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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.
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%).
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.
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.
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 antibiotic doxycycline is effective in treating lymphatic filariasis. Its drawbacks are that it requires 4 to 6 weeks of treatment and should not be used in young children and pregnant women, which limits its use for mass prevention. The parasites responsible for elephantiasis have a population of endosymbiotic bacteria, "Wolbachia", that live inside the worm. When the symbiotic bacteria of the adult worms are killed by the antibiotic, they no longer provide chemicals which the nematode larvae need to develop, which either kills the larvae or prevents their normal development. This permanently sterilizes the adult worms, which additionally die within 1 to 2 years instead of their normal 10 to 14 year lifespan.
Treatments for lymphatic filariasis differ depending on the geographic location of the endemic area. In sub-Saharan Africa, albendazole is being used with ivermectin to treat the disease, whereas elsewhere in the world, albendazole is used with diethylcarbamazine. Geo-targeting treatments is part of a larger strategy to eventually eliminate lymphatic filariasis by 2020.
Additionally, surgical treatment may be helpful for issues related to scrotal elephantiasis and hydrocele. However, surgery is generally ineffective at correcting elephantiasis of the limbs. A vaccine is not yet available but in 2013 the University of Illinois was reporting 95% efficacity in testing against "B. malayi" in mice.
Treatment for podoconiosis consists of consistent shoe-wearing (to avoid contact with the irritant soil) and hygiene - daily soaking in water with an antiseptic (such as bleach) added, washing the feet and legs with soap and water, application of ointment, and in some cases, wearing elastic bandages. Antibiotics are used in cases of infection.
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".
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.
Pinworm infection cannot be totally prevented under most circumstances. This is due to the prevalence of the parasite and the ease of transmission through soiled night clothes, airborne eggs, contaminated furniture, toys and other objects. Infection may occur in the highest strata of society, where hygiene and nutritional status are typically high. The stigma associated with pinworm infection is hence considered a possible over-emphasis. Counselling is sometimes needed for upset parents that have discovered their children are infected, as they may not realize how prevalent the infection is.
Preventative action revolves around personal hygiene and the cleanliness of the living quarters. The "rate" of reinfection can be reduced through hygienic measures, and this is recommended especially in recurring cases.
The main measures are keeping fingernails short, and washing and scrubbing hands and fingers carefully, especially after defecation and before meals. Under ideal conditions, bed covers, sleeping garments, and hand towels should be changed daily. Simple laundering of clothes and linen disinfects them. Children should wear gloves while asleep, and the bedroom floor should be kept clean. Food should be covered to limit contamination with dust-borne parasite eggs. Household detergents have little effect on the viability of pinworm eggs, and cleaning the bathroom with a damp cloth moistened with an antibacterial agent or bleach will merely spread the still-viable eggs. Similarly, shaking clothes and bed linen will detach and spread the eggs.
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
For many years from the 1950s onwards, vast dams and irrigation schemes were constructed, causing a massive rise in water-borne infections from schistosomiasis. The detailed specifications laid out in various UN documents since the 1950s could have minimized this problem. Irrigation schemes can be designed to make it hard for the snails to colonize the water and to reduce the contact with the local population. Even though guidelines on how to design these schemes to minimise the spread of the disease had been published years before, the designers were unaware of them. The dams appear to have reduced the population of the large migratory prawn "Macrobrachium". After the construction of fourteen large dams, greater increases in schistosomiasis occurred in the historical habitats of native prawns than in other areas. Further, at the 1986 Diama Dam on the Senegal River, restoring prawns upstream of the dam reduced both snail density and the human schistosomiasis reinfection rate.
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
The dramatic response to a commonly used drug for filaria (diethylcarbamazine) almost confirms the diagnosis. No universal treatment guidelines have been established for tropical pulmonary eosinophilia. The antifilarial diethylcarbamazine (6 mg/kg/day in three divided doses for 21 days remains the main therapeutic agent, and is generally well tolerated. Reported side effects include headache, fever, pruritus and gastrointestinal upset. The eosinophil count often falls dramatically within 7–10 days of starting treatment.
