Bacteria, Epidemiology, Infectious Diseases, Microbiology, Vaccines

The Great Masquerader: What Is Whipple’s Disease?

Author Chandana Balasubramanian , 07-Mar-2024

Whipple’s disease is a tricky infection that doctors sometimes call “The Great Masquerader” because it can look like a lot of other diseases, making it hard to diagnose. Whipple’s disease is caused by a bacteria called Tropheryma whipplei.


Whipple’s disease is also known as ‘Intestinal Lipodystrophy’ because it affects how the body deals with fats, leading to issues with digesting food properly. However, many aspects of this disease remain a puzzle, including how it spreads!


This blog talks about what makes Whipple’s disease a mystery, why it’s important to figure out if someone has it, and what we know about the bacteria that causes it. 


Let’s learn more about this rare, bacterial infectious disease.



First identified by George Hoyt Whipple in 1907, the condition was initially noted for its effects on the gastrointestinal system. Yet, as understanding of the disease evolved, it became clear that Whipple’s disease could impact various organs, including the Central Nervous System (CNS). 

At the time, Dr. Whipple reported on a 36-year-old man experiencing malabsorption, enlarged lymph nodes in the mesentery, joint pain, and changes in skin color. He termed the condition “Intestinal Lipodystrophy,” and his findings were shared in the Bulletin of Johns Hopkins Hospital.

Here are some important years and discoveries in the history of Whipple’s disease. 

  • 1907: George Hoyt Whipple, an American pathologist, first described the disease, but the causative organism was not identified until 1992. Whipple considered the observed intestinal lipodystrophy to result from a disturbed fat metabolism.
  • 1952: First treatment with antibiotics (chloramphenicol) appeared to be successful. During this time, scientists wondered if a bacteria may be the causative agent of this disease.
  • 1961: Electron microscopic studies provided insights into the disease, showing characteristic features of the bacteria.
  • 1992: Tropheryma whipplei was conclusively identified as the bacterium responsible for Whipple’s disease. Using PCR, scientists were able to amplify specific sections of the bacterium’s 16S rRNA. After further verification and detail enhancement, the bacterium was named Tropheryma whippelii. This name originates from the Greek words “trophe” for nourishment and “eryma” for barrier, highlighting the nutritional absorption issues caused by the infection.
  • 2003: Physicians at Johns Hopkins Hospital developed a diagnostic test for Whipple’s disease that greatly enhanced the precision of its diagnosis.


While Dr. Whipple was instrumental in first discovering Whipple’s disease, his main research at the time was on anemia. As a result, he did receive a Nobel Prize in 1934, but for his work in discovering that a diet rich in liver, kidney, and meat could improve patients with anemia.



Whipple’s disease is a rare condition, with the majority of cases documented in North America and Europe. It is a systemic illness that mainly affects middle-aged caucasian males. Disease onset is often after 50 years of age. The disease is rare in children. 

Whipple’s disease incidence varies in the literature. One study  approximates incidence at 12 new cases per year worldwide. However, the authors note that these numbers were determined before PCR was introduced as a diagnostic tool for Whipple’s disease. As a result, the actual incidence may be higher. 

Some estimate Whipple’s disease incidence anywhere from 1-6 new cases per 10 million persons per year, globally. 

Notable outbreaks

No significant outbreaks of Whipple’s disease have been documented. 


How does it spread?

There is no evidence that Whipple’s disease spreads from person to person. The bacteria has been isolated from feces in the past, which suggests a fecal mode of transmission. However, there is no definitive proof and many people can be asymptomatic carriers of the bacteria.

Since incidence is low and the disease is often misdiagnosed or diagnosis is delayed, it is challenging to figure out exactly how it spreads.

Biology of the disease

Whipple’s disease is believed to be caught by ingesting something that has the T.whipplei  bacteria in it. This assumption is because the symptoms are largely related to the gut. Also, the highest concentration of the bacteria in infected individuals is usually in the small intestine, where it can cross into the body, triggering an immune response.

Scientists have managed to grow the bacteria in the lab using certain cells, but in the body, it usually lives outside cells, thriving in the small intestine’s environment. T.whipplei causes internal ulcers and thickens body tissues. This changes the structure of the small intestine, making it hard for the body to absorb nutrients properly, leading to the symptoms of Whipple’s disease.

Not everyone who gets the bacteria gets sick. Some people, who are predisposed to getting Whipple’s disease may have muted immune systems that may increase their risk of getting infected. People with Whipple’s disease can have lasting changes in their immune system, making them more prone to getting it again, even after treatment. 

However, the exact immune system deficiencies that lead to the disease aren’t fully understood. It’s also noted that people with weakened immune systems might get other infections along with Whipple’s disease, making it even harder to determine the real issue.



Whipple’s disease is a chronic multisystem disorder characterized by weight loss, diarrhea, abdominal and joint pain.

