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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)
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Mycobacterium fortuitum is a nontuberculous species of the phylum actinobacteria (Gram-positive bacteria with high guanine and cytosine content, one of the dominant phyla of all bacteria), belonging to the genus mycobacterium.
The 2007 guideline “Official American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) statement: diagnosis, treatment, and prevention of non-tuberculosis mycobacterial diseases”, notes that M. fortuitum isolates are usually susceptible to multiple oral antimicrobial agents, including the macrolides and quinolones, doxycycline and minocycline, and sulfonamides. Isolates of this mycobacterium are susceptible to the beta-lactam antibiotics, belonging to the carbopenam subgroup, such as Imipenem. Imipenem is a broad spectrum antibiotic produced by the bacteria Streptomyces cattleya. Ondansetron HCL (Zofran) is an antiemetic often given to offset the nausea and vomiting that are a common side effect of Imipenem. Severe infections require IV treatment combined with oral antibiotics for a prolonged period, up to several months. The guideline recommends “for serious skin, bone, and soft tissue M fortuitum disease, a minimum of 4 months of therapy with at least two agents with in vitro activity against the clinical isolate is necessary to provide a high likelihood of cure. Surgery is generally indicated with extensive disease, abscess formation, or where drug therapy is difficult.”
Studies have found that men have a higher risk of getting XDR-TB than women. One study showed that the male to female ratio was more than threefold, with statistical relevance (P<0.05) Studies done on the effect of age and XDR-TB have revealed that individuals who are 65 and up are less likely to get XDR-TB. A study in Japan found that XDR-TB patients are more likely to be younger.
TB is one of the most common infections in people living with HIV/AIDS. In places where XDR-TB is most common, people living with HIV are at greater risk of becoming infected with XDR-TB, compared with people without HIV, because of their weakened immunity. If there are a lot of HIV-infected people in these places, then there will be a strong link between XDR-TB and HIV. Fortunately, in most of the places with high rates of HIV, XDR-TB is not yet widespread. For this reason, the majority of people with HIV who develop TB will have drug-susceptible or ordinary TB, and can be treated with standard first-line anti-TB drugs. For those with HIV infection, treatment with antiretroviral drugs will likely reduce the risk of becoming infected with XDR-TB, just as it does with ordinary TB.
A research study titled "TB Prevalence Survey and Evaluation of Access to TB Care in HIV-Infected and Uninfected TB Patients in Asembo and Gem, Western Kenya", says that HIV/AIDS is fueling large increases in TB incidence in Africa, and a large proportion of cases are not diagnosed.
HIV-infected children less than 12 years of age also develop disseminated MAC. Some age adjustment is necessary when clinicians interpret CD4+ T-lymphocyte counts in children less than 2 years of age. Diagnosis, therapy, and prophylaxis should follow recommendations similar to those for adolescents and adults.
MAI is common in immunocompromised individuals, including senior citizens and those with HIV/AIDS or cystic fibrosis. Bronchiectasis, the bronchial condition which causes unnatural enlargement of the bronchial tubes, is commonly found with MAI infection. Whether the bronchiectasis leads to the MAC infection or is the result of it is not always known.
The "Mycobacterium avium complex" (MAC) includes common atypical bacteria, i.e. nontuberculous mycobacteria (NTM), found in the environment which can infect people with HIV and low CD4 cell count (below 100/microliter); mode of infection is usually inhalation or ingestion.
MAC causes disseminated disease in up to 40% of people with human immunodeficiency virus (HIV) in the United States, producing fever, sweats, weight loss, and anemia. Disseminated MAC characteristically affects people with advanced HIV disease and peripheral CD4+ T-lymphocyte counts less than 100 cells/uL. Effective prevention and therapy of MAC has the potential to contribute substantially to improved quality of life and duration of survival for HIV-infected persons.
Cases of MDR tuberculosis have been reported in every country surveyed. MDR-TB most commonly develops in the course of TB treatment, and is most commonly due to doctors giving inappropriate treatment, or patients missing doses or failing to complete their treatment. Because MDR tuberculosis is an airborne pathogen, persons with active, pulmonary tuberculosis caused by a multidrug-resistant strain can transmit the disease if they are alive and coughing. TB strains are often less fit and less transmissible, and outbreaks occur more readily in people with weakened immune systems (e.g., patients with HIV). Outbreaks among non immunocompromised healthy people do occur, but are less common.
As of 2013, 3.7% of new tuberculosis cases have MDR-TB. Levels are much higher in those previously treated for tuberculosis - about 20%. WHO estimates that there were about 0.5 million new MDR-TB cases in the world in 2011. About 60% of these cases occurred in Brazil, China, India, the Russian Federation and South Africa alone. In Moldova, the crumbling health system has led to the rise of MDR-TB. In 2013, the Mexico–United States border was noted to be "a very hot region for drug resistant TB", though the number of cases remained small.
