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Tetanus

Category: Illness or disabilities

Type

Involuntary

Introduction and description

 

Tetanus, also known as lockjaw, is an infection characterized by muscle spasms.

In the most common type, the spasms begin in the jaw and then progress to the rest of the body.

Many animals can get tetanus, not just humans - dogs, for example, cattle, even camels:

Twenty days after an open castration, a 5-year-old dromedary was presented to the Dubai Camel Hospital with severe central nervous symptoms. The dromedary showed the following signs: off feed, stiff gait with extended neck, external swelling of the preputial sheath and groin region, and foamy saliva drooling from the mouth. The dromedary was unable to swallow. Three days after admission, the camel developed lockjaw, and on the fifth day it was unable to stand owing to paralysis of the hindquarters.  .... C. tetani was isolated from two soil samples of the horse paddock.  PMID: 15080538

Its cause is a bacteria - Clostridium tetani, which is commonly found in soil, saliva, dust, and manure. C. tetani spores have been detected in street dust and the dust and air of surgical operating theaters.  The bacteria generally enter through a break in the skin such as a cut or puncture wound by a contaminated object.  Severity of the wound does not determine the likelihood of infection:

The review of reported cases of tetanus demonstrates that it is not possible to clinically determine which wounds are tetanus prone, as tetanus can occur after minor, seemingly innocuous injuries, yet is rare after severely contaminated wounds. PMID: 15920431

Clostridium tetani produce toxins that interfere with muscle contractions, resulting in the typical symptoms.  It can cause death:

1 million cases of tetanus are estimated to occur worldwide each year, with more than 200,000 deaths. PMID: 27301930

Description of the disease by Hippocrates exists from at least as far back as the 5th century BC.  
Tetanus cases reported world-wide 1990 to 2004, darker colours indicate greater numbers

Symptoms

Incubation

The incubation period of tetanus may be up to several months, but is usually about ten days. In general, the farther the injury site is from the central nervous system, the longer the incubation period. The shorter the incubation period, the more severe the symptoms. In neonatal tetanus, symptoms usually appear from 4 to 14 days after birth, averaging about 7 days.

Diagnosis

The "spatula test" is a clinical test for tetanus that involves touching the posterior pharyngeal wall with a soft-tipped instrument and observing the effect. A positive test result is the involuntary contraction of the jaw (biting down on the "spatula") and a negative test result would normally be a gag reflex attempting to expel the foreign object. A short report in The American Journal of Tropical Medicine and Hygiene states that, in a patient research study, the spatula test had a high specificity (zero false-positive test results) and a high sensitivity (94% of infected patients produced a positive test).  Blood tests give false results and we will see why shortly.

Symptoms in general

 

Tetanus often begins with mild spasms in the jaw muscles—also known as lockjaw or trismus. The spasms can also affect the facial muscles resulting in an appearance called risus sardonicus. Chest, neck, back, abdominal muscles, and buttocks may be affected. Back muscle spasms often cause arching, called opisthotonos. Sometimes the spasms affect muscles that help with breathing, which can lead to breathing problems.

Prolonged muscular action causes sudden, powerful, and painful contractions of muscle groups, which is called "tetany". These episodes can cause fractures and muscle tears. Other symptoms include drooling, excessive sweating, headache, fever, hand or foot spasms, irritability, difficulty swallowing, suffocation, heart attack, breathing problems, irregular heartbeat, and uncontrolled urination or defecation.

It may take months to recover. Even with treatment, about 10% of people who contract tetanus die.

