Tetanus

Tetanus, also known as lockjaw, is a bacterial infection characterized by muscle spasms.[1] In the most common type, the spasms begin in the jaw and then progress to the rest of the body.[1] Each spasm usually lasts a few minutes and spasms occur frequently for three to four weeks.[1] Spasms may be severe enough to cause bone fractures.[6] Other symptoms of tetanus may include fever, sweating, headache, trouble swallowing, high blood pressure, and a fast heart rate.[1][6] Onset of symptoms is typically three to twenty-one days following infection.[1] Recovery may take months.[1] About ten percent of cases prove fatal.[1]

Tetanus is caused by an infection with the bacterium Clostridium tetani,[1] which is commonly found in soil, saliva, dust, and manure.[2] The bacteria generally enter through a break in the skin such as a cut or puncture wound by a contaminated object.[2] They produce toxins that interfere with normal muscle contractions.[3] Diagnosis is based on the presenting signs and symptoms.[1] The disease does not spread between people.[1]

Tetanus can be prevented by immunization with the tetanus vaccine.[1] In those who have a significant wound and have had less than three doses of the vaccine, both vaccination and tetanus immune globulin are recommended.[1] The wound should be cleaned and any dead tissue should be removed.[1] In those who are infected, tetanus immune globulin or, if unavailable, intravenous immunoglobulin (IVIG) is used.[1] Muscle relaxants may be used to control spasms.[3] Mechanical ventilation may be required if a person's breathing is affected.[3]

Tetanus occurs in all parts of the world but is most frequent in hot and wet climates where the soil contains a lot of organic matter.[1] In 2015 there were about 209,000 infections and about 59,000 deaths globally.[4][5] This is down from 356,000 deaths in 1990.[7] Description of the disease by Hippocrates exists from at least as far back as the 5th century BC.[1] The cause of the disease was determined in 1884 by Antonio Carle and Giorgio Rattone at the University of Turin, and a vaccine was developed in 1924.[1]

Tetanus
Opisthotonus in a patient suffering from tetanus - Painting by Sir Charles Bell - 1809
Muscle spasms (specifically opisthotonos) in a person with tetanus. Painting by Sir Charles Bell, 1809.
SpecialtyInfectious disease
SymptomsMuscle spasms, fever, headache[1]
Usual onset3–21 days following exposure[1]
DurationMonths[1]
CausesClostridium tetani[1]
Risk factorsBreak in the skin[2]
Diagnostic methodBased on symptoms[1]
PreventionTetanus vaccine[1]
TreatmentTetanus immune globulin, muscle relaxants, mechanical ventilation[1][3]
Prognosis10% chance of death[1]
Frequency209,000 (2015)[4]
Deaths56,700 (2015)[5]

Signs and symptoms

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.[1]

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 fever, headache, restlessness, irritability, feeding difficulties, breathing problems, burning sensation during urination, urinary retention and loss of stool control.[8]

Even with treatment, about 10% of people who contract tetanus die.[1] The mortality rate is higher in unvaccinated people and people over 60 years of age.[1]

Incubation period

The incubation period of tetanus may be up to several months, but is usually about ten days.[9][10] 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.[11] In neonatal tetanus, symptoms usually appear from 4 to 14 days after birth, averaging about 7 days. On the basis of clinical findings, four different forms of tetanus have been described.[1]

Generalized tetanus

Generalized tetanus is the most common type of tetanus, representing about 80% of cases. The generalized form usually presents with a descending pattern. 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.[1]

Neonatal tetanus

Neonatal tetanus is a form of generalized tetanus that occurs in newborns, usually those born to mothers who themselves have not been vaccinated. If the mother has been vaccinated against tetanus, the infants acquire passive immunity and are thus protected.[12] It usually occurs through infection of the unhealed umbilical stump, particularly when the stump is cut with a non-sterile instrument. As of 1998 neonatal tetanus was common in many developing countries and was responsible for about 14% (215,000) of all neonatal deaths.[13] In 2010 the worldwide death toll was 58,000 newborns. As the result of a public health campaign, the death toll from neonatal tetanus was reduced by 90% between 1990 and 2010, and by 2013 the disease had been largely eliminated from all but 25 countries.[14] Neonatal tetanus is rare in developed countries.

