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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Tuberculosis may infect any part of the body, but 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 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 a Rasmussen's 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.
A diagnosis of latent tuberculosis (LTB), also called latent tuberculosis infection (LTBI) means a patient is infected with "Mycobacterium tuberculosis", but the patient does not have active tuberculosis. Active tuberculosis can be contagious while latent tuberculosis is not, and it is therefore not possible to get TB from someone with latent tuberculosis. The main risk is that approximately 10% of these patients (5% in the first two years after infection and 0.1% per year thereafter) will go on to develop active tuberculosis. This is particularly true, and there is added risk, in particular situations such as medication that suppresses the immune system or advancing age.
The identification and treatment of people with latent TB is an important part of controlling this disease. Various treatment regimens are in use to treat latent tuberculosis, which generally need to be taken for several months.
The co-epidemic of tuberculosis (TB) and human immunodeficiency virus (HIV) is one of the major global health challenges in the present time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006 of whom 7.7% were HIV-infected. Tuberculosis is the most common contagious infection in HIV-Immunocompromised patients leading to death. These both diseases become dreadful in combination as HIV declines the human immunity while tuberculosis becomes progressive due to defective immune system.This condition becomes more severe in case of multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. See Multi-drug-resistant tuberculosis. Tuberculosis can occur at any stage of HIV infection. The risk and severity of tuberculosis increases soon after infection with HIV. A study on gold miners of South Africa revealed that the risk of TB was doubled during the first year after HIV seroconversion. Although tuberculosis can be a relatively early manifestation of HIV infection, it is important to note that the risk of tuberculosis progresses as the CD4 cell count decreases along with the progression of HIV infection. The risk of TB generally remains high in HIV-infected patients above the background risk of the general population even with effective immune reconstitution with ART maintaining high CD4 cell counts.
Extensively drug-resistant tuberculosis (XDR-TB) is a form of tuberculosis caused by bacteria that are resistant to some of the most effective anti-TB drugs. XDR-TB strains have arisen after the mismanagement of individuals with multidrug-resistant TB (MDR-TB).
Almost one in four people in the world is infected with TB bacteria. Only when the bacteria become active do people become ill with TB. Bacteria become active as a result of anything that can reduce the person’s immunity, such as HIV, advancing age, or some medical conditions. TB can usually be treated with a course of four standard, or first-line, anti-TB drugs (i.e., isoniazid, rifampin and any fluoroquinolone). If these drugs are misused or mismanaged, multidrug-resistant TB (MDR-TB) can develop. MDR-TB takes longer to treat with second-line drugs (i.e., amikacin, kanamycin, or capreomycin), which are more expensive and have more side-effects. XDR-TB can develop when these second-line drugs are also misused or mismanaged and therefore also become ineffective.
XDR-TB raises concerns of a future TB epidemic with restricted treatment options, and jeopardizes the major gains made in TB control and progress on reducing TB deaths among people living with HIV/AIDS. It is therefore vital that TB control be managed properly and new tools developed to prevent, treat and diagnose the disease.
The true scale of XDR-TB is unknown as many countries lack the necessary equipment and capacity to accurately diagnose it. It is estimated however that there are around 40,000 cases per year. As of June 2008, 49 countries had confirmed cases of XDR-TB. As of 2017, that number had risen to more than 100.
Symptoms of XDR-TB are no different from ordinary or drug-susceptible TB: a cough with thick, cloudy mucus (or sputum), sometimes with blood, for more than 2 weeks; fever, chills, and night sweats; fatigue and muscle weakness; weight loss; and in some cases shortness of breath and chest pain. A person with these symptoms does not necessarily have XDR-TB, but they should see a physician for diagnosis and a treatment plan. TB patients whose symptoms do not improve after a few weeks of treatment for TB and are taking treatment should inform their clinician or nurse.
Totally drug-resistant tuberculosis (TDR-TB) is a generic term for tuberculosis strains that are resistant to a wider range of drugs than strains classified as extensively drug-resistant tuberculosis. TDR-TB has been identified in three countries; India, Iran, and Italy. The emergence of TDR-TB has been documented in four major publications. However, it is not yet recognised by the World Health Organization.
