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125-451: Several cases of consumption ( tuberculosis ) occurred in the family of George and Mary Brown in Exeter, Rhode Island . Friends and neighbors believed that this was due to the influence of the undead. An attempt was made to remediate. Mercy Brown died January 1892 aged 19. In Exeter, Rhode Island , several members of George and Mary Brown's family suffered a sequence of tuberculosis infections in

250-415: A Rasmussen aneurysm , resulting in massive bleeding. Tuberculosis may become a chronic illness and cause extensive scarring in the upper lobes of the lungs. The upper lung lobes are more frequently affected by tuberculosis than the lower ones. The reason for this difference is not clear. It may be due to either better air flow, or poor lymph drainage within the upper lungs. In 15–20% of active cases,

375-456: 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

500-422: 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

625-673: 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

750-425: 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

875-560: A common ancestor, remains unclear. A comparison of the genes of M. tuberculosis complex (MTBC) in humans to MTBC in animals suggests humans did not acquire MTBC from animals during animal domestication, as researchers previously believed. Both strains of the tuberculosis bacteria share a common ancestor, which could have infected humans even before the Neolithic Revolution . Skeletal remains show some prehistoric humans (4000 BC ) had TB, and researchers have found tubercular decay in

1000-469: 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

1125-399: 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

1250-423: 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

1375-524: 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

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1500-502: 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

1625-434: 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

1750-680: A microscope. Since MTB retains certain stains even after being treated with acidic solution, it is classified as an acid-fast bacillus . The most common acid-fast staining techniques are the Ziehl–Neelsen stain and the Kinyoun stain , which dye acid-fast bacilli a bright red that stands out against a blue background. Auramine-rhodamine staining and fluorescence microscopy are also used. The M. tuberculosis complex (MTBC) includes four other TB-causing mycobacteria : M. bovis , M. africanum , M. canettii , and M. microti . M. africanum

1875-518: 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

2000-404: 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

2125-493: 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

2250-429: 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

2375-432: 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

2500-470: 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

2625-403: 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

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2750-471: 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

2875-411: 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

3000-407: A small decrease in case numbers. Some countries have legislation to involuntarily detain or examine those suspected to have tuberculosis, or involuntarily treat them if infected. The only available vaccine as of 2021 is bacillus Calmette-Guérin (BCG). In children it decreases the risk of getting the infection by 20% and the risk of infection turning into active disease by nearly 60%. It

3125-417: 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

3250-401: A tuberculosis infection does become active, it most commonly involves the lungs (in about 90% of cases). Symptoms may include chest pain and a prolonged cough producing sputum. About 25% of people may not have any symptoms (i.e., they remain asymptomatic). Occasionally, people may cough up blood in small amounts, and in very rare cases, the infection may erode into the pulmonary artery or

3375-432: 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

3500-474: A wide range of symptoms. Tuberculosis is spread from one person to the next through the air when people who have active TB in their lungs cough, spit, speak, or sneeze . People with latent TB do not spread the disease. Active infection occurs more often in people with HIV/AIDS and in those who smoke . Diagnosis of active TB is based on chest X-rays , as well as microscopic examination and culture of bodily fluids. Diagnosis of latent TB relies on

3625-398: Is Mycobacterium tuberculosis (MTB), a small, aerobic , nonmotile bacillus . The high lipid content of this pathogen accounts for many of its unique clinical characteristics. It divides every 16 to 20 hours, which is an extremely slow rate compared with other bacteria, which usually divide in less than an hour. Mycobacteria have an outer membrane lipid bilayer. If a Gram stain

3750-509: 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

3875-491: Is a growing problem, with increasing rates of multiple drug-resistant tuberculosis (MDR-TB). In 2018, one quarter of the world's population was thought to have a latent infection of TB. New infections occur in about 1% of the population each year. In 2022, an estimated 10.6 million people developed active TB, resulting in 1.3 million deaths, making it the second leading cause of death from an infectious disease after COVID-19 . As of 2018, most TB cases occurred in

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4000-445: Is able to reproduce inside the macrophage and will eventually kill the immune cell. The primary site of infection in the lungs, known as the Ghon focus , is generally located in either the upper part of the lower lobe, or the lower part of the upper lobe . Tuberculosis of the lungs may also occur via infection from the blood stream. This is known as a Simon focus and is typically found in

