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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
The initial period following the contraction of HIV is called acute HIV, primary HIV or acute retroviral syndrome. Many individuals develop an influenza-like illness or a mononucleosis-like illness 2–4 weeks post exposure while others have no significant symptoms. Symptoms occur in 40–90% of cases and most commonly include fever, large tender lymph nodes, throat inflammation, a rash, headache, and/or sores of the mouth and genitals. The rash, which occurs in 20–50% of cases, presents itself on the trunk and is maculopapular, classically. Some people also develop opportunistic infections at this stage. Gastrointestinal symptoms, such as vomiting or diarrhea may occur. Neurological symptoms of peripheral neuropathy or Guillain–Barré syndrome also occurs. The duration of the symptoms varies, but is usually one or two weeks.
Due to their nonspecific character, these symptoms are not often recognized as signs of HIV infection. Even cases that do get seen by a family doctor or a hospital are often misdiagnosed as one of the many common infectious diseases with overlapping symptoms. Thus, it is recommended that HIV be considered in people presenting an unexplained fever who may have risk factors for the infection.
There are three main stages of HIV infection: acute infection, clinical latency and AIDS.
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.
A small proportion of humans show partial or apparently complete inborn resistance to HIV, the virus that causes AIDS. The main mechanism is a mutation of the gene encoding CCR5, which acts as a co-receptor for HIV. It is estimated that the proportion of people with some form of resistance to HIV is under 1%.
HIV superinfection (also called HIV reinfection) is a condition in which a person with an established human immunodeficiency virus infection acquires a second strain of HIV, often of a different subtype. The HIV superinfection strain (a recombinant strain) appears when a person becomes simultaneously infected by two different strains, allowing the two viruses to exchange genetic material, resulting in a new unique strain that can possess the resistances of both previous strains. This new strain co-exists with the two prior strains and may cause more rapid disease progression or carry multiple resistances to certain HIV medications.
People with HIV risk superinfection by the same actions that would place a non-infected person at risk of acquiring HIV. These include sharing needles and forgoing condoms with HIV-positive sexual partners. For many years superinfection was thought to occur mainly in high-risk populations. Research from Uganda published in 2012 indicates that HIV superinfection among HIV-infected individuals within a general population remains unknown. Further research from "The Journal of Infectious Diseases" indicates that there have been 16 documented cases of superinfection since 2002.
In 1994, Stephen Crohn became the first person discovered to be completely resistant to HIV in all tests performed. In early 2000, researchers discovered a small group of sex workers in Nairobi, Kenya who were estimated to have sexual contact with 60 to 70 HIV positive clients a year without signs of infection. Researchers from Public Health Agency of Canada have identified 15 proteins unique to those virus-free sex workers. Later, however some sex workers were discovered to have contracted the virus, leading Oxford University researcher Sarah Rowland-Jones to believe continual exposure is a requirement for maintaining immunity.
HIV drug resistance occurs when microevolution causes virions to become tolerant to antiretroviral treatments.
AIDS-related complex, or ARC, was introduced after discovery of the HIV (Human Immunodeficiency Virus) when the medical community became aware of the inherent difficulties associated with treating patients suffering from an advanced case of HIV which gave rise to the term Acquired Immune Deficiency Syndrome (AIDS). The necessity for doctors to quickly and accurately understand the special needs of unknown patients suffering from AIDS in an emergency room situation was addressed with the creation of the term ARC.
ARC is "A prodromal phase of infection with the human immunodeficiency virus (HIV). Laboratory criteria separating AIDS-related complex ( ARC) from AIDS include elevated or hyperactive B-cell humoral immune responses, compared to depressed or normal antibody reactivity in AIDS; follicular or mixed hyperplasia in ARC lymph nodes, leading to lymphocyte degeneration and depletion more typical of AIDS; evolving succession of histopathological lesions such as localization of Kaposi's sarcoma, signaling the transition to the full-blown AIDS."
Clinical use of this term was widely discontinued by the year 2000 in the United States after having been replaced by modern laboratory criteria.
Long-term nonprogressors (LTNPs), sometimes also called "elite controllers", are individuals infected with HIV, who maintain a CD4 count greater than 500 without antiretroviral therapy with a detectable viral load. Many of these patients have been HIV positive for 30 years without progressing to the point of needing to take medication in order not to develop AIDS. They have been the subject of a great deal of research, since an understanding of their ability to control HIV infection may lead to the development of immune therapies or a therapeutic vaccine. The classification "Long-term non-progressor" is not permanent, because some patients in this category have gone on to develop AIDS.
