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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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Avoid ingestion of raw freshwater fish. Adequate cooking or freezing of freshwater fish will kill the encysted fish tapeworm larvae. Also, because human feces is an important mechanism for spreading eggs, proper disposal of sewage can cut down on infection of fish and thus of humans.
The fundamental prevention strategy is hygiene and sanitation. Secondary measures include stricter meat-inspection standards, livestock confinement, health education, safe meat preparation, mass drug therapy, and identifying and treating human and pig carriers. Moreover, a high level of sanitation and prevention of human faecal contamination of pig feeds also plays a major role in prevention. Infection can be prevented with proper disposal of human faeces around pigs, cooking meat thoroughly and/or freezing the meat at −10 °C for 5 days. For human cysticercosis, dirty hands are attributed to be the primary cause, and especially common among food handlers.
Proper cooking of meat is an effective prevention. For example, cooking (56 °C for 5 minutes) of beef viscera destroys cysticerci. Refrigeration, freezing (−10 °C for 9 days) or long periods of salting is also lethal to cysticerci. Inspection of beef and proper disposal of human excreta are also important measures.
Most occurrences are found in areas that lack adequate sanitation and include Southeast Asia, West Africa, and East Africa.
The two drugs that have been well-described for the treatment of hymenolepiasis are praziquantel and niclosamide. Praziquantel, which is parasiticidal in a single dose for all the stages of the parasite, is the drug of choice because it acts very rapidly against "H. nana". Although structurally unrelated to other anthelminthics, it kills both adult worms and larvae. "In vitro", the drug produces vacuolization and disruption of the tegument in the neck of the worms, but not in more posterior portions of the strobila. Praziquantel is well absorbed when taken orally, and it undergoes first-pass metabolism and 80% of the dose is excreted as metabolites in urine within 24 hours.
Repeated treatment is required for "H. nana" at an interval of 7–10 days.
Praziquantel as a single dose (25 mg/kg) is the current treatment of choice for hymenolepiasis and has an efficacy of 96%. Single-dose albendazole (400 mg) is also very efficacious (>95%).
A three-day course of nitazoxanide is 75–93% efficacious. The dose is 1 g daily for adults and children over 12; 400 mg daily for children aged 4 to 11 years; and 200 mg daily for children aged 3 years or younger.
This disease has no vaccination.
Preventative measures can be taken at community and individual levels. Communities and governments can make sure their water supply remains sanitary and free of dog feces. Communities can control wild dog populations, thus preventing infection of the definitive host. Individuals should wash all fruits and vegetables thoroughly before eating and make sure their dogs are not infected with tapeworm.
"H. nana" lodges itself in the intestines and absorbs nutrients from the intestinal lumen. In human adults, the tapeworm is more of a nuisance than a health problem, but in small children, many "H. nana" worms can be dangerous. Usually, the larvae of this tapeworm cause the most problem in children; they burrow into the walls of the intestine, and if enough tapeworms are present in the child, severe damage can be inflicted. This is done by absorbing all the nutrients from the food the child eats. Usually, a single tapeworm will not cause health issues. "H. nana" usually will not cause deaths unless in extreme circumstances and usually in young children or in people who have weakened immune systems. In some parts of the world, individuals who are heavily infected are a result of internal autoinfection.
One treatment for sparganosis is praziquantel, administered at a dose of 120 to 150 mg/kg body weight over 2 days; however, praziquantel has had limited success. In general, infestation by one or a few sparganum larvae is often best treated by surgical removal.
DNA analysis of rare worms removed surgically can provide genome information to identify and characterise each parasite; treatments for the more common tapeworms can be cross-checked to see whether they are also likely to be effective against the species in question.
Tapeworms are treated with medications taken by mouth, usually in a single dose. The drug of choice for tapeworm infections is praziquantel. Niclosamide can also be used.
The disease is more complicated and severe when the oncospheres settle in the CNS tissue. This makes operating more difficult than when the disease presents in the muscles or subcutaneous tissues. The most common and widely recognized treatment for this disease is surgical removal of the cysts. However, this is not always possible. Other treatments that have seen positive results are Praziquantel and Albendazole. Praziquantel causes cell membranes of worms to become permeable. In this way the worm loses intracellular calcium. This in turn causes the worm to become paralyzed. Albendazole causes the worm to produce less ATP eventually leading to its death. Glucocorticoids can be used to help subdue the inflammatory symptoms of the disease.
