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 bacterium 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 bacterium. 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 but can re-emerge if vaccination rates decrease. 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.
|Diphtheria can cause a swollen neck, sometimes referred to as a bull neck.|
|Symptoms||Sore throat, fever, barky cough|
|Usual onset||2–5 days post-exposure|
|Causes||Corynebacterium diphtheriae (spread by direct contact and through the air)|
|Diagnostic method||Throat appearance, culture|
|Frequency||4,500 (reported 2015)|
The symptoms of diphtheria usually begin two to seven days after infection. Symptoms of diphtheria include fever of 38 °C (100.4 °F) or above, chills, fatigue, bluish skin coloration (cyanosis), sore throat, hoarseness, cough, headache, difficulty swallowing, painful swallowing, difficulty breathing, rapid breathing, foul-smelling and bloodstained nasal discharge, and lymphadenopathy. Within two to three days, diphtheria may destroy healthy tissues in the respiratory system. The dead tissue forms a thick, gray coating that can build up in the throat or nose. This thick gray coating is called a “pseudomembrane.” It can cover tissues in the nose, tonsils, voice box, and throat, making it very hard to breathe and swallow. Symptoms can also include cardiac arrhythmias, myocarditis, and cranial and peripheral nerve palsies.
Laryngeal diphtheria can lead to a characteristic swollen neck and throat, or "bull neck". The swollen throat is often accompanied by a serious respiratory condition, characterized by a brassy or "barking" cough, stridor, hoarseness, and difficulty breathing, and historically referred to variously as "diphtheritic croup", "true croup", or sometimes simply as "croup". Diphtheritic croup is extremely rare in countries where diphtheria vaccination is customary. As a result, the term "croup" nowadays most often refers to an unrelated viral illness that produces similar but milder respiratory symptoms.
Human-to-human transmission of diphtheria typically occurs through the air when an infected individual coughs or sneezes. Breathing in particles released from the infected individual leads to infection. Contact with any lesions on the skin can also lead to transmission of diphtheria, but this is uncommon. Indirect infections can occur, as well. If an infected individual touches a surface or object, the bacteria can be left behind and remain viable. Also, some evidence indicates diphtheria has the potential to be zoonotic, but this has yet to be confirmed. Corynebacterium ulcerans has been found in some animals, which would suggest zoonotic potential.
Diphtheria toxin is a single, 60-kDa-molecular weight protein composed of two peptide chains, fragment A and fragment B, held together by a disulfide bond. Fragment B is a recognition subunit that gains the toxin entry into the host cell by binding to the EGF-like domain of heparin-binding EGF-like growth factor on the cell surface. This signals the cell to internalize the toxin within an endosome via receptor-mediated endocytosis. Inside the endosome, the toxin is split by a trypsin-like protease into its individual A and B fragments. The acidity of the endosome causes fragment B to create pores in the endosome membrane, thereby catalysing the release of fragment A into the cell's cytoplasm.
Fragment A inhibits the synthesis of new proteins in the affected cell by catalyzing ADP-ribosylation of elongation factor EF-2—a protein that is essential to the translation step of protein synthesis. This ADP-ribosylation involves the transfer of an ADP-ribose from NAD+ to a diphthamide (a modified histidine) residue within the EF-2 protein. Since EF-2 is needed for the moving of tRNA from the A-site to the P-site of the ribosome during protein translation, ADP-ribosylation of EF-2 prevents protein synthesis.
ADP-ribosylation of EF-2 is reversed by giving high doses of nicotinamide (a form of vitamin B3), since this is one of the reaction's end products, and high amounts drive the reaction in the opposite direction.
Empirical treatment should generally be started in a patient in whom suspicion of diphtheria is high.
Quinvaxem is a widely administered pentavalent vaccine, which is a combination of five vaccines in one that protect babies from diphtheria, among other common childhood diseases. Diphtheria vaccine is usually combined at least with tetanus vaccine (Td) and often with pertussis (DTP, DTaP, TdaP, Tdap) vaccines, as well.
The disease may remain manageable, but in more severe cases, lymph nodes in the neck may swell, and breathing and swallowing are more difficult. People in this stage should seek immediate medical attention, as obstruction in the throat may require intubation or a tracheotomy. Abnormal cardiac rhythms can occur early in the course of the illness or weeks later, and can lead to heart failure. Diphtheria can also cause paralysis in the eye, neck, throat, or respiratory muscles. Patients with severe cases are put in a hospital intensive care unit and given a diphtheria antitoxin (consisting of antibodies isolated from the serum of horses that have been challenged with diphtheria toxin). Since antitoxin does not neutralize toxin that is already bound to tissues, delaying its administration increases risk of death. Therefore, the decision to administer diphtheria antitoxin is based on clinical diagnosis, and should not await laboratory confirmation.
