From Flu to Parkinson’s. Is There a Connection?

For decades, doctors noticed something peculiar after the devastating 1918 influenza pandemic: survivors began developing strange movement disorders that looked remarkably like Parkinson's disease [2]. This observation sparked one of medicine's most intriguing investigations—could common infections actually trigger neurodegeneration? 

Today, researchers are actively investigating whether infections associated with Parkinson's disease represent far more than mere complications. Bacterial and viral infections may serve as environmental catalysts that fundamentally alter brain chemistry, challenging everything we thought we knew about Parkinson's Disease and opening revolutionary pathways for prevention strategies.

While the connection between infections and Parkinson’s is intriguing, it’s important to remember the limitations of this research. Most studies show correlation, not causation — meaning we can’t say for certain that an infection directly causes Parkinson’s disease. Another challenge is that researchers rarely know every virus or bacterium a person has ever been exposed to, since many infections go unrecorded. Often, the studies rely on hospital records, which means they capture only the more severe cases. That raises another possibility: people who end up in the hospital with infections may already have underlying health vulnerabilities that also make them more prone to developing Parkinson’s later. In other words, the infection itself may not be the root cause, but rather one piece of a much larger and more complex puzzle.

Could a Simple Infection Start Your Parkinson's Journey?

The relationship between infection and the risk of Parkinson's disease is a fascinating area of current neurological research. Many studies have shown a connection between infectious agents and this chronic neurological disease. The etiology of Parkinson's Disease appears far more complex than previously understood, with infection and PD connections emerging through multiple pathways [3].

Recent groundbreaking research using Danish health care databases has provided some of the strongest evidence to date. The study found that compared with people who had not had a flu infection, those who had the flu had a 70 percent higher risk of Parkinson's 10 years later, and a 90 percent higher risk 15 years after [5].  Dr. J. Timothy Greenamyre, a neurologist and director of the Pittsburgh Institute for Neurodegenerative Diseases at the University of Pittsburgh, noted: "All in all, despite its limitations, I believe this is a solid, well-done epidemiological study. I think this paper provides the strongest evidence to date that exposure to influenza increases the risk for Parkinson's disease." [5].

Infections associated with Parkinson's disease work through several mechanisms. When an infectious agent enters the body, it can trigger neuroinflammation—a key feature observed in Parkinson's disease brains [3]. This inflammatory response, particularly when it becomes chronic, creates a toxic environment for dopaminergic neurons in the substantia nigra, the brain region most affected in Parkinson's Disease [1].

Scientists believe that the pathogenesis of Parkinson's Disease may begin with infection in the gastrointestinal tract or respiratory system. According to the Braak hypothesis, pathological changes could start in the gut's enteric nervous system or olfactory bulb—both potential entry points for infectious diseases [2]. This explains why constipation and smell loss often appear as non-motor symptoms of Parkinson's Disease years before motor symptoms develop [2]. READ: Is Parkinson's Disease Hereditary? 10 Truths You Need to Know

Which Specific Infections Pose the Greatest Risk?

Bacterial Infections: The Primary Culprits

Helicobacter pylori infection is associated with significantly increased risk of Parkinson's Disease [2]. This specific bacterial pathogen, which causes stomach ulcers, appears particularly relevant to PD risk. Research shows that patients with H. pylori infection not only face a higher risk of developing Parkinson's but also experience impaired levodopa absorption, affecting the treatment of Parkinson's Disease [1]. However, eradicating H. pylori does not seem to alter the risk of PD [2].

Urinary tract infection represents another critical concern, especially for people with Parkinson's Disease. UTI acts as a common precipitant of acute neurological deterioration and is a leading cause of delirium in Parkinson's Disease patients [4]. Patients are significantly more likely to be hospitalized for UTI compared to controls [4], and this systemic infection can dramatically worsen motor symptoms.

