Stridor (from Latin 'creaking/grating noise') 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 .
104-407: Diphtheria is an infection caused by the bacterium Corynebacterium diphtheriae . 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 . In severe cases,
208-456: A prion . The benefits of identification, however, are often greatly outweighed by the cost, as often there is no specific treatment, the cause is obvious, or the outcome of an infection is likely to be benign . The diagnosis is aided by the presenting symptoms in any individual with an infectious disease, yet it usually needs additional diagnostic techniques to confirm the suspicion. Some signs are specifically characteristic and indicative of
312-422: A runny nose . In certain cases, infectious diseases may be asymptomatic for much or even all of their course in a given host. In the latter case, the disease may only be defined as a "disease" (which by definition means an illness) in hosts who secondarily become ill after contact with an asymptomatic carrier . An infection is not synonymous with an infectious disease, as some infections do not cause illness in
416-565: 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 six-year-old child who died of
520-574: A certain type of bacteriophage . Toxinogenicity is determined by phage conversion (also called lysogenic conversion ); 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
624-418: 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
728-425: A colonization is often only a matter of circumstance. Non-pathogenic organisms can become pathogenic given specific conditions, and even the most virulent organism requires certain circumstances to cause a compromising infection. Some colonizing bacteria, such as Corynebacteria sp. and Viridans streptococci , prevent the adhesion and colonization of pathogenic bacteria and thus have a symbiotic relationship with
832-469: A disease and are called pathognomonic signs; but these are rare. Not all infections are symptomatic. In children the presence of cyanosis , rapid breathing, poor peripheral perfusion, or a petechial rash increases the risk of a serious infection by greater than 5 fold. Other important indicators include parental concern, clinical instinct, and temperature greater than 40 °C. Many diagnostic approaches depend on microbiological culture to isolate
936-399: A disease. This amplification of nucleic acid in infected tissue offers an opportunity to detect the infectious agent by using PCR. Third, the essential tools for directing PCR, primers , are derived from the genomes of infectious agents, and with time those genomes will be known if they are not already. Thus, the technological ability to detect any infectious agent rapidly and specifically
1040-696: A foreign body lodged in the airway, or a laryngeal tumor. Stridor should always command attention to establish its cause. Visualization of the airway by medical experts equipped to control the airway may be needed. Stridor may occur as a result of: Stridor is mainly diagnosed on the basis of history and physical examination, with a view to revealing the underlying problem or condition. Chest and neck x-rays , bronchoscopy , CT-scans , and/or MRIs may reveal structural pathology. Flexible fiberoptic bronchoscopy can also be very helpful, especially in assessing vocal cord function or in looking for signs of compression or infection. The first issue of clinical concern in
1144-541: 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 . The neck may also swell, in part due to the enlargement of the facial lymph nodes . Diphtheria can also involve the skin, eyes, or genitals, and can cause complications, including myocarditis (which in itself can result in an abnormal heart rate ), inflammation of nerves (which can result in paralysis ), kidney problems , and bleeding problems due to low levels of platelets . Diphtheria
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#17328517174841248-796: A hospital intensive care unit , and given 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 (CDC) recommends either: In cases that progress beyond
1352-423: A hospital stay. Lastly, a community-acquired infection is one in which the infection is acquired from a whole community. One manner of proving that a given disease is infectious, is to satisfy Koch's postulates (first proposed by Robert Koch ), which require that first, the infectious agent be identifiable only in patients who have the disease, and not in healthy controls, and second, that patients who contract
1456-524: A host with depressed resistance ( immunodeficiency ) or if they have unusual access to the inside of the body (for example, via trauma ). Opportunistic infection may be caused by microbes ordinarily in contact with the host, such as pathogenic bacteria or fungi in the gastrointestinal or the upper respiratory tract , and they may also result from (otherwise innocuous) microbes acquired from other hosts (as in Clostridioides difficile colitis ) or from
1560-502: A host. As bacterial and viral infections can both cause the same kinds of symptoms, it can be difficult to distinguish which is the cause of a specific infection. Distinguishing the two is important, since viral infections cannot be cured by antibiotics whereas bacterial infections can. There is a general chain of events that applies to infections, sometimes called the chain of infection or transmission chain . The chain of events involves several steps – which include
