Next on the to-do list: Wiping out African sleeping sickness.
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The device can be used to help detect malaria, African sleeping sickness, HIV, and tuberculosis.
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Animals are reservoirs for many diseases, including cattle for tuberculosis and African sleeping sickness (trypanosomiasis) and poultry for avian flu.
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Belgium's deputy prime minister Alexander de Croo pledged 25 million euros ($26.81 million) through 2025 to eradicate African sleeping sickness.
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Other researchers are using Crispr to investigate whether changes to genome architecture affects the ability of parasites like Trypanosoma, the cause of African sleeping sickness, to evade the immune system.
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Prescribed for patients with African sleeping sickness, it was also made available to treat patients with pneumocystis pneumonia in the early years of the AIDS epidemic, when few alternatives were available.
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"We've discovered that the parasite causing African sleeping sickness has existed for thousands of years without having sex and is now suffering the consequences of this strategy," said Willie Weir, bioinformatician at the University of Glasgow.
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LONDON (Thomson Reuters Foundation) - An unusual sex life may spell the extinction of the deadly African sleeping sickness parasite, which threatens millions of people in West and Central Africa, an international team of scientists said on Tuesday.
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This pathogen causes damage to the nervous system. African Sleeping Sickness is caused by Trypanosoma brucei rhodensiense and Trypanosoma brucei gambiense, and is transmitted by the tsetse fly. It is diagnosed by a physical exam and blood test. African sleeping sickness causes interstitial inflammation, lethargy, brain swelling, and death within one to three years.
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Suramin, a drug used to treat African sleeping sickness, has shown moderate success with binding to MSP-1 and its derivatives such as MSP-119 to inhibit red blood cell invasion.
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Two coding variants, G1 and G2, for the APOL1 protein are associated with resistance to African trypanosomiasis, or African sleeping sickness, but they also increase the risk of chronic kidney diseases.
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He continued to work with Jacobs, a collaboration that lasted more than nine years and produced 44 papers. They synthesized many chemotherapeutical drugs, namely aromatic arsenicals, for the treatment for infectious diseases, in particular syphilis and African sleeping sickness. In 1919 they developed a variant of Paul Ehrlich's "magic bullet" for syphilis, Salvarsan, which proved effective against trypanosomes, the parasites that cause African sleeping sickness. Variants of tryparsamide, as Flexner named it, continue to be administered today.
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The AOX pathway is found to be the exclusive electron transport pathway in Trypanosoma brucei, the organism that causes African Sleeping Sickness, meaning that SHAM completely shuts down oxygen consumption by this organism.
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Adults of many species are passive vectors of pathogens for diseases such as typhoid fever, dysentery, anthrax, and African sleeping sickness. Larvae of some Atherigona species are important pests in cultivation of cereals, like rice and maize.
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The rather ambitious commitment is to eradicate or prevent transmission of Guinea worm disease; eliminate lymphatic filariasis, leprosy, African sleeping sickness and blinding trachoma; and to control schistosomiasis, soil-transmitted helminthiasis, Chagas disease, visceral leishmaniasis and river blindness.
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The insect vectors for T. brucei are different species of tsetse fly (genus Glossina). The major vectors of T. b. gambiense, causing West African sleeping sickness, are G. palpapalis, G. tachinoides, and G. fuscipes. While the principal vectors of T. b.
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Inhibitors of these organisms are under current investigation. A pyrazole sulfonamide inhibitor has been identified that selectively binds T. brucei, competing for the peptide binding site, thus inhibiting enzymatic activity and eliminating the parasite from the bloodstream of mice with African sleeping sickness.
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Suramin is a medication used to treat African sleeping sickness and river blindness. It is the treatment of choice for sleeping sickness without central nervous system involvement. It is given by injection into a vein. Suramin causes a fair number of side effects.
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For current funding statistics, human African trypanosomiasis is grouped with kinetoplastid infections. Kinetoplastids refer to a group of flagellate protozoa. Kinetoplastid infections include African sleeping sickness, Chagas' disease, and Leishmaniasis. All together, these three diseases accounted for 4.4 million disability adjusted life years (DALYs) and an additional 70,075 recorded deaths yearly. For kinetoplastid infections, the total global research and development funding was approximately $136.3 million in 2012. Each of the three diseases, African sleeping sickness, Chagas' disease, and Leishmaniasis each received approximately a third of the funding, which was about $36.8 million US dollars, $38.7 million US dollars, and $31.7 million US dollars, respectively.
