BackgroundIncreasing affordability of artemisinin combination therapy (ACT) in the African retail sector could be critical to expanding access to effective malaria treatment, but must be balanced by efforts to protect the efficacy of these drugs. Previous research estimates ACT adherence rates among public sector patients, but adherence among retail sector purchasers could differ substantially. This study aimed to estimate adherence rates to subsidized, over-the-counter ACT in rural Uganda.MethodsAn intervention study was conducted with four licensed drug shops in Eastern Uganda in December 2009. Artemether-lumefantrine (AL) was made available for sale at a 95% subsidy over-the counter. Customers completed a brief survey at the time of purchase and then were randomly assigned to one of three study arms: no follow-up, follow-up after two days or follow-up after three days. Surveyors recorded the number of pills remaining through blister pack observation or through self-report if the pack was unavailable. The purpose of the three-day follow-up arm was to capture non-adherence in the sense of an incomplete treatment course ("under-dosing"). The purpose of the two-day follow-up arm was to capture whether participants completed the full course too soon ("over-dosing").ResultsOf the 106 patients in the two-day follow-up sample, 14 (13.2%) had finished the entire treatment course by the second day. Of the 152 patients in the three-day follow-up sample, 49 (32.2%) were definitely non-adherent, three (2%) were probably non-adherent and 100 (65.8%) were probably adherent. Among the 52 who were non-adherent, 31 (59.6%) had more than a full day of treatment remaining.ConclusionsOverall, adherence to subsidized ACT purchased over-the-counter was found to be moderate. Further, a non-trivial fraction of those who complete treatment are taking the full course too quickly. Strategies to increase adherence in the retail sector are needed in the context of increasing availability and affordability of ACT in this sector.

Background Although artemisinin combination therapies (ACTs) are the recommended first-line treatment for uncomplicated malaria in most endemic countries, they have been prohibitively expensive in the retail sector where many suspected malaria cases purchase treatment. ACT subsidies seek to stimulate consumer demand for the drugs over cheaper but often ineffective alternatives by reducing their prices. Recent evidence from eight regions implementing such subsidies suggests that they are generally successful in improving availability of the drugs and decreasing their retail prices, but it remains unclear whether these outcomes translate to improved use by patients with suspected malaria.Methods A systematic literature review was conducted to identify reports of experimental or programmatic ACT subsidies to assess the impact of subsidies on consumer use. Relationships between price, use and potential confounding factors were examined using logistic and repeated measures binomial regression models, and approximate magnitudes of associations were assessed with linear regression. In total, 40 studies, 14 peer-reviewed and 26 non-peer-reviewed, were eligible for inclusion in the analysis. The reviewed studies found a substantial increase in private sector ACT use following the introduction of a subsidy. Overall, each $1 decrease in price was linked to a 24 percentage point increase in the fraction of suspected malaria cases purchasing ACTs (R2 = 0.302). No significant differences were evident in this relationship when comparing the poorest and richest groups, rural vs urban populations or children vs adults.Conclusions These findings suggest that ACT price reductions can increase their use for suspected malaria, even within poorer, more remote populations that may be most at risk of malaria mortality. Whether a subsidy is appropriate will depend upon local context, including treatment-seeking behaviours and malaria prevalence. This review provides an initial foundation for policymakers to make evidence-based decisions regarding ACT price reductions to increase use of potentially life-saving drugs.

We studied modulation of undirected functional connectivity (uFC) in cortical-hippocampal sub-networks during associative learning. Nineteen healthy individuals were studied (fMRI acquired on a Siemens Verio 3T), and uFC was studied between nodes in a network of regions identified by standard activation models based on bivariate correlational analyses of time series data. The paradigm alternated between Memory Encoding, Rest and Retrieval. "Rest" intervals promoted covert consolidation. Over the task, performance was broadly separable into linear (Early) and asymptomatic (Late) regimes, with late performance reflecting successful memory consolidation. Significant modulation of uFC was observed during periods of covert consolidation. The sub-networks which were modulated constituted connections between frontal regions such as the dorsal prefrontal cortex (dPFC) and dorsal anterior cingulate cortex (dACC), the medial temporal lobe (hippocampus, HPC), the superior parietal cortex (SPC) and the fusiform gyrus (FG). uFC patterns were dynamic in that sub-networks modulated during Early learning (dACC ↔ SPC, dACC ↔ FG, dPFC ↔ HPC) were not identical to those modulated during Late learning (dACC ↔ HPC, dPFC ↔ FG, FG ↔ SPC). Covert consolidation exerts systematic effects, and these results add to emerging evidence for the constructive role of the brain's "resting state" in potentiating action.

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