Drug delivery systems in the treatment of African trypanosomiasis infections

Kroubi, Maya; Karembe, Hamadi; Betbeder, Didier

doi:10.1517/17425247.2011.574122

Cited by 19 publications

(12 citation statements)

References 97 publications

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“…Recent studies have also shown that colloidal nanoparticle formulations of diminazene exhibited greater activity against T. brucei brucei in vitro and had increased delivery to the brain in mice (Kroubi et al. , ).…”

Section: Resultsmentioning

confidence: 99%

“…It would, therefore, be of interest to conduct similar studies to establish the protective or curative effects of diminazene aceturate compared to the appropriate control groups. Recent studies have also shown that colloidal nanoparticle formulations of diminazene exhibited greater activity against T. brucei brucei in vitro and had increased delivery to the brain in mice (Kroubi et al 2010(Kroubi et al , 2011.…”

Section: Resultsmentioning

confidence: 99%

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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%

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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“…So far, chemotherapy is the only strategy available to treat the disease, whereby unique organelles of trypanosomes (glycosomes or kinetoplast) that are absent in the mammalian host or trypanosome metabolic pathways that differ from their host counterparts (carbohydrate metabolism, protein and lipid modifications, and programmed cell death) are targeted (25–27). Given that chemotherapy is associated with high drug toxicity, there is an urgent need to optimize trypanocide usage and delivery in order to decrease the risk of toxicity and/or resistance development (28–30). Control of AT is also hampered due to inefficient diagnosis of the infection especially for AAT and T. b. rhodesiense HAT where microscopical parasite detection (cheap but with low sensitivity), detection of the parasite’s DNA (expensive but with high sensitivity), or anti-parasite antibodies remain the only available tools for diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Nanobodies As Tools to Understand, Diagnose, and Treat African Trypanosomiasis

et al. 2017

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African trypanosomes are strictly extracellular protozoan parasites that cause diseases in humans and livestock and significantly affect the economic development of sub-Saharan Africa. Due to an elaborate and efficient (vector)–parasite–host interplay, required to complete their life cycle/transmission, trypanosomes have evolved efficient immune escape mechanisms that manipulate the entire host immune response. So far, not a single field applicable vaccine exists, and chemotherapy is the only strategy available to treat the disease. Current therapies, however, exhibit high drug toxicity and an increased drug resistance is being reported. In addition, diagnosis is often hampered due to the inadequacy of current diagnostic procedures. In the context of tackling the shortcomings of current treatment and diagnostic approaches, nanobodies (Nbs, derived from the heavy chain-only antibodies of camels and llamas) might represent unmet advantages compared to conventional tools. Indeed, the combination of their small size, high stability, high affinity, and specificity for their target and tailorability represents a unique advantage, which is reflected by their broad use in basic and clinical research to date. In this article, we will review and discuss (i) diagnostic and therapeutic applications of Nbs that are being evaluated in the context of African trypanosomiasis, (ii) summarize new strategies that are being developed to optimize their potency for advancing their use, and (iii) document on unexpected properties of Nbs, such as inherent trypanolytic activities, that besides opening new therapeutic avenues, might offer new insight in hidden biological activities of conventional antibodies.

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“…Single-drug use is customarily used for AAT management, but there's renewed interest in development of novel biocompatible formulations that improve therapeutic outcomes (Kroubi et al ., 2011; Giordani et al ., 2016). Randomized clinical trials are necessary to evaluate the benefits and adverse effects attributable to these novel treatments.…”

Section: Discussionmentioning

confidence: 99%

Modelling appropriate use of trypanocides to restrict wide-spread multi-drug resistance during chemotherapy of animal African trypanosomiasis

Wangwe

Wamwenje

Mirieri³

et al. 2018

Parasitology

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Trypanocide resistance remains a huge challenge in the management of animal African trypanosomiasis. Paucity of data on the prevalence of multi-drug resistant trypanosomes has greatly hindered optimal veterinary management practices. We use mathematical model predictions to highlight appropriate drug regimens that impede trypanocide resistance development in cattle. We demonstrate that using drugs in decreasing resistance order results in a negligible increase in number of cattle with resistant infection, in contrast to a more pronounced increase from trypanocide use in increasing resistance order. We demonstrate that the lowest levels of trypanocide resistance are achieved with combination therapy. We also show that increasing the number of cattle treated leads to a progressive reduction in the number of cattle with drug resistant infections for treatments of up to 80% of the cattle population for the combination treatment strategy. Our findings provide an initial evidence-based framework on some essential practices that promote optimal use of the handful of trypanocides. We anticipate that our modest forecasts will improve therapeutic outcomes by appropriately informing on the best choice, and combination of drugs that minimize treatment failure rates.

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Drug delivery systems in the treatment of African trypanosomiasis infections

Cited by 19 publications

References 97 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

Nanobodies As Tools to Understand, Diagnose, and Treat African Trypanosomiasis

Modelling appropriate use of trypanocides to restrict wide-spread multi-drug resistance during chemotherapy of animal African trypanosomiasis

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