described the drug as “promising” and “breakthrough,” respectively. The fourth and fifth clarified that continued approval of the drug depended on the results of additional clinical trials. In the subsequent survey, participants who read that the drug was “promising” or “breakthrough” were more than twice as likely to describe the drug as very or completely effective. While nearly a third of those who read the “breakthrough” description falsely considered the drug’s efficacy to be proven, compared to only 10 to 16 percent of participants who read the clarification regarding continued approval. All participants were then asked to read two descriptions of the same drug and identify which they would take. Ninety percent of respondents chose the description that used the word “breakthrough.”