Local tetanus

Local tetanus is an uncommon form of the disease, in which people 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)[15] and is limited to muscles and nerves in the head.[16] It usually occurs after trauma to the head area, including skull fracture,[17] laceration,[17] eye injury,[16] dental extraction,[18] and otitis media,[19] but it has been observed from injuries to other parts of the body.[20] 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.[18][21] Cephalic tetanus may progress to a more generalized form of the disease.[15][21] Due to its rarity, clinicians may be unfamiliar with the clinical presentation and may not suspect tetanus as the illness.[16] Treatment can be complicated as symptoms may be concurrent with the initial injury that caused the infection.[17] 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.[15][17][21]

Cause

Clostridium Tetani
Clostridium tetani is durable due to its endospores. Pictured is the bacterium alone, with a spore being produced, and the spore alone.

Tetanus is caused by the tetanus bacterium Clostridium tetani.[1] Tetanus is an international health problem, as C. tetani endospores are ubiquitous. Endospores can be introduced into the body through a puncture wound (penetrating trauma). Due to C. tetani being an anaerobic bacterium, it and its endospores thrive in environments that lack oxygen, such as a puncture wound.

The disease occurs almost exclusively in persons inadequately immunized.[22] It is more common in hot, damp climates with soil rich in organic matter. Manure-treated soils may contain spores, as they are widely distributed in the intestines and feces of many animals such as horses, sheep, cattle, dogs, cats, rats, guinea pigs, and chickens.[1] In agricultural areas, a significant number of human adults may harbor the organism.

The spores can also be found on skin surfaces and in contaminated heroin.[1] Heroin users, particularly those that inject the drug subcutaneously, appear to be at high risk of contracting tetanus.[1] Rarely, tetanus can be contracted through surgical procedures, intramuscular injections, compound fractures, and dental infections.[1] Animal bites can transmit tetanus.[1]

Tetanus is often associated with rust, especially rusty nails. Although rust itself does not cause tetanus, objects that accumulate rust are often found outdoors or in places that harbour anaerobic bacteria. Additionally, the rough surface of rusty metal provides a habitat for C. tetani, while a nail affords a means to puncture skin and deliver endospores deep within the body at the site of the wound.[23] An endospore is a non-metabolizing survival structure that begins to metabolize and cause infection once in an adequate environment. Hence, stepping on a nail (rusty or not) may result in a tetanus infection, as the low-oxygen (anaerobic) environment may exist under the skin, and the puncturing object can deliver endospores to a suitable environment for growth.[24] It is a common misconception that rust itself is the cause and that a puncture from a rust-free nail is not a risk.[25][26]

Pathophysiology

Tetanus affects skeletal muscle, a type of striated muscle used in voluntary movement. The other type of striated muscle, cardiac, or heart muscle, cannot be tetanized because of its intrinsic electrical properties.

The tetanus toxin initially binds to peripheral nerve terminals. It is transported within the axon and across synaptic junctions until it reaches the central nervous system. There it becomes rapidly fixed to gangliosides at the presynaptic inhibitory motor nerve endings, and is taken up into the axon by endocytosis. The effect of the toxin is to block the release of inhibitory neurotransmitters glycine and gamma-aminobutyric acid (GABA) across the synaptic cleft, which is required to check the nervous impulse. If nervous impulses cannot be checked by normal inhibitory mechanisms, the generalized muscular spasms characteristic of tetanus are produced. The toxin appears to act by selective cleavage of a protein component of synaptic vesicles, synaptobrevin II, and this prevents the release of neurotransmitters by the cells.

Diagnosis

There are currently no blood tests for diagnosing tetanus. The diagnosis 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 people without tetanus. Laboratory identification of C. tetani can be demonstrated only by production of tetanospasmin in mice.[1] Having recently experienced head trauma may indicate cephalic tetanus if no other diagnosis has been made.

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 affected subject research study, the spatula test had a high specificity (zero false-positive test results) and a high sensitivity (94% of infected people produced a positive test).[27]

Prevention

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 can be prevented by vaccination with tetanus toxoid.[28] The CDC recommends that adults receive a booster vaccine every ten years,[1] and standard care practice in many places is to give the booster to any person with a puncture wound who is uncertain of when he or she was last vaccinated, or if he or she has had fewer than three lifetime doses of the vaccine. The booster may not prevent a potentially fatal case of tetanus from the current wound, however, as it can take up to two weeks for tetanus antibodies to form.[29]

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.[28]

The World Health Organization certifies countries as having eliminated maternal or neonatal tetanus. Certification requires at least two years of rates of less than 1 case per 1000 live births. In 1998 in Uganda, 3,433 tetanus cases were recorded in newborn babies; of these, 2,403 died. After a major public health effort, Uganda in 2011 was certified as having eliminated tetanus.[30]

Post-exposure prophylaxis

Tetanus toxoid can be given in case of a suspected exposure to tetanus. In such cases, it can be given with or without tetanus immunoglobulin (also called tetanus antibodies or tetanus antitoxin[31]). It can be given as intravenous therapy or by intramuscular injection.