4125-500: 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

4250-653: Is also rare and is seen almost only in immunodeficient people, although its prevalence may be significantly underestimated. Other known pathogenic mycobacteria include M. leprae , M. avium , and M. kansasii . The latter two species are classified as " nontuberculous mycobacteria " (NTM) or atypical mycobacteria. NTM cause neither TB nor leprosy , but they do cause lung diseases that resemble TB. When people with active pulmonary TB cough, sneeze, speak, sing, or spit, they expel infectious aerosol droplets 0.5 to 5.0 μm in diameter. A single sneeze can release up to 40,000 droplets. Each one of these droplets may transmit

4375-560: Is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria . Tuberculosis generally affects the lungs , but it can also affect other parts of the body. Most infections show no symptoms, in which case it is known as latent tuberculosis . Around 10% of latent infections progress to active disease that, if left untreated, kill about half of those affected. Typical symptoms of active TB are chronic cough with blood-containing mucus , fever , night sweats , and weight loss . Infection of other organs can cause

4500-423: 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

4625-422: 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

4750-510: 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

4875-444: Is difficult, as is diagnosing the disease in those who have a weakened immune system. A diagnosis of TB should, however, be considered in those with signs of lung disease or constitutional symptoms lasting longer than two weeks. A chest X-ray and multiple sputum cultures for acid-fast bacilli are typically part of the initial evaluation. Interferon-γ release assays (IGRA) and tuberculin skin tests are of little use in most of

5000-503: 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

5125-467: 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

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5250-500: Is not widespread, but it is a significant cause of tuberculosis in parts of Africa. M. bovis was once a common cause of tuberculosis, but the introduction of pasteurized milk has almost eliminated this as a public health problem in developed countries. M. canettii is rare and seems to be limited to the Horn of Africa , although a few cases have been seen in African emigrants. M. microti

5375-479: Is often used to screen people at high risk for TB. Those who have been previously immunized with the Bacille Calmette-Guerin vaccine may have a false-positive test result. The test may be falsely negative in those with sarcoidosis , Hodgkin's lymphoma , malnutrition , and most notably, active tuberculosis. Interferon gamma release assays , on a blood sample, are recommended in those who are positive to

5500-501: Is performed, MTB either stains very weakly "Gram-positive" or does not retain dye as a result of the high lipid and mycolic acid content of its cell wall. MTB can withstand weak disinfectants and survive in a dry state for weeks. In nature, the bacterium can grow only within the cells of a host organism, but M. tuberculosis can be cultured in the laboratory . Using histological stains on expectorated samples from phlegm (also called sputum), scientists can identify MTB under

5625-423: Is poor as of 2019 . The Centers for Disease Control and Prevention (CDC) stopped recommending yearly testing of health care workers without known exposure in 2019. Tuberculosis prevention and control efforts rely primarily on the vaccination of infants and the detection and appropriate treatment of active cases. The World Health Organization (WHO) has achieved some success with improved treatment regimens, and

5750-425: 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

5875-404: 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

6000-501: 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

6125-464: Is termed caseous necrosis . If TB bacteria gain entry to the blood stream from an area of damaged tissue, they can spread throughout the body and set up many foci of infection, all appearing as tiny, white tubercles in the tissues. This severe form of TB disease, most common in young children and those with HIV, is called miliary tuberculosis. People with this disseminated TB have a high fatality rate even with treatment (about 30%). In many people,

6250-439: 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

6375-476: Is the most widely used vaccine worldwide, with more than 90% of all children being vaccinated. The immunity it induces decreases after about ten years. As tuberculosis is uncommon in most of Canada, Western Europe, and the United States, BCG is administered to only those people at high risk. Part of the reasoning against the use of the vaccine is that it makes the tuberculin skin test falsely positive, reducing

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6500-577: 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

6625-588: 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

6750-454: The lymphatic system (in scrofula of the neck), the genitourinary system (in urogenital tuberculosis ), and the bones and joints (in Pott disease of the spine), among others. A potentially more serious, widespread form of TB is called "disseminated tuberculosis"; it is also known as miliary tuberculosis . Miliary TB currently makes up about 10% of extrapulmonary cases. The main cause of TB

