Breakthroughs Blog: Malaria

A new study led by the Harvard T.H. Chan School of Public Health found that Anopheles darlingi mosquitoes, a leading malaria vector in South America, are evolving resistance to insecticides, creating serious challenges for malaria control efforts in the region. Insecticide resistance has only been periodically documented in Anopheles darlingi populations, which have not been heavily targeted with insecticides for vector control, suggesting that some of the resistance may be driven by insecticides used in agriculture. The study is the first to sequence a large number of complete genomes of Anopheles mosquitoes in the Americas, looking at the genomic sequences for more than a thousand mosquitoes across six countries. The research provides a template for additional vector studies and paves the way for future studies that could help inform and improve malaria control efforts and policies to reduce the emergence and spread of dangerous resistant strains of the malaria parasite. Last week, Intelligenome announced that it has been awarded funding through a subaward agreement with Cornell University to develop a rapid, low-cost portable diagnostic test for tuberculosis (TB). The company will contribute its point-of-care testing platform to support the development of a portable, rapid assay capable of detecting TB in non-sputum respiratory and blood samples, which is designed specifically for low-resource settings. This approach integrates a CRISPR-based detection approach. The project is part of a program funded by the US National Institutes of Health aimed at improving access to innovative health technologies.Basilea recently announced that the first participant has been dosed in its first-in-human Phase 1 study of BAL2420, a novel antibiotic designed to treat serious bacterial infections. The antibiotic specifically targets infections, including drug-resistant infections, caused by bacteria in the Enterobacteriaceae family—that includes Escherichia coli and Klebsiella pneumoniae—which are considered high-priority threats for which new treatment options are urgently needed. BAL2420 is part of a novel class of antibiotics with a novel mode of action and has demonstrated promise in preclinical studies. Since 2020, BAL2420’s development has been supported by the Combating Antibiotic Resistant-Bacteria Biopharmaceutical Accelerator (CARB-X).  

A research team has identified a protein in the malaria parasite that could offer a promising new target for antimalarial drug development. The researchers found that the protein Aurora-related kinase 1, or ARK1, is essential for the survival and transmission of the malaria parasite. When the researchers turned it off in the lab, the parasite could no longer replicate or complete its development in either humans or mosquitoes, effectively stopping its ability to transmit disease. The ARK1 in malaria parasites is also very different from the version found in human cells, meaning drugs designed to target the protein could be effective without causing harm to humans.  A Phase 3 trial found that a novel single-tablet combination treatment regimen for HIV provided similar viral suppression compared to a multi-pill therapy in older adults, a significant step toward a simpler option for patients who cannot use currently available single-table regimens. The trial included older adults living with HIV who had sustained viral suppression and long treatment histories and remained on complex regimens because of prior drug resistance, intolerance, or other factors that made single‑tablet options unsuitable. The single-tablet regimen was not only similarly effective, but it was also associated with increased treatment satisfaction, as well as improvements in cholesterol and triglyceride levels. Last week, IAVI announcedthat a large Phase 2b trial of the tuberculosis (TB) vaccine candidate MTBVAC will expand to include a new cohort of 1,200 patients who have never been exposed to the Mycobacterium tuberculosis bacterium that causes TB disease. The additional cohort will enable researchers to gather robust safety and immunological data across patients with and without confirmed previous TB infection, increasing understanding of how the vaccine works across diverse populations. MTBVAC is a single-shot vaccine designed to be accessible in remote and low-resource settings; it’s also the only live-attenuated candidate derived from M. tuberculosis currently in trials.

A two-year citywide experiment in Singapore found that releasing Wolbachia-infected mosquitoes was effective at reducing mosquito numbers and dengue transmission in the densely populated city, supporting their use as a complement to existing vector control methods and vaccines to control transmission of dengue and other mosquito-borne diseases. Wolbachia is a common type of bacteria found in insects that cannot make people or animals sick but can stop the dengue virus from replicating inside the Aedes aegypti mosquitoes that spread dengue and other viruses, reducing mosquito populations and disease transmission. The researchers divided the city into clusters, releasing sterile infected male mosquitoes in some areas while leaving other areas untouched. They found that where the infected mosquitoes were released, mosquito numbers fell sharply, and people living there were about 70 percent less likely to develop symptomatic dengue after a few months of exposure. A Phase 4 randomized controlled trial has provided further evidence of the safety and efficacy of shortened regimens of preventive tuberculosis (TB), which could help improve uptake and completion rates. The trial, conducted in Brazil, tested one- and three-month regimens of isoniazid and rifapentine, much shorter than the current standard regimen of isoniazid, which lasts six to nine months and has seen poor uptake and completion rates. Additional studies are needed to ensure safety and acceptability across diverse populations. A Stanford University research team has developed an affordable, battery/solar-operated microscope called Octopi that uses artificial intelligence (AI) to automatically diagnose malaria in blood samples in minutes, which could greatly improve access to early and accurate diagnosis in low-resource settings. Confirmatory malaria diagnosis is currently done through a long, technical process carried out manually by lab technicians. The team also developed a complementary tool to automate and standardize the process of preparing blood samples, which is open source, requires no electricity, and is cheap. 

