Fighting Konzo Disease in the Democratic Republic of the Congo

A woman who has konzo and her two daughters.

Michael Boivin, professor of psychiatry and of neurology and ophthalmology in MSU's College of Osteopathic Medicine, has worked in sub-Saharan Africa for nearly 30 years, studying the neuropsychology of diseases that arise in children, in conditions of extreme poverty, in the tropics.

According to several sources, the Democratic Republic of the Congo (DRC; formerly Zaire) is the poorest nation on earth. Boivin said the DRC's problems are "bottomless. There's factor after factor and layer after layer. There's economics and risk and exposure, there's treatment and seasonal issues. And they're all immersed within this complex web of poverty, where risk can come at these kids from so many different directions—water insecurity, food insecurity, drought, climate change, insect-borne viruses. Everything is interrelated."

In 1990-1991 Boivin went to the Congo to conduct a year-long, Fulbright-funded study on the effects of public health interventions in rural areas. But within weeks after he left, he said, "the army units began to mutiny and the whole country sort of imploded into this chaos, which culminated in civil war for two decades. It was too unstable to work there."

Deprived of his home base, he began looking for other ways to continue working in Africa. Over the next several years a series of studies followed—cerebral malaria in Senegal and Uganda, pediatric HIV in Uganda—and, finally, when the DRC settled down enough to make working there feasible again, konzo disease in the Congo basin.

A Terrifying, Debilitating Disease

Konzo is a neurological disability, a sudden-onset, partial paralysis of the legs that results from ingesting the cyanide in improperly prepared bitter cassava root, a staple food source for millions of people in drought areas of central and western Africa. Victims of konzo simply wake up one morning unable to walk. The name means "tied legs" in the Yaka language of southwestern Congo, referring to the awkward knock-kneed stance it produces in survivors lucky enough to be able to use their legs at all.

Konzo was first described in 1938 by a team of Belgian and Congolese health workers. However, its cause was not determined until the 1980s, when Swedish physician-professor Hans Rosling and his physician-research fellow, Thorkild Tylleskär, were able to document the connection between the konzo and the cyanide in the cassava.

Working with Rosling and Tylleskär was Desiré Tshala-Katumbay, a young Congolese neurology resident, who was pioneering electrophysiological studies of konzo disease for his thesis project. Tshala-Katumbay, who is now an associate professor at Oregon Health and Science University and a visiting professor at the University of Kinshasa medical school, later became one of Boivin's closest colleagues.

Making Connections

Desiré Tshala-Katumbay is working to develop a community-led konzo intervention that utilizes the "wetting method."

The two met at an NIH-sponsored meeting in 2010. Finding that they shared an interest in konzo, they secured a five-year (2011-2016) NIH grant to look at how physiological biomarkers of cyanide toxicity (Tshala-Katumbay's contribution) and neuropsychological testing (Boivin's) could help detect the pre-clinical stages of konzo disease in children.

This study provided the first conclusive evidence that (1) the disease affected cognitive development as well as motor functions; (2) the cognitive effects could be seen in kids who didn't actually manifest neuro-motor symptoms yet; and (3) the disease process could begin as soon as children were weaned from their mother's milk to cassava porridge. It also led to some landmark publications.^[1]

Boivin said, "We knew the brain must be affected, but we couldn't see it yet. When I came in with the neuro-psych testing and related that to the level of exposure to the cyanide—using the blood, urine, and other biomarkers identified by Desiré from his lab work—we were then able to connect the pre-clinical neurological and motor proficiency effects to those biomarkers. We built a pretty solid case that it's affecting the kids' neurodevelopment. Now we have to get the exposure levels down. There is no way to repair the damage. We have to get in and prevent it."

That became the purpose of the next five-year NIH grant (2016-2021): training mothers through public health outreach programs to prevent konzo by better processing their cassava.

A Preventable—But Still Massive—Problem

Kassava being dried on the roof of a home.

There is no known cure for konzo. However, it is entirely preventable. All you have to do is detoxify the cassava. Water and sun can do that through fermentation and evaporation. Communities have found over time that when cassava roots are soaked in water for several days and allowed to dry in the sun before being ground into flour, the toxic compounds break down and no longer pose a threat to consumers.

The difficulty with this method is that it's time-consuming. War- and famine-stressed villagers are often so hungry that they are apt to go ahead and chew on some unprocessed roots without worrying about how safe it is.

Because bitter cassava is a strategic famine crop that can support food security in areas of very low rainfall, where virtually no other crops will grow, researchers have continued to pursue better ideas for detoxifying it.

Around 2005 an Australian chemist, Howard Bradbury, discovered a way to shorten the processing time from days to hours. Bradbury's "wetting method" involves pounding the roots into flour, mixing the flour with water, flattening the dough, and drying it for two hours in the sun. This process is now being evaluated in a clinical field trial by Tshala-Katumbay, Boivin, and their collaborative team as part of their current five-year NIH award.

Thus, while konzo still has no cure, there exists a prevention protocol for it that is simple, no-cost, low-tech, and nearly 95 percent effective. It has been around for more than 10 years. This disease should be well on its way to being eradicated. Right?

In villages where women are being taught the wetting method, the number of new cases of konzo has indeed dropped. Still, as journalist Amy Maxmen pointed out in a series of articles about konzo for Global Health Now^[2], "the wetting method will not change the fact that people are living on nothing except for a bitter root." In other words, a lasting solution must involve a fundamental change to the principal food staple in this region.

