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Luminol has long been used to detect blood at crime scenes, as it glows bright blue when it comes into contact with the blood protein hemoglobin, however, new research suggests that it could be repurposed to fight malaria in humans. Scientists at Washington University School of Medicine discovered that adding luminol and an amino acid that generates a key component of hemoglobin—heme—to a solution of malaria-infected blood cells triggers a chain reaction, ultimately killing off the malaria parasite. The malaria parasite drills into human blood cells, leaving an opening into the cell. When the amino acid enters the blood cells through that opening, it produces a surplus of heme, which in turn leads to a buildup of the molecule protoporphyrin IX. As the hemoglobin glows in response to the luminol, the light exposure causes protoporphyrin IX to release free radicals, and the free radicals attack the parasite. The team will next test a treatment of luminol, the amino acid, and the existing antimalarial drug artemisinin in animals. Dr. Daniel Goldberg, the study’s lead author, is “optimistic” that the three agents, which are independently safe for use in humans, could “be combined to form an innovative treatment for malaria.” Counterfeit drugs constitute eight percent of global pharmaceutical sales annually, resulting in 700,000 deaths from fake tuberculosis and malaria medicines alone. Dr. Muhammad Zaman, a professor of Biomedical Engineering at Boston University, has built a machine the size of a carry-on suitcase that can test medicines—whether in liquid, powder, or tablet form—to determine the presence and potency of active pharmaceutical ingredients. The device, known as PharmaChk, uses fluorescent probes which bind to the active ingredients in different drugs. If the active ingredient is present, the probe will light up, with its brightness dependent on the potency of the drug. That light is captured by a tiny camera which is then read by the device’s software, telling users exactly how much of the ingredient is present. The kit is currently equipped to test antimalarials and antibiotics and Zaman’s team is developing additional technology to test tuberculosis and postpartum hemorrhage treatments. The test takes fifteen minutes, which is also how long it takes to train a health worker or pharmacist to use the device. The team won a US$2 million grant last year for the advanced development and commercialization of PharmaChk and is currently testing the device in hospitals and pharmacies in Ghana. Photo: CDC / Dr. Mike Miller Researchers at The Ohio State University may have found a way to protect against all strains of influenza by triggering a response in the human immune system without actually introducing any viral material. The immune system constantly generates low levels of the protein IFITM3, which prevents the virus from reproducing and infecting new cells; when a person becomes infected with the flu, an additional protein—known as interferon—accelerates production of IFITM3. The scientists hypothesized that if the immune system created a stockpile of IFITM3 before introduction of the flu virus, it could prevent the infection entirely. However, the team wanted to avoid targeting interferon, as it has serious side effects, including flu-like symptoms. In studying the reaction, they concluded that interferon is not only responsible for ramping up IFITM3 production, but for decreasing production of NEDD4, an enzyme which normally breaks down excess IFITM3. The team determined that suppressing NEDD4 directly in human and mouse cells results in a buildup of IFITM3, without having to involve interferon. At this time, the team is exploring when and how to inhibit NEDD4; while the enzyme is critical to fetal development, it’s unclear what role it plays in adults.

Since its discovery in 2012, cases of Middle East Respiratory Syndrome (MERS)—a disease World Health Organization (WHO) Director-General Dr. Margaret Chan called “a threat to the entire world”— have been reported in 27 countries across four continents. MERS is a type of coronavirus (MERS-CoV)—a common virus that infects the nose, sinuses, and throat—and a close cousin to the Severe Acute Respiratory Syndrome (SARS), infamous for infecting more than 8,000 in the early 2000s. As its name reveals, MERS is a respiratory illness, however, the symptoms are non-specific, and include coughing, sore throat, fever, chills, and muscle pain. The disease can quickly turn into pneumonia, and more than one-third of cases are fatal. History of MERS outbreaks The virus is believed to have passed from bats to camels, and within the last few years, from camels to humans. To date, there have been more than 1,400 lab-confirmed cases resulting in nearly 500 deaths, primarily in the Arabian Peninsula. For the first time since its discovery, a major outbreak has occurred outside of the Middle East, with 186 cases and 36 deaths in South Korea in recent months. Photo: PATH/Teresa Guillien MERS is not particularly contagious. One study from a spring 2014 outbreak in the Middle Eastsuggests that the average MERS patient—outside of a hospital setting—spreads the disease to just one other person. However, the Korean outbreak paints a different picture. Just one man is believed to have spread the disease to more than 20 people. Coronaviruses are particularly adept at mutating, and scientists initially feared that the virus had mutated to become more virulent. While an examination of genetic material from the Korean outbreak debunks this theory, the threat of mutation remains a real possibility. "The fact that MERS has spread around the world is not surprising. The question is, 'Where is it going to spread to next?' It could very easily come to America. Very easily. Any flight could contain someone who was infected in the Middle East." Michael Osterholm, director, Center for Infectious Disease Research and Policy, University of Minnesota Status of MERS R&D According to Ripley Ballou, vice president of Emerging Diseases at GlaxoSmithKline—the sixth largest pharmaceutical company worldwide—“everybody knows what the target for MERS is, it is the core spike protein […] a single protein that can be used to induce an immune response.” Despite this knowledge, there are currently no vaccines or drugs to prevent or treat MERS, and no large pharmaceutical companies have invested in MERS research & development (R&D). In the case of diseases with sporadic outbreaks, investments in R&D can be risky for pharmaceutical companies; if the outbreak is contained, there may no longer be a commercial market for the finished products. However, as Dr. Adrian Hill, director of the Edward Jenner Institute for Vaccine Research at Oxford University, points out “there is no sign of MERS going away. It’s been around since 2012.” The disease is endemic to Saudi Arabia and Hill argues the