Breakthroughs Blog: Antimicrobial resistance

A “who’s who” of politicians, philanthropists, CEOs, and civil society leaders descended upon New York City this week for the annual United Nations General Assembly (UNGA)—a gathering renowned for its policymaking, pledging, and perennial traffic problems. GHTC was on the scene all week—attending side events, tuning into the official debates, and navigating police barriers—to be your eyes and ears on the ground. Here is what we heard and our top four takeaways on global health research and development (R&D): 1. We can’t end TB without new tools, so it’s vital for world leaders to marshal the political will and resources to close the TB R&D funding gap. Tuberculosis (TB) was a top topic at this year’s assembly with the convening of the first high-level meeting (HLM) on TB. Repeatedly, we heard—from advocates and policymakers, at side events and in in the official proceedings—how poor treatment options are a cornerstone of our failure to eradicate TB and of growing drug resistance, and that new vaccines and improved treatments and diagnostics will be key to turning the tide. While much attention focused on this lack of necessary tools, equal attention focused on the lack of political will and resources to end the epidemic. Many speakers lamented how shamefully slow progress has been since the World Health Organization (WHO) declared TB a global emergency 25 years ago and highlighted the urgent need to close the funding gap for TB, including the US $1.3 billion gap for TB R&D.   As the curtain closed on the HLM, world leaders, as expected, endorsed a carefully negotiated political declaration. GHTC was pleased to see it include a commitment to increasing investment in TB R&D by $2 billion and strong recognition of the importance of cross-border, cross-sector collaboration in driving product development. However, we also share concerns raised by other advocates on accountability. For this meeting to catalyze true change, rhetoric must now translate to action, and commitments must be matched with mechanisms that track investments and hold nations accountable. 2. There are many roads on the path to universal health coverage, but innovation can be an accelerator. Universal health coverage (UHC) was another topic that took the spotlight at UNGA 73, championed by the issue’s top “cheerleader in chief” WHO Director-General Dr. Tedros Adhanon Ghebreyus, who has made achieving UHC a centerpiece of his directorship. Given the focus of the world’s doctor on UHC, many advocates at UNGA framed their specific issues through the lens of UHC, highlighting the myriad of steps needed to achieve this ambitious goal‒from building a stronger health workforce, to expanding access to medicines, to tackling leading killers like malaria, HIV and AIDS, and TB. Yet, a common theme heard across these conversations is that along each of these roads, innovation can be an accelerator.   Throughout the week, speakers highlighted how innovations and new technologies can help deliver care more efficiently and effectively, improve access and drive down costs, and accelerate countries along the path to achieving UHC. TB advocates highlighted how shorter treatment regimens can improve care, decrease costs, and free up resources, while digital health advocates argued that better use of data can empower health workers to track and treat patients and allocate precious health resources most effectively. Others highlighted how innovative new tools like point-of-care diagnostics can bring improved care to the community level and to people in the most remote corners of the globe. 3. We need additional resources for R&D, and that requires countries to step up in an equitable way. Domestic resource mobilization and equitable financing were words repeated throughout the week, particularly in conversations around the TB HLM and closing the TB R&D funding gap. Advocates, think tanks, and even government officials, argued that high-burden TB countries need to increase domestic investment in TB R&D and treatment. Some advocates have called for a “fair share” or equitable financing approach to TB R&D financing, with each country committing to spend .1 percent of their GDP on R&D. Others spoke to the potential of the BRICS nations—Brazil, Russia, India, China, and South Africa—to play a greater role in financing R&D.   While much of the TB financing dialogue focused on increasing public sector contributions, conversations also highlighted the impact and further potential of financing models like the airline-tax-funded work of UNITAID or public-private partnership approaches—like product development partnerships and the work of the Global Health Innovative Technology Fund—which have married multisector contributions to bring novel, affordable, accessible tools to market. Other speakers highlighted the opportunity for industry to increase its TB R&D investment, though many lamented that although industry has brought new TB drugs and diagnostics to market in recent years, uptake has been slow due to high product costs. 4. There is reason for optimism and reason for concern. The mood seemed mercurial in midtown Manhattan, as UNGA orators vacillated between optimism and concern about the future of global health and development. In the drumbeat to UNGA, the always-impatient optimists Bill and Melinda Gates unveiled their foundation’s Goalkeepers report. The report’s stylish line graphs, which show a downward trajectory on health issues like child mortality, are uplifting and inspiring—a great reminder of the staggering progress we’ve achieved in global health and what’s possible for the future.   