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)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
The clinical definition of smallpox is an illness with acute onset of fever equal to or greater than followed by a rash characterized by firm, deep seated vesicles or pustules in the same stage of development without other apparent cause. If a clinical case is observed, smallpox is confirmed using laboratory tests.
Microscopically, poxviruses produce characteristic cytoplasmic inclusions, the most important of which are known as Guarnieri bodies, and are the sites of viral replication. Guarnieri bodies are readily identified in skin biopsies stained with hematoxylin and eosin, and appear as pink blobs. They are found in virtually all poxvirus infections but the absence of Guarnieri bodies cannot be used to rule out smallpox. The diagnosis of an orthopoxvirus infection can also be made rapidly by electron microscopic examination of pustular fluid or scabs. All orthopoxviruses exhibit identical brick-shaped virions by electron microscopy. If particles with the characteristic morphology of herpesviruses are seen this will eliminate smallpox and other orthopoxvirus infections.
Definitive laboratory identification of variola virus involves growing the virus on chorioallantoic membrane (part of a chicken embryo) and examining the resulting pock lesions under defined temperature conditions. Strains may be characterized by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Serologic tests and enzyme linked immunosorbent assays (ELISA), which measure variola virus-specific immunoglobulin and antigen have also been developed to assist in the diagnosis of infection.
Chickenpox was commonly confused with smallpox in the immediate post-eradication era. Chickenpox and smallpox can be distinguished by several methods. Unlike smallpox, chickenpox does not usually affect the palms and soles. Additionally, chickenpox pustules are of varying size due to variations in the timing of pustule eruption: smallpox pustules are all very nearly the same size since the viral effect progresses more uniformly. A variety of laboratory methods are available for detecting chickenpox in evaluation of suspected smallpox cases.
The earliest procedure used to prevent smallpox was inoculation (known as variolation after the introduction of smallpox vaccine to avoid possible confusion), which likely occurred in India, Africa, and China well before the practice arrived in Europe. The idea that inoculation originated in India has been challenged, as few of the ancient Sanskrit medical texts described the process of inoculation. Accounts of inoculation against smallpox in China can be found as early as the late 10th century, and the procedure was widely practiced by the 16th century, during the Ming dynasty. If successful, inoculation produced lasting immunity to smallpox. Because the person was infected with variola virus, a severe infection could result, and the person could transmit smallpox to others. Variolation had a 0.5–2 percent mortality rate, considerably less than the 20–30 percent mortality rate of the disease. Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Dr. Martin Lister who received a report by an employee of the East India Company stationed in China and another by Clopton Havers.
Lady Mary Wortley Montagu observed smallpox inoculation during her stay in the Ottoman Empire, writing detailed accounts of the practice in her letters, and enthusiastically promoted the procedure in England upon her return in 1718. In 1721, Cotton Mather and colleagues provoked controversy in Boston by inoculating hundreds. In 1796, Edward Jenner, a doctor in Berkeley, Gloucestershire, rural England, discovered that immunity to smallpox could be produced by inoculating a person with material from a cowpox lesion. Cowpox is a poxvirus in the same family as variola. Jenner called the material used for inoculation vaccine, from the root word "vacca", which is Latin for cow. The procedure was much safer than variolation, and did not involve a risk of smallpox transmission. Vaccination to prevent smallpox was soon practiced all over the world. During the 19th century, the cowpox virus used for smallpox vaccination was replaced by vaccinia virus. Vaccinia is in the same family as cowpox and variola, but is genetically distinct from both. The origin of vaccinia virus and how it came to be in the vaccine are not known. According to Voltaire (1742), the Turks derived their use of inoculation to neighbouring Circassia. Voltaire does not speculate on where the Circassians derived their technique from, though he reports that the Chinese have practiced it "these hundred years".
The current formulation of smallpox vaccine is a live virus preparation of infectious vaccinia virus. The vaccine is given using a bifurcated (two-pronged) needle that is dipped into the vaccine solution. The needle is used to prick the skin (usually the upper arm) a number of times in a few seconds. If successful, a red and itchy bump develops at the vaccine site in three or four days. In the first week, the bump becomes a large blister (called a "Jennerian vesicle") which fills with pus, and begins to drain. During the second week, the blister begins to dry up and a scab forms. The scab falls off in the third week, leaving a small scar.
