Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
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 differential diagnosis in a case of suspected human rabies may initially include any cause of encephalitis, in particular infection with viruses such as herpesviruses, enteroviruses, and arboviruses such as West Nile virus. The most important viruses to rule out are herpes simplex virus type one, varicella zoster virus, and (less commonly) enteroviruses, including coxsackieviruses, echoviruses, polioviruses, and human enteroviruses 68 to 71.
New causes of viral encephalitis are also possible, as was evidenced by the 1999 outbreak in Malaysia of 300 cases of encephalitis with a mortality rate of 40% caused by Nipah virus, a newly recognized paramyxovirus. Likewise, well-known viruses may be introduced into new locales, as is illustrated by the outbreak of encephalitis due to West Nile virus in the eastern United States. Epidemiologic factors, such as season, geographic location, and the patient's age, travel history, and possible exposure to bites, rodents, and ticks, may help direct the diagnosis.
Rabies can be difficult to diagnose, because, in the early stages, it is easily confused with other diseases or with aggressiveness. The reference method for diagnosing rabies is the fluorescent antibody test (FAT), an immunohistochemistry procedure, which is recommended by the World Health Organization (WHO). The FAT relies on the ability of a detector molecule (usually fluorescein isothiocyanate) coupled with a rabies-specific antibody, forming a conjugate, to bind to and allow the visualisation of rabies antigen using fluorescent microscopy techniques. Microscopic analysis of samples is the only direct method that allows for the identification of rabies virus-specific antigen in a short time and at a reduced cost, irrespective of geographical origin and status of the host. It has to be regarded as the first step in diagnostic procedures for all laboratories. Autolysed samples can, however, reduce the sensitivity and specificity of the FAT. The RT PCR assays proved to be a sensitive and specific tool for routine diagnostic purposes, particularly in decomposed samples or archival specimens. The diagnosis can be reliably made from brain samples taken after death. The diagnosis can also be made from saliva, urine, and cerebrospinal fluid samples, but this is not as sensitive and reliable as brain samples. Cerebral inclusion bodies called Negri bodies are 100% diagnostic for rabies infection but are found in only about 80% of cases. If possible, the animal from which the bite was received should also be examined for rabies.
Some light microscopy techniques may also be used to diagnose rabies at a tenth of the cost of traditional fluorescence microscopy techniques, allowing identification of the disease in less-developed countries.
In Haiti, few cases of human rabies are reported to health authorities. In 2016, a report of a woman who had been exposed to rabies three months prior and was showing symptoms went to the hospital where no treatment was administered to her. Even after being reported to both the CDC and the national Department of Epidemiology and Laboratory Research (DELR), as required by Haiti's surveillance program, the woman ended up passing away. This goes to show the lack of communication and effectiveness in caring for human subjects in Haiti, and the continued focus is on eliminating dog-mediated rabies altogether.
Human diploid cell culture rabies vaccine (HDCV) and purified chick embryo cell culture rabies vaccine (PCEC) are used to treat post-exposure immunization against a human rabies infection. Recommendations for treatment are given by governmental health care organizations and in health literature. Health care providers are encouraged to administer a regimen of four 1-mL doses of HDCV or PCEC vaccines. According to the CDC, these injections should be administered intramuscularly to persons who have not yet been vaccinated for rabies.
For those who are unvaccinated, the first of four doses is administered immediately after exposure to the rabies virus. Additional doses are given three, seven, and fourteen days after the first vaccination. Exposure usually means a bite from a rabid animal.
At an individual patient level, post-exposure prophylaxis (PEP) consists of local treatment of the wound, vaccination, and administration of immunoglobulin, if necessary [3]. At the program level, several components are critical, including: adequate and prompt recognition of the need for PEP by the public, if exposed, and by health officials, prompt and sufficient availability of high-quality PEP, and adequate follow-up of PEP use. Health officials' awareness of the need for PEP after a dog bite can only be achieved if the exposure is attended to immediately and communicated effectively.
However, simple husbandry changes and practical midge control measures may help break the livestock infection cycle. Housing livestock during times of maximum midge activity (from dusk to dawn) may lead to significantly reduced biting rates. Similarly, protecting livestock shelters with fine mesh netting or coarser material impregnated with insecticide will reduce contact with the midges. The "Culicoides" midges that carry the virus usually breed on animal dung and moist soils, either bare or covered in short grass. Identifying breeding grounds and breaking the breeding cycle will significantly reduce the local midge population. Turning off taps, mending leaks and filling in or draining damp areas will also help dry up breeding sites. Control by trapping midges and removing their breeding grounds may reduce vector numbers. Dung heaps or slurry pits should be covered or removed, and their perimeters (where most larvae are found) regularly scraped.
