22 research outputs found
Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model
Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo
Inhibition of secretion of proteins and triacylglycerol from isolated rat hepatocytes mediated by benzimidazole carbamate antimicrotubule agents.
Development of a Multiplex Real-Time PCR for the Rapid Detection of the Predominant Beta-Lactamase Genes CTX-M, SHV, TEM and CIT-Type AmpCs in Enterobacteriaceae
Prevalence of Extended-Spectrum β-Lactamase-Producing Escherichia coli on Bavarian Dairy and Beef Cattle Farms
High Proportion of Intestinal Colonization with Successful Epidemic Clones of ESBL-Producing Enterobacteriaceae in a Neonatal Intensive Care Unit in Ecuador
Occurrence of virulence genes, 16S rRNA methylases, and plasmid-mediated quinolone resistance genes in CTX-M-producing Escherichia coli from Pakistan
Superbugs in the supermarket? Assessing the rate of contamination with third-generation cephalosporin-resistant gram-negative bacteria in fresh Australian pork and chicken
Characterization and Comparison of Extended-Spectrum beta-Lactamase (ESBL) Resistance Genotypes and Population Structure of Escherichia coli Isolated from Franklin's Gulls (Leucophaeus pipixcan) and Humans in Chile
We investigated the general level of antibiotic resistance with further analysis of extended-spectrum beta-lactamase (ESBL) prevalence, as well as the population structure of E. coli in fecal flora of humans and Franklin's gulls (Leucophaeus pipixcan) in central parts of Chile. We found a surprisingly high carriage rate of ESBL-producing E. coli among the gulls 112/372 (30.1%) as compared to the human population 6/49 (12.2%.) Several of the E. coli sequence types (STs) identified in birds have previously been reported as Multi Drug Resistant (MDR) human pathogens including the ability to produce ESBLs. This means that not only commensal flora is shared between birds and humans but also STs with pathogenic potential. Given the migratory behavior of Franklin's gulls, they and other migratory species, may be a part of ESBL dissemination in the environment and over great geographic distances. Apart from keeping the antibiotic use low, breaking the transmission chains between the environment and humans must be a priority to hinder the dissemination of resistance