Breakthroughs Blog: Malaria

Photo: Medicines for Malaria Venture The Medicines for Malaria Venture (MMV)—a member of the GHTC—and the University of Dundee’s Drug Discovery Unit have developed an antimalarial compound that could treat drug-resistant cases of malaria with a single dose. The compound has been tested in both human blood and mice and the researchers involved believe it could ultimately be administered for only US$1 per dose. MMV has entered an agreement with pharmaceutical company Merck KGaA to advance the compound through the research and development (R&D) pipeline, transferring the rights to develop and commercialize any resulting product. Researchers at the US National Institutes of Health (NIH) have developed a vaccine that has protected against leishmaniasis in monkeys. Leishmaniasis infects one million people per year and is caused by the Leishmania parasite, transmitted through the bite of phlebotomine sand flies. Scientists noted that monkeys bitten by uninfected phlebotomine sand flies were less susceptible to future infections, and subsequently determined that a protein in the flies’ saliva—known as PdSP15—triggers an immune response. Seven of ten monkeys receiving an injection of PdSP15 developed immune cells against the Leishmania parasite and were significantly less likely to get the disease than members of the control group. Human cells also reacted to PdSP15 in a laboratory setting, indicating the potential of the protein in protecting humans from leishmaniasis. The fastest and most accurate tuberculosis (TB) test is expensive—$17,000 per machine and an additional $10 per test—and not conducive for use in rural settings because it requires electricity, refrigeration, and access to a computer. The test, known as GeneXpert is significantly more sensitive than traditional TB diagnostics, and its use increases successful diagnosis by 39 percent. Its popularity among health officials and donors has demonstrated that there is a major market for TB diagnostics, and has galvanized private-sector investments in TB R&D. There are now 191 TB diagnostics in the pipeline, and the manufacturers of GeneXpert are working to make the technology cheaper and to develop a remote, cloud-based version of the test. Since 2010, the Pediatric Trials Network has been conducting research to determine the safety and appropriate dosage of different medicines for young children, including premature infants. Children are often excluded from clinical trials, due to issues of consent and communication, and consequently, many drugs are not tested on children before entering the market. The NIH-funded Pediatric Trials Network has gathered research from nearly 90 sites and 3,500 children across the United States, and the results have often been counterintuitive. Medical professionals often determine the appropriate dosage of a drug based on a child’s weight, however the Network’s research has indicated that underdeveloped organs, particularly in premature infants, may struggle to fully process the drugs, ultimately requiring a higher dose per pound.

The World Health Organization (WHO) released a statement last week calling for the publication of all data from clinical trials for drugs, vaccines, and medical devices. The pharmaceutical industry has made great strides in reporting the results of clinical trials since the establishment of the WHO International Clinical Trials Registry Platform. However, a report released in conjunction with the WHO statement demonstrates that negative or inconclusive clinical trial results often go unreported, and there is still a need to publish data from older clinical trials. The United States Centers for Disease Control and Prevention (US CDC) is partnering with the African Union to establish an African Centres for Disease Control and Prevention (African CDC) comprised of a Coordinating Center in Addis Ababa, Ethiopia—where the African Union is located—and five Regional Collaborating Centers across the continent. The purpose of the African CDC is to support and connect African ministries of health to monitor and respond to disease outbreaks. The US CDC will provide initial technical expertise and will sponsor ten African epidemiologists and two public health experts from the US CDC to staff the Coordinating Center and Regional Collaborating Centers. Dr. Jack Whitescarver, director of the Office of AIDS Research (OAR) at the National Institutes of Health (NIH), will step down in July after leading the Office for 15 years. Dr. Whitescarver first joined the NIH in 1977 and he was involved in the initial detection and monitoring of the HIV and AIDS epidemic in the United States. He was also a major player in the NIH’s HIV and AIDS outreach and education efforts, prior to the establishment of OAR in 1988. Under his leadership, OAR has supported both international and domestic research efforts, with a focus on HIV and AIDS in minority populations and in women and girls. The United States Patent and Trademark Office (USPTO) at the US Department of Commerce announced the winners of the 2015 Patents for Humanity program. The winners will be granted an expedited patent application, ex parte reexam, or ex parte appeal before USPTO. This year's winners include Sanofi—the manufacturer of a synthetic version of the antimalarial artemisinin—and Novartis, a pharmaceutical company that has discovered a class of compounds that show promise in fighting drug-sensitive and drug-resistant tuberculosis. Sanofi is partnering with GHTC members PATH and the Bill & Melinda Gates Foundation to produce synthetic artemisinin, while Novartis has provided TB Alliance—another member of the GHTC—with the compounds to continue the research and development of treatments for tuberculosis.

Scientists at Karolinska Institutet in Sweden have identified the protein that explains why people with blood type O are protected from coma and death resulting from severe cases of malaria. Plasmodium falciparum, the parasite responsible for nearly all fatal cases of malaria, releases the RIFIN protein, which causes red blood cells to stick to one another and restrict blood flow, resulting in tissue damage and death. The study, published last week, establishes that the RIFIN protein insufficiently attaches to type O blood cells, despite its strong adherence to type A blood cells. This results in different health outcomes for those with type O blood, as they avoid the severe effects of the parasite. An article in Al Jazeera explored the history of Ebola vaccine research and development (R&D) and the barriers to conducting clinical trials in Sierra Leone today. While Ebola vaccine research began more than ten years ago, multiple promising vaccine candidates have remained in limbo due to a paucity of funding. Last fall, the US government partnered with pharmaceutical companies to expedite the R&D of experimental Ebola vaccines in light of the epidemic in West Africa. The US Centers for Disease Control and Prevention (CDC) and pharmaceutical company Merck & Co. are preparing for clinical trials in Sierra Leone involving 6,000-8,000 health workers. Health workers have expressed concern regarding the safety of the vaccine, and outreach to health workers and potential participants—which the CDC plans to conduct a few weeks prior to the start of the trial—may present a greater challenge than originally anticipated. A new diagnostic device, called the Microlife Vital Signs Alert, could save up to 70,000 mothers each year by alerting health care workers when a woman is at risk of going into shock due to blood loss during childbirth, or if her blood pressure is dangerously high. The device, which only costs US $20, is easy to use and interpret, enabling health care workers—regardless of education and training—to identify when a woman needs to be taken to a hospital with a simple red light.

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.”