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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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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.
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.
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.
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.
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.
Smoking cessation and reducing indoor air pollution, such as that from cooking indoors with wood or dung, are both recommended. Smoking appears to be the single biggest risk factor for pneumococcal pneumonia in otherwise-healthy adults. Hand hygiene and coughing into one's sleeve may also be effective preventative measures. Wearing surgical masks by the sick may also prevent illness.
Appropriately treating underlying illnesses (such as HIV/AIDS, diabetes mellitus, and malnutrition) can decrease the risk of pneumonia. In children less than 6 months of age, exclusive breast feeding reduces both the risk and severity of disease. In those with HIV/AIDS and a CD4 count of less than 200 cells/uL the antibiotic trimethoprim/sulfamethoxazole decreases the risk of "Pneumocystis pneumonia" and is also useful for prevention in those that are immunocomprised but do not have HIV.
Testing pregnant women for Group B Streptococcus and "Chlamydia trachomatis", and administering antibiotic treatment, if needed, reduces rates of pneumonia in infants; preventive measures for HIV transmission from mother to child may also be efficient. Suctioning the mouth and throat of infants with meconium-stained amniotic fluid has not been found to reduce the rate of aspiration pneumonia and may cause potential harm, thus this practice is not recommended in the majority of situations. In the frail elderly good oral health care may lower the risk of aspiration pneumonia. Zinc supplementation in children 2 months to five years old appears to reduce rates of pneumonia.
When influenza outbreaks occur, medications such as amantadine or rimantadine may help prevent the condition; however are associated with side effects. Zanamivir or oseltamivir decrease the chance that those exposed will develop symptoms; however, it is recommended that potential side effects are taken into account.
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.
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.
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.”
"Mycobacterium fortuitum" is a fast-growing species that can cause infections. The term "fast growing" is a reference to a growth rate of 3 or 4 days, when compared to other Mycobacteria that may take weeks to grow out on laboratory media. Pulmonary infections of "M. fortuitum" are uncommon, but "Mycobacterium fortuitum" can cause local skin disease, osteomyelitis (inflammation of the bone), joint infections and infections of the eye after trauma. "Mycobacterium fortuitum" has a worldwide distribution and can be found in natural and processed water, sewage, and dirt.
Bacteria classified as Mycobacteria, include the causative agents for tuberculosis and leprosy. Mycobacteria are sometimes referred to as “acid-fast bacteria,” a term referencing their response to a laboratory staining technique. This simply means that when microscopic slides of these bacteria are rinsed with an acidic solution, they retain a red dye. "Mycobacterium fortuitum" is one of the many species of nontuberculosis mycobacteria (NTM) that are commonly found in the environment. These are not involved in tuberculosis. This does not mean, however, that they will not cause an infection in the right circumstances.
"M. fortuitum" infection can be a nosocomial (hospital acquired) disease. Surgical sites may become infected after the wound is exposed directly or indirectly to contaminated tap water. Other possible sources of "M. fortuitum" infection include implanted devices such as catheters, injection site abscesses, and contaminated endoscopes. Recent publication on Rapidly Growing Mycobacteria (RGM) is available provides the following aspects of RGM: (i) its sources, predisposing factors, clinical manifestations, and concomitant fungal infections; (ii) the risks of misdiagnoses in the management of RGM infections in dermatological settings; (iii) the diagnoses and outcomes of treatment responses in common and uncommon infections in immunocompromised and immunocompetent patients; (iv) conventional versus current molecular methods for the detection of RGM; (v) the basic principles of a promising MALDI-TOF MS, sampling protocol for cutaneous or subcutaneous lesions and its potential for the precise differentiation of "M. fortuitum", "M. chelonae", and "M. abscessus"; and (vi) improvements in RGM infection management as described in the recent 2011 Clinical and
Laboratory Standards Institute (CLSI) guidelines, including interpretation criteria of molecular methods and antimicrobial drug panels and their break points [minimum inhibitory concentrations (MICs)], which have been highlighted for the initiation of antimicrobial therapy (Kothavade RJ et al., 2012).
Since opportunistic infections can cause severe disease, much emphasis is placed on measures to prevent infection. Such a strategy usually includes restoration of the immune system as soon as possible, avoiding exposures to infectious agents, and using antimicrobial medications ("prophylactic medications") directed against specific infections.
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.
Opportunistic infections caused by Feline Leukemia Virus and Feline immunodeficiency virus retroviral infections can be treated with Lymphocyte T-Cell Immune Modulator.
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
The prime example for MDR against antiparasitic drugs is malaria. "Plasmodium vivax" has become chloroquine and sulfadoxine-pyrimethamine resistant a few decades ago, and as of 2012 artemisinin-resistant Plasmodium falciparum has emerged in western Cambodia and western Thailand.
