Combating Malaria and Schistosomiasis
From Field to Lab and Back Again
Understanding and protecting against parasitic infections is the life’s work of husband-and-wife research team Jonathan Kurtis, MD, PhD and Jennifer Friedman, MD, MPH, PhD.
Through Rhode Island Hospital’s Center for International Health Research (CIHR)— for which Kurtis is the founder and director and Friedman the director of clinical studies— the pair works to understand the mechanisms that cause tropical infectious diseases, specifically malaria and schistosomiasis, and to harness this knowledge to design improved treatments and vaccines.
To combat these infections, CIHR is integrating community-based epidemiologic studies in the field with laboratory-based, basic science investigations. The researchers work under a series of grants from the National Institutes of Health and the Gates Grand Challenges in Global Health.
“We want to know how these parasites cause disease in the host, when it’s most effective to treat, and how to prioritize the limited health care resources in these developing countries,” says Kurtis. “Ultimately, what drives us is to make something deliverable—a pill, a vaccine... a tool that could protect millions of people from infection and disease.”
New Weapons against Schistosomiasis
Picture a little girl wading in a stream, gathering water in a bucket for her family. Then picture microscopims in the contaminated water burrowing into her unbroken skin. This is how schistosomiasis begins. If left untreated, the worms will lay thousands of eggs per day in her bloodstream and damage her internal organs.
Second only to malaria as the most devastating parasitic disease, but much less widely known, schistosomiasis is caused by tissue-invasive parasitic flatworms and infects more than 250 million people worldwide, contributing to poor health and economic stagnation in endemic areas. While the disease is effectively treated with the drug praziquantel, reinfection occurs so rapidly that public health officials desperately need a vaccine to control this infection.
The CIHR team has developed a vaccine for schistosomiasis that works in mice and is showing promise in water buffalo, which are a major transmitter of the disease. “If you vaccinate buffalos, in some models you’ll reduce transmission to humans by 75 percent. It’s a stepping stone to ultimately vaccinating humans because we’ll be doing safety and toxicity tests on the buffalos as well. Our first trials will take place in rural villages in China and the Philippines,” says Kurtis.
According to Friedman, children and pregnant women are the groups most vulnerable to schistosomiasis, as their immune systems are either not fully developed or are compromised. “Our goal is to develop vaccines and drugs that are safe enough for these patients to take to help guard against this parasite, which can undermine children’s growth and cognitive development.”
For the past six years, Friedman has been leading a randomized controlled trial of praziquantel for schistosomiasis in pregnant women. The drug is safe and effective in non-pregnant individuals but has never been tested during pregnancy—thus, 40 million schistosome-infected pregnant and lactating women worldwide are often excluded from drug treatment campaigns.
“We know that inflammation of any kind results in poor pregnancy outcomes and schistosomiasis is a profound inflammatory insult,” Friedman says. “We hope that by treating schistosome-infected pregnant women, we will reduce their inflammatory responses and improve both their health and the health of their newborns.”
New Pathways for Targeting Malaria
Malaria infects 300 to 500 million people worldwide and kills two to three million people each year. “This disease, caused by a mosquito-transmitted protozoan, is a capricious killer of the innocent. Nothing else on its own kills more people,” says Kurtis.
Current malaria control strategies include insecticide-laden bed nets, drug treatment for infected people, and insecticides to limit mosquito populations. Unfortunately, these interventions are simply not sufficient to prevent the ever-increasing spread of the disease. New strategies, including an effective vaccine, are urgently needed—and CIHR is making great strides in bringing this to fruition.
“A vaccine for malaria has existed for 35 years, but so far it only works in mice,” says Kurtis. “Our approach differs by starting with humans living in the endemic areas—we try to identify why some children are resistant to malaria in the laboratory and then move these discoveries back to the field. We are making headway.”
Together with partners from the NIH and the Seattle Biomedical Research Institute, the CIHR team followed a cohort of 785 children—some with many parasites, others with very few—and used their blood samples in a vaccine discovery effort that has yielded three candidates that are now moving forward on the testing and approval pipeline.
“We identified parasite genes encoding parasite proteins that are uniquely recognized by antibodies in the resistant blood samples, but not recognized by antibodies in the susceptible samples. We then returned to epidemiology studies that showed if you made an antibody to that protein, not a single child got severe malaria. If you didn’t make an antibody to that protein, there were quite a few cases of severe malaria. It looks to us now like antibodies to this protein might in fact mediate resistance.”
Inspiring Tomorrow’s Tropical Health Researchers
Kurtis and Friedman have been leading studies and collecting data for decades in such far-flung places as the Philippines, China, Kenya, Tanzania and Brazil. They now collaborate with an expert team of postdoctoral researchers in Rhode Island as well as with co-investigators and other colleagues in the field.
“Once you get involved with global health initiatives and you’ve spent extensive time in these countries, you can’t do anything else,” says Friedman. “The burden of disease is so massive, like nothing you’ve ever seen in the United States. Our goal is to help level the playing field.”
CIHR researchers have collaborated on tropical infectious diseases for more than two decades with leading experts in both malaria and schistosomiasis. Their long-time collaborator, Remigio M. Olveda, MD from the Research Institute for Tropical Medicine in the Philippines, says, “This intense level of collaboration has allowed us to discover the pro-inflammatory basis for morbidity in schistosomiasis, tackle its treatment during pregnancy and identify and test new vaccine candidates. These interactions will have a durable impact on the health of the poorest Filipinos and are a testament to the dedication of the scientific teams at CIHR and our institute.”