According to the Mayo Clinic, symptoms include: 

  • Stomach cramps
  • Abdominal pain (which gets worse after eating)
  • Weight loss (from nutrient malabsorption)
  • Diarrhea
  • Joint inflammation
  • Tiredness
  • Weakness
  • Anemia


Some infected persons may also have:

  • Fever
  • Cough
  • Enlarged lymph nodes
  • Chest pain, and more. 


A small percentage, 10–15%, of individuals with Whipple’s disease will experience noticeable involvement of the central nervous system (CNS) over time. 

When the CNS is affected, individuals can also have difficulty walking, vision issues, brain fog and confusion, and even memory loss, dementia, psychiatric issues, depression, hypomania, anxiety, and more.

Most symptoms are gastrointestinal, but because Whipple’s disease affects many internal systems, it can also affect the brain and heart.



Diagnosing Whipple’s disease is not easy since symptoms are similar to many other conditions. The steps to diagnose the infection is through physical examination, a tissue biopsy from the small intestine, and blood tests to help determine if a patient is anemic. 

Since Whipple’s disease is often misdiagnosed, differential diagnosis is important. 

The features of Whipple’s disease may be similar to: 

  • Systemic inflammation
  • Celiac disease
  • CNS neoplasm
  • Rheumatoid arthritis
  • Chronic inflammatory rheumatism
  • Crohn’s vasculitis
  • Lymphoma
  • Sepsis, and more. 



Whipple’s disease treatment is through intravenous antibiotics like ceftriaxone or penicillin

There are no clear guidelines on the best frontline therapy for CNS Whipple’s disease, but some recommend intravenous antibiotic therapy for 2 weeks with ceftriaxone or meropenem.



Currently, there is no way to prevent Whipple’s disease. It is not contagious and the bacteria is believed to live in soil, so practicing safe hand hygiene practices may help lower the risk of getting infected. 



Whipple’s disease, often referred to as “The Great Masquerader,” presents a complex challenge in the world of medicine due to its elusive nature and ability to mimic many other conditions. 

From its initial association with gastrointestinal disturbances to the recognition of its impact on the CNS and beyond, we have come a long way in understanding this complex infectious disease. However, there is much more left to learn.

Even with better ways to diagnose it and more knowledge about Tropheryma whipplei, the bacteria causing this condition, Whipple’s disease still confuses doctors and scientists. What’s particularly puzzling is how it spreads and why people’s immune systems react to it differently.

Sure, the disease itself is rare, but the discovery and study of Whipple’s disease has provided insights into how complex our immune response can be when faced with a bacterial infection. It also shows the limitations we have with diagnostic tools to easily identify the root cause of an infectious disease that shares symptoms with many other conditions.


The GIDEON difference

GIDEON is one of the most well-known and comprehensive global databases for infectious diseases. Data is refreshed daily, and the GIDEON API allows medical professionals and researchers access to a continuous stream of data. Whether your research involves quantifying data, learning about specific microbes, or testing out differential diagnosis tools– GIDEON has you covered with a program that has met standards for accessibility excellence.

Learn more about more bacterial infections on the GIDEON platform.



1. Talaro KP, Chess B. Chapter 4: Nutrition and Growth of Bacteria. In: Foundations in Microbiology. 10th edition. New York, NY: McGraw-Hill Education; 2017. Available from:

2. Chaignot C, Weill FX, Mariani-Kurkdjian P, et al. Cluster of cases of haemolytic uraemic syndrome due to unpasteurised cheese. Lancet. 2001;357(9259):1950-1951.

3. Kimmitt PT, Harwood CR, Barer MR. Toxin gene expression by Shiga toxin-producing Escherichia coli: the role of antibiotics and the bacterial SOS response. Emerg Infect Dis. 2000;6(5):458-465.

4. Marvig RL, Sommer LM, Molin S, Johansen HK. Convergent evolution and adaptation of Pseudomonas aeruginosa within patients with cystic fibrosis. Nat Genet. 2015;47(1):57-64.

5. Maxwell MJ, Wilson M. Complications of treatment in end-stage renal disease. Kidney Int. 1999;55(1):1-13.

6. Plummer-Vinson syndrome. In: Medscape. New York, NY: WebMD LLC. Available from:

7. Whipple’s disease. In: Mayo Clinic. Rochester, MN: Mayo Foundation for Medical Education and Research. Available from:

8. Whipple’s disease: Diagnosis & treatment. In: Mayo Clinic. Rochester, MN: Mayo Foundation for Medical Education and Research. Available from:

9. Raoult D, Birg ML, La Scola B, et al. Cultivation of the bacillus of Whipple’s disease. N Engl J Med. 2000;342(9):620-625.

10. Fenollar F, Puéchal X, Raoult D. Whipple’s disease. N Engl J Med. 2007;356(1):55-66.

Chandana Balasubramanian

Chandana Balasubramanian is an experienced healthcare executive who writes on the intersection of healthcare and technology. She is the President of Global Insight Advisory Network, and has a Masters degree in Biomedical Engineering from the University of Wisconsin-Madison, USA.

Articles you won’t delete.
Delivered to your inbox weekly.