Drug resistance in pathogenic African trypanosomes: what hopes for the future?

Anene, B. M.; Onah, D. N.; Nawa, Yukifumi

doi:10.1016/s0304-4017(00)00427-1

Cited by 101 publications

(66 citation statements)

References 70 publications

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“…This approach can be hindered by the emergence of resistant trypanosomes, which can also be spread from humans to cattle and vice versa (Matovu et al 1997). It is also evident that resistance of T. b. brucei to diminazene is a significant problem in trypanosomosis-endemic areas (Ndung'u et al 1999;Anene et al 2001;Anene, Ezeokonkwo, Mmesirionye, Tettey, Brock, Barrett & De Koning 2006).…”

Section: Discussionmentioning

confidence: 99%

Occurrence of multiple drug resistance in Trypanosoma brucei rhodesiense isolated from sleeping sickness patients

Kagira

Maina²

2007

Onderstepoort J Vet Res

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The occurrence of cross-resistance among melarsoprol-resistant Trypanosoma brucei rhodesiense isolates was investigated in this study. The isolates, T. b. rhodesiense KETRI 237, 2538, 1992, 2709, 2694 and 3530, had been obtained from sleeping sickness patients in Kenya and Uganda between 1960 and 1985. Five groups consisting of six mice each were inoculated intraperitoneally with 105 parasites of each isolate, and 24 h later treated with either melarsoprol, homidium chloride, diminazene aceturate or isometamidium chloride. The control group comprised infected but untreated mice. The mice were monitored for cure for a period of 60 days post-treatment. The mean prepatent period in the control mice was 5 days while the mean survival period was 22 days. Five of the stabilates, KETRI 237, 2538, 2709, 2694, and 3530, were confirmed to be melarsoprol resistant. Cross-resistance was observed, with the majority of the isolates being resistant to homidium chloride (5/6) and diminazene aceturate (5/6), but all were sensitive to isometamidium chloride (6/6). However T. b. rhodesiense KETRI 1992, which was previously considered as melarsoprol resistant, was sensitive to all the drugs tested. In conclusion, our study has revealed the existence of cross-resistance among the melarsoprol resistant isolates which could only be cured by isometamidium.

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Section: Discussionmentioning

confidence: 99%

Occurrence of multiple drug resistance in Trypanosoma brucei rhodesiense isolated from sleeping sickness patients

Kagira

Maina²

2007

Onderstepoort J Vet Res

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“…Even for these, relapses and multi-drug resistant population have started to emerge [9][10][11][12][13] . Therefore, the need to source for safer, cheaper and readily available sources of medicaments cannot be over-emphasized.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Anti-trypanosomal Properties of Four Extracts of Leaves, Stem and Root Barks of Prosopis africana in Laboratory Animals

Atawodi¹,

Ogunbusola²

2010

Biokemistri

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Qualitative phytochemical and anti-trypanosomal properties of the petroleum ether, chloroform, methanol and aqueous extracts, obtained by cold extraction from the leaves, stem bark and roots of Prosopis africana were evaluated. The methanolic and aqueous extracts of the stem bark and leaves of the plant contained alkaloids, saponins, tannins and flavonoids. Anthraquinone was present in the stem bark methanolic extract and in the methanolic and aqueous extracts of the root as well as the aqueous extract of the leaves. Resins was present in the petroleum ether and chloroform extracts of the stem bark and leaves, while tannins was detected in the methanol and aqueous extracts of the stem bark and leaves of the plant in addition to the petroleum ether and chloroform extracts of the root bark. All the solvent extracts showed strong in vitro anti-trypanosomal activity and 2 and 4 mg/ml, but in vivo only the methanolic extract of the leaves displayed the most promising anti-trypanosomal effect at 200 mg/kg dose. Hence, Prosopis africana extracts possess significant anti-trypanosomal activity to warrant bioassay-guided evaluation and identification of the active principle.

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“…Although human African trypanosomiasis or sleeping sickness is caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense, animal trypanosomiasis is caused by Trypanosoma congolense, Trypanosoma vivax, T. brucei brucei and Trypanosoma evansi (1,2). Conventional anti-trypanosome treatment of infected hosts faces several problems including high drug toxicity and increasing drug resistance (2)(3)(4). In addition, the wide distribution of trypanosomes throughout the African wildlife reservoir confronts the region with an extensive problem of reinfection (5).…”

mentioning

confidence: 99%

“…Although vaccination against trypanosomes offers the most sustainable long-term solution, so far this strategy is beyond reach. Indeed trypanosomes are extracellular parasites that are adapted to immune confrontation through a mechanism of antigenic variation of GPI-anchored variant surface glycoproteins (VSG) 3 (6,7). During infection, released VSG interacts with various immune cells triggering an effective host anti-parasite immune response, including macrophage and B cell activation and Th1 cell stimulation (8,9).…”

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confidence: 99%

A Glycosylphosphatidylinositol-Based Treatment Alleviates Trypanosomiasis-Associated Immunopathology

Stijlemans

Baral

Guilliams

et al. 2007

The Journal of Immunology

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The GPI-anchored trypanosome variant surface glycoprotein (VSG) triggers macrophages to produce TNF, involved in trypanosomiasis-associated inflammation and the clinical manifestation of sleeping sickness. Aiming at inhibiting immunopathology during experimental Trypanosoma brucei infections, a VSG-derived GPI-based treatment approach was developed. To achieve this, mice were exposed to the GPI before an infectious trypanosome challenge. This GPI-based strategy resulted in a significant prolonged survival and a substantial protection against infection-associated weight loss, liver damage, acidosis, and anemia; the latter was shown to be Ab-independent and correlated with reduced macrophage-mediated RBC clearance. In addition, GPI-based treatment resulted in reduced circulating serum levels of the inflammatory cytokines TNF and IL-6, abrogation of infection-induced LPS hypersensitivity, and an increase in circulating IL-10. At the level of trypanosomiasis-associated macrophage activation, the GPI-based treatment resulted in an impaired secretion of TNF by VSG and LPS pulsed macrophages, a reduced expression of the inflammatory cytokine genes TNF, IL-6, and IL-12, and an increased expression of the anti-inflammatory cytokine gene IL-10. In addition, this change in cytokine pattern upon GPI-based treatment was associated with the expression of alternatively activated macrophage markers. Finally, the GPI-based treatment also reduced the infection-associated pathology in Trypanosoma congolense and Trypanosoma evansi model systems as well as in tsetse fly challenge experiments, indicating potential field applicability for this intervention strategy.

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Drug resistance in pathogenic African trypanosomes: what hopes for the future?

Cited by 101 publications

References 70 publications

Occurrence of multiple drug resistance in <i>Trypanosoma brucei rhodesiense</i> isolated from sleeping sickness patients

Occurrence of multiple drug resistance in <i>Trypanosoma brucei rhodesiense</i> isolated from sleeping sickness patients

Evaluation of Anti-trypanosomal Properties of Four Extracts of Leaves, Stem and Root Barks of <i>Prosopis africana</i> in Laboratory Animals

A Glycosylphosphatidylinositol-Based Treatment Alleviates Trypanosomiasis-Associated Immunopathology

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