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Biomedical subjects

A Willetts

Publications and source records attributed to A Willetts.

14 recordsLinked to original sources

The cost-effectiveness of improving malaria home management: shopkeeper training in rural Kenya.

Home management is a very common approach to the treatment of illnesses such as malaria, acute respiratory infections, tuberculosis, diarrhoea and sexually transmitted infections, frequently through over-the-counter purchase of drugs from shops. Inappropriate drugs and doses are often obtained, but interventions to improve treatment quality are rare. An educational programme for general shopkeepers and communities in Kilifi District, rural Kenya was associated with major improvements in the use of over-the-counter anti-malarial drugs for childhood fevers. The two main components were workshop training for drug retailers and community information activities, with impact maintained through on-going refresher training, monitoring and community mobilization. This paper presents the cost and cost-effectiveness of the programme in terms of additional appropriately treated cases, evaluating both its measured cost-effectiveness in the first area of implementation (early implementation phase) and the estimated cost-effectiveness of the programme recommended for district-level implementation (recommended district programme). The proportion of shop-treated childhood fevers receiving an adequate amount of a recommended antimalarial rose from 2% to 15% in the early implementation phase, at an economic cost of 4.00 US dollars per additional appropriately treated case (2000 US dollars). If the same impact were achieved through the recommended district programme, the economic cost per additional appropriately treated case would be 0.84 US dollars, varying between 0.37 US dollars and 1.36 US dollars in the sensitivity analysis. As with most educational approaches, the programme carries a relatively high initial financial cost, of 11,477 US dollars (0.02 per capita US dollars) for the development phase and 81,450 US dollars (0.17 per capita US dollars) for the set up year, which would be particularly suitable for donor funding, while the annual costs of 18,129 US dollars (0.04 per capita US dollars) thereafter could be contained within the budget of a typical District. To reach the Abuja target of 60% of those suffering from malaria in sub-Saharan Africa having access to affordable and appropriate treatment within 24 hours, improvements in community-based malaria treatment are urgently required. From these results, policymakers can estimate costs for district-scale shopkeeper training programmes, and will be able to assess their relative cost-effectiveness as comparable evaluations become available from home management interventions in the future. Extrapolation of the results using a simple decision tree model to estimate the cost per DALY averted indicates that the intervention is likely to be considered highly cost-effective in comparison with standard benchmarks for interventions in low-income countries.

Antimalarials↗

Improving malaria home treatment by training drug retailers in rural Kenya.

Recent global malaria control initiatives highlight the potential role of drug retailers to improve access to early effective malaria treatment. We report on the findings and discuss the implications of an educational programme for rural drug retailers and communities in Kenya between 1998 and 2001 in a study population of 70,000. Impact was evaluated through annual household surveys of over-the-counter (OTC) drug use and simulated retail client surveys in an early (1999) and a late (2000) implementation area. The programme achieved major improvements in drug selling practices. The proportion of OTC anti-malarial drug users receiving an adequate dose rose from 8% (n = 98) to 33% (n = 121) between 1998 and 1999 in the early implementation area. By 2001, and with the introduction of sulphadoxine pyrimethamine group drugs in accordance with national policy, this proportion rose to 64% (n = 441) across the early and late implementation areas. Overall, the proportion of shop-treated childhood fevers receiving an adequate dose of a recommended anti-malarial drug within 24 h rose from 1% (n = 681) to 28% (n = 919) by 2001. These findings strongly support the inclusion of private drug retailers in control strategies aiming to improve prompt effective treatment of malaria.

Antimalarials↗

Structural studies and synthetic applications of Baeyer-Villiger monooxygenases.

Baeyer-Villiger monooxygenases (BVMOs) are enzymes able to perform highly regio-plus steroselective nucleophilic and electrophilic biooxygenations on various substrates. The resultant chiral products (lactones and sulfoxides) can be valuable for the chemoenzymatic synthesis of a wide range of useful compounds. Recent studies have provided a number of alternative active-site models that attempt to explain the exquisite and unusual selectivity of BVMOs. This article reviews some of the established applications, and considers the merits of the various predictive models.

Amino Acid Sequence↗

Purification, crystallisation and preliminary X-ray analysis of the vanadium-dependent haloperoxidase from Corallina officinalis.

The vanadium-dependent haloperoxidase from the seaweed Corallina officinalis has been purified to homogeneity and crystallised. The protein is reported to be a hexamer of 12 x 64,000 Da, contains no haem, and is dependent on vanadium for activity. The crystals are grown from polyethylene glycol (PEG) 6,000 and 0.4 M potassium chloride. They are stable and diffract to better than 2 A resolution. They are of a cubic space group I23 (or 12(1)3) with cell dimensions a = b = c = 310 A.

Crystallization↗

Ester formation from ethanol by Candida pseudotropicalis.

The production of ethanol, acetate ion and ethyl acetate from glucose by the yeast Candida pseudotropicalis NCYC 143 was investigated under aerobic and anaerobic growth conditions. Acetate and ethyl acetate only accumulated under aerobic conditions, whereas production of the alcohol was favoured by anaerobic conditions. Ester production during aerobic growth was enhanced substantially by growth in iron-deficient media. Possible conditions for optimising ester production from ethanol in dilute product streams were characterized.