6875-468: 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

7000-447: 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

7125-420: The tuberculin skin test (TST) or blood tests. Prevention of TB involves screening those at high risk, early detection and treatment of cases, and vaccination with the bacillus Calmette-Guérin (BCG) vaccine. Those at high risk include household, workplace, and social contacts of people with active TB. Treatment requires the use of multiple antibiotics over a long period of time. Antibiotic resistance

7250-403: 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

7375-693: The Mantoux test. These are not affected by immunization or most environmental mycobacteria , so they generate fewer false-positive results. However, they are affected by M. szulgai , M. marinum , and M. kansasii . IGRAs may increase sensitivity when used in addition to the skin test, but may be less sensitive than the skin test when used alone. The US Preventive Services Task Force (USPSTF) has recommended screening people who are at high risk for latent tuberculosis with either tuberculin skin tests or interferon-gamma release assays . While some have recommend testing health care workers, evidence of benefit for this

7500-533: The Mercy Brown case and used it as a reference in the investigation. American rock band Clutch has a song titled "Mercy Brown" on their 2022 album Sunrise on Slaughter Beach . The story of Mercy Brown is also prominently featured in Paul Tremblay 's novel The Pallbearer's Club . Tuberculosis Tuberculosis ( TB ), also known colloquially as the " white death ", or historically as consumption ,

7625-505: The US , up to 35% of those affected by TB were also infected by HIV. Handling of TB-infected patients in US hospitals was known to create airborne TB that could infect others, especially in unventilated spaces. Infectious disease An infection is 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

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7750-511: The United States test positive via the tuberculin test. Tuberculosis has been present in humans since ancient times . Tuberculosis has existed since antiquity . The oldest unambiguously detected M. tuberculosis gives evidence of the disease in the remains of bison in Wyoming dated to around 17,000 years ago. However, whether tuberculosis originated in bovines, then transferred to humans, or whether both bovine and human tuberculosis diverged from

7875-601: The WHO regions of South-East Asia (44%), Africa (24%), and the Western Pacific (18%), with more than 50% of cases being diagnosed in seven countries: India (27%), China (9%), Indonesia (8%), the Philippines (6%), Pakistan (6%), Nigeria (4%), and Bangladesh (4%). By 2021, the number of new cases each year was decreasing by around 2% annually. About 80% of people in many Asian and African countries test positive, while 5–10% of people in

8000-538: The World Away", which makes explicit reference to the affair. It has also been suggested by scholars that Bram Stoker , the author of the novel Dracula , knew about the Mercy Brown case through newspaper articles and based the novel's character Lucy Westenra upon her. It is also referred to in H. P. Lovecraft 's " The Shunned House ". Mercy Brown's story was the inspiration for the young adult novel Mercy: The Last New England Vampire by Sarah L. Thomson. An account of

8125-435: 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

8250-688: The active disease. Use of certain medications, such as corticosteroids and infliximab (an anti-αTNF monoclonal antibody), is another important risk factor, especially in the developed world . Other risk factors include: alcoholism , diabetes mellitus (3-fold increased risk), silicosis (30-fold increased risk), tobacco smoking (2-fold increased risk), indoor air pollution , malnutrition, young age, recently acquired TB infection, recreational drug use, severe kidney disease, low body weight, organ transplant, head and neck cancer, and genetic susceptibility (the overall importance of genetic risk factors remains undefined ). Tobacco smoking increases

8375-458: The arrival of streptomycin and other antibiotics, although the disease remained a significant threat. In 1946, the development of the antibiotic streptomycin made effective treatment and cure of TB a reality. Prior to the introduction of this medication, the only treatment was surgical intervention, including the " pneumothorax technique", which involved collapsing an infected lung to "rest" it and to allow tuberculous lesions to heal. Because of

8500-423: The bacterium is enveloped by the macrophage and stored temporarily in a membrane-bound vesicle called a phagosome. The phagosome then combines with a lysosome to create a phagolysosome. In the phagolysosome, the cell attempts to use reactive oxygen species and acid to kill the bacterium. However, M. tuberculosis has a thick, waxy mycolic acid capsule that protects it from these toxic substances. M. tuberculosis

