[Clinical-Biological analyses and electrocardiographic follow-up of 104 cases of plasmodium falciparum malaria treated at Camp Kosseï in N'Djamena (Tchad)]. / Analyses clinico-biologiques et suivis électrocardiographiques de 104 cas de paludisme à plasmodium falciparum traités au Camp Kosseï de N'Djamena (Tchad).

Objective: The aim of this study was to assess the commonly accepted potential effects of Artemisinin-based combinaison therapy (ACT) on repolarization and QT. Method: We realized a retrospective study, evaluating epidemiologic, clinical, biological and electrocardiographic data for patients treated for falciparum malaria, between August 31st and November 3rd, 2017 in the Pôle de santé unique on the Camp Kosseï of N'Djamena. Results: One hundred and four patients were included (28,6 years old [0 - 75 years], 72% male). All had fever (38,4 °C [36,6 - 41,5 °C]), asthenia, and main symptoms were headache and arthromyalgia (58%). No significant difference was noted after treatment concerning biological data (especially kaliemia: 3.81 versus 3.91 mmol/l, p = 0.154). There was no significant increase of QTc (415.8 versus 421.4 ms, p = 0.89) with the two ACT treatment used and no adverse events. Discussion: Population is essentially composed of Chadian men, often partly immunized, that can modify clinical presentation. French soldiers' medical follow up in military operations decreases contra-indications of ACT. Conclusions: These results are in favor of a good cardiac tolerance of ACT with piperaquine and it should be proposed not to realize systematic ECG for the French soldiers in external operation when treated with ACT.

A dual transacylation mechanism for polyketide synthase chain release in enacyloxin antibiotic biosynthesis.

Polyketide synthases assemble diverse natural products with numerous important applications. The thioester intermediates in polyketide assembly are covalently tethered to acyl carrier protein domains of the synthase. Several mechanisms for polyketide chain release are known, contributing to natural product structural diversification. Here, we report a dual transacylation mechanism for chain release from the enacyloxin polyketide synthase, which assembles an antibiotic with promising activity against Acinetobacter baumannii. A non-elongating ketosynthase domain transfers the polyketide chain from the final acyl carrier protein domain of the synthase to a separate carrier protein, and a non-ribosomal peptide synthetase condensation domain condenses it with (1S,3R,4S)-3,4-dihydroxycyclohexane carboxylic acid. Molecular dissection of this process reveals that non-elongating ketosynthase domain-mediated transacylation circumvents the inability of the condensation domain to recognize the acyl carrier protein domain. Several 3,4-dihydroxycyclohexane carboxylic acid analogues can be employed for chain release, suggesting a promising strategy for producing enacyloxin analogues.