Breakthroughs Blog: Research Roundup

A new compound has successfully protected monkeys from HIV, according to a study published in Nature last week. The compound stimulates the production of claw-shaped proteins that are able to simultaneously block the two different parts of white blood cells—the CD4 and CCR5 binding sites—to which the HIV virus normally attaches. After scientists at the Scripps Research Institute “vaccinated” monkeys with the compound, they repeatedly tried and failed to infect the monkeys with large doses of varied HIV strains over the course of a year. The team will next test if they are able to slow the replication of virus and the progress of the diseases in monkeys infected with HIV, before starting human trials. Last week, the World Health Organization approved the ReEBOV Antigen Rapid Test for Ebola, which requires only a test tube and a piece of paper and can provide results in approximately 15 minutes. The test is simple to administer and interpret, with the lead developer explaining “a drop of blood is placed on the paper, and if two lines appear, then it’s positive for Ebola.” The use of blood, however, requires a ‘biosafety cabinet’ in the form of either a box or a tent that can protect health workers from the virus. The test also has specificity and sensitivity issues, only detecting 92% of cases and with approximately 15% of uninfected people testing positive for Ebola. CBS correspondent Bob Simon investigated ZMapp, an experimental drug for Ebola, as part of his final story for 60 minutes before his death last month. Prior to the current Ebola epidemic, ZMapp had only been tested on monkeys; however, last summer, it was used to treat seven patients, five of whom survived. The US National Institute of Allergy and Infectious Diseases commenced clinical trials for ZMapp in Liberia on Friday. ZMapp is created using tobacco plants, which are saturated with a gene that stimulates the production of Ebola-fighting antibodies. As the plant grows, increasing rates of antibodies are produced—a process Simon likened to “a Xerox machine for antibodies.” Secretary of State John Kerry testified before the House Foreign Affairs Committee last Wednesday on the US Department of State’s 2016 budget proposal. The Committee’s Ranking Member Eliot Engel (D-NY) emphasized the importance of global health “research, infrastructure, and personnel,” in preventing future epidemics such as the Ebola crisis in West Africa and expressed his dismay at “proposed cuts to global health programs dealing with tuberculosis [and] neglected tropical diseases.”