1664-434: A link between virulence and transmissibility. Diagnosis of infectious disease sometimes involves identifying an infectious agent either directly or indirectly. In practice most minor infectious diseases such as warts , cutaneous abscesses , respiratory system infections and diarrheal diseases are diagnosed by their clinical presentation and treated without knowledge of the specific causative agent. Conclusions about
1768-518: A number of basic dyes due to the electrostatic attraction between negatively charged cellular molecules and the positive charge on the dye. A cell is normally transparent under a microscope, and using a stain increases the contrast of a cell with its background. Staining a cell with a dye such as Giemsa stain or crystal violet allows a microscopist to describe its size, shape, internal and external components and its associations with other cells. The response of bacteria to different staining procedures
1872-404: A particular pathogen at all (no matter how little) but also is often used in a sense implying a clinically apparent infection (in other words, a case of infectious disease). This fact occasionally creates some ambiguity or prompts some usage discussion; to get around this it is common for health professionals to speak of colonization (rather than infection ) when they mean that some of
1976-493: A pathogen from the appropriate clinical specimen. In a microbial culture, a growth medium is provided for a specific agent. A sample taken from potentially diseased tissue or fluid is then tested for the presence of an infectious agent able to grow within that medium. Many pathogenic bacteria are easily grown on nutrient agar , a form of solid medium that supplies carbohydrates and proteins necessary for growth, along with copious amounts of water. A single bacterium will grow into
2080-429: A pathogen. A fluorescence microscope is then used to detect fluorescently labeled antibodies bound to internalized antigens within clinical samples or cultured cells. This technique is especially useful in the diagnosis of viral diseases, where the light microscope is incapable of identifying a virus directly. Other microscopic procedures may also aid in identifying infectious agents. Almost all cells readily stain with
2184-432: A patient's blood or other body fluids for antigens or antibodies that indicate presence of a specific pathogen that the doctor suspects. Other techniques (such as X-rays , CAT scans , PET scans or NMR ) are used to produce images of internal abnormalities resulting from the growth of an infectious agent. The images are useful in detection of, for example, a bone abscess or a spongiform encephalopathy produced by
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#17328517174842288-470: A persistent infection by infecting different cells of the body. Some viruses once acquired never leave the body. A typical example is the herpes virus, which tends to hide in nerves and become reactivated when specific circumstances arise. Persistent infections cause millions of deaths globally each year. Chronic infections by parasites account for a high morbidity and mortality in many underdeveloped countries. For infecting organisms to survive and repeat
2392-403: A result of an infectious disease with immunosuppressive activity (such as with measles , malaria or HIV disease ). Primary pathogens may also cause more severe disease in a host with depressed resistance than would normally occur in an immunosufficient host. While a primary infection can practically be viewed as the root cause of an individual's current health problem, a secondary infection
2496-471: A result of their presence or activity within the normal, healthy host, and their intrinsic virulence (the severity of the disease they cause) is, in part, a necessary consequence of their need to reproduce and spread. Many of the most common primary pathogens of humans only infect humans, however, many serious diseases are caused by organisms acquired from the environment or that infect non-human hosts. Opportunistic pathogens can cause an infectious disease in
2600-411: A severe illness affecting the brain, remain undiagnosed, despite extensive testing using the standard of care ( microbiological culture ) and state-of-the-art clinical laboratory methods. Metagenomic sequencing-based diagnostic tests are currently being developed for clinical use and show promise as a sensitive, specific, and rapid way to diagnose infection using a single all-encompassing test. This test
2704-417: A specific identification of an infectious agent only when such identification can aid in the treatment or prevention of the disease, or to advance knowledge of the course of an illness prior to the development of effective therapeutic or preventative measures. For example, in the early 1980s, prior to the appearance of AZT for the treatment of AIDS , the course of the disease was closely followed by monitoring
2808-427: 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. Diphtheria
2912-432: A visible mound on the surface of the plate called a colony , which may be separated from other colonies or melded together into a "lawn". The size, color, shape and form of a colony is characteristic of the bacterial species, its specific genetic makeup (its strain ), and the environment that supports its growth. Other ingredients are often added to the plate to aid in identification. Plates may contain substances that permit
3016-509: Is a sequela or complication of that root cause. For example, an infection due to a burn or penetrating trauma (the root cause) is a secondary infection. Primary pathogens often cause primary infection and often cause secondary infection. Usually, opportunistic infections are viewed as secondary infections (because immunodeficiency or injury was the predisposing factor). Other types of infection consist of mixed, iatrogenic , nosocomial , and community-acquired infection. A mixed infection
