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Diphtheria is an
infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
caused by the
bacterium Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the ...
''
Corynebacterium diphtheriae ''Corynebacterium diphtheriae'' is a Gram-positive 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 ...
''. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks, the mortality rate approaches 10%. Signs and symptoms may vary from mild to severe, and usually start two to five days after exposure. Symptoms often develop gradually, beginning with a sore throat and
fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
. In severe cases, a grey or white patch develops in the throat, which can block the airway, and create a barking cough similar to what is observed in
croup Croup ( ), also known as croupy cough, 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 "bar ...
. The neck may also swell, in part due to the enlargement of the
facial lymph nodes The facial lymph nodes comprise three groups: * (a) infraorbital or maxillary, scattered over the infraorbital region from the groove between the nose and cheek to the zygomatic arch; * (b) buccinator, one or more placed on the buccinator muscle ...
. Diphtheria can also involve the skin, eyes, or genitals, and can cause complications, including
myocarditis Myocarditis is inflammation of the cardiac muscle. Myocarditis can progress to inflammatory cardiomyopathy when there is associated ventricular remodeling and cardiac dysfunction due to chronic inflammation. Symptoms can include shortness of bre ...
(which in itself can result in an abnormal heart rate), inflammation of nerves (which can result in
paralysis Paralysis (: paralyses; also known as plegia) is a loss of Motor skill, motor function in one or more Skeletal muscle, muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory d ...
),
kidney problems Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...
, and bleeding problems due to low levels of platelets. Diphtheria is usually spread between people by direct contact,
through the air ''Through the Air'' (French title: ''La résistance de l'air'') is a 2015 French-Belgian drama film directed by Fred Grivois. The film concerns an air rifle champion who becomes embroiled in a dangerous plot after accepting a well-paid job offer ...
, or through contact with contaminated objects. Asymptomatic transmission and chronic infection are also possible. Different strains of ''C. diphtheriae'' are the main cause in the variability of lethality, as the lethality and symptoms themselves are caused by the
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, sim ...
produced by the bacteria. Diagnosis can often be made based on the appearance of the throat with confirmation by
microbiological culture A microbiological culture, or microbial culture, is a method of multiplying microorganism, microbial organisms by letting them reproduce in predetermined culture medium under controlled laboratory conditions. Microbial cultures are foundational a ...
. Previous infection may not protect against reinfection. A
diphtheria vaccine Diphtheria vaccine is a toxoid vaccine against diphtheria, an illness caused by ''Corynebacterium diphtheriae''. Its use has resulted in a more than 90% decrease in number of cases globally between 1980 and 2000. The first dose is recommended ...
is effective for prevention, and is available in a number of formulations. Three or four doses, given along with
tetanus vaccine Tetanus vaccine, also known as tetanus toxoid (TT), is a toxoid vaccine used to prevent tetanus. During childhood, five doses are recommended, with a sixth given during adolescence. After three doses, almost everyone is initially immune, but ...
and
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% effect ...
, are recommended during childhood. Further doses of the 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 An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
erythromycin Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used ...
or
benzylpenicillin Benzylpenicillin, also known as penicillin G (PenG) or BENPEN, is an antibiotic used to treat a number of bacterial infections. This includes pneumonia, strep throat, syphilis, necrotizing enterocolitis, diphtheria, gas gangrene, leptospiro ...
. In severe cases a
tracheotomy Tracheotomy (, ), or tracheostomy, is a surgical airway management procedure which consists of making an incision on the front of the neck to open a direct airway to the trachea. The resulting stoma (hole) can serve independently as an airway ...
may be needed to open the airway. 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 Sub-Saharan Africa is the area and regions of the continent of Africa that lie south of the Sahara. These include Central Africa, East Africa, Southern Africa, and West Africa. Geopolitically, in addition to the list of sovereign states and ...
,
South Asia South Asia is the southern Subregion#Asia, subregion of Asia that is defined in both geographical and Ethnicity, ethnic-Culture, cultural terms. South Asia, with a population of 2.04 billion, contains a quarter (25%) of the world's populatio ...
, and
Indonesia Indonesia, officially the Republic of Indonesia, is a country in Southeast Asia and Oceania, between the Indian Ocean, Indian and Pacific Ocean, Pacific oceans. Comprising over List of islands of Indonesia, 17,000 islands, including Sumatra, ...
. 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 A developed country, or advanced country, is a sovereign state that has a high quality of life, developed economy, and advanced technological infrastructure relative to other less industrialized nations. Most commonly, the criteria for eval ...
due to widespread
vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
, but can re-emerge if vaccination rates decrease. In the United States, 57 cases were reported between 1980 and 2004. Death occurs in 5–10% of those diagnosed. The disease was first described in the 5th century BC by
Hippocrates Hippocrates of Kos (; ; ), also known as Hippocrates II, was a Greek physician and philosopher of the Classical Greece, classical period who is considered one of the most outstanding figures in the history of medicine. He is traditionally referr ...
. The bacterium was identified in 1882 by
Edwin Klebs Theodor Albrecht Edwin Klebs (6 February 1834 – 23 October 1913) was a German-Swiss microbiologist. He is mainly known for his work on infectious diseases. His works paved the way for the beginning of modern bacteriology, and inspired Louis Pas ...
.


