The Efficacy of Pentamidine in the Treatment of Early-Late Stage Trypanosoma brucei gambiense Trypanosomiasis *

Doua, F.; Miezan, T. W.; Singaro, J. R. Sanon; Yapo, Félix Boa; Baltz, Théo

doi:10.4269/ajtmh.1996.55.586

Cited by 85 publications

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“…Or, dans une étude récente menée en Côte d'Ivoire, plusieurs sujets dont la PCR du LCR était positive, mais la DC négative et le nombre de cellules compris entre 0 et 5, ont été traités efficacement par la pentamidine (voir Figure 1) [27]. De plus, des sujets ayant entre 0 et 20 cellules/µl ou positifs en DC ont pu être traités efficacement par la pentamidine, ce qui laisse penser que même la présence de trypanosomes dans le LCR ne semble pas justifier l'emploi du mélarsoprol [28]. Même si la PCR/LCR permet d'améliorer le diagnostic de phase de la maladie, son intérêt n'apparaît pas toujours évident dans la décision thérapeutique.…”

Section: Limites Rencontréesunclassified

“…En termes d'application sur le LCR, la PCR peut permettre de déterminer si un malade est en première ou seconde phase, ce qui conditionnera son traitement. Mais a-t-on réellement inté-rêt à utiliser le test le plus sensible pour le diagnostic de phase, alors que plusieurs travaux rapportent que l'on peut traiter avec succès des malades en seconde phase par la pentamidine [28]. En revanche, la PCR présente un intérêt certain dans le suivi du traitement et le diagnostic précoce des rechutes, la mise en évidence d'ADN trypanosomien dans le LCR pouvant être considérée comme la signature d'une réapparition de la maladie.…”

Section: Conclusion Et Perspectivesunclassified

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Apports et limites du diagnostic de la trypanosomiase humaine africaine

et al. 2004

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La trypanosomiase humaine africaine (THA) -ou maladie du sommeil -reste un problème majeur de santé publique en Afrique intertropicale. La prévalence, très souvent sous-estimée en raison de la faible proportion de population à risque sous surveillance, oscillerait entre 300 000 et 500 000 [1]. Cette parasitose, transmise par les glossines ou mouches tsé-tsé, est causée par des protozoaires du genre Trypanosoma : Trypanosoma brucei gambiense (Tb gambiense), responsable d'une forme chronique (forme gambienne) de la maladie en Afrique de l'Ouest et Centrale, et Tb rhodesiense, responsable d'une forme plus aiguë en Afrique de l'Est (forme rhodésienne).Dans le cas de la forme gambienne, le cycle de transmission hommemouche-homme semble prédominer. L'existence d'un réservoir animal a été mise en évidence [2]. Son importance épidémiolo-gique dans la transmission et la persistance de la maladie est toutefois encore mal connue. La forme rhodésienne est une zoonose typique. La transmission à l'homme (souvent considéré comme hôte accidentel) se fait suivant le cycle animal sauvage ou domestique-mouche-homme. Cette différence entre les deux formes de la maladie conditionne les stratégies de lutte : dans la forme gambienne, le traitement de tous les malades, associé à une lutte antivectorielle, devrait théoriquement permettre une éradication de la maladie. Cependant le traitement de tous les malades nécessite un dépistage exhaustif. La THA évolue en deux phases, une première période, lymphatico-sanguine, durant laquelle le parasite se multiplie dans le sang et dans la lymphe, et une deuxième période, méningo-encéphalitique qui correspond au passage du parasite dans le liquide céphalo-rachidien (LCR). Au cours de la première période (qui peut durer plusieurs années dans la forme gambienne,

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Section: Limites Rencontréesunclassified

Section: Conclusion Et Perspectivesunclassified

Apports et limites du diagnostic de la trypanosomiase humaine africaine

et al. 2004

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“…Pharmacokinetic evidence indicates that three injections may be equally effective (Bronner et al 1991;Bronner, 1994) and a respective comparative clinical trial is currently ongoing to evaluate this (ISRCTN55042030). Due to the high potency of pentamidine and the low drug levels detected in the CSF (Bronner et al 1991) the use to treat 'intermediate stage' patients (up to 10 or 20 white blood cells (WBC) mm − 3 in CSF) was suggested (Doua et al 1996). The resulting efficacy in respective studies is equivocal (Ruiz et al 2002;Lejon et al 2003;Balasegaram et al 2006b).…”

Section: P E N T a M I D I N Ementioning

confidence: 99%

Chemotherapy against human African trypanosomiasis: Is there a road to success?

