Research Roundup: repurposing ivermectin to fight malaria, LED lights against dengue fever, rapid diagnostics to slow antimicrobial resistance, and more

PATH/Dan Chang New rapid diagnostics are urgently needed to prevent unnecessary use of antibiotics and curb the growing problem of antimicrobial resistance, according to a new report from the United Kingdom’s Review on Antimicrobial Resistance (AMR). The report calls for greater investment to develop and support adoption of quicker and more precise diagnostics tests. Antibiotic overuse and growing resistance The rise of drug-resistant bacteria poses a significant health threat to people around the world. Unnecessary use of antibiotics is helping drive this rise in resistance, but since the 1940s, there has been little improvement in the way bacterial infections are diagnosed. The report points out that most antibiotic prescriptions are issued by medical professionals who are making a diagnosis empirically without using a diagnostic test. The fact that diagnostic tests are relatively expensive but antibiotics are cheap means it is less expensive for doctors and their patients to skip the test and issue the antibiotic prescription in case it proves helpful. Diagnostic tests are also time-consuming. It can take 36 or more hours to identify whether a person has an infection, so doctors often put sick patients on a treatment before a diagnosis can be confirmed. The scale of this problem can be quite dramatic: The report highlights one study on patients with respiratory problems which found that more than two-thirds of courses of antibiotics were likely to have been inappropriately prescribed for conditions other than infections or for infections caused by viruses, which aren’t responsive to antibiotics. Rapid diagnostic tests—which will allow doctors to identify within minutes whether an infection is present—can prevent unnecessary prescription, and more refined tests—which enable doctors to identify the exact strain of the bacterial infection and the antibiotics to which it is resistant or susceptible—will enable doctors to more precisely prescribe narrow-spectrum antibiotics, which will help slow the development of resistance. Incentivizing development of diagnostics A CDC scientists examines antibiotic resistant bacteria. CDC/ Melissa Dankel While new rapid diagnostics are urgently needed, the report points out that there is little commercial incentive for drug developers to invest in diagnostics, since their use would lead to decreases in the number of antibiotics purchased. The report proposes the use of “Diagnostics Market Stimulus pots” that would provide a revenue stream for developers of products that meet a recognized area of need. These developers would receive “top-off” payments when products are purchased by healthcare providers, thus raising the commercial benefit of investing in diagnostic development to match the societal need for these products. The report also calls for greater investment in early stage research, referring to its previous report which called for an AMR innovation fund of US$2 billion over five years to boost funding for such research. “For far too long we haven't recognized the huge cost to society of increasing resistance when we use antibiotics that we don’t need—such as antibiotics for flu which have no effect except to increase the chances of superbugs developing," said Lord Jim O'Neill, chairman of the AMR review. "To avoid the tragedy of 10 million people dying every year by 2050, the world needs rapid diagnostics to improve our use of antibiotics. They are essential to get patients the right treatment, cut down on the huge amount of unnecessary use, and make our drugs last for longer." A diagnostic “wish list” To inform investment efforts in diagnostic research and development, the report includes a “wish list” of diagnostics that could be game changers in curbing antibiotic resistance. Below are of few of those identified in the report: Rapid diagnostics that could be used at home to indicate bacterial or viral infections. These would potentially reduce visits to the doctor and so reduce healthcare resource consumption. Biomarker panels to distinguish whether patients admitted via A&E [accident and emergency] for pneumonia or fever have bacterial infections or not. A bedside test that would reliably exclude any infection. This should reduce the empirical use of antimicrobials and could also often be used as part of the treatment protocol for sepsis.

