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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.
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".
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%).
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.
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.
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.
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.
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.
In eye disease, surgical removal is necessary for cysts within the eye itself as treating intraocular lesions with anthelmintics will elicit an inflammatory reaction causing irreversible damage to structural components. Cysts outside the globe can be treated with anthelmintics and steroids. Treatment recommendations for subcutaneous cysticercosis includes surgery, praziquantel and albendazole.
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.
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.
For alveolar echinococcosis, surgical removal of cysts combined with chemotherapy (using albendazole and/or mebendazole) for up to two years after surgery is the only sure way to completely cure the disease. However, in inoperable cases, chemotherapy by itself can also be used. In treatment using just chemotherapy, one could use either mebendazole in three doses or albendazole in two doses. Since chemotherapy on its own is not guaranteed to completely rid the patient of disease, patients are often kept on the drugs for extended periods of times (i.e. more than 6 months, years). In addition to surgery and chemotherapy, liver transplants are being looked into as a form of treatment for alveolar echinococcosis although it is seen as incredibly risky since it often leads to echinococcosis re-infection in the patient afterwards.
For simple cases of cystic echinococcosis, the most common form of treatment is open surgical removal of the cysts combined with chemotherapy using albendazole and/or mebendazole before and after surgery. However, if there are cysts in multiple organs or tissues, or the cysts are in risky locations, surgery becomes impractical. For inoperable cases such as these, chemotherapy and/or PAIR (puncture-aspiration-injection-reaspiration) become alternative options of treatment. In the case of alternative treatment using just chemotherapy, albendazole is preferred twice a day for 1–5 months. An alternative to albendazole is mebendazole for at least 3 to 6 months. The other alternative to surgery is PAIR with chemotherapy. PAIR is a minimally invasive procedure that involves three steps: puncture and needle aspiration of the cyst, injection of a scolicidal solution for 20–30 min, and cyst-re-aspiration and final irrigation. Patients who undergo PAIR typically take albendazole or mebendazole from 7 days before the procedure until 28 days after the procedure. While open surgery still remains as the standard for cystic echinococcosis treatment, there have been a number of studies that suggest that PAIR with chemotherapy is more effective than surgery in terms of disease recurrence, and morbidity and mortality. In addition to the three above mentioned treatments, there is currently research and studies looking at new treatment involving percutaneous thermal ablation (PTA) of the germinal layer in the cyst by means of a radiofrequency ablation device. This form of treatment is still relatively new and requires much more testing before being widely used. An alternative to open surgery is laparoscopic surgery, which provides excellent cure rates with minimal morbidity and mortality.
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.
The cornerstone of prevention and treatment of podoconiosis is avoidance of exposure to irritant soils. Wearing shoes in the presence of irritant soils is the primary method of exposure reduction. In Rwanda, a country of high disease prevalence, the government has banned walking barefoot in public, in order to curtail podoconiosis and other soil-borne diseases.
Once the disease has developed, rigorous foot hygiene including daily washing with soap and water, application of an emollient, and nightly elevation of the affected extremity has been shown to reduce swelling and disability. Compression wrapping and decongestive physiotherapy of the affected extremity has been shown to be effective in other forms of lymphedema, but the benefits of these therapies have not been rigorously studied in podoconiosis. Nodules will not resolve with these conservative measures, although surgical removal of the nodules can be performed.
Tuberculosis is the leading cause of death around the world for an infectious disease. This disease is especially prevalent in sub-Saharan Africa, and the Latin American and Caribbean region. While the tuberculosis rate is decreasing in the rest of the world, it is increasing by rate of 6 percent per year in Sub-Saharan Africa. It is the leading cause of death for people with HIV in Africa. Tuberculosis (TB) is closely related to lifestyles of poverty, overcrowded conditions, alcoholism, stress, drug addiction and malnutrition. This disease spreads quickly among people who are undernourished. According to the Center for Disease Control and Prevention, in the United States, tuberculosis is more prevalent among foreign born persons, and ethnic minorities. The rates are especially high among Hispanics, Blacks and Asians.
HIV infection and TB are also closely tied. Being infected with HIV increases the rate of activation of latent TB infections, and having TB, increases the rate of HIV replication, therefore accelerating the progression of AIDS.
Schistosomiasis (bilharzia) is a parasitic disease caused by the parasitic flatworm trematodes. Moreover, more than 80 percent of the 200 million people worldwide who have schistosomiasis live in sub-Saharan Africa. Infections often occur in contaminated water where freshwater snails release larval forms of the parasite. After penetrating the skin and eventually traveling to the intestines or the urinary tract, the parasite lays eggs and infects those organs. It damages the intestines, bladder, and other organs and can lead to anemia and protein-energy deficiency. Along with malaria, schistosomiasis is one of the most important parasitic co-factors aiding in HIV transmission. Epidemiological data shows schistosome-endemic areas coincide with areas of high HIV prevalence, suggesting that parasitic infections such as schistosomiasis increase risk of HIV transmission.