The guidelines for such events in the United States for non-pregnant people 11 years and older are as follows:[1]

Vaccination status Clean, minor wounds All other wounds
Unknown or less than 3 doses of tetanus toxoid containing vaccine Tdap and recommend catch-up vaccination Tdap and recommend catch-up vaccination
Tetanus immunoglobulin
3 or more doses of tetanus toxoid containing vaccine AND less than 5 years since last dose No indication No indication
3 or more doses of tetanus toxoid containing vaccine AND 5–10 years since last dose No indication Tdap preferred (if not yet received) or Td
3 or more doses of tetanus toxoid containing vaccine AND more than 10 years since last dose Tdap preferred (if not yet received) or Td Tdap preferred (if not yet received) or Td

Treatment

Tetanus world map-Deaths per million persons-WHO2012
Tetanus deaths per million persons in 2012
  0-0
  1-1
  2-3
  4-8
  9-13
  14-28
  29-151

Mild tetanus

Mild cases of tetanus can be treated with:[32]

Severe tetanus

Severe cases will require admission to intensive care. In addition to the measures listed above for mild tetanus:[32]

Drugs such as diazepam or other muscle relaxants can be given to control the muscle spasms. In extreme cases it may be necessary to paralyze the person with curare-like drugs and use a mechanical ventilator.

In order to survive a tetanus infection, the maintenance of an airway and proper nutrition are required. An intake of 3,500 to 4,000 calories and at least 150 g of protein per day is often given in liquid form through a tube directly into the stomach (percutaneous endoscopic gastrostomy), or through a drip into a vein (parenteral nutrition). This high-caloric diet maintenance is required because of the increased metabolic strain brought on by the increased muscle activity. Full recovery takes 4 to 6 weeks because the body must regenerate destroyed nerve axon terminals.

Epidemiology

Tetanus world map - DALY - WHO2004
Disability-adjusted life year for tetanus per 100,000 inhabitants in 2004.
  no data
  ≤10
  10-25
  25-50
  50-75
  75-100
  100-125
  125-150
  150-200
  200-250
  250-500
  500-750
  ≥750
Tetanos
Tetanus cases reported worldwide (1990-2004). Ranging from some (in dark red) to very few (in light yellow) (grey, no data).

In 2013 it caused about 59,000 deaths – down from 356,000 in 1990.[7] Tetanus – in particular, the neonatal form – remains a significant public health problem in non-industrialized countries with 59,000 newborns worldwide dying in 2008 as a result of neonatal tetanus.[33][34] In the United States, from 2000 through 2007 an average of 31 cases were reported per year.[1] Nearly all of the cases in the United States occur in unimmunized individuals or individuals who have allowed their inoculations to lapse.[1]

History

Tetanus was well known to ancient people who recognized the relationship between wounds and fatal muscle spasms.[35] 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 person with fatal tetanus into their sciatic nerves.[1]

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. In 1897, Edmond Nocard showed that tetanus antitoxin induced passive immunity in humans, and could be used for prophylaxis and treatment. Tetanus toxoid vaccine was developed by P. Descombey in 1924, and was widely used to prevent tetanus induced by battle wounds during World War II.[1]

Etymology

The word tetanus comes from the Ancient Greek: τέτανος, translit. tetanos, lit. 'taut', which is further from the Ancient Greek: τείνειν, translit. teinein, lit. 'to stretch'.[36]

