Tetanus toxoid vaccine, also known as a “TT”, is a vaccine used to prevent infection by the organism Clostridium tetani. It is made up of tetanus toxoid which is an inactive form of the toxin, tetanospasmin. Tetanospasmin blocks the release of Glycine and GABA, which are inhibitory neurotransmitters leading to uninhibited muscular contractions and spastic paralysis. Clostridium tetani is a ubiquitous organism and can be found everywhere ranging from soil to the surface of an ax. Currently, the tetanus toxoid vaccine is amongst the immunization guidelines released by the World Health Organisation (WHO). It is administered in combination with diphtheria and pertussis toxoid as DTap to infants, adolescents, and children. Booster doses are also routinely given after an injury.
Parkinson’s disease is a degenerative neurological condition characterized by rigidity, bradykinesia, tremor, and loss of postural reflexes. It occurs more in the elderly, progresses with time, and currently has no cure. Treatment options so far address the symptoms and they include dopamine receptor agonists, monoamine oxidase type B inhibitors (MAOI-B), catechol-O-methyltransferase inhibitors (COMT), anticholinergic agents, amantadine, and levodopa. Levodopa has proven to be the single most effective treatment option available.
Recently, researchers have linked the toxins produced by Clostridium tetani to the development and progression of Parkinson’s disease. Studies have recorded a significant amount of clostridium tetani in the gastrointestinal tract of people with the disease and speculations are that the toxins of C. Tetani play a role in the pathogenesis of Parkinson’s. This has led to further speculations that fully immunized people might have reduced lifetime risk of developing Parkinson’s disease.
Tetanus toxoid vaccine causes lesser disease severity
An observational study that recruited 1446 patients has been carried out by Ariel Israel et al. at Leumit Health Services in Israel. The selected patients had been diagnosed with Parkinson’s between ages 45 and 75 years. They found out that vaccinated patients progressed slowly, the progression of the disease was linked to the amount of time after vaccination, and treatment with antibiotics affected the severity of the disease.
When C. Tetani invades the respiratory tract, they damage the olfactory nerve causing the transfer of neurotoxins to the basal ganglia. This destroys the dopaminergic neurons leading to symptoms of movement difficulties and dementia. Areas of the airway that have a greater amount of bacteria are the oropharynx and paranasal sinuses. Over time, the accumulation of neurotoxins gradually destroys the surrounding nervous tissue. Also, the marker for Parkinson’s disease, alpha-synuclein, is said to originate from the toxin and not only what we know to be the cause of Parkinson’s.
They discovered that the probability of developing Parkinson’s within two, five, and ten years after vaccination was 0, 0.17, and 0.26. This shows that as the immunity conferred by the vaccine wears off, the risk of developing the disease increases. They also developed an algorithm that compared the severity of the disease over time with vaccination status and discovered that vaccinated patients had a less severe disease course than patients who were not vaccinated. Furthermore, patients who had taken antibiotics like benzathine penicillin experienced a better disease course because of its anti-bacterial effect on C. Tetani, however, clindamycin made the disease course worse in some patients because it encouraged the multiplication of clostridium difficile, causing colitis.
Clinical Significance
The cause of Parkinson’s disease is multifactorial and includes genetic, environmental, and lifestyle factors, however, the evidence from the study shows that C. Tetani plays a significant role in the development of Parkinson’s disease. Therefore, vaccination against Clostridium tetani can be used as a therapeutic strategy for Parkinson’s disease.
Eliminating the bacteria from patients can produce a better clinical outcome in patients who eventually have the disease. Also, this study helps us to understand better the infection route and proliferation of C. Tetani in human beings.
Reference
Israel, A., Magen, E., Merzon, E., Ruppin, E., Vinker, S., & Giladi, N. (2024, May 10). Tetanus vaccination is associated with decreased incidence of Parkinson’s disease and slower progression. medRxiv (Cold Spring Harbor Laboratory). https://doi.org/10.1101/2024.05.03.24306800
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