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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".
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Another possible drug option is Tetrachloroethylene, a chlorinated hydrocarbon, but its use has been superseded by new antihelminthic drugs (like Praziquantel).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.
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.
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).
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.
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.
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.
Trematodiases refers to a number of different trematode infections, many of which are spread by other animals. In 2015 the food born ones affected about 71 million people.
- Food-borne trematodiases as listed by the WHO:
- Clonorchiasis
- Opisthorchiasis
- Fascioliasis
- Paragonimiasis
- Others:
- Metagonimiasis
- Fasciolopsiasis
- Metorchiasis, caused by the Canadian liver fluke
- Dicrocoeliasis
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.
"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.
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.
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.
Liver fluke infections cause serious medical and veterinary diseases. Fasciolosis of sheep, goats and cattle, is the major cause of economic losses in dairy and meat industry. Fasciolosis of humans produces clinical symptoms such as fever, nausea, swollen liver, extreme abdominal pain, jaundice and anemia.
Clonorchiasis and opisthorchiasis (due to "Opisthorchis viverrini") are particularly dangerous. They can survive for several decades in humans causing chronic inflammation of the bile ducts, epithelial hyperplasia, periductal fibrosis and bile duct dilatation. In many infections these symptoms cause further complications such as stone formation, recurrent pyogenic cholangitis and cancer (cholangiocarcinoma). Opisthorchiasis is particularly the leading cause of cholangiocarcinoma in Thailand and the Lao People's Democratic Republic. Both clonorchiasis and opisthorchiasis are classified as Group 1 human biological agents (carcinogens) by International Agency of Research on Cancer (IARC).
Helminths are common causes of hypereosiophilia and eosinophilia in areas endemic to these parasites. Helminths infections causing increased blood eosinophil counts include: 1) nematodes, (i.e. "Angiostrongylus cantonensis" and Hookworm infections), ascariasis, strongyloidiasis trichinosis, visceral larva migrans, Gnathostomiasis, cysticercosis, and echinococcosis; 2) filarioidea, i.e. tropical pulmonary eosinophilia, loiasis, and onchocerciasis; and 3) flukes, i.e. shistosomiasis, fascioliasis, clonorchiasis, paragonimiasis, and fasciolopsiasis. Other infections associated with increased eosinophil blood counts include: protozoan infections, i.e. "Isospora belli" and "Dientamoeba fragilis") and sarcocystis); fungal infections (i.e. disseminated histoplasmosis, cryptococcosis especially in cases with [[central nervous system]] involvement), and coccidioides); and viral infections, i.e. Human T-lymphotropic virus 1 and HIV.
A wide range of drugs are known to cause hypereosinophilia or eosinophilia accompanied by an array of allergic symptoms. Rarely, these reactions are severe causing, for example, the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. While virtually any drug should be considered as a possible cause of these signs and symptoms, the following drugs and drug classes are some of the most frequently reported causes: penicillins, cephalosporins, dapsone, sulfonamides, carbamazepine, phenytoin, lamotrigine, valproic acid, nevirapine, efavirenz, and ibuprofen. These drugs may cause severely toxic reactions such as the DRESS syndrome. Other drugs and drug classes often reported to cause increased blood eosinophil levels accompanied by less severe (e.g. non-DRESS syndrome) symptoms include tetracyclins, doxycycline, linezolid, nitrofurantoin, metronidazole, carbamazepine, phenobarbital, lamotrigine, valproate, desipramine, amitriptyline, fluoxetine, piroxicam, diclofenac, ACE inhibitors, abacavir, nevirapine, ranitidine, cyclosporin, and hydrochlorothiazide.
The toxic oil syndrome is associated with hypereosinophilia/eosinophilia and systemic symptoms due to one or more contaminants in rapeseed oil and the Eosinophilia–myalgia syndrome, also associated with hypereosinophilia, appears due to trace contaminants in certain commercial batches of the amino acid, L-tryptophan.
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnormal cell division. Cell division is a physiological process that occurs in almost all tissues and under a variety of circumstances. Normally the balance between proliferation and programmed cell death, in the form of apoptosis, is maintained to ensure the integrity of tissues and organs. According to the prevailing accepted theory of carcinogenesis, the somatic mutation theory, mutations in DNA and epimutations that lead to cancer disrupt these orderly processes by disrupting the programming regulating the processes, upsetting the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. Only certain mutations lead to cancer whereas the majority of mutations do not.
Variants of inherited genes may predispose individuals to cancer. In addition, environmental factors such as carcinogens and radiation cause mutations that may contribute to the development of cancer. Finally random mistakes in normal DNA replication may result in cancer causing mutations. A series of several mutations to certain classes of genes is usually required before a normal cell will transform into a cancer cell. On average, for example, 15 "driver mutations" and 60 "passenger" mutations are found in colon cancers. Mutations in genes that regulate cell division, apoptosis (cell death), and DNA repair may result in uncontrolled cell proliferation and cancer.
Cancer is fundamentally a disease of regulation of tissue growth. In order for a normal cell to transform into a cancer cell, genes that regulate cell growth and differentiation must be altered. Genetic and epigenetic changes can occur at many levels, from gain or loss of entire chromosomes, to a mutation affecting a single DNA nucleotide, or to silencing or activating a microRNA that controls expression of 100 to 500 genes. There are two broad categories of genes that are affected by these changes. Oncogenes may be normal genes that are expressed at inappropriately high levels, or altered genes that have novel properties. In either case, expression of these genes promotes the malignant phenotype of cancer cells. Tumor suppressor genes are genes that inhibit cell division, survival, or other properties of cancer cells. Tumor suppressor genes are often disabled by cancer-promoting genetic changes. Finally Oncovirinae, viruses that contain an oncogene, are categorized as oncogenic because they trigger the growth of tumorous tissues in the host. This process is also referred to as viral transformation.
There is a diverse classification scheme for the various genomic changes that may contribute to the generation of cancer cells. Many of these changes are mutations, or changes in the nucleotide sequence of genomic DNA. There are also many epigenetic changes that alter whether genes are expressed or not expressed. Aneuploidy, the presence of an abnormal number of chromosomes, is one genomic change that is not a mutation, and may involve either gain or loss of one or more chromosomes through errors in mitosis. Large-scale mutations involve the deletion or gain of a portion of a chromosome. Genomic amplification occurs when a cell gains many copies (often 20 or more) of a small chromosomal region, usually containing one or more oncogenes and adjacent genetic material. Translocation occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs in chronic myelogenous leukemia, and results in production of the BCR-abl fusion protein, an oncogenic tyrosine kinase. Small-scale mutations include point mutations, deletions, and insertions, which may occur in the promoter of a gene and affect its expression, or may occur in the gene's coding sequence and alter the function or stability of its protein product. Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus, and such an event may also result in the expression of viral oncogenes in the affected cell and its descendants.