Diphtheria Classification and external resources
Diphtheria causes a characteristic swollen neck, sometimes referred to as “bull neck”.
ICD-10	A30.
ICD-9	032
DiseasesDB	3122
MedlinePlus	001608
eMedicine	emerg/138  med/459 oph/674 ped/596
MeSH	D004165

Diphtheria (Greek διφθερα (diphthera) — “pair of leather scrolls") is an upper respiratory tract illness characterized by sore throat, low fever, and an adherent membrane (a pseudomembrane) on the tonsils, pharynx, and/or nasal cavity. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings A00-A79 - Bacterial infections and other intestinal infectious diseases and STDs (A00-A09 Intestinal Infectious diseases ( The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Greek (el ελληνική γλώσσα or simply el ελληνικά — "Hellenic" is an Indo-European language, spoken today by 15-22 million people mainly In Animal physiology, respiration is the transport of Oxygen from the outside air to the cells within tissues and the transport of Carbon dioxide Fever (also known as pyrexia, from the Greek pyretos meaning fire or a febrile response, from the Latin word Febris For the structure in the Cerebellum, see Cerebellar tonsil. The tonsils are areas The pharynx (plural pharynges) is the part of the Neck and Throat situated immediately Posterior to (behind the Mouth and Nasal ^[1] A milder form of diphtheria can be restricted to the skin. It is caused by Corynebacterium diphtheriae, an aerobic Gram-positive bacterium. Corynebacterium diphtheriae is a pathogenic Bacterium that causes Diphtheria. Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have ^[2]

Diphtheria causes the progressive deterioration of myelin sheaths in the central and peripheral nervous system leading to degenerating motor control and loss of sensation. Diphtheria is a contagious disease spread by direct physical contact or breathing the aerosolized secretions of infected individuals. Particulates, alternatively referred to as particulate matter (PM or fine particles, are tiny particles of solid or liquid suspended in a gas Once quite common, diphtheria has largely been eradicated in developed nations through widespread vaccination. Vaccination is the administration of Antigenic material (the Vaccine) to produce immunity to a disease In the United States for instance, there were 52 reported cases of diphtheria between 1980 and 2000; since 2000 there have only been five cases^[3] as the DPT (Diphtheria–Pertussis–Tetanus) vaccine is given to all school children. The United States of America —commonly referred to as the DPT, (sometimes DTP) is a mixture of three Vaccines to immunize against Diphtheria, Pertussis (whooping cough and Tetanus. Pertussis, also known as whooping cough, is a highly contagious Disease caused by the Bacterium Bordetella pertussis; it derived its Tetanus is a medical condition that is characterized by a prolonged contraction of Skeletal muscle fibres Boosters of the vaccine are recommended for adults since the benefits of the vaccine decrease with age without constant re-exposure; they are particularly recommended for those traveling to areas where the disease has not been eradicated.

History

In the 1920s there were an estimated 100,000 to 200,000 cases of diphtheria per year in the United States, causing 13,000 to 15,000 deaths. ^[3] Children represented a large majority of these cases and fatalities. One of the most famous outbreaks of diphtheria was in Nome, Alaska; the 1925 serum run to Nome to deliver diphtheria antitoxin is now celebrated by the "Great Race of Mercy". Nome is a city located on the southern Seward Peninsula coast on Norton Sound of the Bering Sea During the 1925 serum run to Nome, also known as the " Great Race of Mercy " 20 mushers and about 150 Sled dogs relayed Diphtheria

Diphtheria was also prevalent in the British royal family during the late 19th century. The British Royal Family is the group of close relatives of the monarch of the United Kingdom. One famous case includes Queen Victoria's second daughter, Princess Alice of Hesse and her family. Victoria (Alexandrina Victoria 24 May 1819 – 22 January 1901 was from 20 June 1837 the Queen of the United Kingdom of Great Britain and Ireland The Princess Alice (Alice Maud Mary 25 April 1843 &ndash 14 December 1878) was a member of the British Royal Family, the third Princess Alice died of diphtheria after she contracted it from her children in December of 1878 while nursing them. One of Princess Alice's own daughters, Princess May, also died of diphtheria in November of 1878. Princess Marie of Hesse and by Rhine (Marie Victoria Feodore Leopoldine ( 24 May 1874 - 16 November 1878) was the youngest daughter of ^[4]

