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
Chloroquine was used unsuccessfully in attempts to treat opisthorchiasis in 1951-1968. Control of opisthorchiasis relies predominantly on antihelminthic treatment with praziquantel. The single dose of praziquantel of 40 mg/kg is effective against opisthorchiasis (and also against schistosomiasis). Despite the efficacy of this compound, the lack of an acquired immunity to infection predisposes humans to reinfections in endemic regions. In addition, under experimental conditions, the short-term treatment of "Opisthorchis viverrini"-infected hamsters with praziquantel (400 mg per kg of live weight) induced a dispersion of parasite antigens, resulting in adverse immunopathological changes as a result of oxidative and nitrative stresses following re-infection with "Opisthorchis viverrini", a process which has been proposed to initiate and/or promote the development of cholangiocarcinoma in humans. Albendazole can be used as an alternative.
A randomised-controlled trial published in 2011 showed that the broad-spectrum anti-helminthic, tribendimidine, appears to be at least as efficacious as praziquantel. Artemisinin was also found to have anthelmintic activity against "Opisthorchis viverrini".
Effective prevention could be readily achieved by persuading people to consume cooked fish (via education programs), but the ancient cultural custom to consume raw, undercooked or freshly pickled fish persists in endemic areas. One community health program, known as the "Lawa" model, has achieved success in the Lawa Lakes region south of Khon Kaen. Currently, there is no effective chemotherapy to combat cholangiocarcinoma, such that intervention strategies need to rely on the prevention or treatment of liver fluke infection/disease.
Cooking or deep-freezing (-20 °C for 7 days) of food made of fish is sure method of prevention. Methods for prevention of "Opisthorchis viverrini" in aquaculture fish ponds were proposed by Khamboonruang et al. (1997).
Praziquantel is recommended in both adult and pediatric cases with dosages of 75 mg/kg/d in 3 doses for 1 day. Praziquantel is a Praziniozoquinoline derivative that alters the calcium flux through the parasite tectum and causes muscular paralysis and detachment of the fluke. Prizaquantel should be taken with liquids during a meal and as provided commercially as Biltricide. Praziquantel is not approved by the U.S. Food and Drug Administration (FDA) for treatment of metagonimiasis, but is approved for use on other parasitic infections.
Praziquantel has some side effects but they are generally relatively mild and transient and a review of evidence shows it overall a well-tolerated drug. Possible side effects include abdominal pain, allergy, diarrhea, headache, liver problems, nausea or vomiting, exacerbation of porphyries, pruritis, rash, somnolence, vertigo, or dizziness. In fact, in 2002, the World Health Organization recommended the use of Praziquantel in pregnant and lactating women, though controlled trials are still needed to verify this.
Another possible drug option is Tetrachloroethylene, a chlorinated hydrocarbon, but its use has been superseded by new antihelminthic drugs (like Praziquantel). A 1978 study also looked at the efficacy of several drugs on metagonimiasis infection, including bithionol, niclosamide, nicoflan, and Praziquantel. All drugs showed lower prevalence of eggs in feces, however only Praziquantel showed complete radical cure. Therefore, the authors concluded Praziquantel was the most highly effective, was very well tolerated, and was the most promising drug against metagonimiasis.
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.
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.
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.
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 drug of choice for the treatment of uncomplicated strongyloidiasis is ivermectin. Ivermectin does not kill the "Strongyloides" larvae, only the adult worms, therefore repeat dosing may be necessary to properly eradicate the infection. There is an auto-infective cycle of roughly two weeks in which Ivermectin should be re-administered however additional dosing may still be necessary as it will not kill "Strongyloides" in the blood or larvae deep within the bowels or diverticula. Other drugs that are effective are albendazole and thiabendazole (25 mg/kg twice daily for 5 days—400 mg maximum (generally)). All patients who are at risk of disseminated strongyloidiasis should be treated. The optimal duration of treatment for patients with disseminated infections is not clear.
Treatment of strongyloidiasis can be difficult and "Strongyloides" has been known to live in individuals for decades; even after treatment. Continued treatment is thus necessary even if symptoms resolve.
Because of the high cost of Stromectol, the veterinary formula Ivomec can be used. Government programs are needed to help citizens finance lifelong medication.
