Pharmacokinetics, clinical and safety outcomes of Pyronaridine/artesunate Treatment of Acute Plasmodium falciparum Malaria in Uganda

Presented at the conference of the American Society of Tropical Medicine and Hygiene 200

Adherence to a Six-Dose Regimen of Artemether-Lumefantrine for Treatment of Uncomplicated Plasmodium Falciparum Malaria in Uganda.

Measuring baseline levels of adherence and identifying risk factors for non-adherence are important steps before the introduction of new antimalarials. In Mbarara in southwestern Uganda, we assessed adherence to artemether-lumefantrine (Coartem) in its latest World Health Organization blister formulation. Patients with uncomplicated Plasmodium falciparum malaria were prescribed artemether-lumefantrine and received an explanation of how to take the following five doses at home. A tablet count was made and a questionnaire was completed during a home visit. Among 210 analyzable patients, 21 (10.0%) were definitely or probably non-adherent, whereas 189 (90.0%) were probably adherent. Age group was not associated with adherence. Lack of formal education was the only factor associated with non-adherence after controlling for confounders (odds ratio = 3.1, 95% confidence interval [CI] = 1.1-9.7). Mean lumefantrine blood levels were lower among non-adherent (n = 16) (2.76 microg/mL, 95% CI = 1.06-4.45) than among adherent (n = 171) (3.19 microg/mL, 95% CI = 2.84-3.54) patients, but this difference was not statistically significant. The high adherence to artemether-lumefantrine found in our study suggest that this drug is likely to be very effective in Mbarara provided that patients receive clear dosage explanations

Sea level anomaly on the Patagonian continental shelf: Trends, annual patterns and geostrophic flows

We study the annual patterns and linear trend of satellite sea level anomaly (SLA) over the southwest South Atlantic continental shelf (SWACS) between 54S and 36S. Results show that south of 42°S the thermal steric effect explains nearly 100% of the annual amplitude of the SLA, while north of 42°S it explains less than 60%. This difference is due to the halosteric contribution. The annual wind variability plays a minor role over the whole continental shelf. The temporal linear trend in SLA ranges between 1 and 5 mm/yr (95% confidence level). The largest linear trends are found north of 39°S, at 42°S and at 50°S. We propose that in the northern region the large positive linear trends are associated with local changes in the density field caused by advective effects in response to a southward displacement of the South Atlantic High. The causes of the relative large SLA trends in two southern coastal regions are discussed as a function meridional wind stress and river discharge. Finally, we combined the annual cycle of SLA with the mean dynamic topography to estimate the absolute geostrophic velocities. This approach provides the first comprehensive description of the seasonal component of SWACS circulation based on satellite observations. The general circulation of the SWACS is northeastward with stronger/weaker geostrophic currents in austral summer/winter. At all latitudes, geostrophic velocities are larger (up to 20 cm/s) close to the shelf-break and decrease toward the coast. This spatio-temporal pattern is more intense north of 45°S.Fil: Ruiz Etcheverry, Laura Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentina. University of Hawaii at Manoa; Estados UnidosFil: Saraceno, Martin. Universidad de Buenos Aires; Argentina. Instituto Franco Argentino para el Estudio del Clima y sus Impactos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Piola, Alberto Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval; ArgentinaFil: Strub, P. T.. State University of Oregon; Estados Unido

Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda.

BACKGROUND: A six-dose antimalarial regimen of artemether-lumefantrine (A/L) may soon become one of the most widely used drug combination in Africa, despite possible constraints with adherence and poor absorption due to inadequate nutrition, and a lack of pharmacokinetic and effectiveness data. METHODS: Within a trial of supervised versus unsupervised A/L treatment in a stable Ugandan Plasmodium falciparum transmission setting, plasma lumefantrine concentrations were measured in a subset of patients on day 3 (C [lum]day3) and day 7 (C [lum]day7) post-inclusion. Predictors of lumefantrine concentrations were analysed to show how both C [lum]day7 and the weight-adjusted lumefantrine dose affect 28-day recrudescence and re-infection risks. The implications of these novel findings are discussed in terms of the emergence of lumefantrine-resistant strains in Africa. RESULTS: C [lum]day3 and C [lum]day7 distributions among 241 supervised and 238 unsupervised patients were positively skewed. Unsupervised treatment and decreasing weight-adjusted lumefantrine dose were negatively associated with C [lum]day3. Unsupervised treatment and decreasing age showed strong negative associations with C [lum]day7. Both models were poorly predictive (R-squared < 0.25). There were no recrudescences in either arm, but decreasing lumefantrine dose per Kg resulted in up to 13-fold higher adjusted risks of re-infection. Re-infections occurred only among patients with C [lum]day7 below 400 ng/mL (p < 0.001). CONCLUSION: Maintaining the present six-dose regimen and ensuring high adherence and intake are essential to maximize the public health benefits of this valuable drug combination