Signs and symptoms

The symptoms of diphtheria usually begin two to seven days after infection. They include fever of 38 °C (100.4 °F) or above; chills;
fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...
; bluish skin coloration (
cyanosis Cyanosis is the change of Tissue (biology), tissue color to a bluish-purple hue, as a result of decrease in the amount of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Cyanosis is apparent usually in the Tissue (bi ...
); sore throat;
hoarseness A hoarse voice, also known as dysphonia or hoarseness, is when the voice involuntarily sounds breathy, raspy, or strained, or is softer in volume or lower in pitch. A hoarse voice can be associated with a feeling of unease or scratchiness in the ...
;
cough A cough is a sudden expulsion of air through the large breathing passages which can help clear them of fluids, irritants, foreign particles and Microorganism, microbes. As a protective reflex, coughing can be repetitive with the cough reflex fol ...
; headache; difficulty swallowing; painful swallowing; difficulty breathing; rapid breathing; foul-smelling and bloodstained nasal discharge; and
lymphadenopathy Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In c ...
. 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 arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – above 100 beat ...
s,
myocarditis Myocarditis is inflammation of the cardiac muscle. Myocarditis can progress to inflammatory cardiomyopathy when there is associated ventricular remodeling and cardiac dysfunction due to chronic inflammation. Symptoms can include shortness of bre ...
, and
cranial Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek language, Greek roots, describe something in its standard anatomical position. Thi ...
and peripheral nerve palsies.


Diphtheritic croup

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 Stridor () is an extra-thoracic high-pitched breath sound resulting from turbulent air flow in the larynx or lower in the bronchial tree. It is different from a stertor, which is a noise originating in the pharynx. Stridor is a physical sig ...
, 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 Croup ( ), also known as croupy cough, 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 "bar ...
" nowadays most often refers to an unrelated viral illness that produces similar but milder respiratory symptoms.


Transmission

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 case 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 A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a virus, bacterium, parasite, fungi, or prion) that can jump from a non-human vertebrate to a human. When h ...
, but this has yet to be confirmed. ''Corynebacterium ulcerans'' has been found in some animals, which would suggest zoonotic potential.


Mechanism

Diphtheria toxin Diphtheria toxin is an exotoxin secreted mainly by '' Corynebacterium diphtheriae'' but also by ''Corynebacterium ulcerans'' and '' Corynebacterium pseudotuberculosis'', the pathogenic bacterium that causes diphtheria. The toxin gene is enco ...
(DT) is produced only by ''C. diphtheriae'' infected with a certain type of
bacteriophage A bacteriophage (), also known informally as a phage (), is a virus that infects and replicates within bacteria. The term is derived . Bacteriophages are composed of proteins that Capsid, encapsulate a DNA or RNA genome, and may have structu ...
. Toxinogenicity is determined by phage conversion (also called
lysogenic conversion Lysogeny, or the lysogenic cycle, is one of two cycles of viral reproduction (the lytic cycle being the other). Lysogeny is characterized by integration of the bacteriophage nucleic acid into the host bacterium's genome or formation of a circ ...
); i.e., the ability of the bacterium to make DT changes as a consequence of infection by a particular phage. DT is encoded by the ''tox'' gene. Strains of corynephage are either ''tox''+ (e.g., corynephage β) or ''tox'' (e.g., corynephage γ). The ''tox'' gene becomes integrated into the bacterial genome. The chromosome of ''C. diphtheriae'' has two different but functionally equivalent bacterial attachment sites (attB) for integration of β prophage into the chromosome. The diphtheria toxin precursor is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
of
molecular weight A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...
60 
kDa The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted f ...
. Certain proteases, such as trypsin, selectively cleave DT to generate two
peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...
chains, amino-terminal fragment A (DT-A) and carboxyl-terminal fragment B (DT-B), which are held together by a
disulfide bond In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inor ...
. DT-B is a recognition subunit that gains entry of DT into the host cell by binding to the EGF-like domain of
heparin-binding EGF-like growth factor Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of proteins that in humans is encoded by the ''HBEGF'' gene. HB-EGF-like growth factor is synthesized as a membrane-anchored mitogenic and chemotactic glycoprotein. An ...
on the cell surface. This signals the cell to internalize the toxin within an
endosome Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of the endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membra ...
via
receptor-mediated endocytosis Receptor-mediated endocytosis (RME), also called clathrin-mediated endocytosis, is a process by which cells absorb metabolites, hormones, proteins – and in some cases viruses – by the inward budding of the plasma membrane (invagination). This ...
. Inside the endosome, DT is split by a trypsin-like
protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...
into DT-A and DT-B. The acidity of the endosome causes DT-B to create pores in the endosome membrane, thereby catalysing the release of DT-A into the
cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...
. Fragment A inhibits the synthesis of new proteins in the affected cell by catalyzing
ADP-ribosylation ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. It is a reversible post-translational modification that is involved in many cellular processes, including cell signaling, DNA repair, gene regulation and apoptosis ...
of
elongation factor Elongation factors are a set of proteins that function at the ribosome, during protein synthesis, to facilitate translational elongation from the formation of the first to the last peptide bond of a growing polypeptide. Most common elongation ...
EF-2—a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that is essential to the translation step of protein synthesis. This ADP-ribosylation involves the transfer of an
ADP-ribose Adenosine diphosphate ribose (ADPR) is an ester molecule formed into chains by the enzyme poly ADP ribose polymerase. ADPR is created from cyclic ADP-ribose (cADPR) by the CD38 enzyme using nicotinamide adenine dinucleotide (NAD+) as a cofactor. ...
from
NAD+ Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an ade ...
to a
diphthamide Diphthamide is a post-translationally modified histidine amino acid found in archaeal and eukaryotic elongation factor 2 (eEF-2). Dipthamide is named after the toxin produced by the bacterium ''Corynebacterium diphtheriae'', which targets diphth ...
(a modified
histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an Amine, α-amino group (which is in the protonated –NH3+ form under Physiological condition, biological conditions), a carboxylic ...
) residue within the EF-2 protein. Since EF-2 is needed for the moving of
tRNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...
from the A-site to the P-site of the
ribosome Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order s ...
during protein translation, ADP-ribosylation of EF-2 prevents protein synthesis. ADP-ribosylation of EF-2 is reversed by giving high doses of
nicotinamide Nicotinamide (International nonproprietary name, INN, British Approved Name, BAN ) or niacinamide (United States Adopted Name, USAN ) is a form of vitamin B3, vitamin B3 found in food and used as a dietary supplement and medication. As a suppl ...
(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.


