Atoxyl, the first medicinal drug against human African trypanosomiasis (HAT), also known as sleeping sickness, was applied more than 100 years ago. Ever since, the search for more effective, more specific and less toxic drugs continued, leading to a set of compounds currently in use against this devastating disease. Unfortunately, none of these medicines fulfill modern pharmaceutical requirements and may be considered as therapeutic ultima ratio due to the many, often severe side effects. Starting with a historic overview on drug development against HAT, we present a selection of trypanosome specific pathways and enzymes considered as highly potent druggable targets. In addition, we describe cellular mechanisms the parasite uses for differentiation and cell density regulation and present our considerations how interference with these steps, elementary for life cycle progression and infection, may lead to new aspects of drug development. Finally we refer to our recent work about CNS infection that offers novel insights in how trypanosomes hide in an immune privileged area to establish a chronic state of the disease, thereby considering new ways for drug application. Depressingly, HAT specific drug development has failed over the last 30 years to produce better suited medicine. However, unraveling of parasite-specific pathways and cellular behavior together with the ability to produce high resolution structures of essential parasite proteins by X-ray crystallography, leads us to the optimistic view that development of an ultimate drug to eradicate sleeping sickness from the globe might just be around the corner.
This case study has highlighted that through good communication amongst patients, families and professionals and collaborative working across boundaries and organisations, appropriate patients in the critical care setting can have a real choice regarding where they wish to be cared for and die at the end of their life.
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The traditional Western model of biomedicine has been found to be inadequate when dealing with the escalating problems of tuberculosis (TB) and multi-drug resistant TB (MDRTB) in North America Biomedicine has failed to appropriately control this disease and is unable to deal effectively with social problems that cause the spread of TB, prevent adequate utilization of health care facilities, and discourage the appropriate use of medications. An anthropological approach which considers social and cultural issues in TB care and prevention may be useful iIi understanding why people may not use health care facilities, as well as aid in understanding the reasons behind non-compliance in finishing appropriate coW'Ses ofmedication The Primary Health Care Model (PHC) may be a valuable option for providing accessible medical care which is acceptable to more individuals. Directly Observed Therapy Programs (DOT) have also been shown to be effective ways of enhancing patient compliance in completion of therapy, regardless of socio-economic circumstances or cultural diversity. The reliance on treatments which use standard Biomedical paradigms will continue to fail unless local and individual responses to these programs are given consideration.
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