Safety of a fixed-dose combination of artesunate and amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in real-life conditions of use in Côte d’Ivoire

Additional file 2. Adverse-event reporting as a function of the interval between treatment initiation and the home visit

Fixed-Dose Artesunate-Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial

BACKGROUND: Despite increasing evidence of the development of Plasmodium vivax chloroquine (CQ) resistance, there have been no trials comparing its efficacy with that of artemisinin-based combination therapies (ACTs) in Latin America. METHODS: This randomized controlled trial compared the antischizontocidal efficacy and safety of a 3-day supervised treatment of the fixed-dose combination artesunate-amodiaquine Winthrop(R) (ASAQ) versus CQ for treatment of uncomplicated P. vivax infection in Manaus, Brazil. Patients were followed for 42 days. Primary endpoints were adequate clinical and parasitological responses (ACPR) rates at day 28. Genotype-adjustment was performed. RESULTS: From 2012 to 2013, 380 patients were enrolled. In the per-protocol (PP) analysis, adjusted-ACPR was achieved in 100% (165/165) and 93.6% (161/172) of patients in the ASAQ and CQ arm (difference 6.4%, 95% CI 2.7%; 10.1%) at day 28 and in 97.4% (151/155) and 77.7% (129/166), respectively (difference 19.7%, 95% CI 12.9%; 26.5%), at day 42. Apart from ITT D28 assessment, superiority of ASAQ on ACPR was demonstrated. ASAQ presented faster clearance of parasitaemia and fever. Based on CQ blood level measurements, CQ resistance prevalence was estimated at 11.5% (95% CI: 7.5-17.3) up to day 42. At least one emergent adverse event (AE) was recorded for 79/190 (41x6%) in the ASAQ group and for 85/190 (44x7%) in the CQ group. Both treatments had similar safety profiles. CONCLUSIONS: ASAQ exhibited high efficacy against CQ resistant P. vivax and is an adequate alternative in the study area. Studies with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization

Structure of late Variscan Millevaches leucogranite massif in the French Massif Central: AMS and gravity modelling results

In the Limousin area, Variscan leucogranitic plutons are spatially associated with normal faults and major strike-slip shear zones that are a continuation of the South Armorican shear zone. Our study focuses on the large N-S-trending Millevaches granitic massif (Massif Central, France), and intends to highlight, through gravity modelling, structural and anisotropy of magnetic susceptibility (AMS), the massif structure at depth and to discuss the mode of emplacement of granites within a strike-slip tectonic context. The mica subfabric suggests that the magnetic foliations display a general NW-SE sub-horizontal pattern on both sides of the N-S Pradines dextral wrench fault zone that deforms the core of the massif on 5 km width. The magnetic lineation trend exhibits a sigmoïdal pattern, N-S in the Pradines fault zone and NW-SE on both sides of it, which are consistent with a dextral wrench component. The horizontal magnetic foliations and lineations are consistent with the thin granite laccolith model. There is no significant imprint of the extensional Variscan belt collapse on the internal fabric of Millevaches granites than the tectonic dextral transcurrent movement prevailing in this area. © 2005 Elsevier Ltd. All rights reserved

Late orogenic carboniferous extensions in the Variscan French Massif Central

International audienceThe Variscan French Massif Central experienced two successive stages of extension from Middle Carboniferous to Early Permian. In the northern Massif Central, the first stage began in the late Visean, immediately after nappe stacking, and is well recorded by Namurian-Westphalian synkinematic plutonism. The Middle Carboniferous leucogranites widespread in the NW Massif Central (Limousin and Sioule area) were emplaced within a crust extending along a NE-SW direction. At the same time, the hanging wall or "Guéret extensional allochton" moved toward the SE. Several examples of the synextensional plutonism are also recognized in central Limousin: Saint Mathieu dome, La Porcherie, and Cornil leucogranites. These examples illustrate the relationship between granite emplacement and crustal scale deformation characterized by NW-SE stretching and NE-SW shortening. In the central and southern Massif Central (Cévennes, Châtaigneraie, and Margeride areas), plutonism is dominantly granodioritic and exhibits the same structural features: NW-SE maximum stretching and overturning to the SE. Middle Carboniferous (Namurian-Westphalian) extension was parallel to the Variscan belt both in the Massif Central and southern Armorican area. This extensional regime was active from the late Visean in the north, while compression dominated in the southernmost domains (Montagne Noire and Pyrenées). The second extensional stage occurred from Late Carboniferous to Early Permian. This event was responsible for the opening of intramontane coal basins, brittle deformation in the upper crust, and ductile normal faulting localized on the margin of cordierite granite-migmatite domes. Data from the coal basins show that the half-graben is the dominant structural style, except for basins located along submeridianal left-lateral faults which have pull-apart geometries. Late Carboniferous extension occurred along the NE-SW direction. The NE-SW maximum stretching direction can be found in the whole Massif Central but is more developed in the eastern part. The extensional direction is transverse to the general trend of the belt, and top-to-the-NE shearing is dominant. Correlations of these two extension directions with neighboring Variscan massifs are discussed

