Breakthroughs Blog: Malaria

Penicillin, the world’s first antibiotic, works by targeting certain proteins—appropriately named penicillin-binding proteins (PBPs)—that play a critical role in building and maintaining the bacterial cell wall. Now, scientists at Harvard Medical School have identified another class of proteins which play a similar role and could be a target for the next generation of antibiotics. The road to discovery started in 2003, when it was determined that certain bacteria could grow without PBPs. In their absence, the proteins responsible for maintaining cell wall shape, elongation, division, and spore formation (SEDS proteins) continued to function normally, enabling the bacteria to thrive. SEDS proteins are found in more types of bacteria than PBPs, and consequently a treatment targeting SEDS proteins could have even broader application than penicillin. On February 22, the Obama Administration requested US$1.9 billion in emergency funding for the Zika response, and 181 days later, Congress has yet to approve it. Consequently, the Department of Health and Human Services (HHS) has shifted $81 million from other programs to support Zika vaccine research and development—$34 million of which will go to the National Institutes of Health (NIH) and $47 million of which will be allocated to the Biomedical Advanced Research and Development Authority (BARDA). Earlier this year, HHS repurposed $589 million in funding from the Ebola response to combat Zika, however, that funding will run out by the end of this month. The NIH will use its funding for human clinical trials of its leading Zika vaccine candidate, however, the agency will need an additional $196 million for additional trials and to advance a second and third candidate. BARDA’s funding will enable the agency to secure contracts and establish partnerships for Zika vaccine development, however, an additional $342 million will be required to continue its work. New research suggests that infection with the Plasmodium parasite, which causes malaria, could reduce the severity of Ebola infection. A team of scientists at the US National Institute of Allergy and Infectious Diseases has examined 1,868 blood samples from an Ebola treatment unit in Liberia—1,182 of which tested positive for Ebola—concluding that patients co-infected with malaria were 20 percent more likely to survive. These results held true even when controlling for the patient’s age and viral load. Viral load actually correlated with survival rates: those with the highest levels of Plasmodium had an 83 percent survival rate, compared to 46 percent of those only infected with Ebola. At the treatment center, all patients were provided with antimalarials, and consequently, treatment for malaria was not responsible for survival rates. While the reason for this trend remains a mystery, Drs. Emmie de Wit and Kyle Rosenke—the study’s lead scientists—suspect that an existing malaria infection expedites the immune response to Ebola, consequently increasing survival rates.

Researchers at the Durham University in the United Kingdom have received a US$100,000 grant from the Bill & Melinda Gates Foundation to test the feasibility of training dogs to detect malaria. Dogs have been trained to use their keen sense of smell to detect other diseases, including certain cancers, and studies suggest that malaria infection causes a distinct odor, and that unique chemicals can be found on the breath of patients. The team plans to recruit 400 children in the Gambia, including many who are currently infected with malaria. The children will wear nylon socks for 24 hours, which will then be used to train the dogs to identify malaria based on odors in the sweat and skin. If successful, this approach to malaria testing would be quick and cheap, and would not require any equipment or a laboratory setting. A new, commercially-available diagnostic can predict premature births, a critical tool as half of all preterm births occur in women without known risk factors. Between 2011 and 2013, the Utah-based Sera Prognostics enrolled more than 5,500 pregnant women at 11 sites across the United States, and confirmed that the quantity of two proteins in the blood can indicate risk for preterm birth. The test can be administered at 19 or 20 weeks into the pregnancy; pregnancy normally lasts 40 weeks and delivery before 37 weeks is considered preterm. The test—PreTRM®—tells a woman her percentage risk, and currently costs $945, however, Sera Prognostics is working with the Bill & Melinda Gates Foundation to develop tools more suitable for low-income countries. Startup NextGen Jane is developing a “smart tampon” that would collect menstrual blood each month and test for a range of diseases and conditions, including sexually transmitted infections, endometriosis, polycystic ovarian syndrome, uterine fibroids, cervical cancer, and more. Many of these conditions are asymptomatic, and consequently go undetected until significant damage has been done. The team at NextGen Jane has a working prototype—a device that siphons menstrual blood from tampons—and is conducting clinical trials for several of the diagnostics themselves, which identify biomarkers for different conditions in menstrual blood. The tool will connect to a database, allowing women to analyze the data and track their reproductive health over time. The team anticipates having a complete product—combined diagnostics and the delivery mechanism—within the next year, which will be commercially available within three to four years.