Other bacterial infection types linked to increased risk of PD include:

• Mycobacterium tuberculosis, which can induce neuroinflammation through specialized pathways [1]

• Porphyromonas gingivalis from periodontal disease, producing harmful enzymes that interfere with immune function [1]

• Clostridium difficile, particularly within the first two years post-infection [1]

• Proteus mirabilis, elevated in the gut microbiome of PD animals and linked to protein misfolding [3]
  

Viral Infections: The Inflammatory Triggers

Viral infections may pose a significant risk through their ability to induce "cytokine storms." Hepatitis C virus infection shows particularly compelling evidence, with British investigators finding that people with hepatitis B had a 76 percent higher risk of having Parkinson's, and people with hepatitis C a 51 percent higher risk [6]. 

However, Dr. Julia Pakpoor, a researcher at the University of Oxford, cautioned: "We can't be sure what is underlying this association. It could be the treatment for the hepatitis, or it could be that Parkinson's and hepatitis have common risk factors we haven't identified" [6].

Studies demonstrate that HCV infection substantially increases the risk of subsequent Parkinson's development [2]. Remarkably, successful antiviral treatment for chronic Hepatitis C virus infection has been associated with reduced risk of PD [2], suggesting that treating the infection may mitigate neuroinflammation in Parkinson's Disease.

The 1918 influenza virus infection pandemic provided early evidence linking viral infection to Parkinsonism [2]. Recent research confirms this connection is not merely a historical curiosity. Noelle M. Cocoros, a research scientist at the Harvard Pilgrim Health Care Institute, explained: "The association may not be unique to influenza, but it's the infection that has gotten the most attention. We looked at other infections as well, and there are several specific ones — hepatitis C and others — that may be associated with Parkinson's. But we didn't have large enough numbers to analyze them" [5].

While most influenza infections and PD connections involve non-neurotropic viruses, their systemic inflammatory effects can cross the blood-brain barrier and activate microglia, leading to dysfunction in parkinson's disease [2].

Other viruses associated with PD include Epstein-Barr virus, varicella-zoster virus, and various encephalitis-causing viruses that can trigger Postencephalitic Parkinsonism [3].

What Are the Treatment Implications?

The discovery of infections associated with Parkinson's Disease opens exciting therapeutic possibilities. Infection management may not only prevent disease onset but also modify its progression. Several antibiotics show neuroprotective properties beyond their antimicrobial effects:

• Rifampicin can cross the blood-brain barrier and demonstrates anti-inflammatory, anti-oxidant, and anti-apoptotic effects, helping preserve dopaminergic neurons [1]

• Tetracyclines like minocycline and doxycycline reduce neuroinflammation and protect against neurodegeneration by inhibiting microglial activation [1]

• Beta-lactam antibiotics like ceftriaxone show therapeutic efficacy in mouse model of Parkinson's Disease studies, preventing dopaminergic neuron degeneration and reducing abnormal movements [1]
  

For patients with Parkinson's Disease, infection prevention becomes crucial. Urinary tract infection management through proper hygiene, scheduled bladder emptying, and appropriate antibiotic prophylaxis when indicated can prevent acute deteriorations [4]. Some research suggests that probiotic consumption may improve motor scores and metabolic biomarkers, theorizing a decreased neuroinflammatory state [4]. Regarding vaccination, Dr. Cocoros noted: "There are many other good reasons to get a flu shot. But if there is an association with Parkinson's, then vaccination would lessen your risk. Still, it's pretty evident that Parkinson's can be caused by many things. Infection may be one of the many causes" [5].

Could Prevention Start with Infection Control?

Understanding infections associated with Parkinson's Disease suggests that potential risk factor modification might delay or prevent disease onset. This neurological disease represents the second most common neurodegenerative disease [3], making prevention strategies particularly valuable.

However, researchers caution against overinterpretation. Dr. Cocoros emphasized: "We've couched our findings with appropriate limitations. This is not evidence of a causal link between flu infection and Parkinson's. Our study adds to a broader literature, and we shouldn't overstate the results" [5]. Dr. Kelly A. Mills, an associate professor of neurology at Johns Hopkins, added: "The size of this study and the magnitude of the association they found is intriguing. It's a well-done study that brings up some important points to keep investigating" [5].

