Breakthroughs Blog: Diagnostics

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.

GHTC member the Drugs for Neglected Diseases initiative will test an affordable hepatitis C regimen in Malaysia and Thailand, with a guarantee from generic drug manufacturer Pharco Pharmaceuticals that, if successful, the product will be priced at no more than US$294 for the entire regimen. The regimen combines the registered drug sofosbuvir with the candidate ravidasvir, a promising treatment that cured up to 100 percent of patients with Hepatitis C genotype 4—the most common strain of the virus in the Middle East and Africa—in a phase 3 clinical trial in Egypt. The phase 2 and 3 trials in Malaysia and Thailand will test the regimen among 1,000 patients with different genotypes and the trial will be open to patients with varying levels of liver damage and those co-infected with HIV and AIDS. PATH announced last week that two new rapid diagnostics for onchocerciasis (river blindness) and lymphatic filariasis (LF) are now commercially available. Onchocerciasis and LF are neglected tropical diseases, caused by parasitic worms, and spread by blackflies and mosquitoes, respectively. Onchocerciasis primarily affects the skin and eyes, resulting in itching, skin nodules, and blindness, while LF damages the lymphatic system resulting in physical disfigurement and disability. The tests were developed by PATH in partnership with the US National Institutes of Health and Centers for Disease Control and Prevention and will be commercialized by Standard Diagnostics/Alere moving forward. The new tools include a diagnostic for LF and another that tests for both diseases simultaneously. Both provide results in just 30 minutes and can be stored at temperatures ranging from 1 to 40°C (34 to 104°F). These tools offer significant improvements over existing diagnostics for LF and onchocerciasis. Previously, diagnosing LF required health workers to draw blood at night, when the parasites are active and consequently detectable, while onchocerciasis tests relied on a skin snip—the removal of inflamed skin. The tests will be invaluable for surveillance, control, and elimination programs. Researchers from Canada and Mexico are using old tires and milk to reduce the population of Aedes aegypti mosquitoes, which carry the dengue, chikungunya, yellow fever, and Zika viruses. The device, known as an Ovillanta, is comprised of two 50-cm (20-in) sections of old tires—in which A. aegypti mosquitoes often breed—that are stacked to form a mouth-like shape. The Ovillanta is then filled with milk and a piece of wood or paper that floats like a raft. A. aegypti mosquitoes secrete a hormone when they lay eggs, which other mosquitoes use to identify ideal breeding spots. This hormone is initially added to the milk in the Ovantilla, and the mosquitoes are drawn to it, laying their eggs on the floating wood/paper, which are then collected and destroyed. The Ovillanta is an adaptation of the ovitrap, which uses a bucket and water rather than old tires and milk. The team, funded by Grand Challenges Canada, has been testing the Ovillanta in Sayaxché, Guatemala, and over ten months, the Ovillanta has proven seven times more effective than standard ovitraps. The team will next test the device throughout the region and have shared the design online so that anyone can create one for personal use.

