Breakthroughs Blog: Research Roundup

Snakebites, which Médecins Sans Frontières describes as “one of the world's most neglected public health emergencies,” kill 200,000 people each year. This makes snakes the second deadliest animal after mosquitoes. However, not only has research and development for snakebite antivenoms received little investment, but production of existing treatments is also declining due to their low profitability for pharmaceutical companies. Antivenoms are traditionally developed using antibodies produced by animals that have been bitten by snakes, but a number of small biotech companies and even individuals are testing innovative ways to create new, multipurpose antivenoms. Dr. Claire Komives, a professor of Chemical Engineering at San Jose State University, is working to enlist the E. coli bacteria to produce a promising antivenom, as the use of bacteria could make production significantly cheaper and easier to scale up. Meanwhile, a team of researchers across Europe and Central America are developing a treatment for a myriad of common venoms, starting with an antivenom that is effective against three different venoms. Their plan is to identify deadly venoms against which their product is not effective and then develop and incorporate a treatment for that venom into their product. Finally, a team at the California Academy of Sciences is screening chemical compounds in existing, approved drugs to develop a product that could stabilize a bitten patient, giving them more time to seek treatment. The World Health Organization estimates that one-third of the world’s population has latent tuberculosis (TB), only 10 percent of whom will actually contract the disease. However, co-infection with a helminth, a parasitic worm, increases one’s chance of developing TB and exacerbates the symptoms, particularly lung damage. Scientists have long suspected that the parasitic infection impeded the immune system’s ability to fight TB, inhibiting immune cells that provide protection against TB. However, new research out of Washington University in St. Louis suggests that a specific molecule produced by helminths’ eggs prompts an inflammatory immune response that increases one’s susceptibility to TB and its symptoms. The team was able to engineer immune cells that do not produce the molecule, and mice co-infected with TB and the parasite who were given the engineered immune cells did not have the damaging, inflammatory immune response. Analyses of blood samples from TB patients also demonstrated a correlation between the presence of the molecule and the severity of TB symptoms. Photo: PATH/Wendy Stone Researchers at The Scripps Research Institute (TSRI) are developing an HIV and AIDS vaccine candidate that targets a region found on 90 percent of known strains of the HIV virus. The team at TSRI has been conducting experiments to prompt the immune system to generate broadly neutralizing antibodies—proteins which fight multiple strains of the HIV virus—and discovered that four of these antibodies all targeted the same part of the virus, the V2 apex. Further, two of the antibodies have an unusual advantage. While most antibodies mutate from their original form to become more effective at fighting a virus, two of the antibodies were able to bind to the V2 apex in their initial form, consequently speeding up the immune response. However, the body doesn’t naturally make a large number of these antibodies, instead focusing on the further developed antibodies. To address this, the team at TSRI engineered a version of an HIV protein to which those basic antibodies bind with the anticipation that it will lead to their increased production. The engineered protein is being used in a vaccine candidate that will next be tested in animal studies.

Photo: PATH/Eric Becker A new study suggests that the use of anti-parasitic drugs and insecticides in cattle can reduce human cases of Trypanosomiasis (sleeping sickness) by as much as 90 percent. Sleeping sickness is caused by parasites and transmitted by tsetse flies, and while cattle are not susceptible to human sleeping sickness, they do carry the parasite. The study, conducted in rural Uganda, involved injecting 500,000 cattle with two anti-parasitic drugs and spraying their legs, which the tsetse flies bite, with an insecticide. The team estimates that the program saved US$15 to $60 million in health care costs and increased Uganda’s gross national product by $400 million. Researchers at the Washington University School of Medicine in St. Louis have identified antibodies—immune system proteins—that could protect against or treat multiple alphaviruses, including Chikungunya. The antibodies are known as “broadly neutralizing antibodies,” a term which normally refers to antibodies that target different strains of the same virus (i.e., HIV, Hepatitis C) rather than different viruses altogether. The team, led by Dr. Michael Diamond, director of the Division of Infectious Diseases and Vaccine Development at Washington University School of Medicine, evaluated 60 human and mouse antibodies for Chikungunya and identified 10 that are active against three or more alphaviruses. The two most potent antibodies were then used as a treatment for mice infected with Chikungunya as well as two other alphaviruses—O’nyong’nyong and Mayaro virus—and the team confirmed that the antibodies reduced the symptoms of the infections. The team is using their findings to develop more antibodies which will then be tested on animals. New research conducted by professors Drs. Bruce Freedman and Ron Harty of the University of Pennsylvania School of Veterinary Medicine could pave the way for treatments against Ebola, among other viruses. Viruses utilize their hosts’ cells to mature, reproduce, and spread and Freedman and Harty have developed a mutated gene that blocks the pathways that many viruses use to communicate. By blocking those pathways, the virus remains trapped, unable to leave the cell and infect other cells. The team will next test their approach in mice with the ultimate goal of developing an anti-viral medicine effective against any virus that uses those same pathways to communicate.

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.