“Elimination” is a bold word when addressing a disease that strikes more than 216 million people and kills another 445,000 worldwide every year.
But for scientists across the UC system, malaria elimination is a goal, whether it involves creating genetically altered strains of mosquitoes to control malaria transmission, developing tools, strategies and partnerships with nations and regions who share the elimination goal or generating evidence on the cost-effectiveness of eliminating malaria.
From genetically modified mosquitoes to novel treatments
A team of scientists from six UC campuses, led by UC Irvine biologist Anthony James, are cultivating new strains of mosquitoes to fight malaria in Africa. “Our goal is to see if prototype strains developed in partnership with UC San Diego geneticists Valentino Gantz and Ethan Bier can be refined into something appropriate for disrupting malaria transmission in Africa,” James said.
The three scientists are also part of a group, led by UC Riverside entomologist Omar Akbari, studying an innovative genetic technique called “gene drive,” which has the potential to spread desirable genes in wild populations and suppress harmful organisms.
Other UC research focuses on treatment of the disease. Most recently, an international team, including researchers from UCSF Global Health Group’s Malaria Elimination Initiative (MEI) discovered that two different compounds—one, an older malaria drug, the other a common laboratory dye with known antimalarial properties—can safely and effectively be added to treatment regimens to block transmission of the most common form of malaria in Africa.
This development could help reduce the spread of P. falciparum malaria, including its drug-resistant forms, thus speeding progress toward elimination of the disease.
“Although these two drugs have been around for more than half a century, this is the first time that the exciting and impressive effects of each of these drugs on malaria transmission have been so clearly demonstrated in a comparative study,” said Roly Gosling, MEI director and UCSF professor of epidemiology and biostatistics. “Now we can say that the effectiveness of common malaria drugs used for seasonal malaria chemoprevention can be improved, with the potential of removing the threat of malaria to many millions of people across West Africa.”
The findings could help countries moving towards malaria elimination to rapidly reduce population-level transmission of the disease, but formal trials are needed to confirm the optimal scenarios in which these drugs can be used and how their use could be integrated with other malaria strategies and tools.
Meanwhile, at UC San Diego, an international research team led by principal investigator Elizabeth A. Winzeler, PhD, professor in the pediatric division of host-microbe systems and therapeutics in the School of Medicine, is developing new therapies to treat malaria.
“The very long-term goals are to accelerate the development of novel treatments and preventative medicines that can be used to assist with malaria eradication and elimination,” Winzeler said.
Yet another branch of UC research adding to the body of knowledge to help eliminate malaria is a new UC Irvine International Center of Excellence in Malaria Research (ICEMR). Led by Guiyan Yan, professor of public health, the UC Irvine ICEMR aims to assess the effect of human-induced environmental modifications, such as dams, irrigation and changing agricultural practices, on the transmission of malaria. The research based in Ethiopia and Kenya is important to malaria control, Yan said.
Supporting national malaria elimination efforts
While genetically modified mosquitoes, environmental efforts and new drugs are important in eliminating malaria, regional and national partnerships, advocacy to mobilize resources and models to finance the fight against malaria are just as important to drive away malaria and keep the disease from creeping back across borders.
Currently, UCSF’s MEI develops tools and guidance to support countries around the world that are working to eliminate malaria, a goal that several are on target to achieve by 2020, said Allison Phillips, deputy director and MEI founding member in 2008.
“We are considered the elimination experts among many malaria groups,” said Phillips. “And now we are pushing the malaria community to plan for global eradication.”
MEI’s 50 researchers and staff, part of the UCSF Institute for Global Health Sciences, include malaria scientists, spatial epidemiologists, economists, clinical trial investigators and public health specialists. They form an “action tank” that offers scientific evidence, new approaches and tools to country leaders, policymakers and funders.
“We affect practice, strategies and policies at the national, regional and global level. Then we follow up to make sure those changes in strategies or policies are working,” said Roly Gosling.
“Our work has always been impact-driven, so programs getting to zero malaria is our goal,” Gosling said. “To get to zero, we have to get the right interventions to the right people at the right time. Clinical trials alone don’t get to that.”
MEI’s “shrinking the malaria map” strategy has contributed to global efforts that have cut mortality rates in half since 2000 and reduced case incidence rates around the world by 18 percent. The 35 countries actively pursuing evidence-based malaria elimination goals have reduced their collective burden by 91 percent between 2000 and 2014.
Control at the borders
Elimination of malaria should be approached region by region and with collaboration among neighboring countries because mosquitoes carrying the malaria parasite know no boundaries. “Cross-border transmission is a major challenge to eliminating malaria,” said Allison Phillips.
In 2009, MEI – along with bodies such as the World Health Organization and the Southern African Development Community (SADC)– catalyzed the launch of the Elimination (E8) Regional Initiative-Southern Africa. MEI continues to support the development of E8’s strategic plan to eliminate malaria in Botswana, Namibia, South Africa and Swaziland by 2020 and progressively eliminate the disease in Angola, Mozambique, Zambia and Zimbabwe by 2030.
With more than four million registered migrants crossing SADC borders every year, there is a risk of the malaria parasite moving with them and undermining elimination efforts. To combat this risk, E8 countries are collaborating to expand access to timely diagnosis and treatment for mobile and migrant populations moving across the region’s porous borders. By doing so, they also conduct active surveillance – a key element of the elimination strategy – and identify and rid potential transmission reservoirs. The regional initiative deploys dozens of mobile malaria posts and surveillance teams across the borders of the E8 countries to detect malaria and provide care.
Investing in elimination
Despite all of the UC-led research and collaboration with countries to develop elimination plans, malaria cannot be eliminated if resources for low and middle-income countries dry up.
One of the greatest threats to malaria elimination, said Phillips, would be a reduction of the political and financial commitment required to eliminate malaria and prevent reintroduction.
“If you take your foot off the peddle, malaria can come back with a vengeance,” said Phillips.
Look at Sri Lanka, which implemented intensive malaria control measures and saw the number of cases drop from 2.8 million in 1946 to 17 in 1963. But when malaria became invisible to communities, politicians and national leaders, the country did not finish the job.
From 1963 to 1969, the number of cases in Sri Lanka surged to more than 500,000 because it did not sustain its earlier anti-malaria program. The country rebounded with new efforts in the 1990s, and in 2016 was certified malaria-free by the World Health Organization.
But now Sri Lanka faces the risk of re-importation from neighboring countries and it is important that the government sustain its investments in malaria elimination.
In the past two decades, the malaria fight has received unprecedented support from donors and national governments. The projects described above and other UC malaria research has netted more than $60 million in funding from donors in the past two years alone. But funding for some countries on the verge of eliminating malaria has peaked and is even starting to dip.
As a disease-fighting initiative, UCSF’s MEI is unique in that it extends analyses beyond public health and asks and answers critical questions about how malaria elimination efforts are financed and delivered in regions.
MEI generates new economic evidence by researching the costs and benefits of elimination, developing national and regional investment cases for elimination, monitoring financing flows to eliminating countries, analyzing the impact of policy and financing decisions on eliminating countries, studying the cost-effectiveness of interventions and assessing and recommending possible economic solutions.
MEI analysts point out that eliminating malaria in the Asia Pacific region by 2030 not only will save about 400,000 lives and prevent 123 million malaria cases in that region, it also will offer a 6 to 1 return on investment and return more than $90 billion in economic benefits.
The fight against malaria is at something of a tipping point and UC scientists are on the frontlines—from basic scientific research to advocacy, pushing a bold and ambitious agenda to elimination malaria.