Breakthroughs Blog: Research Roundup

Photo: CDC/ Dr. Mae Melvin A recently released clinical report from the US Centers for Disease Control and Prevention details a case of a Colombian man who developed cancerous tumors on his lungs and liver that were comprised of tapeworm cells, rather than human cells. An estimated 75 million people are infected by Hymenolepis nana, the most common human tapeworm, however, this is the first reported case of cancer spreading across species to humans. The team suspects that the tapeworm vector did not have cancer, but rather that one of its eggs mutated within the patient’s gut into cancerous cells. International Partnership for Microbicides (IPM), a member of the GHTC, is conducting Phase I clinical trials of a novel HIV and AIDS prevention method known as DS003. The drug binds to a protein on the surface of the HIV virus, preventing it from entering human immune cells. The trial will involve three stages, during which nine women will receive the drug and three will receive a placebo, enrolling 36 volunteers in total. At each stage, the participants will receive increasingly higher doses, from 1 to 10 mg, assuming that the previous stage demonstrated the drug to be safe and tolerable. The drug will be tested as a vaginal tablet, and if successful, DS003 will likely be tested in vaginal rings and/or in combination with other antiretroviral drugs. The fastest and most accurate tuberculosis (TB) diagnostic test will soon be available as a portable and more affordable device, making it more accessible in low-resource settings. Cepheid Inc.’s GeneXpert was endorsed by the World Health Organization in 2010, and its use increases the accuracy of diagnosis by 39 percent, however, the machine costs US$17,000 and requires electricity, refrigeration, and access to a computer. The new GeneXpert Omni will be rolled out early next year at a fraction of the cost—$2,895 for the machine and $10 per cartridge. The Omni runs on a battery and connects to a smartphone, weighs just 2.2 pounds, and can diagnose drug-resistant TB along with 23 other diseases.

Photo: CDC/ Prof. Woodbridge Foster; Prof. Frank H. Collins Findings of a study presented at the American Society of Tropical Medicine and Hygiene Annual Meeting last week suggest that ivermectin—a drug long used to treat river blindness and elephantiasis—can combat malaria when used in mass drug administration programs. The study, which was conducted by researchers from Colorado State University and the Institut de Recherche en Sciences de la Santé, found that mass distribution of ivermectin (six times, in three week intervals) resulted in a 16 percent decrease in incidence of childhood malaria. Ivermectin isn’t toxic to the malaria parasite; rather, it weakens the mosquito vector, serving as a form of vector control. After a mosquito becomes infected with malaria, it can take up to two weeks before it is able to transmit the parasite to humans. With ivermectin present in the human population, multiple humans might transmit ivermectin to the mosquito before it is able to spread the malaria parasite to even one human. The study was conducted in the West African nation of Burkina Faso, and the leading malaria parasite and mosquito vectors vary between sub-Saharan Africa and Southeast Asia. However, researchers at the US Walter Reed Army Institute of Research have recently determined that ivermectin can inhibit the development of the malaria parasite and kill the mosquito vector endemic to Southeast Asia. Researchers at the University of Malaya in Kuala Lumpur, Malaysia, have developed LED street lights that are environmentally friendly and a public health tool. The street lights are powered by wind and solar energy, and serve a dual purpose of trapping mosquitos to combat dengue fever and other infectious, mosquito-borne diseases. The lamps release carbon dioxide, to which mosquitos are attracted, and use a fan to trap the mosquitos. The lamps are currently being piloted in Malaysia at two different sites. Professors at Duke University have designed a colposcope, a cervical cancer diagnostic tool, to be used in low-resource settings, and will soon begin testing the device in a pilot study in Peru. Existing colposcopes are large and include equipment to magnify and illuminate the cervix (see Image 1), whereas this device, the Point of Care Tampon (POCKeT), includes a camera that provides images of comparable quality. The POCKeT is small (see Image 2), connects to a smartphone or tablet, requires less training, and is expected to be more culturally appropriate than a traditional colposcope. The testing of the POCKeT will be supported by a US$3.7 million grant from the US National Institutes of Health. A recent report from the Review on Antimicrobial Resistance, commissioned by United Kingdom Prime Minister David Cameron to address the growing threat of drug-resistant infections, calls for the research and development of rapid, point-of-care diagnostics to reduce the overuse of antibiotics. Such diagnostics would allow health care workers to pinpoint the cause of an illness and treat it accordingly, rather than prescribe a broad-spectrum antibiotic without confirmation that the cause is bacterial and/or that the pathogen will be susceptible to the drug. The Review notes that drug companies, which benefit from antibiotic sales, have little incentive to invest in diagnostics that could limit those sales. The report includes a diagnostic 'wish list,' which identifies 12 potentially "game-changing" tools, including an at-home test to determine if an illness is an infection at all or to distinguish between bacterial and viral infections.

