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Authored by Elodie Jambert & Elizabeth Poll, Medicines for Malaria Venture, Switzerland; Panayota Bird, GSK; and Dr Marcus Lacerda, Fiocruz, Brazil  The Amazon is a renowned hotspot for biodiversity, but it’s also a hotspot for malaria. Brazil is one of the Latin American countries with the heaviest burden of malaria, with its Amazon region accounting for 99.5 percent of all national cases. Tackling malaria in Brazil is complicated by the fact that the vast majority of the burden is caused by the malaria parasite Plasmodium vivax. After causing an initial bout of malaria symptoms, this species of parasite has the ability to hide dormant in the liver of infected people, only to re-emerge and cause symptoms again several weeks to several months after initial infection. Another compounding issue is that the only medicine currently available to stop such relapse is primaquine–a medicine approved in the 1950s that must be taken for at least seven days. Given this lengthy course of treatment, many patients fail to complete the full course. It’s a challenge to explain to patients why they should take seven days of pills to treat something that appears to have resolved after the third day (the duration of treatment of the initial acute P. vivax malaria bout). As a result, the medicine often doesn’t work, and transmission of relapsing malaria is perpetuated. In Brazil, over the last 20 years, the burden of the more deadly Plasmodium falciparum has fallen from 50 to 10−15 percent. Yet, progress against P. vivax is yet to see the same success; this parasite now causes 89 percent of malaria cases. While P. vivax doesn’t kill as many people as P. falciparum, it is still debilitating, can also be lethal, and has substantial economic impact on families and nations. As such, it’s important to keep the attention of policymakers focused on malaria even in the face of other pressing public health issues, such as Zika and chikungunya viruses.A new solution for relapsing P. vivax in sightChildren in the village of Boa Vista, on the border of the Juma Reserve in the Brazilian Amazon. Photo: Neil Palmer/CIATFortunately, a new solution to tackle relapsing P. vivax malaria could be in sight. Medicines for Malaria Venture (MMV) and GSK have collaborated to develop a new, single-dose anti-relapse medicine, tafenoquine. The medicine was submitted for regulatory review to the US Food and Drug Administration and Australian Therapeutic Goods Administration at the end of 2017. If approved, it could be an important new treatment for individuals suffering from relapsing malaria, and could help to eliminate the disease in the Amazon.MMV and GSK have developed an access strategy together with in-country partners and are preparing the ground for the medicine’s potential launch in endemic countries. Country-level briefings are ongoing with the National Malaria Control Programmes (NMCP) in Brazil and six other endemic countries (Thailand, Ethiopia, Vietnam, Cambodia, Peru, and Colombia); their goal is to assess interest in introducing the new medicine into national practice and to understand what type of evidence NMCPs would need to support policy adoption. Developing diagnostics to make anti-relapse medicines safer for allPATH rapid diagnostic test to support treatment and elimination of P. vivax. Photo: PATHIntroduction of tafenoquine faces one additional challenge: As is the case with primaquine, people with a genetic deficiency in a specific enzyme known as glucose-6-phosphate dehydrogenase (G6PD) can suffer potentially serious side effects. On average, 8 percent of people in malaria-endemic countries are deficient in this enzyme. To reduce the risk of patients suffering this side effect, PATH is supporting development of a point-of-care diagnostic test to identify patients’ G6PD status and determine whether tafenoquine or primaquine can be safely administered. Concomitant use of this point-of-care diagnostic test will be critical for the correct and well-tolerated use of tafenoquine. Despite the World Health Organization’s recommendation that G6PD tests guide the use of primaquine, few endemic countries routinely use such testing today. In Brazil, the prevalence of G6PD deficiency varies depending on the immigration profile of the region. Most published papers on the subject estimate that the average prevalence among men in Brazil is around 5 percent, a statistic recently confirmed with preliminary data from a government-supported prevalence survey in endemic areas of the Brazilian Amazon.In light of this, additional data is being gathered. Initial preparations for an implementation study are underway in Brazil to demonstrate how a quantitative G6PD test would work in practice, prior to use of tafenoquine in the healthcare system. It is planned for the study to begin after regulatory approval of tafenoquine is granted. The team is also working with academics to model the cost effectiveness of the medicine paired with a G6PD test compared to current standard of care (primaquine without a test), as well as the potential impact of tafenoquine on malaria transmission and elimination. The Brazilian government will use these findings as it considers broader deployment of the intervention throughout malaria-endemic areas.Tafenoquine has potential for significant impact both for the individuals that suffer from this disease as well as for the regions focused on malaria elimination. We await the regulatory decisions on the medicine and will continue to work together as a team of partners to prepare the ground in the Brazilian Amazon to help make it malaria-free for all.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign-up now to receive our weekly R&D News Roundup email. In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. While wild poliovirus cases have dropped significantly over the years—with only 22 total reported cases in 2017—surveillance gaps still linger, making future progress in wild polio eradication more fragile. Three countries have yet to be declared free of wild polio transmission: Pakistan, Afghanistan, and Nigeria. Researchers found that health-facility surveillance was limited in these countries due to conflict situations. While community-based surveillance was effective in identifying cases, experts noted that more case searchers are needed in displaced persons camps and more community participation required to reach inaccessible areas. Researchers stressed that strong polio surveillance will still be needed long after eradication and after the oral poliovirus vaccine is discontinued. Researchers have created a new animal model to more effectively study Crimean-Congo hemorrhagic fever, according to new research published in Nature Microbiology. Crimean-Congo hemorrhagic fever, a viral disease spread by ticks, is fatal in nearly one of three cases, and there are no specific treatments or vaccines for the disease. To advance this research, scientists at the National Institute of Allergy and Infectious Diseases conducted a pilot study infecting African green monkeys, rhesus macaques, and cynomolgus macaques with the virus. While the first two monkey species showed no signs of disease, two of the three cynomolgus macaques developed the virus. In a larger study with the cynomolgus macaques, all of the animals developed the virus. Because this species developed the virus in the same way humans do, researchers believe this animal model will be useful in studying how infection interacts with the immune system and ultimately help scientists develop treatments and vaccines. Scientists at the University of Waterloo have developed a new tool to prevent HIV transmission in women. The tool, a vaginal implant that looks similar to an intrauterine device, decreases the number of cells that HIV can target within a woman’s genital tract. HIV infects the body by taking over T cells that the immune system mobilizes in response to the virus; however, if these cells remain in a resting state and do not attempt to respond to the virus, they are not infected. Scientists believe this tool, which releases a medicine to induce T cells into a resting state, could be a more reliable way to encourage the cells not to respond to infection, lowering the rates of HIV transmission. While more research is needed into the reliability and validity of the tool, scientists are optimistic that this may be a useful tool to protect women at high risk for developing HIV.

  Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign-up now to receive our weekly R&D News Roundup email. In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Extra iron in red blood cells may interfere with essential proteins that protect against malaria, according to a new study published in Science. Researchers at the National Institutes of Health discovered extra iron can interfere with the protein ferroportin—a protein that prevents toxic buildup of iron in red blood cells and helps these cells combat malaria. More so, researchers discovered a mutation of ferroportin in African populations that protects against malaria by shielding against a hormone that prevents iron from being removed from the cells. These findings regarding ferroportin help solve a long-standing mystery as to why iron supplements can sometimes worsen malaria infection, while iron deficiency can in some cases be protective. A newly published study suggests children infected with the Zika virus during infancy may be at risk of experiencing brain damage. Researchers infected infant monkeys with the Zika virus, and the monkeys subsequently showed brain changes in the hippocampus—the part of the brain involved in regulating emotions, memory, and spatial navigation. After a year of study, researchers noticed the brains of the infected animals progressed differently than the monkeys who were not infected with Zika, suggesting damage and stunting. Though Zika has been linked to brain damage when it infects a fetus in the womb, this research is to first to link brain damage in infants to Zika infection after birth. While more research is needed into how the Zika virus can affect human babies, researchers believe this data may help inform new parents traveling to Zika-endemic areas and clinicians monitoring infants exposed to the virus. A new blood test is able to predict tuberculosis (TB) development up to two years before onset in individuals living with someone with active TB, according to new research. While individuals who live with someone with active TB are at higher risk of developing TB, only between 5-20 percent of people infected with the TB bacteria actually develop active TB, which means a large number of people are given preventative treatment who may not need it. By jointly measuring the expression levels of four different genes associated with inflammatory responses, this test can more accurately predict the likelihood of developing active TB. Researchers conducted a retrospective study with participants living in homes with people with active TB and found positive results of the blood test in the healthy participants who then later progressed to active TB. While more research is needed on the blood test, researchers are hopeful this test could reduce the number of individuals receiving unnecessary preventative treatments.  

  Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign-up now to receive our weekly R&D News Roundup email. In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week.   A new study suggests that a newly discovered class of antibiotics could potentially wipe out drug-resistant staph infections caused by MRSA, raising hope for progress in the fight against antimicrobial resistance. Scientists at Rhode Island Hospital in Providence focused on MRSA because infection produces “persister” cells—cells that evade common antibiotic treatment by lying dormant in the body. The research team tested thousands of lab-made molecules on roundworms infected with MRSA and discovered two molecules from the retinoid family that not only killed normal MRSA cells, but also the “persister” cells as well. While these retinoids were not effective against another group of antibiotic-resistant bacteria that cause urinary tract infections, pneumonia, and other conditions; they still hold promise in treating persistent and antibiotic-resistant forms of MRSA, which can be lethal to patients. Scientists at Yale University have developed a new experimental RNA therapy, delivered via the nose, to treat West Nile Virus infections. In mice studies, the therapy reduced the viral load in the brain, allowing the organism’s immune system to properly destroy the remainder of the virus throughout the body as well as develop long-term protection against future exposure. By using RNA molecules that are effective against flaviviruses combined with a peptide derived from the rabies virus that is able to interfere with nerve cells and delivering them through the nose, scientists were able to bypass the blood-brain barrier to kill the virus in the brain with 90 percent effectiveness in the mice studies. There is currently no approved vaccine or effective therapy to treat West Nile Virus. A new study published in The Lancet Infectious Diseases suggests that the medication ivermectin can make human blood deadly to malaria-carrying mosquitoes, offering a new potential strategy to fight this deadly disease. Researchers at the Liverpool School of Tropical Medicine found that three high doses of invermectin—a medicine originally developed to combat river blindness and elephantiasis—made human blood toxic to mosquitoes for 28 days after the third treatment, while producing few side effects in patients. In lab tests, 97 percent of mosquitoes died within two weeks of feeding on the blood with ivermectin. While more research is needed, this discovery could offer a potential new approach to complement existing malaria control programs.