“Sleeping sickness” has referred to two very different diseases. The first is a parasitic infection spread by tsetse flies in sub-Saharan Africa, known medically as human African trypanosomiasis, which still exists today. The second is encephalitis lethargica, a mysterious epidemic that swept the world between 1916 and 1926, left roughly a million people ill, and then largely vanished. Both diseases attack the brain, both disrupt sleep in distinctive ways, and both earned the same ominous nickname, but they have almost nothing else in common.
The 1920s Epidemic: Encephalitis Lethargica
Encephalitis lethargica appeared during World War I and spread globally over the next decade. Conservative estimates put the total at around one million cases worldwide, with a mortality rate that may have reached 50%. The highest surges came in 1920 and again in 1924, and case numbers tapered after 1930. Then, almost as suddenly as it arrived, the epidemic stopped. Sporadic cases have appeared since, but nothing close to its original scale.
The disease typically began with disturbances in eye movement and deep drowsiness that could progress to a near-unconscious stupor. It targeted specific areas of the brain: the midbrain, the region that produces dopamine (the substantia nigra), the basal ganglia, and the brainstem. Autopsies showed inflammation concentrated in the brain’s gray matter, swollen blood vessels, and tiny hemorrhages scattered across the brainstem and spinal cord. Despite decades of investigation, no one has identified the cause. No virus was ever isolated from brain tissue, and current theories lean toward an autoimmune reaction, possibly triggered by an infection that has never been pinpointed.
Many survivors who appeared to recover developed severe Parkinson’s-like symptoms years or even decades later. They became rigid, frozen, and unable to initiate movement. These post-encephalitic patients filled hospital wards for the rest of the twentieth century.
The “Awakenings” Story
In 1969, neurologist Oliver Sacks gave a new drug called levodopa (L-dopa) to post-encephalitic patients who had been essentially immobile for decades. The results were dramatic and heartbreaking in equal measure. One patient, who had developed Parkinson’s-like symptoms at age 12, was freed from physical immobility at 49. Another returned to a happiness he said he hadn’t felt in thirty years. But these awakenings were often unstable. That same patient developed extreme sensitivity to the drug within six weeks and had uncontrollable side effects even at tiny doses. One woman, struck by the disease at 21, woke in 1969 to find the world of 1926 had vanished. She remained mentally rooted in the 1920s and eventually stopped responding to treatment altogether. The unpredictability of these responses, sometimes miraculous and sometimes devastating within the same person, became the basis for Sacks’s famous book and the 1990 film.
African Sleeping Sickness: The Parasitic Disease
The other sleeping sickness is caused by a parasite transmitted through the bite of the tsetse fly, found only in sub-Saharan Africa. Two forms exist. The West African form, responsible for more than 94% of cases, is a slow, chronic illness that can simmer for months or years before symptoms become obvious. The East African form is acute and fast-moving, sometimes progressing to a critical state within weeks. Both are almost always fatal without treatment.
Despite the name, sleeping sickness doesn’t simply make people sleep more. It disrupts the boundary between sleep and wakefulness. People with the disease experience sudden intrusions of sleep during the day and wakefulness at night, a pattern that resembles narcolepsy more than ordinary fatigue. This reversal of the sleep-wake cycle is one of the hallmarks that distinguishes the disease from general illness-related drowsiness.
How the Disease Progresses
African sleeping sickness moves through two distinct stages. In the first stage, the parasite circulates in the blood and lymph system. Symptoms at this point resemble a stubborn flu: recurring fevers, headaches, muscle and joint pain, fatigue, and swollen lymph nodes. A raised red sore sometimes appears at the bite site within two weeks, though it isn’t always noticed. People with the East African form are more likely to develop heart inflammation and hormonal disruptions during this early phase.
The second stage begins when the parasite crosses into the brain and central nervous system. This is when the characteristic sleep disruption appears, along with a cascade of neurological symptoms: anxiety, rapidly shifting emotions, hallucinations, confusion, tremors, slurred speech, and heightened skin sensitivity. Seizures can occur. Without treatment, the disease progresses to coma and death. The West African form can take years to reach this point. The East African form can get there in weeks to months.
Diagnosis and Treatment Today
Identifying which stage a patient is in determines treatment, and distinguishing stage one from stage two requires examining spinal fluid. Elevated white blood cells or the presence of parasites in the fluid signal that the infection has reached the brain. In endemic African communities, population-level screening uses a rapid blood card test that flags potential infections, though it isn’t specific enough to confirm a diagnosis on its own.
Treatment has improved enormously. For decades, second-stage sleeping sickness required drugs that were toxic and painful to administer. A major turning point came with fexinidazole, an oral medication taken once daily for 10 days. It works against both stages of the West African form and can be given to patients aged six and older. This replaced earlier treatments that required hospitalization and intravenous infusions, making it far more practical in rural areas where most cases occur.
Where Sleeping Sickness Stands Now
African sleeping sickness has been driven to the edge of elimination. Between 1999 and 2024, reported new cases of the West African form dropped 98%, from nearly 28,000 to 546. The East African form fell 94%, from 619 cases to 37. The World Health Organization has targeted the disease for elimination as a public health problem, and these numbers suggest that goal is within reach. The disease remains endemic in 24 countries for the West African form and 13 for the East African form, so continued surveillance and treatment access are what keep those numbers low.
Encephalitis lethargica, by contrast, remains one of medicine’s unsolved puzzles. No pathogen was ever identified, no vaccine was ever developed, and no satisfying explanation exists for why it appeared, killed or disabled hundreds of thousands of people, and then essentially disappeared. The two sleeping sicknesses share a name and a terrifying ability to dismantle the brain’s control over consciousness, but one is a disease we’ve nearly conquered and the other is a mystery we never solved.