Infection control measures might include:

• Treating H. pylori infection when detected to improve levodopa absorption [1]

• Managing periodontal disease to reduce P. gingivalis exposure [1]

• Getting annual flu vaccinations to prevent respiratory tract infection [5]

• Considering antiviral treatment for chronic viral infections like hepatitis C [2]

• Supporting gut microbiome health through dietary and lifestyle interventions [2]
  

The risk of developing Parkinson's Disease appears to be associated with cumulative infection exposure. Research shows that the combination of antibodies against multiple pathogens was associated with PD compared to controls [2], suggesting that multiple infectious diseases may have additive effects. This "multiple microbe hypothesis" indicates that infection may represent a modifiable risk factor for Parkinson's Disease.

Infection in PD patients also affects medication absorption and effectiveness, making infection control essential for optimal treatment of Parkinson's Disease outcomes [1].

As Dr. Cocoros reflected on the broader implications: "On a purely scientific level, it's really interesting to think about the long-term consequences of an infection we usually just experience, recover from and then forget about. On a broader level, it's helpful to understand what it means for how we respond to infections" [5].

Seek Expert Neurological Care for Infection-Related Parkinson's Concerns

If you're worried about infections associated with Parkinson's disease or notice early signs like tremor or movement changes following an infection, seeking expert neurological evaluation can help assess your risk of developing this condition and create appropriate monitoring plans. Neurology Associates Neuroscience Center in Chandler and Mesa, Arizona, specializes in helping patients understand the complex relationships between infections and Parkinson's disease development.

Our team recognizes how various infectious exposures influence disease patients and parkinson's disease progression. We provide comprehensive assessments that evaluate your infection history while monitoring for early signs of neurodegeneration and implementing preventive strategies to optimize neurological health. Understanding the connection between infections associated with parkinson's disease can feel complex, so we offer detailed consultations about risk factors and personalized care approaches.

IMPORTANT NOTE: This blog post is for informational purposes only and not medical advice. Always consult a qualified healthcare provider for diagnosis or treatment decisions regarding Parkinson's disease, infection management, or any other medical condition. Do not rely on this content as a substitute for professional medical guidance.

References

[1] Sheng, S., Zhao, S., & Zhang, F. (2022). Insights into the roles of bacterial infection and antibiotics in Parkinson’s disease. Frontiers in Cellular and Infection Microbiology, 12, 939085. https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.939085/full

[2] Smeyne, R. J., Noyce, A. J., Byrne, M., Savica, R., & Marras, C. (2021). Infection and Risk of Parkinson’s Disease. Frontiers in Neurology, 11, 7990414. https://pmc.ncbi.nlm.nih.gov/articles/PMC7990414/

[3] Zorina, S. A., Jurja, S., Mehedinti, M., Stoica, A. M., Chita, D. S., Floris, S. A., & Axelerad, A. (2023). Infectious Microorganisms Seen as Etiologic Agents in Parkinson’s Disease. Life, 13(3), 805. https://www.mdpi.com/2075-1729/13/3/805

[4] Hogg, E., Frank, S., Oft, J., Benway, B., Rashid, M. H., & Lahiri, S. (2022). Urinary Tract Infection in Parkinson's Disease. Movement Disorders Clinical Practice. https://journals.sagepub.com/doi/10.3233/JPD-213103

[5] Bakalar, N. (2021, December 20). Can the Flu Contribute to Parkinson's Disease? The New York Times. https://www.nytimes.com/2021/12/20/well/live/flu-parkinsons.html

[6] Bakalar, N. (2017, March 30). Hepatitis Tied to Parkinson's Risk. The New York Times. https://www.nytimes.com/2017/03/30/well/live/hepatitis-tied-to-parkinsons-risk.html