Antibody (Ig) ELISAs are used to detect historical BVDV infection; these tests have been validated in serum, milk and bulk milk samples. Ig ELISAs do not diagnose active infection but detect the presence of antibodies produced by the animal in response to viral infection. Vaccination also induces an antibody response, which can result in false positive results, therefore it is important to know the vaccination status of the herd or individual when interpreting results. A standard test to assess whether virus has been circulating recently is to perform an Ig ELISA on blood from 5–10 young stock that have not been vaccinated, aged between 9 and 18 months. A positive result indicates exposure to BVDV, but also that any positive animals are very unlikely to be PI animals themselves. A positive result in a pregnant female indicates that she has previously been either vaccinated or infected with BVDV and could possibly be carrying a PI fetus, so antigen testing of the newborn is vital to rule this out. A negative antibody result, at the discretion of the responsible veterinarian, may require further confirmation that the animal is not in fact a PI.
At a herd level, a positive Ig result suggests that BVD virus has been circulating or the herd is vaccinated. Negative results suggest that a PI is unlikely however this naïve herd is in danger of severe consequences should an infected animal be introduced. Antibodies from wild infection or vaccination persist for several years therefore Ig ELISA testing is more valuable when used as a surveillance tool in seronegative herds.
Antigen ELISA and rtPCR are currently the most frequently performed tests to detect virus or viral antigen. Individual testing of ear tissue tag samples or serum samples is performed. It is vital that repeat testing is performed on positive samples to distinguish between acute, transiently infected cattle and PIs. A second positive result, acquired at least three weeks after the primary result, indicates a PI animal. rtPCR can also be used on bulk tank milk (BTM) samples to detect any PI cows contributing to the tank. It is reported that the maximum number of contributing cows from which a PI can be detected is 300.
Although no specific treatment for acute infection with SuHV1 is available, vaccination can alleviate clinical signs in pigs of certain ages. Typically, mass vaccination of all pigs on the farm with a modified live virus vaccine is recommended. Intranasal vaccination of sows and neonatal piglets one to seven days old, followed by intramuscular (IM) vaccination of all other swine on the premises, helps reduce viral shedding and improve survival. The modified live virus replicates at the site of injection and in regional lymph nodes. Vaccine virus is shed in such low levels, mucous transmission to other animals is minimal. In gene-deleted vaccines, the thymidine kinase gene has also been deleted; thus, the virus cannot infect and replicate in neurons. Breeding herds are recommended to be vaccinated quarterly, and finisher pigs should be vaccinated after levels of maternal antibody decrease. Regular vaccination results in excellent control of the disease. Concurrent antibiotic therapy via feed and IM injection is recommended for controlling secondary bacterial pathogens.
Outbreaks in southern Europe have been caused by serotypes 2 and 4, and vaccines are available against these serotypes (ATCvet codes: for sheep, for cattle). However, the disease found in northern Europe (including the UK) in 2006 and 2007 has been caused by serotype 8. Vaccine companies Fort Dodge Animal Health (Wyeth), Merial and Intervet were developing vaccines against serotype 8 (Fort Dodge Animal Health has serotype 4 for sheep, serotype 1 for sheep and cattle and serotype 8 for sheep and cattle) and the associated production facilities. A vaccine for this is now available in the UK, produced by Intervet. Fort Dodge Animal Health has their vaccines available for multiple European Countries (vaccination will start in 2008 in Germany, Belgium, Switzerland, Spain and Italy). However, immunization with any of the available vaccines preclude later serological monitoring of affected cattle populations, a problem which could be resolved using next-generation subunit vaccines currently in development.
In January 2015, Indian researchers launched its vaccine. Named 'Raksha Blu', it will protect the animals against five strains of the ‘bluetongue’ virus prevalent in the country.
Globally, 59,000 people die from rabies each year. This is the equivalent of one person dying every nine minutes, with half of the people who die from rabies being under the age of 15. The Pan American Health Organization (PAHO) and the Pan American Center of foot-and-mouth disease (PANAFTOSA) led a mission to eliminate dog-mediated rabies in the American region by 2015. These organizations are cognizant of the regional control of rabies. The PAHO and PANAFTOSA visited Haiti in early December, 2013, and the objectives of the mission were to assess the status of Haiti’s rabies program as delivered by the Haitian Ministry of Agriculture, Natural Resources and Rural Development (MARNDR) and the Ministry of Health (MSPP). The mission was to seek opportunities for collaboration between Haiti, Brazil, and the Centers for Disease Control and Prevention (CDC) in Haiti.
Even in 2017, rabies in Haiti is still identified as a national problem, even with PEP proposed.