Diagnosis

The current
clinical case definition In epidemiology, a clinical case definition, a clinical definition, or simply a case definition lists the clinical criteria by which public health professionals determine whether a person's illness is included as a ''case'' in an outbreak investiga ...
of diphtheria used by the
United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
'
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...
is based on both laboratory and clinical criteria.


Laboratory criteria

* Isolation of ''C. diphtheriae'' from a Gram stain or throat culture from a clinical specimen. * Histopathologic diagnosis of diphtheria by Albert's stain.


Toxin demonstration

* In vivo tests (guinea pig inoculation): Subcutaneous and intracutaneous tests. * In vitro test: Elek's gel precipitation test, detection of tox gene by PCR, ELISA, ICA.


Clinical criteria

* Upper respiratory tract illness with sore throat. * Low-grade fever (above is rare). * An adherent, dense, grey pseudomembrane covering the posterior aspect of the pharynx; in severe cases, it can extend to cover the entire tracheobronchial tree.


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.


Prevention

Vaccination against diphtheria is commonly done in infants, and delivered as a combination vaccine, such as a
DPT vaccine The DPT vaccine or DTP vaccine is a class of combination vaccines to protect against three infectious diseases in humans: diphtheria, pertussis (whooping cough), and tetanus (lockjaw). The vaccine components include diphtheria and tetanus t ...
(diphtheria,
pertussis Whooping cough ( or ), also known as pertussis or the 100-day cough, is a highly contagious, vaccine-preventable bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, bu ...
,
tetanus Tetanus (), also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'' and 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 l ...
).
Pentavalent vaccine A pentavalent vaccine combines five vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of ...
s, which vaccinate against diphtheria and four other childhood diseases simultaneously, are frequently used in disease prevention programs in
developing countries A developing country is a sovereign state with a less-developed Secondary sector of the economy, industrial base and a lower Human Development Index (HDI) relative to developed countries. However, this definition is not universally agreed upon. ...
by organizations such as
UNICEF UNICEF ( ), originally the United Nations International Children's Emergency Fund, officially United Nations Children's Fund since 1953, is an agency of the United Nations responsible for providing Humanitarianism, humanitarian and Development a ...
.


Treatment

The disease may remain manageable, but in more severe cases,
lymph nodes A lymph node, or lymph gland, is a kidney-shaped Organ (anatomy), organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphoc ...
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 Intubation (sometimes entubation) is a medical procedure involving the insertion of a tube into the body. Most commonly, intubation refers to tracheal intubation, a procedure during which an endotracheal tube is inserted into the trachea to supp ...
or a
tracheotomy Tracheotomy (, ), or tracheostomy, is a surgical airway management procedure which consists of making an incision on the front of the neck to open a direct airway to the trachea. The resulting stoma (hole) can serve independently as an airway ...
. Abnormal cardiac rhythms can occur early in the course of the illness or weeks later, and can lead to
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...
. 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 An intensive care unit (ICU), also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU), is a special department of a hospital or health care facility that provides intensive care medicine. An inten ...
, and given diphtheria
antitoxin An antitoxin is an antibody with the ability to neutralize a specific toxin. Antitoxins are produced by certain animals, plants, and bacterium, bacteria in response to toxin exposure. Although they are most effective in neutralizing toxins, the ...
(consisting of
antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
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 (CDC) recommends either: *
Metronidazole Metronidazole, sold under the brand name Flagyl and Metrogyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vagino ...
*
Erythromycin Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used ...
is given (orally or by injection) for 14 days (40 mg/kg per day with a maximum of 2'' ''g/d), or * Procaine penicillin G is given intramuscularly for 14 days (300,000 U/d for patients weighing <10 kg, and 600,000 U/d for those weighing >10 kg); patients with allergies to penicillin G or erythromycin can use
rifampin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires' disease. It is almost always used tog ...
or
clindamycin Clindamycin is a lincosamide antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media (mi ...
. 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 40–50% of those left untreated can die.