TDR-TB has resulted from further mutations within the bacterial genome to confer resistance, beyond those seen in XDR- and MDR-TB. Development of resistance is associated with poor management of cases. Drug resistance testing occurs in only 9% of TB cases worldwide. Without testing to determine drug resistance profiles, MDR- or XDR-TB patients may develop resistance to additional drugs. TDR-TB is relatively poorly documented, as many countries do not test patient samples against a broad enough range of drugs to diagnose such a comprehensive array of resistance. The United Nations' Special Programme for Research and Training in Tropical Diseases has set up a TDR Tuberculosis Specimen Bank to archive specimens of TDR-TB.
Symptoms are similar to tuberculosis (TB), and include fever, fatigue, and weight loss. Pulmonary involvement is similar to TB, while diarrhea and abdominal pain are associated with gastrointestinal involvement.
Multi-drug-resistant tuberculosis (MDR-TB) is a form of tuberculosis (TB) infection caused by bacteria that are resistant to treatment with at least two of the most powerful first-line anti-TB medications (drugs), isoniazid and rifampin. Some forms of TB are also resistant to second-line medications, and are called extensively drug-resistant TB (XDR-TB).
Tuberculosis is caused by infection with the bacteria Mycobacterium tuberculosis. Almost one in four people in the world are infected with TB bacteria. Only when the bacteria become active do people become ill with TB. Bacteria become active as a result of anything that can reduce the person’s immunity, such as HIV, advancing age, diabetes or other immunocompromising illnesses. TB can usually be treated with a course of four standard, or first-line, anti-TB drugs (i.e., isoniazid, rifampin and any fluoroquinolone).
However, beginning with the first antibiotic treatment for TB in 1943, some strains of the TB bacteria developed resistance to the standard drugs through genetic changes (see mechanisms.) Currently the majority of multidrug-resistant cases of TB are due to one strain of TB bacteria called the Beijing lineage. This process accelerates if incorrect or inadequate treatments are used, leading to the development and spread of multidrug-resistant TB (MDR-TB). Incorrect or inadequate treatment may be due to use of the wrong medications, use of only one medication (standard treatment is at least two drugs), not taking medication consistently or for the full treatment period (treatment is required for several months). Treatment of MDR-TB requires second-line drugs (i.e., fluoroquinolones, aminoglycosides, and others), which in general are less effective, more toxic and much more expensive than first-line drugs. Treatment schedules for MDR-TB involving fluoroquinolones and aminoglycosides can run for 2 years, compared to the 6 months of first-line drug treatment, and cost over $100,000 USD.If these second-line drugs are prescribed or taken incorrectly, further resistance can develop leading to XDR-TB.
Resistant strains of TB are already present in the population, so MDR-TB can be directly transmitted from an infected person to an uninfected person. In this case a previously untreated person develops a new case of MDR-TB. This is known as primary MDR-TB, and is responsible for up to 75% of cases. Acquired MDR-TB develops when a person with a non-resistant strain of TB is treated inadequately, resulting in the development of antibiotic resistance in the TB bacteria infecting them. These people can in turn infect other people with MDR-TB.
MDR-TB caused an estimated 480,000 new TB cases and 250,000 deaths in 2015. MDR-TB accounts for 3.3% of all new TB cases worldwide. Resistant forms of TB bacteria, either MDR-TB or rifampin-resistant TB, cause 3.9% of new TB cases and 21% of previously treated TB cases. Globally, most MDR-TB cases occur in South America, Southern Africa, India, China, and the former Soviet Union.
Treatment of MDR-TB requires treatment with second-line drugs, usually four or more anti-TB drugs for a minimum of 6 months, and possibly extending for 18–24 months if rifampin resistance has been identified in the specific strain of TB with which the patient has been infected. Under ideal program conditions, MDR-TB cure rates can approach 70%.
Patients with miliary tuberculosis often experience non-specific signs, such as coughing and enlarged lymph nodes. Miliary tuberculosis can also present with enlarged liver (40% of cases), enlarged spleen (15%), inflammation of the pancreas (<5%), and multiple organ dysfunction with adrenal insufficiency (adrenal glands do not produce enough steroid hormones to regulate organ function). Miliary tuberculosis may also present with unilateral or bilateral pneumothorax rarely. Stool may also be diarrheal in nature and appearance.
