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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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A subclinical infection (sometimes called a preinfection) is an infection that, being , is nearly or completely asymptomatic (no signs or symptoms). A subclinically infected person is thus an asymptomatic carrier of a microbe, intestinal parasite, or virus that usually is a pathogen causing illness, at least in some individuals. Many pathogens spread by being silently carried in this way by some of their host population. Such infections occur both in humans and nonhuman animals. An example of an asymptomatic infection is a mild common cold that is not noticed by the infected individual. Since subclinical infections often occur without eventual overt sign, their existence is only identified by microbiological culture or DNA techniques such as polymerase chain reaction.
Feline zoonosis are the viral, bacterial, fungal, protozoan, nematode and arthropod infections that can be transmitted to humans from the domesticated cat, "Felis catus". Some of these are diseases are reemerging and newly emerging infections or infestations caused by zoonotic pathogens transmitted by cats. In some instances, the cat can display symptoms of infection (these may differ from the symptoms in humans) and sometimes the cat remains asymptomatic. There can be serious illnesses and clinical manifestations in people who become infected. This is dependent on the immune status and age of the person. Those who live in close association with cats are more prone to these infections. But those that do not keep cats as pets are also able to acquire these infections because of the transmission can be from cat feces and the parasites that leave their bodies.
People can acquire cat-associated infections through bites, scratches or other direct contact of the skin or mucous membranes with the cat. This includes 'kissing' or letting the animal lick the mouth or nose. Mucous membranes are easily infected when the pathogen is in the mouth of the cat. Pathogens can also infect people when there is contact with animal saliva, urine and other body fluids or secretions, When fecal material is unintentionally ingested, infection can occur. Feline zooinosis can be acquired by a person by inhalation of aerosols or droplets coughed up by the cat.
In the United States, forty percent of homes have at least one cat. Some contagious infections such as campylobacteriosis and salmonellosis cause visible symptoms of the disease in cats. Other infections, such as cat scratch disease and toxoplasmosis, have no visible symptoms and are carried by apparently healthy cats.
An individual may only develop signs of an infection after a period of subclinical infection, a duration that is called the incubation period. This is the case, for example, for subclinical sexually transmitted diseases such as AIDS and genital warts. Individuals with such subclinical infections, and those that never develop overt illness, creates a reserve of individuals that can transmit an infectious agent to infect other individuals. Because such cases of infections do not come to clinical attention, health statistics can often fail to measure the true prevalence of an infection in a population, and this prevents the accurate modeling of its infectious transmission.
An opportunistic infection is an infection caused by pathogens (bacteria, viruses, fungi, or protozoa) that take advantage of an opportunity not normally available, such as a host with a weakened immune system, an altered microbiota (such as a disrupted gut flora), or breached integumentary barriers. Many of these pathogens do not cause disease in a healthy host that has a normal immune system. However, a compromised immune system, a penetrating injury, or a lack of competition from normal commensals presents an opportunity for the pathogen to infect.
Initial signs of FVR include coughing, sneezing, nasal discharge, conjunctivitis, and sometimes fever (up to 106) and loss of appetite. These usually resolve within four to seven days, but secondary bacterial infections can cause the persistence of clinical signs for weeks. Frontal sinusitis and empyema can also result.
FHV-1 also has a predilection for corneal epithelium, resulting in corneal ulcers, often pinpoint or dendritic in shape. Other ocular signs of FHV-1 infection include conjunctivitis, keratitis, keratoconjunctivitis sicca (decreased tear production), and corneal sequestra. Infection of the nasolacrimal duct can result in chronic epiphora (excess tearing). Ulcerative skin disease can also result from FHV-1 infection. FHV-1 can also cause abortion in pregnant queens, usually at the sixth week of gestation, although this may be due to systemic effects of the infection rather than the virus directly.
In chronic nasal and sinus disease of cats, FHV-1 may play more of an initiating role than an ongoing cause. Infection at an early age may permanently damage nasal and sinus tissue, causing a disruption of ciliary clearance of mucus and bacteria, and predispose these cats to chronic bacterial infections.
