For the Wapogoro people, there are few worse fates than kifafa.
The tribe lives in the Mahenge highlands in deepest Tanzania: a land of rugged mountains, mist-capped forests and rare underground treasures, from fossils to glittering neon-pink gems. They have survived there in isolation for hundreds of years, quietly going about their lives and largely escaping the notice of the wider world.
Or that was the case, until a Norwegian doctor turned up in 1959. Louise Jilek-Aall was just 28 years old, fresh out of medical school and determined to set up a clinic in the area. But no sooner had she started seeing patients than she noticed something peculiar.
Nearly every day, children as young as two would turn up in her office with severe burns. In one case, a little girl was rendered completely unrecognisable; many others died from their wounds. The burns were often overlaid on webs of pale pink scars, which had built up after years of previous scorchings.
When Jilek-Aall tried to find out what was going on, she met with fear and evasion. Even the relatives of affected children flatly refused to explain the sinister trend
In fact, the youngest members of the tribe seemed particularly, some would say suspiciously, susceptible to a wide range of accidents, including regular drownings. When Jilek-Aall tried to find out what was going on, she met with fear and evasion. Even the relatives of affected children flatly refused to explain the sinister trend.
Eventually Jilek-Aall realised that her patients were having seizures, which they called kifafa – Swahili for “the little death” – and falling down. Sometimes they would land in the open hearths where they cooked their food. Occasionally they would end up in the river.
But the mystery didn’t end there. The same children also tended to have stunted growth, intellectual difficulties and characteristic mannerisms, such as an awkward gait and deadpan facial expressions. Most strikingly, there was the "head nodding"; several times a day, they would close their eyes and repeatedly drop their heads to their chests. The illness typically lasted for a number of years and ended with an early death.
Finally, though every member of the Wapogoro was afraid of kifafa to an almost feverish degree, the illness was practically unheard of elsewhere in Tanzania. This was even true of neighbouring tribes.
Nodding syndrome has since been found in pockets across east Africa, from South Sudan to northern Uganda, where it has devastated the lives of thousands of people. In each new location, it seems to appear out of nowhere. What could be behind this deadly plague? And how can we stop it?
People with nodding syndrome often suffer burns and other injuries that result from their seizures (Credit: Provision Charitable Foundation)
To this day, no one knows what causes nodding syndrome. In the past, the illness was generally accepted to be a rare and enigmatic form of epilepsy. But now the latest research has hinted that it might be a neurodegenerative disease, which manifests as a combination of epilepsy and some symptoms of Parkinson’s and Alzheimer’s. In the end, its victims usually succumb to seizure-related complications, such as brain damage and accidents, or poor mental health and neglect.
The tantalising clue emerged from a 2018 study, which found that the brains of teenagers with the illness look remarkably similar to those of elderly patients with the latter two diseases. “It’s generated a new line of enquiry, because now we know that there is a certain type of brain damage occurring,” says Michael Pollanen, a pathologist at the University of Toronto who led the research. “You can think of it like this: if you can figure out what the type of brain damage is, maybe you’ll be able to work backwards to the cause.”
At the very least, the overlap with other diseases adds an extra sense of urgency to the research. Not only does nodding syndrome affect some of the most vulnerable people on the planet, but it may hold the key to understanding several disorders which have long eluded scientists.
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If you compare nodding syndrome to Alzheimer’s, it’s easy to see why. While one has been found in millions of people, with largely dissimilar lifestyles, across almost every continent on the planet, the other only occurs in small, isolated populations. In such communities, it’s easier to pin down what one person – say, a child with nodding syndrome – has experienced that others have not. “My intuition says that this is going to be important,” says Pollanen.
So what do we know so far?
There are plenty of imaginative theories out there. In Mahenge, the locals have linked kifafa to a foreboding dream, in which they are washing themselves, pouring water over their shoulders, savouring the feeling. Then they open their eyes and the water has turned scarlet with blood.
One thing that’s clear is it’s not inherited. “Though it tends to occur in families, this is a disease that comes and goes,” says Peter Spencer, a neurologist at Oregon Institute of Occupational Health Sciences. “It appears in 1997 in northern Uganda, peaks in the early 2000s and then disappears. You cannot explain it as a heritable genetic disorder, because it just would not fit that pattern.”
Louise Jilek-Aall, pictured here (left) in 2009, has conducted much of the work on nodding syndrome (Credit: Provision Charitable Foundation)
A major source of inspiration in the quest to understand nodding syndrome is another equally baffling disease, which is largely based on the island of Guam. This lonely hillock of grass and scrubland is marooned in a remote corner of the Pacific Ocean, a tiny speck, thousands of kilometres from the nearest continent.
