Studying the effect of chloroquine on sporozoite-induced protection and immune responses in Plasmodium berghei malaria

BACKGROUND Sporozoite immunization of animals and humans under a chemo-prophylactic cover of chloroquine (CPS-CQ) efficiently induces sterile protection against malaria. In humans, CPS-CQ is strikingly more efficient than immunization with radiation attenuated sporozoites (RAS), raising the hypothesis that this might be partially due to CQ. Chloroquine, an established anti-malarial drug, is also well known for its immune modulating properties including improvement of cross-presentation. The aim of this study was to investigate whether co-administration of CQ during sporozoite immunization improves cellular responses and protective efficacy in Plasmodium berghei models. METHODS A number of experiments in selected complimentary P. berghei murine models in Balb/cByJ and C57BL/6j mice was performed. First, the effect of CQ administration on the induction of protection and immune responses by RAS immunization was studied. Next, the effect of CQ on the induction of circumsporozoite (CS) protein-specific CD8(+) T cells by immunization with P. berghei parasites expressing a mutant CS protein was investigated. Finally, a direct comparison of CPS-CQ to CPS with mefloquine (MQ), an anti-malarial with little known immune modulating effects, was performed. RESULTS When CQ was co-administered during immunization with graded numbers of RAS, this did not lead to an increase in frequencies of total memory CD8(+) T cells or CS protein-specific CD8(+) T cells. Also parasite-specific cytokine production and protection remained unaltered. Replacement of CQ by MQ for CPS immunization resulted in significantly reduced percentages of IFNγ producing memory T cells in the liver (p = 0.01), but similar protection. CONCLUSIONS This study does not provide evidence for a direct beneficial effect of CQ on the induction of sporozoite-induced immune responses and protection in P. berghei malaria models. Alternatively, the higher efficiency of CPS compared to RAS might be explained by an indirect effect of CQ through limiting blood-stage exposure after immunization or to increased antigen exposure and, therefore, improved breadth of the immune response.EMB was supported by Top Institute Pharma (grant T4-102) and KN was supported by the NWO Mozaiek (grant no. 017.005.011)

Staged Mucosal Advancement Flap versus Staged Fibrin Sealant in the Treatment of Complex Perianal Fistulas

Background. In this prospective randomised study, the staged mucosal advancement flap is compared with staged fibrin sealant application in the treatment of perianal fistulas. Methods. All patients with high complex cryptoglandular fistulas were randomised to closure of the internal opening by a mucosal advancement flap (MF) or injection with fibrin sealant (FS) after treatment with setons. Recurrence rate and incontinence disorders were explored. Results. The MF group (5 females and 10 males) with a median age of 51 years and a median followup of 52 months. The FS group (4 females and 11 males) with a median age of 45 years and a median followup of 49 months. Three (20%) patients of the MF group had a recurrent fistula compared to 9 (60%) of the FS group (P = 0.03). No new continence disorders developed. Conclusion. Staged FS injection has a much lower success rate compared to MF

Potential advantages in heat and power production when biogas is collected from several digesters using dedicated pipelines - A case study in the "Province of West-Flanders" (Belgium)

In the case study “West-Flanders” costs of electricity and heat production are estimated if a dedicated biogas grid using pipelines would be implemented to centralize energy production in a region. Heat may not be used effectively at digester sites, e.g. because of a change in treatment of digestate. A large scale centralized combined heat and power (CHP) engine can produce additional electrical power at a hub, i.e. central collection point, and has lower specific costs compared to decentralized CHPs at digester sites. A biogas transport model is used to calculate transport costs in a grid. These costs, partly balanced by a scale advantage in CHP costs, are attributed to the additional electrical energy (80%) and heat (20%) produced. If the hub is at a digester site, costs of additional electricity can be as low as 4.0 €ct kWhe−1 and are in many cases below 12 €ct kWhe−1, i.e. in the same order of magnitude or lower than costs of electricity from biogas produced using separate CHPs at the different digester sites; costs of heat at the hub show to be lower than 1 €ct kWhth−1 assuming an effective heat use of 50%. In case a hub is situated at a location with high potential heat demand, i.e. a heat sink, transport of biogas from one digester only to a central located hub can provide 3.4 MWth of heat at 1.95 €ct kWhth−1. For such a centrally located hub additional electrical energy costs show to be slightly higher, but with three or more digesters these costs are lower than 20 €ct kWhe−1 and heat costs are around 0.5 €ct kWhth−1. With a centralized hub more renewable energy is produced, i.e. a more efficient use of biomass feedstock. It is concluded that costs for additional electricity and heat can be at a competing level and scale advantages in a CHP can be a driver to collect biogas at a hub using a biogas grid

Tailoring eHealth design to support the self-care needs of patients with cardiovascular diseases:a vignette survey experiment

Self-care support is a key cornerstone of treatment for patients with a cardiovascular disease. The success of any supportive intervention requires adaptation to the distinct needs of individuals. This requirement also applies to eHealth interventions. This study investigates how experts from multiple fields of science assess the potential success of different eHealth design strategies when matched to key self-care needs. An online vignette survey experiment was conducted. Nine vignettes representing different combinations of self-care needs (maintenance, monitoring, management) and eHealth persuasive design strategies (primary task support, dialogue support, social support) were evaluated. In total, 118 experts from 18 different countries participated in the survey. Their evaluations show primary task support as a promising design strategy across all self-care needs. In contrast, dialogue support and social support showed more promise for specific self-care needs. Above all, according to experts, the success of design strategies could be enhanced by (i) personalising the pacing of the intervention and (ii) tailoring the information to the literacy and culture of the person. Adding to that, self-care support should distinctly (iii) support the three self-care needs, be (iv) patient-centered, (v) support the collaboration with caregivers, and (vi) be aligned to the life goals and values of individuals