The antibodies induced by vaccinia vaccine are cross-protective for other orthopoxviruses, such as monkeypox, cowpox, and variola (smallpox) viruses. Neutralizing antibodies are detectable 10 days after first-time vaccination, and seven days after revaccination. Historically, the vaccine has been effective in preventing smallpox infection in 95 percent of those vaccinated. Smallpox vaccination provides a high level of immunity for three to five years and decreasing immunity thereafter. If a person is vaccinated again later, immunity lasts even longer. Studies of smallpox cases in Europe in the 1950s and 1960s demonstrated that the fatality rate among persons vaccinated less than 10 years before exposure was 1.3 percent; it was 7 percent among those vaccinated 11 to 20 years prior, and 11 percent among those vaccinated 20 or more years prior to infection. By contrast, 52 percent of unvaccinated persons died.
There are side effects and risks associated with the smallpox vaccine. In the past, about 1 out of 1,000 people vaccinated for the first time experienced serious, but non-life-threatening, reactions, including toxic or allergic reaction at the site of the vaccination (erythema multiforme), spread of the vaccinia virus to other parts of the body, and to other individuals. Potentially life-threatening reactions occurred in 14 to 500 people out of every 1 million people vaccinated for the first time. Based on past experience, it is estimated that 1 or 2 people in 1 million (0.000198 percent) who receive the vaccine may die as a result, most often the result of postvaccinial encephalitis or severe necrosis in the area of vaccination (called progressive vaccinia).
Given these risks, as smallpox became effectively eradicated and the number of naturally occurring cases fell below the number of vaccine-induced illnesses and deaths, routine childhood vaccination was discontinued in the United States in 1972, and was abandoned in most European countries in the early 1970s. Routine vaccination of health care workers was discontinued in the U.S. in 1976, and among military recruits in 1990 (although military personnel deploying to the Middle East and Korea still receive the vaccination). By 1986, routine vaccination had ceased in all countries. It is now primarily recommended for laboratory workers at risk for occupational exposure.
Cowpox originates on the udders or teats of cows. It is classified as a zoonotic disease, which means it can be transferred from animals to humans and vice versa. Cowpox is an infectious disease. So, the disease can manifest on cows in environments where bacteria thrive, due to unsanitary conditions, or randomly. Cowpox symptoms are similar in whichever host they infect: cow, cat, human. Cowpox symptoms include round, pus filled lesions on the skin at the site of infection. In most cases of humans, the lesions develop on the inner and outer parts of the hand and fingers. In some cases, the infected person can develop a mild fever or inflammation around the lesions. Cowpox can be transferred from human to human by contact of the infected site to another individual. It is very similar in pathology and structure in contrast to small pox. However, cowpox has increased activity in between the ectoderm and endoderm layers of the human skin. Cowpox includes both A type bodies and B type inclusion bodies which largely impacts the pathology of the disease.
Cowpox is an infectious disease caused by the cowpox virus. The virus, part of the orthopoxvirus family, is closely related to the "vaccinia" virus. The virus is zoonotic, meaning that it is transferable between species, such as from animal to human. The transferral of the disease was first observed in dairymaids who touched the udders of infected cows and consequently developed the signature pustules on their hands. Cowpox is more commonly found in animals other than bovines, such as rodents. Cowpox is similar to, but much milder than, the highly contagious and often deadly smallpox disease. Its close resemblance to the mild form of smallpox and the observation that dairymaids were immune from smallpox inspired the first smallpox vaccine, created and administered by English physician Edward Jenner.
The word “vaccination,” coined by Jenner in 1796, is derived from the Latin root "vaccinus", meaning of or from the cow. Once vaccinated, a patient develops antibodies that make them immune to cowpox, but they also develop immunity to the smallpox virus, or "Variola virus". The cowpox vaccinations and later incarnations proved so successful that in 1980, the World Health Organization announced that smallpox was the first disease to be eradicated by vaccination efforts worldwide. Other orthopox viruses remain prevalent in certain communities and continue to infect humans, such as the cowpox virus (CPXV) in Europe, vaccinia in Brazil, and monkeypox virus in Central and West Africa.