Cat-scratch disease commonly presents as tender, swollen lymph nodes near the site of the inoculating bite or scratch or on the neck, and is usually limited to one side. This condition is referred to as regional lymphadenopathy and occurs 1–3 weeks after inoculation. Lymphadenopathy in CSD most commonly occurs in the arms, neck, or jaw, but may also occur near the groin or around the ear. A vesicle or an erythematous papule may form at the site of initial infection. Most patients also develop systemic symptoms such as malaise, decreased appetite, and aches. Other associated complaints include headache, chills, muscular pains, joint pains, arthritis, backache, and abdominal pain. It may take 7 to 14 days, or as long as two months, for symptoms to appear. Most cases are benign and self-limiting, but lymphadenopathy may persist for several months after other symptoms disappear. The disease usually resolves spontaneously, with or without treatment, in one month.
In rare situations, CSD can lead to the development of serious neurologic or cardiac sequelae such as meningoencephalitis, encephalopathy, seizures, or endocarditis. Endocarditis associated with "Bartonella" infection has a particularly high mortality. Parinaud's oculoglandular syndrome is the most common ocular manifestation of CSD, and is a granulomatous conjunctivitis with concurrent swelling of the lymph node near the ear. Optic neuritis or neuroretinitis is one of the atypical presentations.
Immunocompromised patients are susceptible to other conditions associated with "B. henselae" and "B. quintana", such as bacillary angiomatosis or bacillary peliosis. Bacillary angiomatosis is primarily a vascular skin lesion that may extend to bone or be present in other areas of the body. In the typical scenario, the patient has HIV or another cause of severe immune dysfunction. Bacillary peliosis is caused by "B. henselae" that most often affects patients with HIV and other conditions causing severe immune compromise. The liver and spleen are primarily affected, with findings of blood-filled cystic spaces on pathology. In 2015 a Toledo, Ohio woman lost eyesight in an eye after a cat licked it.
Acute toxoplasmosis is often asymptomatic in healthy adults. However, symptoms may manifest and are often influenza-like: swollen lymph nodes, headaches, fever, and fatigue, or muscle aches and pains that last for a month or more. Rarely will a human with a fully functioning immune system develop severe symptoms following infection. People with weakened immune systems are likely to experience headache, confusion, poor coordination, seizures, lung problems that may resemble tuberculosis or Pneumocystis jiroveci pneumonia (a common opportunistic infection that occurs in people with AIDS), or blurred vision caused by severe inflammation of the retina (ocular toxoplasmosis) Young children and immunocompromised people, such as those with HIV/AIDS, those taking certain types of chemotherapy, or those who have recently received an organ transplant, may develop severe toxoplasmosis. This can cause damage to the brain (encephalitis) or the eyes (necrotizing retinochoroiditis). Infants infected via placental transmission may be born with either of these problems, or with nasal malformations, although these complications are rare in newborns. The toxoplasmic trophozoites causing acute toxoplasmosis are referred to as tachyzoites, and are typically found in bodily fluids.
Swollen lymph nodes are commonly found in the neck or under the chin, followed by the armpits and the groin. Swelling may occur at different times after the initial infection, persist, and recur for various times independently of antiparasitic treatment. It is usually found at single sites in adults, but in children, multiple sites may be more common. Enlarged lymph nodes will resolve within one to two months in 60% of cases. However, a quarter of those affected take two to four months to return to normal, and 8% take four to six months. A substantial number (6%) do not return to normal until much later.
Feline viral rhinotracheitis (FVR) is an upper respiratory or pulmonary infection of cats caused by "feline herpesvirus 1", of the family "Herpesviridae". It is also commonly referred to as feline influenza, feline coryza, and feline pneumonia but, as these terms describe other very distinct collections of respiratory symptoms, they are misnomers for the condition. Viral respiratory diseases in cats can be serious, especially in catteries and kennels. Causing one-half of the respiratory diseases in cats, FVR is the most important of these diseases and is found worldwide. The other important cause of feline respiratory disease is "feline calicivirus".