Acetates↗

Bacterial metabolism of ethylene glycol.

Metabolism of ethylene glycol as the sole source of carbon by a species of Flavobacterium was affected by the dissolved oxygen tension of the growth medium. Under strongly aerobic conditions the diol was exclusively metabolised to glycollate by an initial oxidase, subsequently metabolised to acetyl-CoA with no net change in ATP, and then oxidised to CO2 by the tricarboxylic acid cycle yielding large amounts of reduced nicotinamide nucleotides which were used to generate a net gain in ATP by oxidative phosphorylation. Under microaerophilic conditions, some ethylene glycol after initial metabolism to acetyl-CoA by the oxidase-inhibited pathway, was subsequently catabolised to acetyl phosphate and then acetate, yielding a net gain in ATP by substrate-level phosphorylation: additionally some diol was catabolised by an inducible diol dehydratase to acetaldehyde and subsequently reduced to ethanol as a terminal metabolite.

Adenosine Triphosphate↗

Growth of Penicillium janthinellum on glycine as sole carbon and nitrogen source.

Penicillium janthinellum is able to grow on glycine as the sole carbon and nitrogen source. The amino acid is transaminated to glyoxylate which is further metabolised to pyruvate by the glycerate pathway. The reaction product of partially purified glycerate kinase from this fungus is 2-phosphoglycerate. Phosphoglycerate mutase initiates gluconeogenesis from glycine. Partially purified phosphoglycerate mutase is inhibited by fructose 6-phosphate. The possible significance of this regulation is discussed.

Carbon↗

Bacterial metabolism of propane-1,2-diol.

The pathway of propane-1,2-diol metabolism by a species of Flavobacterium able to grow on the diol as the sole source of carbon was influenced by the degree of aeration of the growth medium. Under strongly aerobic conditions the diol was exclusively catabolised to lactaldehyde by an initial diol oxidase, subsequently metabolised to pyruvate and then oxidised to CO2 by the tricarboxylic acid cycle. Under microaerophilic conditions some propane-1,2-diol was catabolised by the oxidase-initiated pathway, but some diol was alternatively catabolised by an inducible diol dehydrase to propionaldehyde and subsequently reduced to n-propanol as an end product of metabolism.

Cell Division↗

Kinetic control of phosphoglycerate mutase from Flavobacterium sp. grown on ethylene glycol.

A species of Flavobacterium able to oxidise ethylene glycol to pyruvate via glyoxylate, glycerate, 2-phosphoglycerate and phosphoenolpyruvate exploits phosphoglycerate mutase to initiate gluconeogenesis. Partially purified phosphoglycerate mutase from this bacterium is independent of adenylate charge control but is activated by phosphoenolpyruvate. The possible significance of this regulation is discussed.

Acetyl Coenzyme A↗

Microbial metabolism of aliphatic glycols. Bacterial metabolism of ethylene glycol.

A species of Flavobacterium isolated from pond water by its ability to grow aerobically on ethylene glycol as the role source of carbon initially oxidised the diol to glyoxylate via glycollate. The glyoxylate was metabolised by the glycerate pathway to acetyl-CoA. The acetyl-CoA was further metabolised by the tricarboxylic acid cycle plus malate synthase acting anaplerotically.

Culture Media↗

Fungal growth on C1 compounds: quantitative aspects of growth of a methanol-utilizing strain of Trichoderma lignorum in batch culture.

A study was made of some salient parameters that influence growth of the methanol-utilizing fungus Trichoderma lignorum growing in batch culture on a minimal medium containing methanol as the sole source of carbon. Maximum cell yield was recorded at the expense of 1.58 g of methanol per liter. Inhibition was observed with methanol concentrations in excess of 4.7 g/liter. The optimum temperature for fungal growth was 23 degrees C. Growth of the fungus was directly proportional to an inorganic nitrogen concentration up to 0.2 g of NH4NO3 per liter. No inhibition of growth occurred at any concentration of NH4NO3 up to 11 g/liter. The pH of the growth medium decreased from 7.0 to 3.5 during growth of the fungus on methanol, which may have been due, in part, to the accumulation of trace amounts of organic acids in the growth medium. An analysis of the commercial potential of the fungus, as a source of edible protein, indicated that the strain of methanol-utilizing T. lignorum used was uneconomical in terms of the yield and the specific growth rate.

Dietary Proteins↗

Fungal growth on C1 compounds: a study of the amino acid composition of a methanol-utilizing strain of Trichoderma lignorum.

The amino acid composition of the C1-utilizing fungus Trichoderma lignorum, growing at the expense of methanol as the sole source of carbon, was determined. With the exception of an insufficient content of methionine, the essential amino acid composition of this novel protein source appears adequate in terms of the Food and Agricultural Organization Reference Protein for both direct and indirect use in the human diet as a food or animal feed, respectively.

Amino Acids↗