Breakthroughs Blog: Antimicrobial resistance

Fungi have existed for hundreds of millions of years, long before dinosaurs walked the Earth, but fungal infections have become a rapidly growing challenge for human health in recent decades.Fungal diseases affect more than 300 million people each year, disproportionately impacting people in low-resource settings and those with weakened immune systems, including people living with HIV, cancer patients, and transplant recipients. Most fungal infections affect superficial tissue like the skin, nails, or hair and can cause chronic illness and productivity loss. Though less common, invasive fungal infections can spread throughout the body and are associated with high mortality.Why fungal diseases are becoming harder to ignoreThe rising incidence of fungal infections is driven by a variety of factors, including conflict, poverty, urbanization, pollution, travel, and climate change, which increase exposure, heighten vulnerability, and expand the reach of dangerous fungal pathogens. At the same time, advances in medicine mean more people are living longer with conditions that weaken the immune system, increasing the number of people at greater risk. Growing antifungal resistance is also making infections harder to treat and further limiting already scarce treatment options.Despite the mounting burden, fungal disease remains underprioritized, underdiagnosed, under-surveilled, and underfunded, making it one of the world’s most neglected global health threats.Why innovation is falling behindFungal infections receive less than 1.5 percent of all infectious disease research and development (R&D) funding, contributing to sparse pipelines for both therapeutics and diagnostics. Closing these gaps will require greater investment in R&D, particularly for tools designed for resource-constrained settings and targeting the pathogens that pose the greatest threat to human health. Stronger regulatory and procurement systems and international collaboration will also be essential to ensure emerging tools are affordable and accessible worldwide.Despite persistent gaps, several promising innovations demonstrate the potential for R&D to transform the global response to fungal disease.Promising advances in antifungal treatmentThere are currently only four classes of antifungal medicine available, many of which are associated with serious side effects or require lengthy, hospital-administered treatment courses. The pipeline of new antifungal therapies also remains thin.The World Health Organization (WHO) reported last year that only nine antifungal therapies were in clinical development to address WHO’s designated top four priority pathogens, including three in Phase 3 development. Although the Phase 3 trial for one of those candidates has since been terminated, another candidate, olorofim, developed by Shionogi and F2G, recently reported positive Phase 3 trial results. If approved, it could become the first antifungal treatment with a novel mechanism of action for that infection in more than 20 years.Earlier-stage research is also yielding promising advances. Researchers recently discovered that an antibiotic could target a priority fungal pathogen by switching it back from its invasive form to a less harmful form. This antibiotic could help existing antifungal drugs target dangerous fungal pathogens, allowing lower, less toxic doses of those drugs to be used.Together, these advances offer hope of a new generation of antifungal therapies.The future of fungal diagnosticsDiagnostic tools for critical fungal pathogens exist but with significant limitations, including invasive sampling requirements, long turnaround times, limited pathogen coverage, and inadequate sensitivity. Many also depend on sophisticated laboratories and highly trained staff, making them difficult to deploy in resource-constrained settings globally that bear a disproportionate burden of fungal disease.The MycoMEIA® assay developed at Johns Hopkins University and commercialized by Pearl Diagnostics represents a recent advance in antifungal diagnostics. The test received US Food and Drug Administration clearance in 2025. It uses a urine sample, which is much simpler and less invasive for patients than current options, and provides results in just a few hours.Another promising research development illustrates where fungal diagnostics may be headed next. Researchers at the Mayo Clinic and Zepto Life Technology recently reported early results from a new diagnostic platform that was able to identify 18 different fungal pathogens with a single test. While still in development, such approaches could not only streamline diagnosis for health care providers and patients, but also reduce costs and resource requirements, making them well-suited for resource-constrained settings.Closing the innovation gap Fungal diseases and antifungal resistance are attracting greater international attention, but the response still lags behind the scale and pace of this growing threat. Increased investment in the R&D of fit-for-purpose innovations, paired with stronger regulatory and health systems and global coordination, will be crucial to ensure new diagnostics and treatments emerge from the pipeline and reach the patients who need them most. 

