The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Peter G. E. Kennedy - One of the best experts on this subject based on the ideXlab platform.
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Clinical features, diagnosis, and treatment of human African Trypanosomiasis (sleeping sickness)
The Lancet. Neurology, 2012Co-Authors: Peter G. E. KennedyAbstract:Human African Trypanosomiasis, or sleeping sickness, is caused by infection with parasites of the genus Trypanosoma, transmitted by the tsetse fly. The disease has two forms, Trypanosoma brucei (T b) rhodesiense and T b gambiense; and is almost always fatal if untreated. Despite a recent reduction in the number of reported cases, patients with African Trypanosomiasis continue to present major challenges to clinicians. Because treatment for CNS-stage disease can be very toxic, diagnostic staging to distinguish early-stage from late-stage disease when the CNS in invaded is crucial but remains problematic. Melarsoprol is the only available treatment for late-stage T b rhodesiense infection, but can be lethal to 5% of patients owing to post-treatment reactive encephalopathy. Eflornithine combined with nifurtimox is the first-line treatment for late-stage T b gambiense. New drugs are in the pipeline for treatment of CNS human African Trypanosomiasis, giving rise to cautious optimism.
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The continuing problem of human African Trypanosomiasis (sleeping sickness)
Annals of Neurology, 2008Co-Authors: Peter G. E. KennedyAbstract:Human African Trypanosomiasis, also known as sleeping sickness, is a neglected disease, and it continues to pose a major threat to 60 million people in 36 countries in sub-Saharan Africa. Transmitted by the bite of the tsetse fly, the disease is caused by protozoan parasites of the genus Trypanosoma and comes in two types: East African human African Trypanosomiasis caused by Trypanosoma brucei rhodesiense and the West African form caused by Trypanosoma brucei gambiense. There is an early or hemolymphatic stage and a late or encephalitic stage, when the parasites cross the blood-brain barrier to invade the central nervous system. Two critical current issues are disease staging and drug therapy, especially for late-stage disease. Lumbar puncture to analyze cerebrospinal fluid will remain the only method of disease staging until reliable noninvasive methods are developed, but there is no widespread consensus as to what exactly defines biologically central nervous system disease or what specific cerebrospinal fluid findings should justify drug therapy for late-stage involvement. All four main drugs used for human African Trypanosomiasis are toxic, and melarsoprol, the only drug that is effective for both types of central nervous system disease, is so toxic that it kills 5% of patients who receive it. Eflornithine, alone or combined with nifurtimox, is being used increasingly as first-line therapy for gambiense disease. There is a pressing need for an effective, safe oral drug for both stages of the disease, but this will require a significant increase in investment for new drug discovery from Western governments and the pharmaceutical industry.
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Diagnostic and neuropathogenesis issues in human African Trypanosomiasis.
International journal for parasitology, 2006Co-Authors: Peter G. E. KennedyAbstract:Human African Trypanosomiasis, also known as sleeping sickness, is caused by protozoan parasites of the genus Trypanosoma, and is a major cause of human mortality and morbidity. The East African and West African variants, caused by Trypanosma brucei rhodesiense and Trypanosoma brucei gambiense, respectively, differ in their presentation but the disease is fatal if untreated. Accurate staging of the disease into the early haemolymphatic stage and the late encephalitic stage is critical as the treatment for the two stages is different. The only effective drug for late stage disease, melarsoprol, which crosses the blood–brain barrier, is followed by a severe post-treatment reactive encephalopathy in 10% of cases of which half die. There is no current consensus on the diagnostic criteria for CNS involvement and the specific indications for melarsoprol therapy also differ. There is a pressing need for a quick, simple, cheap and reliable diagnostic test to diagnose Human African Trypanosomiasis in the field and also to determine CNS invasion. Cerebrospinal fluid and plasma analyses in patients with Human African Trypanosomiasis have indicated a role for both pro-inflammatory and counter-inflammatory cytokines in determining the severity of the meningoencephalitis of late stage disease, and, at least in T. b. rhodesiense infection, the balance of these opposing cytokines may be critical. Rodent models of Human African Trypanosomiasis have proved very useful in modelling the post-treatment reactive encephalopathy of humans and have demonstrated the central role of astrocyte activation and cytokine balances in determining CNS disease. Such animal models have also allowed a greater understanding of the more direct mechanisms of trypanosome infection on CNS function including the disruption of circadian rhythms, as well as the immunological determinants of passage of trypanosomes across the blood–brain barrier.