Antibiotics have not been demonstrated to affect healing of local infection in diphtheria patients treated with antitoxin. Antibiotics are used in patients or carriers to eradicate C. diphtheriae and prevent its transmission to others. The Centers for Disease Control and Prevention recommends either:
In cases that progress beyond a throat infection, diphtheria toxin spreads through the blood and can lead to potentially life-threatening complications that affect other organs, such as the heart and kidneys. Damage to the heart caused by the toxin affects the heart's ability to pump blood or the kidneys' ability to clear wastes. It can also cause nerve damage, eventually leading to paralysis. About 40% to 50% of those left untreated can die.
Diphtheria is fatal in between 5% and 10% of cases. In children under five years and adults over 40 years, the fatality rate may be as much as 20%. In 2013, it resulted in 3,300 deaths, down from 8,000 deaths in 1990.
The number of cases has changed over the course of the last 2 decades, specifically throughout developing countries. Better standards of living, mass immunization, improved diagnosis, prompt treatment, and more effective health care have led to the decrease in cases worldwide. However, although outbreaks are rare, they still occur worldwide, especially in developed nations such as Germany among unvaccinated children.
After the breakup of the former Soviet Union in the early 1990s, vaccination rates in its constituent countries fell so low that an explosion of diphtheria cases occurred. In 1991, 2,000 cases of diphtheria occurred in the USSR. Between 1991 and 1998 as many as 200,000 cases in the Commonwealth of Independent States were reported, with 5,000 deaths.
In 1613, Spain experienced an epidemic of diphtheria. The year is known as El Año de los Garrotillos (The Year of Strangulations) in the history of Spain.
In 1735, a diphtheria epidemic swept through New England.
Before 1826, diphtheria was known by different names across the world. In England, it was known as Boulogne sore throat, as it spread from France. In 1826, Pierre Bretonneau gave the disease the name diphthérite (from Greek diphthera "leather") describing the appearance of pseudomembrane in the throat.
In 1883, Edwin Klebs identified the bacterium causing diphtheria and named it Klebs-Loeffler bacterium. The club shape of this bacterium helped Edwin to differentiate it from other bacteria. Over the period of time, it was called Microsporon diphtheriticum, Bacillus diphtheriae, and Mycobacterium diphtheriae. Current nomenclature is Corynebacterium diphtheriae.
Friedrich Loeffler was the first person to cultivate C. diphtheriae in 1884. He used Koch's postulates to prove association between C. diphtheriae and diphtheria. He also showed that the bacillus produces an exotoxin.
In 1890, Shibasaburo Kitasato and Emil von Behring immunized guinea pigs with heat-treated diphtheria toxin. They also immunized goats and horses in the same way and showed that an "antitoxin" made from serum of immunized animals could cure the disease in non-immunized animals. Behring used this antitoxin (now known to consist of antibodies that neutralize the toxin produced by C. diphtheriae) for human trials in 1891, but they were unsuccessful. Successful treatment of human patients with horse-derived antitoxin began in 1894, after production and quantification of antitoxin had been optimized. Von Behring won the first Nobel Prize in medicine in 1901 for his work on diphtheria.
In 1895, H. K. Mulford Company of Philadelphia started production and testing of diphtheria antitoxin in the United States. Park and Biggs described the method for producing serum from horses for use in diphtheria treatment.
In 1897, Paul Ehrlich developed a standardized unit of measure for diphtheria antitoxin. This was the first ever standardization of a biological product, and played an important role in future developmental work on sera and vaccines.
In 1901, 10 of 11 inoculated St. Louis children died from contaminated diphtheria antitoxin. The horse from which the antitoxin was derived died of tetanus. This incident, coupled with a tetanus outbreak in Camden, New Jersey, played an important part in initiating federal regulation of biologic products.
On 7 January 1904, Ruth Cleveland died of diphtheria at the age of 12 years in Princeton, New Jersey. Ruth was the eldest daughter of former President Grover Cleveland and the former first lady Frances Folsom.
In 1905, Franklin Royer, from Philadelphia's Municipal Hospital, published a paper urging timely treatment for diphtheria and adequate doses of antitoxin. In 1906, Clemens Pirquet and Béla Schick described serum sickness in children receiving large quantities of horse-derived antitoxin.
Between 1910 and 1911, Béla Schick developed the Schick test to detect pre-existing immunity to diphtheria in an exposed person. Only those who were not exposed to diphtheria were preferably vaccinated. A massive, five-year campaign was coordinated by Dr. Schick. As a part of the campaign, 85 million pieces of literature were distributed by the Metropolitan Life Insurance Company with an appeal to parents to "Save your child from diphtheria." A vaccine was developed in the next decade, and deaths began declining significantly in 1924.
