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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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One strategy to control the disease in areas where it is common is the treatment of entire groups of people regardless of symptoms via mass drug administration. This is often done among school-age children and is known as deworming. While testing and treating children who are infected looks like it is effective, there is insufficient evidence to conclude that routine deworming, in the absence of a positive test, improves nutrition, haemoglobin, school attendance or school performance.
For this purpose, broad-spectrum benzimidazoles such as mebendazole and albendazole are the drugs of choice recommended by WHO. These anthelminthics are administered in a single dose are safe, relatively inexpensive, and effective for several months. Mebendazole can be given with a single dose twice a day for three consecutive days. Albendazole is given at a single dose. WHO recommends annual treatment in areas where between 20 and 50% of people are infected, and a twice a year treatment if it is over 50%; and in low risk situation (i.e. less than 20% prevalence) case-by-case treatment. In addition to these, pyrantel pamoate is also equally effective on ascaris. However, it has been reported that albendazole, mebendazole, and pyrantel pamoate are not entirely effective against "T. trichiura" with single oral doses in population-based control.
Broad-spectrum benzimidazoles (such as albendazole and mebendazole) are the first line treatment of intestinal roundworm and tapeworm infections. Macrocyclic lactones (such as ivermectin) are effective against adult and migrating larval stages of nematodes. Praziquantel is the drug of choice for schistosomiasis, taeniasis, and most types of food-borne trematodiases. Oxamniquine is also widely used in mass deworming programmes. Pyrantel is commonly used for veterinary nematodiasis. Artemisinins and derivatives are proving to be candidates as drugs of choice for trematodiasis.
Anti-helminthics are often used to kill off the worms, however in some cases this may cause patients to worsen due to toxins released by the dying worms. Albendazole, ivermectin, mebendazole, and pyrantel are all commonly used, though albendazole is usually the drug of choice. Studies have shown that anti-helminthic drugs may shorten the course of the disease and relieve symptoms. Therefore anti-helminthics are generally recommended, but should be administered gradually so as to limit the inflammatory reaction.
In cases of coinfection, combination therapy with ivermectin and diethylcarbamazine is advocated. However coinfection with malaria and HIV, especially among African women, does not respond well to the current combination therapies. It is more pressing for trichuriasis that the recommended drugs fail to provide positive results. A novel drug tribendimidine, which was approved in China by the CCDC for human use in 2004, has been subjected to clinical trials showing that they are highly effective against major human flukes, ascaris (>90% cure rate) and hookworm (>82%); however with low cure rate for whipworm (<37%).
Anti-helminthics should generally be paired with corticosteroids in severe infections to limit the inflammatory reaction to the dying parasites. Studies suggest that a two-week regimen of a combination of mebendazole and prednisolone significantly shortened the course of the disease and length of associated headaches without observed harmful side effects. Other studies suggest that albendazole may be more favorable, because it may be less like to incite an inflammatory reaction. The Chinese herbal medicine long-dan-xie-gan-tan (LDGXT) has also been shown to have a similar anti inflammatory effect, and in mild cases may be used alone to relieve symptoms while infection resolves itself.
The highest clearance rates are obtained by combining mebendazole or albendazole with ivermectin. Ivermectin's safety in children under and pregnant women has not yet been established.
People with diarrhea may be treated with loperamide to increase the amount of drug contact with the parasites.
Mebendazole is 90% effective in the first dose, and albendazole may also be offered as an anti-parasitic agent. Adding iron to the bloodstream helps solve the iron deficiency and rectal prolapse. Difetarsone is also an effective treatment.
The most common treatment for hookworm are benzimidazoles, specifically albendazole and mebendazole. BZAs kill adult worms by binding to the nematode’s β-tubulin and subsequently inhibiting microtubule polymerization within the parasite. In certain circumstances, levamisole and pyrantel pamoate may be used. A 2008 review found that the efficacy of single-dose treatments for hookworm infections were as follows: 72% for albendazole, 15% for mebendazole, and 31% for pyrantel pamoate. This substantiates prior claims that albendazole is much more effective than mebendazole for hookworm infections. Also of note is that the World Health Organization does recommend anthelmintic treatment in pregnant women after the first trimester. It is also recommended that if the patient also suffers from anemia that ferrous sulfate (200 mg) be administered three times daily at the same time as anthelmintic treatment; this should be continued until hemoglobin values return to normal which could take up to 3 months.
