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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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Congenital disease occurs due to the acquisition of the organism by a pregnant woman exposed to tissue cysts or oocytes in uncooked meat or substances contaminated with cat feces. Spontaneous abortion may result if the disease is acquired during the first trimester.
Congenital toxoplasmosis may lead to hydrocephalus, seizures, lymphadenopathy, hepatosplenomegaly, rash, and fever. However, retinochoroiditis is the most common manifestation, occurring in 3/4 of cases.
In congenital toxoplasmosis, the disease is bilateral in 65–85% of cases and involves the macula in 58%.
Chronic or recurrent maternal infection during pregnancy is not thought to confer a risk of congenital toxoplasmosis because maternal immunity protects against fetal transmission. In contrast, pregnant women without serologic evidence of prior exposure to Toxoplasma should take sanitary precautions when cleaning up after cats and avoid undercooked meats.
"Toxoplasma" infection can be prevented in large part by:
- cooking meat to a safe temperature (i.e., one sufficient to kill "Toxoplasma")
- peeling or thoroughly washing fruits and vegetables before eating
- cleaning cooking surfaces and utensils after they have contacted raw meat, poultry, seafood, or unwashed fruits or vegetables
- pregnant women avoiding changing cat litter or, if no one else is available to change the cat litter, using gloves, then washing hands thoroughly
- not feeding raw or undercooked meat to cats to prevent acquisition of "Toxoplasma"
Prolonged and intense rainfall periods are significantly associated with the reactivation of toxoplasmic retinochoroiditis. Changes promoted by this climatic condition concern both the parasite survival in the soil as well as a putative effect on the host immune response due to other comorbidities.
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.
Congenital toxoplasmosis is a specific form of toxoplasmosis in which an unborn fetus is infected via the placenta. Congenital toxoplasmosis is associated with fetal death and abortion, and in infants, it is associated with neurologic deficits, neurocognitive deficits, and chorioretinitis. A positive antibody titer indicates previous exposure and immunity, and largely ensures the unborn fetus' safety. A simple blood draw at the first prenatal doctor visit can determine whether or not a woman has had previous exposure and therefore whether or not she is at risk. If a woman receives her first exposure to "T. gondii" while pregnant, the fetus is at particular risk.
Not much evidence exists around the effect of education before pregnancy to prevent congenital toxoplasmosis. However educating parents before the baby is born has been suggested to be effective because it may improve food, personal and pet hygiene. More research is needed to find whether antenatal education can reduce congenital toxoplasmosis.
For pregnant women with negative antibody titers, indicating no previous exposure to "T. gondii", serology testing as frequent as monthly is advisable as treatment during pregnancy for those women exposed to "T. gondii" for the first time dramatically decreases the risk of passing the parasite to the fetus. Since a baby's immune system does not develop fully for the first year of life, and the resilient cysts that form throughout the body are very difficult to eradicate with antiprotozoans, an infection can be very serious in the young.
Despite these risks, pregnant women are not routinely screened for toxoplasmosis in most countries, for reasons of cost-effectiveness and the high number of false positives generated; Portugal, France, Austria, Uruguay, and Italy are notable exceptions, and some regional screening programmes operate in Germany, Switzerland and Belgium. As invasive prenatal testing incurs some risk to the fetus (18.5 pregnancy losses per toxoplasmosis case prevented), postnatal or neonatal screening is preferred. The exceptions are cases where fetal abnormalities are noted, and thus screening can be targeted.
Pregnant women should avoid handling raw meat, drinking raw milk (especially goat milk) and be advised to not eat raw or undercooked meat regardless of type. Because of the obvious relationship between "Toxoplasma" and cats it is also often advised to avoid exposure to cat feces, and refrain from gardening (cat feces are common in garden soil) or at least wear gloves when so engaged. Most cats are not actively shedding oocysts, since they get infected in the first six months of their life, when they shed oocysts for a short period of time (1–2 weeks.) However, these oocysts get buried in the soil, sporulate and remain infectious for periods ranging from several months to more than a year. Numerous studies have shown living in a household with a cat is not a significant risk factor for "T. gondii" infection, though living with several kittens has some significance.
In 2006, a Czech research team discovered women with high levels of toxoplasmosis antibodies were significantly more likely to have baby boys than baby girls. In most populations, the birth rate is around 51% boys, but women infected with "T. gondii" had up to a 72% chance of a boy. In mice, the sex ratio was higher in early latent toxoplasmosis and lower in later latent toxoplasmosis.
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.
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.
When a pregnant woman is diagnosed with acute toxoplasmosis, amniocentesis can be used to determine whether the fetus has been infected or not. When a pregnant woman develops acute toxoplasmosis, the tachyzoites have approximately a 30% chance of entering the placental tissue, and from there entering and infecting the fetus. As gestational age at the time of infection increases, the chance of fetal infection also increases.