One of the first effective treatments for diphtheria was discovered in the 1880s by U. S. physician Joseph O'Dwyer (1841-1898). Joseph O'Dwyer (1841–1898 was a Catholic American Physician. O'Dwyer developed tubes that were inserted into the throat, and prevented victims from suffocating due to the membrane sheath that grows over and obstructs airways. In Medicine, intubation refers to the placement of a tube into an external or internal orifice of the body In the 1890s, the German physician Emil von Behring developed an antitoxin that did not kill the bacteria, but neutralized the toxic poisons that the bacteria releases into the body. Emil Adolf von Behring ( March 15, 1854 &ndash March 31, 1917) was a German Physiologist who received the 1901 von Behring discovered that animal blood has antitoxins in and so he took the blood, removed the clotting agents and injected it into human patients. von Behring was awarded the first Nobel Prize in Medicine for his role in the discovery, and development of a serum therapy for diphtheria. The Nobel Prize (Nobelpriset (Nobelprisen is a Swedish prize established in the 1895 will of Swedish chemist Alfred Nobel; it was first awarded in Peace, Literature (Americans William H. Park and Anna Wessels Williams; and Pasteur Institute scientists Emile Roux and Auguste Chaillou also independently developed diphtheria antitoxin in the 1890s. William Hallock Park (1863-1939 was an American Bacteriologist and Laboratory Director New York City Board of Health Division of Pathology Dr Anna Wessels Williams (1863 - 1954 worked as a Bacteriologist at the first municipal diagnostic laboratory in the United States, helped develop the The Pasteur Institute (Institut Pasteur is a French Non-profit private foundation dedicated to the study of Biology, Micro-organisms Diseases Pierre Paul Emile Roux (b December 17, 1853, Confolens ( Charente) France, d Auguste Chaillou ( August 21, 1866 - April 23, 1915) was a French Biologist and physician who was born in Parennes in the department ) The first successful vaccine for diphtheria was developed in 1913 by Behring. However, antibiotics against diphtheria were not available until the discovery and development of sulfa drugs following World War II. There are several sulfonamide-based groups of drugs The original antibacterial sulfonamides (sometimes called simply sulfa drugs are synthetic antimicrobial agents that contain the sulfonamide World War II, or the Second World War, (often abbreviated WWII) was a global military conflict which involved a majority of the world's nations, including

The Schick test, invented between 1910 and 1911, is a test used to determine whether or not a person is susceptible to diphtheria. The Schick test, invented between 1910 and 1911 is a test used to determine whether or not a person is susceptible to Diphtheria. Year 1910 ( MCMX) was a Common year starting on Saturday (link will display calendar of the Gregorian calendar (or a Common year starting Year 1911 ( MCMXI) was a Common year starting on Sunday (link will display the full calendar of the Gregorian calendar (or a Common year It was named after its inventor, Béla Schick (1877-1967), a Hungarian-born American pediatrician. Béla Schick ( July 16, 1877 - December 6, 1967) was a Hungarian -born American Pediatrician. Year 1877 ( MDCCCLXXVII) was a Common year starting on Monday (link will display the full calendar of the Gregorian calendar (or a Common Year 1967 ( MCMLXVII) was a Common year starting on Sunday (link will display full calendar of the 1967 Gregorian calendar. A massive five-year campaign was coordinated by Dr. Schick. As a part of the campaign, 85 million pieces of literature were distributed by Metropolitan Life Insurance Company with an appeal to parents to "Save your child from diphtheria. MetLife Inc is the holding corporation for the Metropolitan Life Insurance Company or MetLife for short " A vaccine was developed in the next decade, and deaths began declining in earnest in 1924. Year 1924 ( MCMXXIV) was a Leap year starting on Tuesday (link will display the full calendar of the Gregorian calendar. [1]