Other symptoms include fever, hypercalcemia, chorodial tubercles and cutaneous lesions.
Firstly, many patients can experience a fever lasting several weeks with daily spikes in morning temperatures.
Secondly, hypercalcemia prevails in 16 to 51% of tuberculosis cases. It is thought that hypercalcemia occurs as a response to increased macrophage activity in the body. Such that, 1,25 dihydroxycholecalciferol (also referred to as calcitriol) improves the ability of macrophages to kill bacteria; however, higher levels of calcitriol lead to higher calcium levels, and thus hypercalcemia in some cases. Thus, hypercalcemia proves to be an important symptom of miliary tuberculosis.
Thirdly, chorodial tubercules, pale lesions on the optic nerve, typically indicate miliary tuberculosis in children. These lesions may occur in one eye or both; the number of lesions varies between patients. Chorodial tubercules may serve as important symptoms of miliary tuberculosis, since their presence can often confirm suspected diagnosis.
Lastly, between 10 and 30% of adults, and 20–40% of children with miliary tuberculosis have tuberculosis meningitis. This relationship results from myobacteria from miliary tuberculosis spreading to the brain and the subarachnoid space; as a result, leading to tuberculosis meningitis.
The risk factors for contracting miliary tuberculosis are being in direct contact with a person who has it, living in unsanitary conditions, and having an unhealthy diet. In the U.S., risk factors for contracting the disease include homelessness and HIV/AIDS.
Miliary tuberculosis is a form of tuberculosis that is characterized by a wide dissemination into the human body and by the tiny size of the lesions (1–5 mm). Its name comes from a distinctive pattern seen on a chest radiograph of many tiny spots distributed throughout the lung fields with the appearance similar to millet seeds—thus the term "miliary" tuberculosis. Miliary TB may infect any number of organs, including the lungs, liver, and spleen. Miliary tuberculosis is present in about 2% of all reported cases of tuberculosis and accounts for up to 20% of all extra-pulmonary tuberculosis cases.
Blastomycosis can present in one of the following ways:
- a flu-like illness with fever, chills, arthralgia (joint pain), myalgia (muscle pain), headache, and a nonproductive cough which resolves within days.
- an acute illness resembling bacterial pneumonia, with symptoms of high fever, chills, a productive cough, and pleuritic chest pain.
- a chronic illness that mimics tuberculosis or lung cancer, with symptoms of low-grade fever, a productive cough, night sweats, and weight loss.
- a fast, progressive, and severe disease that manifests as ARDS, with fever, shortness of breath, tachypnea, hypoxemia, and diffuse pulmonary infiltrates.
- skin lesions, usually asymptomatic, can be verrucous (wart-like) or ulcerated with small pustules at the margins.
- bone lytic lesions can cause bone or joint pain.
- prostatitis may be asymptomatic or may cause pain on urinating.
- laryngeal involvement causes hoarseness.
- 40% immunocompromised individuals have CNS involvement and present as brain abscess, epidural abscess or meningitis.
In cattle, the main signs of paratuberculosis are diarrhea and wasting. Most cases are seen in 2- to 6-year-old animals. The initial signs can be subtle, and may be limited to weight loss, decreased milk production, or roughening of the hair coat. The diarrhea is usually thick, without blood, mucus, or epithelial debris, and may be intermittent. Several weeks after the onset of diarrhea, a soft swelling may occur under the jaw. Known as "bottle jaw" or intermandibular edema, this symptom is due to protein loss from the bloodstream into the digestive tract. Paratuberculosis is progressive; affected animals become increasingly emaciated and usually die as the result of dehydration and severe cachexia.
Signs are rarely evident until two or more years after the initial infection, which usually occurs shortly after birth. Animals are most susceptible to the infection in the first year of life. Newborns most often become infected by swallowing small amounts of infected manure from the birthing environment or udder of the mother. In addition, newborns may become infected while in the uterus or by swallowing bacteria passed in milk and colostrum. Animals exposed at an older age, or exposed to a very small dose of bacteria at a young age, are not likely to develop clinical disease until they are much older than two years.
