Fatigue can stem from a variety of illnesses and life stressors, but when that exhaustion lasts for months — often following an infection — it may indicate a condition called chronic fatigue syndrome.

Approximately 3.3 million people in the United States currently have the syndrome, with about one in four people confined to their bed at some point during the illness, according to the Centers for Disease Control and Prevention.

Despite its prevalence, experts say it’s a poorly understood condition that physicians frequently miss, with past research suggesting that only about 15% of those affected are diagnosed correctly.

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What is chronic fatigue syndrome?

Formally known as myalgic encephalomyelitis (ME), chronic fatigue syndrome (CFS) is a chronic disease that causes fatigue so severe that it impairs the ability to perform daily activities.

The National Academy of Medicine defines the syndrome as having the following three symptoms that last at least six months.

• Severe fatigue that is 1) new and 2) decreases the ability to perform activities that you did normally prior to illness
• “Malaise” that worsens after physical or mental effort that previously was well-tolerated
• Unrestful sleep

People may also experience trouble with thinking and memory (often called “brain fog”) or lightheadedness when standing up. 

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There are no tests to confirm chronic fatigue, so doctors diagnose it by talking to their patients, examining them and excluding other disorders, like hypothyroidism and depression, that often share the same symptoms.

“CFS, fibromyalgia and long COVID are all related conditions with different names,” Dr. Jacob Teitelbaum, author of “From Fatigued to Fantastic” — whose research focuses on chronic fatigue syndrome — told Fox News Digital. “What these illnesses have in common is that they are immune disorders, and immune disorders predominantly affect women.”

Many genes related to immune disorders are on the X chromosome, suggesting a genetic component, the doctor added.

Causes of chronic fatigue

Chronic fatigue syndrome may be triggered by infection or other physiologic stressors, but its causes and symptoms can vary widely from person to person, according to Dr. Julia Oh, a professor in dermatology, molecular genetics and microbiology, and integrative immunobiology at the Duke University School of Medicine in North Carolina.

Teitelbaum compared the condition to a “severe energy crisis” in the body. When energy drops low enough, the “control center” in the brain — the hypothalamus, which regulates sleep, hormones, blood pressure and pulse — may not work as well.

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Although hypothalamic dysfunction can trigger dozens of other symptoms, the hallmark signs are insomnia (despite exhaustion), brain fog and widespread pain, the doctor said.

Anything that causes severe energy depletion can trigger the syndrome, including chronic life stressors, nutritional deficiencies, thyroid and stress hormone imbalances, and sleep problems.

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These triggers are usually associated with a gradual onset of CFS, but sudden onset can be caused by certain infections, with two classic ones being COVID and mononucleosis, past research has shown.

Head and neck trauma and sudden hormonal shifts after pregnancy can also trigger chronic fatigue, Teitelbaum warned.

There aren’t currently any blood tests to uniformly diagnose the syndrome, but Dr. Oh said she is hopeful that will change in the future.

Her research team developed an experimental artificial intelligence-based tool, BioMapAI, that has been shown to identify the condition with high accuracy by analyzing stool, blood and other common lab tests, according to early research published in July in the journal Nature Medicine.

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“Instead of finding one smoking gun for the disease, our AI model uncovered a distinct biological fingerprint that was dysregulated in the patients, which spanned changes in gut bacteria, hyperactive immune cells and disrupted metabolism,” Oh told Fox News Digital.

Treatments and therapies

Given how differently chronic fatigue syndrome can affect people, there is no universally effective therapy, according to Oh.

The CDC recommends that patients with CFS work with their doctors to create a management plan based on the symptoms that most affect quality of life.

There are no tests to confirm chronic fatigue, so doctors diagnose it by evaluating symptoms and excluding other disorders.

Treatments generally include a combination of lifestyle changes, therapies and medications. Patients and their physicians should weigh the potential benefits and risks of any approach.

There are some alternative therapies that have shown to be effective for some. Teitelbaum developed a protocol called SHINE, which focuses on sleep, hormones and hypotension, infections, nutrition and exercise. Some research has shown that this approach can help to improve the quality of life for people with CFS and fibromyalgia.

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Others may find alternative treatments, like physiotherapy (physical therapy) to be helpful.

Those who experience persistent fatigue that hinders their ability to participate in regular activities or impacts their quality of life should speak with a doctor.

Long before the Black Death killed millions across Europe in the Middle Ages, an earlier, more elusive version of the plague spread across much of Eurasia.

For years, scientists were unsure how the ancient disease managed to spread so widely during the Bronze Age, which lasted from roughly 3300 to 1200 B.C., and stick around for nearly 2,000 years, especially since it wasn’t spread by fleas like later plagues. Now, researchers say a surprising clue may help explain it, a domesticated sheep that lived more than 4,000 years ago.

Researchers found DNA from the plague bacterium Yersinia pestis in the tooth of a Bronze Age sheep discovered in what is now southern Russia, according to a study recently published in the journal Cell. It is the first known evidence that the ancient plague infected animals, not just people, and offers a missing clue about how the disease spread.

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“It was alarm bells for my team,” study co-author Taylor Hermes, a University of Arkansas archaeologist who studies ancient livestock and disease spread, said in a statement. “This was the first time we had recovered the genome from Yersinia pestis in a non-human sample.”

And it was a lucky discovery, according to the researchers.

“When we test livestock DNA in ancient samples, we get a complex genetic soup of contamination,” Hermes said. “This is a large barrier … but it also gives us an opportunity to look for pathogens that infected herds and their handlers.”

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The highly technical and time-consuming work requires researchers to separate tiny, damaged fragments of ancient DNA from contamination left by soil, microbes and even modern humans. The DNA they recover from ancient animals is often broken into tiny pieces sometimes just 50 “letters” long, compared to a full human DNA strand, which contains more than 3 billion of those letters.

Animal remains are especially tough to study because they are often poorly preserved compared to human remains that were carefully buried, the researchers noted.

The finding sheds light on how the plague likely spread through close contact between people, livestock and wild animals as Bronze Age societies began keeping larger herds and traveling farther with horses. The Bronze Age saw more widespread use of bronze tools, large-scale animal herding and increased travel, conditions that may have made it easier for diseases to move between animals and humans.

When the plague returned in the Middle Ages during the 1300s, known as the Black Death, it killed an estimated one-third of Europe’s population.

“It had to be more than people moving,” Hermes said. “Our plague sheep gave us a breakthrough. We now see it as a dynamic between people, livestock and some still unidentified ‘natural reservoir’ for it.”

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Researchers believe sheep likely picked up the bacteria from another animal, like rodents or migratory birds, that carried it without getting sick and then passed it to humans. They say the findings highlight how many deadly diseases begin in animals and jump to humans, a risk that continues today as people move into new environments and interact more closely with wildlife and livestock.

“It’s important to have a greater respect for the forces of nature,” Hermes said.

The study is based on a single ancient sheep genome, which limits how much scientists can conclude, they noted, and more samples are needed to fully understand the spread.

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The researchers plan to study more ancient human and animal remains from the region to determine how widespread the plague was and which species may have played a role in spreading it. 

They also hope to identify the wild animal that originally carried the bacteria and better understand how human movement and livestock herding helped the disease travel across vast distances, insights that could help them better anticipate how animal-borne diseases continue to emerge.

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The research was led by scientists at the Max Planck Institute for Infection Biology, with senior authors Felix M. Key of the Max Planck Institute for Infection Biology and Christina Warinner of Harvard University and the Max Planck Institute for Geoanthropology.

The research was supported by the Max Planck Society, which has also funded follow-up work in the region.

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