Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: Double-blind randomised controlled trial

Background: Increasing resistance to sulfadoxine-pyrimethamine is leading to a decline in its effectiveness. We aimed to assess the safety profile of chlorproguanil-dapsone (CD), and to compare the safety and efficacy of this drug with that of sulfadoxine-pyrimethamine (SP) as treatment for uncomplicated falciparum malaria. Methods: We undertook a double-blind, randomised trial in 1850 consecutively recruited children with uncomplicated falciparum malaria, pooling data from five African countries. Analyses were based on all randomised patients with available data. Findings: CD was significantly more efficacious than SP (odds ratio 3·1 [95% CI 2·0-4·8]); 1313 patients (96%) given CD and 306 (89%) given SP achieved acceptable clinical and parasitological response by day 14. Adverse events were reported in 46% and 50% of patients randomised to CD and SP, respectively (treatment difference -4·4%, [95% CI -10·1 to 1·3]). Haemoglobin in the CD group was significantly lower than in the SP group at day 7, a difference of -4 g/L (95% CI -6 to -2). Mean day 14 haemoglobin (measured only for the small number of patients whose day 7 data caused concern) was 94 g/L (92-96) and 97 g/L (92-102) after CD and SP, respectively. Glucose-6-phosphate dehydrogenase deficient patients on CD had greater odds than those on SP of having a fall of 20 g/dL or more in haemoglobin when baseline temperature was high. Methaemoglobinaemia was seen in the CD group (n=320, mean 0·4% [95% CI 0·4-0·4]) before treatment, 4·2% (95% CI 3·8-4·6) (n=301) at day 3, and 0·6% (0·6-0·7) (n=300) at day 7). Interpretation: CD had greater efficacy than SP in Africa and was well tolerated. Haematological adverse effects were more common with CD than with SP and were reversible. CD is a useful alternative where SP is failing due to resistance

The science commons in health research: structure, function, and value

The “science commons,” knowledge that is widely accessible at low or no cost, is a uniquely important input to scientific advance and cumulative technological innovation. It is primarily, although not exclusively, funded by government and nonprofit sources. Much of it is produced at academic research centers, although some academic science is proprietary and some privately funded R&D enters the science commons. Science in general aspires to Mertonian norms of openness, universality, objectivity, and critical inquiry. The science commons diverges from proprietary science primarily in being open and being very broadly available. These features make the science commons particularly valuable for advancing knowledge, for training innovators who will ultimately work in both public and private sectors, and in providing a common stock of knowledge upon which all players—both public and private—can draw readily. Open science plays two important roles that proprietary R&D cannot: it enables practical benefits even in the absence of profitable markets for goods and services, and its lays a shared foundation for subsequent private R&D. The history of genomics in the period 1992–2004, covering two periods when genomic startup firms attracted significant private R&D investment, illustrates these features of how a science commons contributes value. Commercial interest in genomics was intense during this period. Fierce competition between private sector and public sector genomics programs was highly visible. Seemingly anomalous behavior, such as private firms funding “open science,” can be explained by unusual business dynamics between established firms wanting to preserve a robust science commons to prevent startup firms from limiting established firms’ freedom to operate. Deliberate policies to create and protect a large science commons were pursued by nonprofit and government funders of genomics research, such as the Wellcome Trust and National Institutes of Health. These policies were crucial to keeping genomic data and research tools widely available at low cost. Copyright Springer Science+Business Media, LLC 2007Patents, Genomics, Public domain, Open science, Intellectual property, Innovation, 031, 032, 034, 038,