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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 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.
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.
HIV infection rates in central Africa are generally moderate to high.
HIV infection rates in eastern Africa are generally moderate to high.
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.
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.
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
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).
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.
Researchers had hoped that nonoxynol-9, a vaginal microbicide would help decrease STI risk. Trials, however, have found it ineffective and it may put women at a higher risk of HIV infection.
More than 300 million people worldwide have asthma. The rate of asthma increases as countries become more urbanized and in many parts of the world those who develop asthma do not have access to medication and medical care. Within the United States, African Americans and Latinos are four times more likely to suffer from severe asthma than whites. The disease is closely tied to poverty and poor living conditions. Asthma is also prevalent in children in low income countries. Homes with roaches and mice, as well as mold and mildew put children at risk for developing asthma as well as exposure to cigarette smoke.
Unlike many other Western countries, the mortality rate for asthma has steadily risen in the United States over the last two decades. Mortality rates for African American children due to asthma are also far higher than that of other racial groups. For African Americans, the rate of visits to the emergency room is 330 percent higher than their white counterparts. The hospitalization rate is 220 percent higher and the death rate is 190 percent higher. Among Hispanics, Puerto Ricans are disporpotionatly affected by asthma with a disease rate that is 113 percent higher than non-Hispanic Whites and 50 percent higher than non-Hispanic Blacks. Studies have shown that asthma morbidity and mortality are concentrated in inner city neighborhoods characterized by poverty and large minority populations and this affects both genders at all ages. Asthma continues to have an adverse effects on the health of the poor and school attendance rates among poor children. 10.5 million days of school are missed each year due to asthma.
Though heart disease is not exclusive to the poor, there are aspects of a life of poverty that contribute to its development. This category includes coronary heart disease, stroke and heart attack. Heart disease is the leading cause of death worldwide and there are disparities of morbidity between the rich and poor. Studies from around the world link heart disease to poverty. Low neighborhood income and education were associated with higher risk factors. Poor diet, lack of exercise and limited (or no) access to a specialist were all factors related to poverty, though to contribute to heart disease.
Both low income and low education were predictors of coronary heart disease, a subset of cardiovascular disease. Of those admitted to hospital in the United States for heart failure, women and African Americans were more likely to reside in lower income neighborhoods. In the developing world, there is a 10 fold increase in cardiac events in the black and urban populations.
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.
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.
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.
The practice of breastfeeding for HIV positive mothers is a highly contested and controversial global public health concern. Programs for prevention of mother to child transmission (PMTCT) and other international guidelines offer preventative interventions to address mother to child transmission(MTCT) of HIV in Third World countries. PMTCT programs provide HIV-positive women with recommendations and services including antiretroviral therapy (ART), modifications in infant feeding practices (i.e., exclusive breastfeeding or exclusive replacement feeding), and counseling.
Although prevention of mother to child transmission (PMTCT) programs have been implemented across different regions, their success in resource-constrained settings is still widely debated upon. In 2008, the majority of sub-Saharan Africa as a whole had an estimate of 430,000 HIV infections among children under the age of 15. HIV-positive women's lack of participation and adherence to PMTCT services and infant feeding guidelines has made the success of these policies difficult, despite the knowledge and technology that has been dedicated to them. Many women fear knowing their HIV status. Generally speaking, HIV-positive mothers lack support, especially from males, thus resulting in their stigmatization and exclusion by members of the community. It is because of this that most women end up losing contact with development programs, which end soon after the mother delivers. The discontinuation of these programs makes a knowledge and understanding of different feeding options difficult for these mothers, because these programs are not there to present them with the necessary information.
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.
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.
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.
HIV develops resistance when it evades the effects of these treatments.
HIV drug resistance reduces the possible HIV medications a person can take due to cross resistance. In cross resistance, an entire medication class is considered ineffective in lowering a patient's HIV viral load because all the drugs in a given HIV class share the same mechanism of action. Therefore, development of resistance to one medication in a class precludes the use of all other medications in the same class. A blood test should be done to determine which drugs may be effective prior to initiation of treatment or during treatment to ensure resistance has not developed.
In 2004, one study estimated the percentage of the American HIV positive population with some form of drug resistance to be 76.3%. Certain intrinsic features of HIV facilitate its widespread resistance, most importantly its extremely high mutation rate.
In their 2017 HIV Drug Resistance Report, the World Health Organization conducted surveys in 14 countries to estimate the prevalence of resistance to HIV medications. One subgroup included only HIV-positive patients who have just initiated antiretroviral therapy in order to assess the prevalence of HIV drug resistance in treatment-naive patients, deemed "pretreatment drug resistance." Resistance to NNRTIs in this patient population ranged from 2.7% (in Myanmar) to 15.9% (in Uganda). Resistance to NRTIs ranged from 0.3% (in Namibia) to 6.8% (in Nicaragua). Resistance to protease inhibitors ranged from 0.3% (in Carmeroon and Myanmar) to 2.6% (in Mexico). Resistance to NNRTI + NRTI combination therapy ranged from 0.2% (in Myanmar) to 4.6% (in Uganda).
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.
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.
Exposure to antiretroviral treatments has led to the evolution of HIV in response to selection pressure that eliminates strains of HIV that do not express resistance mechanisms. Drug resistance occurs in all antiretroviral treatments if patients are non-adherent, meaning that they do not take their medication regimens as prescribed. Lack of adherence may result from unreliable access to the medication, due to prohibitive cost or inadequate supply.
Current medical and scientific opinion is mixed on the most effective treatment methods, but is focused on drug cocktails and the importance of first-line regimens . The World Health Organization advocates a public-health approach to HIV treatment in order to make treatment uniform and available to patients around the world. As of July 2017, the WHO is implementing the Global Action Plan on HIV drug resistance 2017-2021. It is a 5-year initiative intended to help countries around the world manage HIV drug resistance.
Among treatment methods, the World Health Organization acknowledges the importance of successful first-line treatments. First-line treatments are known to affect the virus’ future response to other treatments, making the effectiveness of first-line treatments an issue of vital importance. The most successful treatments are combinations of three drugs used simultaneously, as this greatly reduces the probability of the virus developing resistance.
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.