3120-500: Is active but does not produce noticeable symptoms may be called inapparent, silent, subclinical , or occult . An infection that is inactive or dormant is called a latent infection . An example of a latent bacterial infection is latent tuberculosis . Some viral infections can also be latent, examples of latent viral infections are any of those from the Herpesviridae family. The word infection can denote any presence of
3224-423: Is an infection that is caused by two or more pathogens. An example of this is appendicitis , which is caused by Bacteroides fragilis and Escherichia coli . The second is an iatrogenic infection. This type of infection is one that is transmitted from a health care worker to a patient. A nosocomial infection is also one that occurs in a health care setting. Nosocomial infections are those that are acquired during
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3328-422: Is an initial site of infection from which organisms travel via the bloodstream to another area of the body. Among the many varieties of microorganisms , relatively few cause disease in otherwise healthy individuals. Infectious disease results from the interplay between those few pathogens and the defenses of the hosts they infect. The appearance and severity of disease resulting from any pathogen depend upon
3432-619: Is based on both laboratory and clinical criteria. Empirical treatment should generally be started in a patient in whom suspicion of diphtheria is high. Vaccination against diphtheria is commonly done in infants, and delivered as a combination vaccine, such as a DPT vaccine (diphtheria, pertussis , tetanus ). Pentavalent vaccines , which vaccinate against diphtheria and four other childhood diseases simultaneously, are frequently used in disease prevention programs in developing countries by organizations such as UNICEF . The disease may remain manageable, but in more severe cases, lymph nodes in
3536-510: Is currently available. The only remaining blockades to the use of PCR as a standard tool of diagnosis are in its cost and application, neither of which is insurmountable. The diagnosis of a few diseases will not benefit from the development of PCR methods, such as some of the clostridial diseases ( tetanus and botulism ). These diseases are fundamentally biological poisonings by relatively small numbers of infectious bacteria that produce extremely potent neurotoxins . A significant proliferation of
3640-453: 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
3744-497: 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. In 1613, Spain experienced an epidemic of diphtheria, referred to as El Año de los Garrotillos (The Year of Strangulations). In 1705,
3848-503: Is injured. All multicellular organisms are colonized to some degree by extrinsic organisms, and the vast majority of these exist in either a mutualistic or commensal relationship with the host. An example of the former is the anaerobic bacteria species, which colonizes the mammalian colon , and an example of the latter are the various species of staphylococcus that exist on human skin . Neither of these colonizations are considered infections. The difference between an infection and
3952-467: Is not an enzyme and has no metabolic function. Serological methods are highly sensitive, specific and often extremely rapid tests used to identify microorganisms. These tests are based upon the ability of an antibody to bind specifically to an antigen. The antigen, usually a protein or carbohydrate made by an infectious agent, is bound by the antibody. This binding then sets off a chain of events that can be visibly obvious in various ways, dependent upon
4056-425: Is referred to as infectious diseases . Infections are caused by infectious agents ( pathogens ) including: The signs and symptoms of an infection depend on the type of disease. Some signs of infection affect the whole body generally, such as fatigue , loss of appetite, weight loss, fevers , night sweats, chills, aches and pains. Others are specific to individual body parts, such as skin rashes , coughing , or
4160-404: Is referred to as colonization. Most humans are not easily infected. Those with compromised or weakened immune systems have an increased susceptibility to chronic or persistent infections. Individuals who have a suppressed immune system are particularly susceptible to opportunistic infections . Entrance to the host at host–pathogen interface , generally occurs through the mucosa in orifices like
4264-501: Is similar to current PCR tests; however, an untargeted whole genome amplification is used rather than primers for a specific infectious agent. This amplification step is followed by next-generation sequencing or third-generation sequencing , alignment comparisons , and taxonomic classification using large databases of thousands of pathogen and commensal reference genomes . Simultaneously, antimicrobial resistance genes within pathogen and plasmid genomes are sequenced and aligned to
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4368-965: 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 5–10% 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. They 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
