Yale researchers identify protein that could help neutralize deadly bite of the tsetse fly

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(Yale School of Public Health) Researchers at the Yale School of Public Health have identified a family of surface proteins that could be promising new vaccine candidates to help control African sleeping sickness, a devastating disease passed on by the bite of infected tsetse flies.

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Parasites, including African trypanosomes, utilize several immune evasion strategies to ensure their survival and completion of their life cycles within their hosts. The defense factors activated by the host to resolve inflammation and restore homeostasis during active infection could be exploited and/or manipulated by the parasites in an attempt to ensure their survival and propagation. This often results in the parasites evading the host immune responses as well as the host sustaining some self-inflicted collateral tissue damage. During infection with African trypanosomes, both effector and suppressor cells are activated…

Life scientists from UCLA and the University of Bern have identified a key gene in the transmission of African sleeping sickness — a severe disease transmitted by the bite of infected tsetse flies, which are common in sub-Saharan Africa.The disease is fatal if untreated, as the parasite responsible moves from the bloodstream to the central nervous system. Tens of millions of people in 36 African countries are at risk. There is no vaccine, and conventional drug treatments, which include an arsenic derivative, are antiquated, not very effective and have severe side effects.The research,  published in the journal N…

Abstract
Trypanosoma brucei, a flagellated protozoan causing the deadly tropical disease Human African Trypanosomiasis (HAT), affects people in sub-Saharan Africa. HAT therapy relies upon drugs which use is limited by toxicity and rigorous treatment regimes, while development of vaccines remains elusive, due to the effectiveness of the parasite´s antigenic variation. Here, we evaluate a hypothetical protein Tb427.10.13790, as a potential drug target. This protein is conserved among all kinetoplastids, but lacks homologs in all other pro- and eukaryotes. Knockdown of Tb427.10.13790 resulted in appearance of m…

Source: Acta TropicaCategory: Infectious Diseases Authors: Tags: Acta Trop Source Type: research

This study provides functional information of T.b.brucei for experimental studies to identify potential targets for diagnosis and therapeutics development.
PMID: 30006035 [PubMed – as supplied by publisher]

Source: GenomicsCategory: Genetics & Stem Cells Authors: Tags: Genomics Source Type: research

Abstract
The CRISPR-Cas system, which was originally identified as a prokaryotic defense mechanism, is increasingly being used for the functional study of genes. This technology, which is simple, inexpensive and efficient, has aroused a lot of enthusiasm in the scientific community since its discovery, and every month many publications emanate from very different communities reporting on the use of CRISPR-Cas9. Currently, there are no vaccines to control neglected tropical diseases (NTDs) caused by Trypanosomatidae, particularly Human African Trypanosomiasis (HAT) and Animal African Trypanosomoses (AAT), and treat…

Source: Infection, Genetics and EvolutionCategory: Genetics & Stem Cells Authors: Tags: Infect Genet Evol Source Type: research

Abstract
The trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp, are causative agents of important human diseases such African sleeping sickness, Chagas’ disease and Leishmaniasis, respectively. The high impact of these diseases on human health and economy worldwide, the unsatisfactory available chemotherapeutic options and the absence of human effective vaccines, strongly justifies the search for new drugs. The pentose phosphate pathway has been proposed to be a viable strategy to defeat several infectious diseases, including those from trypanosomatids, as it includes an oxidative branch, i…

Source: Current Medicinal ChemistryCategory: Chemistry Authors: Tags: Curr Med Chem Source Type: research

Abstract
African sleeping sickness is a parasitic disease in humans and livestock caused by Trypanosoma brucei throughout sub-Saharan Africa. Absence of appropriate vaccines and prevalence of drug resistance proclaim that a new way of therapeutic interventions is essential against African trypanosomiasis. In the present study, we have looked into the effect of andrographolide (andro), a diterpenoid lactone from Andrographis paiculata on Trypanosoma brucei PRA 380. Although andro has been recognized as a promosing anti-cancer drug, its usefulness against Trypanosoma spp remained unexplored. Andro showed promising a…

Source: Acta TropicaCategory: Infectious Diseases Authors: Tags: Acta Trop Source Type: research

Publication date: Available online 30 June 2017 Source:The Lancet Author(s): Philippe Büscher, Giuliano Cecchi, Vincent Jamonneau, Gerardo Priotto Human African trypanosomiasis (sleeping sickness) is a parasitic infection that almost invariably progresses to death unless treated. Human African trypanosomiasis caused devastating epidemics during the 20th century. Thanks to sustained and coordinated efforts over the past 15 years, the number of reported cases has fallen to an historically low level. Fewer than 3000 cases were reported in 2015, and the disease is targeted for elimination by WHO. Despite these recent suc…

Source: The LancetCategory: General Medicine Source Type: research

Abstract
There is an urgent need for the identification and validation of new therapeutic targets in protozoan parasites because currently available drugs are limited in number and usefulness, and no vaccines are available. The discovery that alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, is an efficacious treatment for African Sleeping Sickness caused by the protozoan parasite Trypanosoma brucei, has validated the polyamine pathway as a target in protozoan parasites. Polyamines are ubiquitous organic cations that play critical roles in key cellular processes such as growth, differentiation…

Source: Current Pharmaceutical DesignCategory: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research

AbstractTransmission of infectious agents might be associated with iatrogenic actions of charitable help in health care. An example is the vaccination against yellow fever in USA that transmitted hepatitis B virus. Another example is injections of praziquantel for treatment and cure of schistosomiasis in Central and Northern Africa, with a focus in Egypt that has spread hepatitis C virus. There is no indication that human T-lymphotropic virus type 1 was spread by injection treatment for African trypanosomiasis, syphilis and treponematosis, but these treatments might have contributed to the early spread of human immunodefic…



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