Oral anti-parasitic drugs such as praziquantel are the treatment of choice. Treatment with praziquantel has been approved by the U.S. Food and Drug Administration and is quite effective against these parasites. Usual treatments are with praziquantel (5–10 mg/kg, single-administration) or niclosamide (adults and children over 6 years: 2 g, single-administration after a light breakfast, followed after 2 hours by a laxative; children aged 2–6 years: 1 g; children under 2 years: 500 mg). Albendazole is also highly effective. Atrabine is quite effective but has adverse effects in humans.
Upon diagnosis, treatment is quite simple and effective. The standard treatment for diphyllobothriasis, as well as many other tapeworm infections is a single dose of praziquantel, 5–10 mg/kg orally once for both adults and children. An alternative treatment is niclosamide, 2 g orally once for adults or 50 mg/kg (max 2 g) for children. Praziquantel is not FDA-approved for this indication and niclosamide is not available for human or even animal use in the United States. Reportedly, albendazole can also be effective. Another interesting potential diagnostic tool and treatment is the contrast medium, Gastrografin, introduced into the duodenum, which allows both visualization of the parasite, and has also been shown to cause detachment and passing of the whole worm.
In regions where helminthiasis is common, mass deworming treatments may be performed, particularly among school-age children, who are a high-risk group. Most of these initiatives are undertaken by the World Health Organization (WHO) with positive outcomes in many regions. Deworming programs can improve school attendance by 25 percent. Although deworming improves the health of an individual, outcomes from mass deworming campaigns, such as reduced deaths or increases in cognitive ability, nutritional benefits, physical growth, and performance, are uncertain or not apparent.
Because sparganosis is a rare infection, public health strategies have not made its prevention a priority. Public health strategies focusing on providing basic access to clean water may help to reduce future sparganosis infections. In their retrospective study of 25 cases of cerebral sparganosis, Song et al. found that 12 patients (48%) had eaten raw or uncooked frog or snake that was infected with sparganum, 5 patients (20%) had applied an animal's flesh as a poultice to an open wound, 4 patients had drunk contaminated water, and the cause of infection was not known for 4 patients. As a result of these findings, Song et al. conclude that health education about sparganosis and the importance of food sanitation should be implemented in all rural endemic areas. It has been recommended that water consumed in endemic areas should be boiled or treated to prevent ingestion of Cyclops or Spirometra larvae. Especially in areas where ponds or ditches provide potential habitats for infected copepods, public health strategies should include education campaigns about how to identify drinking water that could potentially be infected. Strategies should warn people against ingesting the raw flesh of the intermediate hosts, such as snakes and frogs, and against using them as poultices.
Even with the concurrent treatment of humans and pigs, complete elimination is hard to achieve. In one study conducted in 12 villages in Peru, both humans and porcine were treated with praziquantel and oxfendazole, with the coverage of more than 75% in humans and 90% in pigs The result shows a decrease in prevalence and incidence in the intervention area; however the effect did not completely eliminate "T. solium". The possible reason includes the incomplete coverage and re-infection. Even though "T. solium "could be eliminated through mass treatment of human and porcine population, it is not sustainable. Moreover, both tapeworm carriers of humans and pigs tend to spread the disease from endemic to non-endemic areas resulting in periodic outbreaks of cysticercosis or outbreaks in new areas.
Asymptomatic cysts, such as those discovered incidentally on neuroimaging done for another reason, may never lead to symptomatic disease and in many cases do not require therapy. Calcified cysts have already died and involuted. Further antiparasitic therapy will be of no benefit.
Neurocysticercosis may present as hydrocephalus and acute onset seizures, thus the immediate therapy is emergent reduction of intracranial pressure and anticonvulsant medications. Once the seizures have been brought under control, antihelminthic treatments may be undertaken. The decision to treat with antiparasitic therapy is complex and based on the stage and number of cysts present, their location, and the persons specific symptoms.