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African trypanosomiasis is also known as African sleeping sickness. There are fewer than 10,000 cases currently. Human African trypanosomiasis is vector- borne, and spread through the bite of the tsetse fly. The most common symptoms are fever, headache, lymphadenopathy, nocturnal sleeping pattern, personality changes, cognitive decline, and coma.
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African trypanosomiasis, also known as African sleeping sickness or simply sleeping sickness, is an insect-borne parasitic infection of humans and other animals. It is caused by the species Trypanosoma brucei. Humans are infected by two types, Trypanosoma brucei gambiense (TbG) and Trypanosoma brucei rhodesiense (TbR). TbG causes over 98% of reported cases.
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Recent findings indicate that the parasite is unable to survive in the bloodstream without its flagellum. This insight gives researchers a new angle with which to attack the parasite. Trypanosomiasis vaccines are undergoing research. Additionally, the Drugs for Neglected Disease Initiative has contributed to the African sleeping sickness research by developing a compound called fexinidazole.
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Because ergosterol is present in cell membranes of fungi, yet absent in those of animals, it is a useful target for antifungal drugs. Ergosterol is also present in the cell membranes of some protists, such as trypanosomes. This is the basis for the use of some antifungals against West African sleeping sickness. Amphotericin B, an antifungal drug, targets ergosterol.
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Sleep inversion may be a symptom of elevated blood ammonia levels and is often an early symptom of hepatic encephalopathy. Sleep inversion is a feature of African trypanosomiasis after which the disease takes its common name "African sleeping sickness"; sleep-wake cycle disturbances are the most common indication that the disease has reached the stage where infection spreads into the central nervous system.
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In some older systems of classification, Zoomastigophora is a phylum (more commonly known as zooflagellates) within the kingdom Protista. Organisms within this group have a spherical, elongated body with a single central nucleus. They are single-celled, heterotrophic eukaryotes and may form symbiotic relationships with other organisms, including Trichomonas. Some species are parasitic, causing diseases such as the African Sleeping Sickness, caused by the zooflagellate Trypanosoma brucei.
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Despite these atrocities, the main cause of the population decline was disease, which was exacerbated by the social disruption caused by the Free State. A number of epidemics, notably African sleeping sickness, smallpox, swine influenza, and amoebic dysentery, ravaged indigenous populations. In 1901 alone it was estimated that 500,000 Congolese had died from sleeping sickness. Disease, famine and violence combined to reduce the birth-rate while excess deaths rose.
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In trypanosomes, a group of flagellated protozoans, the kinetoplast exists as a dense granule of DNA within the large mitochondrion. Trypanosoma brucei, the parasite which causes African trypanosomiasis (African sleeping sickness), is an example of a trypanosome with a kinetoplast. Its kinetoplast is easily visible in samples stained with DAPI, a fluorescent DNA stain, or by the use of fluorescent in situ hybridization (FISH) with BrdU, a thymidine analogue.
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At the age of 29 he became Chair of Military Diseases and Epidemics at the École de Val-de-Grâce. At the end of his tenure in 1878 he worked in Algeria, where he made his major achievements. He discovered that the protozoan parasite Plasmodium was responsible for malaria, and that Trypanosoma caused trypanosomiasis or African sleeping sickness. In 1894 he returned to France to serve in various military health services.
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This downwards trend leaves a gap for other funders, such as philanthropic foundations and private pharmaceutical companies to fill. Much of the progress that has been made in African sleeping sickness and neglected disease research as a whole is a result of the other non-public funders. One of these major sources of funding has come from foundations, which have increasingly become more committed to neglected disease drug discovery in the 21st century.
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The original endorsers with their basic strategies were: #Abbott: A US-based global pharmaceutical and health care company works for the prevention, diagnosis and treatment of all major neglected diseases. It provides innovative technologies, drug compounds and scientific expertise, academic research and health education. #AstraZeneca: A British-Swedish multinational pharmaceutical and biologics company headquartered in London. #Bayer HealthCare Pharmaceuticals: A division of Germany's pharmaceutical company supports the fight against Chagas disease and African sleeping sickness.
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Montane voles have been reported to form up to 80% of the diet of great horned owls in Idaho. Montane voles have also been used in the laboratory in studies of African sleeping sickness, since they suffer similar symptoms to humans when infected with the parasite. Montane voles are nocturnal during the summer, but primarily diurnal during winter. They often inhabit abandoned gopher burrows, although they are also capable of digging their own.
