Tetanus Prevention/Treatment: Evidence Review & Call for missing trials

Tetanus is a very severe disease that results in an inability of the brain and the nervous system to control the muscles in the body, resulting episodes in involuntary skeletal muscles spasms, some severe enough to fracture bones. It can also interfere with normal functioning of heart muscles and cause severe disturbances in heart rate, heart rythm, and blood pressure. It can also interfere with lung muscles and disrupt breathing and thus cause death. Even if treated early with the “state-of-the-art” techniques, over 10% of the patients die. Depending on different studies, this number can be as high as 50%. I discuss these and other tetanus epidemiology studies and highlight some findings not usually mentioned in articles about tetanus, e.g. about what kind of injuries are tetanus prone.

There are vaccines to prevent tetanus. Although they appear to be effective and a RCT (Randomized Controlled Trial) has shown them to be 98% causally effective in preventing tetanus during birth from unsanitary cord cutting, there is no such gold-standard evidence to estimate the effectiveness of tetanus vaccines in preventing tetanus after birth, e.g. in adults sustaining injuries. I review many observational studies and trials in animals that may help estimate this number.

In the last few decades, some of the tetanus vaccines, especially DTP, has been found to have a wide range of deleterious effects, although many claim these are less severe than tetanus. I discuss evidence of deleterious effects in depth but let the reader decide whether those risks outweigh the benefits. I call for and sketch the design of trials that would make it much easier to make this decision: the decision would be very easy if there was a very safe and 100% effective treatment of tetanus: numerous animal trials and (only) 1 human trial have shown a very safe substance to be 100% effective in treating tetanus. Also, the same treatment has also 100% effectiveness in animal trials in treating many other diseases with a similar mechanism: toxin producing bacteria, e.g. Diptheria, Pertussis (the D and P in DTP/ DTaP vaccines). Animal experiments suggest it likely works by neutralizing the toxins. But because of the severity of the tetanus, more confirmatory/refuting trials are needed before that treatment can be taken seriously or dismissed entirely. missing image. please report to the author

Disease Mechanism

In this article, I will describe many experiments about tetanus. These disparate experiments can be hard to follow/remember without a unifying theory explaining them. So I start with one, which is essentially the currently accepted “mainstream” theory.

(I have illustrated in other articles why mechanistic theories in medicine often mislead entire generation of medical researchers. They should only be used to come up with new hypothesis which should be tested end-to-end empirically. Always take such mechanistic theories with a grain of salt and try to think of other theories that may explain more experiments better. Later I point out some experiments this theory doesn’t explain well/easily.)

Several animal experiments have been done to understand the mechanisms of tetanus. These experiments suggest that tetanus is caused by the bacteria Clostridium tetani via the following mechanism:

  1. spores of Clostridium tetani get into a wound, typically during injury

  2. if the wound environment is conducive, e.g. anerobic (low oxygen) conditions in a wound that isn’t healing well, these spores germinate into Clostridium tetani bacteria and the bacteria then multiply.

  3. the bacteria produces a toxin called tetanospasmin which is the main driver of the disease. tetanospasmin eventually reaches the brain and interferes with motor neuron functioning and results in loss of control over muscles.

Tetanus is similar to Ditpheria and Pertussis (other disease that the DTP/DTaP vaccines are supposed to protect against) in that once the

The exact mechanism by which tetanospasmin travels from injury site to brain is somewhat disputed: although it is widely claimed that it transported from nerve endings local to the injury to the brain via the chains of neurons, some studies showing the lack of correlation between the neuronal distance of the injury site from the brain and the delay between injury and onset of tetanus suggest that all or part of the transportation may be happening via the blood.

Later in this article, we will discuss the animal experiments elucidating mechamisms, e.g. while discussing why certain treatments work and work only at certain times, and while discussing some interesting features of how tetanus presents.

Incidence rate, who gets it

Tetanus-susceptible wound types

No wound or obvious source of infection could be found in 7.4 per cent of all cases. This observation is consistent with other large series and probably reflects the presence of mall lesions that were not noted. src:paper: Tetanus in the US

“State-of-the-art” treatments: effectiveness

Safety is not too important here because these patients are already quite sick and without treatment, they have a very high chance of dying. Safety is important for vaccines which are given to healthy kids for a disease that was rare even before vaccination.

Tetanus Prevention

Vaccines before injury

Vaccines just after injury

Tetanus Immunoglbulin just after injury

Antibiotics just after injury

paper: Penicillin in Prevention of Tetanus

(mention vitamin C as a forward link)

Safety of Tetanus Vaccines

DTP experiment in Guinea Bissau (10x deaths), Atopic dermatitis lower on delaying DTaP, more SIDS with pentavalent in India/AIIMS study

Are TT/DT safer than DTaP? How much safer is DTaP vs DTP? Take a live vaccine just after the tetanus shot?

TT suffices for tetanus immunity: but TD actually has lower Aluminium (content measurements in Dr. Sears book)

One dose of tetanus toxoid confers little, if any, long- lasting immunity. A second dose confers protection in approximately 90% of individuals within 2–4 weeks, but immunity is short-lived in many individuals. A third dose ensures almost universal protection for at least 5 years.48 Tetanus toxoid vaccine is available as a monovalent tetanus toxoid, a bivalent toxoid combined with diphtheria or reduced diphtheria toxoid content, or a trivalent vaccine combined with diphtheria and whole cell or acellular pertussis (DTP vaccine).

Is there a safe 100% effective treatment?