Epidemiology

Diphtheria is fatal in 5–10% 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. Better standards of living, mass immunization, improved diagnosis, prompt treatment, and more effective health care have led to a decrease in cases worldwide.


History

In 1613,
Spain Spain, or the Kingdom of Spain, is a country in Southern Europe, Southern and Western Europe with territories in North Africa. Featuring the Punta de Tarifa, southernmost point of continental Europe, it is the largest country in Southern Eur ...
experienced an epidemic of diphtheria, referred to as (The Year of Strangulations). In 1705, the
Mariana Islands The Mariana Islands ( ; ), also simply the Marianas, are a crescent-shaped archipelago comprising the summits of fifteen longitudinally oriented, mostly dormant volcanic mountains in the northwestern Pacific Ocean, between the 12th and 21st pa ...
experienced an epidemic of diphtheria and
typhus Typhus, also known as typhus fever, is a group of infectious diseases that include epidemic typhus, scrub typhus, and murine typhus. Common symptoms include fever, headache, and a rash. Typically these begin one to two weeks after exposu ...
simultaneously, reducing the population to about 5,000 people. In 1735, a diphtheria epidemic swept through
New England New England is a region consisting of six states in the Northeastern United States: Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont. It is bordered by the state of New York (state), New York to the west and by the ...
. Before 1826, diphtheria was known by different names across the world. In
England England is a Countries of the United Kingdom, country that is part of the United Kingdom. It is located on the island of Great Britain, of which it covers about 62%, and List of islands of England, more than 100 smaller adjacent islands. It ...
, it was known as "Boulogne sore throat," as the illness had spread from
France France, officially the French Republic, is a country located primarily in Western Europe. Overseas France, Its overseas regions and territories include French Guiana in South America, Saint Pierre and Miquelon in the Atlantic Ocean#North Atlan ...
. In 1826,
Pierre Bretonneau Pierre-Fidèle Bretonneau (3 April 1778 – 18 February 1862) was a French medical doctor. Biography Born in Saint-Georges-sur-Cher, in the Loir-et-Cher département. His father was a surgeon. He studied with his uncle, the vicar at Chenonce ...
gave the disease the name ''diphthérite'' (from Greek διφθέρα, ''diphthera'' 'leather'), describing the appearance of pseudomembrane in the throat. In 1856, Victor Fourgeaud described an epidemic of diphtheria in
California California () is a U.S. state, state in the Western United States that lies on the West Coast of the United States, Pacific Coast. It borders Oregon to the north, Nevada and Arizona to the east, and shares Mexico–United States border, an ...
. In 1878, Princess Alice (
Queen Victoria Victoria (Alexandrina Victoria; 24 May 1819 – 22 January 1901) was Queen of the United Kingdom of Great Britain and Ireland from 20 June 1837 until Death and state funeral of Queen Victoria, her death in January 1901. Her reign of 63 year ...
's second daughter) and her family became infected with diphtheria; Princess Alice and her four-year-old daughter, Princess Marie, both died. In 1883,
Edwin Klebs Theodor Albrecht Edwin Klebs (6 February 1834 – 23 October 1913) was a German-Swiss microbiologist. He is mainly known for his work on infectious diseases. His works paved the way for the beginning of modern bacteriology, and inspired Louis Pas ...
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 time, it has been called ''Microsporon diphtheriticum'', ''Bacillus diphtheriae'', and ''Mycobacterium diphtheriae''. Current nomenclature is ''Corynebacterium diphtheriae''. In 1884, German
bacteriologist A bacteriologist is a microbiologist, or similarly trained professional, in bacteriology— a subdivision of microbiology that studies bacteria, typically Pathogenic bacteria, pathogenic ones. Bacteriologists are interested in studying and learnin ...
Friedrich Loeffler Friedrich August Johannes Loeffler (; 24 June 18529 April 1915) was a German bacteriologist at the University of Greifswald. Biography He obtained his M.D. degree from the University of Berlin in 1874. He worked with Robert Koch from 1879 to 188 ...
became the first person to cultivate ''C. diphtheriae''. He used
Koch's postulates Koch's postulates ( ) are four criteria designed to establish a causality, causal relationship between a microbe and a disease. The postulates were formulated by Robert Koch and Friedrich Loeffler in 1884, based on earlier concepts described by ...
to prove association between ''C. diphtheriae'' and diphtheria. He also showed that the bacillus produces an exotoxin. In 1885, Joseph P. O'Dwyer introduced the O'Dwyer tube for laryngeal intubation in patients with an obstructed larynx. It soon replaced
tracheostomy Tracheotomy (, ), or tracheostomy, is a surgical airway management procedure which consists of making an incision on the front of the neck to open a direct airway to the trachea. The resulting stoma (hole) can serve independently as an airway ...
as the emergency diphtheric intubation method. In 1888,
Emile Roux Emile or Émile may refer to: * Émile (novel) (1827), autobiographical novel based on Émile de Girardin's early life * Emile, Canadian film made in 2003 by Carl Bessai * '' Emile: or, On Education'' (1762) by Jean-Jacques Rousseau, a treatise o ...
and
