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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 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.
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.
HIV is transmitted by three main routes: sexual contact, significant exposure to infected body fluids or tissues, and from mother to child during pregnancy, delivery, or breastfeeding (known as vertical transmission). There is no risk of acquiring HIV if exposed to feces, nasal secretions, saliva, sputum, sweat, tears, urine, or vomit unless these are contaminated with blood. It is possible to be co-infected by more than one strain of HIV—a condition known as HIV superinfection.
Estimates of the rate of HCV vertical transmission range from 2–8%; a 2014 systematic review and meta-analysis found the risk to be 5.8% in HCV-positive, HIV-negative women. The same study found the risk of vertical transmission to be 10.8% in HCV-positive, HIV-positive women. Other studies have found the risk of vertical transmission to be as high as 44% among HIV-positive women. The risk of vertical transmission is higher when the virus is detectable in the mother's blood.
Evidence does not indicate that mode of delivery (i.e. vaginal vs. cesarean) has an effect on vertical transmission.
For women who are HCV-positive and HIV-negative, breastfeeding is safe; however, CDC guidelines suggest avoiding breastfeeding if a woman's nipples are "cracked or bleeding" to reduce the risk of transmission.
Many of these viruses are controlled through laboratory screening tests. These fall into three basic varieties: antibody tests, nucleic acid tests (NAT), and surrogate tests. Antibody tests look for the immune system's response to the infection. Nucleic acid tests look for the genetic material of the virus itself. The third variety are tests that are not specific to the disease but look for other related conditions.
High risk activities for transfusion transmitted infections vary, and the amount of caution used for screening donors varies based on how dangerous the disease is. Most of the viral diseases are spread by either sexual contact or by contact with blood, usually either drug use, accidental needle injuries among health care workers, unsterilized tattoo and body piercing equipment, or through a blood transfusion or transplant. Other vectors exist.
Whether a donor is considered to be at "too high" of a risk for a disease to be allowed to donate is sometimes controversial, especially for sexual contact. High risk sexual activity is defined in many different ways, but usually includes:
- Sex in exchange for money or drugs.
- Men who have sex with men, the most controversial criterion.
- A recent history of sexually transmitted disease.
- Sex with a person who has had a positive test or was at high risk for a disease that can be spread in blood transfusions.
HIV can be transmitted from mother to child during pregnancy, during delivery, or through breast milk, resulting in the baby also contracting HIV. This is the third most common way in which HIV is transmitted globally. In the absence of treatment, the risk of transmission before or during birth is around 20% and in those who also breastfeed 35%. As of 2008, vertical transmission accounted for about 90% of cases of HIV in children. With appropriate treatment the risk of mother-to-child infection can be reduced to about 1%. Preventive treatment involves the mother taking antiretrovirals during pregnancy and delivery, an elective caesarean section, avoiding breastfeeding, and administering antiretroviral drugs to the newborn. Antiretrovirals when taken by either the mother or the infant decrease the risk of transmission in those who do breastfeed. However, many of these measures are not available in the developing world. If blood contaminates food during pre-chewing it may pose a risk of transmission.
If a woman is untreated, two years of breastfeeding results in an HIV/AIDS risk in her baby of about 17%. Treatment decreases this risk to 1 to 2% per year. Due to the increased risk of death without breastfeeding in many areas in the developing world, the World Health Organization recommends either: (1) the mother and baby being treated with antiretroviral medication while breastfeeding being continued (2) the provision of safe formula. Infection with HIV during pregnancy is also associated with miscarriage.
Persons infected with HIV have a particularly high burden of HIV-HCV co-infection. In a recent study by the WHO, the likelihood of being infected with hepatitis C virus was six times greater in individuals who also had HIV. The prevalence of HIV-HCV co-infection worldwide was estimated to be 6.2% representing more than 2.2 million people. Intravenous drug use was an independent risk factor for HCV infection. In the WHO study, the prevalence of HIV-HCV co-infection was markedly higher at 82.4% in those who injected drugs compared to the general population (2.4%). In a study of HIV-HCV co-infection among HIV positive men who have sex with men (MSM), the overall prevalence of anti-hepatitis C antibodies was estimated to be 8.1% and increased to 40% among HIV positive MSM who also injected drugs.