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Sleeping sickness – human African Trypanosomiasis
Practical Neurology, 2005Co-Authors: Peter G. E. KennedyAbstract:INTRODUCTION One of the great advantages of working with veterinary colleagues is the insight they often bring to the pathogenesis of human disease through their studies of natural animal diseases and animal models. In 1988 Professor Max Murray of the University of Glasgow Veterinary School introduced me to the problem of African Trypanosomiasis in animals, its close relationship to its human counterpart that is known as sleeping sickness, and the unsolved problems of neurological involvement in that condition. We have now been investigating the neuropathogenesis of human African Trypanosomiasis (HAT) in the laboratory and the African field for the last 16 years (Fig. 1). Neurologists will realize of course that HAT is not to be confused with the other ‘sleeping sickness’ known as encephalitis lethargica, famous for the pandemic during the first quarter of the 20th century, and which still occurs sporadically. While the cause of the latter disease has
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Human African Trypanosomiasis of the CNS: current issues and challenges
The Journal of clinical investigation, 2004Co-Authors: Peter G. E. KennedyAbstract:Human African Trypanosomiasis (HAT), also known as sleeping sickness, is a major cause of mortality and morbidity in sub-Saharan Africa. Current therapy with melarsoprol for CNS HAT has unacceptable side-effects with an overall mortality of 5%. This review discusses the issues of diagnosis and staging of CNS disease, its neuropathogenesis, and the possibility of new therapies for treating late-stage disease.
José R. Franco - One of the best experts on this subject based on the ideXlab platform.
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Human African Trypanosomiasis.
Handbook of clinical neurology, 2013Co-Authors: Veerle Lejon, Marina Bentivoglio, José R. FrancoAbstract:Human African Trypanosomiasis or sleeping sickness is a neglected tropical disease that affects populations in sub-Saharan Africa. The disease is caused by infection with the gambiense and rhodesiense subspecies of the extracellular parasite Trypanosoma brucei, and is transmitted to humans by bites of infected tsetse flies. The disease evolves in two stages, the hemolymphatic and meningoencephalitic stages, the latter being defined by central nervous system infection after trypanosomal traversal of the blood-brain barrier. African Trypanosomiasis, which leads to severe neuroinflammation, is fatal without treatment, but the available drugs are toxic and complicated to administer. The choice of medication is determined by the infecting parasite subspecies and disease stage. Clinical features include a constellation of nonspecific symptoms and signs with evolving neurological and psychiatric alterations and characteristic sleep-wake disturbances. Because of the clinical profile variability and insidiously progressive central nervous system involvement, disease staging is currently based on cerebrospinal fluid examination, which is usually performed after the finding of trypanosomes in blood or other body fluids. No vaccine being available, control of human African Trypanosomiasis relies on diagnosis and treatment of infected patients, assisted by vector control. Better diagnostic tools and safer, easy to use drugs are needed to facilitate elimination of the disease.
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risk for human African Trypanosomiasis central africa 2000 2009
Emerging Infectious Diseases, 2011Co-Authors: Pere P. Simarro, Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Raffaele C. Mattioli, José A. Ruiz Postigo, Jean JanninAbstract:Comprehensive georeference records for human African Trypanosomiasis in Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea, and Gabon were combined with human population layers to estimate a kernel-smoothed relative risk function. Five risk categories were mapped, and ≈3.5 million persons were estimated to be at risk for this disease.