Long-term nonprogressors typically have viral loads under 10,000 copies RNA/ml blood, do not take antiretrovirals, and have CD4+ counts within the normal range. Most people with HIV not on medication have viral loads which are much higher.
It is estimated that around 1 in 300 people with HIV are long-term nonprogressors. Without the symptoms of AIDS, many LTNP patients may not know they are infected.
Genetic traits that confer greater resistance or more robust immune response to HIV are thought to explain why LTNP patients are able to live much longer with HIV than patients who are not LTNP. Some LTNP are infected with a weakened or inactive form of HIV, but it is now known that many LTNP patients carry a fully virulent form of the virus. Genetic traits that may affect progression include:
- Gene mutation. A mutation in the FUT2 gene affects the progression of HIV-1 infection. 20% of Europeans who have that mutation are called "non secretor" because of their absence of a certain type of antigen that also provides strong resistance against norovirus.
- Mitochondrial DNA. Different mitochondrial DNA haplotypes in humans may increase or decrease rates of AIDS progression. Haplotypes associated with more loosely coupled mitochondrial respiration, with reduced ATP and ROS generation, have been associated with faster progression and vice versa.
- Receptor mutations. A low percentage of long-term nonprogressors have been shown to have inherited mutations of the CCR5 receptor of T cell lymphocytes. HIV uses CCR5 to enter these cells. It is believed that the Δ32 (delta 32) variant of CCR5 impairs HIV ability to infect cells and cause disease. An understanding of this mechanism led to the development of a class of HIV medicines, the entry inhibitors. The presence of this mutation, however, is not a unifying theme among LTNPs and is observed in an exceedingly small number of these patients.
- HLA type has also been correlated with long-term non-progressor cohorts. In particular, strong correlations have been found between possessing the class 1 HLA-B*5701, HLA-B*5703, and/or HLA-B*2705 alleles and ability to exert control over HIV.
- Antibody production. All individuals with HIV make antibodies against the virus. In most patients, broadly neutralizing antibodies do not emerge until approximately 2–4 years after the initial infection. At this point, the latent reservoir has already been established and the presence of broadly neutralizing antibodies is not enough to prevent disease progression. In some rare patients, these antibodies emerge earlier and can result in a delayed disease course. These patients, however, are not typically classified as LTNPs, but rather as slow progressors, who will eventually develop AIDS. Induction of broadly neutralizing antibodies in healthy individuals is a potential strategy for a preventive HIV vaccine, as is the elicitation of these antibodies through rationally designed immunogens. Direct production of these antibodies in somatic tissue through plasmid transfection also pose a viable method for making these antibodies available in a large number of humans.
- APOBEC3G protein production. In a small number of people infected with HIV, the virus is naturally suppressed without medical treatment. These people may carry high quantities of a protein called APOBEC3G that disrupts viral replication in cells. APOBEC3G, or "A3" for short, is a protein that sabotages reverse transcription, the process HIV relies on for its replication. This process involves the virus transcribing its singe-stranded RNA genome into double-stranded DNA that is incorporated into the cell's genome. A3 usually stops dormant viruses in the human genome, called endogenous retroviruses, from reawakening and causing infections.
A Transfusion transmitted infection (TTI) is a virus, parasite, or other potential pathogen that can be transmitted in donated blood through a transfusion to a recipient. The term is usually limited to known pathogens, but also sometimes includes agents such as Simian foamy virus which are not known to cause disease.
Preventing the spread of these diseases by blood transfusion is addressed in several ways. In many cases, the blood is tested for the pathogen, sometimes with several different methodologies. Donors of blood are also screened for signs and symptoms of disease and for activities that might put them at risk for infection. If a local supply is not safe, blood may be imported from other areas. Human immunodeficiency virus (HIV) leads to the best known of the transfusion transmitted diseases, acquired immune deficiency syndrome (AIDS).
Blood that is processed into medications by fractionation is treated in a multi-step process called pathogen inactivation that is analogous to pasteurization: it destroys most viruses and bacteria in the blood. Donors are still screened and tested.