Babies can also become infected by their mothers during birth. Some infectious agents may be transmitted to the embryo or fetus in the uterus, while passing through the birth canal, or even shortly after birth. The distinction is important because when transmission is primarily during or after birth, medical intervention can help prevent infections in the infant.
During birth, babies are exposed to maternal blood, body fluids, and to the maternal genital tract without the placental barrier intervening. Because of this, blood-borne microorganisms (hepatitis B, HIV), organisms associated with sexually transmitted disease (e.g., "Neisseria gonorrhoeae" and "Chlamydia trachomatis"), and normal fauna of the genitourinary tract (e.g., "Candida albicans") are among those commonly seen in infection of newborns.
HIV/AIDS may be vertically transmitted from a mother to her child. This means the infection may be spread during pregnancy, labor, delivery, or breastfeeding. 70% of transmissions are believed to occur during delivery when the baby comes into direct contact with the mother's infected blood or genital secretions/fluid in the birth canal. 30% of infections occur in utero during the pregnancy with 66% occurring within the last 14 days of a pregnancy. The mechanism for in utero infection is not well understood, but the current belief is that infected maternal secretions may cross the placenta during the pregnancy.
The risk of HIV transmission from a mother to child is most directly related to the plasma viral load of the mother. Untreated mothers with a viral load >100,000 copies/ml have a transmission risk of over 50%. For women with a viral load < 1000 copies/ml, the risk of transmission is less than 1%. In general, the lower the viral load the lower the risk of transmission. For this reason, ART is recommended throughout the pregnancy so that viral load levels remain as low as possible and the risk of transmission is reduced.
Women with an established diagnosis of HIV often begin ART before becoming pregnant to treat the infection. It is recommended that all pregnant women begin ART regardless of CD4 counts or viral load to reduce the risk of transmission. The earlier ART is initiated, the more likely the viral load is to be suppressed by the time of delivery. Some women are concerned about using ART early in the pregnancy as babies are most susceptible to drug toxicities during the first trimester. However, delay in ART initiation may prove less effective in reducing infection transmission.
Antiretroviral therapy is used at the following times in pregnancy to reduce the risk of mother-to-child transmission of HIV:
- During pregnancy: pregnant women infected with HIV receive an oral regimen of at least three different anti-HIV medications.
- During labor and delivery: pregnant women infected with HIV and already on triple ART are recommended to continue to their oral regimen. If their viral load is >1,000 copies or there is question about whether medications have been taken consistently, then intravenous zidovudine (AZT) is added at the time of delivery. Pregnant women who have not been on ART prior to delivery should also be given intravenous zidovudine (AZT).
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.
Many viral infections of the central nervous system occur in seasonal peaks or as epidemics, whereas others, such as herpes simplex encephalitis, are sporadic. In endemic areas it is mostly a disease of children, but as the disease spreads to new regions, or nonimmune travelers visit endemic regions, nonimmune adults are also affected.
In couples where the male and female are both HIV positive, conception may occur normally without concern for disease transmission. However, in couples where only one partner is HIV positive, there is risk of transmitting the infection to the uninfected partner. These couples, known as serodiscordant couples, are advised not to engage in unprotected intercourse. Instead, assisted reproductive methods are recommended. In all serodiscordant couples, the infected partner is advised to begin ART so that levels of the infection are undetectable prior to attempting conception.
In couples where the woman is HIV negative and the man is HIV positive, sperm is collected from the male partner using a technique called sperm washing. This process is then followed by intrauterine insemination (IUI) or in vitro fertilization (IVF). Couples may also use donor sperm from a non-infected male if desired.
In couples where the woman is HIV positive and the man is HIV negative, artificial insemination is recommended.
In areas where assisted reproductive techniques such as IUI or IVF are not available, techniques to reduce the transmission of HIV during conception can be attempted to reduce, but not eliminate, the risks. Most importantly, the HPTN 052 trial showed that when HIV infected partners were on ART there was 96% less transmission of HIV and none from partners with undetectable viral loads.