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Risk for Human African Trypanosomiasis, Central Africa, 2000–2009
Emerging infectious diseases, 2011Co-Authors: Pere P. Simarro, Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Raffaele C. Mattioli, José A. Ruiz Postigo, Jean JanninAbstract:Comprehensive georeference records for human African Trypanosomiasis in Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea, and Gabon were combined with human population layers to estimate a kernel-smoothed relative risk function. Five risk categories were mapped, and ≈3.5 million persons were estimated to be at risk for this disease.
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Towards the Atlas of human African Trypanosomiasis
International journal of health geographics, 2009Co-Authors: Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Jose Antonio Ruiz, Raffaele C. Mattioli, Pere P. SimarroAbstract:Background Updated, accurate and comprehensive information on the distribution of human African Trypanosomiasis (HAT), also known as sleeping sickness, is critically important to plan and monitor control activities. We describe input data, methodology, preliminary results and future prospects of the HAT Atlas initiative, which will allow major improvements in the understanding of the spatial distribution of the disease.
Bernard Bouteille - One of the best experts on this subject based on the ideXlab platform.
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The sheep (Ovis aries) as an experimental model for African Trypanosomiasis
Annals of Tropical Medicine and Parasitology, 2016Co-Authors: Bernard Bouteille, Dumas M, J. C. Breton, M. Pestre-alexandre, G Catanzano, Marie Laure Darde, A. NicolasAbstract:Sheep that have been experimentally infected with a strain of Trypanosoma brucei brucei reproduce the clinical symptomatology of human African Trypanosomiasis. We measured two biochemical parameter...
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Serum Arginase, a Biomarker of Treatment Efficacy in Human African Trypanosomiasis
Journal of clinical microbiology, 2013Co-Authors: Romaric Nzoumbou-boko, Bernard Bouteille, Raymond Cespuglio, Alain Buguet, Mariette Dethoua, Frédéric Gabriel, Pierrette Courtois, Sylvie Daulouède, Stéphane Ngampo, Ghislain MpandzouAbstract:Arginase serum levels were increased in human African Trypanosomiasis patients and returned to control values after treatment. Arginase hydrolyzes l-arginine to l-ornithine, which is essential for parasite growth. Moreover, l-arginine depletion impairs immune functions. Arginase may be considered as a biomarker for treatment efficacy.
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Management of African Trypanosomiasis of the CNS: polysomnography as a noninvasive staging tool
Future Neurology, 2012Co-Authors: Alain Buguet, Bernard Bouteille, Florian Chapotot, Stéphane Ngampo, Raymond CespuglioAbstract:Human African Trypanosomiasis staging follows human African Trypanosomiasis diagnosis (trypanosomes in blood and/or lymph glands, trypanosome-positive). Staging determines treatment, as stage 2 medications are toxic and/or difficult to administer. It relies on cerebrospinal fluid examination: stage 1 (no cerebrospinal fluid trypanosome, trypanosome-negative; white blood cell count ≤5/µl); stage 2 (trypanosome-positive and/or white blood cell count ≥20/µl); intermediate stage (6–19 white blood cell/µl; trypanosome-negative). Lumbar puncture is repeated biannually during the 24-month post-treatment follow-up to confirm cure or detect relapse. Sleep disorders are major at stage 2, with a two-symptom polysomnographic syndrome: sleep–wake circadian disruptions; and sleep-onset rapid eye movement sleep periods. Polysomnography (PSG) was proposed as a noninvasive diagnostic tool, and 24-h PSG recordings were performed throughout a 5-year survey in Congo. Before treatment, 76 patients were included and recorded. ...
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In vitro induction of microglial and endothelial cell apoptosis by cerebrospinal fluids from patients with human African Trypanosomiasis.