HIV in pregnancy is the presence of the HIV virus in a woman while pregnant. There are concerns because women diagnosed with HIV/AIDS may transmit the infection to their child during pregnancy. The infection be transmitted to the infant during the pregnancy, childbirth, or breastfeeding. However, the risk of mother-to-child transmission of HIV may be reduced by the use of HIV medications known as antiretroviral therapy (ART). These medications may be used by women before, during, and after pregnancy. After delivery, children are also given the medication to reduce the risk of infection. Because HIV may be spread through breast milk, mothers with the infection are encouraged to avoid breastfeeding.
Infection with HIV/AIDS is not a contraindication to pregnancy. Women with the disease may choose to become pregnant if they desire, however, they are encouraged to talk with their doctors beforehand. Some women are unaware they have the disease until they become pregnant. In this case, they should begin antiretroviral therapy as soon as possible. With the appropriate treatment, the risk of mother-to-child infection can be reduced to below 1%. Without treatment, the risk of transmission is 15-45%.
There are approximately 1.4 million HIV positive women who become pregnant and contribute to more than 300,000 neonatal and fetal deaths each year. With the use of ART, transmission of HIV from the mother to child has decreased according to reports by the World Health Organization (WHO). In 2009, there were an estimated 400,000 children born with HIV and by 2013, there were 240,000. Countries in Southern Africa are worst affected by the HIV/AIDS pandemic. In 2010, 30% of all pregnancies in the region were affected by HIV. In 2011, HIV was responsible for 50% of the deaths for children below the age of 5. In the United States, fewer than 200 babies are born with HIV every year.
As of 2015, Cuba has become the first country in the world to eradicate mother-to-child transmission of HIV. In 2010, the WHO partnered with the Pan American Health Organization (PAHO) to implement an initiative that would provide early prenatal care and HIV testing for all pregnant women in the country. For women who tested positive, ART was provided for both the mother and child, cesarean sections were performed, and alternatives to breastfeeding were provided. In implementing these measures, the country was successfully able to eradicate HIV transmission during pregnancy.
Breastfeeding by HIV-infected mothers is the practice of breastfeeding of HIV-infected mothers and include those who may want to or are currently breastfeeding . HIV can be transmitted to the infant through breastfeeding. The risk of transmission varies and depends on the viral load in the mother's milk. A infant can be infected with HIV throughout the duration of the pregnancy or during childbirth (intrapartum).
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.
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.
AIDS dysmorphic syndrome, also called HIV embryopathy, is a cluster of facial malformations seen in children with perinatal HIV infection. Its status as a syndrome is disputed by the research community. Common symptoms of perinatal HIV infection include candidiasis, lymphocytic interstitial pneumonitis, hepatosplenomegaly, and lymphadenopathy.
The 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 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 a host.
Immune reconstitution inflammatory syndrome (IRIS) (also known as immune recovery syndrome) is a condition seen in some cases of AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the symptoms of infection worse.
In microbiology, coinfection is the simultaneous infection of a host by multiple pathogen species. In virology, coinfection includes simultaneous infection of a single cell by two or more virus particles. An example is the coinfection of liver cells with Hepatitis B virus and Hepatitis D virus, which can arise incrementally by initial infection followed by superinfection.
Global prevalence or incidence of coinfection among humans is unknown, but it is thought to be commonplace, sometimes more common than single infection. Coinfection with helminths affects around 800 million people worldwide.
Coinfection is of particular human health importance because pathogen species can interact within the host. The net effect of coinfection on human health is thought to be negative. Interactions can have either positive or negative effects on other parasites. Under positive parasite interactions, disease transmission and progression are enhanced and this is also known as syndemism. Negative parasite interactions include microbial interference when one bacterial species suppresses the virulence or colonisation of other bacteria, such as "Pseudomonas aeruginosa" suppressing pathogenic "Staphylococcus aureus" colony formation. The general patterns of ecological interactions between parasite species are unknown, even among common coinfections such as those between sexually transmitted infections. However, network analysis of a food web of coinfection in humans suggests that there is greater potential for interactions via shared food sources than via the immune system.
A globally common coinfection involves tuberculosis and HIV. In some countries, up to 80% of tuberculosis patients are also HIV-positive. The potential for dynamics of these two infectious diseases to be linked has been known for decades. Other common examples of coinfections are AIDS, which involves coinfection of end-stage HIV with opportunistic parasites and polymicrobial infections like Lyme disease with other diseases.