Alastrim, also known as variola minor, was the milder strain of the variola virus that caused smallpox. The last known case of variola minor was in Somalia, Africa in 1977. Smallpox was formally declared eradicated in May 1980.
Variola minor is of the genus orthopoxvirus, which are DNA viruses that replicate in the cytoplasm of the affected cell, rather than in its nucleus. Like variola major, alastrim was spread through inhalation of the virus in the air, which could occur through face-to-face contact or through fomites. Infection with variola minor conferred immunity against the more dangerous variola major.
Variola minor was a less common form of the virus, and much less deadly. Although alastrim had the same incubation period and pathogenetic stages as smallpox, alastrim is believed to have had a mortality rate of less than 1%, as compared to smallpox's 30%.
Because alastrim was a less debilitating disease than smallpox, patients were more frequently ambulant and thus able to infect others more rapidly. As such, variola minor swept through the USA, Great Britain, and South Africa in the early 20th century, becoming the dominant form of the disease in those areas and thus rapidly decreasing mortality rates.
Alastrim was also called white pox, kaffir pox, Cuban itch, West Indian pox, milk pox, and pseudovariola.
Like smallpox, alastrim has now been totally eradicated from the globe thanks to the 1960s Global Smallpox Eradication campaign. The last case of indigenous variola minor was reported in a Somalian cook, Ali Maow Maalin, in October 1977, and smallpox was officially declared eradicated worldwide in May 1980.
Variola caprina (goat pox) is a contagious viral disease caused by a pox virus that affects goats. The virus usually spreads via the respiratory system, and sometimes spreads through abraded skin. It is most likely to occur in crowded stock. Sources of the virus include cutaneous lesions, saliva, nasal secretions and faeces. There are two types of the disease: the papulo-vesicular form and the nodular form (stone pox). The incubation period is usually 8–13 days, but it may be as short as four days.
It is thought the same virus spreads sheep pox, to which European sheep breeds are highly susceptible. The virus may be present in dried scabs for up to six months.
In endemic areas the morbidity rate is 70–90% and the mortality rate is 5–10%. The mortality rate may reach nearly 100% in imported animals. Resistant animals may show only a mild form of the disease, which may be missed as only a few lesions are present, usually around the ears or the tail.
Goat pox is found in the part of Africa north of the equator, the Middle East, Central Asia and India. It may be spread between animals by:
- Direct contact
- Indirect transmission by contaminated implements, vehicles or products such as litter or fodder
- Indirect transmission by insects (mechanical vectors).
- Contamination by inhalation, intradermal or subcutaneous inoculation, or by respiratory, transcutaneous and transmucosal routes
Hemorrhagic smallpox, sometimes called bloody pox, fulminant smallpox, and blackpox, is a severe and rare form of smallpox and is usually fatal. Like all forms of smallpox it is caused by the variola virus. It is characterized by an incubation period of 7 to 14 days. It has two stages, the first begins with fever, headache, chills, nausea, vomiting and severe muscle aches. The skin flushes in a deep-purple, uneven pattern across the face. The early stage is often mistaken for measles. The late stage is characterized by the appearance of small blisters resembling a severe form of chickenpox. These small blisters then flatten until they are even with the skin, and change into reddish lesions similar to those seen in measles. The skin then turns a deep purple. Lesions appear inside the mouth and active bleeding from oral and nasal mucous membranes is common. This is followed by active bleeding in the gastrointestinal tract, and blood appears in the stool and urine. Blood studies resemble the clinical values of disseminated intravascular coagulation.
Poultry diseases are diseases that afflict poultry. Major types of poultry include the chicken, turkey, duck, goose and ostrich.
The eradication of poultry disease is very important to the poultry industry.
Diagnosis is based on the characteristic appearance of non-healing raised, scaling lesions that may ulcerate and become secondarily infected with organisms such as "Staphylococcus aureus", in someone who has returned from an endemic area.
The gold standard for diagnosis is PCR (polymerase chain reaction) helps DNA polymerase to create new strands of DNA equivalent to template given.