4472-439: Is that microbial colonization is very common even in environments that humans think of as being nearly sterile . Because it is normal to have bacterial colonization, it is difficult to know which chronic wounds can be classified as infected and how much risk of progression exists. Despite the huge number of wounds seen in clinical practice, there are limited quality data for evaluated symptoms and signs. A review of chronic wounds in
4576-450: 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 (DT) is produced only by C. diphtheriae infected with
4680-577: Is used in the taxonomic classification of microbes as well. Two methods, the Gram stain and the acid-fast stain, are the standard approaches used to classify bacteria and to diagnosis of disease. The Gram stain identifies the bacterial groups Bacillota and Actinomycetota , both of which contain many significant human pathogens. The acid-fast staining procedure identifies the Actinomycetota genera Mycobacterium and Nocardia . Biochemical tests used in
4784-413: Is usually spread between people by direct contact, through the air , 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 produced by the bacteria. Diagnosis can often be made based on
4888-887: The Imperial Japanese Army did not release supplies of anti-diphtheria serum. In 1943, diphtheria outbreaks accompanied war and disruption in Europe . The 1 million cases in Europe resulted in 50,000 deaths. During 1948 in Kyoto , 68 of 606 children died after diphtheria immunization due to improper manufacture of aluminum phosphate toxoid. In 1974, the World Health Organization included DPT vaccine in their Expanded Programme on Immunization for developing countries . In 1975, an outbreak of cutaneous diphtheria in Seattle, Washington ,
4992-588: The Journal of the American Medical Association 's "Rational Clinical Examination Series" quantified the importance of increased pain as an indicator of infection. The review showed that the most useful finding is an increase in the level of pain [likelihood ratio (LR) range, 11–20] makes infection much more likely, but the absence of pain (negative likelihood ratio range, 0.64–0.88) does not rule out infection (summary LR 0.64–0.88). Disease can arise if
5096-456: The Mariana Islands experienced an epidemic of diphtheria and typhus simultaneously, reducing the population to about 5,000 people. 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 the illness had spread from France . In 1826, Pierre Bretonneau gave
5200-534: The Schick test 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 , with an appeal to parents to "Save your child from diphtheria." A vaccine
5304-468: The oral cavity , nose, eyes, genitalia, anus, or the microbe can enter through open wounds. While a few organisms can grow at the initial site of entry, many migrate and cause systemic infection in different organs. Some pathogens grow within the host cells (intracellular) whereas others grow freely in bodily fluids. Wound colonization refers to non-replicating microorganisms within the wound, while in infected wounds, replicating organisms exist and tissue
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#17328517174845408-447: The polymerase chain reaction (PCR) method will become nearly ubiquitous gold standards of diagnostics of the near future, for several reasons. First, the catalog of infectious agents has grown to the point that virtually all of the significant infectious agents of the human population have been identified. Second, an infectious agent must grow within the human body to cause disease; essentially it must amplify its own nucleic acids to cause
5512-403: The "strep test", they can be inexpensive. Complex serological techniques have been developed into what are known as immunoassays . Immunoassays can use the basic antibody – antigen binding as the basis to produce an electro-magnetic or particle radiation signal, which can be detected by some form of instrumentation. Signal of unknowns can be compared to that of standards allowing quantitation of
5616-488: 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, DT is split by a trypsin-like protease 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 . Fragment A inhibits
5720-560: 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 B 3 ), 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
5824-515: 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 ; 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
5928-435: The ability of that pathogen to damage the host as well as the ability of the host to resist the pathogen. However, a host's immune system can also cause damage to the host itself in an attempt to control the infection. Clinicians, therefore, classify infectious microorganisms or microbes according to the status of host defenses – either as primary pathogens or as opportunistic pathogens . Primary pathogens cause disease as
6032-606: 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
6136-583: The antitoxin level in the blood. Diphtheria can be prevented in those exposed, as well as treated with the antibiotics erythromycin or benzylpenicillin .In severe cases a tracheotomy is sometimes 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 , South Asia , and Indonesia . In 2015, it resulted in 2,100 deaths, down from 8,000 deaths in 1990. In areas where it
6240-468: The appearance of the throat with confirmation by microbiological culture . Previous infection may not protect against reinfection. A diphtheria vaccine is effective for prevention, and is 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 the diphtheria–tetanus vaccine are recommended every ten years. Protection can be verified by measuring
6344-537: 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 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, Shibasaburō Kitasato and Emil von Behring immunized guinea pigs with heat-treated diphtheria toxin. They also immunized goats and horses in