Types of Tetanus

The medical profession classify the symptoms of tetanus under the following headings:

  • Generalized tetanus  - is the most common type of tetanus, representing about 80% of cases. The first sign is trismus, or lockjaw, and the facial spasms called risus sardonicus, followed by stiffness of the neck, difficulty in swallowing, and rigidity of pectoral and calf muscles. Other symptoms include elevated temperature, sweating, elevated blood pressure, and episodic rapid heart rate. Spasms may occur frequently and last for several minutes with the body shaped into a characteristic form called opisthotonos. Spasms continue for up to four weeks, and complete recovery may take months.
  • Sympathetic overactivity (SOA)  - is common in severe tetanus and manifests as labile hypertension, tachycardia, dysrhythmia, peripheral vasculature constriction, profuse sweating, fever, increased carbon dioxide output, increased catecholamine excretion and late development of hypotension. Death can occur within four days.
  • Neonatal tetanus - Neonatal tetanus is a form of generalized tetanus that occurs in newborns. It usually occurs through infection of the unhealed umbilical stump, particularly when the stump is cut with a non-sterile instrument.
  • Local tetanus - is an uncommon form of the disease, in which patients have persistent contraction of muscles in the same anatomic area as the injury. The contractions may persist for many weeks before gradually subsiding. Local tetanus is generally milder; only about 1% of cases are fatal, but it may precede the onset of generalized tetanus.
  • Cephalic tetanus - Cephalic tetanus is the rarest form of the disease (0.9–3% of cases) and is limited to muscles and nerves in the head. It usually occurs after trauma to the head area, including skull fracture, laceration, eye injury, dental extraction, and otitis media, but it has been observed from injuries to other parts of the body. Paralysis of the facial nerve is most frequently implicated, which may cause lockjaw, facial palsy, or ptosis, but other cranial nerves can also be affected. Cephalic tetanus may progress to a more generalized form of the disease.  Cephalic tetanus is more likely than other forms of tetanus to be fatal, with the progression to generalized tetanus carrying a 15–30% case fatality rate.

Causes

 

Tetanus is caused by an infection with the bacterium Clostridium tetani.  

Clostridium tetani is strongly durable due to its endospores. Pictured is the bacterium alone, with a spore being produced, and the spore alone.  Because C. tetani is an anaerobic bacterium, it and its endospores thrive in environments that lack oxygen

Clostridium tetani is thus a gram-positive, spore-forming, motile, anaerobic bacillus. Typically measuring 0.3 to 0.5 μm in width and 2 to 2.5 μm in length, the vegetative form often develops long filament-like cells in culture. Motility is produced by peritrichous flagellae coating the cell surface. With sporulation, C. tetani loses its flagellae and takes on the more characteristic drumstick-like appearance reflecting spore formation in the terminal position. C. tetani is a strict anaerobe that grows optimally at 33° to 37° C; however, depending on the strain, growth can occur at 14° to 43° C.

Sporulation depends on a variety of factors that include pH, temperature, and medium composition. Spores can be promoted at 37° C and in the presence of oleic acid, phosphates, 1% to 2% sodium chloride, protein, and magnesium.  In contrast, acidification, high (≥ 41° C) or low (≤ 25° C) temperatures, glucose, assorted saturated fatty acids, antibiotics, and potassium inhibit spore formation. The germination of spores requires anaerobic conditions and is enhanced by the presence of lactic acid and chemicals toxic to cells.  Spores are resistant to boiling and a variety of disinfectants.

Unlike many infectious diseases, recovery from naturally acquired tetanus does not usually result in immunity to tetanus. This is due to the extreme potency of the tetanospasmin toxin. Tetanospasmin will likely be lethal before it will provoke an immune response. 

Tetanus toxin

Tetanus toxin is an extremely potent neurotoxin produced by the vegetative cell of Clostridium tetani in anaerobic conditions, causing tetanus.  It is also called spasmogenic toxin, or TeNT. The LD50 of this toxin has been measured to be approximately 2.5-3 ng/kg.  C. tetani also produces the exotoxin tetanolysin, a hemolysin, that causes destruction of tissues.

Tetanus toxin spreads through tissue spaces into the lymphatic and vascular systems. It enters the nervous system at the neuromuscular junctions and migrates through nerve trunks and into the central nervous system (CNS) by retrograde axonal transport by using dyneins.

