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African Trypanosomiasis

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Peter G. E. Kennedy – One of the best experts on this subject based on the ideXlab platform.

  • Clinical features, diagnosis, and treatment of human African Trypanosomiasis (sleeping sickness)
    The Lancet. Neurology, 2012
    Co-Authors: Peter G. E. Kennedy
    Abstract:

    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.

  • The continuing problem of human African Trypanosomiasis (sleeping sickness)
    Annals of Neurology, 2008
    Co-Authors: Peter G. E. Kennedy
    Abstract:

    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.

  • Diagnostic and neuropathogenesis issues in human African Trypanosomiasis.
    International journal for parasitology, 2006
    Co-Authors: Peter G. E. Kennedy
    Abstract:

    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.

José R. Franco – One of the best experts on this subject based on the ideXlab platform.

  • Human African Trypanosomiasis.
    Handbook of clinical neurology, 2013
    Co-Authors: Veerle Lejon, Marina Bentivoglio, José R. Franco
    Abstract:

    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.

  • risk for human African Trypanosomiasis central africa 2000 2009
    Emerging Infectious Diseases, 2011
    Co-Authors: Pere P. Simarro, Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Raffaele C. Mattioli, José A. Ruiz Postigo, Jean Jannin
    Abstract:

    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.

  • Risk for Human African Trypanosomiasis, Central Africa, 2000–2009
    Emerging infectious diseases, 2011
    Co-Authors: Pere P. Simarro, Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Raffaele C. Mattioli, José A. Ruiz Postigo, Jean Jannin
    Abstract:

    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.

Bernard Bouteille – One of the best experts on this subject based on the ideXlab platform.

Pere P. Simarro – One of the best experts on this subject based on the ideXlab platform.

  • risk for human African Trypanosomiasis central africa 2000 2009
    Emerging Infectious Diseases, 2011
    Co-Authors: Pere P. Simarro, Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Raffaele C. Mattioli, José A. Ruiz Postigo, Jean Jannin
    Abstract:

    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.

  • Risk for Human African Trypanosomiasis, Central Africa, 2000–2009
    Emerging infectious diseases, 2011
    Co-Authors: Pere P. Simarro, Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Raffaele C. Mattioli, José A. Ruiz Postigo, Jean Jannin
    Abstract:

    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.

  • Towards the Atlas of human African Trypanosomiasis
    International journal of health geographics, 2009
    Co-Authors: Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Jose Antonio Ruiz, Raffaele C. Mattioli, Pere P. Simarro
    Abstract:

    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.

Jean Jannin – One of the best experts on this subject based on the ideXlab platform.

  • risk for human African Trypanosomiasis central africa 2000 2009
    Emerging Infectious Diseases, 2011
    Co-Authors: Pere P. Simarro, Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Raffaele C. Mattioli, José A. Ruiz Postigo, Jean Jannin
    Abstract:

    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.

  • Risk for Human African Trypanosomiasis, Central Africa, 2000–2009
    Emerging infectious diseases, 2011
    Co-Authors: Pere P. Simarro, Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, Raffaele C. Mattioli, José A. Ruiz Postigo, Jean Jannin
    Abstract:

    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.