Bill & Melinda Gates Foundation.

SummaryBackgroundArtemether–lumefantrine and artesunate–amodiaquine are used as first-line artemisinin-based combination therapies (ACTs) in west Africa. Pyronaridine–artesunate and dihydroartemisinin–piperaquine are potentially useful for diversification of ACTs in this region, but further safety and efficacy data are required on malaria retreatment.MethodsWe did a randomised, multicentre, open-label, longitudinal, controlled phase 3b/4 clinical trial at seven tertiary centres in Burkina Faso, Guinea, and Mali. Eligible participants for first malaria episode and all retreatment episodes were adults and children aged 6 months and older with microscopically confirmed Plasmodium spp malaria (>0 to <200 000 parasites per μL of blood) and fever or history of fever in the previous 24 h. Individuals with severe or complicated malaria, an alanine aminotransferase concentration of more than twice the upper limit of normal, or a QTc greater than 450 ms were excluded. Using a randomisation list for each site, masked using sealed envelopes, participants were assigned to either pyronaridine–artesunate or dihydroartemisinin–piperaquine versus either artesunate–amodiaquine or artemether–lumefantrine. Block sizes were two or four if two treatments were allocated, and three or six if three treatments were allocated. Microscopists doing the parasitological assessments were masked to treatment allocation. All treatments were once-daily or twice-daily tablets or granules given orally and dosed by bodyweight over 3 days at the study centre. Patients were followed up as outpatients up to day 42, receiving clinical assessments on days 0, 1, 2, 3, 7, 14, 21, 28, 35, and 42. Two primary outcomes were compared for non-inferiority: the 2-year incidence rate of all microscopically confirmed, complicated and uncomplicated malaria episodes in patients in the intention-to-treat population (ITT; non-inferiority margin 20%); and adequate clinical and parasitological response (ACPR) in uncomplicated malaria across all episodes (unadjusted and PCR-adjusted for Plasmodium falciparum and unadjusted for other Plasmodium spp) in the per-protocol population on days 28 and 42 (non-inferiority margin 5%). Safety was assessed in all participants who received one dose of study drug. This study is registered at the Pan African Clinical Trials Registry (PACTR201105000286876).FindingsBetween Oct 24, 2011, and Feb 1, 2016, we assigned 4710 eligible participants to the different treatment strategies: 1342 to pyronaridine–artesunate, 967 to artemether–lumefantrine, 1061 to artesunate–amodiaquine, and 1340 to dihydroartemisinin–piperaquine. The 2-year malaria incidence rate in the ITT population was non-inferior for pyronaridine–artesunate versus artemether–lumefantrine (1·77, 95% CI 1·63–1·93 vs 1·87, 1·72–2·03; rate ratio [RR] 1·05, 95% CI 0·94–1·17); and versus artesunate–amodiaquine (1·39, 95% CI 1·22–1·59 vs 1·35, 1·18–1·54; RR 0·97, 0·87–1·07). Similarly, this endpoint was non-inferior for dihydroartemisinin–piperaquine versus artemether–lumefantrine (1·16...

SummaryBackgroundChloroquine was used for malaria treatment until resistant Plasmodium falciparum was identified. Because 4-aminoquinolines with modified side chains, such as AQ-13, are active against resistant parasites, we compared AQ-13 against artemether plus lumefantrine for treatment of uncomplicated P falciparum malaria.MethodsWe did a randomised, non-inferiority trial. We screened men (≥18 years) with uncomplicated malaria in Missira (northeast Mali) and Bamako (capital of Mali) for eligibility (≥2000 asexual P falciparum parasites per μL of blood). Eligible participants were randomly assigned to either the artemether plus lumefantrine group or AQ-13 group by permuting blocks of four with a random number generator. Physicians and others caring for the participants were masked, except for participants who received treatment and the research pharmacist who implemented the randomisation and provided treatment. Participants received either 80 mg of oral artemether and 480 mg of oral lumefantrine twice daily for 3 days or 638·50 mg of AQ-13 base (two oral capsules) on days 1 and 2, and 319·25 mg base (one oral capsule) on day 3. Participants were monitored for parasite clearance (50 μL blood samples twice daily at 12 h intervals until two consecutive negative samples were obtained) and interviewed for adverse events (once every day) as inpatients during week 1. During the 5-week outpatient follow-up, participants were examined for adverse events and recurrent infection twice per week. All participants were included in the intention-to-treat analysis and per-protocol analysis, except for those who dropped out in the per-protocol analysis. The composite primary outcome was clearance of asexual parasites and fever by day 7, and absence of recrudescent infection by parasites with the same molecular markers from days 8 to 42 (defined as cure). Non-inferiority was considered established if the proportion of patients who were cured was higher for artemether plus lumefantrine than for AQ-13 and the upper limit of the 95% CI was less than the non-inferiority margin of 15%. This trial is registered at ClinicalTrials.gov, number NCT01614964.FindingsBetween Aug 6 and Nov 18, 2013, and between Sept 18 and Nov 20, 2015, 66 Malian men with uncomplicated malaria were enrolled. 33 participants were randomly assigned to each group. There were no serious adverse events (grade 2–4) and asexual parasites were cleared by day 7 in both groups. 453 less-severe adverse events (≤grade 1) were reported: 214 in the combination group and 239 in the AQ-13 group. Two participants withdrew from the AQ-13 group after parasite clearance and three were lost to follow-up. In the artemether plus lumefantrine group, two participants had late treatment failures (same markers as original isolates). On the basis of the per-protocol analysis, the AQ-13 and artemether plus lumefantrine groups had similar proportions cured (28 [100%] of 28 vs 31 [93·9%] of 33; p=0·50) and AQ-13 was not inferior to artemether plus lumefantrine (difference −6·1%, 95% CI −...

