Chemotherapy of Human African Trypanosomiasis

Bacchi, Cyrus J.

doi:10.1155/2009/195040

Cited by 48 publications

(44 citation statements)

References 36 publications

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“…Berenil ® is not licensed for human use but has been used successfully in the treatment of human African Trypanosomiasis in the early stages of the infection (Abaru et al. ; Bacchi ; Hutchinson and Watson ). Berenil ® was reported to be effective in curing a case of human babesiosis, although the patient subsequently developed acute idiopathic polyneuritis (Landry‐Guillain‐Barré Syndrome) (Ruebush et al.…”

Section: Resultsmentioning

confidence: 99%

The In Vitro Efficacy of Antimicrobial Agents Against the Pathogenic Free‐Living Amoeba Balamuthia mandrillaris

Ahmad

Heaselgrave

Andrew

et al. 2013

J Eukaryotic Microbiology

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The free-living amoeba Balamuthia mandrillaris causes usually fatal encephalitis in humans and animals. Only limited studies have investigated the efficacy of antimicrobial agents against the organism. Assay methods were developed to assess antimicrobial efficacy against both the trophozoite and cyst stage of B. mandrillaris (ATCC 50209). Amphotericin B, ciclopirox olamine, miltefosine, natamycin, paromomycin, pentamidine isethionate, protriptyline, spiramycin, sulconazole and telithromycin had limited activity with amoebacidal levels of > 135-500 μM. However, diminazene aceturate (Berenil(®) ) was amoebacidal at 7.8 μM and 31.3-61.5 μM for trophozoites and cysts, respectively. Assays for antimicrobial testing may improve the prognosis for infection and aid in the development of primary selective culture isolation media.

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Section: Resultsmentioning

confidence: 99%

The In Vitro Efficacy of Antimicrobial Agents Against the Pathogenic Free‐Living Amoeba Balamuthia mandrillaris

Ahmad

Heaselgrave

Andrew

et al. 2013

J Eukaryotic Microbiology

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“…Quinine was the drug of choice for close to 100 years before it was replaced with artemisinin isolated from Artemisia annua due to the emergence of resistant parasites. There are however reports of artemisinin failure in South East Asia making it necessary to develop new effective chemotherapy (Adeyemi et al, ; Bacchi, ; Balunas & Kinghorn, ; Singh & Sivakumar, ). Despite the use of medicinal plants in the treatment of ailments including those caused by protozoan pathogens in Africa (Ankrah et al, ; Barrett, Boykin, Brun, & Tidwell, ; Okpekon et al, ; Rahmatullah et al, ; Trouiller et al, ), scientific evidence of the medicinal properties of these plants have not been fully evaluated (Abu & Uchendu, ; Fathuddin, ; M. A. Ibrahim et al, ; N. Nweze, Anene, & Asuzu, ; Nweze, ; Ogbadoyi, Kabiru, & Omotosho, ; Wurochekke & Anyanwu, ).…”

Section: Introductionmentioning

confidence: 99%

In vitro antiprotozoan activity and mechanisms of action of selected Ghanaian medicinal plants against Trypanosoma, Leishmania, and Plasmodium parasites

Ohashi

Amoa-Bosompem

Kwofie

et al. 2018

Phytotherapy Research

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Trypanosomiasis, leishmaniasis, and malaria are protozoan infections of public health importance with thousands of new cases recorded annually. Control of these infection(s) with existing chemotherapy is limited by drug toxicity, lengthy parenteral treatment, affordability, and/or the emergence of resistant strains. Medicinal plants on the other hand are used in the treatment of various infectious diseases although their chemical properties are not fully evaluated. In this study, we screened 112 crude extracts from 72 selected Ghanaian medicinal plants for anti-Trypanosoma, anti-Leishmania, and anti-Plasmodium activities in vitro and investigated their mechanisms of action. Twenty-three extracts from 20 plants showed significant antiprotozoan activity against at least 1 of 3 protozoan parasites screened with IC values less than 20 μg/ml. Eleven extracts showed high anti-Trypanosoma activity with Bidens pilosa whole plant and Morinda lucida leaf extracts recording the highest activities. Their IC (selectivity index [SI]) values were 5.51 μg/ml (35.00) and 5.96 μg/ml (13.09), respectively. Nine extracts had high anti-Leishmania activity with Annona senegalensis and Cassia alata leaf extracts as the most active. Their IC (SI) values were 10.8 μg/ml (1.50) and 10.1 μg/ml (0.37), respectively. Six extracts had high anti-Plasmodium activity with the leaf and stem-bark extracts of Terminalia ivorensis recording the highest activity. Their IC (SI) values were 7.26 μg/ml (129.36) and 17.45 μg/ml (17.17), respectively. Only M. lucida at 25 μg/ml induced significant apoptosis-like cell death in Trypanosoma parasites. Anti-Leishmania active extracts induced varying morphological changes in Leishmania parasites such as multiple nuclei and/or kinetoplast, incomplete flagella division, or nuclear fragmentation. Active extracts may be potential sources for developing new chemotherapy against these infections.

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“…brucei and T.b. gambiense [24], the latter is often found to be more susceptible to drugs than other T. brucei subspecies, as is the case for eflornithine and pentamidine [15,16,25-27]. Several factors hamper inclusion of 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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Chemotherapy of Human African Trypanosomiasis

Cited by 48 publications

References 36 publications

The In Vitro Efficacy of Antimicrobial Agents Against the Pathogenic Free‐Living Amoeba Balamuthia mandrillaris

The In Vitro Efficacy of Antimicrobial Agents Against the Pathogenic Free‐Living Amoeba Balamuthia mandrillaris

In vitro antiprotozoan activity and mechanisms of action of selected Ghanaian medicinal plants against Trypanosoma, Leishmania, and Plasmodium parasites

Luminescent multiplex viability assay for Trypanosoma brucei gambiense

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