See also

References

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  14. ^ "Elimination of Maternal and Neonatal Tetanus". UNICEF. Archived from the original on 21 February 2014. Retrieved 17 February 2014.
  15. ^ a b c Doshi A, Warrell C, Dahdaleh D, Kullmann D (February 2014). "Just a graze? Cephalic tetanus presenting as a stroke mimic". Pract Neurol. 14 (1): 39–41. doi:10.1136/practneurol-2013-000541. PMID 24052566.
  16. ^ a b c Del Pilar Morales E, Bertrán Pasarell J, Cardona Rodriguez Z, Almodovar Mercado JC, Figueroa Navarro A (2014). "Cephalic tetanus following penetrating eye trauma: a case report". Bol Asoc Med P R. 106 (2): 25–9. PMID 25065047.
  17. ^ a b c d Adeleye, A. O.; Azeez, A. L. (October 2012). "Fatal tetanus complicating an untreated mild open head injury: a case-illustrated review of cephalic tetanus". Surg Infect (Larchmt). 13 (5): 317–20. doi:10.1089/sur.2011.023. PMID 23039234.
  18. ^ a b Ajayi E, Obimakinde O (July 2011). "Cephalic tetanus following tooth extraction in a Nigerian woman". J Neurosci Rural Pract. 2 (2): 201–2. doi:10.4103/0976-3147.83597. PMC 3159367. PMID 21897694.
  19. ^ Ugwu GI, Okolugbo NE (2012). "Otogenic tetanus: case series". West Afr J Med. 31 (4): 277–9. PMID 23468033.
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  21. ^ a b c Seo DH, Cho DK, Kwon HC, Kim TU (February 2012). "A case of cephalic tetanus with unilateral ptosis and facial palsy". Ann Rehabil Med. 36 (1): 167–70. doi:10.5535/arm.2012.36.1.167. PMC 3309317. PMID 22506253.
  22. ^ Wells CL, Wilkins TD (1996). "Clostridia: Sporeforming Anaerobic Bacilli". In Baron S. Baron's Medical Microbiology. Univ of Texas Medical Branch. ISBN 978-0-9631172-1-2. Archived from the original on 2009-02-06.
  23. ^ Edmonds, Molly. "Causes of Tetanus". HowStuffWorks. Archived from the original on 22 November 2015. Retrieved 9 November 2015.
  24. ^ Todar, Kenneth. "Tetanus". Lectures in Microbiology. University of Wisconsin, Madison - Dept. of Bacteriology. Archived from the original on 2013-03-11.
  25. ^ O'Connor, Anahad (February 22, 2005), "The Claim: Stepping on a Rusty Nail Can Cause Tetanus", The New York Times
  26. ^ Jennings K (2013-10-08). Because I Said So!: The Truth Behind the Myths, Tales, and Warnings Every Generation Passes Down to Its Kids. Simon and Schuster. pp. 13–. ISBN 978-1-4767-0696-2.
  27. ^ Apte NM, Karnad DR (October 1995). "Short Report: The Spatula Test: A Simple Bedside Test to Diagnose Tetanus". American Journal of Tropical Medicine and Hygiene. 53 (4): 386–7. doi:10.4269/ajtmh.1995.53.386. PMID 7485691. Archived from the original on 2008-02-15.
  28. ^ a b Hopkins, A.; Lahiri, T.; Salerno, R.; Heath, B. (1991). "Diphtheria, tetanus, and pertussis: recommendation for vaccine use and other preventive measures. Recommendations of the Immunization Practices Advisory committee (ACIP)". MMWR Recomm Rep. 40 (RR–10): 1–28. doi:10.1542/peds.2006-0692. PMID 1865873.
  29. ^ Porter JD, Perkin MA, Corbel MJ, Farrington CP, Watkins JT, Begg NT (1992). "Lack of early antitoxin response to tetanus booster". Vaccine. 10 (5): 334–6. doi:10.1016/0264-410X(92)90373-R. PMID 1574917.
  30. ^ "Uganda announces elimination of Maternal and Neonatal Tetanus". Archived from the original on 2015-02-11. Retrieved 2011-07-14.
  31. ^ a b tetanus in Encyclopædia Britannica. Last Updated 7-17-2013
  32. ^ a b World Health Organization. "Current recommendations for treatment of tetanus during humanitarian emergencies". Disease Control in Humanitarian Emergencies (English). WHO. Archived from the original on 13 March 2014. Retrieved 12 June 2013.
  33. ^ "Maternal and Neonatal Tetanus Elimination Initiative" (PDF). Pampers UNICEF 2010 Campaign: 2. Archived (PDF) from the original on 2014-02-01.
  34. ^ Black, RE; Cousens, S; Johnson, HL; Lawn, JE; Rudan, I; Bassani, DG; Jha, P; Campbell, H; Walker, CF; Cibulskis, R; Eisele, T; Liu, L; Mathers, C; Child Health Epidemiology Reference Group of WHO and UNICEF (Jun 5, 2010). "Global, regional, and national causes of child mortality in 2008: a systematic analysis". Lancet. 375 (9730): 1969–87. doi:10.1016/S0140-6736(10)60549-1. PMID 20466419.
  35. ^ Pearce JM (1996). "Notes on tetanus (lockjaw)". Journal of Neurology, Neurosurgery, and Psychiatry. 60 (3): 332. doi:10.1136/jnnp.60.3.332. PMC 1073859. PMID 8609513.
  36. ^ tetanus Archived 2012-06-26 at the Wayback Machine. CollinsDictionary.com. Collins English Dictionary - Complete & Unabridged 11th Edition. Retrieved October 01, 2012