Maxmen also noted that rather than depending on philanthropic help from outside the community, "Desiré Tshala-Katumbay, a Congolese neurologist and biochemist...who has long worked with konzo-affected people, wishes instead for solutions that are made sustainable through community leadership."

Sustainable solutions, driven by community leadership, are the strategy that Tshala-Katumbay, Boivin, and their colleagues are developing now, in the implementation phase of their work.

Getting Them to Do It

A woman retrieves cassava roots that have been soaking in a stream outside of Kahemba.

Even if their cassava flour has been poorly prepared, the women can detoxify it through the wetting method, said Boivin. "It's just a matter of teaching them and getting them to do it."

The problem is the "getting them to do it" part: "What we're seeing is that we can teach the method, the moms will understand, but getting them to keep doing it? Because it's a lot of work. It's labor intensive—in a setting where so much already depends on them—to add this every time they prepare food."

Boivin got to thinking. Back when he was working on pediatric HIV in Uganda, in the mid-1990s, he came across a model for training caregivers of very young children—the Mediational Intervention for Sensitizing Caregivers (MISC)— developed by psychologist Pnina Klein of Bar Ilan University, Israel. His idea at that time was to adapt Klein's approach for the caregivers in his HIV study in Uganda. Anti-retroviral medications were just becoming available, but the moms still clearly needed support. If they had the medicines, could they be trained to administer them reliably? Could Klein's model help sensitize the moms to their children's medical, nutritional, and developmental needs?

Boivin poses with Robert Tukei, a Ugandan physician who served as a medical officer on one of the malaria studies at Mulago Hospital. He came to MSU to pursue a master's degree in epidemiology through the support of the MasterCard Foundation.

After a year-long study, the answer was a resounding yes. "The kids were surviving longer, there were better developmental outcomes, plus the moms were less depressed," said Boivin. "They had social support and a practical strategy. We began to understand how medical support and care had to be bundled within a training program for moms that emphasized good nutrition and cognitive stimulation. It was not enough to simply give them their medications at their monthly clinical appointment."

So now his thought was, "Could we once again adapt the same development model that we used in Uganda with the HIV caregivers, this time for the konzo-affected kids? Could we embed the wetting method training right into a comprehensive program to mobilize and motivate the mothers, not just to detoxify cassava flour, but to enrich their children's developmental context?"

These questions are what Boivin, Tshala-Katumbay, and co-investigator Espérance Kashala-Abotnes (of the University of Kinshasa and the University of Bergen) are currently working on.

Kashala-Abotnes came into the picture in 2014, when Boivin was in Uganda doing clinical trials of the MISC training for caregivers of HIV-affected children. "She wanted to work on early child development in the Congo, as affected by konzo but also more broadly," said Boivin.

He trained Kashala-Abotnes in the neurodevelopmental assessment protocol with very young children and the MISC caregiver training. Since then, with Boivin and Tshala-Katumbay as mentors, she has been working on neurodevelopmental outcomes in very young children gathered at the principal konzo research site in Kahemba. "This is the first time these konzo-related risk factors have been studied in very young children," said Kashala-Abotnes. "The assessment protocol appropriate for very young children affected by konzo disease in the DRC is now the central focus of my postdoctoral work."

New graduates of MISC training in Kikwit, DR Congo, 2018.

With support from an MSU Alliance for African Partnership grant, the investigators recently launched a six-month intervention program to better prevent konzo disease in infants and toddlers using the same strategies that proved effective in Uganda. Grant negotiations are also being finalized with the Canada Grand Challenges Saving Brains program, a DRC Ministry of Health partnership with the Canadian government, and other major donors such as the Bill and Melinda Gates Foundation. With this support, they hope to evaluate how best to bring this intervention to scale through the Ministry of Health.

Meanwhile, the current NIH grant is covering some of the costs of developing, implementing, and evaluating a standalone wetting method intervention. "Desiré has all that," said Boivin. "He is regularly funded by the International Brain Research Organization to build neuroscience and neurotoxology research capacity in sub-Saharan Africa. The DRC Ministry of Health, with support from WHO, wants to go in and begin prevention work in the areas that are most at risk. Desiré is partnering with Banea Mayumbu, former head and now senior advisor of the Ministry's program to prevent konzo, so there is a partnership between the science part and the program/ policy part to go in and develop an intervention model."

In addition, Tshala-Katumbay said, "the Congo National Institute of Biomedical Research, the National Laboratory of the Ministry of Health, has set up a research hub for us thanks to the active involvement of Professor Dieudonne Mumba Ngoyi and Tamfum Muyembe, both prominent tropical medicine Congolese scientists."

Boivin said that one of the most rewarding things to see is how years of clinical work in Uganda, with HIV-affected households, can now cross-fertilize the konzo initiative. He hopes that by learning how to sensitize the moms to their child's health and development, a host of other infectious diseases, as well as other nutritional and risk factors, can also be reined in. The key, he said, is to establish a foundation, beginning with the moms, early on.

Sources

1. See, e.g.: Boivin, M. J., Okitundu, D., Makila-Mabe Bumoko, G., Sombo, M.-T., Mumba, D., Tylleskar, T., Page, C. F., Tamfum Muyembe, J.-J., & Tshala-Katumbay, D. (2013). Neuropsychological effects of konzo: A neuromotor disease associated with poorly processed cassava. Pediatrics, 131, e1231-e1239. doi: 10.1542/peds.2012-3011 Back to Citation 1
2. https://www.globalhealthnow.org/2016-10/bitter-harvestcassava-and-konzo-crippling-disease-0 Back to Citation 2