|Diphtheria can cause a swollen neck, sometimes referred to as a bull neck.|
|Symptoms||Sore throat, fever, barking 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)|
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 which 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 prevented in those exposed as well as treated with the antibiotics erythromycin or benzylpenicillin. 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 diagnosed. The disease was first described in the 5th century BC by Hippocrates. The bacterium was identified in 1882 by Edwin Klebs.
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 produced by C. diphtheriae' only when infected with a bacteriophage that integrates the toxin-encoding genetic elements into the bacteria.
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.
The current clinical case definition of diphtheria used by the United States' Centers for Disease Control and Prevention is based on both laboratory and clinical criteria.
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 recommendseither:
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,[ disputed ] 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. In Nazi Germany contagious diseases such as diphtheria were among the leading causes of morbidity; they increased "after the mid-1920s, doubled again between 1932 and 1937, and reached extremely high levels during the war only to decline rapidly thereafter".
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 1856, Victor Fourgeaud described an epidemic of diphtheria in California.
In 1878, Queen Victoria's daughter Princess Alice and her family became infected with diphtheria, causing two deaths, Princess Marie of Hesse and by Rhine and Princess Alice herself.
In 1883, Edwin Klebs identified the bacterium causing diphtheriaand 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. [ citation needed ]He used Koch's postulates to prove association between C. diphtheriae and diphtheria. He also showed that the bacillus produces an exotoxin.
Joseph P. O’Dwyer introduced the O'Dwyer tube for laryngeal intubation in patients with an obstructed larynx in 1885. It soon replaced tracheostomy as the emergency diphtheric intubation method.
In 1888, Emile Roux and Alexandre Yersin showed that a substance produced by C. diphtheriae caused symptoms of diphtheria in animals.
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. [ citation needed ]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.[ citation needed ]
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, each year an estimated 100,000 to 200,000 diphtheria cases and 13,000 to 15,000 deaths occurred in the United States.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.[ citation needed ]
In 1949, 68 of 606 children died after diphtheria immunization due to improper manufacture of aluminum phosphate toxoid.[ citation needed ]
In 1974, the World Health Organization included DPT vaccine in their Expanded Programme on Immunization for developing countries.[ citation needed ]
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 2013, three children died of diphtheria in Hyderabad, India.
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.
In March 2016, a 3-year-old girl died of diphtheria in the University Hospital of Antwerp, Belgium.
In June 2016, a 3-year-old, 5-year-old, and 7-year-old girl died of diphtheria in Kedah, Malacca and Sabah, Malaysia.
In January 2017, more than 300 cases were recorded in Venezuela.
In November and December 2017, an outbreak of diphtheria occurred in Indonesia with more than 600 cases found and 38 fatalities.
In November 2019, two cases of diphtheria occurred in the Lothian area of Scotland.Additionally, in November 2019 an 8-year-old boy died of diphtheria in Athens, Greece.
Tetanus, also known as lockjaw, is a bacterial 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. Each spasm usually lasts a few minutes. Spasms occur frequently for three to four weeks. Some spasms may be severe enough to fracture bones. Other symptoms of tetanus may include fever, sweating, headache, trouble swallowing, high blood pressure, and a fast heart rate. Onset of symptoms is typically three to twenty-one days following infection. Recovery may take months. About ten percent of cases prove fatal.
Whooping cough, also known as pertussis or the 100-day cough, is a highly contagious bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, but these are followed by weeks of severe coughing fits. Following a fit of coughing, a high-pitched whoop sound or gasp may occur as the person breathes in. The coughing may last for 10 or more weeks, hence the phrase "100-day cough". A person may cough so hard that they vomit, break ribs, or become very tired from the effort. Children less than one year old may have little or no cough and instead have periods where they do not breathe. The time between infection and the onset of symptoms is usually seven to ten days. Disease may occur in those who have been vaccinated, but symptoms are typically milder.
Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a hoarse voice. Symptoms usually last 3–5 days. Complications can include sinusitis and acute otitis media. Pharyngitis is a type of upper respiratory tract infection.