Alexandre Yersin Alexandre Émile John Yersin (22 September 1863 – 1 March 1943) was a Swiss- French physician and bacteriologist. He is remembered as the co-discoverer (1894) of the bacillus responsible for the bubonic plague or pest, which was later named in ...
showed that a substance produced by ''C. diphtheriae'' caused symptoms of diphtheria in animals. In 1890, Shibasaburō Kitasato and
Emil von Behring Emil von Behring (; Emil Adolf von Behring: born 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 in that field, for his discovery ...
immunized guinea pigs with heat-treated diphtheria toxin. They also immunized goats and horses in the same way, and showed that an "
antitoxin An antitoxin is an antibody with the ability to neutralize a specific toxin. Antitoxins are produced by certain animals, plants, and bacterium, bacteria in response to toxin exposure. Although they are most effective in neutralizing toxins, the ...
" made from serum of immunized animals could cure the disease in non-immunized animals. Behring used this antitoxin (now known to consist of
antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
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. In 1901, Von Behring won the first
Nobel Prize in medicine The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute, Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single ...
for his work on diphtheria. In 1895, H. K. Mulford Company of
Philadelphia Philadelphia ( ), colloquially referred to as Philly, is the List of municipalities in Pennsylvania, most populous city in the U.S. state of Pennsylvania and the List of United States cities by population, sixth-most populous city in the Unit ...
started production and testing of diphtheria antitoxin in the United States.
Park A park is an area of natural, semi-natural or planted space set aside for human enjoyment and recreation or for the protection of wildlife or natural habitats. Urban parks are urban green space, green spaces set aside for recreation inside t ...
and
Biggs Biggs may refer to: Arts and entertainment * Biggs (TV channel), a Portuguese television channel formerly for kids, teens and youth and now for teens and youth. * Biggs Darklighter, a character in ''Star Wars Episode IV: A New Hope'' * Biggs, a re ...
described the method for producing serum from horses for use in diphtheria treatment. In 1897,
Paul Ehrlich Paul Ehrlich (; 14 March 1854 – 20 August 1915) was a Nobel Prize-winning German physician and scientist who worked in the fields of hematology, immunology and antimicrobial chemotherapy. Among his foremost achievements were finding a cure fo ...
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 St. Louis ( , sometimes referred to as St. Louis City, Saint Louis or STL) is an independent city in the U.S. state of Missouri. It lies near the confluence of the Mississippi and the Missouri rivers. In 2020, the city proper had a populatio ...
children died from contaminated diphtheria antitoxin. The horse from which the antitoxin was derived died of
tetanus Tetanus (), also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'' and 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 l ...
. This incident, coupled with a tetanus outbreak in
Camden, New Jersey Camden is a City (New Jersey), city in Camden County, New Jersey, Camden County, in the U.S. state of New Jersey. It is part of the Delaware Valley metropolitan region. The city was incorporated on February 13, 1828.Snyder, John P''The Story of ...
, played an important part in initiating federal regulation of biologic products. On 7 January 1904,
Ruth Cleveland Ruth Eva Cleveland (October 3, 1891 – January 7, 1904), popularly known as Baby Ruth or Babe Ruth, was the eldest of five children born to United States President Grover Cleveland and First Lady Frances Cleveland. She is the purported namesa ...
died of diphtheria at the age of 12 years in
Princeton, New Jersey The Municipality of Princeton is a Borough (New Jersey), borough in Mercer County, New Jersey, United States. It was established on January 1, 2013, through the consolidation of the Borough of Princeton, New Jersey, Borough of Princeton and Pri ...
. Ruth was the eldest daughter of former
President President most commonly refers to: *President (corporate title) * President (education), a leader of a college or university *President (government title) President may also refer to: Arts and entertainment Film and television *'' Præsident ...
Grover Cleveland Stephen Grover Cleveland (March 18, 1837June 24, 1908) was the 22nd and 24th president of the United States, serving from 1885 to 1889 and from 1893 to 1897. He was the first U.S. president to serve nonconsecutive terms and the first Hist ...
and the former First Lady,
Frances Folsom Frances Clara Cleveland Preston (, christened Frank Clara; July 21, 1864 – October 29, 1947) was the first lady of the United States from 1886 to 1889 and again from 1893 until 1897, as the wife of President Grover Cleveland. She was the ...
. 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 Serum sickness in humans is a adverse drug reaction, reaction to proteins in antiserum derived from a non-human animal source, occurring 5–10 days after exposure. Symptoms often include a rash, Arthralgia, joint pain, fever, and lymphadenopathy. ...
in children receiving large quantities of horse-derived antitoxin. Between 1910 and 1911, Béla Schick developed the