Burri

2010

Parasitology

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S U M M A R YFor over fifty years, human African trypanosomiasis (HAT, sleeping sickness) has been treated with suramin, pentamidine and the very toxic organo-arsenical melarsoprol that was the only drug available for effective treatment of the second stage of the disease. Recently there have been significant efforts using molecular and biochemical approaches to drug design, including high-throughput screening, but the number of lead compounds with promising activity against T. brucei spp. and an acceptable toxicity index has remained astonishingly small. Clinical research continues to be difficult due to the economic constraints and the complexity of trials on a low prevalence disease in remote and impoverished African regions. Despite those limitations the situation for the patients is improving thanks to the combination of a number of critical factors. By the late 1990s the disease had reached epidemic levels that triggered political support. WHO would sign a donation agreement with the manufacturers for all drugs to treat HAT. A result of this agreement was that eflornithine which is much safer than melarsoprol became available and widely used by non-governmental organizations. The IMPAMEL I and II programmes demonstrated that against all odds the conduct of clinical trials on HAT was feasible. This allowed the initiation of trials on combination therapies which eventually resulted in the nifurtimox-eflornithine combination treatment (NECT). This combination is currently being introduced as first line treatment, and there is even the prospect of having a new compound, fexinidazole, in the development pipeline. This review summarizes the key information about the existing drugs and gives a comprehensive summary about the recent and currently ongoing efforts towards new drugs.

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“…A pentamidina, além de ser relativamente eficaz na terapia da leishmaniose, é eficaz no tratamento de casos incipientes de tripanossomíase gambiense ou rodesiana 26 . 27 .…”

Section: Outros Agentes Quimioterápicos Utilizados No Tratamento Da Lunclassified

Antimoniais empregados no tratamento da leishmaniose: estado da arte

Rath¹,

Trivelin²,

Imbrunito³

et al. 2003

Quím. Nova

123

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are the drugs of choice for the treatment of leishmaniasis over 90 years, a disease that currently affects 12 million people worldwide. Its introduction was based on 19 th century concepts of therapeutic effects of metal salts as arsenicals and other metals, most of them abandoned due to toxic effects or better drugs. In the last three decades, there was a great improvement in the knowledge of cell biology and immunology of those infections, but chemotherapy has not been improved in the same strength. The structure and mechanism of action of the two pentavalent antimonial drugs of choice, meglumine antimoniate and sodium stibogluconate, are not well known and the contamination of those pharmaceutical by toxic contaminants have been verified. Keywords: antimony; leishmaniasis; therapy. INTRODUÇÃO LeishmanioseA leishmaniose é uma doença infecciosa zoonótica, amplamente distribuída em todo mundo, que afeta o homem e os animais. Esta parasitose ocorre na Ásia, Europa, África e Américas, sendo que existem relatos sobre a doença, no continente americano, desde a época colonial. Em 1571, Pedro Pizarro relatou que os povos situados nos vales quentes do Peru eram dizimados por uma doença que desfigurava o nariz, a qual foi posteriormente caracterizada como leishmaniose 1 . A importância desta doença era tamanha, que as deformações provocadas 2 chegaram a ser registradas em peças cerâmi-cas por artistas da época.A Em 1993, a Organização Mundial da Saúde considerou a Leishmaniose como a segunda doença de importância pública, causada por protozoário. VETORESOs vetores da leishmaniose são dípteros da família Psychodida, hematófagos pertencentes aos gêneros Phlebotomus (Velho Mundo) e Lutzomyia (Novo Mundo), com vasta distribuição nos climas quentes e temperados. Somente as fêmeas são hematófagas. Pertencem ao tipo dos dípteros de atividade crepuscular e pós-crepuscular, abrigando-se durante o dia em lugares úmidos, sombrios e bem protegidos dos ventos. São encontrados em tocas de animais silvestres, buracos de pau, ocos de bambu 4 . Os flebótomos, dos gêneros Lutzomyia e Psychopopygus, infectam-se ao picar o animal portador da doença, aspirando macró-fagos parasitados ou amastigotas livres no sangue ou tecidos e podem, assim, transmitir a doença ao homem 5 . Os mamíferos portadores da leishmaniose são geralmente animais silvestres como a preguiça, o tamanduá, roedores, raposas e outros, sendo que grande parte das lesões nestes não é aparente. No Brasil, o mais importante reservatório animal é o cão e a raposa 6 . A partir de estudos patofisiológicos foi verificado que a Leishmania se desenvolve no tubo intestinal do hospedeiro invertebrado, na forma promastigota, e essa, uma vez introduzida nos mamíferos através da picada, transforma-se na forma amastigota. Enquanto a forma promastigota é flagelada e extracelular, a forma amastigota é intracelular e sem movimento. A multiplicação dos amastigotas ocorre no interior de vacúolos parasi-

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The Efficacy of Pentamidine in the Treatment of Early-Late Stage Trypanosoma brucei gambiense Trypanosomiasis *

Cited by 85 publications

References 0 publications

Apports et limites du diagnostic de la trypanosomiase humaine africaine

Apports et limites du diagnostic de la trypanosomiase humaine africaine

Chemotherapy against human African trypanosomiasis: Is there a road to success?

Antimoniais empregados no tratamento da leishmaniose: estado da arte

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