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Epidemiologists do some impressive sleuthing, rapidly tracking down the causes of outbreaks from the Chipotle food poisonings to the spike in microcephaly in Brazil. But in some cases, years and even decades after an outbreak, the answers are still lacking.

Below, some notable scientific mysteries that researchers are still scratching their heads over.

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1. Disease by dust

People living in the Western United States are particularly vulnerable to the fungal infection known as Coccidioidomycosis, or valley fever, which is what those most familiar with the condition have called it for over 100 years.

The disease, caused when fungal spores are inhaled into the lungs, has had spikes of activity in the West for reasons that remain a mystery. Kern County, Calif., saw a big jump in cases in the early 1990s; in the early 2000s, two more waves of valley fever swept through two state prisons in the area, killing dozens of inmates. Nationally, more than 20,000 cases of the disease were reported in 2011, which has since subsided again. In a small number of cases, and for reasons doctors still don’t understand, the fungus spreads to other parts of the body, causing so-called disseminated coccidioidomycosis, which can cause swelling of the brain. 

2. Polio redux

More than 30 years after the last known case of polio in the US, 20 children in California came down with a disabling illness causing polio-like effects in 2014. Since then the Centers for Disease Control and Prevention has verified 120 cases of what it called acute flaccid myelitis across 34 states. Those afflicted, who were mostly teens and younger, exhibited the weak muscles, spinal cord abnormalities, and difficulty walking usually associated with polio.

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But they tested negative for polio. In a recent study, some tested positive for enterovirus D68, which doctors believe can sometimes cause physical disability. But, the CDC said, “the specific causes of this illness are still under investigation.”

3. Strange sleep

Between 1917 and 1925, 1 million people around the world came down with a disease that scientists still don’t understand. It was called encephalitis lethargica: People went from eating, walking, or talking to falling into a deep, still sleep that could last for days. Around half of them died. Those that survived later showed higher rates of Parkinson’s-like symptoms and psychiatric illnesses.

At the time, Viennese neurologist Constantin Von Economo found hypothalamic swelling in the brains of these patients. In the 1960s, neurologist Oliver Sacks revived the research, treating 60 sufferers at a Bronx hospital with the Parkinson’s drug L-dopa, though the effects didn’t last. The research project became the subject of his book “Awakenings” and a later film with Robin Williams.

4. Teen tics

Flailing arms, jerking heads, and stuttering speech were some of the symptoms that began strangely cropping up in teenage girls in Le Roy, N.Y., at the end of 2011. While one boy and an adult woman were affected, as well, most of the sufferers were high school girls, whose strange tics persisted for months with no discernible cause.

Parents wondered about the nearby Jell-O factory, a 1970 train accident, and chemical spill. Psychologists suggested stress and mass hysteria, particularly when widespread media coverage was followed by more young women claiming to have symptoms. A least one neurologist blamed PANDAS, or pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. For now, the prevailing theory is “conversion disorder”: people developing outward tics as a manifestation of internal stress.

5. Genital fears

Hysteria isn’t just for women. Several times in history, there have been spontaneous occurrences of large numbers of young men and boys claiming that their penises were shrinking, retracting, or missing altogether. A famous case of so-called koro happened in Singapore in 1967. In one day, nearly 100 men went to doctors claiming to feel their penises retracting; hundreds in total fell victim to the panic.

Other outbreaks, from Europe to Asia to Africa, have occurred as recently as 2003. Most doctors dismissed the outbreak as a type of anxiety brought on by cultural stigma and fears around male fertility.

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