The basis of our optimism about the world has always been our belief in the power of innovation to redefine what’s possible – Bill and Melinda Gates   Yet, three years in, it has also become clear the world is not on track to meet the Global Goals. And even the optimistic Gates are reminding us that though we hold the blueprint for a healthier world, continued progress is not inevitable. The choices our policymakers implement today will determine whether progress continues or stalls. Throughout the week, many speakers gave voice to fears, highlighting concerns that foreign aid spending is under increased attack in leading donors countries like the United States—a notion echoed in President Trump’s speech to the Assembly—and that political changes like Brexit and an “America First” doctrine signal a movement toward isolationism over collective action. Given significant global health R&D funding comes through foreign aid budgets and the necessity of collaborative global action to deliver the cures of tomorrow, these developments are worrisome. Will these trends threaten progress, or will momentum continue? That’s a question we’ll surely continue to reflect on for many UNGAs to come.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign-up now to receive our weekly R&D News Roundup email. Germ-eating microbes may offer a new line of defense in fighting back against antibiotic-resistant bacteria, according to lab studies funded by the Defense Advanced Research Projects Agency. The most impressive predatory bacteria from the studies was an organism called Bdellovibrio, which preyed upon 145 of the 168 human pathogens tested, invading larger bacteria and eating them from the inside out. Researchers collected remaining ‘survivor’ bacteria, allowing them to reproduce to see if they were able to mutate and resist attacks from Bdellovibrio; however, no direct mutants ever became resistant. This microbe-eating method has been shown effective in fighting bacterial lung disease in rats. No germ-eating microbe experiments have been performed in humans to date. The government of Burkina Faso has granted scientists permission to release genetically engineered mosquitoes, marking a key step in using bioengineering to eventually eliminate malaria in the region. The impending release will also mark the first time a genetically engineered animal will be released into the wild in Africa. The mosquitoes being released will be mostly male with a ‘sterile male’ mutation, meaning none will be able to produce offspring. Although these mosquitoes won’t have any specific mutations related to malaria transmission, researchers hope this release will foster improved trust in science and research among government regulators and local residents and inform future releases. This inaugural release will lay the groundwork for teams in Burkina Faso, Mali, and Uganda to eventually release “gene drive” mosquitoes that will dramatically and rapidly reduce the mosquito population. NASA is using weather satellites to track and predict disease outbreaks before they occur, deploying this technology to track cholera outbreaks in Yemen. Given cholera infections typically result from drinking contaminated water, the team at NASA used environmental data such as rainfall levels and water and air temperatures to build their prediction map and pinpoint where the worst cholera outbreaks will likely occur. NASA’s model proved 92 percent accurate in predicting cholera outbreaks in Yemen, though the information came too late to be useful to the medical teams on the ground. Researchers have continued to improve their prediction algorithm and hope to deploy their data this year to direct health workers to critical areas and save lives.

Authored by Elodie Jambert & Elizabeth Poll, Medicines for Malaria Venture, Switzerland; Panayota Bird, GSK; and Dr Marcus Lacerda, Fiocruz, Brazil  The Amazon is a renowned hotspot for biodiversity, but it’s also a hotspot for malaria. Brazil is one of the Latin American countries with the heaviest burden of malaria, with its Amazon region accounting for 99.5 percent of all national cases. Tackling malaria in Brazil is complicated by the fact that the vast majority of the burden is caused by the malaria parasite Plasmodium vivax. After causing an initial bout of malaria symptoms, this species of parasite has the ability to hide dormant in the liver of infected people, only to re-emerge and cause symptoms again several weeks to several months after initial infection. Another compounding issue is that the only medicine currently available to stop such relapse is primaquine–a medicine approved in the 1950s that must be taken for at least seven days. Given this lengthy course of treatment, many patients fail to complete the full course. It’s a challenge to explain to patients why they should take seven days of pills to treat something that appears to have resolved after the third day (the duration of treatment of the initial acute P. vivax malaria bout). As a result, the medicine often doesn’t work, and transmission of relapsing malaria is perpetuated. In Brazil, over the last 20 years, the burden of the more deadly Plasmodium falciparum has fallen from 50 to 10−15 percent. Yet, progress against P. vivax is yet to see the same success; this parasite now causes 89 percent of malaria cases. While P. vivax doesn’t kill as many people as P. falciparum, it is still debilitating, can also be lethal, and has substantial economic impact on families and nations. As such, it’s important to keep the attention of policymakers focused on malaria even in the face of other pressing public health issues, such as Zika and chikungunya viruses.A new solution for relapsing P. vivax in sightChildren in the village of Boa Vista, on the border of the Juma Reserve in the Brazilian Amazon. Photo: Neil Palmer/CIATFortunately, a new solution to tackle relapsing P. vivax malaria could be in sight. Medicines