Schick test The Schick test, developed in 1913, is a skin test used to determine whether or not a person is susceptible to diphtheria. It was named after its inventor, Béla Schick (1877–1967), a Hungarian-born American pediatrician. Procedure The test i ...
to detect pre-existing immunity to diphtheria in an exposed person. Only those who had not been exposed to diphtheria were 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 MetLife, Inc. is the holding corporation for the Metropolitan Life Insurance Company (MLIC), better known as MetLife, and its affiliates. MetLife is among the largest global providers of insurance, annuities, and employee benefit programs, w ...
, 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 Dallas () is a city in the U.S. state of Texas and the most populous city in the Dallas–Fort Worth metroplex, the List of Texas metropolitan areas, most populous metropolitan area in Texas and the Metropolitan statistical area, fourth-most ...
, 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. The manufacturer of the antitoxin, the Mulford Company of Philadelphia, paid damages in every case. During the 1920s, an annual estimate of 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 occurred in 1925, in
Nome, Alaska Nome (; , , also ''Sitŋazuaq'', ''Siqnazuaq'') is a city in the Nome Census Area, Alaska, Nome Census Area in the Unorganized Borough, Alaska, Unorganized Borough of the US state of Alaska. The city is located on the southern Seward Peninsula c ...
; the "Great Race of Mercy" to deliver diphtheria antitoxin is now celebrated by the
Iditarod Trail Sled Dog Race The Iditarod Trail Sled Dog Race, more commonly known as The Iditarod (), is an annual long-distance sled dog race held in Alaska in early March. It travels from Anchorage to Nome. Mushers and a team of between 12 and 16 dogs, of which at lea ...
. In 1926, Alexander Thomas Glenny increased the effectiveness of diphtheria
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, wherea ...
(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 1939, Dr.
Nora Wattie Nora Wattie (20 May 1900–14 July 1994) Bachelor of Medicine, Bachelor of Surgery, MBChB (University of Aberdeen, Aberdeen), DPH (University of Cambridge, Cambridge) was a pioneer of social medicine, setting up Glasgow’s internationally renown ...
, who was the Principal Medical Officer (Maternity and Child Welfare) of Glasgow between 1934– 1964, introduced immunisation clinics across
Glasgow Glasgow is the Cities of Scotland, most populous city in Scotland, located on the banks of the River Clyde in Strathclyde, west central Scotland. It is the List of cities in the United Kingdom, third-most-populous city in the United Kingdom ...
, and promoted mother and child health education, resulting in virtual eradication of the infection in the city. Widespread vaccination pushed cases in the United States down from 4.4 per 100,000 inhabitants in 1932 to 2.0 in 1937. In
Nazi Germany Nazi Germany, officially known as the German Reich and later the Greater German Reich, was the German Reich, German state between 1933 and 1945, when Adolf Hitler and the Nazi Party controlled the country, transforming it into a Totalit ...
, where authorities preferred treatment and isolation over vaccination (until about 1939–1941), cases rose over the same period from 6.1 to 9.6 per 100,000 inhabitants. Between June 1942 and February 1943, 714 cases of diphtheria were recorded at
Sham Shui Po Barracks Sham Shui Po Barracks was a British Army facility built in the 1920s in the Sham Shui Po area of Kowloon, Hong Kong. The base was bounded by Fuk Wa Street to the east, by Yen Chow Street and to the west by Tonkin Street and Camp Street. The b ...
, resulting in 112 deaths because the
Imperial Japanese Army The Imperial Japanese Army (IJA; , ''Dai-Nippon Teikoku Rikugun'', "Army of the Greater Japanese Empire") was the principal ground force of the Empire of Japan from 1871 to 1945. It played a central role in Japan’s rapid modernization during th ...
did not release supplies of anti-diphtheria serum. In 1943, diphtheria outbreaks accompanied war and disruption in
Europe Europe is a continent located entirely in the Northern Hemisphere and mostly in the Eastern Hemisphere. It is bordered by the Arctic Ocean to the north, the Atlantic Ocean to the west, the Mediterranean Sea to the south, and Asia to the east ...
. The 1 million cases in Europe resulted in 50,000 deaths. During 1948 in
Kyoto Kyoto ( or ; Japanese language, Japanese: , ''Kyōto'' ), officially , is the capital city of Kyoto Prefecture in the Kansai region of Japan's largest and most populous island of Honshu. , the city had a population of 1.46 million, making it t ...
, 68 of 606 children died after diphtheria immunization due to improper manufacture of aluminum phosphate toxoid. In 1974, the
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
included
DPT vaccine The DPT vaccine or DTP vaccine is a class of combination vaccines to protect against three infectious diseases in humans: diphtheria, pertussis (whooping cough), and tetanus (lockjaw). The vaccine components include diphtheria and tetanus t ...
in their
Expanded Programme on Immunization Expansion may refer to: Arts, entertainment and media * ''L'Expansion'', a French monthly business magazine * ''Expansion'' (album), by American jazz pianist Dave Burrell, released in 2004 * ''Expansions'' (McCoy Tyner album), 1970 * ''Expansi ...
for
developing countries A developing country is a sovereign state with a less-developed Secondary sector of the economy, industrial base and a lower Human Development Index (HDI) relative to developed countries. However, this definition is not universally agreed upon. ...