FVR is very contagious and can cause severe disease, including death from pneumonia in young kittens. It can cause flat-chested kitten syndrome, but most evidence for this is anecdotal. All members of the "Felidae" family are susceptible to FVR; in fact, FHV-1 has caused a fatal encephalitis in lions in Germany.
BVDV infection has a wide manifestation of clinical signs including fertility issues, milk drop, pyrexia, diarrhoea and fetal infection. Occasionally, a severe acute form of BVD may occur. These outbreaks are characterized by thrombocytopenia with high morbidity and mortality. However, clinical signs are frequently mild and infection insidious, recognised only by BVDV’s immunosuppressive effects perpetuating other circulating infectious diseases (particularly scours and pneumonias).
Cryptic Infections: an infection caused by an as yet unidentified pathogen which serves as the direct target of the immune response (inflammation).
Bovine viral diarrhea (BVD) or bovine viral diarrhoea (UK English), and previously referred to as bovine virus diarrhoea (BVD), is a significant economic disease of cattle that is endemic in the majority of countries throughout the world. The causative agent, bovine viral diarrhea virus (BVDV), is a member of the "Pestivirus" genus of the family Flaviviridae.
BVD infection results in a wide variety of clinical signs, due to its immunosuppressive effects, as well as having a direct effect on respiratory disease and fertility. In addition, BVD infection of a susceptible dam during a certain period of gestation can result in the production of a persistently infected (PI) fetus.
PI animals recognise intra-cellular BVD viral particles as ‘self’ and shed virus in large quantities throughout life; they represent the cornerstone of the success of BVD as a disease.
Some disease-carrying arthropods use cats as a vector, or carrier. Fleas and ticks can carry pathogenic organisms that infect a person with Lyme disease, tick borne encephalitis, and Rocky mountain spotted fever
Cat-scratch disease (CSD) is a common and usually benign infectious disease caused by the bacterium "Bartonella henselae". It is most commonly found in children following a scratch or bite from a cat within about one to two weeks.
Toxoplasmosis is a parasitic disease caused by "Toxoplasma gondii". Infections with toxoplasmosis usually cause no obvious symptoms in adults. Occasionally there may be a few weeks or months of mild flu-like illness such as muscle aches and tender lymph nodes. In a small number of people, eye problems may develop. In those with a weak immune system, severe symptoms such as seizures and poor coordination may occur. If infected during pregnancy, a condition known as congenital toxoplasmosis may affect the child.
Toxoplasmosis is usually spread by eating poorly cooked food that contains cysts, exposure to infected cat feces, and from a mother to a child during pregnancy if the mother becomes infected. Rarely the disease may be spread by blood transfusion. It is not otherwise spread between people. The parasite is only known to reproduce sexually in the cat family. However, it can infect most types of warm-blooded animals, including humans. Diagnosis is typically by testing blood for antibodies or by testing amniotic fluid for the parasite's DNA.
Prevention is by properly preparing and cooking food. It is also recommended that pregnant women do not clean cat litter boxes. Treatment of otherwise healthy people is usually not needed. During pregnancy spiramycin or pyrimethamine/sulfadiazine and folinic acid may be used for treatment.
Up to half of the world's population is infected by toxoplasmosis but have no symptoms. In the United States about 23% are affected and in some areas of the world this is up to 95%. About 200,000 cases of congenital toxoplasmosis occur a year. Charles Nicolle and Louis Manceaux first described the organism in 1908. In 1941 transmission during pregnancy from a mother to a child was confirmed.