Hookworm infection can be treated with local cryotherapy when the hookworm is still in the skin.
Albendazole is effective both in the intestinal stage and during the stage the parasite is still migrating under the skin.
In case of anemia, iron supplementation can cause relief symptoms of iron deficiency anemia. However, as red blood cell levels are restored, shortage of other essentials such as folic acid or vitamin B12 may develop, so these might also be supplemented.
The drug of choice for the treatment of hookworm disease is mebendazole which
is effective against both species, and in addition, will remove the intestinal
worm Ascaris also, if present. The drug is very efficient, requiring only a
single dose and is inexpensive. However, treatment requires
more than giving the anthelmintic, the patient should also receive dietary
supplements to improve their general level of health, in particular iron
supplementation is very important. Iron is an important constituent of a
multitude of enzyme systems involved in energy metabolism, DNA synthesis and
drug detoxification.
An infection of "N. americanus" parasites can be treated by using benzimidazoles, albendazole, and mebendazole. A blood transfusion may be necessary in severe cases of anemia. Light infections are usually left untreated in areas where reinfection is common. Iron supplements and a diet high in protein will speed the recovery process. In a case study involving 56–60 men with "Trichuris trichiura" and/or "N. americanus" infections, both albendazole and mebendazole were 90% effective in curing "T. trichiura". However, albendazole had a 95% cure rate for "N. americanus", while mebendazole only had a 21% cure rate. This suggests albendazole is most effective for treating both "T. trichiura" and "N. americanus".
Other important issues related to the treatment of hookworm are reinfection and drug resistance. It has been shown that reinfection after treatment can be extremely high. Some studies even show that 80% of pretreatment hookworm infection rates can be seen in treated communities within 30–36 months. While reinfection may occur, it is still recommended that regular treatments be conducted as it will minimize the occurrence of chronic outcomes. There are also increasing concerns about the issue of drug resistance. Drug resistance has appeared in front-line anthelmintics used for livestock nematodes. Generally human nematodes are less likely to develop resistance due to longer reproducing times, less frequent treatment, and more targeted treatment. Nonetheless, the global community must be careful to maintain the effectiveness of current anthelmintic as no new anthelmintic drugs are in the late-stage development.
An infection of "N. americanus" parasites can be treated by using benzimidazoles: albendazole or mebendazole. A blood transfusion may be necessary in severe cases of anemia. Light infections are usually left untreated in areas where reinfection is common. Iron supplements and a diet high in protein will speed the recovery process. In a case study involving 56-60 men with "Trichuris trichiura" and/or "N. americanus" infections, both albendazole and mebendazole were 90% effective in curing "T. trichiura". However, albendazole had a 95% cure rate for "N. americanus", while mebendazole only had a 21% cure rate. This suggests albendazole is most effective for treating both "T. trichiura" and "N. americanus".
Cryotherapy by application of liquid nitrogen to the skin has been used to kill cutaneous larvae migrans, but the procedure has a low cure rate and a high incidence of pain and severe skin damage, so it now is passed over in favor of suitable pharmaceuticals. Topical application of some pharmaceuticals has merit, but requires repeated, persistent applications and is less effective than some systemic treatments.