As 2015 draws to a close, the Global Health Technologies Coalition is reflecting on the past year in global health innovation. Below, in no particular order, are our picks for the top global health research and development (R&D) news and stories that shaped 2015. First ever vaccine against dengue virus approved The world’s first vaccine against dengue fever was approved by the national regulatory authority of Mexico, marking an important initial step in preventing this mosquito-borne infection, which is spreading worldwide. Nearly half the world’s population now lives in dengue-endemic countries, and an estimated 390 million infections occur each year. The vaccine’s developer Sanofi spent over 20 years and US$1.65 billion developing the vaccine and is now pursuing regulatory approval in 19 other countries. Sanofi has stated it will make the vaccine available for sale at a “fair, affordable, equitable, and sustainable price.” NIH finally receives funding boost Christmas came early for the US National Institutes of Health (NIH). After years of stagnated funding, NIH—the world’s leading public funder of neglected disease R&D—will finally receive a funding boost in 2016. In the fiscal year 2016 omnibus spending package, Congress approved a $2 billion—nearly 7 percent—increase in funding for NIH from $30 billion to $32 billion. NIH has lost 22 percent of its purchasing power since 2003 due to inflation, so this boost will provide critically-needed funding for the agency to continue to build upon its record of leadership in global health R&D. Photo: PATH/Satvir Malhotra Availability of the first child-friendly, appropriately-dosed TB medicines announced Health workers will soon have a critically-needed new tool to improve treatment for the one million children infected with tuberculosis (TB) each year. In November, TB Alliance and partners announced that the first-ever appropriate, child-friendly tuberculosis (TB) medicine in the correct dose will be available in early 2016. At the moment, TB medicines are not available in appropriate doses for children, so parents must crush or cut the pills to administer. This arduous process—combined with the bitter taste—leads to poor adherence. The new treatments are strawberry- and raspberry-flavored, appropriately-dosed versions of the three most commonly used TB medicines. These new treatments are expected to significantly improve TB treatment and adherence among children. Global Health Innovation Act passes House An important new piece of global health legislation championed by GHTC—the Global Health Innovation Act—passed the US House of Representatives earlier this month. This legislation would strengthen global health R&D programming at the US Agency for International Development (USAID) by directing USAID to incorporate R&D across its global health programming and requiring the agency to report annually to Congress on its R&D programs and activities. In 2016 the hard work will begin again to get the Senate to introduce and pass companion legislation so the bill can move another step closer to becoming US law. Ebola product development advanced at lightning speed After years of slow and stunted progress in the development of drugs, vaccines, and diagnostic tools to fight Ebola, product development jumped forward by leaps and bounds in 2015. Thanks to the collaboration of developers, regulatory agencies, and the World Health Organization, six Ebola diagnostics were developed and deployed in West Africa under emergency measures, early-stage clinical trials are underway for at least two Ebola drug candidates with others in development, and at least 15 vaccine candidates are in development with two candidates undergoing Phase II/III trials. The most advanced vaccine candidate VSV-EBOV was shown to offer near-total protection, according to preliminary data analysis from the trials. While these products arrived too late to have a major impact during the epidemic, the accelerated development approaches and mechanisms used may be able to be emulated to speed product development in the future. New pediatric malaria treatment receives positive scientific opinion paving path for regulatory approval A new pediatric malaria medicine— Pyramax® Granules—will soon be available for children worldwide. In November, Pyramax® Granules received a positive scientific opinion from the European Medicines Agency (EMA) under Article 58, a mechanism which facilitates regulatory approval of the product in malaria-endemic countries. The medicine, which was developed by Medicines for Malaria Venture (MMV) in partnership with Shin Poong Pharmaceutical Co. Ltd, is a combination of two antimalarials and is designed to be easy for children to consume. It is taken in liquid form and is flavored to mask the bitter taste. Next, MMV and Shin Poong will work to introduce Pyramax® Granules as well as Pyramax®, the tablet version which is suitable for adults, in malaria-endemic countries. Several promising global health products advancing through development The pipeline of global health technologies is growing and maturing with several exciting products moving through critical development stages. For example, a new medicine for drug-resistant TB became the first new TB drug to advance into clinical trials in six years when it entered Phase I trials in February, a vaginal microbicide containing a novel antiretroviral drug to prevent HIV entered Phase I trials in November, a drug candidate with the potential to become the first ever, oral-only, single-dose treatment for sleeping sickness completed Phase I trials in September, and a microbicide vaginal ring is completing Phase II trials with results expected in early 2016. Due to increased attention and investment over the last 15 years, there are now nearly 500 neglected disease product candidates in the pipeline. Global goals recognize importance of health R&D In September, global leaders ratified a new set of global goals, called the Sustainable Development Goals (SDGs), which will guide global development efforts for the next 15 years. GHTC was excited to see these goals recognize the importance of global health R&D with inclusion of a target supporting R&D of vaccines and medicines for diseases primarily affecting developing nations. It’s been broadly recognized that we cannot reach the ambitious SDG health targets—to reduce maternal and child mortality and end the epidemics of HIV/AIDS, TB, and neglected tropical diseases— by 2030 with the health technologies we have today. Now that the goals and targets are in place, accountability is key. We must ensure the SDGs translate into greater investment and political commitment from all nations to catalyze development of the next generation of health technologies needed to transform global health.

Photo credit: TB Alliance GHTC member TB Alliance announced last week the creation of the first-ever child-friendly tuberculosis (TB) medicines, which are currently undergoing regulatory review by the World Health Organization and should be available in early 2016. While TB is curable, a patient must take multiple drugs a day for six months, and existing medicines are not available in appropriate doses for children. Consequently, parents must crush or cut the pills. This arduous process—combined with the bitter taste—makes the six-month regimen difficult to follow. The new treatment is comprised of strawberry- and raspberry-flavored, child-friendly doses of the three most commonly used TB medicines. The new regimen is expected to significantly enhance adherence to treatment for the 1 million children diagnosed with TB each year. Researchers at Texas A&M University have developed a device that, when attached to a smartphone, can diagnose malaria in minutes. Using a polarized light and the phone’s camera, the device serves as a microscope. The photos taken by the device are then analyzed by a software app that diagnoses infection by counting both red blood cells and Hemozoin crystals, which are produced by the malaria parasite. The device, which is expected to cost less than US$50 and be used with cartridges costing $1 each, will be tested in Rwanda next summer. A preclinical study conducted by GHTC member Population Council in partnership with CONRAD suggests that candidate microbicide gel MZC could be even more effective against HIV than tenofovir gel, a leading microbicide candidate. Containing a potent antiretroviral, a zinc-based salt, and the compound carrageenan, the gel is intended to protect against HIV, human papillomavirus (HPV), and herpes simplex virus 2 (HSV-2). The study demonstrated that MZC was more potent than tenofovir against both HIV and HSV-2. While the study did not test the gel’s efficacy against HPV, existing research suggests that carrageenan is one of the most potent compounds against HPV. Next, MZC will be tested in delivery systems, including vaginal rings and rectal gels, as well as in combination with a hormonal contraceptive. In other microbicide news, GHTC Member the International Partnership for Microbicides (IPM) has entered an agreement with pharmaceutical company Janssen Sciences that provides IPM the rights to develop a microbicide using the antiretroviral darunavir, which is currently available in pill form and marketed as PREZISTA®. IPM is also conducting a phase III clinical trial of a vaginal ring using antiretroviral dapirivine, licensed to the organization through a partnership with Janssen initiated in 2004.