Pilot feasibility study of an emergency paediatric kit for intra-rectal quinine administration used by the personnel of community-based health care units in Senegal

<p>Abstract</p> <p>Background</p> <p>Quinine injection is the reference treatment for malaria when oral administration is impossible. Quinine can also be administered by the intra-rectal route and, over the last ten years, a series of studies have been conducted in children to determine the ideal dose and dilution in the African situation. The aim of the present study was to evaluate the feasibility and usefulness of a kit for an immediate administration of quinine alkaloids (Quinimax^®) by community health workers, prior to transfer of the child to a more sophisticated health care establishment.</p> <p>Methods</p> <p>A prospective, open, descriptive community intervention study conducted in northern Senegal at six village Health Units in children fewer than ten years of age with non-per-os malaria. Controls were given the routine care prior to transfer to a Health Center, and cases were in addition administered Quinimax^®(20 mg/ml) via the intra-rectal route before transfer. Patients were followed through complete cure and parasitological tests were carried out on Days 0, 3 and 7.</p> <p>Results</p> <p>134 patients (79 cases/55 controls) were recruited between November 2003 and May 2004 or October and November 2004. The two groups were comparable at inclusion. In the case group, oral drugs could be administered after a mean of <it>16.8 hours </it>versus <it>33.6 hours </it>in the control group. Time-to cure was shorter in cases than in controls. Complete parasite clearance was obtained in all patients by Day 7. The kit was well accepted by all concerned and more than 80% of community health workers judged the kit easy to use.</p> <p>Conclusion</p> <p>The emergency paediatric kit is a useful tool in the management of malaria in children who cannot be treated orally. It is feasible and easy to use for health workers in community-based Health Units where, according to the WHO, nearly 80% of malarial morbidity and mortality occurs.</p

Acceptability and efficacy of intra-rectal quinine alkaloids as a pre-transfer treatment of non-per os malaria in peripheral health care facilities in Mopti, Mali

<p>Abstract</p> <p>Background</p> <p>The acceptability and efficacy of a new kit with a new formulation of quinine alkaloids designed for the intra-rectal administration in the treatment of non-per os malaria was assessed in the peripheral health care system of Mopti, Mali.</p> <p>Methods</p> <p>A single-arm trial was conducted from August 2003 to January 2004. An initial dose of diluted quinine alkaloids (20 mg/kg Quinimax^®) was administered by the intra-rectal route to children with presumptive non per-os malaria at six peripheral heath care centres. The children were then referred to two referral hospitals where standard inpatient care including intravenous route were routinely provided. A malaria thick smear was done at inclusion and a second malaria thick smear after arrival at the referral facility, where a more complete clinical examination and laboratory testing was done to confirm diagnosis. Confirmed cases of severe malaria or others diseases were treated according to national treatment guidelines. Cases of non per-os malaria received a second dose of intra rectal quinine alkaloids. Primary outcome was acceptability of the intra rectal route by children and their parents as well as the ease to handle the kit by health care workers.</p> <p>Results</p> <p>The study included 134 children with a median age of 33 months and 53.7% were male. Most of the children (67%) and 92% of parents or guardians readily accepted the intra-rectal route; 84% of health care workers found the kit easy to use. At the peripheral health care centres, 32% of children had a coma score ≤ 3 and this was reduced to 10% at the referral hospital, following one dose of intra-rectal quinine alkaloids (IRQA). The mean time to availability of oral route treatment was 1.8 ± 1.1 days. Overall, 73% of cases were confirmed severe malaria and for those the case fatality rate was 7.2%.</p> <p>Conclusion</p> <p>IRQA was well accepted by children, their parents/guardians and by the health workers at peripheral health facilities in Mopti, Mali. There was also a quick recovery from deep coma and a reduced case fatality rate in severe malaria.</p

Transpressional tectonics and Carboniferous magmatism in the Limousin, Massif Central, France: Structural and ⁴⁰Ar/³⁹Ar investigations

New structural, microstructural, and 40Ar/39 Ar data from the NW Massif Central (France) provide additional constraints on the timing and tectonic setting of late Variscan granite magmatism. Previous studies had emphasized the role of late orogenic extension in the emplacement of granite plutons in the Limousin region. In contrast, the new data set is consistent with syntectonic emplacement of magma in a dextral simple shear active from 350 to 300 Ma in a transpressional regime. As an alternative hypothesis to late orogenic extension, we propose that magmas migrated into tensional bridges between active P shears associated with a lithospheric shear zone comparable to a pop-up structure. The Galician region, in the western end of the Ibero-Armorican tectonic arc, exhibits major left-lateral ductile shear zones which can be interpreted as conjugate structures to the Limousin and Armorican shear zones. Copyright 2007 by the American Geophysical Union