Primacy of effective communication and its influence on adherence to artemether-lumefantrine treatment for children under five years of age: a qualitative study.

BACKGROUND\ud \ud Prompt access to artemesinin-combination therapy (ACT) is not adequate unless the drug is taken according to treatment guidelines. Adherence to the treatment schedule is important to preserve efficacy of the drug. Although some community based studies have reported fairly high levels of adherence, data on factors influencing adherence to artemether-lumefantrine (AL) treatment schedule remain inadequate. This study was carried-out to explore the provider's instructions to caretakers, caretakers' understanding of the instructions and how that understanding was likely to influence their practice with regard to adhering to AL treatment schedule.\ud \ud METHODS\ud \ud A qualitative study was conducted in five villages in Kilosa district, Tanzania. In-depth interviews were held with providers that included prescribers and dispensers; and caretakers whose children had just received AL treatment. Information was collected on providers' instructions to caretakers regarding dose timing and how to administer AL; and caretakers' understanding of providers' instructions.\ud \ud RESULTS\ud \ud Mismatch was found on providers' instructions as regards to dose timing. Some providers' (dogmatists) instructions were based on strict hourly schedule (conventional) which was likely to lead to administering some doses in awkward hours and completing treatment several hours before the scheduled time. Other providers (pragmatists) based their instruction on the existing circumstances (contextual) which was likely to lead to delays in administering the initial dose with serious treatment outcomes. Findings suggest that, the national treatment guidelines do not provide explicit information on how to address the various scenarios found in the field. A communication gap was also noted in which some important instructions on how to administer the doses were sometimes not provided or were given with false reasons.\ud \ud CONCLUSIONS\ud \ud There is need for a review of the national malaria treatment guidelines to address local context. In the review, emphasis should be put on on-the-job training to address practical problems faced by providers in the course of their work. Further research is needed to determine the implication of completing AL treatment prior to scheduled time

Climate Change Impacts on the Patagonian Shelf Break Front

We characterize long-term trends of sea surface temperature (SST), absolute dynamic topography, and chlorophyll-a (CHL) in the Patagonian shelf break front (SBF) using 27 years (1993–2019) of satellite data. Warming of the Argentinean shelf waters and the southwestward displacement of the Brazil-Malvinas Confluence (BMC) impact the northernmost extension of the SBF. Cooling of the Malvinas Current (MC) and the concurrent warming of the adjacent shelf waters lead to a significant increase of SST gradients along the outer shelf. The southwestward displacement of the BMC implies a similar shift of the SBF. An increase in CHL trend appears to be associated with southerly wind anomalies along the shelf break. We estimate a southward shift of the northernmost penetration of the MC of −0.11 ± 0.076°/decade.Fil: Franco, Barbara Cristie. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Ruiz Etcheverry, Laura Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Marrari, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Piola, Alberto Ricardo. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Matano, R. P.. State University of Oregon; Estados Unido

