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Background and Objectives: Acoziborole is a novel boron-containing candidate developed as an oral drug for the treatment of human African trypanosomiasis (HAT). Results from preclinical studies allowed progression to Phase 1 trials. We aimed to determine the best dose regimen for all stages of HAT. Methods: Acoziborole was assessed in 128 healthy adult males of sub-Saharan African origin living in France. The study included a single oral administration of a 20- to 1200-mg dose in a randomised double-blind study in cohorts of 8 (6 active, 2 placebo) to assess safety, tolerability, and pharmacokinetics. In three additional open cohorts of 6 participants, the effect of activated charcoal was evaluated, bioequivalence of capsules versus tablets was assessed, and safety in the 960-mg tablet cohorts was monitored. Results: Acoziborole was well tolerated at all doses tested; no dose-related adverse events were observed. The drug appeared rapidly in plasma (at 1 h), reached tmax between 24 and 72 h, and remained stable for up to 96 h, after which a slow decrease was quantifiable until 14 weeks after dosing. Charcoal had little impact on the enterohepatic recirculation effect, except for the 20-mg dose. Bioequivalence between capsule and tablet formulations was demonstrated. The therapeutic single dose for administration under fasted conditions was fixed to 960 mg. The maximum administered dose was 1200 mg. Conclusions: This study showed that acoziborole could be safely assessed in patients as a potential single-dose oral cure for both stages of gambiense HAT. Trial Registration: The study was registered with ClinicalTrials.gov: NCT01533961. [ABSTRACT FROM AUTHOR]

The article offers information on the involvement of France in the fight against neglected tropical diseases (NTD) affecting the world's poorest populations living in endemic areas. Topics covered include examples of the recent involvement of French scientists in the field of NTD, such as the design of a dengue vaccine, and the launch of the Re Âseau Francophone sur les Maladies Tropicales Ne Âglige Âes (RFMTN) aimed to promote NTD research collaborations.

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Drug toxicity and resistance were prominent topics in the annual reports of the Service Autonome General de la Maladie du Sommeil (SAGMS), the sleeping sickness service that operated in French West Africa (AOF) from 1939 to 1944. This article closely examines the expression and meaning of the reports' vigilance to unintended drug effects. Reading these reports alongside the scholarly literature on French colonial public health as well as hagiographies of Eugene Jamot, I suggest that this vigilance is best situated within the history of contests over the powers, ethics and value of the French model of sleeping sickness medicine. This reading reveals the ways in which reporting on unintended drug effects served to legitimate the powers and practices of the SAGMS. Like Jamot's biographers, the authors of SAGMS reports drew trypanocide toxicity as well as resistance into the defence of a particular relationship between politics and public health. [ABSTRACT FROM PUBLISHER]

Antibodies directed against nitrosylated epitopes have been found in sera from patients suffering from human African trypanosomiasis (HAT) but not in sera from control subjects living in the same endemic area or African control subjects living in France. We conjugated amino acids to albumin by glutaraldehyde (conjugates) and then nitrosylated the conjugates. Both conjugates and nitrosylated conjugates were analysed by enzyme-linked immunosorbent assay (ELISA). We detected antibodies directed against nitrosylatedl-cysteine andl-tyrosine conjugates; antibody levels were higher in stage II patients than in stage I. Patients with severe clinical signs had higher antibody levels, and antibody levels were highest in patients with major neurological signs. Antibody response was only associated with the IgM isotype. We evaluated antibody specificity and avidity by competition experiments using conjugates and nitrosylated conjugates. Avidity was around 2 ×10−6 mfor the S-nitroso-cysteine epitope and 2 × 10−8 mfor the S-nitroso-tyrosine epitope. Detection of circulating antibodies to S-nitroso-cysteine and S-nitroso-tyrosine epitopes provides indirect evidence for nitric oxide (NO) involvement in HAT and their levels are correlated with disease severity. [ABSTRACT FROM AUTHOR]

This article describes a case of human African trypanosomiasis (HAT) in an expatriate returning to France from Libreville, Gabon. HAT is caused by the Trypanosoma brucei parasites that are transmitted to humans by tsetse flies of the Glossina morsitans group. The patient is a 58-year-old man who presented with a two-month history of intermittent fever, fatigue and a ten-kilogram weight loss. He recalled a painful insect bite on his thigh two months before in his garden in Libreville.

Chagas disease (CD) is endemic to Latin America; its prevalence is highest in Bolivia. CD is sometimes seen in the United States and Canada among migrants from Latin America, whereas it is rare in Europe. We report 9 cases of imported CD in France from 2004 to 2006. [ABSTRACT FROM AUTHOR]