If the parasite has not yet reached the fetus, spiramycin can help to prevent placental transmission. If the fetus has been infected, the pregnant woman can be treated with pyrimethamine and sulfadiazine, with folinic acid, after the first trimester. They are treated after the first trimester because pyrimethamine has an antifolate effect, and lack of folic acid can interfere with fetal brain formation and cause thrombocytopaenia. Infection in earlier gestational stages correlates with poorer fetal and neonatal outcomes, particularly when the infection is untreated.
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.
Developing countries are more severely affected by TORCH syndrome.
TORCH syndrome can be prevented by treating an infected pregnant person, thereby preventing the infection from affecting the fetus.
Chorioretinitis is often caused by toxoplasmosis and cytomegalovirus infections (mostly seen in immunodeficient subjects such as people with HIV or on immunosuppressant drugs). Congenital toxoplasmosis via transplacental transmission can also lead to sequelae such as chorioretinitis along with hydrocephalus and cerebral calcifications. Other possible causes of chorioretinitis are syphilis, sarcoidosis, tuberculosis, Behcet's disease, onchocerciasis, or West Nile virus. Chorioretinitis may also occur in presumed ocular histoplasmosis syndrome (POHS); despite its name, the relationship of POHS to "Histoplasma" is controversial.
In contrast to visceral larva migrans, ocular toxocariasis usually develops in older children or young adults with no history of pica. These patients seldom have eosinophilia or visceral manifestations.
Chorioretinitis is usually treated with a combination of corticosteroids and antibiotics. However, if there is an underlying cause such as HIV, specific therapy can be started as well.
A 2012 Cochrane Review found weak evidence suggesting that ivermectin could result in reduced chorioretinal lesions in patients with onchocercal eye disease. More research is needed to support this finding.
The eye involvement can cause the following inflammatory disorders:
- endophthalmitis
- uveitis
- chorioretinitis
Pregnant women are more severely affected by influenza, hepatitis E, herpes simplex and malaria. The evidence is more limited for coccidioidomycosis, measles, smallpox, and varicella. Pregnancy may also increase susceptibility for toxoplasmosis.
During the 2009 H1N1 pandemic, as well as during interpandemic periods, women in the third trimester of pregnancy were at increased risk for severe
disease, such as disease requiring admission to an intensive care unit or resulting in death, as compared with women in an earlier stage of pregnancy.
For hepatitis E, the case fatality rate among pregnant women has been estimated to be between 15% and 25%, as compared with a range of 0.5 to 4% in the population overall, with the highest susceptibility in the third trimester.
Primary herpes simplex infection, when occurring in pregnant women, has an increased risk of dissemination and hepatitis, an otherwise rare complication in immunocompetent adults, particularly during the third trimester. Also, recurrences of herpes genitalis increase in
frequency during pregnancy.
The risk of severe malaria by "Plasmodium falciparum" is three times as high in pregnant women, with a median maternal mortality of 40% reported in studies in the Asia–Pacific region. In women where the pregnancy is not the first, malaria infection is more often asymptomatic, even at high parasite loads, compared to women having their first pregnancy. There is a decreasing susceptibility to malaria with increasing parity, probably due to immunity to pregnancy-specific antigens. Young maternal age and increases the risk. Studies differ whether the risk is different in different . Limited data suggest that malaria caused by "Plasmodium vivax" is also more severe during pregnancy.
Severe and disseminated coccidioidomycosis has been reported the occur in increased frequency in pregnant women in several reports and case series, but subsequent large surveys, with the overall risk being rather low.
Varicella occurs at an increased rate during pregnancy, but mortality is not higher than that among men and non-pregnant women.
Listeriosis mostly occurs during the third trimester, with Hispanic women appearing to be at particular risk. Listeriosis is a vertically transmitted infection that may cause miscarriage, stillbirth, preterm birth, or serious neonatal disease.
Some infections are vertically transmissible, meaning that they can affect the child as well.
Cytomegalic inclusion body disease (CIBD) is a series of signs and symptoms caused by cytomegalovirus infection, toxoplasmosis or other rare infections such as herpes or rubella viruses. It can produce massive calcification of the central nervous system, and often the kidneys.
Cytomegalic inclusion body disease is the most common cause of congenital abnormalities in the United States. It can also cause pneumonia and other diseases in immunocompromised patients, such as those with HIV/AIDS or recipients of organ transplants.
The immune reconstitution inflammatory syndrome (IRIS) has been described in those with normal immune function with meningitis caused by "C. gattii" and "C. grubii". Several weeks or even months into appropriate treatment, there can be deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms. IRIS is however much more common in those with poor immune function (≈25% vs. ≈8%).
Magnetic resonance imaging shows increase in the size of brain lesions, and CSF abnormalities (white cell count, protein, glucose) increase. Radiographic appearance of cryptococcal IRIS brain lesions can mimic that of toxoplasmosis with ring enhancing lesions on head computed tomography (CT). CSF culture is sterile, and there is no increase in CSF cryptococcal antigen titre.
The increasing inflammation can cause brain injury or be fatal.