In 1919, in Dallas, Texas, 10 children were killed and 60 others made seriously ill by toxic antitoxin which had passed the tests of the New York State Health Department. Mulford Company of Philadelphia (manufacturers) paid damages in every case.
In the 1920s, an estimated 100,000 to 200,000 cases of diphtheria occurred per year in the United States, causing 13,000 to 15,000 deaths per year. Children represented a large majority of these cases and fatalities. One of the most infamous outbreaks of diphtheria was in Nome, Alaska; the "Great Race of Mercy" to deliver diphtheria antitoxin is now celebrated by the Iditarod Trail Sled Dog Race.
In 1926, Alexander Thomas Glenny increased the effectiveness of diphtheria toxoid (a modified version of the toxin used for vaccination) by treating it with aluminum salts. Vaccination with toxoid was not widely used until the early 1930s.
In 1943, diphtheria outbreaks accompanied war and disruption in Europe. The 1 million cases in Europe resulted in 50,000 deaths.
In 1949, 68 of 606 children died after diphtheria immunization due to improper manufacture of aluminum phosphate toxoid.
In 1975, an outbreak of cutaneous diphtheria in Seattle, Washington, was reported .
In 1994, the Russian Federation had 39,703 diphtheria cases. By contrast, in 1990, only 1,211 cases were reported. Between 1990 and 1998, diphtheria caused 5000 deaths in the countries of the former Soviet Union.
In early May 2010, a case of diphtheria was diagnosed in Port-au-Prince, Haiti, after the devastating 2010 Haiti earthquake. The 15-year-old male patient died while workers searched for antitoxin.
In early June 2015, a case of diphtheria was diagnosed at Vall d'Hebron University Hospital in Barcelona, Spain. The 6-year-old child who died of the illness had not been previously vaccinated due to parental opposition to vaccination. It was the first case of diphtheria in the country since 1986 as reported by "El Mundo" or from 1998, as reported by WHO.
Balto (1919 – March 14, 1933) was a Siberian husky and sled dog who led his team on the final leg of the 1925 serum run to Nome, in which diphtheria antitoxin was transported from Anchorage, Alaska, to Nenana, Alaska, by train and then to Nome by dog sled to combat an outbreak of the disease. Balto was named after the Sami explorer Samuel Balto. Balto rested at the Cleveland Zoo until his death on March 14, 1933, at the age of 14. After he died, his body was stuffed and kept in the Cleveland Museum of Natural History, where it remains today.Corynebacterium diphtheriae
Corynebacterium diphtheriae is the pathogenic bacterium that causes diphtheria. It is also known as the Klebs-Löffler bacillus, because it was discovered in 1884 by German bacteriologists Edwin Klebs (1834–1912) and Friedrich Löffler (1852–1915).Croup
Croup, also known as laryngotracheobronchitis, is a type of respiratory infection that is usually caused by a virus. The infection leads to swelling inside the trachea, which interferes with normal breathing and produces the classic symptoms of "barking" cough, stridor, and a hoarse voice. Fever and runny nose may also be present. These symptoms may be mild, moderate, or severe. Often it starts or is worse at night. It normally lasts one to two days.Croup can be caused by a number of viruses including parainfluenza and influenza virus. Rarely is it due to a bacterial infection. Croup is typically diagnosed based on signs and symptoms after potentially more severe causes, such as epiglottitis or an airway foreign body, have been ruled out. Further investigations—such as blood tests, X-rays, and cultures—are usually not needed.Many cases of croup are preventable by immunization for influenza and diphtheria. Croup is usually treated with a single dose of steroids by mouth. In more severe cases inhaled epinephrine may also be used. Hospitalization is required in one to five percent of cases.Croup is a relatively common condition that affects about 15% of children at some point. It most commonly occurs between 6 months and 5 years of age but may rarely be seen in children as old as fifteen. It is slightly more common in males than females. It occurs most often in autumn. Before vaccination, croup was frequently caused by diphtheria and was often fatal. This cause is now very rare in the Western world due to the success of the diphtheria vaccine.Cutaneous diphtheria infection
Cutaneous diphtheria is an infection of the skin by Corynebacterium diphtheriae. It is also known as "desert sore".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.Denileukin diftitox
Denileukin diftitox (trade name Ontak) was an antineoplastic agent, an engineered protein combining Interleukin-2 and Diphtheria toxin. Denileukin diftitox could bind to Interleukin-2 receptors and introduce the diphtheria toxin into cells that express those receptors, killing the cells. In some Leukemias and Lymphomas malignant cells express these receptors, so denileukin diftitox can target these.