Most infected cats have been healthy before a very sudden onset of severe disease. The course of clinical disease is often swift with clinical signs of lethargy and inappetence within 5 to 20 days after the tick bite. Cats develop a high fever, but the temperature may become low before death. Other clinical findings can be: dehydration, icterus (jaundice), enlarged liver and spleen, lymphadenopathy, pale mucus membranes, respiratory distress, tachycardia or bradycardia, and tick infestation (although ticks are not often found on infected cats since cats typically groom ticks off their fur). Signs of disease seen on blood work include hemolytic anemia, thrombocytopenia, increased or decreased white blood cell numbers, icterus, and elevated liver enzymes. Death usually follows the onset of clinical signs within a few days. However, more recent studies show not all cats develop clinical signs after infection, and some cats survive the infection.
Immunodeficiency or immunosuppression can be caused by:
- Malnutrition
- Fatigue
- Recurrent infections
- Immunosuppressing agents for organ transplant recipients
- Advanced HIV infection
- Chemotherapy for cancer
- Genetic predisposition
- Skin damage
- Antibiotic treatment leading to disruption of the physiological microbiome, thus allowing some microorganisms to outcompete others and become pathogenic (e.g. disruption of intestinal flora may lead to "Clostridium difficile" infection
- Medical procedures
- Pregnancy
- Ageing
- Leukopenia (i.e. neutropenia and lymphocytopenia)
The lack of or the disruption of normal vaginal flora allows the proliferation of opportunistic microorganisms and will cause the opportunistic infection - bacterial vaginosis.
Cytauxzoon felis is a protozoal organism transmitted to domestic cats by tick bites, and whose natural reservoir host is the bobcat. "C. felis" has been found in other wild felid species such as Florida bobcat, eastern bobcat, Texas cougar, and a white tiger in captivity. "C. felis" infection is limited to the family felidae which means that "C. felis" poses no zoonotic (transmission to humans) risk or agricultural (transmission to farm animals) risk. Until recently it was believed that after infection with "C. felis", pet cats almost always died. As awareness of "C. felis" has increased it has been found that treatment is not always futile. More cats have been shown to survive the infection than was previously thought. New treatments offer as much as 60% survival rate.
Respiratory infection is usually asymptomatic in pigs more than 2 months old, but it can cause abortion, high mortality in piglets, and coughing, sneezing, fever, constipation, depression, seizures, ataxia, circling, and excess salivation in piglets and mature pigs. Mortality in piglets less than one month of age is close to 100%, but it is less than 10% in pigs between one and six months of age. Pregnant swine can reabsorb their litters or deliver mummified, stillborn, or weakened piglets. In cattle (see next section), symptoms include intense itching followed by neurological signs and death. In dogs, symptoms include intense itching, jaw and pharyngeal paralysis, howling, and death Any infected secondary host generally only lives two to three days.
Genital infection appears to have been common in a great part of the 20th century in many European countries in swine herds, where boars from boar centres were used for natural service of sows or gilts. This disease manifestation has always been asymptomatic in affected pigs, and presence of the infection on a farm was detected only because of cases in cattle showing pruritus on the hindquarters (vaginal infection, see below).
In susceptible animals other than swine, infection is usually fatal, and the affected animals most often show intense pruritus in a skin area.
Pruritus in Aujeszky's disease is considered a phantom sensation, and virus has never been found at the site of pruritus.
Immune reconstitution inflammatory syndrome (IRIS) (also known as immune recovery syndrome) is a condition seen in some cases of AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the symptoms of infection worse.
Aujeszky's disease, usually called pseudorabies in the United States, is a viral disease in swine that has been endemic in most parts of the world. It is caused by "Suid herpesvirus 1" (SuHV1). Aujeszky's disease is considered to be the most economically important viral disease of swine in areas where hog cholera has been eradicated. Other mammals, such as humans, cattle, sheep, goats, cats, dogs, and raccoons, are also susceptible. The disease is usually fatal in these animal species bar humans.
The term "pseudorabies" is found inappropriate by many people, as SuHV1 is a herpesvirus and not related to the rabies virus.
Research on SuHV1 in pigs has pioneered animal disease control with genetically modified vaccines. SuHV1 is now used in model studies of basic processes during lytic herpesvirus infection, and for unravelling molecular mechanisms of herpesvirus neurotropism.