The best treatment for cutaneous leishmaniasis is not known. Treatments that work for one species of leishmania may not work for another; it is recommended that advice of a tropical medicine or geographical medicine specialist be sought. Ideally, every effort should be made to establish the species of leishmania by molecular techniques (PCR) prior to starting treatment. In the setting of a developing country, there is often only one species present in a particular locality, so it is usually unnecessary to speciate every infection. Unfortunately, leishmaniasis is an orphan disease in developed nations, and almost all the current treatment options are toxic with significant side effects. The most sound treatment for cutaneous leishmaniasis thus far is prevention.
- "Leishmania major" :"L. major" infections are usually considered to heal spontaneously and do not require treatment, but there have been several reports of severe cases caused by "L. major" in Afghanistan. In Saudi Arabia, a six-week course of oral fluconazole 200 mg daily has been reported to speed up healing. In a randomized clinical trial from Iran, fluconazole 400 mg daily was shown to be significantly more effective than fluconazole 200 mg daily in the treatment of cutaneous leishmaniasis.
- "Leishmania braziliensis" :Treatment with pentavalent antimonials or amphotericin is necessary, because of the risk of developing disfiguring mucocutaneous lesions.
- "Leishmania infantum" :"L. infantum" causes cutaneous leishmaniasis in southern France.
New treatment options are arising from the new oral drug miltefosine (Impavido) which has shown in several clinical trials to be very efficient and safe in visceral and cutaneous leishmaniasis. Recent studies from Bolivia show a high cure rate for mucocutaneous leishmaniasis. Comparative studies against pentavalent antimonials in Iran and Pakistan are also beginning to show a high cure rate for "L. major" and "L. tropica". It is registered in many countries of Latin America, as well in Germany. In October 2006 it received orphan drug status from the US Food and Drug administration. The drug is generally better tolerated than other drugs. Main side effects are gastrointestinal disturbances in the 1–2 days of treatment which does not affect the efficacy.
Secondary bacterial infection (especially with "Staphylococcus aureus") is common and may require antibiotics. Clinicians who are unfamiliar with cutaneous leishmaniasis may mistake the lesion for a pure bacterial infection (especially after isolation of "S. aureus" from bacterial skin swabs) and fail to consider the possibility of leishmaniasis.
Erythema multiforme is frequently self-limiting and requires no treatment. The appropriateness of glucocorticoid therapy can be uncertain, because it is difficult to determine if the course will be a resolving one.
A canine vector-borne disease (CVBD) is one of "a group of globally distributed and rapidly spreading illnesses that are caused by a range of pathogens transmitted by arthropods including ticks, fleas, mosquitoes and phlebotomine sandflies." CVBDs are important in the fields of veterinary medicine, animal welfare, and public health. Some CVBDs are of zoonotic concern.
Many CVBD infect humans as well as companion animals. Some CVBD are fatal; most can only be controlled, not cured. Therefore, infection should be avoided by preventing arthropod vectors from feeding on the blood of their preferred hosts. While it is well known that arthropods transmit bacteria and protozoa during blood feeds, viruses are also becoming recognized as another group of transmitted pathogens of both animals and humans.
Some "canine vector-borne pathogens of major zoonotic concern" are distributed worldwide, while others are localized by continent. Listed by vector, some such pathogens and their associated diseases are the following:
- Phlebotomine sandflies (Psychodidae): "Leishmania amazonensis", "L. colombiensis", and "L. infantum" cause visceral leishmaniasis (see also canine leishmaniasis). "L. braziliensis" causes mucocutaneous leishmaniasis. "L. tropica" causes cutaneous leishmaniasis. "L. peruviana" and "L. major" cause localized cutaneous leishmaniasis.
- Triatomine bugs (Reduviidae): "Trypanosoma cruzi" causes trypanosomiasis (Chagas disease).
- Ticks (Ixodidae): "Babesia canis" subspecies ("Babesia canis canis", "B. canis vogeli", "B. canis rossi", and "B. canis gibsoni" cause babesiosis. "Ehrlichia canis" and "E. chaffeensis" cause monocytic ehrlichiosis. "Anaplasma phagocytophilum" causes granulocytic anaplasmosis. "Borrelia burgdorferi" causes Lyme disease. "Rickettsia rickettsii" causes Rocky Mountain spotted fever. "Rickettsia conorii" causes Mediterranean spotted fever.