Tetanus toxin causes violent spastic paralysis by blocking the release of γ-aminobutyric acid (GABA). GABA is a neurotransmitter that inhibits motor neurons.

Bacteriophage and plasmids

 

One of the interesting questions that arise from examining this bacteria is why everyone who suffers from a puncture wound of some sort does not get tetanus. 

C. tetani spores are ubiquitous.

They are more common in hot, damp climates with soil rich in organic matter, but manure-treated soils may contain spores, and they are widely distributed in the intestines and faeces of many animals such as horses, sheep, cattle, dogs, cats, rats, guinea pigs, and chickens.

We too harbour this bacteria all the time, but it doesn’t produce any toxins nor do us any harm.  There are indications that this bacteria is part of our intestinal flora:

Clostridium tetani, the bacterium causing tetanus, can be found both in the soil and intestinal normal flora. PMID:  24605433

It is also worth pointing out that there are currently no blood tests for diagnosing tetanus, because the bacteria can be found in the blood of healthy people.  The diagnosis of tetanus is based on the presentation of tetanus symptoms and does not depend upon isolation of the bacterium, which is recovered from the wound in only 30% of cases and can be isolated from patients without tetanus.

All this leads us to the interesting question, why do some bacteria release this toxin and not others?  And what part of the bacteria does the releasing?

There are two candidates for the releasing mechanism - plasmids and bacteriophage and it appears that some of these bacteria do harbour bacteriophages.

Two C. tetani strains used for toxin production spontaneously produce two varieties of phage-like particles with isometric heads. Type A has a contractile tail, whereas type B shows a non-contractile tail with a long, wavy tail fiber.  PMID:  353909

There are a number of papers on PubMed supporting this conclusion, for example:

The isolation of hexagonal-headed, tailless, bacteriophage-like particles from uninduced cultures of Clostridium tetani is described. Clear, round, 1--3 mm diameter plaques were noted on Clostrisel agar plates, which were overlaid with soft agar inoculated with 7--14 day broth cultures. Particles were detected by transmission electron microscopy from broth cultures seeded with scrapings from the plaques. Both electron dense and electron lucent heads were noted. An electron dense head was observed attached to the surface of a dividing bacterium.  PMID: 354626

 

BUT, the evidence actually points to the fact that in this case the bacteria use Plasmids. 

A plasmid is a small DNA molecule within a cell that is physically separated from a chromosomal DNA and can replicate independently. In nature, plasmids often carry genes that may benefit the survival of the organism, for example antibiotic resistance.

Plasmid-encoded virulence factors are important in the pathogenesis of diseases caused by spore-forming bacteria. Unlike many other bacteria, the most common virulence factors encoded by plasmids in Clostridium and Bacillus species are protein toxins. ….. Genetic studies have led to the determination of the role of these toxins in disease pathogenesis. The genes for these toxins are generally carried on large conjugative plasmids that have common core replication, maintenance, and conjugation regions. …. Toxin genes may also be plasmid-encoded in the neurotoxic clostridia. The tetanus toxin gene is located on a plasmid in Clostridium tetani. PMID:  26104459

 

The plasmids are known to allow the organism to utilize particular organic compounds that would be advantageous when nutrients are scarce. 

In other words the plasmids are a survival mechanism for these bacteria, in an age when soils are depleted of nutrients, we should expect the increase of plasmid carrying Clostridium tetani.  Contrary to what science has indicated therefore, it is not manure or enriched soils that harbour these plasmid armed bacteria, but poor depleted soils.

The use of antibiotics in farming may also increase the prevalence of these plasmid carrying bacteria.

