How MSU’s Center for Global Neuropsychiatry Research is fighting Konzo


Previously a research group, the Center for Global Neuropsychiatry Research was recently approved to become a research center at the university level. Together, the center’s core faculty members participate in approximately a dozen NIH-sponsored research projects, including neurodevelopmental intervention and assessment programs that look at severe malaria in African children, people living with HIV across the lifespan, and the effects of Zika exposure in early child development.  

The center is led by Dr. Michael J. Boivin, Professor in the Departments of Psychiatry and Neurology & Ophthalmology in the College of Osteopathic Medicine. Alla Sikorskii and Drs. Amara Ezeamama and Itziar Familiar-Lopez are faculty core members in the center, along with research associate Dr. Jorem Awadu. In their work, they collaborate with other affiliate investigators around the country, as well as those from countries in sub-Saharan Africa and Latin America.

One research program led by Boivin attempts to understand the neurocognitive effects of konzo disease, a neurological condition caused by the toxic effects of cyanide from poorly-processed bitter cassava. Bitter cassava has long been a dietary staple in much of the Democratic Republic of Congo (DRC) and in many areas of central and western Africa due to poor agricultural conditions combined with food and water insecurity.

“We're doing a lot of really good things in different parts of the world,” Boivin said. “But if I had to pick what's nearest and dearest to my heart, it's what we're doing to prevent konzo—a disease which really impacts the poorest of the poor.”

Konzo isn’t as well-known as other diseases in the region, but it has lasting effects, and it primarily affects children and families. In the center’s previous work, Boivin and his team observed that poorly-processed cassava can cause not only neuromotor impairment, but also neurocognitive impairment in children, perhaps beginning at the point at which they are weaned from breast milk to cassava porridge in the first years of life. In a four-year follow up of more severely affected children at school age, they confirmed that these effects don’t get better over time; they get worse as children consume more poorly-processed cassava.

Long-term, the solution is to enable communities to rely on something other than toxic cassava as their basic food staple. But that requires change at a level that likely won’t happen in our lifetime, Boivin said. “Konzo is a disease of extreme poverty. That's why remediating it isn't just a quick fix with a genetically engineered crop. It means addressing the more pervasive complex web of poverty within which these communities have existed for generation after generation.”

For this reason, current interventions focus on methods of detoxifying cassava by removing the cyanide through processing. There’s a reliable, low-cost method for doing this known as the wetting method, which involves mixing cassava flour with water, then leaving it to sit for a thin layer for 2 hours in the sun, or 5 hours in the shade. It’s a simple method, but labor intensive.

Understanding the feasibility, effectiveness, and potential impact of using the wetting method to prevent konzo is one of the center’s primary interests now. A recent publication in Nature Food, funded by a Grand Challenges Canada grant led by Boivin and University of Bergen and University of Kinshasa colleague Dr. Esperance Kashala-Abotnes, utilized analytical methods pioneered by senior author Dr. Felicia Wu, John A. Hannah Distinguished Professor in Food Safety, Toxicology, and Risk Assessment, to do just that.

Previously, Wu worked with the World Health Organization (WHO) using a similar cost-benefit analysis to estimate the global burden of disease caused by aflatoxin and arsenic in food. Pioneering this work at a global level, Wu co-authored the WHO 2015 report on the Global Burden of Foodborne Disease. Building on the analytical techniques used in this earlier work, Wu and Dr. Chen Chen, a research assistant professor in Wu’s lab, evaluated how konzo was really affecting families in the DRC. Their recent publication in Nature Food using this cost-benefit strategy is a first of its kind, and has the potential to be a landmark accomplishment in the global effort to prevent konzo disease in the sub-Sahara.

In the paper, the pair looked at the disease burden of konzo in Congolese children in terms of IQ decrement and disability adjusted life years, and what the potential improvement could be if the wetting method were adopted. What they discovered was striking. “We were able to show that by implementing this wetting method, you can improve children’s neurocognitive outcomes to reduce the burden of disease all their lives, and it amounts to something that can be really beneficial at a population level,” Wu explained.

This research is a huge step forward, because it’s the first time an intervention for konzo has been investigated. Forthcoming research will share what happened when mothers were taught to use the wetting method compared to the wetting method plus early childhood learning techniques. The initial results are promising, Boivin said. He’s seen similar results in his research in HIV-affected households in Uganda, where sensitizing moms to their children’s early development resulted in better overall health outcomes for children.

These results also show the power of collaboration across departments and colleges within MSU, and global collaboration with other universities and partners. The next steps in the project involve working on a larger scale to assess the neurodevelopmental benefits of preventing konzo disease for at-risk regions in the DRC and throughout central and western Africa. Together, the results of Wu and Chen’s cost-benefit and disease burden analysis and Boivin’s interventional trials with his fellow Congolese principal investigators and research partners can be used to demonstrate the need for this type of work to donors and ministries of health for the DRC and other affected countries.

“We can make a real difference here, and it doesn't cost that much, because it's a low-tech intervention that is affordable and sustainable,” Boivin said. Research and intervention programs to prevent disease that can cause a lifetime of disability for children and their families are at the very core of the center’s mission, he added. “It is what we have the training, vision, and passion to accomplish as a collaborative team within this newest center at MSU.”