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In return, he provided them room, board, and plenty of work, which on the isolated and virtually inaccessible Gilo River meant first hacking an airstrip out of the forest. Among the early volunteers were the McClures' son, Don Jr., and daughter, Lyda. By this time, the church established at Gilo could be served by a trained Anuak pastor. No cattle could be raised at Gilo because it was an area that suffered from trypanosomiasis, or African sleeping sickness.
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The two phases actually overlap and are difficult to distinguish based on clinical features alone; determining the actual stage is achieved by examining the cerebrospinal fluid for the presence of the parasite. Sleep disorders Sleep-wake disturbances are a leading feature of neurological stage and gave the disease its common name African sleeping sickness. Infected individuals experience a disorganized and fragmented sleep-wake cycle. Those affected experience sleep inversion resulting in daytime sleep and somnolence, and nighttime periods of wakefulness and insomnia.
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Such screening efforts are important because early symptoms are not evident or serious enough to warrant people with gambiense disease to seek medical attention, particularly in very remote areas. Also, diagnosis of the disease is difficult and health workers may not associate such general symptoms with trypanosomiasis. Systematic screening allows early-stage disease to be detected and treated before the disease progresses, and removes the potential human reservoir. A single case of sexual transmission of West African sleeping sickness has been reported.
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Certain NMTs are therapeutic targets for development of drugs against bacterial infections. Myristoylation has been shown to be necessary for the survival of a number of disease-causing fungi, among them C. albicans and C. neoformans. In addition to prokaryotic bacteria, the NMTs of numerous disease-causing eukaryotic organisms have been identified as drug targets as well. Proper NMT functioning in the protozoa Leishmania major and Leishmania donovani (leishmaniasis), Trypanosoma brucei (African sleeping sickness), and P. falciparum (malaria) is necessary for survival of the parasites.
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An example of a mechanical vector is a housefly, which lands on cow dung, contaminating its appendages with bacteria from the feces, and then lands on food prior to consumption. The pathogen never enters the body of the fly. In contrast, biological vectors harbor pathogens within their bodies and deliver pathogens to new hosts in an active manner, usually a bite. Biological vectors are often responsible for serious blood-borne diseases, such as malaria, viral encephalitis, Chagas disease, Lyme disease and African sleeping sickness.
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FTIs can also be used to inhibit farnesylation in parasites such as Trypanosoma brucei (African sleeping sickness) and Plasmodium falciparum (malaria). These parasites seem to be more vulnerable to inhibition of Farnesyltransferase than humans, even though the drugs tested selectively target human FTase. In some cases the reason for this may be the parasites lack Geranylgeranyltransferase I. This vulnerability may pave the way for the development of selective, low toxicity, FTI based anti-parasitic drugs 'piggybacking' on the development of FTIs for cancer research.
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Nifurtimox has also been used to treat African trypanosomiasis (sleeping sickness), and is active in the second stage of the disease (central nervous system involvement). When nifurtimox is given on its own, about half of all patients will relapse, but the combination of melarsoprol with nifurtimox appears to be efficacious. Trials are awaited comparing melarsoprol/nifurtimox against melarsoprol alone for African sleeping sickness. Combination therapy with eflornithine and nifurtimox is safer and easier than treatment with eflornithine alone, and appears to be equally or more effective.
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Although PDE5 inhibitors main use has been for erectile dysfunction there has been a great interest in PDE5 inhibitors as a promising new therapeutic agents for treatment of other diseases, such as Alzheimer's disease. Elevation of cGMP levels through inhibition of PDE5 provides a way of improving memory and learning. PDE5 has also been considered as a potential therapeutic agent for parasitic disease such as African sleeping sickness. Strategic changes were made to the structure of sildenafil so the molecule could project into a parasite-specific pocket (the p-pocket).
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L-R Percival Mackie, Lady Bruce, Sir David Bruce, H. R. Bateman, A. E. Hamerton. Photo courtesy of Peter and Joanna Mackie A pressing issue at the time was the possibility of African sleeping sickness (trypanosomiasis) spreading to India via similar blood- sucking insect vectors. In September 1908, at the request of the Indian Government, Captain Mackie was attached to the Royal Society’s Sleeping Sickness Commission headed by Sir David Bruce F.R.S. Based at Mpumo, Uganda. Mackie was one of Bruce's youthful “Three Musketeers,” the others being Captains H.R. Bateman and Albert Ernest Hamerton.