Amphistomiasis is considered a neglected tropical disease, with no prescription drug for treatment and control. Therefore, management of infestation is based mainly on control of the snail population, which transmit the infective larvae of the flukes. However, there are now drugs shown to be effective including resorantel, oxyclozanide, clorsulon, ivermectin, niclosamide, bithional and levamisole. An in vitro demonstration shows that plumbagin exhibits high efficacy on adult flukes. Since the juvenile flukes are the causative individuals of the disease, effective treatment means control of the immature fluke population. Prophylaxis is therefore based on disruption of the environment (such as proper drainage) where the carrier snails inhabit, or more drastic action of using molluscicides to eradicate the entire population. For treatment of the infection, drugs effective against the immature flukes are recommended for drenching. For this reason oxyclozanide is advocated as the drug of choice. It effectively kills the flukes within a few hours and it effective against the flukes resistant to other drugs. The commercially prescribed dosage is 5 mg/kg body weight or 18.7 mg/kg body weight in two divided dose within 72 hours. Niclosamide is also extensively used in mass drenching of sheep. Successfully treated sheep regain appetite within a week, diarrhoea stops in about three days, and physiological indicators (such as plasma protein and albumin levels) return to normal in a month.
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.
Limited access to essential medicine poses a challenge to the eradication of trichuriasis worldwide. Also, it is a public health concern that rates of post-treatment re-infection need to be determined and addressed to diminish the incidence of untreated re-infection. Lastly, with mass drug administration strategies and improved diagnosis and prompt treatment, detection of an emergence of antihelminthic drug resistance should be examined.
Mass Drug Administration (preventative chemotherapy) has had a positive effect on the disease burden of trichuriasis in East and West Africa, especially among children, who are at highest risk for infection.
Education, improved sanitation, and controlled disposal of human feces are critical for prevention. Nonetheless, wearing shoes in endemic areas helps reduce the prevalence of infection.
Control of this parasite should be directed against reducing the level of
environmental contamination. Treatment of heavily infected individuals is one
way to reduce the source of contamination (one study has estimated that 60% of
the total worm burden resides in less than 10% of the population). Other
obvious methods are to improve access to sanitation, e.g. toilets, but also
convincing people to maintaining them in a clean, functional state, thereby making
them conducive to use.
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.
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
The preventative measure of keeping cats inside in areas with high infection rates can prevent infection. Approved tick treatments for cats can be used but have been shown not to fully prevent tick bites.
The most often used treatments for cytauxzoonosis are imidocarb dipropionate and a combination of atovaquone and azithromycin. Although imidocarb has been used for years, it is not particularly effective. In a large study, only 25% of cats treated with this drug and supportive care survived. 60% of sick cats treated with supportive care and the combination of the anti-malarial drug atovaquone and the antibiotic azithromycin survived infection.
Quick referral to a veterinarian equipped to treat the disease may be beneficial. All infected cats require supportive care, including careful fluids, nutritional support, treatment for complications, and often blood transfusion.
Cats that survive the infection should be kept indoors as they can be persistent carriers after surviving infection and might indirectly infect other cats after being themselves bitten by a vector tick.
Concomitant pinworm infection should also be excluded, although the association has not been proven. Successful treatment of the infection with iodoquinol, doxycycline, metronidazole, paromomycin, and secnidazole has been reported. Resistance requires the use of combination therapy to eradicate the organism. All persons living in the same residence should be screened for "D. fragilis", as asymptomatic carriers may provide a source of repeated infection. Paromomycin is an effective prophylactic for travellers who will encounter poor sanitation and unsafe drinking water.
The medications prescribed for acute toxoplasmosis are the following:
- Pyrimethamine — an antimalarial medication
- Sulfadiazine — an antibiotic used in combination with pyrimethamine to treat toxoplasmosis
- Combination therapy is usually given with folic acid supplements to reduce incidence of thrombocytopaenia.
- Combination therapy is most useful in the setting of HIV.
- Clindamycin
- Spiramycin — an antibiotic used most often for pregnant women to prevent the infection of their children.
(other antibiotics, such as minocycline, have seen some use as a salvage therapy).
If infected during pregnancy, spiramycin is recommended in the first and early second trimesters while pyrimethamine/sulfadiazine and leucovorin is recommended in the late second and third trimesters.
In people with latent toxoplasmosis, the cysts are immune to these treatments, as the antibiotics do not reach the bradyzoites in sufficient concentration.
