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
Medications that are used to kill roundworms are called ascaricides. Those recommended by the World Health Organization for ascariasis are: albendazole, mebendazole, levamisole and pyrantel pamoate. Other effective agents include tribendimidine and nitazoxanide. Pyrantel pamoate may induce intestinal obstruction in a heavy worm load. Albendazole is contraindicated during pregnancy and children under two years of age. Thiabendazole may cause migration of the worm into the esophagus, so it is usually combined with piperazine.
Piperazine is a flaccid paralyzing agent that blocks the response of Ascaris muscle to acetylcholine, which immobilizes the worm. It prevents migration when treatment is accomplished with weak drugs such as thiabendazole. If used by itself, it causes the worm to be passed out in the feces and may be used when worms have caused blockage of the intestine or the biliary duct.
Corticosteroids can treat some of the symptoms, such as inflammation.
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.
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%).
Drugs are frequently used to kill parasites in the host. In earlier times, turpentine was often used for this, but modern drugs do not poison intestinal worms directly. Rather, anthelmintic drugs now inhibit an enzyme that is necessary for the worm to make the substance that prevents the worm from being digested.
For example, tapeworms are usually treated with a medicine taken by mouth. The most commonly used medicine for tapeworms is praziquantel.
In some cases with severe infestation the worms may cause bowel obstruction, requiring emergency surgery. The bowel obstruction may be due to all the worms or twisting of the bowel. During the surgery the worms may be manually removed.
Parasitic infections can usually be treated with antiparasitic drugs.
Albendazole and mebendazole have been the treatments administered to entire populations to control hookworm infection. However, it is a costly option and both children and adults become reinfected within a few months after deparasitation occurs raising concerns because the treatment has to repeatedly be administered and drug resistance may occur.
Another medication administered to kill worm infections has been pyrantel pamoate. For some parasitic diseases, there is no treatment and, in the case of serious symptoms, medication intended to kill the parasite is administered, whereas, in other cases, symptom relief options are used. Recent papers have also proposed the use of viruses to treat infections caused by protozoa.
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.
Treatment is not always necessary as the infection usually resolves on its own. However, if the illness is acute or symptoms persist and medications are needed to treat it, a nitroimidazole medication is used such as metronidazole, tinidazole, secnidazole or ornidazole.
The World Health Organization and Infectious Disease Society of America recommend metronidazole as first line therapy. The US CDC lists metronidazole, tinidazole, and nitazoxanide as effective first-line therapies; of these three, only nitazoxanide and tinidazole are approved for the treatment of giardiasis by the US FDA. A meta-analysis done by the Cochrane Collaboration found that compared to the standard of metronidazole, albendazole had equivalent efficacy while having fewer side effects, such as gastrointestinal or neurologic issues. Other meta-analyses have reached similar conclusions. Both medications need a five to 10 day long course; albendazole is taken once a day, while metronidazole needs to be taken three times a day. The evidence for comparing metronidazole to other alternatives such as mebendazole, tinidazole or nitazoxanide was felt to be of very low quality. While tinidazole has side effects and efficacy similar to those of metronidazole, it is administered with a single dose.
Resistance has been seen clinically to both nitroimidazoles and albendazole, but not nitazoxanide, though nitazoxanide resistance has been induced in research laboratories so is theoretically possible. The exact mechanism of resistance to all of these medications is not well understood. In the case of nitroimidazole-resistant strains of Giardia, other drugs are available which have showed efficacy in treatment including quinacrine, nitazoxanide, bacitracin zinc, furazolidone and paromomycin.
During pregnancy, paromomycin is the preferred treatment drug because of its poor intestinal absorption, and thus less exposure to the fetus. Alternatively, metronidazole can be used after the first trimester as there has been wide experience in its use for trichomonas in pregnancy.
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.
Medication is the primary treatment for pinworm infection. They are so effective that many medical scientists regard hygienic measures as impractical. However, reinfection is frequent regardless of the medication used. Total elimination of the parasite in a household may require repeated doses of medication for up to a year or more. Because the drugs kill the adult pinworms, but not the eggs, the first retreatment is recommended in two weeks. Also, if one household member spreads the eggs to another, it will be a matter of two or three weeks before those eggs become adult worms and thus amenable to treatment. Asymptomatic infections, often in small children, can serve as reservoirs of infection, and therefore the entire household should be treated regardless of whether or not symptoms are present.
The benzimidazole compounds albendazole (brand names e.g., "Albenza", "Eskazole", "Zentel" and "Andazol") and mebendazole (brand names e.g., "Ovex", "Vermox", "Antiox" and "Pripsen") are the most effective. They work by inhibiting the microtubule function in the pinworm adults, causing glycogen depletion, thereby effectively starving the parasite. A single 100 milligram dose of mebendazole with one repetition after a week, is considered the safest, and is usually effective with cure rate of 96%. Mebendazole has no serious side effects, although abdominal pain and diarrhea have been reported. Pyrantel pamoate (also called pyrantel embonate, brand names e.g., "Reese's Pinworm Medicine", "Pin-X", "Combantrin", "Anthel", "Helmintox", and "Helmex") kills adult pinworms through neuromuscular blockade, and is considered as effective as the benzimidazole compounds and is used as a second-line medication. Other medications are piperazine, which causes flaccid paralysis in the adult pinworms, and pyrvinium pamoate (also called pyrvinium embonate), which works by inhibiting oxygen uptake of the adult pinworms. Pinworms located in the genitourinary system (in this case, female genital area) may require other drug treatments.