- Mosquitoes (Culicidae): "Dirofilaria immitis" and "D. repens" cause dirofilariasis.
Many suspected aetiologic factors have been reported to cause EM.
- Infections: Bacterial (including Bacillus Calmette-Guérin (BCG) vaccination, haemolytic "Streptococci", legionellosis, leprosy, "Neisseria meningitidis, Mycobacterium, "Pneumococcus, "Salmonella" species, "Staphylococcus" species, "Mycoplasma pneumoniae), "Chlamydial.
- Fungal (Coccidioides immitis)
- Parasitic ("Trichomonas" species, "Toxoplasma gondii), "
- Viral (especially Herpes simplex)
- Drug reactions, most commonly to: antibiotics (including, sulphonamides, penicillin), anticonvulsants (phenytoin, barbiturates), aspirin, antituberculoids, and allopurinol and many others.
- Physical factors: radiotherapy, cold, sunlight
- Others: collagen diseases, vasculitides, non-Hodgkin lymphoma, leukaemia, multiple myeloma, myeloid metaplasia, polycythemia
EM minor is regarded as being triggered by HSV in almost all cases. A herpetic aetiology also accounts for 55% of cases of EM major. Among the other infections, "Mycoplasma" infection appears to be a common cause.
Herpes simplex virus suppression and even prophylaxis (with acyclovir) has been shown to prevent recurrent erythema multiforme eruption.
It occurs in less than 5% of patients with rheumatic fever, but is considered a major Jones criterion when it does occur. The four other major criteria include carditis, polyarthritis, Sydenham's Chorea, and subcutaneous nodules. In this case, it is often associated with Group A streptococcal infection, otherwise known as "Streptococcus pyogenes" infection, which can be detected with an ASO titer.
It is an early feature of rheumatic fever and not pathognomonic of it. It may be associated with mild myocarditis (inflammation of heart muscle). It is also seen in conditions like allergic drug reactions, sepsis and glomerulonephritis.
It often occurs as a harbinger of attacks in hereditary angioedema. In this case it may occur several hours or up to a day before an attack.
Erythema marginatum is a type of erythema (redness of the skin or mucous membranes) involving pink rings on the torso and inner surfaces of the limbs which come and go for as long as several months. It is found primarily on extensor surfaces.
An association with bradykinin has been proposed in the case of hereditary angioedema.
Transfusion therapy lowers the risk for a new silent stroke in children who have both abnormal cerebral artery blood flow velocity, as detected by transcranial Doppler, and previous silent infarct, even when the initial MRI showed no abnormality. A finding of elevated TCD ultrasonographic velocity warrants MRI of the brain, as those with both abnormalities who are not provided transfusion therapy are at higher risk for developing a new silent infarct or stroke than are those whose initial MRI showed no abnormality.
Preventive measures that can be taken to avoid sustaining a silent stroke are the same as for stroke. Smoking cessation is the most immediate step that can be taken, with the effective management of hypertension the major medically treatable factor.
Though BLSII is an attractive candidate for gene therapy, bone marrow transplant is currently the only treatment.
Treatment is usually supportive treatment, that is, treatment to reduce any symptoms rather than to cure the condition.
- Enucleation of the odontogenic cysts can help, but new lesions, infections and jaw deformity are usually a result.
- The severity of the basal-cell carcinoma determines the prognosis for most patients. BCCs rarely cause gross disfigurement, disability or death .
- Genetic counseling
NBCCS has an incidence of 1 in 50,000 to 150,000 with higher incidence in Australia. One aspect of NBCCS is that basal-cell carcinomas will occur on areas of the body which are not generally exposed to sunlight, such as the palms and soles of the feet and lesions may develop at the base of palmar and plantar pits.
One of the prime features of NBCCS is development of multiple BCCs at an early age, often in the teen years. Each person who has this syndrome is affected to a different degree, some having many more characteristics of the condition than others.