The clinical signs are similar in other ruminants. In sheep and goats, the wool or hair is often damaged and easily shed, and diarrhea is uncommon. In deer, paratuberculosis can progress rapidly. Intestinal disease has also been reported in rabbits and nonhuman primates.
Unlike cattle and sheep, infections in deer often present with clinical illness in animals under one year of age.
An emerging infectious disease (EID) is an infectious disease whose incidence has increased in the past 20 years and could increase in the near future. Emerging infections account for at least 12% of all human pathogens. EIDs are caused by newly identified species or strains (e.g. Severe acute respiratory syndrome, HIV/AIDS) that may have evolved from a known infection (e.g. influenza) or spread to a new population (e.g. West Nile fever) or to an area undergoing ecologic transformation (e.g. Lyme disease), or be "reemerging" infections, like drug resistant tuberculosis. Nosocomial (hospital-acquired) infections, such as methicillin-resistant Staphylococcus aureus are emerging in hospitals, and extremely problematic in that they are resistant to many antibiotics. Of growing concern are adverse synergistic interactions between emerging diseases and other infectious and non-infectious conditions leading to the development of novel syndemics. Many emerging diseases are zoonotic - an animal reservoir incubates the organism, with only occasional transmission into human populations.
"Mycobacterium avium-intracellulare" infection (MAI) is an atypical mycobacterial infection, i.e. one with nontuberculous mycobacteria or NTM, caused by "Mycobacterium avium" complex ("MAC"), which is made of three mycobacteria species, "M. avium", "M. intracellulare", and "M. chimaera". This infection causes respiratory illness in birds, pigs, and humans, especially in immunocompromised people. In the later stages of AIDS it can be very severe. It usually first presents as a persistent cough. It is typically treated with a series of three antibiotics for a period of at least six months.
"M. avium", "M. intracellulare", and "M. chimaera" are each saprotrophic organisms present in soil and water; entry into hosts is usually via the gastrointestinal tract, but also can be via the lungs.
MAC infections can cause fevers, diarrhea, malabsorption, as well as loss of appetite and weight loss, and can disseminate to the bone marrow. Therapy for MAI is typically resistant to standard mycobacterial therapies.
Paratuberculosis or Johne's disease is a contagious, chronic and sometimes fatal infection that primarily affects the small intestine of ruminants. It is caused by the bacterium "Mycobacterium avium" subspecies "paratuberculosis". Infections normally affect ruminants (mammals that have four compartments of their stomachs, of which the rumen is one), but have also been seen in a variety of nonruminant species, including rabbits, foxes, and birds. Horses, dogs, and nonhuman primates have been infected experimentally. Paratuberculosis is found worldwide, with some states in Australia (where it is usually called bovine Johne's disease or BJD) as the only areas proven to be free of the disease.
Some sources define "paratuberculosis" by the lack of "Mycobacterium tuberculosis", rather than the presence of any specific infectious agent, leaving ambiguous the appropriateness of the term to describe Buruli ulcer or Lady Windermere syndrome.
Blastomycosis (also known as "North American blastomycosis", "Blastomycetic dermatitis", and "Gilchrist's disease") is a fungal infection of humans and other animals, notably dogs and occasionally cats, caused by the organism "Blastomyces dermatitidis". Endemic to portions of North America, blastomycosis causes clinical symptoms similar to histoplasmosis. The disease occurs in several endemic areas, the most important of which is in eastern North America, particularly in the western and northern periphery of the Great Lakes Basin, extending eastward along the south shore of the St. Lawrence River Valley and southward in the territory spanned by the central Appalachian Mountains in the east, to the Mississippi River Valley in the west. Sporadic cases have been reported in continental Africa, the Arabian Peninsula and the Indian subcontinent.
BRD often develops within 4 weeks of cattle transport. The biggest sign of the pneumonia that BRD causes is depression, shown as droopy ears, dull eyes, and social isolation. Additionally, most cows will have a fever above . Other symptoms include coughing, decreased appetite, and breathing difficulty.