government of Saudi Arabia could afford to fund MERS R&D. Currently, several small biotech companies and academic institutions are engaged in preclinical research for experimental MERS vaccines and drugs. Below GHTC examines the current R&D pipeline for MERS: Vaccines Greffex, Inc., a biotech company that specializes in the rapid development and production of vaccines, created an experimental vaccine for MERS in 2013, which was tested on mice the following year by the US National Institute of Allergy and Infectious Diseases (NIAID). Within just two months, Greffex produced and tested the vaccine and a complementary booster shot, which resulted in the production of protective antibodies—proteins developed by the immune system to fight a specific virus—in every single mouse. Greffex CEO John R. Price believes the company could produce a stockpile of vaccines for human clinical trials for “pennies on the dollar” in just three weeks, however the company could not afford costly clinical trials. “How long are we going to wait around and just follow these outbreaks before we get serious about making vaccines?" Adrian Hill, professor and director, Edward Jenner Institute for Vaccine Research, Oxford University Dr. Matthew Frieman, a professor of Microbiology and Immunology at the University of Maryland School of Medicine, partnered with Novavax, Inc. to develop and test another experimental vaccine for MERS. This candidate also triggered the production of antibodies in mice and was tested in conjunction with a booster, and similarly, progress has ground to a halt, due to the lack of funding for clinical trials. “There's nothing standing in our way from pushing this forward other than the money and the will to do it,” Dr. Frieman told the International Business Times. Fortunately, human clinical trials are planned for a third candidate, developed by a team of researchers at the Ludwig Maximilian University of Munich, thanks to funding from the German Center for Infection Research. Rather than using antibodies against MERS-CoV, this vaccine triggers the recipient’s immune system to produce its own antibodies against the virus by introducing a weakened poxvirus that has been genetically altered to express the characteristic MERS-CoV spike protein. The body recognizes the poxvirus as foreign, and develops antibodies against that spike protein, without ever seeing the MERS virus itself. While three different vaccine candidates may seem like a foolproof defense against an outbreak, the work has only just begun. Clinical trials are not only expensive, but can take years to complete. For example, the US National Institutes of Health (NIH) announced the success of an Ebola vaccine in monkeys as early as 2000 and initiated a human clinical trial in 2003. However it wasn’t until 2006 that the results were published. While the vaccine seemed safe and effective, research ground to a halt until the recent Ebola outbreak in West Africa, and clinical trials continue to this day. Photo: PATH/Teresa Guillien Drugs Outbreaks are unpredictable, and given the costs and difficulty of vaccinating the entire world against MERS, treatment options are absolutely critical for this disease that kills more than one-third of those infected. In South Korea, two hospitals are testing an experimental treatment for MERS known as convalescent plasma therapy, which uses blood plasma from survivors of the disease to boost the immune response of a current patient. The technique was also tested in the ongoing Ebola outbreak in West Africa and the 2000-2003 SARS outbreak in southern China. During the SARS outbreak, it decreased mortality by 23 percent. Plasma therapy is fast and inexpensive, and while it isn’t “medically proven” it’s “often carried out in the absence of other treatments,” a representative of the Hallym University Medical Center told The Korea Times. In addition to his vaccine research, Dr. Frieman has partnered with Regeneron Pharmaceuticals Inc. to search for a treatment for MERS. The researchers genetically modified mice so that their cells would display the human version of a receptor protein—known as DPP4—to which the MERS virus attaches during an infection. This allowed them to mirror the human immune response to the virus. The team then examined more than 1,000 antibodies from the immune systems of the mice and tested the ability of those antibodies to prevent the MERS virus from latching on to human cells (via the DPP4 receptor). Left with 30 promising antibodies, the team needed to find two different antibodies that would not compete against each other and could be paired together, thereby producing a treatment that would be more effective against the mutability of the virus because it contained two different antibodies. The team identified two such antibodies that could work together, known as REGN3051 and REGN3048. Dr. Frieman is also exploring the possibility of using drugs which are approved for other conditions to treat MERS. With NIAID funding, Frieman tested 290 different compounds, 27 of which were active against MERS-CoV in test tubes. The team will next examine the efficacy of these compounds in combatting MERS-CoV in mice. Several of these compounds are the basis of treatments for cancer or psychiatric conditions; similarly, Zoloft and Vascor—drugs for depression and angina, respectively—have been shown to be effective in combatting Ebola in mice. Scientists at Purdue University have discovered a certain enzyme that plays a key role in the replication of the MERS virus, calling it the “Achilles’ heel of the virus.” They have since identified molecules that can stop the enzyme, making it much harder for the virus to replicate. However, that same molecule actually helped the virus spread at low doses, so determining the perfect amount of the molecule to administer will be a major barrier to translating their findings into a safe and effective treatment. Other treatments are in development as well. Shanghai Kaibo Pharmaceutical plans to unveil an injectable treatment for MERS, however no information on the product has been released. Researchers at Fudan University in Shanghai, China have partnered with the NIH to develop an antibody against MERS known as m336 that they believe is even more promising than other antibodies against the virus. As with vaccine candidates, the search for drugs and treatments against MERS is far from over. Not only do vaccines, medicines, and other tools need to be tested in clinical trials, but they need to be manufactured and distributed in adequate quantities to ensure a rapid response to an outbreak. Since its discovery in 2012, MERS has been widely considered a contender for the next major outbreak, or even pandemic. Researchers and public health advocates alike are wondering: will we learn from the Ebola outbreak and invest in R&D to create the tools needed to respond to a MERS pandemic, or will we wait until it’s too late?

