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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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Recommendations for pregnant women with regard to CMV infection:
- Throughout the pregnancy, practice good personal hygiene, especially handwashing with soap and water, after contact with diapers or oral secretions (particularly with a child who is in day care). Sharing of food, eating and drinking utensils, and contact with toddlers' saliva should be avoided.
- Women who develop a mononucleosis-like illness during pregnancy should be evaluated for CMV infection and counseled about the possible risks to the unborn child.
- Laboratory testing for antibody to CMV can be performed to determine if a woman has already had CMV infection.
- Recovery of CMV from the cervix or urine of women at or before the time of delivery does not warrant a cesarean section.
- The demonstrated benefits of breast-feeding outweigh the minimal risk of acquiring CMV from the breast-feeding mother.
- There is no need to either screen for CMV or exclude CMV-excreting children from schools or institutions because the virus is frequently found in many healthy children and adults.
Treatment with hyperimmune globulin in mothers with primary CMV infection has been shown to be effective in preventing congenital disease in several studies. One study did not show significant decrease in the risk of congenital cytomegalovirus infection.
Most healthy people working with infants and children face no special risk from CMV infection. However, for women of child-bearing age who previously have not been infected with CMV, there is a potential risk to the developing unborn child (the risk is described above in the Pregnancy section). Contact with children who are in day care, where CMV infection is commonly transmitted among young children (particularly toddlers), may be a source of exposure to CMV. Since CMV is transmitted through contact with infected body fluids, including urine and saliva, child care providers (meaning day care workers, special education teachers, as well as mothers) should be educated about the risks of CMV infection and the precautions they can take. Day care workers appear to be at a greater risk than hospital and other health care providers, and this may be due in part to the increased emphasis on personal hygiene in the health care setting.
Recommendations for individuals providing care for infants and children:
- Employees should be educated concerning CMV, its transmission, and hygienic practices, such as handwashing, which minimize the risk of infection.
- Susceptible nonpregnant women working with infants and children should not routinely be transferred to other work situations.
- Pregnant women working with infants and children should be informed of the risk of acquiring CMV infection and the possible effects on the unborn child.
- Routine laboratory testing for CMV antibody in female workers is not specifically recommended due to its high occurrence, but can be performed to determine their immune status.
Sixty percent of mothers of preterm infants are infected with cytomegalovirus (CMV). Infection is asymptomatic in most instances but 9% to 12% of postnatally infected low birth weight, preterm infants have severe, sepsis-like infection. CMV infection duration can be long and result in pneumonitis in association with fibrosis. CMV infection in infants has an unexpected effect on the white blood cells of the immune system causing them to prematurely age. This leads to a reduced immune response similar to that found in the elderly.
Human immunodeficiency virus type I (HIV) infection can occur during labor and delivery, in utero through mother-to-child transmission or postnatally by way of breastfeeding. Transmission can occur during pregnancy, delivery or breastfeeding. Most transmission occurs during delivery. In women with low detectable levels of the virus, the incidence of transmission is lower. Transmission risk can be reduced by:
- providing antiretroviral therapy during pregnancy and immediately after birth
- delivery by caesarean section
- not breastfeeding
- antiretroviral prophylaxis in infants born to mothers with HIV.
A low number of women whose HIV status are unknown until after the birth, do not benefit from interventions that could help lower the risk of mother-to-child HIV transmission.
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).
Pregnant women with HIV may still receive the trivalent inactivated influenza vaccine and the tetanus, diphtheria, and pertussis (Tdap) vaccination during pregnancy.
Many patients who are HIV positive also have other health conditions known as comorbidities. Hepatitis B, hepatitis C, tuberculosis and injection drug use are some of the most common comorbidities associated with HIV. Women who screen positive for HIV should also be tested for these conditions so that they may be adequately treated or controlled during the pregnancy. The comorbidities may have serious adverse effects on the mother and child during pregnancy, so it is extremely important to identify them early during the pregnancy.
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.
The cause of immunodeficiency varies depending on the nature of the disorder. The cause can be either genetic or acquired by malnutrition and poor sanitary conditions. Only for some genetic causes, the exact genes are known. Although there is no true discrimination to who this disease affects, the genes are passed from mother to child, and on occasion from father to child. Women tend not to show symptoms due to their second X chromosome not having the mutation while man are symptomatic, due to having one X chromosome.
Secondary immunodeficiencies, also known as acquired immunodeficiencies, can result from various immunosuppressive agents, for example, malnutrition, aging, particular medications (e.g., chemotherapy, disease-modifying antirheumatic drugs, immunosuppressive drugs after organ transplants, glucocorticoids) and environmental toxins like mercury and other heavy metals, pesticides and petrochemicals like styrene, dichlorobenzene, xylene, and ethylphenol. For medications, the term "immunosuppression" generally refers to both beneficial and potential adverse effects of decreasing the function of the immune system, while the term "immunodeficiency" generally refers solely to the adverse effect of increased risk for infection.
Many specific diseases directly or indirectly cause immunosuppression. This includes many types of cancer, particularly those of the bone marrow and blood cells (leukemia, lymphoma, multiple myeloma), and certain chronic infections. Immunodeficiency is also the hallmark of acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV). HIV directly infects a small number of T helper cells, and also impairs other immune system responses indirectly.
Various hormonal and metabolic disorders can also result in immune deficiency including anemia, hypothyroidism, diabetes and hypoglycemia.
Smoking, alcoholism and drug abuse also depress immune response.
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.
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.
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 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.
Being pregnant decreases the risk of relapse in multiple sclerosis; however, during the first months after delivery the risk increases. Overall, pregnancy does not seem to influence long-term disability. Multiple sclerosis does not increase the risk of congenital abnormality or miscarriage.
In an effort to further refine the United Nations guideline for optimal infant feeding options for HIV-infected mothers, the World Health Organization (WHO) held a three-day convention in Geneva in 2006 to review new evidence that had been established since they last established a guideline in 2000. Participants included UN agencies, representative from nongovernmental organizations, researchers, infant feeding experts, and WHO headquarters departments. The convention concluded with the following recommendations: If replacement feeding is acceptable, feasible, affordable and safe, HIV-infected mothers are recommended to use replacement feeding. Otherwise, exclusive breastfeeding is recommended. At six months, if replacement feeding is still not available, HIV-infected mothers are encouraged to slowly introduce food while continuing breastfeeding. Those with HIV-infected infants are recommended to continue breastfeeding even after 6 months.
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.
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.
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.
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 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 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.
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.
Hypercoagulability in pregnancy is the propensity of pregnant women to develop thrombosis (blood clots). Pregnancy itself is a factor of hypercoagulability (pregnancy-induced hypercoagulability), as a physiologically adaptive mechanism to prevent "post partum" bleeding. However, when combined with an additional underlying hypercoagulable states, the risk of thrombosis or embolism may become substantial.