Clothes and sheets must be washed with enzyme washing powder and dried on hot daily.
Several public health prevention strategies could help lower the rates of metagonimiasis. One is to control the intermediate host (snails). This can be done through use of molluscidals. Another is to use education to ensure all people, especially in areas were the disease regularly occurs, fully cook all fish. This could potentially be problematic and not as effective as hoped as many of the people affected by metagonimiasis eat raw or pickled fish as part of a traditional, long-seated dietary practice. Additionally, implementing more sanitary water conditions would reduce the continual reintroduction of eggs to water sources, thus restarting the lifecycle. Complete control of metagonimiasis presents several potential problems because it does have several reservoir hosts, thus eradication is unlikely.
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.
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.
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.
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.
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 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.
Clonorchiasis is an infectious disease caused by the Chinese liver fluke, "Clonorchis sinensis", and two related species.
Clonorchiasis is a known risk factor for the development of cholangiocarcinoma, a neoplasm of the biliary system.
Symptoms of opisthorchiasis caused by "Opisthorchis viverrini" and by "Opisthorchis felineus" are indistinguishable from clonorchiasis caused by "Clonorchis sinensis", so the disease by these three parasites should be referred as clonorchiasis.
Liver fluke is a collective name of a polyphyletic group of parasitic trematodes under the phylum Platyhelminthes.
They are principally parasites of the liver of various mammals, including humans. Capable of moving along the blood circulation, they can occur also in bile ducts, gallbladder, and liver parenchyma. In these organs, they produce pathological lesions leading to parasitic diseases. They have complex life cycles requiring two or three different hosts, with free-living larval stages in 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
The body of liver flukes is leaf-like, and flattened. The body is covered with a tegument. They are hermaphrodites having complete sets of both male and female reproductive systems. They have simple digestive systems, and primarily feed on blood. The anterior end is the oral sucker opening into the mouth. Inside, mouth lead to a small pharynx which is followed by an extended intestine that runs through the entire length of the body. The intestine is heavily branched and anus is absent. Instead the intestine runs along an excretory canal that opens at the posterior end. Adult flukes produce eggs which are passed out through the excretory pore. The eggs infect different species of snails (as intermediate hosts) in which they grow into larvae. The larvae are released into the environment from where the definitive hosts (humans and other mammals) get the infection. In some species, another intermediate host is required, generally a cyprinid fish. In this case, the definitive hosts are infected from eating infected fish. Hence, they are food-borne parasites.
"Clonorchiasis sinensis" is a trematode (fluke) which is part of the phylum Platyhelminthes. It is a hermaphroditic fluke that requires two intermediate hosts. The parasitic worm is as long as 10 to 25mm and lives in the bile ducts of the liver. The eggs of the worms are passed through fecal matter which are then ingested by mollusks. One becomes infected by eating undercooked, smoked, pickled salted freshwater fish. Freshwater fish are a second intermediate host for the parasitic worm. They become infected when the larvae (cercaria) of the worm penetrates the flesh of the fish. The water snail is the first intermediate host in which a miracidium (an embryonated egg discharged in stool) goes through its developmental stages (sporocyst, rediae and cercariae). Clonorchiasis is endemic in the Far East, especially in Korea, Japan, Taiwan, and Southern China. Clonorchiasis has been reported in non endemic areas (including the United States). In such cases, the infection follows the ingestion of imported, undercooked or pickled freshwater fish containing metacercariae.
Cholangitis requires admission to hospital. Intravenous fluids are administered, especially if the blood pressure is low, and antibiotics are commenced. Empirical treatment with broad-spectrum antibiotics is usually necessary until it is known for certain which pathogen is causing the infection, and to which antibiotics it is sensitive. Combinations of penicillins and aminoglycosides are widely used, although ciprofloxacin has been shown to be effective in most cases, and may be preferred to aminoglycosides because of fewer side effects. Metronidazole is often added to specifically treat the anaerobic pathogens, especially in those who are very ill or at risk of anaerobic infections. Antibiotics are continued for 7–10 days. Drugs that increase the blood pressure (vasopressors) may also be required to counter the low blood pressure.
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.