In biology, immunity is the balanced state of multicellular organisms having adequate biological defenses to fight infection, disease, or other unwanted biological invasion, while having adequate tolerance to avoid allergy, and autoimmune diseases.
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 and normally lasts one to two days.
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.
An antitoxin is an antibody with the ability to neutralize a specific toxin. Antitoxins are produced by certain animals, plants, and bacteria in response to toxin exposure. Although they are most effective in neutralizing toxins, they can also kill bacteria and other microorganisms. Antitoxins are made within organisms, and can be injected into other organisms, including humans, to treat an infectious disease. This procedure involves injecting an animal with a safe amount of a particular toxin. The animal's body then makes the antitoxin needed to neutralize the toxin. Later, blood is withdrawn from the animal. When the antitoxin is obtained from the blood, it is purified and injected into a human or other animal, inducing temporary passive immunity. To prevent serum sickness, it is often best to use an antitoxin obtained from the same species.
DPT is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis, and tetanus. The vaccine components include diphtheria and tetanus toxoids and killed whole cells of the bacterium that causes pertussis. The vaccine is also known as "DTP" or "DTwP", where the lower-case "w" indicates whole-cell inactivated pertussis.
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).
The schedule of childhood immunizations in the United States is given by the Centers for Disease Control and Prevention (CDC). The vaccination schedule is broken down by age: birth to six years of age, seven to eighteen, and adults nineteen and older. Childhood Immunizations are key in preventing children for diseases that were once epidemics.
Pneumococcal conjugate vaccine (PCV) is a pneumococcal vaccine and a conjugate vaccine used to protect infants, young children, and adults against disease caused by the bacterium Streptococcus pneumoniae (pneumococcus). It contains purified capsular polysaccharide of pneumococcal serotypes conjugated to a carrier protein to improve antibody response compared to the pneumococcal polysaccharide vaccine. The World Health Organization (WHO) recommends the use of the conjugate vaccine in routine immunizations given to children.
Diphtheria antitoxin (DAT) is a medication made up of antibodies used in the treatment of diphtheria. It is no longer recommended for prevention of diphtheria. It is given by injection into a vein or muscle.
Passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when high levels of antibodies specific to a pathogen or toxin are transferred to non-immune persons through blood products that contain antibodies, such as in immunoglobulin therapy or antiserum therapy. Passive immunization is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of ongoing or immunosuppressive diseases. Passive immunization can be provided when people cannot synthesize antibodies, and when they have been exposed to a disease that they do not have immunity against.
Immunization during pregnancy, that is the administration of a vaccine to a pregnant woman, is not a routine event as it is generally preferred to administer vaccines either prior to conception or in the postpartum period. When widespread vaccination is used, the risk for an unvaccinated pregnant patient to be exposed to a related infection is low, allowing for postponement, in general, of routine vaccinations to the postpartum period. Nevertheless, immunization during pregnancy may occur either inadvertently, or be indicated in a special situation, when it appears prudent to reduce the risk of a specific disease for a potentially exposed pregnant woman or her fetus.
William Hallock Park was an American bacteriologist and laboratory director at the New York City Board of Health, Division of Pathology, Bacteriology, and Disinfection from 1893 to 1936.
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.
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.
Elek's test or the Elek plate test is an in vitro test of virulence performed on specimens of Corynebacterium diphtheriae, the bacteria that causes diphtheria. It is used to test for toxigenicity of C. diphtheriae strains.
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 ten 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 pregnant women are up to date on their tetanus immunization can prevent neonatal tetanus.
Corynebacterium ulcerans is a rod-shaped, aerobic, and gram-positive bacteria. Most Corynebacterium are harmless but some cause serious illness in humans, especially in immunocompromised humans. C. ulcerans has been known to cause diphtheria and diphtheria-like infections in patients. Previously thought to simply be contaminants recovered from diphtheria patients, “coryneform” or “diphtheroids” are now believed to be the cause of such infections.