Researchers Highlight Urgent Need For New Malaria Treatments

For more than 20 years, Dr. Roland Cooper, professor of biology at Dominican University of California, and his students have investigated the molecular mechanisms of how drugs work against the human malaria parasite, Plasmodium falciparum, both in the laboratory and in Africa. Dr. Cooper came to Dominican in 2011 from Old Dominion University in Norfolk, Va. Prior to that, he was a post-doctoral fellow at the National Institutes of Health's Laboratory of Parasitic Diseases from 1997-2002.

Dr. Cooper’s research focuses on parasite drug resistance, which has complicated malaria control ever since the emergence of chloroquine resistance in the late 1950s. Currently, resistance to the components of artemisinin combination therapies (ACTs), the worldwide standard treatment for Plasmodium falciparum malaria, is a serious concern in Asia and now appears to be emerging in areas of Dr. Cooper’s studies in Uganda.

Malaria parasites, transmitted by female mosquitoes of the genus Anopheles, infect and destroy the red blood cells of their human hosts, resulting in nearly half a million deaths from the hundreds of millions of clinical cases annually. According to the World Health Organization, malaria is, in fact, resurgent in Africa and other areas due to the lack of safe, affordable and efficacious drugs available for impoverished populations and decreased support control interventions such as bed nets and insecticide spraying for mosquitoes.

Furthermore, effective malaria vaccines for malaria are in the early stages of testing, and likely are years away from having a significant impact on disease burden. The impact of COVID-19 on malaria control has yet to be determined, but badly needed resources are being diverted away from malaria control efforts.

Last September, Dr. Cooper and his team published a milestone paper in the journal Lancet Microbe, entitled “Drug susceptibility of Plasmodium falciparum in eastern Uganda: a longitudinal phenotypic and genotypic study.” The report shows that the genetics of the parasites circulating in the region have evolved over the last decade, resulting in dramatically altered sensitivity to several drugs currently used to treat malaria. The authors surmise that these changes correspond to the introduction of the ACT used to treat malaria, called CoArtem, based on the Ugandan national malaria treatment policy established in 2006. This knowledge of how parasites have evolved under widespread CoArtem usage can guide recommendations for treatment strategies against the disease in the near future. The 10-year study was led by Dr. Cooper and Dr. Philip Rosenthal from the Department of Medicine at the University of California San Francisco (UCSF). Several Dominican University biology and chemistry students in the School of Health and Natural Sciences provided valuable experimental by working in Africa and appear as co-authors on the study.

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Additionally, co-author Dr. Brett Bayles from Dominican’s Global Public Health program performed the complex statistical analysis, and critical support with the genetic analysis of the parasites came from researchers at UCSF and Brown University in Rhode Island. Importantly however, Dr. Cooper gives praise to their talented Ugandan colleagues, led by Patrick Tumwebaze, who has been with the team since 2008, in studying data from nearly 1,000 malaria patients for the project.

“Without the diligence, guidance and support of our team members in Uganda, studies of this magnitude and complexity would not be possible,” Dr. Cooper noted.

The need for new and innovative approaches to malaria therapies was further underscored in a Viewpoint article published last month in the The Journal of Experimental Medicine by Dr. Cooper and Dr. Laura Kirkman from Weill Cornell Medicine. The opinion piece examines how repurposing older, well-studied drugs utilized for other diseases could play a role in controlling malaria.

“Innovative drug treatments for malaria, optimally with novel targets, are needed to combat the threat of parasite drug resistance,” the co-authors write. “As drug development efforts continue, there may be a role for a repurposed cancer drug administered together with an artemisinin combination therapy that was shown to improve the speed of recovery from a malaria infection.” The authors highlight a recent small clinical study in Vietnam, where a safe and affordable anti-cancer drug called imatinib was able to improve recovery times of malaria, which could potentially reduce the ability of parasites to become resistant to current therapies.

“A silver lining of time away from the laboratory and field studies due to the COVID-19 pandemic was our team’s ability to focus on getting work from many studies written and published,” Dr. Cooper said.

In 2021, Dr. Cooper and his collaborators published nine peer-reviewed papers on malaria, many including Dominican University students as co-authors. Dr. Cooper notes that “we have been fortunate to join wonderful collaborators from institutions around the world, have the involvement of talented students from Dominican and other universities, as well as generous funding from the National Institutes of Health, the Geneva NGO, Medicines for Malaria Venture, and from the UC Berkeley Center for Emerging and Neglected Diseases in support of our students.” 

Above photo of Dr. Roland Cooper (right) with Dominican Biological Sciences alumna Frida Ceja ’17 and Martin Okitwi on summit of Tororo Rock in Uganda.