External links

External resources
ATC code J07

ATC code J07 Vaccines is a therapeutic subgroup of the Anatomical Therapeutic Chemical Classification System, a system of alphanumeric codes developed by the WHO for the classification of drugs and other medical products. Subgroup J07 is part of the anatomical group J Antiinfectives for systemic use.National issues of the ATC classification may include additional codes not present in this list, which follows the WHO version.

Clostridia

The Clostridia are a highly polyphyletic class of Firmicutes, including Clostridium and other similar genera. They are distinguished from the Bacilli by lacking aerobic respiration. They are obligate anaerobes and oxygen is toxic to them. Species of the class Clostridia are often but not always Gram-positive (see Halanaerobium hydrogenoformans) and have the ability to form spores. Studies show they are not a monophyletic group, and their relationships are not entirely certain. Currently, most are placed in a single order called Clostridiales, but this is not a natural group and is likely to be redefined in the future.

Most species of the genus Clostridium are saprophytic organisms found in many places in the environment, most notably the soil. However, the genus does contain some human pathogens (outlined below).

The toxins produced by certain members of the genus Clostridium are among the most dangerous known. Examples are tetanus toxin (known as tetanospasmin) produced by C. tetani and botulinum toxin produced by C. botulinum. Some species have been isolated from women with bacterial vaginosis.Notable species of this class include:

Clostridium perfringens (gangrene, food poisoning)

Clostridium difficile (pseudomembranous colitis)

Clostridium tetani (tetanus)

Clostridium botulinum (botulism)

Clostridium acetobutylicum

Clostridium haemolyticum

Clostridium novyi

Clostridium oedematiensHeliobacteria and Christensenella are also members of the class Clostridia.

Some of the enzymes produced by this group are used in bioremediation.

Clostridium tetani

Clostridium tetani is a common soil bacterium and the causative agent of tetanus. When growing in soil, C. tetani are rod-shaped and up to 2.5 micrometres long. However, when forming spores C. tetani becomes substantially enlarged at one end, resembling tennis rackets or drumsticks. C. tetani spores are extremely hardy and can be found globally in soil or in the gastrointestinal tract of animals. If inoculated into a wound, C. tetani can grow and produce a potent toxin, tetanospasmin, which interferes with motor neurons, causing tetanus. All mammals are susceptible to the disease [1]. The toxin's action can be prevented with tetanus toxoid vaccines, which are often administered to children worldwide.

DPT vaccine

DPT (also DTP and DTwP) is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis (whooping cough), and tetanus. The vaccine components include diphtheria and tetanus toxoids and killed whole cells of the bacterium that causes pertussis (wP).

DTaP and Tdap refer to similar combination vaccines in which the component "P" or "p" with lower case "a" is acellular.

Also available are the DT and Td vaccines, which lack the pertussis component.

In the United Kingdom, the Netherlands and France, the abbreviation DTP refers to a combination vaccine against diphtheria, tetanus, and poliomyelitis. In the Netherlands, pertussis is known as kinkhoest and DKTP refers to a combination vaccine against diphtheria, kinkhoest, tetanus, and polio.

The usual course of childhood immunization in the United States is five doses between 2 months and 15 years. For adults, Td boosters are recommended every 10 years.

In the latter 20th century, vaccinations helped to reduce the incidence of childhood pertussis in the United States. Despite this, reported instances of the disease increased twenty-fold in the early 21st century, resulting in numerous fatalities. Over this time, many parents declined to vaccinate their children against pertussis for fear of side effects. In 2009, the journal Pediatrics concluded the largest risk among unvaccinated children was not the contraction of side effects, but rather the disease that the vaccination aims to protect against.DTP was licensed in 1949.