Maximilian Geigenmueller, advocacy officer at the Berlin office of DSW, answers questions about the German PDP funding call. Earlier this month, Germany’s Federal Ministry of Education and Research (BMBF) the renewal of the German funding program for product development partnerships (PDPs) conducting research and development (R&D) for health technologies to combat poverty-related and neglected diseases (PRNDs). The call for proposals for €50 million over five years (2016–2021) is expected to be published shortly. GHTC Breakthroughs blog is joined by Maximilian Geigenmueller, advocacy officer at the Berlin office of Deutsche Stiftung Weltbevoelkerung (DSW)—an international development organization that conducts global healthR&D advocacy—to learn more about this funding call and its importance in advancing R&D for lifesaving global health technologies. Q: Why is this funding call significant among efforts to advance global health R&D? A: This funding call is very significant in the sense that it ensures the continuation of German PDP funding. The first funding round was considered to be a pilot, and it was by no means a given that there would be a second one. Germany was late in joining the group of governments funding PDPs in 2011, when the United States and United Kingdom had already been funding the model for years. Germany also started out at a small scale—€20 million over four years. Over the duration of this time, it was gradually increased to over €26 million, which I think was an indication that the German government began to understand and increasingly appreciate the PDP model. This was further reinforced by an independent evaluation of the first funding round which was very positive. I think with this second call Germany has established itself as a PDP supporter in the medium and long term—albeit at a still rather modest funding level. Q: How does this second funding call differ from the first? A: First of all, there will be more money: €50 million over five years from 2016 to 2021, which is still not quite what we had hoped for but almost double the first funding round. Secondly, this call will be open for proposals not only on the 17 neglected tropical diseases (NTDs) and malaria, which were included in the first funding round, but also HIV and AIDS and tuberculosis (TB). Q: The announcement of this funding call occurred at the G7 Research Ministers conference which Germany chaired. How does this funding call reflect Germany’s broader global health priorities? And how does it align or differ with the priorities agreed upon at the G7 conference? Photo: PATH/Jennifer Fox A: I think the German government finally decided it was time to take on a leadership role in global health that appropriately reflects the country’s economic and financial standing in the world. I am sure the Ebola crisis—an outbreak of an infectious disease spreading at a breathtaking rate with no immediate treatment available and relatively close to home—had a lot to do with it. The prioritization of PRNDs/NTDs, antimicrobial resistance, and Ebola on the G7 agenda has given a lot of visibility to health issues in the international debate this year. For a while it looked like the G7 were leaving out the big three diseases of poverty—HIV and AIDS, malaria, and TB—and would only discuss NTDs, particularly as the G7 leaders’ summit communiqué only referred to NTDs. Fortunately, at the G7 Research Minister Conference in Berlin on October 8–9, the ministers of research included not only NTDs but also explicitly mentioned malaria, tuberculosis, HIV and AIDS, and several other infectious diseases. There are some interesting commitments in the communiqué, such as better coordination of research efforts. Germany’s Minister of Research Johanna Wanka has offered to host a brainstorming workshop on this in 2016. Also, the communiqué states the intent to develop a joint G7 pilot research activity for R&D projects to build research capacities in high PRND/NTD burden countries. Combined with the Japanese 2016 G7 presidency which is very likely to have health as one of its priorities as well, I think we have a good chance that health is going to stay at the center of the international agenda for a while. Q: As a global health R&D advocate, what excites and disappoints you about this funding call? A: I am excited about it being out and that there is significantly more budget available this time. It is of course not enough, not by a long shot, but maybe there will be some top-ups to the second funding round, as was the case in the first funding round when Germany started out with €20 million and ended up with €26 million. There is also the prospect of institutionalizing German PDP funding, moving away from providing limited funding for a number of years to making it a permanent feature in the German budget, but this is most likely only going to happen at the end of the second funding round. What was also really exciting was the process of ensuring this second funding round happened. I think all advocates—PDPs, nonprofits, philanthropic organizations, and others—did a great job in keeping global health R&D in the political debate. For example, during the summer the All Parliamentary Group on Population and Development of the German Bundestag wrote a letter to Chancellor Angela Merkel voicing their support for global health R&D and the PDP model, which was signed by 19 members of parliament (MP). I think nineteen MPs coming together from three out of the four parties in the Bundestag to sign a letter in support of a measure which represents only a minuscule share of the research ministry’s annual budget is fairly remarkable.