Contribution of physical factors to handpump borehole functionality in Africa.

Handpumps are the main water supply for rural communities across sub-Saharan Africa. However, studies show that >25 % of handpumps are non-functional at any time. We present results from a systematic field study of handpump borehole functionality. The study was designed to investigate the contribution of physical factors to functionality outcomes, including; hydrogeology, borehole configuration, and handpump components. To achieve this, we deconstructed and examined 145 handpump boreholes in Ethiopia, Uganda and Malawi. Pumping tests showed that 19 % of boreholes were located in aquifers with transmissivity below the minimum required to sustain a handpump. Water levels, measured during the dry season, had a complex relationship with borehole configuration and transmissivity. The handpump cylinder was <10 m below the water table at 38 % of sites, which increases the risk of the handpump running dry during intensive use and/or in areas of low transmissivity. The water column was <20 m at 23 % of sites and screens were <10 m long at 29 % of sites and often sub-optimally positioned in the borehole. Borehole depth had no clear relationship with functionality. Using multinomial regression and four functionality categories (functional; unreliable; low yield; unreliable and low yield) as dependant variables, we found that transmissivity is a significant risk factor for the classification of handpump boreholes as low yield. The configuration of the borehole (e.g. cylinder position, screen/casing configuration and water column) is a statistically significant risk factor for the classification of handpump boreholes as unreliable. Handpump components were in poor overall condition but rising main pipes were a particular problem with 53 % of galvanised pipes corroded and 82 % of uPVC pipes damaged, with implications for handpump performance. Our study highlights the importance of; understanding aquifer properties, investing in borehole siting, construction (including supervision) and commissioning, and improving the quality of components and maintenance of handpumps.

Enhancing titres of therapeutic viral vectors using the transgene repression in vector production (TRiP) system.

A key challenge in the field of therapeutic viral vector/vaccine manufacturing is maximizing production. For most vector platforms, the 'benchmark' vector titres are achieved with inert reporter genes. However, expression of therapeutic transgenes can often adversely affect vector titres due to biological effects on cell metabolism and/or on the vector virion itself. Here, we exemplify the novel 'Transgene Repression In vector Production' (TRiP) system for the production of both RNA- and DNA-based viral vectors. The TRiP system utilizes a translational block of one or more transgenes by employing the bacterial tryptophan RNA-binding attenuation protein (TRAP), which binds its target RNA sequence close to the transgene initiation codon. We report enhancement of titres of lentiviral vectors expressing Cyclo-oxygenase-2 by 600-fold, and adenoviral vectors expressing the pro-apoptotic gene Bax by >150,000-fold. The TRiP system is transgene-independent and will be a particularly useful platform in the clinical development of viral vectors expressing problematic transgenes.