Every year, World Mosquito Day brings renewed attention to mosquito-borne diseases like malaria. But attention is not enough. What matters now is whether we are using the tools we have effectively and whether those tools will still work tomorrow. Malaria drug resistance is not new. Until the early 2000s, chloroquine was the backbone of treatment. It was widely available and highly effective until resistance spread and treatments began to fail. Health systems were caught off guard, deaths rose, and the world learned a painful lesson: once resistance takes hold, recovery is slow, costly, and measured in lives lost. Today, we are seeing warning signs again. Resistance to existing first-line drugs is emerging in parts of East Africa, the Horn of Africa, Southeast Asia, and South America. At the same time, malaria deaths rose to 610,000 in 2024, up from 597,000 the year before, a trend unfolding against a backdrop of severe financing shortfalls. Global funding reached only $3.9 billion in 2024, less than half the $9.3 billion required. Sustained underinvestment has well-documented consequences: fewer preventive measures, overstretched health systems, and reduced capacity to respond when resistance emerges. The economic case for doing more is equally stark. According to a recently published analysis, reducing malaria cases by 90 percent by 2030 could increase Africa's GDP by $126 billion and expand global trade by $80.7 billion. Now urgency matters more than ever. We cannot afford to wait for existing tools to fail before acting. In the words of Dr. Brenda Akia, Africa representative and Vice Chair of the Committee on the United Nations Convention on the Elimination of All Forms of Discrimination against Women: "Malaria was killing people even when the drugs were working. Now that the drugs are failing, we are cooked if we do not act fast." Cooked, mingled and served as gourmet food at the banquet where the mosquitoes will gather to celebrate their victory over humanity. This is not an exaggeration. The impact of chloroquine resistance—the memories of the increasing death tolls, the desperation to save lives with a tool that was becoming blunt— still lingers on. The response must be twofold. We need sustained financial commitment to ensure countries can procure and deliver existing tools through their health systems, and we need investment in new tools to stay ahead of resistance. Both are essential, and neither is optional. On the innovation front, there is encouraging progress. New medicines are advancing through development to better protect those most at risk. Through the work of Medicines for Malaria Venture and its partners, triple combination therapies designed to preserve the effectiveness of existing drugs are in development. In addition, ganaplacide-lumefantrine, a novel combination therapy developed with Novartis, has completed a Phase 3 trial with positive results. Looking ahead, long-acting injectable medicines that could provide protection against malaria for up to six months are also in development. Beyond new medicines, innovations in vector control are further strengthening the fight against malaria. These include new spatial emanator repellents that can provide protection for up to 12 months and dual-insecticide nets designed to combat insecticide resistance. Together, these advances reinforce our belief that ending malaria within a generation is within reach.However, as Brazil's Minister of Health Alexandre Padilha said recently, "Innovations that are not in the hands of those who need them are no good." As was done for the COVID-19 response, we must accelerate regulatory processes for innovations. Mechanisms must be put in place to make these critical innovations affordable and accessible. The health workforce must also be trained to deploy them effectively, and civil society organizations and community groups must also lead the way in raising awareness of the threat posed by drug resistance and the need for new tools. Countries are already showing leadership. For example, Thailand is strengthening its national strategy with a focus on surveillance and resistance response. Kenya is deepening community engagement. Rwanda is investing in stronger data systems. Uganda is supporting local manufacturing. These are concrete actions, not intentions. Countries have the capacity, but they need sustained and predictable financing to deliver new tools effectively. This is the moment for malaria elimination. Progress will not be secured by innovation alone, nor by financing alone, but by aligning both with strong country delivery systems. We call on the entire global health ecosystem to unite under one final “Big Push.” It is time to turn hope into well-funded action and finally take us across the finish line to a malaria-free world.

Researchers from Stanford University and the Broad Institute have used artificial intelligence to create functional bacteriophages capable of destroying strains of bacteria that have evolved resistance to naturally occurring phages. Bacteriophages are common viruses that target and kill bacteria. The engineered bacteriophages performed comparably to naturally occurring relatives and were able to rapidly clear strains of Escherichia coli that had evolved resistance. This research could lead to the development of phage therapies capable of targeting rapidly evolving pathogens, although experts warn that safeguards are urgently needed to prevent the technology from being used for harm.A newly published study led by Oregon Health & Science University found that a one-time treatment regimen designed to be given to newborns with HIV within three days of birth permanently cleared the virus in nonhuman primates, offering hope of a way to mitigate the need for lifelong treatment for newborns infected with HIV. The therapy consists of neutralizing antibodies, standard antiretroviral therapy, and the experimental monoclonal antibody leronlimab, which, in previous studies, have failed individually to permanently clear the virus. Antiretroviral therapy is already approved, so pending the outcomes of ongoing clinical trials of the broadly neutralizing antibodies and leronlimab, the next step is to evaluate the combination regimen in people, initially in newly exposed adults.  A team of UK scientists have found in a first-in-human trial that a reformulated temperature-stable tetanus-diphtheria vaccine is comparable in safety and efficacy to two approved vaccines. Current vaccines need to be kept very cool throughout transport and storage, a very expensive and resource-intensive requirement that can lead to wasted supplies and limited access in low-resource settings. The scientists reformulated a licensed vaccine by drying it into a powder with trehalose, a sugar used by plants to survive in dry conditions, which is then reconstituted with water before administration. A larger trial is set to begin soon, which could be the last evaluation required because the original vaccine is already licensed. 

Last week, the Merck-Wellcome joint venture Hilleman Laboratories announced that it will manufacture doses of a promising vaccine candidate for the Bundibugyo strain of Ebola, which is behind the worrying outbreak in the Democratic Republic of the Congo. There are no specific vaccines or treatments available for Bundibugyo, so global partners have worked rapidly to advance candidates into testing since the declaration of the outbreak. Hilleman Laboratories will manufacture doses of IAVI’s single-dose vaccine candidate, which uses the same vaccine platform as Merck’s approved vaccine for the more common Zaire strain of Ebola and has been identified by the World Health Organization as the most promising candidate currently in development. The lab expects to be able to produce tens of thousands of doses to be used in early-stage trials, potentially by the end of this year. Alveo Technologies is partnering with the University of Texas Medical Branch to develop a molecular point-of-care diagnostic test for Lassa fever, a hemorrhagic illness endemic in parts of West Africa for which access to laboratory testing is limited. Improving access to reliable, point-of-care testing could greatly improve Lassa control in endemic regions, as well as limit its potential to spread more widely—the virus has been designated as a dangerous pathogen with pandemic potential. The diagnostic test will be evaluated at clinical sites in Nigeria and Sierra Leone. The partners are also collaborating on field testing of Alveo’s diagnostic platform for avian influenza surveillance in Peru. The Global Antibiotic Research & Development Partnership (GARDP) announced last week that the Thai Food and Drug Administration has approved zoliflodacin, a first-in-class, single-dose, oral antibiotic for gonorrhea treatment, marking the drug’s second global approval. Zoliflodacin, developed as part of a public-private partnership between GARDP and Innoviva Specialty Therapeutics, was approved earlier this year by the US Food and Drug Administration. Beyond the potential of this innovative treatment to help address the rising global threat of antibiotic resistance, the rapid follow-up approval of the drug beyond the high-income market also represents an important step toward ensuring expedited global access to innovative new antibiotics.