Malaria transmission largely depends on environmental, climatic, and hydrological conditions. In Mali, malaria epidemiological patterns are nested within three ecological zones. This study aimed at assessing the relationship between those conditions and the incidence of malaria in Dangassa and Koila, Mali. Malaria data was collected through passive case detection at community health facilities of each study site from June 2015 to January 2017. Climate and environmental data were obtained over the same time period from the Goddard Earth Sciences (Giovanni) platform and hydrological data from Mali hydraulic services. A generalized additive model was used to determine the lagged time between each principal component analysis derived component and the incidence of malaria cases, and also used to analyze the relationship between malaria and the lagged components in a multivariate approach. Malaria transmission patterns were bimodal at both sites, but peak and lull periods were longer lasting for Koila study site. Temperatures were associated with malaria incidence in both sites. In Dangassa, the wind speed (p = 0.005) and river heights (p = 0.010) contributed to increasing malaria incidence, in contrast to Koila, where it was humidity (p < 0.001) and vegetation (p = 0.004). The relationships between environmental factors and malaria incidence differed between the two settings, implying different malaria dynamics and adjustments in the conception and plan of interventions.

Enhancement of lead zirconate (PbZrO3) polarization is achieved by using a titanium seed layer on alumina polycrystalline substrate. Thanks to the reduction of the lattice mismatch between the platinum electrode (3.92 Å) and the PbZrO3 films (4.14 Å), lead zirconate thin films oriented along the (111) direction with an orientation factor of around 65 % has been obtained. The (111) PbZrO3 presents an increase of 56% of the polarization compared to the (100) PbZrO3. This enhancement is responsible of the higher recoverable energy storage density obtained in the (111) PbZrO3 thin films (8 J/cm 3 at 600 kV/cm with an efficiency of 72%). The (111) PbZrO3 also has a higher figure of merit, which indicates that the (111) crystallographic plan is the most favorable direction for energy storage.

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Competitiveness is a hot debate between policy-makers and businessmen in the world, which has been subject to little rigorous economic analysis. We present a method that draws on economic theory to measure its sources at thefirm and industry levels, using the case of Mali. In Mali, manufactures are competitive only on their local market where protecti'on offsets a fundamental lack of comparative advantage. Regional integration and trade liberalization thus constitue major challenges and only the tsm'le sector appears to be in a position to exploit the resulting export opportunities. However, the situation is not hopeless for the other industries, and areas for improvement in firm performance and policy reform are pointed out. Given Mali's low wages, its manufacturingpotential lies in labour-intensive industries rather than in the capital-and material input-intensive activities that have predominated in the past. La concurrence est en plein ddbat entre les ddcideurs et les entreprises du monde. Cependant aucune analyse dconomique rigourme n'a &d faite rf ce sujet. Nous prhentons une analyse basbe sur la thkorie kconomique qui mesure la concurrence et dktetmine ses origines au niveau des entreprises et des industries, et utilisant comme exemple le Mali. Au Mali, les entreprises manufacturi2res ne peuvent faire la concurrence qu'au niveau local oh la protection compense un manque fondamental d'avantage comparatif: Duns ce contexte, I'intkgration rkgionale et la libkralisation du commerce constitue un Cadian grand d@, oh seulement les manufactures textiles semblent &re en position &exploiter les loumal of possibilit& offktes par l'exportation. Mais la situation n'est pas dksespkrante pour les I)eelopment autres entreprises h ou l'on peut amdiorer la productivitk. Vu les bas salaires au Mali, le Studies potentiel manufacturier rdside dans les activitks intensives en travail plut8t que celles intensives en capital et en intrants importks qui ont prkdomink dans le passk.

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