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Giardia lamblia, an infectious protozoan Protozoan infections are parasitic diseases caused by organisms formerly classified in the Kingdom Protozoa. They are usually contracted by either an insect vector or by contact with an infected substance or surface and include organisms that are now classified in the supergroups Excavata, Amoebozoa, SAR, and Archaeplastida. Protozoan infections are responsible for diseases that affect many different types of organisms, including plants, animals, and some marine life. Many of the most prevalent and deadly human diseases are caused by a protozoan infection, including African Sleeping Sickness, amoebic dysentery, and malaria.
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His main research interests concern the biochemistry of protozoan parasites that cause tropical diseases, particularly the trypanosomatida that cause human African sleeping sickness, Chagas' disease and leishmaniasis. He was heavily involved in establishing the new Drug Discovery Unit at the University of Dundee and is also co-Director of the Dundee Proteomics Facility. He still continues to play a role in Research Strategy and directs the Discovery Centre for Translational and Interdisciplinary Research which opened in 2014. He is also a member of the Board of Governors for The Wellcome Trust and the Board of Directors of the Medicines for Malaria Venture (MMV).
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While an undergraduate at Stanford University, Parazynski studied antigenic shift in African sleeping sickness, using sophisticated molecular biology techniques. While in medical school, he was awarded a NASA graduate student fellowship and conducted research at NASA Ames Research Center on fluid shifts that occur during human space flight. Additionally, he has been involved in the design of several exercise devices that are being developed for long-duration space flight, and has conducted research on high-altitude acclimatization. Parazynski has numerous publications in the field of space physiology, and has a particular expertise in human adaptation to stressful environments.
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Pafuramidine (formulated as the maleic acid salt pafuramidine maleate) is an experimental drug for the treatment of pneumocystis pneumonia (PCP). In 2006, pafuramidine was given orphan drug status by the US Food and Drug Administration for PCP in patients with HIV/AIDS. Preliminary clinical trials indicated that pafuramide was effective against pneumocystis pneumonia and had the potential for fewer side effects than the standard treatment with trimethoprim/sulfamethoxazole (TMP-SMX). Pafuramidine also reached Phase III clinical trials for the treatment of first stage African sleeping sickness, but development was halted in 2008 over concerns about kidney toxicity.
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The monophyly of the genus Trypanosoma is not supported by a number of different methods. Rather, the American and African trypanosomes constitute distinct clades, implying that the major human disease agents T. cruzi (cause of Chagas’ disease) and T. brucei (cause of African sleeping sickness) are not closely related to each other.Environmental kinetoplastid-like 18S rRNA sequences and phylogenetic relationships among Trypanosomatidae: Paraphyly of the genus Trypanosoma. Helen Piontkivska and Austin L. Hughes, Molecular and Biochemical Parasitology, November 2005, Volume 144, Issue 1, Pages 94–99, Phylogenetic analyses suggest an ancient split into a branch containing all Salivarian trypanosomes and a branch containing all non-Salivarian lineages.
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Trypanosoma brucei gambiense (T. b. gambiense) is a species of African trypanosomes which are protozoan hemoflagellates responsible for trypanosomiasis (more commonly known as African sleeping sickness) in humans and other animals. The protozoa are transferred via Tsetse flies where they multiply and can be transferred to yet another animal host during the fly's blood meal feeding. Outbreaks of sleeping sickness in certain human communities have been eliminated but only temporarily as constant re- introduction from unknown sources statistically suggests the presence of a non-human reservoir where spillback of the pathogen is maintained in a sylvatic cycle and re-introduced into the urban cycle.
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This provision adds to the market-based incentives available for the development of new medicines for developing world diseases such as malaria, tuberculosis and African sleeping sickness. The prize was initially proposed by Duke University faculty Henry Grabowski, Jeffrey Moe, and David Ridley in their 2006 Health Affairs paper: "Developing Drugs for Developing Countries."Developing Drugs For Developing Countries – Ridley et al. 25 (2): 313 – Health Affairs Brownback supports a bill that would introduce price transparency to the U.S. health care industry,PR Newswire: Senators and Hospital Groups Support New GPO Transparency Initiative, July 12, 2005 as well as a bill which would require the disclosure of Medicare payment rate information.