Environmental antibiotic resistance has drawn increasing attention due to its great threat to human health. In this study, we investigated concentrations of antibiotics (tetracyclines, sulfonamides and (fluoro)quinolones) and abundances of antibiotic resistance genes (ARGs), including tetracycline resistance genes, sulfonamide resistance genes, and plasmid-mediated quinolone resistance genes, and analyzed bacterial community composition in aquaculture environment in Guangdong, China. The concentrations of sulfametoxydiazine, sulfamethazine, sulfamethoxazole, oxytetracycline, chlorotetracycline, doxycycline, ciprofloxacin, norfloxacin, and enrofloxacin were as high as 446 μg kg(-1) and 98.6 ng L(-1) in sediment and water samples, respectively. ….. The genera associated with pathogens were also observed, such as Acinetobacter, Arcobacter, and Clostridium. …. The results [also] indicated that fish ponds are reservoirs of ARGs and the presence of potential resistant and pathogen-associated taxonomic groups in fish ponds might imply the potential risk to human health.   PMID:  25753824

So not just animal farming, but fish farming as well.  We pose a great threat to these bacteria and the toxin and plasmid is a defence mechanism. Search as we might, we could find not a single research paper that described the role of these bacteria in the ecosystem, and yet they are clearly extremely important given their ubiquity.  The virulence of the toxin produced is also a signal that these bacteria are essential to the healthy balance of the planet's ecology.

 

Prevention

Clearly, from the analysis above, the main ways to prevent Tetanus, is to stop the use of antibiotics in farming and also reduce the use of antibiotics in all but the most essential of cases in human health. It is also essential we start to employ farming methods that enrich the soil again naturally, using compost and manure.  If this bacteria is threatened less it may cease to produce as many toxins in defence.

And we can also help ourselves.  One of the obvious reasons why the bacteria may enter the body is if we have any form of compromised skin immunity.  Under normal circumstances the skin is well supplied with defences against bacteria, that ensure the bacteria does not enter the blood stream, but as this paper shows any very extreme forms of stress and emotion, such as fear or terror, may cause the immune system to be compromised:

Delayed-type hypersensitivity (DTH) reactions are antigen-specific, cell-mediated immune responses that, depending on the antigen, mediate beneficial (resistance to viruses, bacteria, fungi) or harmful (allergic dermatitis, autoimmunity) aspects of immunity.

 

Contrary to the widely held notion that stress is immunosuppressive, we have shown that under certain conditions, stress can enhance immune function. …. Studies have shown that acute stress administered immediately before antigen exposure significantly enhances skin DTH. In contrast, chronic stress significantly suppresses skin DTH. Stress-induced changes in leukocyte distribution may contribute to these bidirectional effects of stress, since acute stress induces a significant mobilization of leukocytes from the blood to the skin, whereas chronic stress suppresses leukocyte mobilization. ….. Thus, the timing and duration of stress may significantly affect the nature (enhancing versus suppressive) of the effects of stress on skin immune function. These results suggest that during acute stress, stress hormones may help enhance immune function by informing the immune system about impending challenges ….., the brain may send a warning signal to the immune system, just as it does to other fight/flight systems in the body.  PMID:  11268419

As such methods that help to relax and calm a person whilst allowing their immune defences to come into play may be very beneficial. 

Note that bacterial wipes may actually harm the skin’s defences instead of removing the harmful bacteria.  Abundant clean water is the best way to wash any wound.

Treatment

Diet

There is the possibility that adjustment of the diet may help in removing any bacteria from the intestines that are the toxin producing kind.  Please do not assume that this is some kind of preventative measure, as the reverse may be true.  If the intestine contains non toxin producing versions of the bacteria, then depending of their eventual role, we may find it is better to feed them!  Spores can be promoted in the presence of

  • oleic acid,
  • phosphates
  • sodium chloride
  • protein and
  • magnesium  

Thus temporary reduction of these things from the diet may help in treatment of those with tetanus.  Since

  • Acidification
  • assorted saturated fatty acids, and
  • potassium

inhibit spore formation, then again a diet rich in these should help to reduce spore formation in treatment of those with tetanus.