The medications prescribed for latent toxoplasmosis are:
- Atovaquone — an antibiotic that has been used to kill "Toxoplasma" cysts inside AIDS patients
- Clindamycin — an antibiotic that, in combination with atovaquone, seemed to optimally kill cysts in mice
Helminths are extremely successful parasites capable of establishing long-lasting infections within a host. During this time, helminths compete with the host organism's cells for nutrient resources and thus possess the potential to cause harm. However, the number of organisms hosted by individuals undergoing helminthic therapy is very small and any side effects are typically only encountered in the first three months of infection. In the long term, the vast majority of clinically infected individuals are asymptomatic, with no significant nutrient loss. In fact, nutrient uptake can be enhanced in some subjects who are hosting a small number of helminths. If the side effects from helminthic therapy were to become unmanageable, they can be alleviated by the use of anthelminthic medications.[1][7][8] The most common clinical symptoms which may be encountered while undergoing helminthic therapy can include:
- Fatigue
- Gastrointestinal discomfort
- Anemia
- Fever
- Abdominal pain
- Weight loss
- Anorexia
- Diarrhea
- General malaise
Inclusion of NTDs into initiatives for malaria, HIV/AIDS, and tuberculosis, as well as integration of NTD treatment programs, may have advantages given the strong link between these diseases and NTDs. Some neglected tropical diseases share common vectors (sandflies, black flies, and mosquitos). Both medicinal and vector control efforts may be combined.
A four-drug rapid-impact package has been proposed for widespread proliferation. Administration may be made more efficient by targeting multiple diseases at once, rather than separating treatment and adding work to community workers. This package is estimated to cost US$0.40 per patient. When compared to stand-alone treatment, the savings are estimated to be 26–47%. While more research must be done in order to understand how NTDs and other diseases interact in both the vector and the human stages, safety assessments have so far produced positive results.
Many neglected tropical diseases and other prevalent diseases share common vectors, creating another opportunity for treatment and control integration. One such example of this is malaria and lymphatic filariasis. Both diseases are transmitted by the same or related mosquito vectors. Vector control, through the distribution of insecticide treated nets, reduces the human contact with a wide variety of disease vectors. Integrated vector control may also alleviate pressure on mass drug administration, especially with respect to rapidly evolving drug resistance. Combining vector control and mass drug administration deemphasizes both, making each less susceptible to resistance evolution.
Biotechnology companies in the developing world have targeted neglected tropical diseases due to need to improve global health.
Mass drug administration is considered a possible method for eradication, especially for lymphatic filariasis, onchocerciasis, and trachoma, although drug resistance is a potential problem. According to Fenwick, Pfizer donated 70 million doses of drugs in 2011 to eliminate trachoma through the International Trachoma Initiative. Merck has helped The African Programme for the Control of Onchocerciasis (APOC) and Oncho Elimination Programme for the Americas to greatly diminished the effect of Onchocerciasis by donating ivermectin. Merck KGaA pledged to give 200 million tablets of praziquantel over 10 years, the only cure for schistosomiasis. GlaxoSmithKline has donated two billion tablets of medicine for lymphatic filariasis and pledged 400 million deworming tablets per year for five years in 2010. Johnson & Johnson has pledged 200 million deworming tablets per year. Novartis has pledged leprosy treatment, EISAI pledged two billion tablets to help treat lymphatic filariasis.
Amphistomiasis or paramphistomiasis (alternatively spelled amphistomosis or paramphistomosis) is a parasitic disease of livestock animals, more commonly of cattle and sheep, and humans caused by immature helminthic flatworms belonging to the order Echinostomida. The term amphistomiasis is used for broader connotation implying the disease inflicted by members of Echinostomida including the family Paramphistomidae/Gastrodiscidae (to be precise, the species "Gastrodiscoides hominis"); whereas paramphistomiasis is restricted to that of the members of the family Paramphistomatidae only. "G. discoides" and "Watsonius watsoni" are responsible for the disease in humans, while most paramphistomes are responsible in livestock animals, and some wild mammals. In livestock industry the disease causes heavy economic backlashes due to poor production of milk, meat and wool.