It has been known for many years that INH-resistant TB is less virulent in guinea pigs, and the epidemiological evidence is that MDR strains of TB do not dominate naturally. A study in Los Angeles, California found that only 6% of cases of MDR-TB were clustered. Likewise, the appearance of high rates of MDR-TB in New York City in the early 1990s was associated with the explosion of AIDS in that area. In New York City, a report issued by city health authorities states that fully 80 percent of all MDR-TB cases could be traced back to prisons and homeless shelters. When patients have MDR-TB, they require longer periods of treatment—about two years of multidrug regimen. Several of the less powerful second-line drugs, which are required to treat MDR-TB, are also more toxic, with side effects such as nausea, abdominal pain, and even psychosis. The Partners in Health team had treated patients in Peru who were sick with strains that were resistant to ten and even twelve drugs. Most such patients require adjuvant surgery for any hope of a cure.
Immunodeficiency or immunosuppression can be caused by:
- Malnutrition
- Fatigue
- Recurrent infections
- Immunosuppressing agents for organ transplant recipients
- Advanced HIV infection
- Chemotherapy for cancer
- Genetic predisposition
- Skin damage
- Antibiotic treatment leading to disruption of the physiological microbiome, thus allowing some microorganisms to outcompete others and become pathogenic (e.g. disruption of intestinal flora may lead to "Clostridium difficile" infection
- Medical procedures
- Pregnancy
- Ageing
- Leukopenia (i.e. neutropenia and lymphocytopenia)
The lack of or the disruption of normal vaginal flora allows the proliferation of opportunistic microorganisms and will cause the opportunistic infection - bacterial vaginosis.
Opportunistic infections caused by Feline Leukemia Virus and Feline immunodeficiency virus retroviral infections can be treated with Lymphocyte T-Cell Immune Modulator.
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.
Common multidrug-resistant organisms are usually bacteria:
- Vancomycin-Resistant Enterococci (VRE)
- Methicillin-Resistant "Staphylococcus" "aureus" (MRSA)
- Extended-spectrum β-lactamase (ESBLs) producing Gram-negative bacteria
- "Klebsiella" "pneumoniae" carbapenemase (KPC) producing Gram-negatives
- Multidrug-Resistant gram negative rods (MDR GNR) MDRGN bacteria such as "Enterobacter species", "E.coli", "Klebsiella pneumoniae", "Acinetobacter baumannii", "Pseudomonas aeruginosa"
A group of gram-positive and gram-negative bacteria of particular recent importance have been dubbed as the ESKAPE group ("Enterococcus faecium", "Staphylococcus aureus", "Klebsiella pneumoniae", "Acinetobacter baumannii", "Pseudomonas aeruginosa" and Enterobacter species).
- Multi-drug-resistant tuberculosis
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.
There are several elements of the Russian prison system that enable the spread of MDR-TB and heighten its severity. Overcrowding in prisons is especially conducive to the spread of tuberculosis; an inmate in a prison hospital has (on average) 3 meters of personal space, and an inmate in a correctional colony has 2 meters. Specialized hospitals and treatment facilities within the prison system, known as TB colonies, are intended to isolate infected prisoners to prevent transmission; however, as Ruddy et al. demonstrate, there are not enough of these colonies to sufficiently protect staff and other inmates. Additionally, many cells lack adequate ventilation, which increases likelihood of transmission. Bobrik et al. have also noted food shortages within prisons, which deprive inmates of the nutrition necessary for healthy functioning.
Comorbidity of HIV within prison populations has also been shown to worsen health outcomes. Nachega & Chaisson articulate that while HIV-infected prisoners are not more susceptible MDR-TB infection, they are more likely to progress to serious clinical illness if infected. According to Stern, HIV infection is 75 times more prevalent in Russian prison populations than in the civilian population. Therefore, prison inmates are both more likely to become infected with MDR-TB initially and to experience severe symptoms because of previous exposure to HIV.
Shin et al. emphasize another factor in MDR-TB prevalence in Russian prisons: alcohol and substance use. Ruddy et al. showed that risk for MDR-TB is three times higher among recreational drug users than non-users. Shin et al.’s study demonstrated that alcohol usage was linked to poorer outcomes in MDR-TB treatment; they also noted that a majority of subjects within their study (many of whom regularly used alcohol) were nevertheless cured by their aggressive treatment regimen.