Cleaning teeth

The germination of spores is enhanced by the presence of lactic acid.  Lactic acid bacteria convert simple carbohydrates such as glucose, sucrose, or galactose to lactic acid. These bacteria can grow in the mouth; the acid they produce is responsible for the tooth decay known as caries.  Thus it may be helpful to reduce sugar intake considerably and regularly clean your teeth.

Rest and sleep

The germination of spores is enhanced by the presence of lactic acid.  The concentration of blood lactate is usually 1–2 mmol/L at rest, but can rise to over 20 mmol/L during intense exertion and as high as 25 mmol/L afterward.  Thus it is essential that one rests, and sleeps

Vaccines

The medical community advocate the use of immunization, with the tetanus vaccine as a preventative.  The vaccine is not based on the bacteria, as the cause of the tetanus is the toxin.  Tetanus vaccine, also known as tetanus toxoid (TT), is thus an inactive vaccine based on the toxin, used to prevent tetanus.

The development of this vaccine started in the 1800s.  In 1884, Arthur Nicolaier isolated the strychnine-like toxin of tetanus from free-living, anaerobic soil bacteria. The etiology of the disease was further elucidated in 1884 by Antonio Carle and Giorgio Rattone, two pathologists of the University of Turin, who demonstrated the transmissibility of tetanus for the first time. They produced tetanus in rabbits by injecting pus from a patient with fatal tetanus into their sciatic nerves.  In 1891, C. tetani was isolated from a human victim by Kitasato Shibasaburō, who later showed that the organism could produce disease when injected into animals, and that the toxin could be neutralized by specific antibodies.  And it is from this discovery that the vaccine was eventually developed.

It is extremely difficult to judge the efficacy of this vaccine.  At the time it was introduced mass migrations of people into the urban environment and improved hygiene and living conditions resulted in general improvements in health.  Farming became more mechanised, meaning that many farm workers were no longer exposed to the bacteria in the soil. 

In developed countries, neonatal tetanus was actually eradicated before the development of passive immunization against tetanus. For example, in Finland, the last case of neonatal tetanus was reported in 1915. This is attributable most likely to good birth practices because the systematic immunization of infants against tetanus did not commence there until relatively recently—in 1957.

There are also concerns about the continued efficacy of the vaccine, and the possibility that the bacteria are reacting to the onslaught we have waged upon them with new and different types of toxin, meaning the vaccine is ineffective:

We report a case of generalised tetanus in a 22-year-old woman that arose despite the protective antitoxin antibody in her serum. The patient received all her vaccinations in the USA; her last vaccination was 6 years ago. The case was unusual because the patient had received all standard vaccinations, had no defined port of entry at disease onset, and had symptoms lasting for 6 months. PMID:  27301930

There have also been severe reactions to the vaccine:

Children experiencing severe reactions within 48 hours of DTP immunization [were] evaluated within 24 hours of the reaction. Severe reactions included encephalopathy, persistent crying > or = 3 hours, hypotonic-hyporesponsive episodes (collapse episodes), fever > or = 40.5 degrees C, or seizures. …… ….Sixty children experienced severe reactions within 48 hours of DTP immunization: ….. Some relatively elevated insulin values were noted; however, this finding was also noted in the comparison group of children experiencing febrile seizures unrelated to immunization. ….   PMID:  8502521

In children under the age of seven, the tetanus vaccine is often administered as a combined vaccine, DPT/DTaP vaccine, which also includes vaccines against diphtheria and pertussis. For adults and children over seven, the Td vaccine (tetanus and diphtheria) or Tdap (tetanus, diphtheria, and acellular pertussis) is commonly used.

Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b JAMA 2012, Yuelian Sun, Jakob Christensen, Anders Hviid, Jiong Li

Summary: "DTaP-IPV-Hib vaccination was associated with an increased risk of febrile seizures on the day of the first 2 vaccinations given at 3 and 5 months."