DTaP-IPV-HepB vaccine

DTaP-IPV-HepB vaccine is a combination vaccine whose generic name is diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus vaccine or DTaP-IPV-Hep B. It protects against the infectious diseases diphtheria, tetanus, pertussis, poliomyelitis, and hepatitis B.

A branded formulation is marketed in the USA as Pediarix by GlaxoSmithKline.

DTaP-IPV/Hib vaccine

DTaP-IPV/Hib vaccine is a combination vaccine whose generic name is diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated poliovirus and haemophilus B conjugate (tetanus toxoid conjugate) vaccine. It is also known as DTaP-IPV/Hib or DTaP-IPV-Hib. It protects against the infectious diseases diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type B.

A branded formulation marketed in the USA is Pentacel, manufactured by Sanofi Pasteur. Pentacel is known in the UK and Canada as Pediacel. An equivalent vaccine marketed in the UK and Canada by GlaxoSmithKline is Infanrix IPV + Hib. This is a two-part vaccine. The DTaP-IPV component is supplied as a sterile liquid, which is used to reconstitute lyophilized (freeze-dried) Hib vaccine.

Pentaxim is a liquid formulation marketed by Sanofi Pasteur.

Diphtheria

Diphtheria is an infection caused by the bacterium Corynebacterium diphtheriae. Signs and symptoms may vary from mild to severe. They usually start two to five days after exposure. Symptoms often come on fairly gradually, beginning with a sore throat and fever. In severe cases, a grey or white patch develops in the throat. This can block the airway and create a barking cough as in croup. The neck may swell in part due to enlarged lymph nodes. A form of diphtheria that involves the skin, eyes, or genitals also exists. Complications may include myocarditis, inflammation of nerves, kidney problems, and bleeding problems due to low levels of platelets. Myocarditis may result in an abnormal heart rate and inflammation of the nerves may result in paralysis.Diphtheria is usually spread between people by direct contact or through the air. It may also be spread by contaminated objects. Some people carry the bacteria without having symptoms, but can still spread the disease to others. The three main types of C. diphtheriae cause different severities of disease. The symptoms are due to a toxin produced by the bacteria. Diagnosis can often be made based on the appearance of the throat with confirmation by microbiological culture. Previous infection may not protect against future infection.A diphtheria vaccine is effective for prevention and available in a number of formulations. Three or four doses, given along with tetanus vaccine and pertussis vaccine, are recommended during childhood. Further doses of diphtheria-tetanus vaccine are recommended every ten years. Protection can be verified by measuring the antitoxin level in the blood. Diphtheria can be treated with the antibiotics erythromycin or benzylpenicillin. These antibiotics may also be used for prevention in those who have been exposed to the infection. A tracheotomy is sometimes needed to open the airway in severe cases.In 2015, 4,500 cases were officially reported worldwide, down from nearly 100,000 in 1980. About a million cases a year are believed to have occurred before the 1980s. Diphtheria currently occurs most often in sub-Saharan Africa, India, and Indonesia. In 2015, it resulted in 2,100 deaths, down from 8,000 deaths in 1990. In areas where it is still common, children are most affected. It is rare in the developed world due to widespread vaccination. In the United States, 57 cases were reported between 1980 and 2004. Death occurs in 5% to 10% of those affected. The disease was first described in the 5th century BC by Hippocrates. The bacterium was identified in 1882 by Edwin Klebs.

George Montagu (naturalist)

George Montagu (1753 – 20 June 1815) was an English army officer and naturalist. He was known for his pioneering Ornithological Dictionary of 1802, which for the first time accurately defined the status of Britain's birds. He is remembered today for species such as the Montagu's harrier, named for him.

Hexavalent vaccine

A hexavalent vaccine, or 6-in-1 vaccine, is a combination vaccine with six individual vaccines conjugated into one, intended to protect people from multiple diseases. The principal example is a pediatric vaccine, used in more than 90 countries around the world including in Europe, Canada, Australia, and New Zealand that protects against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus B, and hepatitis B.

Microbial toxin

Microbial toxins are toxins produced by micro-organisms, including bacteria and fungi. Microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Some bacterial toxins, such as Botulinum neurotoxins, are the most potent natural toxins known. However, microbial toxins also have important uses in medical science and research. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.

