In vitro drug sensitivity of Trypanosoma gambiense isolates

Brun, Reto; Baeriswyl, S.; Kunz, Christina

doi:10.1016/0001-706x(89)90049-1

Cited by 13 publications

(3 citation statements)

References 13 publications

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“…As positive controls the commercial drugs suramin and amphotericin B for treatment of sleeping sickness and leishmaniasis, respectively, were investigated. The ED 50 values of these drugs ( Table 1) were in the range of those reported for bloodstream forms of T. brucei (16), (18), (19) and promastigotes of L. major (9), (20).…”

Section: Gc Methodmentioning

confidence: 51%

In vitro Effect of Essential Oils and Isolated Mono- and Sesquiterpenes on Leishmania major and Trypanosoma brucei

Mikus¹,

Harkenthal²,

Steverding³

et al. 2000

Planta Med

134

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The effect of different essential oils as well as of isolated mono- and sesquiterpenes on the viability of bloodstream forms of Trypanosoma brucei, promastigotes of Leishmania major and human HL-60 cells was evaluated using the Almar Blue assay. Of the 12 essential oils and 8 terpenes investigated, only three essential oils, Melissa officinalis (balmmint) oil, Thymus vulgaris (thyme) oil, and Melaleuca alternifolia (tea tree) oil were about 50-fold and 80-fold more toxic to bloodstream forms of T. brucei than to HL-60 cells, respectively. Terpinen-4-ol, the main compound of the Australian tea tree oil, was even 1000-fold more toxic to trypanosomes than to the human cells. On the other hand, none of the essential oils and terpenes tested were more toxic to promastigotes of L. major than to HL-60 cells.

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Section: Gc Methodmentioning

confidence: 51%

In vitro Effect of Essential Oils and Isolated Mono- and Sesquiterpenes on Leishmania major and Trypanosoma brucei

Mikus¹,

Harkenthal²,

Steverding³

et al. 2000

Planta Med

134

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“…The overall rate of treatment failures and relapses in our study was 7.1% (144/2020), a value that compares well with those in the literature (5%-8% [24]). However, because alarmingly high rates-up to 30%-have been documented in some areas (Uganda [23], Angola [25], and Sudan [26]), failure rates by disease focus should be reported more carefully. In our study, most of the relapses (136/144) were reported in southern Sudanese centers, which may be explained (at least partially) by the enhanced follow-up activities conducted by the executing organizations, which resulted in a 12.2% (136/ 1111) failure rate in this area.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of a 10‐Day Melarsoprol Schedule for the Treatment of Late‐Stage Human African Trypanosomiasis: Confirmation from a Multinational Study (ImpamelII)

Schmid

Richer²,

Bilenge

et al. 2005

J INFECT DIS

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The 10-day treatment schedule was well implemented in the field and was effective. It reduces treatment duration, drug amount, and hospitalization costs per patient, and it increases treatment-center capacity. The shorter protocol has been recommended by the International Scientific Council for Trypanosomiasis Research and Control for the treatment of late-stage HAT caused by Trypanosoma brucei gambiense.

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“…gambiense leads to silent or chronic infections in mice with hardly detectable parasites [29]. Generally, bloodstream form parasites from in vivo or in vitro cultures are exposed to compounds for up to 72 hours, whereafter the remaining viability of the cells is assessed using either radioactive, colorimetric, fluorimetric, or luminescent detection [5,9,26,30,31]. The fluorimetric resazurin viability assay is very cost-effective, but performance is limited with T.b.…”

Section: Introductionmentioning

confidence: 99%

Luminescent multiplex viability assay for Trypanosoma brucei gambiense

et al. 2013

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BackgroundNew compounds for the treatment of human African trypanosomiasis (HAT) are urgently required. Trypanosoma brucei (T.b.) gambiense is the leading cause of HAT, yet T.b. gambiense is often not the prime target organism in drug discovery. This may be attributed to the difficulties in handling this subspecies and the lack of an efficient viability assay to monitor drug efficacy.MethodsIn this study, a T.b. gambiense strain, recently isolated in the D.R. Congo, was made bioluminescent by transfection with Renilla luciferase (RLuc) without altering its in vitro and in vivo growth characteristics. A luminescent multiplex viability assay (LMVA), based on measurement of the Renilla luciferase activity and the ATP content of the cells within the same experiment, was investigated as an alternative to the standard fluorimetric resazurin viability assay for drug sensitivity testing of T.b. gambiense.ResultsIn a 96-well format, the RLuc transfected strain showed a detection limit of 2 × 104 cells ml-1 for the Renilla luciferase measurement and 5 × 103 cells ml-1 for the ATP measurement. Both assays of the LMVA showed linearity up to 106 cells ml-1 and correlated well with the cell density during exponential growth of the long slender bloodstream forms. The LMVA was compared to the fluorimetric resazurin viability assay for drug sensitivity testing of pentamidine, eflornithine, nifurtimox and melarsoprol with both the wild type and the RLuc transfected population. For each drug, the IC50 value of the RLuc population was similar to that of the wild type when determined with either the fluorimetric resazurin method or the LMVA. For eflornithine, nifurtimox and melarsoprol we found no difference between the IC50 values in both viability assays. In contrast, the IC50 value of pentamidine was higher when determined with the fluorimetric resazurin method than in both assays of the LMVA.ConclusionsLMVA has some advantages for viability measurement of T.b. gambiense: it requires less incubation time for viability detection than the fluorimetric resazurin assay and in LMVA, two sensitive and independent viability assays are performed in the same experiment.

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In vitro drug sensitivity of Trypanosoma gambiense isolates

Cited by 13 publications

References 13 publications

In vitro Effect of Essential Oils and Isolated Mono- and Sesquiterpenes on Leishmania major and Trypanosoma brucei

In vitro Effect of Essential Oils and Isolated Mono- and Sesquiterpenes on Leishmania major and Trypanosoma brucei

Effectiveness of a 10‐Day Melarsoprol Schedule for the Treatment of Late‐Stage Human African Trypanosomiasis: Confirmation from a Multinational Study (ImpamelII)

Luminescent multiplex viability assay for Trypanosoma brucei gambiense

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