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Cairns M Ghani A Okell L Gosling R Carneiro I Anto F Asoala V Owusu-Agyei S Greenwood B Chandramohan D Milligan P 《PloS one》2011,6(4):e18947
Background
Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is recommended by WHO where malaria incidence in infancy is high and SP resistance is low. The current delivery strategy is via routine Expanded Program on Immunisation contacts during infancy (EPI-IPTi). However, improvements to this approach may be possible where malaria transmission is seasonal, or where the malaria burden lies mainly outside infancy.Methods and Findings
A mathematical model was developed to estimate the protective efficacy (PE) of IPT against clinical malaria in children aged 2-24 months, using entomological and epidemiological data from an EPI-IPTi trial in Navrongo, Ghana to parameterise the model. The protection achieved by seasonally-targeted IPT in infants (sIPTi), seasonal IPT in children (sIPTc), and by case-management with long-acting artemisinin combination therapies (LA-ACTs) was predicted for Navrongo and for sites with different transmission intensity and seasonality. In Navrongo, the predicted PE of sIPTi was 26% by 24 months of age, compared to 16% with EPI-IPTi. sIPTc given to all children under 2 years would provide PE of 52% by 24 months of age. Seasonally-targeted IPT retained its advantages in a range of transmission patterns. Under certain circumstances, LA-ACTs for case-management may provide similar protection to EPI-IPTi. However, EPI-IPTi or sIPT combined with LA-ACTs would be substantially more protective than either strategy used alone.Conclusion
Delivery of IPT to infants via the EPI is sub-optimal because individuals are not protected by IPT at the time of highest malaria risk, and because older children are not protected. Alternative delivery strategies to the EPI are needed where transmission varies seasonally or the malaria burden extends beyond infancy. Long-acting ACTs may also make important reductions in malaria incidence. However, delivery systems must be developed to ensure that both forms of chemoprevention reach the individuals who are most exposed to malaria. 相似文献134.
Ansong D Asante KP Vekemans J Owusu SK Owusu R Brobby NA Dosoo D Osei-Akoto A Osei-Kwakye K Asafo-Adjei E Boahen KO Sylverken J Adjei G Sambian D Apanga S Kayan K Janssens MH Lievens MJ Olivier AC Jongert E Dubois P Savarese BM Cohen J Antwi S Greenwood BM Evans JA Agbenyega T Moris PJ Owusu-Agyei S 《PloS one》2011,6(4):e18891
Background
The Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against malaria in sub-Saharan Africa. RTS,S formulated with the liposome based adjuvant AS01E or the oil-in-water based adjuvant AS02D induces P. falciparum circumsporozoite (CSP) antigen-specific antibody and T cell responses which have been associated with protection in the experimental malaria challenge model in adults.Methods
This study was designed to evaluate the safety and immunogenicity induced over a 19 month period by three vaccination schedules (0,1-, 0,1,2- and 0,1,7-month) of RTS,S/AS01E and RTS,S/AS02D in children aged 5–17 months in two research centers in Ghana. Control Rabies vaccine using the 0,1,2-month schedule was used in one of two study sites.Results
Whole blood antigen stimulation followed by intra-cellular cytokine staining showed RTS,S/AS01E induced CSP specific CD4 T cells producing IL-2, TNF-α, and IFN-γ. Higher T cell responses were induced by a 0,1,7-month immunization schedule as compared with a 0,1- or 0,1,2-month schedule. RTS,S/AS01E induced higher CD4 T cell responses as compared to RTS,S/AS02D when given on a 0,1,7-month schedule.Conclusions
These findings support further Phase III evaluation of RTS,S/AS01E. The role of immune effectors and immunization schedules on vaccine protection are currently under evaluation.Trial Registration
ClinicalTrials.gov NCT00360230相似文献135.
McGilchrist P Pethick DW Bonny SP Greenwood PL Gardner GE 《Animal : an international journal of animal bioscience》2011,5(6):875-884
The aim of this experiment was to evaluate the impact of selection for greater muscling on the adrenaline responsiveness of muscle, adipose and liver tissue, as reflected by changes in plasma levels of the intermediary metabolites lactate, non-esterified fatty acids (NEFA) and glucose. This study used 18-month-old steers from an Angus herd visually assessed and selected for divergence in muscling for over 15 years. Ten low muscled (Low), 11 high muscled (High) and 3 high muscled heterozygotes for myostatin mutation (High(Het)) steers were challenged with adrenaline doses ranging between 0.2 to 3.0 μg/kg live weight. For each challenge, 16 blood samples were taken between -30 and 130 min relative to adrenaline administration. Plasma was analysed for NEFA, lactate and glucose concentration and area under curve (AUC) over time was calculated to reflect the tissue responses to adrenaline. Sixteen basal plasma samples from each animal were also assayed for growth hormone. Muscle glycogen and lactate concentration were analysed from four muscle biopsies taken from the semimembranosus, semitendinosus and longissimus thoracis et lumborum of each animal at 14, 90 and 150 days on an ad libitum grain-based diet and at slaughter on day 157. In response to the adrenaline challenges, the High steers had 30% lower lactate AUC than the Low steers at challenges greater than 2 μg/kg live weight, indicating lower muscle responsiveness at the highest adrenaline doses. Aligning with this decrease in muscle response in the High animals were the muscle glycogen concentrations which were 6.1% higher in the High steers. These results suggest that selection for muscling could reduce the incidence of dark, firm, dry meat that is caused by low levels of glycogen at slaughter. At all levels of adrenaline challenge, the High steers had at least 30% greater NEFA AUC, indicating that their adipose tissue was more responsive to adrenaline, resulting in greater lipolysis. In agreement with this response, the High steers had a higher plasma growth hormone concentration, which is likely to have contributed to the increased lipolysis evident in these animals in response to adrenaline. This difference in lipolysis may in part explain the reduced fatness of muscular cattle. There was no effect of selection for muscling on liver responsiveness to adrenaline. 相似文献
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JG Hansen W Gao J Dupuis GT O’Connor W Tang M Kowgier A Sood SA Gharib LJ Palmer M Fornage SR Heckbert BM Psaty SL Booth SUNLIGHT Consortium Patricia A Cassano 《Respiratory research》2015,16(1)
Background
Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.Methods
We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.Results
We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).Conclusions
Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users. 相似文献139.
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