Opisthotonus

Opisthotonus or opisthotonos (from Ancient Greek: ὄπισθεν, translit. opisthen, lit. 'behind' and τόνος, tonos, 'tension') is a state of severe hyperextension and spasticity in which an individual's head, neck and spinal column enter into a complete "bridging" or "arching" position.This extreme arched pose is an extrapyramidal effect and is caused by spasm of the axial muscles along the spinal column. It has been shown to occur naturally only in birds and placental mammals, among existing animals; it is observed in some articulated dinosaur fossils.

Pentavalent vaccine

A pentavalent vaccine, or 5-in-1 vaccine, is a combination vaccine with five individual vaccines conjugated into one, intended to actively protect people from multiple diseases.

The most widely-used example is a vaccine that protects against Haemophilus influenzae type B (a bacterium that causes meningitis, pneumonia and otitis), whooping cough, tetanus, hepatitis B and diphtheria. The generic name for this vaccine is diphtheria, tetanus, pertussis (whole cell), hepatitis B (rDNA) and Haemophilus influenzae type B conjugate vaccine (absorbed) or DTP-HepB-Hib. This pentavalent vaccine has largely supplanted other pediatric combination vaccines, especially in middle- and low-income countries. By 2013, pentavalent vaccines accounted for 100% of the DTP-containing vaccines procured by UNICEF, which supplies vaccines to a large proportion of the world's children.

Pertussis vaccine

Pertussis vaccine is a vaccine that protects against whooping cough (pertussis). There are two main types: whole-cell vaccines and acellular vaccines. The whole-cell vaccine is about 78% effective while the acellular vaccine is 71–85% effective. The effectiveness of the vaccines appears to decrease by between 2 and 10% per year after vaccination with a more rapid decrease with the acellular vaccines. Vaccinating the mother during pregnancy may protect the baby. The vaccine is estimated to have saved over 500,000 lives in 2002.The World Health Organization and Center for Disease Control and Prevention recommend all children be vaccinated for pertussis and that it be included in routine vaccinations. This includes for people who have HIV/AIDS. Three doses starting at six weeks of age are typically recommended in young children. Additional doses may be given to older children and adults. The vaccine is only available in combination with tetanus and diphtheria vaccines.The acellular vaccines are more commonly used in the developed world due to fewer adverse effects. Between 10 and 50% of people given the whole-cell vaccines develop redness at the injection site or fever. Febrile seizures and long periods of crying occur in less than 1% of people. With the acellular vaccines a brief period of non-serious swelling of the arm may occur. Side effects with both types of vaccines, but especially the whole-cell vaccine, are less common the younger the child. The whole-cell vaccines should not be used after seven years of age. Serious long term neurological problems are not associated with either type.The pertussis vaccine was developed in 1926. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. A version that also includes tetanus, diphtheria, polio, and Hib vaccine is available wholesale in the developing world at a cost of 15.41 USD per dose as of 2014.

Tetanolysin

Tetanolysin is a toxin produced by Clostridium tetani bacteria. Its function is unknown but it is believed to contribute to the pathogenesis of tetanus.The other C. tetani toxin, tetanospasmin, is more definitively linked to tetanus.

Tetanolysin belongs to a family of protein toxins known as cytolysins which bind to cholesterol. Cytolysins form pores in the cytoplasmic membrane that allows for the passage of ions and other molecules into the cell. The molecular weight of tetanolysin is approximately 55,000 daltons.[1]

Tetanospasmin

Tetanus toxin is an extremely potent neurotoxin produced by the vegetative cell of Clostridium tetani in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normally encountered. It is also called spasmogenic toxin, or TeNT. The LD50 of this toxin has been measured to be approximately 2.5-3 ng/kg, making it second only to botulinum toxin (LD50 2 ng/kg) as the deadliest toxin in the world. However, these tests are conducted solely on mice, which may react to the toxin differently from humans and other animals.

