Breakthroughs Blog: Malaria

Photo: National Institute of Allergy and Infectious Diseases (NIAID) Gavi, the Vaccine Alliance, signed an advanced purchase commitment, pledging to spend US$5 million on an Ebola vaccine currently under development by pharmaceutical company Merck & Co. The vaccine candidate was tested on 4,000 people in Guinea last year, and the results were promising: despite all participants having close contact with at least one Ebola patient, none developed the disease more than ten days after vaccination (several days are required for a vaccine to confer protection). The vaccine candidate—VSV-EBOV—was developed and tested in partnership with the Canadian and US governments, however, without the urgency of an outbreak, public-sector support moving forward is limited. The agreement guarantees that there will be a market for the vaccine, assuring Merck & Co. that they can recover investments in advanced development and manufacturing. This move will also enable Gavi to establish a stockpile of the vaccine so that it can be rapidly deployed in future outbreaks. New research suggests that 2.6 million stillbirths occur each year, 420,000 of which are attributable to malaria or syphilis infections. These results underscore the need for testing and treatment of malaria and syphilis in pregnant women, particularly in endemic regions. Fortunately, there are low-cost interventions that could drastically reduce adverse pregnancy outcomes attributable to malaria and syphilis infections. The malaria parasite is able to reside in the placenta, even when undetectable in the mother’s blood, and thus, preventative treatment for malaria is critical. The antimalarial sulphadoxine-pyrimethamine, which costs a mere $0.20 per patient, is recommended for use in pregnant women in endemic areas. In east and southern Africa, an estimated 5 percent of pregnant women are infected with syphilis and in Tanzania, up to half of stillbirths are caused by syphilis. However, one dose of penicillin can cure both maternal and congenital syphilis and prevent stillbirth—at just $1.40 per person. While malaria- and syphilis-related stillbirths can be prevented with the scale-up of existing medicines, many more could be prevented with interventions that are not appropriate for low-resource settings, which is particularly concerning as 98 percent of stillbirths occur in low- and middle-income countries. Further, the cause of stillbirth is often unknown, according to the Global Alliance to Prevent Prematurity and Stillbirth, and additional research is needed to determine and address these causes. There is little incentive for pharmaceutical companies to invest in antimicrobial research and development (R&D): antibiotics are prescribed for short periods of time and competition among antibiotics keeps prices low. However, with the spread of drug resistance, the “[financial] value assigned to antibiotics and diagnostics often does not reflect the benefits they bring to society,” according to a declaration authored by 80 pharmaceutical and diagnostic companies and released at this year‘s World Economic Forum in Davos, Switzerland. The declaration calls on governments to work with the pharmaceutical industry to spur antimicrobial R&D, identifying innovative financing mechanisms, including prizes (a Market Entry Rewards initiative) and intellectual property–related incentives. In response, the companies pledge to invest in R&D for new antibiotics, as well as improved diagnostics to prevent the unnecessary use of antibiotics (i.e., for viral conditions).

President Obama 2016 State of the Union address. Photo: White HouseGHTC has long championed US leadership in global health and innovation, and we were encouraged to see President Barack Obama highlight these themes in his State of the Union address.On combating the 2014 Ebola epidemic in West Africa, the president highlighted a coordinated domestic and international effort to leverage expertise, resources, and value-add of all partners—a strategy we support for advancing global health R&D. He stated: Fortunately, there’s a smarter approach, a patient and disciplined strategy that uses every element of our national power. It says America will always act, alone if necessary, to protect our people and our allies; but on issues of global concern, we will mobilize the world to work with us, and make sure other countries pull their own weight… That’s how we stopped the spread of Ebola in West Africa. Our military, our doctors, and our development workers set up the platform that allowed other countries to join us in stamping out that epidemic. The president also discussed US investments in global health and development as a core piece of American foreign policy and national security, nodding to the Global Health Security Agenda, which coordinates domestic and international efforts to prevent, detect, and respond to global disease epidemics. In addition, his message called for renewed commitment and funding for US efforts to end the epidemics of HIV and AIDS and malaria: Leadership means a wise application of military power, and rallying the world behind causes that are right. It means seeing our foreign assistance as part of our national security, not charity. When we help African countries feed their people and care for the sick, that prevents the next pandemic from reaching our shores. Right now, we are on track to end the scourge of HIV and AIDS, and we have the capacity to accomplish the same thing with malaria — something I’ll be pushing this Congress to fund this year. President Obama also highlighted the transformative power of medical research to end endemic and emerging health threats: For the loved ones we’ve all lost, for the family we can still save, let’s make America the country that cures cancer once and for all. Medical research is critical. GHTC is pleased to see President Obama echo themes we have long advocated: partnerships and innovation are key to advancing health at home, and around the world.To curb the spread of emerging disease epidemics, we will need domestic and international commitment to work together and develop new tools and technologies to monitor, track, diagnose, and treat infectious disease. To finally end the scourge of malaria and achieve an AIDS-free generation, we will need renewed commitment to develop innovative vaccines and treatments that move us beyond current interventions. To cure noncommunicable diseases and other health challenges that plague developed and lower-income countries, we need continued investment in research and development for health technologies.GHTC looks forward to working with the president and his administration to drive these issues forward in 2016.