Erythema multiforme major (also known as "erythema multiforme majus") is a form of rash with skin loss or epidermal detachment.
The term "erythema multiforme majus" is sometimes used to imply a bullous (blistering) presentation.
According to some sources, there are two conditions included on a spectrum of this same disease process:
- Stevens–Johnson syndrome (SJS)
- Toxic epidermal necrolysis (TEN) which described by Alan Lyell and previously called Lyell syndrome.
In this view, EM major, SJS and TEN are considered a single condition, distinguished by degree of epidermal detachment.
However, a consensus classification separates erythema multiforme minor, erythema multiforme major, and SJS/TEN as three separate entities.
Bare lymphocyte syndrome is a condition caused by mutations in certain genes of the major histocompatibility complex or involved with the processing and presentation of MHC molecules. It is a form of severe combined immunodeficiency.
Treatments used to combat autoimmune diseases and conditions caused by eosinophils include:
- corticosteroids – promote apoptosis. Numbers of eosinophils in blood are rapidly reduced
- monoclonal antibody therapy – e.g., mepolizumab or reslizumab against IL-5, prevents eosinophilopoiesis
- antagonists of leukotriene synthesis or receptors
- imatinib (STI571) – inhibits PDGF-BB in hypereosinophilic leukemia
Monoclonal antibodies such as dupilumab and lebrikizumab target IL-13 and its receptor, which reduces eosinophilic inflammation in pateints with asthma due to lowering the number of adhesion molecules present for eosinophils to bind to, thereby decreasing inflammation. Mepolizumab and benralizumab are other treatment options that target the alpha subunit of the IL-5 receptor, thereby inhibiting its function and reducing the number of developing eosinophils as well as the number of eosinophils leading to inflammation through antibody-dependent cell-mediated cytotoxicity and eosinophilic apoptosis.
The diagnosis of this syndrome can be made on clinical examination and perinatal autopsy.
Koenig and Spranger (1986) noted that eye lesions are apparently nonobligatory components of the syndrome. The diagnosis of Fraser syndrome should be entertained in patients with a combination of acrofacial and urogenital malformations with or without cryptophthalmos. Thomas et al. (1986) also emphasized the occurrence of the cryptophthalmos syndrome without cryptophthalmos and proposed diagnostic criteria for Fraser syndrome. Major criteria consisted of cryptophthalmos, syndactyly, abnormal genitalia, and positive family history. Minor criteria were congenital malformation of the nose, ears, or larynx, cleft lip and/or palate, skeletal defects, umbilical hernia, renal agenesis, and mental retardation. Diagnosis was based on the presence of at least 2 major and 1 minor criteria, or 1 major and 4 minor criteria.
Boyd et al. (1988) suggested that prenatal diagnosis by ultrasound examination of eyes, digits, and kidneys should detect the severe form of the syndrome. Serville et al. (1989) demonstrated the feasibility of ultrasonographic diagnosis of the Fraser syndrome at 18 weeks' gestation. They suggested that the diagnosis could be made if 2 of the following signs are present: obstructive uropathy, microphthalmia, syndactyly, and oligohydramnios. Schauer et al. (1990) made the diagnosis at 18.5 weeks' gestation on the basis of sonography. Both the female fetus and the phenotypically normal father had a chromosome anomaly: inv(9)(p11q21). An earlier born infant had Fraser syndrome and the same chromosome 9 inversion.
Van Haelst et al. (2007) provided a revision of the diagnostic criteria for Fraser syndrome according to Thomas et al. (1986) through the addition of airway tract and urinary tract anomalies to the major criteria and removal of mental retardation and clefting as criteria. Major criteria included syndactyly, cryptophthalmos spectrum, urinary tract abnormalities, ambiguous genitalia, laryngeal and tracheal anomalies, and positive family history. Minor criteria included anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies. Cleft lip and/or palate, cardiac malformations, musculoskeletal anomalies, and mental retardation were considered uncommon. Van Haelst et al. (2007) suggested that the diagnosis of Fraser syndrome can be made if either 3 major criteria, or 2 major and 2 minor criteria, or 1 major and 3 minor criteria are present in a patient.