International Journal for Parasitology, 2003Co-Authors: Murielle Girard, Bernard Bouteille, Sylvie Bisser, Bertrand Courtioux, Claudine Vermot-desroches, John Wijdenes, Jean-louis Preud'homme, Marie-odile Jauberteau-marchanAbstract:In human African Trypanosomiasis, trypanosomes first develop in the blood and lymph (Stage 1), then spread to the central nervous system (CNS) (Stage 2). Disruption of the blood-brain barrier of unknown mechanism occurs in Stage 2 disease. The hypothesis that cerebrospinal fluids (CSF) from African Trypanosomiasis patients might contain factor(s) able to induce apoptosis in endothelial cells led us to evaluate this effect by two methods, the TdT-mediated dUTP nick end labelling (TUNEL) method and the measurement of soluble nucleosomes released by apoptotic cells in culture supernatant by ELISA. Apoptosis induction by CSF was also studied with microglial cells, the resident macrophages in the brain, which participate in the blood-brain barrier in the perivascular area. In contrast with control CSF, African Trypanosomiasis patients' CSF induced apoptosis in both microglial and endothelial cells. The results obtained with the two methods correlated well, and showed that Stage 2 CSF induced apoptosis at higher levels in microglial cells, whereas the disease stage was not decisive for apoptosis induction in endothelial cells. We measured soluble Fas ligand (sFasL) and anti-Fas antibodies levels, two potent inducers of the Fas signalling pathway leading to apoptosis, in CSF from African Trypanosomiasis patients and controls. CSF from African Trypanosomiasis patients contained sFasL, and anti-Fas antibodies at higher levels than in controls. Stage 2 CSF contained more sFasL than Stage 1 CSF, and anti-Fas antibodies were detected only in Stage 2 CSF. Caspase-8 inhibitor effect and statistical data suggest that other pro-apoptotic factors may be involved in some CSF-induced apoptosis. Apoptosis induction may participate in the pathogenesis during African Trypanosomiasis, and the presence of sFasL and anti-Fas antibodies may provide new tools for diagnosis and prognosis of the disease.
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Treatment of human African Trypanosomiasis
Bulletin of the World Health Organization, 2000Co-Authors: Michel Dumas, Bernard BouteilleAbstract:Human African Trypanosomiasis presents a health challenge to the international community -- a challenge both to poor countries and to rich countries (where there is often a shocking surfeit of health resources). In the year 2000, human African Trypanosomiasis is on the increase, even though we know how to tackle it since the tsetse fly, which transmits the trypanosomes that cause the disease, can survive only in tropical Africa and there is no human-to-human transmission. Although control and perhaps eradication of the disease are therefore theoretically possible, its incidence is on the rise despite having been well under control 50 years ago. The emergence of independent nations, political upheaval, the frequent state of insecurity that results, and the consequent disappearance of the health monitoring systems established during the colonial era, are some of the factors behind this. To these must be added the growing poverty of the countries affected by the disease. A further complication has been the need to take immediate action to deal with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), while there has been a background of marked demographic growth in the countries concerned. Over and above all this there is, however, a much more basic reason: the absence of a non-toxic treatment that is easily administered, reasonably priced, and effective at every stage of the disease, especially the neurological. Suramin and pentamidine are effective drugs during the initial phase of the disease but are almost totally ineffective in the neurological phase, since they are not able to cross the blood-brain barrier. Melarsoprol is effective against all stages of the disease but is particularly so against the neurological and is consequently kept in reserve for this purpose; it is also toxic and expensive (ca US$ 100 per patient). Elfornithine is an alternative to melarsoprol and is active against all stages of the disease, but has the great advantage of being less toxic; however, it is prohibitively expensive (ca US$ 700 per patient) and recipients have to be hospitalized and given the drug by perfusion for at least two weeks. With an effort from wealthy countries, these financial considerations could be overcome, although the necessary medical facilities are rarely to be found outside of towns in the areas where the patients with sleeping sickness live. The challenge presented by human African Trypanosomiasis must be taken up by developed countries. The disease can be curtailed because it is geographically limited. Smallpox has been eradicated; and poliomyelitis is on the way to elimination thanks to vaccination strategies that have been pursued despite political upheavals, wars and other tragedies. A political willingness, in particular the release of funds, has facilitated these successes. Trypanosomiasis, whose very existence preserves underdevelopment, could enjoy a similar fate. …
Pere P. Simarro - One of the best experts on this subject based on the ideXlab platform.