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#17328517174846448-565: 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 Friedrich Loeffler became the first person to cultivate C. diphtheriae . He used Koch's postulates to prove association between C. diphtheriae and diphtheria. He also showed that
6552-458: The basis of a biochemical diagnosis of an infectious disease. For example, humans can make neither RNA replicases nor reverse transcriptase , and the presence of these enzymes are characteristic., of specific types of viral infections. The ability of the viral protein hemagglutinin to bind red blood cells together into a detectable matrix may also be characterized as a biochemical test for viral infection, although strictly speaking hemagglutinin
6656-463: The case of viral identification, a region of dead cells results from viral growth, and is called a "plaque". Eukaryotic parasites may also be grown in culture as a means of identifying a particular agent. In the absence of suitable plate culture techniques, some microbes require culture within live animals. Bacteria such as Mycobacterium leprae and Treponema pallidum can be grown in animals, although serological and microscopic techniques make
6760-472: The causative agent, Trypanosoma cruzi in a patient, which therefore makes it difficult to definitively make a diagnosis. In this case, xenodiagnosis involves the use of the vector of the Chagas agent T. cruzi , an uninfected triatomine bug, which takes a blood meal from a person suspected of having been infected. The bug is later inspected for growth of T. cruzi within its gut. Another principal tool in
6864-436: The cause of the disease are based upon the likelihood that a patient came in contact with a particular agent, the presence of a microbe in a community, and other epidemiological considerations. Given sufficient effort, all known infectious agents can be specifically identified. Diagnosis of infectious disease is nearly always initiated by medical history and physical examination. More detailed identification techniques involve
6968-399: The chromosome. The diphtheria toxin precursor is a protein of molecular weight 60 kDa . Certain proteases, such as trypsin, selectively cleave DT to generate two peptide chains, amino-terminal fragment A (DT-A) and carboxyl-terminal fragment B (DT-B), which are held together by a disulfide bond . DT-B is a recognition subunit that gains entry of DT into the host cell by binding to
7072-453: 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 , 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 , resulting in 112 deaths because
7176-431: The composition of patient blood samples, even though the outcome would not offer the patient any further treatment options. In part, these studies on the appearance of HIV in specific communities permitted the advancement of hypotheses as to the route of transmission of the virus. By understanding how the disease was transmitted, resources could be targeted to the communities at greatest risk in campaigns aimed at reducing
7280-484: The culture of infectious agents isolated from a patient. Culture allows identification of infectious organisms by examining their microscopic features, by detecting the presence of substances produced by pathogens, and by directly identifying an organism by its genotype. Many infectious organisms are identified without culture and microscopy. This is especially true for viruses, which cannot grow in culture. For some suspected pathogens, doctors may conduct tests that examine
7384-400: The destruction of the virus. Instrumentation can be used to read extremely small signals created by secondary reactions linked to the antibody – antigen binding. Instrumentation can control sampling, reagent use, reaction times, signal detection, calculation of results, and data management to yield a cost-effective automated process for diagnosis of infectious disease. Technologies based upon
7488-428: The diagnosis of infectious disease is microscopy . Virtually all of the culture techniques discussed above rely, at some point, on microscopic examination for definitive identification of the infectious agent. Microscopy may be carried out with simple instruments, such as the compound light microscope , or with instruments as complex as an electron microscope . Samples obtained from patients may be viewed directly under
7592-498: 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 . In 1878, Princess Alice ( Queen Victoria '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 identified
7696-445: The environment as a result of traumatic introduction (as in surgical wound infections or compound fractures ). An opportunistic disease requires impairment of host defenses, which may occur as a result of genetic defects (such as chronic granulomatous disease ), exposure to antimicrobial drugs or immunosuppressive chemicals (as might occur following poisoning or cancer chemotherapy ), exposure to ionizing radiation , or as
7800-426: The expression of symptoms is often atypical, making a clinical diagnosis based on presentation more difficult. Thirdly, diagnostic methods that rely on the detection of antibodies are more likely to fail. A rapid, sensitive, specific, and untargeted test for all known human pathogens that detects the presence of the organism's DNA rather than antibodies is therefore highly desirable. There is usually an indication for