8625-458: 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

8750-463: 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

8875-425: The cattle and human tuberculosis diseases were similar, which delayed the recognition of infected milk as a source of infection. During the first half of the 1900s, the risk of transmission from this source was dramatically reduced after the application of the pasteurization process. Koch announced a glycerine extract of the tubercle bacilli as a "remedy" for tuberculosis in 1890, calling it "tuberculin". Although it

9000-472: 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

9125-480: The cause of pulmonary tuberculosis. J. L. Schönlein first published the name "tuberculosis" (German: Tuberkulose ) in 1832. Between 1838 and 1845, John Croghan, the owner of Mammoth Cave in Kentucky from 1839 onwards, brought a number of people with tuberculosis into the cave in the hope of curing the disease with the constant temperature and purity of the cave air; each died within a year. Hermann Brehmer opened

9250-436: 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

9375-431: 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

9500-484: 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

9625-442: The dead family members was a vampire , although they did not use that name, and had caused Edwin's illness. This was in accordance with threads of contemporary folklore , which linked multiple deaths in one family to undead activity. Consumption was a poorly understood condition at the time and the subject of much superstition. George Brown was persuaded to give permission to exhume several bodies of his family members. Villagers,

9750-700: The declaration of a global health emergency by the World Health Organization (WHO) in 1993. There is a popular misconception that tuberculosis is purely a disease of the lungs that manifests as coughing . Tuberculosis may infect many organs, even though it most commonly occurs in the lungs (known as pulmonary tuberculosis). Extrapulmonary TB occurs when tuberculosis develops outside of the lungs, although extrapulmonary TB may coexist with pulmonary TB. General signs and symptoms include fever, chills , night sweats, loss of appetite , weight loss, and fatigue . Significant nail clubbing may also occur. If

9875-400: 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

10000-640: The developing world. IGRA have similar limitations in those with HIV. A definitive diagnosis of TB is made by identifying M. tuberculosis in a clinical sample (e.g., sputum, pus , or a tissue biopsy ). However, the difficult culture process for this slow-growing organism can take two to six weeks for blood or sputum culture. Thus, treatment is often begun before cultures are confirmed. Nucleic acid amplification tests and adenosine deaminase testing may allow rapid diagnosis of TB. Blood tests to detect antibodies are not specific or sensitive , so they are not recommended. The Mantoux tuberculin skin test

10125-428: 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

10250-596: The disease became common among the urban poor. In 1815, one in four deaths in England was due to "consumption". By 1918, TB still caused one in six deaths in France. After TB was determined to be contagious, in the 1880s, it was put on a notifiable-disease list in Britain. Campaigns started to stop people from spitting in public places, and the infected poor were "encouraged" to enter sanatoria that resembled prisons. The sanatoria for

10375-620: The disease, since the infectious dose of tuberculosis is very small (the inhalation of fewer than 10 bacteria may cause an infection). People with prolonged, frequent, or close contact with people with TB are at particularly high risk of becoming infected, with an estimated 22% infection rate. A person with active but untreated tuberculosis may infect 10–15 (or more) other people per year. Transmission should occur from only people with active TB – those with latent infection are not thought to be contagious. The probability of transmission from one person to another depends upon several factors, including

10500-463: The emergence of multidrug-resistant tuberculosis (MDR-TB), surgery has been re-introduced for certain cases of TB infections. It involves the removal of infected chest cavities ("bullae") in the lungs to reduce the number of bacteria and to increase exposure of the remaining bacteria to antibiotics in the bloodstream. Hopes of eliminating TB ended with the rise of drug-resistant strains in the 1980s. The subsequent resurgence of tuberculosis resulted in

10625-445: 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

10750-597: The events as told by the remaining descendants of Mercy is available in Michael E. Bell's Food for the Dead: On the Trail of New England's Vampires . The Mercy Brown story was the main subject of the first episode of the Lore podcast in 2015, as well as the first episode of the television adaptation of the same title in 2017. The MonsterQuest episode "Vampires In America" investigated

10875-426: 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

11000-412: The final two decades of the 19th century. Tuberculosis was called "consumption" at the time, and was a devastating and much-feared disease. The mother, Mary Eliza, was the first to die of the disease, followed in 1884 by their eldest daughter, Mary Olive, according to her grave stone. In 1891, daughter Mercy and son Edwin also contracted the disease. Friends and neighbors of the family believed that one of