US Navy Lt. Kimberly Edgel, left, and Christian Baldeviano examine a positive malaria blood smear at Naval Medical Research Unit (NAMRU) 6 in Callao, Peru.This afternoon, the US Senate voted to protect critical medical research programs at the Department of Defense (DoD). In a vote of 66 to 32, the Senate approved Senator Durbin’s (D-IL) Amendment 4369 to the Fiscal Year 2017 National Defense Authorization Act (FY17 NDAA), which strikes sections 898 and 756 in the underlying bill, designed to enact enough restrictions and red tape on DoD medical research to effectively end all existing programs. With this vote, the majority of the Senate signified that medical research is a critical function of the DoD, and must continue to be a priority. Infectious disease and other medical research at DoD plays a vital role in serving the Department’s overarching mission: supporting our military men and women. Not only does DoD infectious disease research directly benefit service members overseas—who experience neglected infectious diseases alongside local communities—but it also plays a key role in domestic health preparedness initiatives that prevent, detect, and respond to infectious diseases that threaten the health of American civilians at home. Beyond threat reduction to Americans, DoD research can often be translated for other contexts, and serves as an important component of US global health efforts to address HIV and AIDS, tuberculosis, malaria, and neglected tropical diseases in low-income countries.For example, malaria, which threatens the lives of nearly 3.2 billion people in tropical and poor regions of the world, is also a significant threat to the operational readiness of the US military. More person-days were lost among US military personnel due to malaria than to bullets during every military campaign fought in malaria-endemic regions during the 20th century. Thanks to ongoing research at DoD, nearly all of the most effective and widely used antimalarials—used to protect our service members overseas and adapted for widespread use in endemic regions—were developed in part by US military researchers. DoD medical research is also critical to medical advances that directly benefit US civilians at home: One of every four vaccines approved by the US Food and Drug Administration in the last century was developed with the participation of DoD. The 2014 Ebola epidemic in West Africa offers yet another example: the Department’s quick work to advance the development of Ebola countermeasures and safety protocols during troop deployment to West Africa was vital to protecting lives of service members and civilians in the region and remains vital to ongoing response efforts.On May 25th, GHTC sent a letter to members of the Senate, urging them to uphold the DoD’s critical medical research programs and oppose provisions in Sections 756 and 898 of the FY17 NDAA, which would limit our nation’s ability to develop medical countermeasures necessary to protect our troops and save lives around the world.GHTC commends Senator Durbin’s leadership on a bipartisan effort to remove these troubling provisions and extend our thanks to the co-sponsors of Amendment 4369: Cochran (R-MS), Reid (D-NV), Blunt (R-MO), Mikulski (R-AK), Murkowski (D-MD), Murray (D-WA), Collins (R-ME), Feinstein (D-CA), Shelby (R-AL), Casey (D-PA), Gillibrand (D-NY), Baldwin (D-WI), Bennet (D-CO), Markey (D-MA), Brown (D-OH), Leahy (D-VT), Hirono (D-HI), Reed (D-RI), Menendez (D-NJ), Tester (D-MT), Coons (D-DE), Kirk (R-IL), Klobuchar (D-MN), Udall (D-NM), Boxer (D-CA), Schatz (D-HI), Moran (R-KS), Sanders (D-VT), Warren (D-MA), Cardin (D-MD), Schumer (D-NY).

Ebola is hard to diagnose in low-resource settings. It requires specialized laboratories and trained personnel, blood samples must remain in cooled containers when transported from health clinics to labs, and the test itself takes several hours. However, researchers at the American Chemical Society have developed a handheld device that can diagnose Ebola and determine a patient’s viral load in less than 40 minutes. The tool tests four samples at once—two from the patient and two controls—and requires a small amount of blood which can be obtained via finger prick. The team hopes that the device could also be used to monitor the virus in survivors' semen and breast milk, which is particularly critical as increasing evidence suggests the disease remains transmissible through bodily fluids long after a patient has recovered. During their time at the International Institute of Water and Environment in Burkina Faso, two students developed a shea butter–based soap to fight malaria, using lemongrass and other oils that are natural mosquito repellants and larvicides. The students received a US$25,000 grant from University of California Berkeley as part of the Global Social Ventures Competition and are now hosting a crowdfunding campaign to finance the testing and production of the soap. The inventors, Gerard Niyondiko of Burundi and Moctar Dembele of Burkina Faso, hope that with adequate funding the soap could save 100,000 lives by 2018. In addition to the benefits of using the soap—which repels mosquitos for several hours after use—the discarded soapy water is expected to kill mosquito larvae, as it is often thrown into the street or dumped in stagnant water. The bacteria Bacillus thuringiensis israelensis has been approved for use as a pesticide by the US Environmental Protection Agency, as it kills mosquito and blackfly larvae but does not harm humans. However, its use in mosquito control was expensive until Dr. Palmira Ventosilla, a microbiologist at the Universidad Peruana Cayetano Heredia in Lima, Peru, devised an innovative system of delivery. Ventosilla has created kits for individuals, without any scientific training, to inoculate coconuts with the bacteria at home. The coconuts are then opened and left in small bodies of water (i.e., ponds), eliminating 90 percent of mosquito larvae within four days and keeping the water larvae-free for twelve days. The mosquitoes don’t develop resistance to the bacteria, as they do with chemical pesticides, and the bacteria is completely safe—even in human drinking water.