Parasitic worms have been used as a medical treatment for various diseases, particularly those involving an overactive immune response. As humans have evolved with parasitic worms, proponents argue they are needed for a healthy immune system. Scientists are looking for a connection between the prevention and control of parasitic worms and the increase in allergies such as hay-fever in developed countries. Parasitic worms may be able to damp down the immune system of their host, making it easier for them to live in the intestine without coming under attack. This may be one mechanism for their proposed medicinal effect.
One study suggests a link between the rising rates of metabolic syndrome in the developed worlds and the largely successful efforts of Westerners to eliminate intestinal parasites. The work suggests eosinophils (a type of white blood cell) in fat tissue play an important role in preventing insulin resistance by secreting interleukin 4, which in turn switches macrophages into "alternative activation". Alternatively-activated macrophages are important to maintaining glucose homeostasis (i.e., blood sugar regulation). Helminth infection causes an increase in eosinophils. In the study, the authors fed rodents a high-fat diet to induce metabolic syndrome, and then injected them with helminths. Helminth infestation improved the rodents' metabolism. The authors concluded:
Although sparse in blood of persons in developed countries, eosinophils are often elevated in individuals in rural developing countries where intestinal parasitism is prevalent and metabolic syndrome rare. We speculate that eosinophils may have evolved to optimize metabolic homeostasis during chronic infections by ubiquitous intestinal parasites….
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.
Helminths (), also commonly known as parasitic worms, are large multicellular organisms, which can generally be seen with the naked eye when they are mature. They are often referred to as intestinal worms even though not all helminths reside in the intestines. For example, schistosomes are not intestinal worms, but rather reside in blood vessels. The word helminth comes from Greek "hélmins", a kind of worm.
There is no consensus on the taxonomy of helminths. It is simply a commonly used term to describe certain worms with some similarities. These are flatworms (platyhelminthes), namely cestodes (tapeworms) and trematodes (flukes), and roundworms or nemathelminths (nematodes) – both of these are parasitic worm types – and the annelida, which are not parasitic or at the most ectoparasites like the leeches.
Helminths are worm-like organisms living in and feeding on living hosts. They receive nourishment and protection while disrupting their hosts' nutrient absorption. This can cause weakness and disease of the host. Those helminths that live inside the digestive tract are called intestinal parasites. They can live inside humans and other animals. In their adult form, helminths cannot multiply in humans. Helminths are able to survive in their mammalian hosts for many years due to their ability to manipulate the immune response by secreting immunomodulatory products. All helminths produce eggs (also called ova) for reproduction. These eggs have a strong shell that protects them against a range of environmental conditions. The eggs can therefore survive in the environment, outside their hosts, for many months or years.
Many, but not all, of the worms referred to as helminths belong to the group of intestinal parasites. An infection by a helminth is known as helminthiasis, helminth infection or intestinal worm infection. There is a naming convention which applies to all helminths: the ending "-asis" (or in veterinary science: "-osis") is added at the end of the name of the worm to denote the infection with that particular worm. For example, "Ascaris" is the name of a type of helminth, and ascariasis is the name of the infectious disease caused by that helminth.
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.
Strongyloidiasis is a human parasitic disease caused by the nematode called "Strongyloides stercoralis", or sometimes "S. fülleborni" which is a type of helminth. It belongs to a group of nematodes called roundworms. This intestinal worm can cause a number of symptoms in people, principally skin symptoms, abdominal pain, diarrhea and weight loss. In some people, particularly those who require corticosteroids or other immunosuppressive medication, "Strongyloides" can cause a hyperinfection syndrome that can lead to death if untreated. The diagnosis is made by blood and stool tests. The medication ivermectin is widely used to treat strongyloidiasis.
Strongyloidiasis is a type of soil-transmitted helminthiasis. It is thought to affect 30–100 million people worldwide, mainly in tropical and subtropical countries. It belongs to the group of neglected tropical diseases, and worldwide efforts are aimed at eradicating the infection.