"Ureaplasma urealyticum" is a species in the genus "Ureaplasma" that can cause infection. Though most bacteria possess a cell wall, "U urealyticum" does not. It is found in about 70% of sexually active humans. It can be found in cultures in cases of pelvic inflammatory disease and is transmitted through sexual activity or from mother to infant during birth. It is not a commensal of the healthy uterine or amniotic microbiome. Infection with "U. realyticum" can contribute neonatal infection and negative birth outcomes.
IRIS is particularly problematic in cryptococcal meningitis as IRIS is fairly common and can be fatal.
IRIS has been described in immunocompetent hosts who have meningitis caused by "Cryptococcus gattii" and "Cryptococcus neoformans" var. "grubii", environmental fungi which often affect immunocompetent hosts. Several weeks or even months into appropriate treatment, there is a sudden onset deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms.
Magnetic resonance imaging shows increase in the size of brain lesions, and CSF abnormalities (white cell count, protein, glucose) increase. CSF culture is typically sterile, and there is no increase in CSF cryptococcal antigen titer.
The increasing inflammation can cause brain injury or be fatal.
The general mechanism behind IRIS is increased inflammation as the recovering immune system recognizes the antigens of the fungus as immunosuppression is reversed. Cryptococcal IRIS has three phases:
1. before HAART, with a paucity of cerebrospinal fluid (CSF) inflammation and defects in antigen clearance;
2. during initial HAART immune recovery, with pro-inflammatory signaling by antigen-presenting cells without an effector response; and
3. at IRIS, a cytokine storm with a predominant type-1 helper T-cell interferon-gamma response.
Three clinical predictors of cryptococcal-related paradoxical IRIS risk include:
1. lack of initial CSF pleocytosis (i.e. low CSF white blood cell count);
2. elevated C-reactive protein;
3. failure to sterilize the CSF before immune recovery.
IRIS may be the cause of paradoxically worse outcomes for cryptococcal meningitis in immunocompetent compared with immunocompromised hosts, in whom "Cryptococcus neoformans" is the usual pathogen. Treatment with systemic corticosteroids during IRIS may be beneficial in preventing death or progressive neurological deterioration. Steroids given to persons with anti-fungal treatment failure / cryptococcal relapse (in whom CSF cultures are not sterile) can be a fatal iatrogenic error.
It had also been associated with a number of diseases in humans, including nonspecific urethritis, and infertility.
The signs and symptoms of a vertically transmitted infection depend on the individual pathogen. It may cause subtle signs such as a influenza-like illness and may not even be noticed by the mother during the pregnancy. In such cases, the effects may be seen first at birth.
Symptoms of a vertically transmitted infection may include fever and flu like symptoms. The newborn is often small for gestational age. A petechial rash on the skin may be present, with small reddish or purplish spots due to bleeding from capillaries under the skin. An enlarged liver and spleen (hepatosplenomegaly) is common, as is jaundice. However, jaundice is less common in hepatitis B because a newborn's immune system is not developed well enough to mount a response against liver cells, as would normally be the cause of jaundice in an older child or adult. Hearing impairment, eye problems, mental retardation, autism, and death can be caused by vertically transmitted infections. The mother often has a mild infection with few or no symptoms.
The genetic conditions of Aicardi-Goutieres syndrome are possibly present in a similar manner.
Clinically, neonates with omphalitis present within the first two weeks of life with signs and symptoms of a skin infection (cellulitis) around the umbilical stump (redness, warmth, swelling, pain), pus from the umbilical stump, fever, fast heart rate (tachycardia), low blood pressure (hypotension), somnolence, poor feeding, and yellow skin (jaundice). Omphalitis can quickly progress to sepsis and presents a potentially life-threatening infection. In fact, even in cases of omphalitis without evidence of more serious infection such as necrotizing fasciitis, mortality is high (in the 10% range).