Though Guam is technically US soil, it’s home to the Chamorro people, who have lived with an enigmatic disease since at least 1904. Scientists call it the Western Pacific Amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC). To locals, it’s simply known as lytico-bodig. The disease was discovered after death certificates recorded that several patients had died from muscle wasting, and reached its peak in the 1950s, when it rapidly became the leading killer on the island.
The disease can take two forms. There’s lytico, which resembles the neurodegenerative disease ALS (motor neurone disease), which the late physicist Stephen Hawking lived with for decades. Then there’s the bodig part, which is strikingly similar to nodding syndrome; both have elements typical of Parkinson’s and dementia. Technically speaking, lytico and bodig are two separate diseases, but they’re lumped together because of their overlapping ranges and the fact that they have the same unknown cause.
“The important thing is that this disease was familial and assumed to be genetic in the 1950s,” says Spencer. “By the 2000s, it was clearly disappearing, but geneticists were still desperately trying to come up with some genetic risk factor. Well today it has disappeared from Guam and it’s clearly an environmental disease.”
It might sound surprising that the search for nodding syndrome is at such an early stage. But for years, scientists may have been following a false lead. It started with an outbreak of nodding syndrome in South Sudan in 2002, and the discovery that patients tended to be more heavily infested with two different kinds of parasitic worms. One type, Onchocerca volvulus, became the focus of intense efforts to prove a link.
Onchocerciasis is a particularly gruesome disease, which begins when a black fly sinks its saw-like mouth into a victim’s skin, leaving behind a generous dose of parasitic worm larvae. Over the course of several months, they mature and eventually form homes out of raised lumps in the skin, where they mate and start their own worm families. They’ll produce up to 1,500 babies, or microfilariae, every single day, which migrate all around the body – invading nearly every organ and tissue.
Nodding syndrome was once thought to be caused by the same parasitic worms that also lead to river blindness (Credit: Getty Images)
Incredibly enough, the worms themselves aren’t much of a problem. It’s when they die that the body launches a potent, highly damaging immune response against their carcasses. This was the suggested trigger for nodding syndrome.
There are some serious snags to the theory, however, including the fact that the worms are known to infect people in certain parts of Central and South America – where nodding syndrome doesn’t exist. With this in mind, blaming worms seems like a bit of a stretch.
But there are other intriguing leads.
“Head nodding is most unusual,” says Spencer. “It’s been described in just one other case – of a post-measles disorder, which most recently had outbreaks in Israel and Germany, and likely will again in Europe.”
The rare disease, known as subacute sclerosing panencephalitis (SSPE), can develop if measles is caught at an early age. Just like nodding syndrome, typical symptoms include intellectual difficulties and head drooping. And just like nodding syndrome, it tends to surface in childhood. Could nodding syndrome be related to measles, too?
In northern Uganda, the idea fits remarkably well.
From the late 1980s to 2006, the region was the epicentre of a fierce civil war, as a trio of factions battled to take control, including the notorious child-kidnapper, warlord and self-proclaimed prophet Joseph Kony, who led his own guerrilla force. More than a million people fled their homes, moving to internal camps which were crawling with diseases such as cholera, measles and rubella.
Measles can lead to subacute sclerosing panencephalitis, the symptoms of which resemble nodding syndrome - another reason why vaccination is important (Credit: Getty Images)
The civil war is now long over and Kony has a $5 million (£3.8 million) bounty on his head. But for the general public, the consequences may be lingering on. Though cases are still emerging to this day, reports of nodding syndrome in northern Uganda peaked in the mid-2000s, which is around five years after the war’s most bloody phase, when people were flooding into infested camps.
The timing is spot on, since the measles virus has a cruel affinity for infants and very young children, and SSPE takes several years to develop; the affected children in Uganda were usually around seven years old.
Now scientists just need to figure out if the idea makes sense in Tanzania and South Sudan. “If we’re going to find an answer to this disease, then it’s going to have to be relevant to all three geographic isolates,” says Spencer. “And we can say that a common feature of all isolates of nodding syndrome is a failure of the normal practice of vaccination.”
Spencer is keen to point out that measles is not the only possible cause. Rubella is also known to cause a similar condition to SSPE – and since both viruses cause similar symptoms, and are prevented with the same vaccine, it’s not clear which one is likely to be behind Uganda’s epidemic. It could be neither; no possibility is off the table, including some kind of as-yet-undiscovered virus.