Rabies can be contracted in horses if they interact with rabid animals in their pasture, usually being bitten on the muzzle or lower limbs. Signs include aggression, incoordination, head-pressing, circling, lameness, muscle tremors, convulsions, colic and fever. Horses that experience the paralytic form of rabies have difficulty swallowing, and drooping of the lower jaw due to paralysis of the throat and jaw muscles. Incubation of the virus may range from 2–9 weeks. Death often occurs within 4–5 days of infection of the virus. There are no effective treatments for rabies in horses. Veterinarians recommend an initial vaccination as a foal at three months of age, repeated at one year and given an annual booster.
Rabies is a viral zoonotic neuroinvasive disease which causes inflammation in the brain and is usually fatal. Rabies, caused by the rabies virus, primarily infects mammals. In the laboratory it has been found that birds can be infected, as well as cell cultures from birds, reptiles and insects. Animals with rabies suffer deterioration of the brain and tend to behave bizarrely and often aggressively, increasing the chances that they will bite another animal or a person and transmit the disease. Most cases of humans contracting the disease from infected animals are in developing nations. In 2010, an estimated 26,000 people died from rabies, down from 54,000 in 1990.
Outbreaks of zoonoses have been traced to human interaction with and exposure to animals at fairs, petting zoos, and other settings. In 2005, the Centers for Disease Control and Prevention (CDC) issued an updated list of recommendations for preventing zoonosis transmission in public settings. The recommendations, developed in conjunction with the National Association of State Public Health Veterinarians, include educational responsibilities of venue operators, limiting public and animal contact, and animal care and management.
The diagnosis is aided by obtaining a history of the circumstances surrounding the bite. The time the bite was experienced, the location of the bite, and examination of the bite is noted. The person may have drainage from the site of the bite. They may also be febrile. Swelling may also occur. Because the wound from the bite may have healed over the punctures, the wound it may be opened and explored. The site is anesthetized prior to exploration of the wound for is examined for damage. Neurovascular status is assessed. Immune status may determine treatment as does
the presence of transplanted tissue or organs, rheumatic disease, diabetes, HIV/AIDS and sickle cell disease.
Swollen glands (lymph nodes) and red streaks radiating upward may be evident.
The diagnosis of a cat with rabies is evident by observing the cat. Cats with rabies may also appear restless, pant, and attack other animals, people, or objects. Animals with rabies typically die within a few days of appearing sick. Vaccination of the cat can prevent rabies being transmitted by the cat through a bite. If the cat is suspected of being infected with rabies, the person begins treatment with rabies vaccine.
SuHV1 can be used to analyze neural circuits in the central nervous system (CNS). For this purpose the attenuated (less virulent) Bartha SuHV1 strain is commonly used and is employed as a retrograde and anterograde transneuronal tracer. In the retrograde direction, SuHV1-Bartha is transported to a neuronal cell body via its axon, where it is replicated and dispersed throughout the cytoplasm and the dendritic tree. SuHV1-Bartha released at the synapse is able to cross the synapse to infect the axon terminals of synaptically connected neurons, thereby propagating the virus; however, the extent to which non-synaptic transneuronal transport may also occur is uncertain. Using temporal studies and/or genetically engineered strains of SuHV1-Bartha, second, third, and higher order neurons may be identified in the neural network of interest.
Contact with farm animals can lead to disease in farmers or others that come into contact with infected animals. Glanders primarily affects those who work closely with horses and donkeys. Close contact with cattle can lead to cutaneous anthrax infection, whereas inhalation anthrax infection is more common for workers in slaughterhouses, tanneries and wool mills. Close contact with sheep who have recently given birth can lead to clamydiosis, or enzootic abortion, in pregnant women, as well as an increased risk of Q fever, toxoplasmosis, and listeriosis in pregnant or the otherwise immunocompromised. Echinococcosis is caused by a tapeworm which can be spread from infected sheep by food or water contaminated with feces or wool. Bird flu is common in chickens. While rare in humans, the main public health worry is that a strain of bird flu will recombine with a human flu virus and cause a pandemic like the 1918 Spanish flu. In 2017, free range chickens in the UK were temporarily ordered to remain inside due to the threat of bird flu. Cattle are an important reservoir of cryptosporidiosis and mainly affects the immunocompromised.
A doctor or veterinarian will perform a physical exam which includes asking about the medical history and possible sources of exposure.
The following possible test could include:
- Blood samples (detect antibodies)
- Culture samples of body fluids(check for the bacteria "Yersinia pestis")
- Kidney and liver testing
- Check lymphomic system for signs of infection
- Examine body fluids for abnormal signs
- Check for swelling
- Check for signs of dehydration
- Check for fever
- Check for lung infection
Cat bites can often be prevented by:
- instructing children not to tease cats or other pets.
- being cautious with unfamiliar cats.
- approaching cats with care, even if they appear to be friendly.
- avoiding rough play with cats and kittens.
Rough play causes is perceived as aggressive. This will lead to the cat being defensive when approached by people. Preventing cat bites includes not provoking the cat.