Adult "Taenia solium" are easily treated with niclosamide, and is most commonly used in taeniasis. However cysticercosis is a complex disease and requires careful medication. Praziquantel (PZQ) is the drug of choice. In neurocysticercosis praziquantel is widely used. Albendazole appears to be more effective and a safe drug for neurocysticercosis. In complicated situation a combination of praziquantel, albendazole and steroid (such as corticosteroids to reduce the inflammation) is recommended. In the brain the cysts can be usually found on the surface. Most cases of brain cysts are found by accident, during diagnosis for other ailments. Surgical removals are the only option of complete removal even if treated successfully with medications.
Antiparasitic treatment should be given in combination with corticosteroids and anticonvulsants to reduce inflammation surrounding the cysts and lower the risk of seizures. When corticosteroids are given in combination with praziquantel, cimetidine is also given, as corticosteroids decrease action of praziquantel by enhancing its first pass metabolism. Albendazole is generally preferable over praziquantel due to its lower cost and fewer drug interactions.
Surgical intervention is much more likely to be needed in cases of intraventricular, racemose, or spinal neurocysticercosis. Treatments includes direct excision of ventricular cysts, shunting procedures, and removal of cysts via endoscopy.
If complications of helminthiasis, such as intestinal obstruction occur, emergency surgery may be required. Patients who require non-emergency surgery, for instance for removal of worms from the biliary tree, can be pre-treated with the anthelmintic drug albendazole.
The capture, transportation and culture of bait fish can spread damaging organisms between ecosystems, endangering them. In 2007, several American states, including Michigan, enacted regulations designed to slow the spread of fish diseases, including viral hemorrhagic septicemia, by bait fish. Because of the risk of transmitting "Myxobolus cerebralis" (whirling disease), trout and salmon should not be used as bait. Anglers may increase the possibility of contamination by emptying bait buckets into fishing venues and collecting or using bait improperly. The transportation of fish from one location to another can break the law and cause the introduction of fish and parasites alien to the ecosystem.
Moderate hookworm infections have been demonstrated to have beneficial effects on hosts suffering from diseases linked to overactive immune systems. This is possibly explained by the hygiene hypothesis. Research at the University of Nottingham conducted in Ethiopia observed a small subset of people with hookworm infections were half as likely to experience asthma or hay fever. Potential benefits have also been hypothesized in cases of multiple sclerosis, Crohn's Disease and diabetes.
Some research conducted has shown favourable results using hookworms to treat coeliac disease. Though research points to anti-allergenic properties associated with hook worm infections, the FDA does not currently recognize hookworms as a treatment.
Though not a health concern in thoroughly cooked fish, parasites are a concern when human consumers eat raw or lightly preserved fish such as sashimi, sushi, ceviche, and gravlax. The popularity of such raw fish dishes makes it important for consumers to be aware of this risk. Raw fish should be frozen to an internal temperature of −20 °C (−4 °F) for at least 7 days to kill parasites. It is important to be aware that home freezers may not be cold enough to kill parasites.
Traditionally, fish that live all or part of their lives in fresh water were considered unsuitable for sashimi due to the possibility of parasites (see Sashimi article). Parasitic infections from freshwater fish are a serious problem in some parts of the world, particularly Southeast Asia. Fish that spend part of their life cycle in salt water, like salmon, can also be a problem. A study in Seattle, Washington showed that 100% of wild salmon had roundworm larvae capable of infecting people. In the same study farm raised salmon did not have any roundworm larvae.
Parasite infection by raw fish is rare in the developed world (fewer than 40 cases per year in the U.S.), and involves mainly three kinds of parasites: Clonorchis sinensis (a trematode/fluke), Anisakis (a nematode/roundworm) and Diphyllobothrium (a cestode/tapeworm). Infection by the fish tapeworm "Diphyllobothrium latum" is seen in countries where people eat raw or undercooked fish, such as some countries in Asia, Eastern Europe, Scandinavia, Africa, and North and South America. Infection risk of anisakis is particularly higher in fishes which may live in a river such as salmon ("shake") in Salmonidae, mackerel ("saba"). Such parasite infections can generally be avoided by boiling, burning, preserving in salt or vinegar, or freezing overnight. Even Japanese people never eat raw salmon or ikura (salmon roe), and even if they seem raw, these foods are not raw but are frozen overnight to prevent infections from parasites, particularly anisakis.
