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Melarsoprol
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Eflornithine and nifurtimox have been introduced for the treatment of second-stage disease caused by T. brucei gambiense (West African sleeping sickness) (see Chapter 196, Eflornithine and Chapter 193, Nifurtimox). Emerging evidence suggests the combination of eflornithine and nifurtimox, an agent used previously for Chagas disease in South America, may be most effective and less toxic than melarsoprol. This nifurtimox-eflornithine combination therapy (NECT) is now the preferred regimen for this form of disease (Kennedy, 2008; WHO, 2016), and nifurtimox was recently listed as an essential drug by the World Health Organization (WHO, 2009) (see Chapter 193, Nifurtimox). Eflornithine is ineffective against T. brucei rhodesiense, meaning that melarsoprol remains the only effective drug against second-stage East African sleeping sickness (Chappuis, 2007).
The Renewal of Interest in Nitroaromatic Drugs
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Nicolas Primas, Caroline Ducros, Patrice Vanelle, Pierre Verhaeghe
In 2001, a clinical trial compared three drug combination treatments for second-stage HAT due to T. b. gambiense: melarsoprol (4) with eflornithine (16), melarsoprol (4) with nifurtimox (8), and eflornithine (16) with nifurtimox (8) (Priotto et al. 2006). The existing anti-trypanosomal drugs were combined as a way of reducing the required dosages to avoid the related toxicities and the emergence of drug-resistance. Against all expectations, the trial was interrupted prematurely due to high drug-related mortality in the melarsoprol arms. Fortunately, Nifurtimox-Eflornithine Combination Therapy (NECT) demonstrated good tolerance and sufficient efficacy for further investigations to be performed. Cure rates with the NECT drug-combination (96.5%) were comparable with monotherapy using eflornithine (16), but with lower side-effects. Moreover, it allowed the dose and the duration of the eflornithine (16) infusion to be reduced (Priotto et al. 2009). The Drugs for Neglected Diseases Initiative (DNDi) successfully repositioned nifurtimox (8), originally designed as an antichagasic drug, and prompted the WHO in 2009 to add NECT to the Model Lists of Essential Medicines, as more than 60% of late-stage T. b. gambiense HAT could be treated using this combination. NECT represented a significant achievement, providing the first new drug regimen for HAT in nearly two decades. DNDi is a public-private partnership that focuses on drug discovery and clinical development. It has developed target product profiles (TPPs) and compound progression criteria for trypanosomatid diseases (Don and Ioset 2014). The ideal TPPs focus on new regimens that are active against all strains/subspecies, with good oral bioavailability, short treatment durations, improved safety to efficacy ratios and low cost. Alongside the NECT success, the potential of the old nitroimidazole megazol (7) was rediscovered in combination with suramin (3) and showed to be curative in a stage 2 HAT-infected mouse model (Enanga et al. 1998, Darsaud et al. 2004), although the study was stopped due to the genotoxicity of megazol (7) (Enanga et al. 2003). Drugs used in the combination therapy are shown in Figure 3.
Personal narratives and the pursuit of purpose and possibility in psychosis: directions for developing recovery-oriented treatments
Published in Expert Review of Neurotherapeutics, 2023
Courtney N Wiesepape, John T Lysaker, Sarah E Queller, Paul H Lysaker
A somewhat more established treatment explicitly focused on enhancing narratives in the wake of stigma of mental illness is Narrative Enhancement and Cognitive Therapy (NECT) [65]. NECT is a group-based therapy that aims to target self-stigma via focus on psychoeducation, cognitive restructuring, and narrative enhancement. In this approach participants spend up eight weeks of the intervention writing and revising narratives about both their experiences of psychosis as well as narrative accounts of their strengths and abilities. Each group session includes encouraging persons to share their narratives with group members who are then invited to reflect upon those narratives with their author. Members thus work to enhance their own narratives while supporting the enhancement of others’ narratives.
Emerging compounds and therapeutic strategies to treat infections from Trypanosoma brucei: an overhaul of the last 5-years patents
Published in Expert Opinion on Therapeutic Patents, 2023
Francesco Melfi, Simone Carradori, Cristina Campestre, Entela Haloci, Alessandra Ammazzalorso, Rossella Grande, Ilaria D’Agostino
Despite the efforts in the search for new potent and selective anti-Trypanosoma agents, the presence of a few well-organized health systems in hospitals to host patients severely limits the efficacy of the treatment. The nifurtimox–eflornithine combination therapy (based on nifurtimox three times per day per os for 10 days/eflornithine two times per day intravenously through lumbar puncture for 7 days) can be challenging in low-income countries, which cannot provide high resources to assist patients. After the introduction of the orally available fexinidazole, the Drugs for Neglected Diseases initiative was assisted by Anacor Pharmaceuticals and Scynexis to test the safety and efficacy of a structurally benzoxaborole analogue (acoziborole, 960 mg, per os) in a multicentre, prospective, open-label, single-arm phase II/III study (2016–2019) against the late-stage Tbg HAT. The recently published results proved that a single dose of this drug displayed good tolerability, suitable bioavailability in blood and cerebrospinal fluid, a shorter duration of the treatment, an efficacy of the treatment regimen greater than 95%, and a higher compliance of the patients (≥15 years old) [107]. Other follow-ups in comparison with placebo and NECT are currently ongoing.
Psychometric evaluation of the Swedish version of Rosenberg’s self-esteem scale
Published in Nordic Journal of Psychiatry, 2018
Mona Eklund, Martin Bäckström, Lars Hansson
Sample 2 consisted of participants in a study investigating the effectiveness of a group-based anti-self-stigma intervention, narrative enhancement and cognitive therapy (NECT), with regard to changes in self-stigma, self-esteem, and subjective quality of life [22]. NECT is a structured, group-based intervention comprising 20 weekly 1-h sessions [23]. After screening for eligibility (scoring above a defined cutoff on a self-stigma questionnaire), 106 participants were included in a randomized controlled trial. Assessments were made at baseline and at termination of the intervention after 20 weeks. The intervention was given as an add-on to treatment as usual. Further inclusion criterion was an ability to read and speak Swedish since participant manuals are only available in Swedish.