Non-compliance with treatment plans is often cited as a contributor to MDR-TB transmission and mortality. Indeed, of the 80 newly-released TB-infected inmates in Fry et al.’s study, 73.8% did not report visiting a community dispensary for further treatment. Ruddy et al. cite release from facilities as one of the main causes of interruption in prisoner’s TB treatment, in addition to non-compliance within the prison and upon reintegration into civilian life. Fry et al.’s study also listed side effects of TB treatment medications (especially in HIV positive individuals), financial worries, housing insecurities, family problems, and fear of arrest as factors that prevented some prisoners from properly adhering to TB treatment. They also note that some researchers have argued that the short-term gains TB-positive prisoners receive, such as better food or work exclusion, may dis-incentivize becoming cured. In their World Health Organization article, Gelmanova et al. posit that non-adherence to TB treatment indirectly contributes to bacterial resistance. Although ineffective or inconsistent treatment does not “create” resistant strains, mutations within the high bacterial load in non-adherent prisoners can cause resistance.
Nachega & Chaisson argue that inadequate TB control programs are the strongest driver of MDR-TB incidence. They note that prevalence of MDR-TB is 2.5 times higher in areas of poorly controlled TB. Russian-based therapy (i.e., not DOTS) has been criticized by Kimerling et al. as “inadequate” in properly controlling TB incidence and transmission. Bobrik et al. note that treatment for MDR-TB is equally inconsistent; the second-line drugs used to treat the prisoners lack specific treatment guidelines, infrastructure, training, or follow-up protocols for prisoners reentering civilian life.
If left untreated, miliary tuberculosis is almost always fatal. Although most cases of miliary tuberculosis are treatable, the mortality rate among children with miliary tuberculosis remains 15 to 20% and for adults 25 to 30%. One of the main causes for these high mortality rates includes late detection of disease caused by non-specific symptoms. Non-specific symptoms include: coughing, weight loss, or organ dysfunction. These symptoms may be implicated in numerous disorders, thus delaying diagnosis. Misdiagnosis with tuberculosis meningitis is also a common occurrence when patients are tested for tuberculosis, since the two forms of tuberculosis have high rates of co-occurrence.
A number of factors make people more susceptible to TB infections. The most important risk factor globally is HIV; 13% of all people with TB are infected by the virus. This is a particular problem in sub-Saharan Africa, where rates of HIV are high. Of people without HIV who are infected with tuberculosis, about 5–10% develop active disease during their lifetimes; in contrast, 30% of those coinfected with HIV develop the active disease.
Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal diseases of poverty. Those at high risk thus include: people who inject illicit drugs, inhabitants and employees of locales where vulnerable people gather (e.g. prisons and homeless shelters), medically underprivileged and resource-poor communities, high-risk ethnic minorities, children in close contact with high-risk category patients, and health-care providers serving these patients.
Chronic lung disease is another significant risk factor. Silicosis increases the risk about 30-fold. Those who smoke cigarettes have nearly twice the risk of TB compared to nonsmokers.
Other disease states can also increase the risk of developing tuberculosis. These include alcoholism and diabetes mellitus (three-fold increase).
Certain medications, such as corticosteroids and infliximab (an anti-αTNF monoclonal antibody), are becoming increasingly important risk factors, especially in the developed world.
Genetic susceptibility also exists, for which the overall importance remains undefined.
Progression from TB infection to overt TB disease occurs when the bacilli overcome the immune system defenses and begin to multiply. In primary TB disease (some 1–5% of cases), this occurs soon after the initial infection. However, in the majority of cases, a latent infection occurs with no obvious symptoms. These dormant bacilli produce active tuberculosis in 5–10% of these latent cases, often many years after infection.
The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV. In people coinfected with "M. tuberculosis" and HIV, the risk of reactivation increases to 10% per year. Studies using DNA fingerprinting of "M. tuberculosis" strains have shown reinfection contributes more substantially to recurrent TB than previously thought, with estimates that it might account for more than 50% of reactivated cases in areas where TB is common. The chance of death from a case of tuberculosis is about 4% as of 2008, down from 8% in 1995.
MAP is capable of causing Johne's-like symptoms in humans, though difficulty in testing for MAP infection presents a diagnostic hurdle.
Clinical similarities are seen between Johne's disease in ruminants and inflammatory bowel disease in humans, and because of this, some researchers contend the organism is a cause of Crohn's disease. However, epidemiologic studies have provided variable results; in certain studies, the organism (or an immune response directed against it) has been much more frequently found in patients with Crohn's disease than asymptomatic people.
When HIV-negative children take isoniazid after they have been exposed to tuberculosis, their risk to contract tuberculosis is reduced. A Cochrane review investigated whether giving isoniazid to HIV-positive children can help to prevent this vulnerable group from getting tuberculosis. They included three trials conducted in South Africa and Botswana and found that isoniazid given to all children diagnosed with HIV may reduce the risk of active tuberculosis and death in children who are not on antiretroviral treatment. For children taking antiretroviral medication, no clear benefit was detected.