. In 1975, an outbreak of cutaneous diphtheria in
Seattle, Washington Seattle ( ) is the List of municipalities in Washington, most populous city in the U.S. state of Washington (state), Washington and in the Pacific Northwest region of North America. With a population of 780,995 in 2024, it is the List of Unit ...
, was reported. After the breakup of the former
Soviet Union The Union of Soviet Socialist Republics. (USSR), commonly known as the Soviet Union, was a List of former transcontinental countries#Since 1700, transcontinental country that spanned much of Eurasia from 1922 until Dissolution of the Soviet ...
in 1991, 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 were reported in the
Commonwealth of Independent States The Commonwealth of Independent States (CIS) is a regional organization, regional intergovernmental organization in Eurasia. It was formed following the dissolution of the Soviet Union, dissolution of the Soviet Union in 1991. It covers an ar ...
, and resulted in 5,000 deaths. In 1994, the
Russian Federation Russia, or the Russian Federation, is a country spanning Eastern Europe and North Asia. It is the list of countries and dependencies by area, largest country in the world, and extends across Time in Russia, eleven time zones, sharing Borders ...
had 39,703 diphtheria cases. By contrast, in 1990, only 1,211 cases were reported. In early May 2010, a case of diphtheria was diagnosed in
Port-au-Prince Port-au-Prince ( ; ; , ) is the Capital city, capital and List of cities in Haiti, most populous city of Haiti. The city's population was estimated at 1,200,000 in 2022 with the metropolitan area estimated at a population of 2,618,894. The me ...
,
Haiti Haiti, officially the Republic of Haiti, is a country on the island of Hispaniola in the Caribbean Sea, east of Cuba and Jamaica, and south of the Bahamas. It occupies the western three-eighths of the island, which it shares with the Dominican ...
, after the devastating
2010 Haiti earthquake The 2010 Haiti earthquake was a catastrophic Moment magnitude scale, magnitude 7.0 Mw earthquake that struck Haiti at 16:53 local time (21:53 UTC) on Tuesday, 12 January 2010. The epicenter was near the town of Léogâne, Ouest (departm ...
. The 15-year-old male patient died while workers searched for antitoxin. In 2013, three children died of diphtheria in
Hyderabad, India Hyderabad is the capital and largest city of the Indian state of Telangana. It occupies on the Deccan Plateau along the banks of the Musi River (India), Musi River, in the northern part of Southern India. With an average altitude of , much ...
. In early June 2015, a case of diphtheria was diagnosed at Vall d'Hebron University Hospital in
Barcelona Barcelona ( ; ; ) is a city on the northeastern coast of Spain. It is the capital and largest city of the autonomous community of Catalonia, as well as the second-most populous municipality of Spain. With a population of 1.6 million within c ...
,
Spain Spain, or the Kingdom of Spain, is a country in Southern Europe, Southern and Western Europe with territories in North Africa. Featuring the Punta de Tarifa, southernmost point of continental Europe, it is the largest country in Southern Eur ...
. The six-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 the Spanish daily newspaper '' El Mundo,'' or from 1998, as reported by the WHO. In March 2016, a three-year-old girl died of diphtheria in the University Hospital of
Antwerp Antwerp (; ; ) is a City status in Belgium, city and a Municipalities of Belgium, municipality in the Flemish Region of Belgium. It is the capital and largest city of Antwerp Province, and the third-largest city in Belgium by area at , after ...
,
Belgium Belgium, officially the Kingdom of Belgium, is a country in Northwestern Europe. Situated in a coastal lowland region known as the Low Countries, it is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeas ...
. In June 2016, a three-year-old, five-year-old, and seven-year-old girl died of diphtheria in
Kedah Kedah (), also known by its honorific Darul Aman (Islam), Aman (دار الأمان; Arabic for 'The Safe Abode') and historically as Queda, is a States and federal territories of Malaysia, state of Malaysia, located in the northwestern part of ...
,
Malacca Malacca (), officially the Historic State of Malacca (), is a States and federal territories of Malaysia, state in Malaysia located in the Peninsular Malaysia#Other features, southern region of the Malay Peninsula, facing the Strait of Malacca ...
, and
Sabah Sabah () is a States and federal territories of Malaysia, state of Malaysia located in northern Borneo, in the region of East Malaysia. Sabah has land borders with the Malaysian state of Sarawak to the southwest and Indonesia's North Kalima ...
,
Malaysia Malaysia is a country in Southeast Asia. Featuring the Tanjung Piai, southernmost point of continental Eurasia, it is a federation, federal constitutional monarchy consisting of States and federal territories of Malaysia, 13 states and thre ...
. In January 2017, more than 300 cases were recorded in
Venezuela Venezuela, officially the Bolivarian Republic of Venezuela, is a country on the northern coast of South America, consisting of a continental landmass and many Federal Dependencies of Venezuela, islands and islets in the Caribbean Sea. It com ...
. In 2017, outbreaks occurred in a Rohingya refugee camp in Bangladesh, and amongst children unvaccinated due to the Yemeni Civil War. In November and December 2017, an outbreak of diphtheria occurred in