The TB Alliance, a member of the Global Health Technologies Coalition, announced last week that it will be starting Phase 1 clinical trials for a new tuberculosis (TB) drug candidate. The drug, known as TBA-354, is the first new TB drug to advance to clinical trials in six years, despite the paucity of highly effective and easily administered TB treatments. TBA-354 was developed by the TB Alliance, in partnership with the University of Auckland and the University of Illinois-Chicago, using compounds from the nitroimidazole class of chemicals, which are known to be effective against drug-resistant strands of TB. The World Health Organization (WHO) estimates that US$2 billion per year is needed for TB research and development (R&D), yet in 2013, only $676.7 million was invested. The Atlantic took an in-depth look at gaps in reproductive health R&D, highlighting common side effects of leading contraceptives and reviewing the results of clinical trials conducted between 2008 and 2011 for a contraceptive injection for men. The article also identifies contraceptive technologies currently in the pipeline, including a reversible version of a vasectomy, an improved diaphragm, a remote-controlled implant, and more. A drug-resistant form of malaria endemic to Cambodia and found in Southeastern Myanmar has spread north to the border Myanmar shares with India. While the strain is resistant to artemisinin, the most effective agent against malaria, it can still be combatted with other drugs. Dr. Charles Woodrow, the lead author on the study, explained that in Cambodia, treatment for the resistant strain involves "combining three drugs, extending courses from three days up to five days." Scientists fear that if this new strand were to establish a foothold in India, it could rapidly spread across the globe. WHO estimates that US$750 million annually is needed to prevent and treat neglected tropical diseases (NTDs), yet current foreign aid amounts to only $300 million per year. Due to the financial climate in donor countries, WHO is calling for increased domestic funding in countries where NTDs are endemic. Dirk Engels, Director of the Department of Control of NTDs at WHO, has stressed the importance of interventions that combat multiple NTDs, such as large-scale, affordable vector control programs and diagnostic interventions.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Newsweek took an in-depth look at the work of Sanaria, a small biotechnology organization striving to develop a vaccine to effectively eradicate malaria. Naturally-acquired immunity is common in malaria-endemic regions, however, it takes an estimated three years for children to develop even partial immunity. The team at Sanaria has produced a vaccine that is considered the safest and most effective vaccine to date, preventing malaria in 100 percent of participants in initial trials. The vaccine defends against Plasmodium falciparum, the parasite responsible for nearly all fatal cases of malaria. Despite the success of initial trials and accolades such as the 2014 Vaccine Industry Excellence Award for “Best Prophylactic Vaccine,” Sanaria struggles to get adequate coverage or funding to continue, let alone escalate, the development of the vaccine. A virulent new form of HIV has been reported in Cuba, leading to an accelerated transition from HIV to AIDS. The HIV virus must attach itself to certain 'receptors,' or proteins on the cell membrane, before entering the human cell. The virus has historically attached itself first to the protein CCR5, and after several years it develops the ability to attach to the CXCR4 protein, a development which often correlates to the transition to AIDS. The aggressive new strand is recombinant, a variant of the virus resulting from a combination of multiple strands of HIV. Researchers at the Ku Leuven’s Laboratory for Clinical and Epidemiological Virology have seen particularly high levels of both the virus and the RANTES molecule in patients. The RANTES molecule, a natural part of the human immune response, combats HIV by attaching to the CCR5 proteins, which prevents the virus’s ability to enter the cells, resulting in the virus adapting to attach to the CXCR4 proteins. Patients with the new, recombinant strand may develop AIDS within just three years of infection, before many are even diagnosed with HIV. Mother Jones examined the impact of climate change on the spread of infectious diseases, and the role that vaccines can play in mitigating that impact. Climate change, and in particular, extreme climate events, can not only weaken existing health systems, but higher temperatures and levels of rainfall are actually correlated to increased cases of certain diseases, such as rotavirus. As Alistair Woodward, an epidemiologist at the University of Auckland explained, “ensuring that people are vaccinated is a logical thing to do as part of managing the risks of a rapidly changing climate.”

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. US Food and Drug Administration (FDA) Commissioner Dr. Margaret Hamburg announced last week that she intends to resign from her position in March. The FDA’s Chief Scientist Dr. Stephen Orstroff will serve as the interim Commissioner. Dr. Robert Califf, founding director of the Clinical Research Institute at Duke University, and recently appointed deputy commissioner for Medical Products and Tobacco at the FDA, is expected to be the principal candidate to fill the role permanently. The Global Health Innovative Technology (GHIT) Fund and the Gates Foundation launched a Grand Challenge last week to combat neglected diseases, including malaria, tuberculosis, Chagas disease, and visceral leishmaniasis. The Fund intends to grant US$2 million per year for the research and development (R&D) of new drugs, vaccines, or diagnostics, and up to $1 million per year for each product. GHIT also announced last week that it will invest $637,000 into the development and testing of chemical compounds in the pursuit of more effective products to prevent and treat malaria. The funding will be directed into a partnership between GHTC member Medicines for Malaria Venture and Japanese pharmaceutical company Daiichi Sankyo. Policy Cures—an independent research group and author of the annual G-FINDER report which analyzes global spending on global health R&D—released its first-ever report on reproductive health R&D for developing countries. The report reveals that just $88 million was spent on developing country-specific reproductive health R&D in 2013, $63 million of which was spent on contraceptive R&D. The report explores the limited funding and major gaps in reproductive health R&D, highlighting the need for affordable products that are easily delivered, administered, or stored; have multiple purposes; and do not have major side-effects. A recent study reveals that the United Kingdom’s top 25 universities—in terms of public funding for medical research—spend just 1.7 percent of their health research budgets on neglected diseases. The London School of Hygiene & Tropical Medicine topped the list, spending 68 percent of their health research on diseases that impact people in developing countries, however, all but 5 of the top 25 allocated less than 10 percent of their medical research budgets to neglected diseases.