Mechanism

Diphtheria toxin catalyzes the ADP-ribosylation of, and inactivates, the elongation factor eEF-2. Elongation factors are a set of proteins that facilitate the events of translational elongation the steps in protein synthesis from the formation of the first Peptide bond [6] In this way, it acts to inhibit translation during eukaryotic protein synthesis. Translation is the first stage of Protein biosynthesis (part of the overall process of Gene expression) The toxin enters the host cell and is hydrolysed by a trypsin-like protease to give a fragment with enzymatic activity. The toxin then transfers an ADP-ribose from NAD⁺ to a diphthamide residue, a modified histidine (amino acid), which is found within the EF-2 protein. Nicotinamide adenine dinucleotide, abbreviated NAD+, is a Coenzyme found in all living cells The compound is a dinucleotide since it consists Diphthamide is a modified Histidine Amino acid found in eukaryotic elongation factor 2 (eEF-2 Histidine (abbreviated as His or H) is one of the 20 standard Amino acids present in Proteins In the Nutritional sense in EF-2 is needed for translocation of tRNA from the A-site to the P-site of the ribosome during traslation. The ADP-ribosylation is reversible by administering high concentrations of nicotinamide, one of the reaction products. Nicotinamide, also known as niacinamide and nicotinic acid amide, is the Amide of Nicotinic acid (vitamin B3

Signs and symptoms

The respiratory form has an incubation period of 2-5 days. Incubation period is the Time elapsed between exposure to a Pathogenic Organism, or Chemical or radiation, and when Symptoms The onset of disease is usually gradual. Symptoms include fatigue, fever, a mild sore throat and problems swallowing. Children infected have symptoms that include nausea, vomiting, chills, and a high fever, although some do not show symptoms until the infection has progressed further. In 10% of cases, patients experience neck swelling. These cases are associated with a higher risk of death.

In addition to symptoms at the site of infection (sore throat), the patient may experience more generalized symptoms, such as listlessness, pallor, and fast heart rate. These symptoms are caused by the toxin released by the bacterium. A toxin ( Greek:, toxikon, lit (poison for use on arrows is a Poisonous substance produced by living cells or organisms that is active at very low Low blood pressure may develop in these patients. In Physiology and Medicine, hypotension refers to an abnormally low Blood pressure. Longer-term effects of the diphtheria toxin include cardiomyopathy and peripheral neuropathy (sensory type). Cardiomyopathy, which literally means "heart muscle disease" is the deterioration of the function of the Myocardium (i Peripheral neuropathy is the term for damage to Nerves of the Peripheral nervous system, which may be caused either by diseases of the Nerve or from the ^[5]

A diphtheria skin lesion on the leg.

The cutaneous form of diphtheria is often a secondary infection of a preexisting skin disease. An infection is the detrimental Colonization of a host Organism by a foreign Species. Signs of cutaneous diphtheria infection develop an average of seven days after the appearance of the primary skin disease.

Diagnosis

The current definition of diphtheria used by the Centers for Disease Control and Prevention (CDC) is based on both laboratory and clinical criteria. The Centers for Disease Control and Prevention (or CDC) is an agency of the United States Department of Health and Human Services based in unincorporated

Laboratory criteria

• Isolation of Corynebacterium diphtheriae from a clinical specimen, or
• Histopathologic diagnosis of diphtheria. Corynebacterium diphtheriae is a pathogenic Bacterium that causes Diphtheria.

Clinical criteria

• Upper respiratory tract illness with sore throat
• Low-grade fever, and
• An adherent pseudomembrane of the tonsil(s), pharynx, and/or nose.