And there are considerable concerns about the excipient used in these vaccines, the following has been extracted from the Wikipedia entry for list of vaccine ingredients

vaccine

Excipient and adjuvant

DT (diphtheria vaccine plus tetanus vaccine) (Sanofi)

Aluminum potassium sulfate, bovine extract, formaldehyde, thimerosal

DTaP (DAPTACEL)

Aluminum phosphate, formaldehyde, Glutaraldehyde, 2-phenoxyethanol

DTaP (Infanrix)

Aluminum hydroxide, bovine extract, formaldehyde, glutaraldhyde, polysorbate 80

DTaP (Tripedia)

Aluminum potassium sulfate, ammonium sulfate, bovine extract, formaldehyde, gelatin, peptone, polysorbate 80, sodium phosphate, thimerosal

DTaP/Hib (TriHIBit)

Aluminum potassium sulfate, ammonium sulfate, bovine extract, formaldehyde or formalin, gelatin, polysorbate 80, sucrose, thimerosal

DTaP-IPV (KINRIX)

Aluminum hydroxide, calf serum, formaldehyde, glutaraldehyde, lactalbumin hydrolysate, neomycin sulfate, polymyxin B, polysorbate 80

DTaP-HepB-IPV (Pediarix)

Aluminum hydroxide, aluminum phosphate, calf serum, lactalbumin hydrolysate, formaldehyde, glutaraldhyde, neomycin sulfate, polymyxin B, polysorbate 80, yeast protein

DtaP-IPV/Hib (Pentacel)

Aluminum phosphate, bovine serum albumin, formaldehyde, glutaraldehyde, MRC-5 cellular protein, neomycin, polymyxin B sulfate, polysorbate 80, 2-phenoxyethanol

 Aluminium is known to destroy the blo

References and further reading

  • Ann N Y Acad Sci. 2000;917:876-93.  Acute stress enhances while chronic stress suppresses skin immunity. The role of stress hormones and leukocyte trafficking.  Dhabhar FS1.
  • Rev Can Biol. 1978 Mar;37(1):43-6.  [Phage-like particles produced by Clostridium tetani].  [Article in French]  Ackermann HW, Fredette TV, Vinet G.
  • Aust J Exp Biol Med Sci. 1978 Apr;56(2):139-45.  Isolation of bacteriophage-like particles from uninduced Clostridium tetani cultures.  Brown KJ, Brown PA.
  • Microbiol Spectr. 2014 Dec;2(6). doi: 10.1128/microbiolspec.PLAS-0024-2014.  Virulence Plasmids of Spore-Forming Bacteria.  Adams V, Li J, Wisniewski JA, Uzal FA, Moore RJ, McClane BA, Rood JI.
  • Microb Ecol. 2015 Aug;70(2):425-32. doi: 10.1007/s00248-015-0583-x. Epub 2015 Mar 10.  Antibiotics, Antibiotic Resistance Genes, and Bacterial Community Composition in Fresh Water Aquaculture Environment in China.   Xiong W1, Sun Y, Zhang T, Ding X, Li Y, Wang M, Zeng Z.   National Laboratory of Safety Evaluation (Environmental Assessment) of Veterinary Drugs, College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou, 510642, China.  
  • Lancet Infect Dis. 2016 Jun;16(6):746-752. doi: 10.1016/S1473-3099(16)00075-X.  An unexpected tetanus case.  Ergonul O1, Egeli D2, Kahyaoglu B3, Bahar M2, Etienne M4, Bleck T5.
  • Features of C. Tetani - C. Louise Thwaites, Lam Minh Yen, in Manson's Tropical Infectious Diseases (Twenty-third Edition), 2014 - Pathology and Pathophysiology
  • Bacterial and Mycotic Diseases of Nonhuman Primates - Joe Simmons, Susan Gibson, in Nonhuman Primates in Biomedical Research (Second Edition), 2012
  • Infectious or Acquired Motor Neuron Diseases - Manikum Moodley, ... Alan R. Seay, in Neuromuscular Disorders of Infancy, Childhood, and Adolescence (Second Edition), 2015

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