7904-400: The first Nobel Prize in medicine for his work on diphtheria. In 1895, H. K. Mulford Company of Philadelphia started production and testing of diphtheria antitoxin in the United States. Park and Biggs described the method for producing serum from horses for use in diphtheria treatment. In 1897, Paul Ehrlich developed a standardized unit of measure for diphtheria antitoxin. This was
8008-558: The first ever standardization of a biological product, and played an important role in future developmental work on sera and vaccines. In 1901, 10 of 11 inoculated St. Louis children died from contaminated diphtheria antitoxin. The horse from which the antitoxin was derived died of tetanus . This incident, coupled with a tetanus outbreak in Camden, New Jersey , played an important part in initiating federal regulation of biologic products. On 7 January 1904, Ruth Cleveland died of diphtheria at
8112-403: The growth of some bacteria and not others, or that change color in response to certain bacteria and not others. Bacteriological plates such as these are commonly used in the clinical identification of infectious bacterium. Microbial culture may also be used in the identification of viruses : the medium, in this case, being cells grown in culture that the virus can infect, and then alter or kill. In
8216-484: The host's protective immune mechanisms are compromised and the organism inflicts damage on the host. Microorganisms can cause tissue damage by releasing a variety of toxins or destructive enzymes. For example, Clostridium tetani releases a toxin that paralyzes muscles, and staphylococcus releases toxins that produce shock and sepsis . Not all infectious agents cause disease in all hosts. For example, less than 5% of individuals infected with polio develop disease. On
8320-598: The host, preventing infection and speeding wound healing . The variables involved in the outcome of a host becoming inoculated by a pathogen and the ultimate outcome include: As an example, several staphylococcal species remain harmless on the skin, but, when present in a normally sterile space, such as in the capsule of a joint or the peritoneum , multiply without resistance and cause harm. An interesting fact that gas chromatography–mass spectrometry , 16S ribosomal RNA analysis, omics , and other advanced technologies have made more apparent to humans in recent decades
8424-532: The identification of infectious agents include the detection of metabolic or enzymatic products characteristic of a particular infectious agent. Since bacteria ferment carbohydrates in patterns characteristic of their genus and species , the detection of fermentation products is commonly used in bacterial identification. Acids , alcohols and gases are usually detected in these tests when bacteria are grown in selective liquid or solid media. The isolation of enzymes from infected tissue can also provide
8528-559: 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 , Belgium . Infection An infection is
8632-413: The infection cycle in other hosts, they (or their progeny) must leave an existing reservoir and cause infection elsewhere. Infection transmission can take place via many potential routes: The relationship between virulence versus transmissibility is complex; with studies have shown that there were no clear relationship between the two. There is still a small number of evidence that partially suggests
8736-506: The infectious agent also develop the disease. These postulates were first used in the discovery that Mycobacteria species cause tuberculosis . Stridor Stridor is a physical sign which is caused by a narrowed or obstructed airway . It can be inspiratory , expiratory or biphasic , although it is usually heard during inspiration. Inspiratory stridor often occurs in children with croup . It may be indicative of serious airway obstruction from severe conditions such as epiglottitis ,
8840-399: The infectious agent does not occur, this limits the ability of PCR to detect the presence of any bacteria. Given the wide range of bacterial, viral, fungal, protozoal, and helminthic pathogens that cause debilitating and life-threatening illnesses, the ability to quickly identify the cause of infection is important yet often challenging. For example, more than half of cases of encephalitis ,
8944-402: The infectious agent, reservoir, entering a susceptible host, exit and transmission to new hosts. Each of the links must be present in a chronological order for an infection to develop. Understanding these steps helps health care workers target the infection and prevent it from occurring in the first place. Infection begins when an organism successfully enters the body, grows and multiplies. This
9048-867: The invasion of tissues by pathogens , their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease , also known as a transmissible disease or communicable disease , is an illness resulting from an infection. Infections can be caused by a wide range of pathogens , most prominently bacteria and viruses . Hosts can fight infections using their immune systems . Mammalian hosts react to infections with an innate response, often involving inflammation , followed by an adaptive response. Specific medications used to treat infections include antibiotics , antivirals , antifungals , antiprotozoals , and antihelminthics . Infectious diseases resulted in 9.2 million deaths in 2013 (about 17% of all deaths). The branch of medicine that focuses on infections
9152-425: The light microscope, and can often rapidly lead to identification. Microscopy is often also used in conjunction with biochemical staining techniques, and can be made exquisitely specific when used in combination with antibody based techniques. For example, the use of antibodies made artificially fluorescent (fluorescently labeled antibodies) can be directed to bind to and identify a specific antigens present on