Case classification

• Probable: a clinically compatible case that is not laboratory-confirmed and is not epidemiologically linked to a laboratory-confirmed case
• Confirmed: a clinically compatible case that is either laboratory-confirmed or epidemiologically linked to a laboratory-confirmed case

Empirical treatment should generally be started in a patient in whom suspicion of diphtheria is high.

Treatment

The disease may remain manageable, but in more severe cases lymph nodes in the neck may swell, and breathing and swallowing will be more difficult. A Lymph node ( lɪmf noʊd is an organ consisting of many types of cells and is a part of the Lymphatic system. People in this stage should seek immediate medical attention, as obstruction in the throat may require intubation or a tracheotomy. In Medicine, intubation refers to the placement of a tube into an external or internal orifice of the body Tracheotomy and tracheostomy are Surgical procedures on the neck to open a direct airway through an incision in the trachea (the windpipe In addition, the hyper sensitivity of the larynx may cause cardiac arrest around the intubation. A cardiac arrest, also known as cardiorespiratory arrest, cardiopulmonary arrest or circulatory arrest, is the abrupt cessation of normal circulation of Diphtheria can also cause paralysis in the eye, neck, throat, or respiratory muscles. Patients with severe cases will be put in a hospital intensive care unit (ICU) and be given a diphtheria anti-toxin. An intensive care unit (ICU critical care unit (CCU intensive therapy unit or intensive treatment unit (ITU is a specialized department used in Since antitoxin does not neutralize toxin that is already bound to tissues, delaying its administration is associated with an increase in mortality risk. 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 CDC recommends^[6] either:

• Erythromycin (orally or by injection) for 14 days (40 mg/kg per day with a maximum of 2 g/d), or
• Procaine penicillin G given intramuscularly for 14 days (300,000 U/d for patients weighing <10 kg and 600,000 U/d for those weighing >10 kg). Erythromycin is a Macrolide Antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of Penicillin, and is often used for people Penicillin (sometimes abbreviated PCN or pen) is a group of Beta-lactam antibiotics used in the treatment of Bacterial Infections Patients with allergies to penicillin G or erythromycin can use rifampin or clindamycin. Rifampicin ( INN) (rɪˈfæmpəsɪn or rifampin ( USAN) is a Bactericidal Antibiotic drug of the Rifamycin group Clindamycin ( rINN; klɪndəˈmaɪsɨn is a lincosamide Antibiotic.

Epidemiology

Diphtheria cases reported to the World Health Organization between 1997 and 2006 (see description for legend).

Diphtheria is a serious disease, with fatality rates between 5% and 10%. In children under 5 years and adults over 40 years, the fatality rate may be as much as 20%. ^[3] Outbreaks, though very rare, still occur worldwide, even in developed nations. After the breakup of the former Soviet Union in the late 1980s, vaccination rates in its constituent countries fell so low that there was an explosion of diphtheria cases. The Union of Soviet Socialist Republics (USSR was a constitutionally Socialist state that existed in Eurasia from 1922 to 1991 In 1991 there were 2,000 cases of diphtheria in the USSR. By 1998, according to Red Cross estimates, there were as many as 200,000 cases in the Commonwealth of Independent States, with 5,000 deaths. The International Red Cross and Red Crescent Movement is an International humanitarian movement with approximately 97 million volunteers worldwide who stated This was so great an increase that diphtheria was cited in the Guinness Book of World Records as "most resurgent disease". Guinness World Records, known until 2000 as The Guinness Book of Records (and in previous U

References

Further reading

• Holmes RK, Diphtheria and other corynebacterial infections. in Harrison's Principles of Internal Medicine, 16th Ed. (2005)
• Antitoxin dars 1735 and 1740. " The William and Mary Quarterly, 3rd Ser. , Vol 6, No 2. p. 338. See Also: Shulman, Stanford (2004) [2] The History of Pediatric Infectious Diseases (Html by Google)] Pediatric Research. Vol. 55, No. 1

External links