Hunting Down a Mysterious Malady

An SDSU virologist is searching for a cryptic virus that may be responsible for a society-shattering disease in Central Africa.

SAN DIEGO (February 4, 2015) — In the Democratic Republic of Congo, they call it “epupuluga.” To Western medicine, it’s known as nodding syndrome. Several thousand people have come down with this terrifying, fatal disease over the past several years in various Central African countries, yet nobody knows what causes it.

Last year, San Diego State University virologist John Mokili and some of his international colleagues recently journeyed to the affected region to collect samples in hopes of learning whether an unknown virus is behind the disease. Using cutting-edge genomic techniques, they’re on the cusp of finding an answer.

Nodding syndrome typically affects children between the ages of 5 and 15. The children slip into epileptic seizures for several minutes, and then come out of the seizures with no memory of what’s happened. Next, they nod their heads — repeatedly and almost unconsciously — sometimes for 10 to 15 minutes. These episodes occur several times per day. The children stop growing and developing. They stop going to school. Their families miss work to take care of them. Eventually, they die, by falling on top of a fire or drowning during a seizure, or from the disease itself.

Even among other rare, mysterious maladies, nodding syndrome is poorly understood and understudied, Mokili noted. The World Health Organization, which operates a series of programs targeting neglected tropical diseases, lacks any kind of formal program for nodding syndrome.

There have been reports that the disease is triggered by certain foods, or by exposure to cold. Many villagers think its roots are supernatural.

“What causes nodding syndrome is not really known,” explained Mokili. “When it doesn’t have a cause, it’s easy to believe the child has been affected by witchcraft.”

Congolese native

Mokili, a Congolese native, has been on the forefront of some recent, major discoveries in his field. Last year, he and fellow researchers in SDSU’s Viromics Information Institute, along with their international partners, discovered a novel virus lurking in the intestines of between half and three-quarters of the world population. They made the discovery using a new computational technique that makes it easier to identify stretches of genetic code that could harbor viruses.

Mokili hopes to use this same technique to determine whether nodding syndrome is caused by a virus by gathering genetic data from the people and environment — the metagenome — where the disease runs rampant.

In March, Mokili was invited to join an international coalition of clinicians, epidemiologists, and entomologists banding together to look more closely at nodding syndrome. The team used Land Cruisers and motorbikes to visit three remote villages in the DRC: Dingila, Liguga and Titule.

“In Dingila, every third house we visited had nodding syndrome,” Mokili said. “In some places, they were saying it made malaria seem like nothing.”

In all, the research team was able to collect genetic samples from about 140 children, half with nodding syndrome and half without.

They also collected more than 700 samples of a tiny culprit who might be spreading the disease: the black fly.

The flies swarm in thick clouds around the region’s rivers, and the villagers bathe in these rivers almost every day. Mokili thinks it’s possible these flies carry a heretofore unknown virus that’s responsible for nodding syndrome.

Virus hunting

Back in his lab at SDSU, Mokili is currently generating data, and will work with SDSU computer science professor Rob Edwards to analyze the metagenomic data the team collected. They are looking for sequences of DNA and RNA only present in the samples from people with nodding syndrome. If they can identify such sequences, they might be looking at the genetic structure of the virus behind nodding syndrome.

“If we know the cause of the disease, it will lead to new research,” he said. “If we discover the virus causing nodding syndrome, we can start thinking about vaccine development. That’s the best way of preventing children from acquiring this disease in the first place. But the bottleneck right now is knowing the cause.”

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