A recent clinical trial found that convalescent plasma therapy, a treatment in which the blood plasma is taken from survivors of a disease and used to treat current patients, did not prove to be effective against Ebola. The blood plasma of survivors includes antibodies against the pathogen, in this case the Ebola virus, which can boost a patient’s immune response. Convalescent plasma therapy has been used for more than 100 years, and was first used against Ebola in 1976. In the trial, plasma therapy was used to treat 84 patients, and an additional 418 patients that had been treated at the same facility served as the control group. The treatment reduced death rates by a mere 2.6 percent, and the result was not statistically significant. However, the trial did demonstrate that the collection and transfusion of blood plasma from survivors to patients was safe and feasible in low-resource settings. During the trial, the therapy did appear to be particularly effective in pregnant women and infants, however, the sample size was too small to confirm. Plasma samples from the trial will now be sent to a facility in France where researchers will assess the concentration of antibodies in the samples to determine if the quantity of antibodies affected survival rates. A recent study suggests that the antimalarial artesunate/amodiaquine (ASAQ) could be more effective against Ebola than artemether/lumefantrine (AL), an antimalarial previously used to treat Ebola, due to the diseases’ overlapping symptoms. During the outbreak, a Médecins Sans Frontières treatment center in Liberia initially used AL to treat patients, however, after running out of AL, they began to use ASAQ. The death rate for patients receiving ASAQ was 50.7 percent, compared to 64.4 percent of patients on AL. While ASAQ appears to be a promising treatment, additional trials are needed to investigate ASAQ’s efficacy in reducing Ebola mortality. Strains of the bacteria responsible for the sexually transmitted infection gonorrhea are becoming increasingly resistant to antibiotics. In the United States, one-third of gonorrhea cases are resistant to at least one antibiotic. Public officials, both in the United States and Britain, are urging doctors to follow prescription recommendations to prevent the spread of drug-resistant strains. In Britain, many doctors continue to prescribe ciprofloxacin, which has not been recommended for gonorrhea in 10 years. In the United States, doctors have historically prescribed ceftriaxone, however, between 2011 and 2013—after new guidelines led doctors to prescribe ceftriaxone in combination with azithromycin—ceftriaxone-resistant strains decreased by two-thirds from 1.4 percent to .4 percent of cases. Cow standing in a grassy field. (Photo: PATH/Eric Becker) The bacteria Mycobacterium bovis, which causes bovine tuberculosis (TB), is a rising cause of human TB, and while it’s responsible for just 1.4 percent of cases globally (and 1.5 percent of cases in America), up to 44 percent of TB-infected Latino Americans have the bovine version. Bovine TB is found in two dozen mammal species and is usually transmitted to humans through unpasteurized dairy products. In Mexico, 40 percent of dairy products are unpasteurized, and consequently the proportion of bovine TB cases among Americans are highest along the US-Mexico border. Two-thirds of bovine cases in the United States are extra-pulmonary—outside of the lungs—and are consequently undetectable by standard diagnostic techniques. The remaining third, confined to the lungs, could presumably be spread between humans through coughing or sneezing.

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.