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risk for human African Trypanosomiasis central africa 2000 2009
Emerging Infectious Diseases, 2011Co-Authors: Pere P. Simarro, Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Raffaele C. Mattioli, José A. Ruiz Postigo, Jean JanninAbstract:Comprehensive georeference records for human African Trypanosomiasis in Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea, and Gabon were combined with human population layers to estimate a kernel-smoothed relative risk function. Five risk categories were mapped, and ≈3.5 million persons were estimated to be at risk for this disease.
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Risk for Human African Trypanosomiasis, Central Africa, 2000–2009
Emerging infectious diseases, 2011Co-Authors: Pere P. Simarro, Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Raffaele C. Mattioli, José A. Ruiz Postigo, Jean JanninAbstract:Comprehensive georeference records for human African Trypanosomiasis in Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea, and Gabon were combined with human population layers to estimate a kernel-smoothed relative risk function. Five risk categories were mapped, and ≈3.5 million persons were estimated to be at risk for this disease.
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Towards the Atlas of human African Trypanosomiasis
International journal of health geographics, 2009Co-Authors: Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Jose Antonio Ruiz, Raffaele C. Mattioli, Pere P. SimarroAbstract:Background Updated, accurate and comprehensive information on the distribution of human African Trypanosomiasis (HAT), also known as sleeping sickness, is critically important to plan and monitor control activities. We describe input data, methodology, preliminary results and future prospects of the HAT Atlas initiative, which will allow major improvements in the understanding of the spatial distribution of the disease.
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The Mandoul human African Trypanosomiasis focus in Chad: from evaluation to control
Medecine tropicale : revue du Corps de sante colonial, 2009Co-Authors: F J Louis, Ngaroroum A Djimadoum, Tongue L Kohagne, Pere P. SimarroAbstract:The Mandoul focus of human African Trypanosomiasis in southern Chad was first described by Gaston Muraz in the 1920s. After 40 years of control measures case reports became rare and the focus was forgotten. However the number of cases began to increase in 1993 and coordinated control measures were implemented in 2002. The first phase of control consisted of mapping out the focus that was shown to involve 45 villages and camps on both sides of the Mandoul River. The estimated number of inhabitants in the area is 20.000 and the endemic prevalence was 3.78%. Dynamic passive screening and regular active screening undertaken in the framework of the Chadian human African Trypanosomiasis control program with the assistance of expert technicians from the subregion reduced the prevalence to 0.77% in 2006. Although this reduction is encouraging control measures must be maintained and greater involvement of the health care system will be needed to achieve sustainable control of the disease and ultimately to eliminate human African Trypanosomiasis as a public health problem.
Jean Jannin - One of the best experts on this subject based on the ideXlab platform.
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risk for human African Trypanosomiasis central africa 2000 2009
Emerging Infectious Diseases, 2011Co-Authors: Pere P. Simarro, Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Raffaele C. Mattioli, José A. Ruiz Postigo, Jean JanninAbstract:Comprehensive georeference records for human African Trypanosomiasis in Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea, and Gabon were combined with human population layers to estimate a kernel-smoothed relative risk function. Five risk categories were mapped, and ≈3.5 million persons were estimated to be at risk for this disease.
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Risk for Human African Trypanosomiasis, Central Africa, 2000–2009
Emerging infectious diseases, 2011Co-Authors: Pere P. Simarro, Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Raffaele C. Mattioli, José A. Ruiz Postigo, Jean JanninAbstract:Comprehensive georeference records for human African Trypanosomiasis in Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea, and Gabon were combined with human population layers to estimate a kernel-smoothed relative risk function. Five risk categories were mapped, and ≈3.5 million persons were estimated to be at risk for this disease.