The US Food and Drug Administration (FDA) approved the first 3D-printed drug last week, paving the way for the technology to be used to customize medical care to individual patients. 3D printing is a manufacturing process that involves using a computer to create an object one layer at a time. In the case of the recently approved Spritam—a treatment for epilepsy—the printing allowed for greater control over formulation of the drugs, resulting in the creation of the first 1,000 milligram tablets that remain easily dissolvable despite their large size. The use of 3D printers could ultimately enable hospitals to produce their own medicines, adjusting the dose for individual patients. Meanwhile, at the University College London School of Pharmacy, researchers are exploring the possibility of using 3D printing to create uniquely shaped drugs. Drugs are absorbed at different rates depending on the surface area and volume of the tablet, and by adjusting the shape of a tablet (i.e., creating a pyramid or doughnut shaped pill) the rate at which a drug’s active ingredients are released could be manipulated. Leaders at the FDA and the US Department of Health and Human Services propose mechanisms and protocol to expedite drug development in public health emergencies in The New England Journal of Medicine, stating “if we are to act on lessons learned [from the Ebola outbreak] there is no time to waste.” The authors note that limited research capacity delayed the testing of experimental treatments, calling for efforts to strengthen clinical trial infrastructure globally. The outbreak also prompted debate about research ethics in emergency settings (i.e., whether it was ethical to administer untested therapies and the ethics of using placebos in an outbreak). Consequently, the authors recommend that processes for ethical review of studies in outbreaks be streamlined. Finally, the authors stress the need for coordination between health and regulatory authorities, researchers, and product developers. In the Ebola outbreak, the US government partnered with West African governments, academic institutions in both regions, and product developers at every stage. Clinical trials of different therapies were conducted concurrently, allowing partners to have a single, shared control group. The authors note that to facilitate collaboration for rapid drug development in outbreaks, there is a need to establish “model agreements” regarding data management and intellectual property rights. BiondVax Pharmaceuticals announced last week that those vaccinated with an experimental flu vaccine in 2012 had stronger immune responses to strands of influenza that didn’t even exist three years ago. The vaccine was developed to provide broad protection against different strands of influenza, in contrast to the seasonal flu vaccine which protects against the three to four strands of influenza predicted to be the most virulent that year. In 2012, the vaccine (M-001) was tested in phase II clinical trials in which 90 participants—all aged 65 or older—received the vaccine and 30 served as the control group. The vaccine successfully triggered an immune response, including the development of antibodies against several different strains of influenza. Earlier this year, BiondVax exposed blood plasma collected from participants in the 2012 trial to a strain of influenza that did not exist in 2012, and discovered protective antibodies against the strain in 50 percent of the plasma samples from those that received the vaccine, compared to just 10 percent of the samples from those in the control group. As BiondVax’s President Ron Babecoff explains, the vaccine “provides a safety net by broadening the immunogenicity [immune response] to existing and future flu strains.” Next, the vaccine will be tested in phase 3 clinical trials. Blood smear revealing Trypanosoma brucei parasites, which cause African sleeping sickness. (Photo: CDC/ Dr. Mae Melvin) A simple innovation—blue cloth and fine netting sprayed with insecticide between two sticks—could wipe out African sleeping sickness in a mere five to six years. African sleeping sickness is transmitted by tsetse flies, which breed along rivers looking for “something that contrasts with the green vegetation,” according to entomologist Steve Torr, “and for some reason they’re especially attracted to bright blue.” The flies are attracted to the blue cloth and the insecticide kills them within three minutes. The contraption is currently being tested in northern Uganda, where more than 17,000 have been installed over 1,500 square miles; in less than two years, the population of tsetse flies has been reduced by 90 percent. Only 1 in 1,000 flies carry the parasite, and the flies only reproduce once every nine days—whereas mosquitoes lay hundreds of eggs each day—bringing Torr’s team to the estimate of five to six years to both reduce the tsetse population, and eliminate the parasite from the remaining population.