Characteristics of a viral infection can include pain, swelling, redness, impaired function, fever, drowsiness, confusion and convulsions.
The most common diseases caused by chronic viral infections are subacute-sclerosing panencephalitis, progressive multifocal leukoencephalopathy, retrovirus disease and spongiform encephalopathies.
It is unknown what aspects of the natural immune response to HIV may protect someone from superinfection, but it has been shown that cytotoxic lymphocyte responses do not seem to be protective. In addition, it has been demonstrated that superinfection can occur in individuals that demonstrate a robust anti-HIV antibody response. The anti-HIV antibody response broadens and strengthens in individuals post-superinfection.
Taken with the finding that super-infection is common and occurs within and between HIV subtypes it has been suggested that the immune response elicited by primary infection may confer limited protection and raises concerns that HIV-vaccine strategies designed to replicate the natural anti-HIV immune response may have limited effectiveness in preventing new infections. However at the same time, HIV-infected individuals at high risk for super-infection who do not become superinfected may also provide a very interesting avenue for new vaccine research.
Infection is the invasion of an organism's body tissues by disease-causing agents, their multiplication, and the reaction of host tissues to the infectious agents and the toxins they produce. Infectious disease, also known as transmissible disease or communicable disease, is illness resulting from an infection.
Infections are caused by infectious agents including viruses, viroids, prions, bacteria, nematodes such as parasitic roundworms and pinworms, arthropods such as ticks, mites, fleas, and lice, fungi such as ringworm, and other macroparasites such as tapeworms and other helminths.
Hosts can fight infections using their immune system. 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 is referred to as infectious disease.
Cryptococcosis, also known as cryptococcal disease, is a potentially fatal fungal disease. It is caused by one of two species; "Cryptococcus neoformans" and "Cryptococcus gattii". These were all previously thought to be subspecies of "C. neoformans" but have now been identified as distinct species.
Cryptococcosis is believed to be acquired by inhalation of the infectious propagule from the environment. Although the exact nature of the infectious propagule is unknown, the leading hypothesis is the basidiospore created through sexual or asexual reproduction.
Sexually transmitted infections (STI), also referred to as sexually transmitted diseases (STD) and venereal diseases (VD), are infections that are commonly spread by sex, especially vaginal intercourse, anal sex or oral sex. Many times STIs initially do not cause symptoms. This results in a greater risk of passing the disease on to others. Symptoms and signs of disease may include vaginal discharge, penile discharge, ulcers on or around the genitals, and pelvic pain. STIs can be transmitted to an infant before or during childbirth and may result in poor outcomes for the baby. Some STIs may cause problems with the ability to get pregnant.
More than 30 different bacteria, viruses, and parasites can be transmitted through sexual activity. Bacterial STIs include chlamydia, gonorrhea, and syphilis among others. Viral STIs include genital herpes, HIV/AIDS, and genital warts among others. Parasitic STIs include trichomoniasis among others. While usually spread by sex, some STIs can be spread by non-sexual contact with donor tissue, blood, breastfeeding, or during childbirth. STI diagnostic tests are usually easily available in the developed world, but this is often not the case in the developing world.
The most effective way of preventing STIs is by not having sex. Some vaccinations may also decrease the risk of certain infections including hepatitis B and some types of HPV. Safer sex practices such as use of condoms, having a smaller number of sexual partners, and being in a relationship where each person only has sex with the other also decreases the risk. Circumcision in males may be effective to prevent some infections. Most STIs are treatable or curable. Of the most common infections, syphilis, gonorrhea, chlamydia, trichomoniasis are curable, while herpes, hepatitis B, HIV/AIDS, and HPV are treatable but not curable. Resistance to certain antibiotics is developing among some organisms such as gonorrhea.
In 2015, about 1.1 billion people had STIs other than HIV/AIDS. About 500 million were infected with either syphilis, gonorrhea, chlamydia or trichomoniasis. At least an additional 530 million people have genital herpes and 290 million women have human papillomavirus. STIs other than HIV resulted in 108,000 deaths in 2015. In the United States there were 19 million new cases of sexually transmitted infections in 2010. Historical documentation of STIs date back to at least the Ebers papyrus around 1550 BC and the Old Testament. There is often shame and stigma associated with these infections. The term "sexually transmitted infection" is generally preferred over "sexually transmitted disease" or "venereal disease", as it includes those who do not have symptomatic disease.