Human Plasmodium knowlesi Infection Detected by Rapid Diagnostic Tests for Malaria

We describe a PCR-confirmed case of Plasmodium knowlesi infection with a high parasitemia level and clinical signs of severe malaria in a migrant worker from Malaysian Borneo in the Netherlands. Investigations showed that commercially available rapid antigen tests for detection of human Plasmodium infections can detect P. knowlesi infections in humans.     

The fallacy of coverage: uncovering disparities to improve immunization rates through evidence. Results from the Canadian International Immunization Initiative Phase 2 - Operational Research Grants

Immunization can and does save lives. However, the presence of vaccines does not easily translate into every child being vaccinated, and this is what the studies in this journal supplement reveal. From South Asia to West Africa,the evidence presented here reveals what we are calling the fallacy of coverage, going beyond uncovering the real vaccination rates to providing evidence on the reasons for the lack of effective coverage.The evidence for the fallacy of coverage is part of an operational research program entitled the Canadian International Immunization Initiative Phase 2 (CIII2). Through a competitive peer review process, six research grants were awarded to increase access to and enhance immunization services. This journal supplement provides a forum for the presentation of the results of five of the six studies.The story of the fallacy of coverage is made up of five theme areas of evidence - timeliness of immunization, social and gender inequities, vaccine efficacy, understanding demand side issues to tailor interventions, and national data sets masking actual district level coverage rates - that reveal the discrepancies in immunization coverage rates and the reasons behind these discrepancies. As part of the story, and to turn around the fallacy of coverage, the studies also provide proof of effective and locally relevant solutions.Policies and funding, while keeping an eye on future diseases, clearly need to maintain and increase support to address existing vaccine-preventable diseases to increase coverage such that by 2015 we can achieve 90% national vaccination coverage and reach the MDG of reducing mortality rates among children under five by two-thirds.The results from the operational research grants of the CIII2 offer some answers on how to reach this goal by demonstrating how locally generated evidence can inform immunization strategies to ensure that children who need to get vaccinated will get vaccinated, and vaccinated on time.     

Crimean Congo hemorrhagic fever virus infects human monocyte-derived dendritic cells

For some patients infection with Crimean Congo hemorrhagic fever virus (CCHFV) causes a severe disease characterized by fever, vascular leakage and coagulopathy. Knowledge of CCHF pathogenesis is limited and today there is no information about the specific target cells of CCHFV. In this study we analyzed the permissiveness of human peripheral blood mononuclear cells (PBMCs) including monocyte-derived dendritic cells (moDCs) to CCHFV infection. Interestingly, we found that moDCs are the most permissive to CCHFV infection and this infection induced cytokine release from moDCs. Furthermore, supernatants from infected moDCs were found to activate human endothelial cells.     

Drug use and sexually transmitted diseases among female and male arrested youths

Knowledge of the rates and correlates of juvenile offenders’ sexually transmitted diseases (STD) has been limited to samples of incarcerated youths comprised mostly of males. Data collected on 442 female and 506 male youths processed at a centralized intake facility enabled us to study this important public health problem among a sample of juvenile offenders at the front end of the justice system. Female–male, multi-group latent class analyses identified two subgroups, High Risk and Lower Risk, of youths described by a latent construct of risk based on drug test results, STD test results, and a classification for the seriousness of arrest charge. The results found: (1) a similar classification distinguished High Risk and Lower Risk male and female youths, and (2) important gender group differences in sexual risk related factors (e.g., substance use during sexual encounters). Among the youths in this sample who tested positive for an STD, 66% of the girls and 57% of the boys were released back into the community after arrest. Overall, our findings raise serious public health and social welfare concerns, for both the youths and the community. Prevention and intervention implications of these findings are also discussed.

Import of tRNAs and aminoacyl-tRNA synthetases into mitochondria

During evolution, most of the bacterial genes from the ancestral endosymbiotic α-proteobacteria at the origin of mitochondria have been either lost or transferred to the nuclear genome. A crucial evolutionary step was the establishment of macromolecule import systems to allow the come back of proteins and RNAs into the organelle. Paradoxically, the few mitochondria-encoded protein genes remain essential and must be translated by a mitochondrial translation machinery mainly constituted by nucleus-encoded components. Two crucial partners of the mitochondrial translation machinery are the aminoacyl-tRNA synthetases and the tRNAs. All mitochondrial aminoacyl-tRNA synthetases and many tRNAs are imported from the cytosol into the mitochondria in eukaryotic cells. During the last few years, their origin and their import into the organelle have been studied in evolutionary distinct organisms and we review here what is known in this field.     