Many serodiscordant couples use pre-exposure prophylaxis (PrEP) to limit transmission of the infection to the uninfected partner. Daily use of PrEP has been shown to decrease transmission of the infection by an average of 63-75%. However, use of PrEP during pregnancy has not yet been studied and its long-term effects are unknown and should not be the only safety feature in the prevention process.
Although assisted reproductive techniques are available for serodiscordant couples, there are still limitations to achieving a successful pregnancy. Women with HIV have been shown to have decreased fertility which can affect available reproductive options. Women with HIV are also more likely to be infected with other sexually transmitted diseases, placing them at higher risk for infertility. Males with HIV appear to have decreased semen volume and sperm motility which decreases their fertility. Antiretroviral drugs may also affect both male and female fertility and some drugs can be toxic to newly developed embryos. Additionally, there have been cases where an HIV-negative partner was infected with the disease despite using processed artificial insemination.
The embryo and fetus have little or no immune function. They depend on the immune function of their mother. Several pathogens can cross the placenta and cause (perinatal) infection. Often, microorganisms that produce minor illness in the mother are very dangerous for the developing embryo or fetus. This can result in spontaneous abortion or major developmental disorders. For many infections, the baby is more at risk at particular stages of pregnancy. Problems related to perinatal infection are not always directly noticeable.
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.
Meningitis is a very common in children. Newborns can develop herpes virus infections through contact with infected secretions in the birth canal. Other viral infections are acquired by breathing air contaminated with virus-containing droplets exhaled by an infected person. Arbovirus infections are acquired from bites by infected insects (called epidemic encephalitis). Viral central nervous system infections in newborns and infants usually begin with fever. The inability of infants to communicate directly makes it difficult to understand their symptoms. Newborns may have no other symptoms and may initially not otherwise appear ill. Infants older than a month or so typically become irritable and fussy and refuse to eat. Vomiting is common. Sometimes the soft spot on top of a newborn's head (fontanelle) bulges, indicating an increase in pressure on the brain. Because irritation of the meninges is worsened by movement, an infant with meningitis may cry more, rather than calm down, when picked up and rocked. Some infants develop a strange, high-pitched cry. Infants with encephalitis often have seizures or other abnormal movements. Infants with severe encephalitis may become lethargic and comatose and then die. To make the diagnosis of meningitis or the diagnosis of encephalitis, doctors do a spinal tap (lumbar puncture) to obtain cerebrospinal fluid (CSF) for laboratory analysis in children.
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.
The virus that causes AIDS is the best known of the transfusion-transmitted infections because of high-profile cases such as Ryan White, a haemophiliac who was infected through factor VIII, a blood-derived medicine used to treat the disease. Another person who died of medically acquired HIV/AIDS was Damon Courtenay, who died in 1991 due to a bad batch of factor VIII.
The standard test for HIV is an enzyme immunoassay test that reacts with antibodies to the virus. This test has a window period where a person will be infected but not yet have an immune response. Other tests are used to look for donors during this period, specifically the p24 antigen test and nucleic acid testing.
In addition to the general risk criteria for viruses, blood donors are sometimes excluded if they have lived in certain parts of Africa where subtypes of HIV that are not reliably detected on some tests are found, specifically HIV group O. People who have been in prison for extended periods are also excluded for HIV risk.
HIV infection rates in central Africa are generally moderate to high.
The duration of the visible blistering caused by varicella zoster virus varies in children usually from 4 to 7 days, and the appearance of new blisters begins to subside after the fifth day. Chickenpox infection is milder in young children, and symptomatic treatment, with sodium bicarbonate baths or antihistamine medication may ease itching. It is recommended to keep new infants from birth up to age 6 months away from an infected person for 10 to 21 days because their immune systems are not developed enough to handle the stress it can bring on. Paracetamol (acetaminophen) is widely used to reduce fever. Aspirin, or products containing aspirin, should not be given to children with chickenpox, as it can cause Reye's Syndrome.
