277 research outputs found
Low Dosages of Interleukin 1 Protect Mice against Lethal Cerebral Malaria
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14851.pdf (publisher's version ) (Open Access
The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection
Controlled human malaria infection (CHMI) in healthy human volunteers is an important and powerful tool in clinical malaria vaccine development. However, power calculations are essential to obtain meaningful estimates of protective efficacy, while minimizing the risk of adverse events. To optimize power calculations for CHMI-based malaria vaccine trials, we developed a novel non-linear statistical model for parasite kinetics as measured by qPCR, using data from mosquito-based CHMI experiments in 57 individuals. We robustly account for important sources of variation between and within individuals using a Bayesian framework. Study power is most dependent on the number of individuals in each treatment arm; inter-individual variation in vaccine efficacy and the number of blood samples taken per day matter relatively little. Due to high inter-individual variation in the number of first-generation parasites, hepatic vaccine trials required significantly more study subjects than erythrocytic vaccine trials. We provide power calculations for hypothetical malaria vaccine trials of various designs and conclude that so far, power calculations have been overly optimistic. We further illustrate how upcoming techniques like needle-injected CHMI may reduce required sample sizes
Plasma and whole blood exchange in meningococcal sepsis
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4755.pdf (publisher's version ) (Open Access
Interference of circulating azathioprine but not methotrexate or sulfasalazine with measurements of interleukin-6 bioactivity
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4779.pdf (publisher's version ) (Open Access
Inflammatory mediators in children with protein-energy malnutrition1-3
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Correlation between proinflammatory cytokines and antiinflammatory mediators and the severity of disease in meningococcal infections
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4804.pdf (publisher's version ) (Open Access
Circulating interleukin-6 receptor in patients with sepsis syndrome
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Circulating soluble tumor necrosis factor receptors, interleukin-2 receptors, tumor necrosis factor-á, and interleukin-6 levels in rheumatoid arthritis. Longitudinal evaluation during methotrexate and azathioprine therapy
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4749.pdf (publisher's version ) (Open Access
Differential expression of proinflammatory cytokines and their inhibitors during the course of meningococcal infections
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4764.pdf (publisher's version ) (Open Access
Variation in susceptibility of African Plasmodium falciparum malaria parasites to TEP1 mediated killing in Anopheles gambiae mosquitoes
Anopheles gambiae s.s. mosquitoes are efficient vectors for Plasmodium falciparum, although variation exists in their susceptibility to infection. This variation depends partly on the thioester-containing protein 1 (TEP1) and TEP depletion results in significantly elevated numbers of oocysts in susceptible and resistant mosquitoes. Polymorphism in the Plasmodium gene coding for the surface protein Pfs47 modulates resistance of some parasite laboratory strains to TEP1-mediated killing. Here, we examined resistance of P. falciparum isolates of African origin (NF54, NF165 and NF166) to TEP1-mediated killing in a susceptible Ngousso and a refractory L3-5 strain of A. gambiae. All parasite clones successfully developed in susceptible mosquitoes with limited evidence for an impact of TEP1 on transmission efficiency. In contrast, NF166 and NF165 oocyst densities were strongly reduced in refractory mosquitoes and TEP1 silencing significantly increased oocyst densities. Our results reveal differences between African P. falciparum strains in their capacity to evade TEP1-mediated killing in resistant mosquitoes. There was no significant correlation between Pfs47 genotype and resistance of a given P. falciparum isolate for TEP1 killing. These data suggest that polymorphisms in this locus are not the sole mediators of immune evasion of African malaria parasites
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