Below are some life cycles of fish parasites that can infect humans:
While annual or semi-annual mass antihelminthic administration is a critical aspect of any public health intervention, many have begun to realize how unsustainable it is due to aspects such as poverty, high rates of re-infection, and diminished efficacy of drugs with repeated use. Current research, therefore, has focused on the development of a vaccine that could be integrated into existing control programs. The goal of vaccine development is not necessarily to create a vaccine with sterilizing immunity or complete protection against immunity. A vaccine that reduces the likelihood of vaccinated individuals developing severe infections and thus reduced blood and nutrient levels could still have a significant impact on the high burden of disease throughout the world.
Current research focuses on targeting two stages in the development of the worm: the larval stage and the adult stage. Research on larval antigens has focused on proteins that are members of the pathogenesis-related protein superfamily, "Ancylostoma" Secreted Proteins. Although they were first described in "Anyclostoma", these proteins have also been successfully isolated from the secreted product of "N. americanus". "N. americanus" ASP-2 (Na-ASP-2) is currently the leading larval-stage hookworm vaccine candidate. A randomized, double-blind, placebo-controlled study has already been performed; 36 healthy adults without a history of hookworm infection were given three intramuscular injections of three different concentrations of Na-ASP-2 and observed for six months after the final vaccination. The vaccine induced significant anti-Na-ASP-2 IgG and cellular immune responses. In addition, it was safe and produced no debilitating side effects. The vaccine is now in a phase one trial; healthy adult volunteers with documented evidence of previous infection in Brazil are being given the same dose concentration on the same schedule used in the initial study. If this study is successful, the next step would be to conduct a phase two trial to assess the rate and intensity of hookworm infection among vaccinated persons. Because the Na-ASP-2 vaccine only targets the larval stage, it is critical that all subjects enrolled in the study be treated with antihelminthic drugs to eliminate adult worms prior to vaccination.
Adult hookworm antigens have also been identified as potential candidates for vaccines. When adult worms attach to the intestinal mucosa of the human host, erythrocytes are ruptured in the worm’s digestive tract which causes the release of free hemoglobin which is subsequently degraded by a proteolytic cascade. Several of these proteins that are responsible for this proteolytic cascade are also essential for the worm’s nutrition and survival. Therefore, a vaccine that could induce antibodies for these antigens could interfere with the hookworm’s digestive pathway and impair the worm’s survival. Three proteins have been identified: the aspartic protease-hemoglobinase APR-1, the cysteine protease-hemoglobinase CP-2, and a glutathione S-transferase.
Anecdotal data gathered from helminth self-treaters and their physicians and presented in socio-medical studies suggest that a much larger number of diseases may be amenable to helminthic therapy than are currently being investigated by formal clinical trials.
Evidence in support of the idea that helminthic infections reduce the severity of autoimmune diseases is primarily derived from animal models. Studies conducted on mice and rat models of colitis, muscular sclerosis, type 1 diabetes, and asthma have shown helminth-infected subjects to display protection from the disease. While helminths are often considered a homogenous group, considerable differences exist between species and the utilization of species in clinical research varies between human and animal trials. As such, caution must be exercised when interpreting the results from animal models.
Helminthic therapy is currently being studied as a treatment for several (non-viral) autoimmune diseases in humans including celiac disease, Crohn's disease, multiple sclerosis, ulcerative colitis, and atherosclerosis. It is currently unknown which clinical dose or species of helminth is the most effective method of treatment. Hookworms have been linked to reduced risk of developing asthma, while "Ascaris lumbricoides" (roundworm infection) was associated with an "increased" risk of asthma. Similarly, "Hymenolepis nana", "Trichoris trichiura", "Ascaris lumbricoides", "Strongyloides stercolaris", "Enterobius vermicularis", and "Trichuris suis" ova have all been found to lower the number of symptom exacerbations, reduce the number of symptom relapses, and decrease the number of new or enlarging brain lesions in patients with multiple sclerosis at doses ranging from 1,180 to 9,340 eggs per gram. However, "Ascaris lumbricoides", "Strongyloides stercolaris" and "Enterobius vermicularis" are not considered suitable for therapeutic use in humans because they do not meet the criteria for a therapeutic helminth.