for Malaria Venture (MMV) and GSK have collaborated to develop a new, single-dose anti-relapse medicine, tafenoquine. The medicine was submitted for regulatory review to the US Food and Drug Administration and Australian Therapeutic Goods Administration at the end of 2017. If approved, it could be an important new treatment for individuals suffering from relapsing malaria, and could help to eliminate the disease in the Amazon.MMV and GSK have developed an access strategy together with in-country partners and are preparing the ground for the medicine’s potential launch in endemic countries. Country-level briefings are ongoing with the National Malaria Control Programmes (NMCP) in Brazil and six other endemic countries (Thailand, Ethiopia, Vietnam, Cambodia, Peru, and Colombia); their goal is to assess interest in introducing the new medicine into national practice and to understand what type of evidence NMCPs would need to support policy adoption. Developing diagnostics to make anti-relapse medicines safer for allPATH rapid diagnostic test to support treatment and elimination of P. vivax. Photo: PATHIntroduction of tafenoquine faces one additional challenge: As is the case with primaquine, people with a genetic deficiency in a specific enzyme known as glucose-6-phosphate dehydrogenase (G6PD) can suffer potentially serious side effects. On average, 8 percent of people in malaria-endemic countries are deficient in this enzyme. To reduce the risk of patients suffering this side effect, PATH is supporting development of a point-of-care diagnostic test to identify patients’ G6PD status and determine whether tafenoquine or primaquine can be safely administered. Concomitant use of this point-of-care diagnostic test will be critical for the correct and well-tolerated use of tafenoquine. Despite the World Health Organization’s recommendation that G6PD tests guide the use of primaquine, few endemic countries routinely use such testing today. In Brazil, the prevalence of G6PD deficiency varies depending on the immigration profile of the region. Most published papers on the subject estimate that the average prevalence among men in Brazil is around 5 percent, a statistic recently confirmed with preliminary data from a government-supported prevalence survey in endemic areas of the Brazilian Amazon.In light of this, additional data is being gathered. Initial preparations for an implementation study are underway in Brazil to demonstrate how a quantitative G6PD test would work in practice, prior to use of tafenoquine in the healthcare system. It is planned for the study to begin after regulatory approval of tafenoquine is granted. The team is also working with academics to model the cost effectiveness of the medicine paired with a G6PD test compared to current standard of care (primaquine without a test), as well as the potential impact of tafenoquine on malaria transmission and elimination. The Brazilian government will use these findings as it considers broader deployment of the intervention throughout malaria-endemic areas.Tafenoquine has potential for significant impact both for the individuals that suffer from this disease as well as for the regions focused on malaria elimination. We await the regulatory decisions on the medicine and will continue to work together as a team of partners to prepare the ground in the Brazilian Amazon to help make it malaria-free for all.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign-up now to receive our weekly R&D News Roundup email. In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Researchers discovered that the meal times of malaria-infected organisms may impact the rate at which the malaria parasite multiplies in the host’s blood. A team at the University of Edinburgh studied the parasitic rhythms of reproduction and invasion of red blood cells in malaria-infected mice and found that the parasites timed their daily multiplication rhythms to match when the animals were fed. When the mice’s feeding time changed, the parasites altered the timing in which they invaded red blood cells. Researchers believe that interfering with the biological processes that link eating to these parasite rhythms—through diet, drugs, or other approaches—could reduce the spread of malaria infection A team of scientists recently created a prototype oral flu vaccine that does not need to be temperature controlled—paving the way for potential new oral vaccines that do not require refrigeration or freezing. Unlike traditional biological vaccines, which are made from part of a virus or bacteria and must be temperature controlled to remain stable, this oral vaccine prototype contains manmade peptides that mimic peptides in real viruses. Scientists found the prototype triggered a strong immune response when tested in human cell cultures and in mice. While more research is needed, these early results are promising. A heat-stable oral vaccine would be easier to transport and store, which could improve care in low-resource, hard-to-reach communities were immunization supply chains may be insufficient. Scientists at the Jena and Friedrich Schiller University Hospital are working to develop a rapid antibiotic resistance test. Current diagnostics for drug-resistant infections can take up to 72 hours to deliver results—a long amount of time for these infections, which can be acutely life-threatening. Using light-based analytical methods combined with microfluidic sample processes—which the researchers colloquially referred to as a miniature Lab-on-a-Chip system—the scientists were able to clearly identify bacterial strains and their resistances in fewer than three hours. New rapid tests for antibiotic-resistant infections could help get patients on treatment more quickly and reduce the overprescription of antibiotics.