The mechanism behind IRIS in cryptococcal meningitis is primarily immunologic. With reversal of immunosuppression, there is paradoxical increased inflammation as the recovering immune system recognises the fungus. In severe IRIS cases, treatment with systemic corticosteroids has been utilized - although evidence-based data are lacking.
DES (diethylstilbestrol) is a drug that mimics estrogen, a female hormone. From 1938 until 1971 doctors prescribed this drug to help some pregnant women who had had miscarriages or premature deliveries on the theory that miscarriages and premature births occurred because some pregnant women did not produce enough estrogen naturally to sustain the pregnancy for full term . An estimated 5-10 million pregnant women and the children born during this period were exposed to DES. Currently, DES is known to increase the risk of breast cancer, and cause a variety of birth-related adverse outcomes exposed female offsprings such as spontaneous abortion, second-trimester pregnancy loss, preterm delivery, stillbirth, neonatal death, sub/infertility and cancer of reproductive tissues . DES is an important developmental toxicant which links the fetal basis of adult disease.
Uveitis may be an immune response to fight an infection inside the eye. While representing the minority of patients with uveitis, such possible infections include:
- brucellosis
- leptospirosis
- Lyme disease
- presumed ocular histoplasmosis syndrome
- syphilis
- toxocariasis
- toxoplasmic chorioretinitis
- tuberculosis
- Zika fever
Cryptococcosis is a defining opportunistic infection for AIDS, and is the second-most-common AIDS-defining illness in Africa. Other conditions that pose an increased risk include certain lymphomas (e.g., Hodgkin's lymphoma), sarcoidosis, liver cirrhosis, and patients on long-term corticosteroid therapy.
Distribution is worldwide in soil. The prevalence of cryptococcosis has been increasing over the past 20 years for many reasons, including the increase in incidence of AIDS and the expanded use of immunosuppressive drugs.
In humans, "C. neoformans" causes three types of infections:
- Wound or cutaneous cryptococcosis
- Pulmonary cryptococcosis
- Cryptococcal meningitis.
Cryptococcal meningitis (infection of the meninges, the tissue covering the brain) is believed to result from dissemination of the fungus from either an observed or unappreciated pulmonary infection. Often there is also silent dissemination throughout the brain when meningitis is present. "Cryptococcus gattii" causes infections in immunocompetent people (fully functioning immune system), but "C. neoformans v. grubii", and "v. neoformans" usually only cause clinically evident infections in persons with some form of defect in their immune systems (immunocompromised persons). People with defects in their cell-mediated immunity, for example, people with AIDS, are especially susceptible to disseminated cryptococcosis. Cryptococcosis is often fatal, even if treated. It is estimated that the three-month case-fatality rate is 9% in high-income regions, 55% in low/middle-income regions, and 70% in sub-Saharan Africa. As of 2009 there were globally approximately 958,000 annual cases and 625,000 deaths within three months after infection.
Although the most common presentation of cryptococcosis is of "C. neoformans" infection in an immunocompromised person (such as persons living with AIDS), the "C. gattii" is being increasingly recognised as a pathogen in what is presumed to be immunocompetent hosts, especially in Canada and Australia. This may be due to rare exposure and high pathogenicity, or to unrecognised isolated defects in immunity, specific for this organism.
Uveitis is usually an isolated illness, but can be associated with many other medical conditions.
In anterior uveitis, no associated condition or syndrome is found in approximately one-half of cases. However, anterior uveitis is often one of the syndromes associated with HLA-B27. Presence of this type of HLA allele has a relative risk of evolving this disease by approximately 15%.
The most common form of uveitis is acute anterior uveitis (AAU). It is most commonly associated with HLA-B27, which has important features: HLA-B27 AAU can be associated with ocular inflammation alone or in association with systemic disease. HLA-B27 AAU has characteristic clinical features including male preponderance, unilateral alternating acute onset, a non-granulomatous appearance, and frequent recurrences, whereas HLA-B27 negative AAU has an equivalent male to female onset, bilateral chronic course, and more frequent granulomatous appearance. Rheumatoid arthritis is not uncommon in Asian countries as a significant association of uveitis.
Methylmercury and inorganic mercury is excreted in human breast milk and infants are particularly susceptible to toxicity due to this compound. The fetus and infant are especially vulnerable to mercury exposures with special interest in the development of the CNS since it can easily cross across the placental barrier, accumulate within the placenta and fetus as the fetus cannot eliminate mercury and have a negative effect on the fetus even if the mother does not show symptoms. Mercury causes damage to the nervous system resulting from prenatal or early postnatal exposure and is very likely to be permanent.
Various systems are affected.
- CNS abnormalities – microcephaly, mental retardation, spasticity, epilepsy, periventricular calcification
- Eye – choroidoretinitis and optic atrophy
- Ear – sensorineural deafness
- Liver – hepatosplenomegaly and jaundice due to hepatitis
- Lung – pneumonitis (interstitial pneumonitis)
- Heart – myocarditis
- Thrombocytopenic purpura, haemolytic anaemia
- Late sequelae in individuals asymptomatic at birth – hearing defects and reduced intelligence