Women are steadily reshaping the landscape of global health research. In 2022, they made up 41 percent of researchers worldwide, representing considerable progress toward closing the gender gap in science. Yet women remain underrepresented in many scientific fields and in senior roles, are published and cited less frequently than men, and file far fewer patent applications. Despite these systemic barriers, women researchers are having an outsized impact on global policy and progress. Research led by women is more likely to address topics aligned with the Sustainable Development Goals, and publications with women authors are more frequently cited in policy documents.  Expanding women’s participation and leadership in science is not just a matter of equity, it is essential to ensuring research priorities reflect women’s lived experiences. Although women spend more of their lives in poor health than men, only 1 percent of global health research and development funding targets female-specific conditions beyond cancer. Even as gaps persist, women scientists are already at the forefront of innovation, driving cutting-edge technologies that could transform the future of global health. Advancing promising HIV vaccine strategies Developing an HIV vaccine capable of preventing infection has long challenged researchers due to the virus’s extraordinary ability to mutate and evade the immune system. Still, many experts believe such a vaccine will be essential to ending the global pandemic.A Phase 1 trial, launched in August of last year, is evaluating an investigational HIV vaccine candidate designed to induce an immune response scientists believe could effectively target vulnerable parts of HIV-infected cells. Three distinguished female principal investigators—Dr. Tariro Makadzange of the Mutala Trust, Dr. Theodorah Rirhandzu Ndzhukule of the Desmond Tutu Health Foundation, and Dr. Limakatso Lebina of the Africa Health Research Institute—are overseeing the study across clinical trial sites in Harare, Zimbabwe; Cape Town, South Africa; and Durban, South Africa, respectively.  Another Phase 1 trial, launched just last month, is testing a different novel approach. Researchers are evaluating whether highly specialized vaccine immunogens, delivered in a specific sequence, can train the immune system to produce broadly neutralizing antibodies against HIV, widely considered one of the keys to achieving broad protection against the virus. The trial is led by Dr. Linda-Gail Bekker, CEO of the Desmond Tutu Health Foundation and a leading HIV clinician-scientist. These vaccines have the potential to transform the lives of women and girls, who bear a disproportionate burden of HIV and AIDS, particularly in sub-Saharan Africa. The leadership of these scientists underscores how women researchers are driving forward breakthroughs that address urgent global health needs. Trialing promising TB vaccine candidates New tuberculosis (TB) vaccine candidates also hold promise for reshaping global TB efforts, particularly as rising drug resistance makes the disease harder to fight. The only currently approved TB vaccine is more than 100 years old and is effective at preventing some forms of TB in infants but offers limited protection against pulmonary TB in adults.  One next-generation vaccine candidate, MTBVAC, was co-designed by Dr. Brigitte Gicquel of the Institut Pasteur, who is a pioneer in TB research. MTBVAC is the only live-attenuated candidate in the pipeline, meaning it contains a weakened form of the bacteria that causes TB, and aims to offer more effective, longer-lasting protection for newborns while also preventing TB disease in adolescents and adults, for whom no effective vaccine exists.In a Phase 1a/2b trial published last year, MTBVAC was found to be safe and capable of generating immune responses comparable to or stronger than the current TB vaccine. The study was led by Dr. Angelique Luabeya of the South African Tuberculosis Vaccine Initiative, who has considerable experience leading novel TB and COVID-19 vaccine trials. MTBVAC is now being evaluated in a Phase 2 trial in people living with HIV, co-chaired by the aforementioned Dr. Limakatso Lebina. Another leading vaccine candidate, M72/AS01E, is currently undergoing a large Phase 3 trial to determine whether it can protect adolescents and adults from pulmonary TB. Dr. Lee Fairlie of Wits RHI at the University of the Witwatersrand, an infectious disease expert with extensive experience leading major clinical studies, is serving as national principal investigator for the trial in South Africa. These vaccine candidates could dramatically alter the trajectory of the global TB epidemic, reflecting the critical contributions of women researchers in advancing solutions to one of the world’s oldest and deadliest infectious diseases. Driving forward antimalarial drugs for a long-excluded group Last fall, a global consortium launched the first-ever Phase 2 adaptive platform trial evaluating the efficacy and safety of antimalarial drugs during the first trimester of pregnancy. This landmark study addresses a long-standing gap in safe and effective evidence-based treatment options for pregnant women at risk of malaria. Pregnant women, particularly those in early pregnancy, have historically been excluded from clinical trials, leaving major unanswered questions about how best to treat malaria and other conditions in this high-risk group.  Among the study’s co-principal investigators are Dr. Myriam El Gaaloul from the Medicines for Malaria Venture, Dr. Stephanie Dellicour from the Liverpool School of Tropical Medicine, and Dr. Hellen Barsosio of the Centre for Global Health Research at the Kenya Medical Research Institute, who bring deep expertise in clinical trials, malaria, and maternal and newborn health. This trial has the potential to not only reshape care for pregnant women at risk of malaria but also set a powerful precedent for more inclusive research. It illustrates how greater gender diversity in research leadership can help ensure studies prioritize and better reflect the needs of the people they aim to serve. Across the global health innovation pipeline, women scientists are driving transformative progress. Accelerating gender diversity across research teams, investing in early-career women researchers, and strengthening pathways to leadership will advance gender equity while ensuring that scientific breakthroughs are more inclusive, accessible, and reflective of the needs of all people.