"Toxoplasma gondii" can also become resistant to artemisinin, as well as atovaquone and sulfadiazine, but is not usually MDR
Antihelminthic resistance is mainly reported in the veterinary literature, for example in connection with the practice of livestock drenching and has been recent focus of FDA regulation.
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.
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 studies have reported associations between pathogen load in an area and human behavior. Higher pathogen load is associated with decreased size of ethnic and religious groups in an area. This may be due high pathogen load favoring avoidance of other groups, which may reduce pathogen transmission, or a high pathogen load preventing the creation of large settlements and armies that enforce a common culture. Higher pathogen load is also associated with more restricted sexual behavior, which may reduce pathogen transmission. It also associated with higher preferences for health and attractiveness in mates. Higher fertility rates and shorter or less parental care per child is another association that may be a compensation for the higher mortality rate. There is also an association with polygyny which may be due to higher pathogen load, making selecting males with a high genetic resistance increasingly important. Higher pathogen load is also associated with more collectivism and less individualism, which may limit contacts with outside groups and infections. There are alternative explanations for at least some of the associations although some of these explanations may in turn ultimately be due to pathogen load. Thus, polygny may also be due to a lower male:female ratio in these areas but this may ultimately be due to male infants having increased mortality from infectious diseases. Another example is that poor socioeconomic factors may ultimately in part be due to high pathogen load preventing economic development.
For infecting organisms to survive and repeat 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:
- Droplet contact, also known as the "respiratory route", and the resultant infection can be termed airborne disease. If an infected person coughs or sneezes on another person the microorganisms, suspended in warm, moist droplets, may enter the body through the nose, mouth or eye surfaces.
- Fecal-oral transmission, wherein foodstuffs or water become contaminated (by people not washing their hands before preparing food, or untreated sewage being released into a drinking water supply) and the people who eat and drink them become infected. Common fecal-oral transmitted pathogens include "Vibrio cholerae", "Giardia" species, rotaviruses, "Entameba histolytica", "Escherichia coli", and tape worms. Most of these pathogens cause gastroenteritis.
- Sexual transmission, with the resulting disease being called sexually transmitted disease
- Oral transmission, Diseases that are transmitted primarily by oral means may be caught through direct oral contact such as kissing, or by indirect contact such as by sharing a drinking glass or a cigarette.
- Transmission by direct contact, Some diseases that are transmissible by direct contact include athlete's foot, impetigo and warts
- Vehicle Transmission, transmission by an inanimate reservoir (food, water, soil).
- Vertical transmission, directly from the mother to an embryo, fetus or baby during pregnancy or childbirth. It can occur when the mother gets an infection as an intercurrent disease in pregnancy.
- Iatrogenic transmission, due to medical procedures such as injection or transplantation of infected material.
- Vector-borne transmission, transmitted by a vector, which is an organism that does not cause disease itself but that transmits infection by conveying pathogens from one host to another.
The relationship between "virulence versus transmissibility" is complex; if a disease is rapidly fatal, the host may die before the microbe can be passed along to another host.
"TB Bacteria Are Spread Only from a Person with Active TB Disease ... In people who develop active TB of the lungs, also called pulmonary TB, the TB skin test will often be positive. In addition, they will show all the signs and symptoms of TB disease, and can pass the bacteria to others. So, if a person with TB of the lungs sneezes, coughs, talks, sings, or does anything that forces the bacteria into the air, other people nearby may breathe in TB bacteria. Statistics show that approximately one-third of people exposed to pulmonary TB become infected with the bacteria, but only one in ten of these infected people develop active TB disease during their lifetimes."
However, exposure to tuberculosis is very unlikely to happen when one is exposed for a few minutes in a store or in a few minutes social contact. "It usually takes prolonged exposure to someone with active TB disease for someone to become infected.
After exposure, it usually takes 8 to 10 weeks before the TB test would show if someone had become infected." "Depending on ventilation and other factors, these tiny droplets [from the person who has active tuberculosis] can remain suspended in the air for several hours. Should another person inhale them, he or she may become infected with TB. The probability of transmission will be related to the infectiousness of the person with TB, the environment where the exposure occurred, the duration of the exposure, and the susceptibility of the host." In fact, "it isn't easy to catch TB. You need consistent exposure to the contagious person for a long time. For that reason, you're more likely to catch TB from a relative than a stranger."
If a person had latent tuberculosis, they do not have active/contagious tuberculosis. Once exposed, people very often have latent tuberculosis. To convert to active tuberculosis, the bacteria must become active.
People have medical privacy or "confidentiality" and do not have to reveal their active tuberculosis case to family, friends, or co-workers; therefore, the person who gets latent tuberculosis may never know who had the active case of tuberculosis that caused the latent tuberculosis diagnosis for them. Only by required testing (required in some jobs)
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.
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.
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.