C. tetani also produces the exotoxin tetanolysin, a hemolysin, that causes destruction of tissues.

Tetanus vaccine

Tetanus vaccine, also known as tetanus toxoid (TT), is an inactive vaccine used to prevent tetanus. During childhood five doses are recommended, with a sixth given during adolescence. Additional doses every 10 years are recommended. After three doses almost everyone is initially immune. In those who are not up to date on their tetanus immunization a booster should be given within 48 hours of an injury. In those with high risk injuries who are not fully immunized tetanus antitoxin may also be recommended. Making sure women who are pregnant are up to date on their tetanus immunization and, if not, immunizing them can prevent neonatal tetanus.The vaccine is very safe including during pregnancy and in those with HIV/AIDS. Redness and pain at the site of injection occur in between 25% and 85% of people. Fever, feeling tired, and minor muscles pains occur in less than 10% of people. Severe allergic reactions occur in less than one in 100,000 people.A number of vaccine combinations include the tetanus vaccine such as DTaP and Tdap which contain diphtheria, tetanus, and pertussis vaccine, and DT and Td which contain diphtheria and tetanus vaccine. DTaP and DT are given to children less than seven years old while Tdap and Td are given to those seven years old and older. The lowercase d and p denote lower strengths of diphtheria and pertussis vaccines.The tetanus vaccine was developed in 1924 and became available in the United States in the 1940s. Its use resulted in a 95% decrease in the rate of tetanus. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is between 0.17 and 0.65 USD per dose as of 2014. In the United States a course of tetanus vaccine is between 25 and 50 USD.

Tetany

Tetany or tetanic seizure is a medical sign consisting of the involuntary contraction of muscles, which may be caused by disease or other conditions that increase the action potential frequency of muscle cells or the nerves that innervate them. Notably, muscle cramps caused by the disease tetanus are not classified as tetany; rather, they are due to a lack of inhibition to the neurons that supply muscles. Tetanic contractions (physiologic tetanus) are a broad range of muscle contraction types, of which tetany is only one.

Toxoid

A toxoid is an inactivated toxin (usually an exotoxin) whose toxicity has been suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained. Toxins are secreted by bacteria, whereas toxoids are altered form of toxins; toxoids are not secreted by bacteria. Thus, when used during vaccination, an immune response is mounted and immunological memory is formed against the molecular markers of the toxoid without resulting in toxin-induced illness. In international medical literature the preparation also is known as anatoxin or anatoxine. There are toxoids for prevention of diphtheria, tetanus and botulism.Toxoids are used as vaccines because they induce an immune response to the original toxin or increase the response to another antigen since the toxoid markers and toxin markers are preserved. For example, the tetanus toxoid is derived from the tetanospasmin produced by Clostridium tetani. The latter causes tetanus and is vaccinated against by the DTaP vaccine. Botulin is produced by Clostridium botulinum and causes the deadly disease botulism. While patients may sometimes complain of side effects after a vaccine, these are associated with the process of mounting an immune response and clearing the toxoid, not the direct effects of the toxoid. The toxoid does not have virulence as the toxin did before inactivation.

Multiple doses of tetanus toxoid are used by many plasma centers in the United States for the development of highly immune persons for the production of human anti-tetanus immune globulin (tetanus immune globulin (TIG), HyperTet (c)), which has replaced horse serum-type tetanus antitoxin in most of the developed world.

Vaccination schedule

A vaccination schedule is a series of vaccinations, including the timing of all doses, which may be either recommended or compulsory, depending on the country of residence. This topic can cause much controversy over whether or not it could impact health after dosage at an early age.

A vaccine is an antigenic preparation used to produce active immunity to a disease, in order to prevent or reduce the effects of infection by any natural or "wild" pathogen. Many vaccines require multiple doses for maximum effectiveness, either to produce sufficient initial immune response or to boost response that fades over time. For example, tetanus vaccine boosters are often recommended every 10 years. Vaccine schedules are developed by governmental agencies or physicians groups to achieve maximum effectiveness using required and recommended vaccines for a locality while minimizing the number of health care system interactions. Over the past two decades, the recommended vaccination schedule has grown rapidly and become more complicated as many new vaccines have been developed.Some vaccines are recommended only in certain areas (countries, sub national areas, or at-risk populations) where a disease is common. For instance, yellow fever vaccination is on the routine vaccine schedule of French Guiana, is recommended in certain regions of Brazil but in the United States is only given to travelers heading to countries with a history of the disease. In developing countries, vaccine recommendations also take into account the level of health care access, the cost of vaccines and issues with vaccine availability and storage. Sample vaccination schedules discussed by the World Health Organization show a developed country using a schedule which extends over the first five years of a child's life and uses vaccines which cost over $700 including administration costs while a developing country uses a schedule providing vaccines in the first 9 months of life and costing only $25. This difference is due to the lower cost of health care, the lower cost of many vaccines provided to developing nations, and that more expensive vaccines, often for less common diseases, are not utilized.

Bacilli
Clostridia
Mollicutes

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