Buruli ulcer commonly affects poor people in remote rural areas with limited access to health care. The disease can affect all age groups, although children under the age of 15 years (range 2–14 years) are predominantly affected. There are no sex differences in the distribution of cases among children. Among adults, some studies have reported higher rates among women than males (Debacker "et al." accepted for publication). No racial or socio-economic group is exempt from the disease. Most ulcers occur on the extremities; lesions on the lower extremities are almost twice as common as those on the upper extremities. Ulcers on the head and trunk accounted for less than 8% of cases in one large series.
In an endemic herd, only a minority of the animals develops clinical signs; most animals either eliminate the infection or become asymptomatic carriers. The mortality rate is about 1%, but up to 50% of the animals in the herd can be asymptomatically infected, resulting in losses in production. Once the symptoms appear, paratuberculosis is progressive and affected animals eventually die. The percentage of asymptomatic carriers that develop overt disease is unknown.
An individual may only develop signs of an infection after a period of subclinical infection, a duration that is called the incubation period. This is the case, for example, for subclinical sexually transmitted diseases such as AIDS and genital warts. Individuals with such subclinical infections, and those that never develop overt illness, creates a reserve of individuals that can transmit an infectious agent to infect other individuals. Because such cases of infections do not come to clinical attention, health statistics can often fail to measure the true prevalence of an infection in a population, and this prevents the accurate modeling of its infectious transmission.
Buruli ulcer has been reported from at least 32 countries around the world, mostly in tropical areas:
- West Africa: Benin, Burkina Faso, Côte d'Ivoire, Ghana, Liberia, Nigeria, Togo, Guinea, Sierra Leone.
- Other African Countries: Angola, Cameroon, Congo, Democratic Republic of Congo, Equatorial Guinea, Gabon, Sudan, Uganda.
- Western Pacific: Australia, Papua New Guinea, Kiribati.
- Americas: French Guiana, Mexico, Peru, Suriname.
- Asia: China, Malaysia, Japan.
In several of these countries, the disease is not considered to be a public health problem, hence the current distribution and the number of cases are not known. Possible reasons include:
- the distribution of the disease is often localized in certain parts of endemic countries;
- Buruli ulcer is not a notifiable disease
- In most places where the disease occurs, patients receive care from private sources such as voluntary mission hospitals and traditional healers. Hence the existence of the disease may not come to the attention of the ministries of health.
It most commonly occurs in Africa: Congo and Cameroon in Central Africa, Côte d'Ivoire, Ghana and Benin in West Africa. Some Southeast Asian countries (Papua New Guinea) and Australia have major foci, and there have been a few patients reported from South America (French Guyana and Surinam) and Mexico. Focal outbreaks have followed flooding, human migrations, and man-made topographic modifications such as dams and resorts. Deforestation and increased basic agricultural activities may significantly contribute to the recent marked increases in the incidence of "M. ulcerans" infections, especially in West Africa, where the disease is rapidly emerging.
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.
Fever and sickness behavior and other signs of infection are often taken to be due to them. However, they are evolved physiological and behavioral responses of the host to clear itself of the infection. Instead of incurring the costs of deploying these evolved responses to infections, the body opts to tolerate an infection as an alternative to seeking to control or remove the infecting pathogen.
Subclinical infections are important since they allow infections to spread from a reserve of carriers. They also can cause clinical problems unrelated to the direct issue of infection. For example, in the case of urinary tract infections in women, this infection may cause preterm delivery if the person becomes pregnant without proper treatment.
Ghon's complex is a lesion seen in the lung that is caused by tuberculosis. The lesions consist of a calcified focus of infection and an associated lymph node. These lesions are particularly common in children and can retain viable bacteria, so are sources of long-term infection and may be involved in reactivation of the disease in later life.
In countries where cow milk infected with "Mycobacterium bovis" has been eliminated (due to culling of infected cows and pasteurization), primary tuberculosis is usually caused by "Mycobacterium tuberculosis" and almost always begins in the lungs. Typically, the inhaled bacilli implant in the distal airspaces of the lower part of the upper lobe or the upper part of the lower lobe, usually close to the pleura. As sensitization develops, a 1- to 1.5-cm area of gray-white inflammation with consolidation emerges, known as the Ghon focus. In most cases, the center of this focus undergoes caseous necrosis. Tubercle bacilli, either free or within phagocytes, drain to the regional nodes, which also often caseate. This combination of parenchymal lung lesion and nodal involvement is referred to as the Ghon complex. During the first few weeks there is also lymphatic and hematogenous dissemination to other parts of the body.
In approximately 95% of cases, development of cell-mediated immunity controls the infection.