Comparative phenotypic analysis of articular chondrocytes cultured within type I or type II collagen scaffolds

Among the existing repair strategies for cartilage injury, tissue engineering approach using biomaterials and chondrocytes offers hope for treatments. In this context, collagen-based biomaterials are good candidates as scaffolds for chondrocytes in cell transplantation procedures. These scaffolds are provided under different forms (gel or crosslinked sponge) made with either type I collagen or type I or type II atelocollagen molecules. The present study was undertaken to investigate how bovine articular chondrocytes sense and respond to differences in the structure and organization of these collagen scaffolds, over a 12-day culture period. When chondrocytes were seeded in the collagen scaffolds maintained in free-floating conditions, cells contracted gels to 40-60% and sponges to 15% of their original diameter. Real-time polymerase chain reaction analysis indicated that the chondrocyte phenotype, assessed notably by the ratio of COL2A1/COL1A2 mRNA and alpha10/alpha11 integrin subunit mRNA, was comparatively better sustained in type I collagen sponges when seeded at high cell density, also in type I atelocollagen gels. Besides, proteoglycan accumulation in the different scaffolds, as assessed by measuring the sulfated glycosaminoglycan content, was found be highest in type I collagen sponges seeded at high cell density. In addition, gene expression of matrix metalloproteinase-13 increased dramatically (up to 90-fold) in chondrocytes cultured in the different gels, whereas it remained stable in the sponges. Our data taken together reveal that type I collagen sponges seeded at high cell density represent a suitable material for tissue engineering of cartilage.     

Cell labeling for magnetic resonance imaging with the T1 agent manganese chloride

There is growing interest in using MRI to track cellular migration. To date, most work in this area has been performed using ultra-small particles of iron oxide. Immune cells are difficult to label with iron oxide particles. The ability of adoptively infused tumor specific T cells and N cells to traffic to the tumor microenvironment may be a critical determinant of their therapeutic efficacy. We tested the hypothesis that lymphocytes and B cells would label with MnCl2 to a level that would allow their detection by T1-weighted MRI. Significant signal enhancement was observed in human lymphocytes after a 1 h incubation with 0.05-1.0 mM MnCl2. A flow cytometry-based evaluation using propidium iodide and Annexin V staining showed that lymphocytes did not undergo apoptosis or necrosis immediately after and 24 h following a 1 h incubation with up to 1.0 mM MnCl2. Importantly, NK cells and cytotoxic T cells maintained their in vitro killing capacity after being incubated with up to 0.5 mM MnCl2. This is the first report to describe the use of MnCl2 to label lymphocytes. Our data suggests MnCl2 might be an alternative to iron oxide cell labeling for MRI-based cell migration studies.     

Sensitivities of four new commercial hepatitis B virus surface antigen (HBsAg) assays in detection of HBsAg mutant forms

Mutations in hepatitis B virus surface antigen (HBsAg) involving amino acid substitution within the immunodominant "a" determinant may affect the performance of commercial HBsAg assays. The performances of four HBsAg assays that recently received Conformité Européene marking, Advia Centaur HBsAg (Bayer), Monolisa HBsAg Ultra (Bio-Rad), Liaison HBsAg (Dia Sorin), and Vidas HBsAg Ultra (bioMérieux), were compared with that of the routinely used HBsAg assay AxSYM HBsAg V2 (Abbott). Assays were evaluated for (i) analytical sensitivity performance with a national reference HBsAg panel (including 10 samples with calibrated HBsAg concentrations from 0.04 to 2.24 ng/ml) and (ii) the detection of HBsAg mutants by studying a panel of 35 HBsAg mutants (23 collected from patients and 12 recombinant mutants). The limits of detection of these assays were <0.15 ng/ml (from 0.089 to 0.121 ng/ml). The sensitivity performances for mutant virus detection varied, ranging from 37.1% to 91.4%. The lack of detection of these mutants by commercial assays was probably due to the epitope recognition of the anti-HBs assay reagents in the capture phase and in the conjugates. The prevalence and clinical impact of HBsAg mutants are under investigation. However, the manufacturers must be vigilant in the design of the assays in order to reduce the risk of missing a broad range of described S gene mutants.