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Jaenimonas drosophilae is a trypanosomatid parasite of mushroom-feeding flies, first characterized in Drosophila neotestacea and Drosophila falleni. Jaenimonas takes up residence in the gut of the fly, and infection leads to reduced fecundity of its fly host. The species is named for John Jaenike, a prominent ecologist and evolutionary biologist whose work on mushroom-feeding flies laid the foundation for studies on mycophagous Drosophila. Of note, Jaenimonas is the only identified trypanosomatid parasite of a Drosophila species, and can facilitate study of insect-trypanosome infection dynamics; Drosophila have powerful genetic tools, and many trypanosomes are vectored by insects and are responsible for diseases such as African sleeping sickness, Chagas disease, and Leishmaniasis.
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In 1903, Hector Duff wrote of how spotted hyenas in the Mzimba district of Angoniland would wait at dawn outside people's huts and attack them when they opened their doors. In 1908–09 in Uganda, spotted hyenas regularly killed sufferers of African sleeping sickness as they slept outside in camps.Roosevelt, Theodore (1910) African Game Trails: An Account of the African Wanderings of an American Hunter, Naturalist, New York, C. Scribner's sons Spotted hyenas are widely feared in Malawi, where they have been known to occasionally attack people at night, particularly during the hot season when people sleep outside. Hyena attacks were widely reported in Malawi's Phalombe plain, to the north of Michesi Mountain. Five deaths were recorded in 1956, five in 1957 and six in 1958.
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Since NADPH is required by both thioredoxin reductase and glutathione reductase to reduce oxidized thioredoxin and glutathionine, 6-phosphogluconate dehydrogenase is believed to be involved in protecting cells from oxidative damage. Several studies have linked oxidative stress to diseases such as Alzheimer's disease, as well as cancer, These studies have found phosphogluconate dehydrogenase activity to be up-regulated, both in tumor cells and in relevant cortical regions of Alzheimer's patient brains, most likely as a compensatory reaction to highly oxidative environments. Recently, phosphogluconate dehydrogenase has been posited as a potential drug target for African sleeping sickness (trypanosomiasis). The pentose phosphate pathway protects the trypanosomes from oxidative stress via the generation of NADPH and provides carbohydrate intermediates used in nucleotide synthesis.
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In 1953 the king of Belgium, colonial ruler of parts of Africa in which African sleeping sickness had been endemic, honored Heidelberger and Jacobs for their discovery. In 1921 Heidelberger transferred to the laboratory of Donald D. Van Slyke at the Rockefeller hospital, where he spent the next two years developing a method for preparing large quantities of purified oxyhemoglobin, with its oxygen-carrying capacity intact, for Van Slyke's studies of the uptake and release of oxygen in the blood. When Karl Landsteiner, the famous Austrian immunologist and discoverer of human blood groups, arrived at the institute in 1922, Heidelberger embarked with him on studies of the antigenic properties of different types of hemoglobin. Throughout his life Heidelberger was proud to state that he first learned immunology from Landsteiner.
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In the late 19th century, derivatives of aniline such as acetanilide and phenacetin emerged as analgesic drugs, with their cardiac-suppressive side effects often countered with caffeine.Wilcox RW, "The treatment of influenza in adults", Medical News, 1900 Dec 15;77():931-2, p 932. During the first decade of the 20th century, while trying to modify synthetic dyes to treat African sleeping sickness, Paul Ehrlich – who had coined the term chemotherapy for his magic bullet approach to medicine – failed and switched to modifying Béchamp's atoxyl, the first organic arsenical drug, and serendipitously obtained a treatment for syphilis – salvarsan – the first successful chemotherapy agent. Salvarsan's targeted microorganism, not yet recognized as a bacterium, was still thought to be a parasite, and medical bacteriologists, believing that bacteria were not susceptible to the chemotherapeutic approach, overlooked Alexander Fleming's report in 1928 on the effects of penicillin.
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Cerami has led research programs into genetic, metabolic and infectious diseases, with the goal of translating scientific discovery into drugs and diagnostic tests. He received funding from the Rockefeller Foundation to study neglected tropical diseases and traveled to Africa, where he became interested in the wasting, one of the symptoms of African sleeping sickness. He developed and validated a measurement of glycated hemoglobin to monitor control of blood sugar in people with diabetes, and a paper he published in 1985 using polyclonal antibodies against tumour necrosis factor-alpha was important in the field of immunology for demonstrating that TNF-alpha causes disease and blocking it could be a treatment. Work that he did while he was at Rockefeller on advanced glycation end-products (AGEs) and protein cross-linking and their roles in metabolic diseases and aging was patented by Rockfeller and licensed to Alteon Inc.
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