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.
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.
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 drug of choice to treat paragonimiasis is praziquantel, although bithionol may also be used.
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".
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.
There are two drugs available, praziquantel and oxamniquine, for the treatment of schistosomiasis. They are considered equivalent in relation to efficacy against "S. mansoni" and safety. Because of praziquantel's lower cost per treatment, and oxaminiquine's lack of efficacy against the urogenital form of the disease caused by "S. haematobium", in general praziquantel is considered the first option for treatment. The treatment objective is to cure the disease and to prevent the evolution of the acute to the chronic form of the disease. All cases of suspected schistosomiasis should be treated regardless of presentation because the adult parasite can live in the host for years.
Schistosomiasis is treatable by taking by mouth a single dose of the drug praziquantel annually.
The WHO has developed guidelines for community treatment based on the impact the disease has on children in villages in which it is common:
- When a village reports more than 50 percent of children have blood in their urine, everyone in the village receives treatment.
- When 20 to 50 percent of children have bloody urine, only school-age children are treated.
- When fewer than 20 percent of children have symptoms, mass treatment is not implemented.
Other possible treatments include a combination of praziquantel with metrifonate, artesunate, or mefloquine. A Cochrane review found tentative evidence that when used alone, metrifonate was as effective as praziquantel.
Another agent, mefloquine, which has previously been used to treat and prevent malaria, was recognised in 2008–2009 to be effective against "Schistosoma".
Currently, no therapeutic drugs are prescribed for the disease. Therefore, prevention is the sole mode of treatment. This disease can only be prevented by quarantining sick birds and preventing migration of birds around the house, causing them to spread the disease. Deworming of birds with anthelmintics can reduce exposure to the cecal nematodes that carry the protozoan. Good management of the farm, including immediate quarantine of infected birds and sanitation, is the main useful strategy for controlling the spread of the parasitic contamination. The only drug used for the control (prophylaxis) in the United States is nitarsone at 0.01875% of feed until 5 days before marketing. Natustat and nitarsone were shown to be effective therapeutic drugs. Nifurtimox, a compound with known antiprotozoal activity, was demonstrated to be significantly effective at 300–400 ppm, and well tolerated by turkeys.
Treatment for Eustrongylidosis is limited in the wading bird population due to the extensive amount of perforation in the stomach lining and limited funds available for treatment. In humans who are infected with Eustrongylidosis, surgery is required to remove the parasite from the intestinal wall. As surgery is not a feasible treatment option for wading fowl in the wild "en masse", treatment of the infected birds (a large portion of wild populations) has not been found, nor will likely be practical. There is the possibility that killing/removing the nematodes could do more harm to the host specimen than actual good.
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.
Toxocariasis will often resolve itself, because the "Toxocara" larvae cannot mature within human hosts. Corticosteroids are prescribed in severe cases of VLM or if the patient is diagnosed with OLM. Either albendazole (preferred) or mebendazole (“second line therapy”) may be prescribed. Granulomas can be surgically removed, or laser photocoagulation and cryoretinopexy can be used to destroy ocular granulomas.
Visceral toxocariasis in humans can be treated with antiparasitic drugs such as albendazole or mebendazole, tiabendazole or diethylcarbamazine usually in combination with anti-inflammatory medications. Steroids have been utilized with some positive results. Anti-helminthic therapy is reserved for severe infections (lungs, brain) because therapy may induce, due to massive larval killing, a strong inflammatory response. Treatment of ocular toxocariasis is more difficult and usually consists of measures to prevent progressive damage to the eye.
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.
Good hygiene is necessary to avoid reinfection. The Rockefeller Foundation's hookworm campaign in Mexico in the 1920s was extremely effective at eliminating hookworm from humans with the use of anthelmintics. However, preventative measures were not adequately introduced to the people that were treated. Therefore, the rate of reinfection was extremely high and the project evaluated through any sort of scientific method was a marked failure. More education was needed to inform the people of the importance of wearing shoes, using latrines (better access to sanitation), and good hygiene.
Intestinal parasite prevention methods are not isolated to specific geographical areas; however, many of the research-based interventions have primarily taken place in underdeveloped countries and regions, where sanitation is a large concern for spreading disease.Current best practice behaviors that prevent intestinal parasites include: using proper hand washing practices, using correctly-built latrines with ample ventilation, having a piped water source, and wearing shoes. Currently, in some parts of Ethiopia where disease prevalence is high, up to 80% of people in a population lack access to washing facilities. While is this high, 93% did have access to a latrine, but only 29.2% of those latrines had proper construction to decrease parasitic infections.Behavioral interventions have focused on promoting washing, sometimes with soap, in context of education at schools and child care facilities. In recent studies, the best interventions follow a multidisciplinary approach by:
- Increasing environmental sanitation to promote hand washing and shoe wearing habits
- Educating children at young ages at school and at home
Specific evidence-based interventions that may lower disease prevalence include:
- Interventions at schools, focusing on the construction of pit latrines (ventilated and improved), providing clean drinking water and educating the students about hygiene
- The SAFE (surgery, antibiotics, facial cleanliness, environmental sanitation) strategy to address trachoma, primarily the facial cleanliness and the environmental sanitation components
- Hand-washing with soap at critical times and nail clipping to decrease reinfection rates, although further research is needed to develop and implement similar interventions at scale
- Programs combining anthelmintic drug administration with interventions to increase environmental sanitation (such as decreasing fecal contamination)