11125-541: The first TB sanatorium in 1859 in Görbersdorf (now Sokołowsko ) in Silesia . In 1865, Jean Antoine Villemin demonstrated that tuberculosis could be transmitted, via inoculation, from humans to animals and among animals. (Villemin's findings were confirmed in 1867 and 1868 by John Burdon-Sanderson . ) Robert Koch identified and described the bacillus causing tuberculosis, M. tuberculosis , on 24 March 1882. In 1905, he

11250-570: The first genuine success in immunization against tuberculosis in 1906, using attenuated bovine-strain tuberculosis. It was called bacille Calmette–Guérin (BCG). The BCG vaccine was first used on humans in 1921 in France, but achieved widespread acceptance in the US, Great Britain, and Germany only after World War II. By the 1950s mortality in Europe had decreased about 90%. Improvements in sanitation, vaccination, and other public-health measures began significantly reducing rates of tuberculosis even before

11375-403: 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

11500-431: The host's immune system. Macrophages and dendritic cells in the granulomas are unable to present antigen to lymphocytes; thus the immune response is suppressed. Bacteria inside the granuloma can become dormant, resulting in latent infection. Another feature of the granulomas is the development of abnormal cell death ( necrosis ) in the center of tubercles . To the naked eye, this has the texture of soft, white cheese and

11625-484: 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

11750-598: 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

11875-532: 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

12000-400: The infected macrophages. When other macrophages attack the infected macrophage, they fuse together to form a giant multinucleated cell in the alveolar lumen. The granuloma may prevent dissemination of the mycobacteria and provide a local environment for interaction of cells of the immune system. However, more recent evidence suggests that the bacteria use the granulomas to avoid destruction by

12125-413: 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

12250-439: The infection spreads outside the lungs, causing other kinds of TB. These are collectively denoted as extrapulmonary tuberculosis. Extrapulmonary TB occurs more commonly in people with a weakened immune system and young children. In those with HIV, this occurs in more than 50% of cases. Notable extrapulmonary infection sites include the pleura (in tuberculous pleurisy), the central nervous system (in tuberculous meningitis ),

12375-613: The infection waxes and wanes. Tissue destruction and necrosis are often balanced by healing and fibrosis . Affected tissue is replaced by scarring and cavities filled with caseous necrotic material. During active disease, some of these cavities are joined to the air passages ( bronchi ) and this material can be coughed up. It contains living bacteria and thus can spread the infection. Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue. Diagnosing active tuberculosis based only on signs and symptoms

12500-399: 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 ,

12625-402: 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

12750-487: The life from the other family members. Although Richard Morton established the pulmonary form associated with tubercles as a pathology in 1689, due to the variety of its symptoms, TB was not identified as a single disease until the 1820s. Benjamin Marten conjectured in 1720 that consumptions were caused by microbes which were spread by people living close to each other. In 1819, René Laennec claimed that tubercles were

12875-425: 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

13000-448: The local doctor, and a newspaper reporter exhumed the bodies on March 17, 1892. The bodies of both Mary and Mary Olive exhibited the expected level of decomposition , so they were thought not to be the cause. However, the corpse of a daughter, Mercy, exhibited almost no decomposition, and still had blood in the heart. This was taken as a sign that the young woman was undead and the agent of young Edwin's condition. Her lack of decomposition

13125-525: The middle and upper classes offered excellent care and constant medical attention. What later became known as the Alexandra Hospital for Children with Hip Disease (tuberculous arthritis) was opened in London in 1867. Whatever the benefits of the "fresh air" and labor in the sanatoria, even under the best conditions, 50% of those who entered died within five years ( c. 1916). Robert Koch did not believe

13250-596: The newly infected person becomes infectious enough to transmit the disease to others. A number of factors make individuals more susceptible to TB infection and/or disease. The most important risk factor globally for developing active TB is concurrent HIV infection; 13% of those with TB are also infected with HIV. This is a particular problem in sub-Saharan Africa , where HIV infection rates are high. Of those without HIV infection who are infected with tuberculosis, about 5–10% develop active disease during their lifetimes; in contrast, 30% of those co-infected with HIV develop