Infectious bovine keratoconjunctivitis, or IBK, is a veterinary infection of cattle caused by "Moraxella bovis", a Gram-negative, β-haemolytic, aerobic, rod-shaped bacterium. It is spread by direct contact or by flies serving as vectors. It is the most common ocular disease of cattle (mostly beef). IBK is similar to human pink eye and causes severe infection of the conjunctiva, edema, corneal opacity, and ulceration. This disease is highly contagious and occurs worldwide. Younger animals are more susceptible, but recovery with minimal damage is usual, if they are treated early. The disease is also known as pinkeye, New Forest eye or blight.
Swine brucellosis is a zoonosis affecting pigs, caused by the bacterium "Brucella suis". The disease typically causes chronic inflammatory lesions in the reproductive organs of susceptible animals or orchitis, and may even affect joints and other organs. The most common symptom is abortion in pregnant susceptible sows at any stage of gestation. Other manifestations are temporary or permanent sterility, lameness, posterior paralysis, spondylitis, and abscess formation. It is transmitted mainly by ingestion of infected tissues or fluids, semen during breeding, and suckling infected animals.
Since brucellosis threatens the food supply and causes undulant fever, "Brucella suis" and other "Brucella" species ("B. melitensis, B. abortis, B. ovis, B. canis") are recognized as potential agricultural, civilian, and military bioterrorism agents.
Bovine respiratory disease (BRD) is the most common and costly disease affecting beef cattle in the world. It is a complex, bacterial infection that causes pneumonia in calves and can possibly be fatal. The infection is usually a sum of three codependent factors: stress, an underlying viral infection, and a new bacterial infection.
The diagnosis of the disease is complex since there are multiple possible causes.
The disease manifests itself most often in calves within four weeks of weaning, when calves are sorted and often sold to different farms. This gives it a common nickname, "shipping fever." It is not known whether the stress itself, co-mingling, or travel conditions are at most to blame, and while studies have identified general stressing factors like transport and cold weather conditions, there is still no conclusive evidence on more specific factors (e.g. distance, transport mode, temperature, or temperature volatility.
The bacteria invade the lacrimal glands of the eye, causing keratitis, uveitis, and corneal ulceration. Cattle show signs of pain, increased lacrimation, excessive blinking, and conjunctivitis. More severe cases may show systemic signs such as anorexia and weight loss. Chronic untreated cases can become blind. Diagnosis is usually based on the clinical signs, but the bacteria can be cultured from lacrimal swabs, or visualised on smears of lacrimal secretions.
Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to multiple antimicrobial drugs. The types most threatening to public health are MDR bacteria that resist multiple antibiotics; other types include MDR viruses, fungi, and parasites (resistant to multiple antifungal, antiviral, and antiparasitic drugs of a wide chemical variety). Recognizing different degrees of MDR, the terms extensively drug resistant (XDR) and pandrug-resistant (PDR) have been introduced. The definitions were published in 2011 in the journal "Clinical Microbiology and Infection" and are openly accessible.
A study conducted on 452 patients revealed that the genotype responsible for higher IL-10 expression makes HIV infected people more susceptible to tuberculosis infection. Another study on HIV-TB co-infected patients also concluded that higher level of IL-10 and IL-22 makes TB patient more susceptible to Immune reconstitution inflammatory syndrome (IRIS). It is also seen that HIV co-infection with tuberculosis also reduces concentration of immunopathogenic matrix metalloproteinase (MMPs) leading to reduced inflammatory immunopathology.
Contagious bovine pleuropneumonia (CBPP - also known as lung plague), is a contagious bacterial disease that afflicts the lungs of cattle, buffalo, zebu, and yaks.
It is caused by the bacterium "Mycoplasma mycoides", and the symptoms are pneumonia and inflammation of the lung membranes. The incubation period is 20 to 123 days. It was particularly widespread in the United States in 1879, affecting herds from several states. The outbreak was so severe that it resulted in a trade embargo by the British government, blocking U.S. cattle exports to Britain and Canada. This prompted the United States to establish the Bureau of Animal Industry, set up in 1884 to eradicate the disease, which it succeeded in doing by 1892.
Louis Willems, a Belgian doctor, began pioneering work in the 1850s on animal inoculation against the disease.
The bacteria are widespread in Africa, the Middle East, Southern Europe, as well as parts of Asia. It is an airborne species, and can travel up to several kilometres in the right conditions.