In adults, the disease is more severe, though the incidence is much less common. Infection in adults is associated with greater morbidity and mortality due to pneumonia (either direct viral pneumonia or secondary bacterial pneumonia), bronchitis (either viral bronchitis or secondary bacterial bronchitis), hepatitis, and encephalitis. In particular, up to 10% of pregnant women with chickenpox develop pneumonia, the severity of which increases with onset later in gestation. In England and Wales, 75% of deaths due to chickenpox are in adults. Inflammation of the brain, or encephalitis, can occur in immunocompromised individuals, although the risk is higher with herpes zoster. Necrotizing fasciitis is also a rare complication.
Varicella can be lethal to adults with impaired immunity. The number of people in this high-risk group has increased, due to the HIV epidemic and the increased use of immunosuppressive therapies. Varicella is a particular problem in hospitals, when there are patients with immune systems weakened by drugs (e.g., high-dose steroids) or HIV.
Secondary bacterial infection of skin lesions, manifesting as impetigo, cellulitis, and erysipelas, is the most common complication in healthy children. Disseminated primary varicella infection usually seen in the immunocompromised may have high morbidity. Ninety percent of cases of varicella pneumonia occur in the adult population. Rarer complications of disseminated chickenpox include myocarditis, hepatitis, and glomerulonephritis.
Hemorrhagic complications are more common in the immunocompromised or immunosuppressed populations, although healthy children and adults have been affected. Five major clinical syndromes have been described: febrile purpura, malignant chickenpox with purpura, postinfectious purpura, purpura fulminans, and anaphylactoid purpura. These syndromes have variable courses, with febrile purpura being the most benign of the syndromes and having an uncomplicated outcome. In contrast, malignant chickenpox with purpura is a grave clinical condition that has a mortality rate of greater than 70%. The cause of these hemorrhagic chickenpox syndromes is not known.
HIV infection rates in eastern Africa are generally moderate to high.
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.
Specific age groups, persons who participate in risky sexual behavior, or those have certain health conditions may require screening. The CDC recommends that sexually active women under the age of 25 and those over 25 at risk should be screened for chlamydia and gonorrhea yearly. Appropriate times for screening are during regular pelvic examinations and preconception evaluations. Nucleic acid amplification tests are the recommended method of diagnosis for gonorrhea and chlamydia. This can be done on either urine in both men and women, vaginal or cervical swabs in women, or urethral swabs in men. Screening can be performed:
- to assess the presence of infection and prevent tubal infertility in women
- during the initial evaluation before infertility treatment
- to identify HIV infection
- for men who have sex with men
- for those who may have been exposed to hepatitis C
- for HCV
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.
Any age may be affected although it is most common in children aged five to fifteen years. By the time adulthood is reached about half the population will have become immune following infection at some time in their past. Outbreaks can arise especially in nursery schools, preschools, and elementary schools. Infection is an occupational risk for school and day-care personnel. There is no vaccine available for human parvovirus B19, though attempts have been made to develop one.
Breastfeeding with HIV guidelines established by the WHO suggest that HIV-infected mothers (particularly those in resource-poor countries) practice exclusive breastfeeding only, rather than mixed breastfeeding practices that involve other dietary supplements or fluids. Many studies have revealed the high benefit of exclusive breastfeeding to both mother and child, documenting that exclusive breastfeeding for a period of 6 months significantly reduces transmission, provides the infant with a greater chance of survival in the first year of life, and helps the mother to recover from the negative health effects of birth much more quickly.
Despite these positive indicators, other studies have determined that bottle-fed babies of HIV-infected mothers approximately has a 19 percent chance of becoming infected, in comparison to breastfed babies who had an approximate 49 percent chance of infection. Such a variance in findings makes it difficult to institute a proper set of guidelines for HIV-infected women in third-world or developing countries, where alternative forms of feeding are not always acceptable, feasible, affordable, sustainable, and safe (AFASS). Thus after much research, the benefits and/or consequences of breastfeeding with HIV are still currently under debate.