13375-599: The number of infectious droplets expelled by the carrier, the effectiveness of ventilation, the duration of exposure, the virulence of the M. tuberculosis strain , the level of immunity in the uninfected person, and others. The cascade of person-to-person spread can be circumvented by segregating those with active ("overt") TB and putting them on anti-TB drug regimens. After about two weeks of effective treatment, subjects with nonresistant active infections generally do not remain contagious to others. If someone does become infected, it typically takes three to four weeks before

13500-531: 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

13625-455: 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

13750-514: 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

13875-539: 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

14000-435: The risk of developing active TB increases to nearly 10% a year. If effective treatment is not given, the death rate for active TB cases is up to 66%. TB infection begins when the mycobacteria reach the alveolar air sacs of the lungs, where they invade and replicate within endosomes of alveolar macrophages . Macrophages identify the bacterium as foreign and attempt to eliminate it by phagocytosis . During this process,

14125-414: The risk of infections (in addition to increasing the risk of active disease and death). Additional factors increasing infection susceptibility include young age. About 90% of those infected with M. tuberculosis have asymptomatic , latent TB infections (sometimes called LTBI), with only a 10% lifetime chance that the latent infection will progress to overt, active tuberculous disease. In those with HIV,

14250-535: The spines of Egyptian mummies dating from 3000 to 2400 BC. Genetic studies suggest the presence of TB in the Americas from about AD 100. Before the Industrial Revolution , folklore often associated tuberculosis with vampires . When one member of a family died from the disease, the other infected members would lose their health slowly. People believed this was caused by the original person with TB draining

14375-457: 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

14500-559: 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,

14625-465: The test's usefulness as a screening tool. Several vaccines are being developed. Intradermal MVA85A vaccine in addition to BCG injection is not effective in preventing tuberculosis. Public health campaigns which have focused on overcrowding, public spitting and regular sanitation (including hand washing) during the 1800s helped to either interrupt or slow spread which when combined with contact tracing, isolation and treatment helped to dramatically curb

14750-503: 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

14875-565: The top of the lung. This hematogenous transmission can also spread infection to more distant sites, such as peripheral lymph nodes, the kidneys, the brain, and the bones. All parts of the body can be affected by the disease, though for unknown reasons it rarely affects the heart , skeletal muscles , pancreas , or thyroid . Tuberculosis is classified as one of the granulomatous inflammatory diseases. Macrophages , epithelioid cells , T lymphocytes , B lymphocytes , and fibroblasts aggregate to form granulomas, with lymphocytes surrounding

15000-462: The transmission of both tuberculosis and other airborne diseases which led to the elimination of tuberculosis as a major public health issue in most developed economies. Other risk factors which worsened TB spread such as malnutrition were also ameliorated, but since the emergence of HIV a new population of immunocompromised individuals was available for TB to infect. During the HIV/AIDS epidemic in

15125-411: 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

15250-514: Was awarded the Nobel Prize in Physiology or Medicine for this discovery. In Europe, rates of tuberculosis began to rise in the early 1600s to a peak level in the 1800s, when it caused nearly 25% of all deaths. In the 18th and 19th century, tuberculosis had become epidemic in Europe , showing a seasonal pattern. Tuberculosis caused widespread public concern in the 19th and early 20th centuries as

15375-602: Was buried in the cemetery of the Baptist Church in Exeter after being desecrated. In the end, the father, George Brown, was one of very few never to contract tuberculosis , living until 1922, just long enough to see bacteriologists Albert Calmette and Camille Guérin discover the BCG vaccine which was widely used to treat and cure tuberculosis. The Mercy Brown incident was the inspiration for Caitlín R. Kiernan 's short story "So Runs

15500-449: Was more likely due to her body being stored in freezer-like conditions in an above-ground crypt during the two months following her death. As superstition dictated, Mercy's heart and liver were burned, and the ashes were mixed with water to create a tonic and was given to the sick Edwin to drink, as an effort to resolve his illness and stop the influence of the undead. The young man died two months later. What remained of Mercy's body

15625-468: Was not effective, it was later successfully adapted as a screening test for the presence of pre-symptomatic tuberculosis. World Tuberculosis Day is marked on 24 March each year, the anniversary of Koch's original scientific announcement. When the Medical Research Council formed in Britain in 1913, it initially focused on tuberculosis research. Albert Calmette and Camille Guérin achieved

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