Finding a better way to take a bite out of malaria’s power

Fred Hutch and collaborators launch new trials to infect – and quickly treat – volunteers to test experimental drugs
Malaria, a parasitic disease transmitted by infected mosquitoes , kills more than 600,000 people a year, according to the World Health Organization. Photo by Will Betz / Seattle BioMed

Dr. Jim Kublin knows firsthand the wrath of malaria. In the early ‘80s, he went to Nicaragua to work on a campaign to eradicate the disease. He became infected himself and experienced the full force of its fevers, chills and hallucinations.

Now, years later, he’s still focused on getting rid of malaria, a parasitic disease transmitted by infected mosquitoes that kills more than 600,000 people a year, most of them young children in sub-Saharan Africa.

And as part of his effort to do that, he and other Seattle researchers are going to deliberately infect people with malaria – and then quickly treat them.

The series of clinical research studies is part of a collaboration between Fred Hutchinson Cancer Research Center, where Kublin is a researcher in the Vaccine and Infectious Disease Division, and Seattle Biomedical Research Institute. The studies are designed to test experimental drugs that could one day be used to prevent or treat the disease. Some volunteers will get experimental drugs and others placebo before being bitten by mosquitos carrying the parasite that causes malaria.

All of the trial participants will be “challenged,” as the practice is called, with a strain of malaria that is easy to diagnose and responsive to conventional treatment.

But that doesn’t mean recruiting volunteers will be easy.

“It takes a really strong commitment and an altruistic outlook,” said Kim Louis, community outreach manager for the Seattle Vaccine Trials Unit (VTU), a Fred Hutch program that ordinarily conducts HIV-related trials and research. The VTU has worked with the Hutch and the University of Washington on research studies since 1987. The partnership with Seattle Biomed will be its first malaria trials.

Half the world’s population — more than 3 billion people — live in malaria-endemic areas. Seattle is far from the tropical and subtropical regions where malaria is transmitted, so while volunteers for other trials are often motivated because they know someone affected, that’s less likely to be the case with malaria. But Louis is hoping to engage people whose awareness of malaria and other global diseases is high due to the presence of the Bill and Melinda Gates Foundation and other global health powerhouses based in Seattle.

One of only four ‘insectaries’ in the world

Fred Hutch is part of that group. The Hutch is home to the HIV Vaccine Trials Network, the world’s largest publicly funded international collaboration supporting development of vaccines to prevent HIV; the Seattle trials unit is part of the network. The Hutch’s global oncology program investigates links between infectious diseases and cancer in Africa and other regions.  

And Seattle BioMed houses the Malaria Clinical Trials Center, one of only four places in the world and the only non-military center in the United States with an “insectary” for breeding malaria-carrying mosquitos and conducting human challenge trials. 

The link between the Hutch and Seattle BioMed is Kublin, executive director of the Hutch’s HIV vaccine network and medical director of Seattle BioMed’s malaria center, who will be the principal investigator for the upcoming trials. An expert on both diseases, he was one of the first researchers to document the interaction between HIV and malaria, noting that, in areas of sub-Saharan Africa where there is a substantial overlap between the two diseases, an HIV infection made people more susceptible to malaria and malaria increased the viral load of those infected with HIV.

In 2010, Seattle BioMed conducted a study to demonstrate its ability to infect human volunteers with malaria and then reliably treat them within its Seattle facility. The Walter Reed Army Institute of Research in Maryland has used the human challenge method for the past 30 years to test vaccines to prevent malaria and drugs to treat it.

In several upcoming trials, both researchers and volunteers will be “blinded,” or kept unaware, of which subjects receive the experimental drug and which receive the placebo. All volunteers will be closely monitored using molecular diagnostics that can detect malaria before symptoms are evident. Then those who are infected will be immediately treated.

“They’ll get malaria, but they won’t even feel it,” said Kublin.

Respect for the ‘elegance and biology’ of malaria

Kublin’s early experience with malaria inspired a fascination with the “elegance and biology” of the parasite, and set him on a path to a medical and research career that included directing an integrated malaria initiative in Malawi. 

What makes human challenge trials such a useful tool is that they allow researchers to weed out drug or vaccine candidates that don’t work before going to the time and expense of testing them in the field. They also allow researchers to study parasite growth and immune response.

The “human challenge” method of testing drugs is possible because rapid testing and effective treatments exist for malaria, Kublin said. Challenges can’t be done for HIV because there is no cure or for tuberculosis because treatment is lengthy.

Although there are several medications that treat malaria, new treatments are being investigated because malaria parasites are known for developing resistance. Resistance to artemisinin, the key ingredient in the combination therapy that is the current gold standard treatment, is being seen in Southeast Asia, according to the World Health Organization. 

Efforts to prevent and treat malaria, including the use of artemisinin-based therapies to replace treatment that had lost effectiveness and the distribution of insecticide-treated mosquito nets, have helped reduce mortality rates by 42 percent globally since 2000 and among African children by 54 percent, according to the WHO. Still, in Africa, a child dies of malaria every minute. There were an estimated 207 million cases of malaria worldwide in 2012.

For information about screening for the malaria clinical research trials, visit or call 206-256-7101. 

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Mary Engel is a former staff writer at Fred Hutchinson Cancer Center. Previously, she covered medicine and health policy for the Los Angeles Times, where she was part of a team that won a Pulitzer Prize for Public Service. She was also a fellow at the Knight Science Journalism Program at MIT. Follow her on Twitter @Engel140.

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