Infections may be to blame for a surprising number of cases of neurodegenerative disease, including Alzheimer’s and multiple sclerosis
Regardless, any viral trigger would slot in nicely with recent discoveries. It turns out that infections may be to blame for a surprising number of cases of neurodegenerative disease, from the herpes simplex virus, which drastically increases the chances of developing Alzheimer’s disease (along with several other culprits, including the bacteria that cause gum disease), to the Epstein-Barr virus, which is found in the vast majority of patients with multiple sclerosis.
The viruses are accused of entering the brain, where they stir up generalised inflammation and kickstart the production of certain key proteins, which permanently impair the normal functioning of the brain.
The civil war in Uganda led to the spread of diseases such as measles, which may explain the emergence of nodding syndrome in the worst affected regions (Credit: Getty Images)
One such protein is beta-amyloid. It has antimicrobial properties and may play a role in fighting the infections. But when Pollanen looked at the brains of Ugandan children who had died of nodding syndrome, it was curiously absent. In fact, though the team did find abundant evidence of neurodegenerative disease – such as large tangles of another important protein called tau – there were no signs of infection whatsoever.
“We don’t see inflammation that looks like it’s from a virus, we don’t see parasites, we don’t see evidence of a bacterial infection,” says Pollanen. “We don’t see the markers of those types of cellular or tissue damage that we would see. But does the absence of that totally exclude a virus? We don’t know.”
Spencer is equally ambivalent. “Now Michael Pollanen will correctly say that there is no evidence of the type of pathology you would expect to see in these post-measles, post-rubella, late-onset illnesses,” he says. “But I think it’s also fair to say that you do not see evidence of infection in the brains of Alzheimer’s disease patients... so it’s a very complex discussion.”
Back on Guam, the latest findings about lytico-bodig may provide an intriguing alternative: diet.
The Chamorro people like to eat the ground-up seeds of cycads – giant, fern-like trees which have been around since the reign of the dinosaurs. They’re rich in the chemical BMAA, which has been shown to cause the same characteristic brain damage found in patients with the disorder. Could dietary toxins also play a role in nodding syndrome?
The disease occurs in some of the most deprived communities in Africa, and as such, affected children often have poor diets. During the Ugandan civil war, hunger drove the families who were staying in temporary camps to eat various dubious foods, including mouldy maize and seeds which had been coated with pesticides – they were provided by emergency relief programs and intended for planting. Those who ate these were more likely to also report having a child with nodding syndrome.
Louise Jilek-Aall's continued work with epileptic patients in Tanzania is being supported by the Provision Charitable Foundation (Credit: Provision Charitable Foundation)
Even in good times, staples such as cassava and sorghum can put children at risk. Both contain chemicals that break down into cyanide, a potentially lethal compound beloved of Victorian murderers. They’re thought to protect the plants from being eaten by insects and have already been implicated in the crippling neurodegenerative disease konzo, which has been stalking the poorest and hungriest parts of East and Central Africa for generations.
Though cassava root is rich in carbohydrates, calcium and vitamin C, if it’s not properly processed – chopped up and soaked in water for several days, to reduce the cyanide content – then it will slowly poison whoever is desperate enough to eat it. The toxin destroys the neurons that carry signals from the brain to the muscles, and the end result is irreversible paralysis. Many victims end up as quadriplegics.
If nodding syndrome has a dietary cause, then uncovering it could have a significant global impact, as the disease’s strange twin has already shown; since the discovery that BMAA could be driving lytico-bodig, scientists have checked to see if it could also be involved in the development of other neurodegenerative diseases. It turns out that this might be the case – and a chemical known to protect against such damage is currently in clinical trials. It may soon provide a new way of treating patients with ALS and early-stage dementia.
“I can tell you that I am totally committed to continuing this research and I will be assembling a multi-disciplinary team that I believe will make a significant contributions,” says Pollanen. “This work can only be done as a team, and it is obvious that no one expert is going to have the total knowledge needed to solve this problem. So that is the approach that we are going to take.”
For now, the mystery of nodding syndrome drags on. Who knows, perhaps one day this obscure East African illness could provide a vital clue that unlocks treatments for many other diseases worldwide. But Pollanen is keen to point out the dangers of viewing the human tragedy in entirely clinical terms – almost as though it’s an experiment. “Particularly in my discipline, we tend to focus on the immediate consequences of internal armed conflict. We forget that these acts resonate for far longer,” he says. “And what we are seeing with nodding syndrome is part of a humanitarian crisis in the region. There’s more than a scientific reason to ensure the welfare of these children.”
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