Some conventional parasitological techniques (CPT) such as wet blood film, and stained blood smears are used because so far, the best identifier is looking at the blood of the potentially infected host. Other tissues can be looked at, but the gold standard is identifying trypanosomes in the blood. Before the infection becomes severe, it is difficult to catch as many times these cryptic infections are undetectable by direct microscopy. Since CPT is not very sensitive, it cannot be used as a sole method of diagnosis.
The Haematocrit Centrifugation Technique (HCT) is a much better alternative. Using HCT trypanosomes can be detected in the blood even in field conditions. Buffy coat can be used to increase detection. Detection with this method is approx 85 trypanosomes per millilitre.
Rather than using live animals as test subjects, Canada used serological tests such as complement fixation tests to detect trypanosomes, and have been very successful. Other tests used look at detecting antibodies generated by the host species against T.evansi antigens. This is done using the enzyme-linked immunosorbent assays (ELISA) method. Now polymerase chain reaction (PCR) and DNA probes are being used to detect Surra in animals.
No vaccine is licensed for use in the U.S. Infection with either of these bacteria results in nonspecific symptoms and can be either acute or chronic, impeding rapid diagnosis. The lack of a vaccine for either bacterium also makes them potential candidates for bioweaponization. Together with their high rate of infectivity by aerosols and resistance to many common antibiotics, both bacteria have been classified as category B priority pathogens by the US NIH and US CDC, which has spurred a dramatic increase in interest in these microorganisms. Attempts have been made to develop vaccines for these infections, which would not only benefit military personnel, a group most likely to be targeted in an intentional release, but also individuals who may come in contact with glanders-infected animals or live in areas where melioidosis is endemic.
FVRCP vaccines have also come under scrutiny of late due to possible risks to long term health. A study at Colorado State University noted an association between vaccination with parenteral (injectable) FVRCP vaccinations and development of antibodies against feline kidney tissue. Antibody development is hypothesized to develop when the immune system reacts to protein contaminants from the cell line used to cultivate vaccinial viruses. The cell line in question, the Crandell-Rees Feline Kidney (CRFK) cell line, was derived from a cat kidney. It is currently unknown whether this antibody development can lead to renal disease, though a recent follow-up study demonstrated evidence of inflammation on re-biopsy samples from some of the study cats.
In the 2010 recommendations of the international Vaccination Guidelines Group (VGG), they emphasized the importance of administering "non-adjuvanted" vaccines whenever possible.
The VGG also prefers serological testing over unnecessary re-vaccination or boosters of core vaccines after the initial 12-month booster that follows the puppy/kitten series of modified live virus [MLV] vaccines. This is because core vaccines show an excellent correlation between the presence of antibody and protective immunity and have a long DOI (Duration of Immunity). Antibody tests can be used to demonstrate the DOI after vaccination with core vaccines, though not for non-core vaccines.
The main methods of controlling surra has been chemotherapy, and chemoprophylaxis in animals.
In 2012, the World Health Organization estimated that vaccination prevents 2.5 million deaths each year. If there is 100% immunization, and 100% efficacy of the vaccines, one out of seven deaths among young children could be prevented, mostly in developing countries, making this an important global health issue. Four diseases were responsible for 98% of vaccine-preventable deaths: measles, "Haemophilus influenzae" serotype b, pertussis, and neonatal tetanus.
The Immunization Surveillance, Assessment and Monitoring program of the WHO monitors and assesses the safety and effectiveness of programs and vaccines at reducing illness and deaths from diseases that could be prevented by vaccines.
Vaccine-preventable deaths are usually caused by a failure to obtain the vaccine in a timely manner. This may be due to financial constraints or to lack of access to the vaccine. A vaccine that is generally recommended may be medically inappropriate for a small number of people due to severe allergies or a damaged immune system. In addition, a vaccine against a given disease may not be recommended for general use in a given country, or may be recommended only to certain populations, such as young children or older adults. Every country makes its own vaccination recommendations, based on the diseases that are common in its area and its healthcare priorities. If a vaccine-preventable disease is uncommon in a country, then residents of that country are unlikely to receive a vaccine against it. For example, residents of Canada and the United States do not routinely receive vaccines against yellow fever, which leaves them vulnerable to infection if travelling to areas where risk of yellow fever is highest (endemic or transitional regions).
The following steps and precautions should be used to avoid infection of the septicemic plague:
- Caregivers of infected patients should wear masks, gloves, goggles and gowns
- Take antibiotics if close contact with infected patient has occurred
- Use insecticides throughout house
- Avoid contact with dead rodents or sick cats
- Set traps if mice or rats are present around the house
- Do not allow family pets to roam in areas where plague is common
- Flea control and treatment for animals (especially rodents)
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.