9256-447: 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
9360-531: The number of new infections. The specific serological diagnostic identification, and later genotypic or molecular identification, of HIV also enabled the development of hypotheses as to the temporal and geographical origins of the virus, as well as a myriad of other hypothesis. The development of molecular diagnostic tools have enabled physicians and researchers to monitor the efficacy of treatment with anti-retroviral drugs . Molecular diagnostics are now commonly used to identify HIV in healthy people long before
9464-455: The onset of illness and have been used to demonstrate the existence of people who are genetically resistant to HIV infection. Thus, while there still is no cure for AIDS, there is great therapeutic and predictive benefit to identifying the virus and monitoring the virus levels within the blood of infected individuals, both for the patient and for the community at large. Symptomatic infections are apparent and clinical , whereas an infection that
9568-514: The other hand, some infectious agents are highly virulent. The prion causing mad cow disease and Creutzfeldt–Jakob disease invariably kills all animals and people that are infected. Persistent infections occur because the body is unable to clear the organism after the initial infection. Persistent infections are characterized by the continual presence of the infectious organism, often as latent infection with occasional recurrent relapses of active infection. There are some viruses that can maintain
9672-539: The pathogens are present but that no clinically apparent infection (no disease) is present. Different terms are used to describe how and where infections present over time. In an acute infection, symptoms develop rapidly; its course can either be rapid or protracted. In chronic infection, symptoms usually develop gradually over weeks or months and are slow to resolve. In subacute infections, symptoms take longer to develop than in acute infections but arise more quickly than those of chronic infections. A focal infection
9776-417: 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
9880-492: 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. In 1901, Von Behring won
9984-423: The setting of stridor is whether or not tracheal intubation or tracheostomy is immediately necessary. A reduction in oxygen saturation is considered a late sign of airway obstruction, particularly in a child with healthy lungs and normal gas exchange. Some patients will need immediate tracheal intubation. If intubation can be delayed for a period, a number of other potential options can be considered, depending on
10088-502: 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
10192-457: The target antigen. To aid in the diagnosis of infectious diseases, immunoassays can detect or measure antigens from either infectious agents or proteins generated by an infected organism in response to a foreign agent. For example, immunoassay A may detect the presence of a surface protein from a virus particle. Immunoassay B on the other hand may detect or measure antibodies produced by an organism's immune system that are made to neutralize and allow
10296-559: The taxonomically classified pathogen genomes to generate an antimicrobial resistance profile – analogous to antibiotic sensitivity testing – to facilitate antimicrobial stewardship and allow for the optimization of treatment using the most effective drugs for a patient's infection. Metagenomic sequencing could prove especially useful for diagnosis when the patient is immunocompromised . An ever-wider array of infectious agents can cause serious harm to individuals with immunosuppression, so clinical screening must often be broader. Additionally,
10400-503: The test. For example, " Strep throat " is often diagnosed within minutes, and is based on the appearance of antigens made by the causative agent, S. pyogenes , that is retrieved from a patient's throat with a cotton swab. Serological tests, if available, are usually the preferred route of identification, however the tests are costly to develop and the reagents used in the test often require refrigeration . Some serological methods are extremely costly, although when commonly used, such as with
10504-481: 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 , who was the Principal Medical Officer (Maternity and Child Welfare) of Glasgow between 1934– 1964, introduced immunisation clinics across Glasgow , and promoted mother and child health education, resulting in virtual eradication of the infection in
10608-411: The use of live animals unnecessary. Viruses are also usually identified using alternatives to growth in culture or animals. Some viruses may be grown in embryonated eggs. Another useful identification method is Xenodiagnosis, or the use of a vector to support the growth of an infectious agent. Chagas disease is the most significant example, because it is difficult to directly demonstrate the presence of
10712-659: 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 . 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
10816-671: Was reported. After the breakup of the former Soviet Union 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 , and resulted in 5,000 deaths. In 1994, the Russian Federation had 39,703 diphtheria cases. By contrast, in 1990, only 1,211 cases were reported. In early May 2010,
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