Indonesia Indonesia, officially the Republic of Indonesia, is a country in Southeast Asia and Oceania, between the Indian Ocean, Indian and Pacific Ocean, Pacific oceans. Comprising over List of islands of Indonesia, 17,000 islands, including Sumatra, ...
, with more than 600 cases found and 38 fatalities. In November 2019, two cases of diphtheria occurred in the
Lothian Lothian (; ; ) is a region of the Scottish Lowlands, lying between the southern shore of the Firth of Forth and the Lammermuir Hills and the Moorfoot Hills. The principal settlement is the Scottish capital, Edinburgh, while other signific ...
area of
Scotland Scotland is a Countries of the United Kingdom, country that is part of the United Kingdom. It contains nearly one-third of the United Kingdom's land area, consisting of the northern part of the island of Great Britain and more than 790 adjac ...
. Additionally, in November 2019, an unvaccinated 8-year-old boy died of diphtheria in
Athens Athens ( ) is the Capital city, capital and List of cities and towns in Greece, largest city of Greece. A significant coastal urban area in the Mediterranean, Athens is also the capital of the Attica (region), Attica region and is the southe ...
,
Greece Greece, officially the Hellenic Republic, is a country in Southeast Europe. Located on the southern tip of the Balkan peninsula, it shares land borders with Albania to the northwest, North Macedonia and Bulgaria to the north, and Turkey to th ...
. In July 2022, two cases of diphtheria occurred in northern
New South Wales New South Wales (commonly abbreviated as NSW) is a States and territories of Australia, state on the Eastern states of Australia, east coast of :Australia. It borders Queensland to the north, Victoria (state), Victoria to the south, and South ...
,
Australia Australia, officially the Commonwealth of Australia, is a country comprising mainland Australia, the mainland of the Australia (continent), Australian continent, the island of Tasmania and list of islands of Australia, numerous smaller isl ...
. In October 2022, there was an outbreak of diphtheria at the former Manston airfield, a former
Ministry of Defence A ministry of defence or defense (see American and British English spelling differences#-ce.2C -se, spelling differences), also known as a department of defence or defense, is the part of a government responsible for matters of defence and Mi ...
(MoD) site in
Kent Kent is a Ceremonial counties of England, ceremonial county in South East England. It is bordered by Essex across the Thames Estuary to the north, the Strait of Dover to the south-east, East Sussex to the south-west, Surrey to the west, and Gr ...
,
England England is a Countries of the United Kingdom, country that is part of the United Kingdom. It is located on the island of Great Britain, of which it covers about 62%, and List of islands of England, more than 100 smaller adjacent islands. It ...
, which had been converted to an asylum seeker processing centre. The capacity of the processing centre was 1,000 people, although about 3,000 were living at the site, with some accommodated in tents. The
Home Office The Home Office (HO), also known (especially in official papers and when referred to in Parliament) as the Home Department, is the United Kingdom's interior ministry. It is responsible for public safety and policing, border security, immigr ...
, the government department responsible for asylum seekers, refused to confirm the number of cases. In December 2023 there was an outbreak at a school in
Luton Luton () is a town and borough in Bedfordshire, England. The borough had a population of 225,262 at the 2021 census. Luton is on the River Lea, about north-west of London. The town's foundation dates to the sixth century as a Saxon settleme ...
, in the
United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...
.
UK Health Security Agency The UK Health Security Agency (UKHSA) is a government agency responsible for all health security in England, and some reserved public health protection matters across the whole of the United Kingdom. It is an executive agency of the Department ...
(UKHSA) issued a statement saying specialists have been providing public health support following confirmation of the diphtheria case at a primary school in Luton. The agency said it is working closely with local and national partners "to ensure all necessary public health measures are implemented" following the discovery of the new case. The statement added: "We have conducted a risk assessment and close contacts of the case have been identified and where appropriate, vaccination and advice will be given to prevent the spread of the infection."


References


Further reading

* Hammonds, Evelynn Maxine.  ''Childhood's Deadly Scourge: The Campaign to Control Diphtheria in New York City, 1880-1930'' (1999) ** Hammonds, Evelynn Maxine.   "The search for perfect control: A social history of diphtheria, 1880-1930" (PhD dissertation, Harvard University; ProQuest Dissertations & Theses,  1993. 9318671). * * "Antitoxin dars 1735 and 1740." ''The William and Mary Quarterly'', 3rd Ser., Vol 6, No 2. p. 338. *


External links

*
Mapping diphtheria-pertussis-tetanus vaccine coverage in Africa, 2000–2016: a spatial and temporal modelling study
{{Authority control Bacterial diseases Wikipedia medicine articles ready to translate Wikipedia emergency medicine articles ready to translate Vaccine-preventable diseases Rare infectious diseases