In 1999 Ontak was approved by the U.S. Food and Drug Administration (FDA) for treatment of Cutaneous T-cell lymphoma (CTCL).There is some evidence tying it to vision loss and in 2006 the FDA added a black box warning to the drug's label.In 2014 marketing of Ontak was discontinued in the US.Diphtheria toxin
Diphtheria toxin is an exotoxin secreted by Corynebacterium, the pathogenic bacterium that causes diphtheria. The toxin gene is encoded by a prophage (a virus that has inserted itself into the genome of the host bacterium). The toxin causes the disease in humans by gaining entry into the cell cytoplasm and inhibiting protein synthesis.Diphtheria vaccine
Diphtheria vaccine is a vaccine against Corynebacterium diphtheriae, the bacterium that causes diphtheria. Its use has resulted in a more than 90% decrease in number of cases globally between 1980 and 2000. The first dose is recommended at six weeks of age with two additional doses four weeks apart, after which it is about 95% effective during childhood. Three further doses are recommended during childhood. It is unclear if further doses later in life are needed.The diphtheria vaccine is very safe. Significant side effects are rare. Pain may occur at the injection site. A bump may form at the site of injection that lasts a few weeks. The vaccine is safe in both pregnancy and among those who have a poor immune function.The diphtheria vaccine is delivered in several combinations. Some combinations (Td and DT vaccines) include tetanus vaccine, others (known as DPT vaccine or DTaP vaccine depending on the pertussis antigen used) comes with the tetanus and pertussis vaccines, and still others include additional vaccines such as Hib vaccine, hepatitis B vaccine, or inactivated polio vaccine. The World Health Organization has recommended its use since 1974. About 84% of the world population is vaccinated. It is given as a intramuscular injection. The vaccine needs to be kept cold but not frozen.The diphtheria vaccine was developed in 1923. 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 price in the developing world of a version that contains tetanus toxoid is between 0.12 and 0.99 USD per dose as of 2014. In the United States it is less than 25 USD.Emil von Behring
Emil von Behring (Emil Adolf von Behring), born as Emil Adolf Behring (15 March 1854 – 31 March 1917), was a German physiologist who received the 1901 Nobel Prize in Physiology or Medicine, the first one awarded, for his discovery of a diphtheria antitoxin. He was widely known as a "saviour of children," as diphtheria used to be a major cause of child death. He was honored with Prussian nobility in 1901, henceforth being known by the surname "von Behring."Exotoxin
An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host-pathogen interface.
They may exert their effect locally or produce systemic effects. Well-known exotoxins include: botulinum toxin produced by Clostridium botulinum; Corynebacterium diphtheriae toxin, produced during life-threatening symptoms of diphtheria; tetanospasmin produced by Clostridium tetani. The toxic properties of most exotoxins can be inactivated by heat or chemical treatment to produce a toxoid. These retain their antigenic specificity and can be used to produce antitoxins and, in the case of diphtheria and tetanus toxoids, are used as vaccines.
Exotoxins are susceptible to antibodies produced by the immune system, but many exotoxins are so toxic that they may be fatal to the host before the immune system has a chance to mount defenses against them. For this reason antitoxin, anti-serum containing antibodies, is injected to provide passive immunity.Gallid alphaherpesvirus 1
Gallid alphaherpesvirus 1 (GaHV-1) (also known as Avian herpesvirus 1) is a virus of the family Herpesviridae that causes avian infectious laryngotracheitis. It was originally recognized as a disease of chickens in the United States in 1926. The disease also occurs in pheasants.The disease is usually referred to as infectious laryngotracheitis or simply LT in the poultry industry. It is widely viewed as one of the most contagious viruses that affect the poultry industry. A confirmed case will usually result in the establishment of a quarantine zone around the farm. Inside this quarantine zone, poultry workers will avoid poultry farms to prevent the spread of the virus.
GaHV-1 is shed in respiratory secretions and transmitted by droplet inhalation or via fomites. A previously unexposed flock will develop cases for two to eight weeks following introduction. The incubation period is two to eight days.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.List of notifiable diseases
The following is a list of notifiable diseases arranged by country.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.Pseudomonas exotoxin
The Pseudomonas exotoxin (or exotoxin A) is an exotoxin produced by Pseudomonas aeruginosa. Vibrio cholerae produces a similar protein called the Cholix toxin (Q5EK40).It inhibits elongation factor-2. It does so by ADP-ribosylation of EF2 using NAD+. This then causes the elongation of polypeptides to cease. This mechanism is similar to that of diphtheria toxin.It has been investigated as a treatment for hepatitis B and cancer.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.Tetanus antiserum was developed in 1890 with its protective effects lasting a few weeks. The tetanus toxoid vaccine was developed in 1924 and came into common use for soldiers in World War II. 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.