Malvinas-slope water intrusions on the northern Patagonia continental shelf

The Patagonia continental shelf located off southeastern South America is bounded offshore by the Malvinas Current, which extends northward from northern Drake Passage (~55&amp;deg; S) to nearly 38&amp;deg; S. The transition between relatively warm-fresh shelf waters and Subantarctic Waters from the western boundary current is characterized by a thermohaline front extending nearly 2500 km. We use satellite derived sea surface temperature, and chlorophyll-&lt;I&gt;a&lt;/I&gt; data combined with hydrographic and surface drifter data to document the intrusions of slope waters onto the continental shelf near 41&amp;deg; S. These intrusions create vertically coherent localized negative temperature and positive salinity anomalies extending onshore about 150 km from the shelf break. The region is associated with a center of action of the first mode of non-seasonal sea surface temperature variability and also relatively high chlorophyll-&lt;I&gt;a&lt;/I&gt; variability, suggesting that the intrusions are important in promoting the local development of phytoplankton. The generation of slope water penetrations at this location may be triggered by the inshore excursion of the 100 m isobath, which appears to steer the Malvinas Current waters over the outer shelf

The flow of the Antarctic circumpolar current over the North Scotia Ridge

The transports associated with the Subantarctic Front (SAF) and the Polar Front (PF) account for the majority of the volume transport of the Antarctic Circumpolar Current (ACC). After passing through Drake Passage, the SAF and the PF veer northward over the steep topography of the North Scotia Ridge. Interaction of the ACC with the North Scotia Ridge influences the sources of the Malvinas Current. This ridge is a major obstacle to the flow of deep water, with the majority of the deep water passing through the 3100 m deep gap in the ridge known as Shag Rocks Passage. Volume transports associated with these fronts were measured during the North Scotia Ridge Overflow Project, which included the first extensive hydrographic survey of the ridge, carried out in April and May 2003. The total net volume transport northward over the ridge was found to be . The total net transport associated with the SAF was approximately , and the total transport associated with the PF was approximately . Weddell Sea Deep Water was not detected passing through Shag Rocks Passage, contrary to some previous inferences

The present and future system for measuring the Atlantic meridional overturning circulation and heat transport

of the global combined atmosphere-ocean heat flux and so is important for the mean climate of the Atlantic sector of the Northern Hemisphere. This meridional heat flux is accomplished by both the Atlantic Meridional Overturning Circulation (AMOC) and by basin-wide horizontal gyre circulations. In the North Atlantic subtropical latitudes the AMOC dominates the meridional heat flux, while in subpolar latitudes and in the subtropical South Atlantic the gyre circulations are also important. Climate models suggest the AMOC will slow over the coming decades as the earth warms, causing widespread cooling in the Northern hemisphere and additional sea-level rise. Monitoring systems for selected components of the AMOC have been in place in some areas for decades, nevertheless the present observational network provides only a partial view of the AMOC, and does not unambiguously resolve the full variability of the circulation. Additional observations, building on existing measurements, are required to more completely quantify the Atlantic meridional heat transport. A basin-wide monitoring array along 26.5°N has been continuously measuring the strength and vertical structure of the AMOC and meridional heat transport since March 31, 2004. The array has demonstrated its ability to observe the AMOC variability at that latitude and also a variety of surprising variability that will require substantially longer time series to understand fully. Here we propose monitoring the Atlantic meridional heat transport throughout the Atlantic at selected critical latitudes that have already been identified as regions of interest for the study of deep water formation and the strength of the subpolar gyre, transport variability of the Deep Western Boundary Current (DWBC) as well as the upper limb of the AMOC, and inter-ocean and intrabasin exchanges with the ultimate goal of determining regional and global controls for the AMOC in the North and South Atlantic Oceans. These new arrays will continuously measure the full depth, basin-wide or choke-point circulation and heat transport at a number of latitudes, to establish the dynamics and variability at each latitude and then their meridional connectivity. Modeling studies indicate that adaptations of the 26.5°N type of array may provide successful AMOC monitoring at other latitudes. However, further analysis and the development of new technologies will be needed to optimize cost effective systems for providing long term monitoring and data recovery at climate time scales. These arrays will provide benchmark observations of the AMOC that are fundamental for assimilation, initialization, and the verification of coupled hindcast/forecast climate models

Dispersible formulation of artemether/lumefantrine: specifically developed for infants and young children

Infants and children under five years of age are the most vulnerable to malaria with over 1,700 deaths per day from malaria in this group. However, until recently, there were no WHO-endorsed paediatric anti-malarial formulations available