"Trichuris suis" ova has been used in most cases to treat autoimmune disorders because it is thought to be non-pathogenic in humans and therefore has been rendered as safe.
The use of "Trichuris suis" ova has been granted by the USA Food and Drug Administration as an investigational medicinal product (IMP). While in the UK, the hookworm "Necator americanus" has been granted an IMP license by the Medicines and Healthcare Regulatory Authority. This hookworm is likely to be relatively safe, although it can cause temporary gastrointestinal side effects, especially following the initial inoculation and with larger doses.
The general ideal characteristics for a therapeutic helminth are as follows:
- Little or no pathogenic potential
- Does not multiply in the host
- Cannot be directly spread to close contacts
- Produces a self-limited colonization in humans
- Produces an asymptomatic colonization in humans
- Does not alter behaviour in patients with depressed immunity
- Is not affected by most commonly used medications
- Can be eradicated with an anti-helminthic drug
- Can be isolated free of other potential pathogens
- Can be isolated or produced in large numbers
- Can be made stable for transport and storage
- Easy to administer
Currently there are no human vaccines against any form of echinococcosis. However, there are studies being conducted that are looking at possible vaccine candidates for an effective human vaccine against echinococcosis.
While a number of control and prevention strategies deal with cystic and alveolar echinococcosis, there are few methods to control and prevent polycystic echinococcosis. This is probably due to the fact that polycystic echinococcosis is restricted to Central and South America, and that the way that humans become accidental hosts of "E. oligarthrus" and "E. vogeli" is still not completely understood.
There is a lack of scientific study to support the efficacy of any particular treatment. An additional review published in 2009 made a similar conclusion, noting that because the diagnostics in use have been unreliable, it has been impossible to determine whether a drug has eradicated the infection, or just made the patient feel better. Historical reports, such as one from 1916, note difficulty associated with eradication of "Blastocystis" from patients, describing it as "an infection that is hard to get rid of."
A 1999 "in vitro" study from Pakistan found 40% of isolates are resistant to common antiprotozoal drugs. A study of isolates from patients diagnosed with IBS found 40% of isolates resistant to metronidazole and 32% resistant to furazolidone. Drugs reported in studies to be effective in eradicating "Blastocystis" infection have included metronidazole, trimethoprim, TMP-SMX (only trimethoprim is active with sulphamethoxazole demonstrating no activity), tetracycline, doxycycline, nitazoxanide, pentamidine, paromomycin and iodoquinol. Iodoquinol has been found to be less effective in practice than in-vitro. Miconazole and quinacrine have been reported as effective agents against "Blastocystis" growth in-vitro. Rifaximin, and albendazole have shown promise as has ivermectin which demonstrated high effectiveness against blastocystis hominis isolates in an in vitro study. There is also evidence that the probiotic yeast "Saccharomyces boulardii", and the plant mallotus oppositifolius may be effective against "Blastocystis" infections.
Physicians have described the successful use of a variety of discontinued antiprotozoals in treatment of "Blastocystis" infection. Emetine was reported as successful in cases in early 20th century with British soldiers who contracted "Blastocystis" infection while serving in Egypt. "In vitro" testing showed emetine was more effective than metronidazole or furazolidone. Emetine is available in the United States through special arrangement with the Center for Disease Control. Clioquinol (Entero-vioform) was noted as successful in treatment of "Blastocystis" infection but removed from the market following an adverse event in Japan. Stovarsol and Narsenol, two arsenic-based antiprotozoals, were reported to be effective against the infection. Carbarsone was available as an anti-infective compound in the United States as late as 1991, and was suggested as a possible treatment. The reduction in the availability of antiprotozoal drugs has been noted as a complicating factor in treatment of other protozoal infections. For example, in Australia, production of diloxanide furoate ended in 2003, paromomycin is available under special access provisions, and the availability of iodoquinol is limited.