Photo: National Institute of Allergy and Infectious Diseases (NIAID) Researchers at Tulane University successfully tested an experimental aerosol tuberculosis (TB) vaccine in monkeys, demonstrating that the candidate was more effective in protecting against infection than BCG—the only TB vaccine on the market. To create the vaccine, the researchers genetically modified the TB bacterium, removing a gene that plays a key role in infection. The vaccine was then administered to seven monkeys, while another seven each received either an aerosol version of BCG or no vaccine. After eight weeks, the monkeys were exposed to TB at a lethal level. The experimental vaccine not only was more protective than BCG, but it also induced a stronger immune response in the lungs, which is thought to be key to preventing infection. A new formulation and coating for existing HIV and AIDS medicines could significantly decrease the frequency with which the drugs must be taken. Researchers at the University of Nebraska Medical Center used a process called nanoformulation, which involves modifying drugs at the most basic level (i.e., atomic or molecular level) in order to convert them into nanoparticle crystals. In this experiment, the antiretroviral medicine crystals were coated with fat and protein, allowing them to last much longer in the body. In the lab, the drug proved to be effective in combatting HIV and AIDS. The team hopes its findings could eventually lead to the development of an HIV and AIDS treatment that could be administered once or twice per year, rather than daily. Resistance to the leading antimalarial—artemisinin—was first reported in Cambodia in 2008, and a new study in Nature Communications suggests that the drug-resistant parasite has the ability to infect African mosquito species. A team of researchers at the US National Institute of Allergy and Infectious Disease infected two Asian and one African mosquito species with the drug-resistant malaria parasite, and all three species proved to be susceptible. Furthermore, the African species were no less vulnerable to infection, which came as quite a surprise as the species have evolved independently for more than 30 million years. Health officials from the United States and Saudi Arabia are considering a collaboration for the development of a vaccine against Middle East Respiratory Syndrome (MERS), which has infected more than 1,500 people across 27 countries. There are currently a number of MERS vaccines in development and several have yielded promising results in animal studies. The Saudi Ministry of Health has US$70 million available for the project; however, the proposed role of the US government remains unknown.

Dr. Robert Gallo co-discovered the HIV virus and subsequently led the development of the first HIV and AIDS blood test. Now, his team at the University of Maryland School of Medicine is initiating human clinical trials of an experimental HIV and AIDS vaccine that aims to prevent the virus from attaching to immune cells. The HIV virus uses a protein on its surface—gp120—to bind onto one part of human immune cells—the CD4 receptor—and then subsequently bind onto a second part of the cell—CCR5. This vaccine candidate interrupts this process by preventing the HIV virus from attaching to CCR5, therefore disrupting the process of infection. While many vaccines target specific viral strains, this candidate is intended to neutralize all strains of the HIV-1 virus. The first phase of the trial will enroll 60 healthy, adult volunteers to determine the vaccine’s safety and to ascertain if it successfully triggers an immune response. A 23-year-old engineer has developed an inflatable incubator that is designed to be easy to transport, use, and maintain, which could dramatically reduce deaths of premature babies in refugee camps. Developer Briton James Roberts has created electronic and functional prototypes which indicate that the incubator, known as MOM, will provide the required warm, stable, and sterile environment. Roberts designed the product with Syrian refugee camps in mind, as an estimated three-fourths of premature infant deaths in camps could be prevented with proper incubation. The incubator can be collapsed (see Figure 1) to fit in care packages commonly distributed in refugee camps and while it does require electricity, it can run off of a car battery or solar power. Roberts recently won two cash prizes to support product development and manufacturing but is continuing to fundraise to support the costly process of regulatory approval for medical devices. Roberts believes the product could be ready for market by 2018. Photo: CDC/ Dr. Scott Smith The US Department of Defense (DoD) and National Institutes of Health (NIH) have both supported the research and development (R&D) of drugs and vaccines for Ebola since the early 2000s. In both agencies, budget constraints halted progress despite promising clinical trials. In 2004, a researcher at army installation Fort Detrick was exposed to Ebola, prompting the DoD to partner with pharmaceutical company Sarepta Therapeutics to rapidly develop an experimental treatment for Ebola. The treatment was given emergency approval by the US Food and Drug Administration (FDA), but the researcher did not become infected and the treatment remained unused. In 2010, the DoD awarded Sarepta a US$291 million contract to continue its work. Sarepta’s drug demonstrated 60 to 80 percent efficacy in clinical trials with primates and proved safe for use in phase 1 human clinical trials. In September 2012, the FDA granted Sarepta’s drug fast-track status—to expedite its regulatory review—but just one month later, the DoD discontinued the project, in light of looming budget cuts that seemed inevitable due to congressional gridlock. In mid-2014, after the onset of the Ebola epidemic in West Africa, Sarepta CEO Chris Garabedian approached the DoD about the possibility of continuing their work, however, the agency chose to fund products that were not as far along as Sarepta’s. While the DoD has since reconsidered—inviting Sarepta to apply for funding for phase II trials—Sarepta declined, and under new leadership, has terminated their Ebola R&D. The US Department of Agriculture (USDA) has contracted two veterinary pharmaceutical companies—Harrisvaccines and Ceva Santé Animale—to manufacture, store, and ship vaccines to prevent the strain of avian influenza which caused an outbreak and consequent shortage of eggs and turkey in the United States earlier this year. The contract requires the companies to store the vaccines for up to five years, regularly testing them for quality assurance, and will ship them within ten days to anywhere in the United States if requested by the USDA National Veterinary Stockpile. To improve clarity and expediency of communication—for which the agency was criticized by veterinary, poultry, and egg groups during this year’s outbreak—the USDA has also worked with Iowa State University to translate avian influenza–related biosecurity materials for Spanish-speaking farm workers.