The occurrence of Enterobacteriaceae producing KPC carbapenemases in a general hospital in Curacao.

BACKGROUND: Although the presence of Carbapenemase-producing Enterobacteriaceae (CPE) are extensively documented in North and South America. CPE have not been reported from Curacao. However, recently intercontinental spread was suggested of a KPC carbapenemase producing Klebsiella pneumoniae in a patient in the United Kingdom with previous admission to a hospital in Curacao in 2009. FINDINGS: After the introduction of the CLSI 2010 revised breakpoints, seven patients with carbapenemase-producing Enterobacteriaceae were found in a general hospital in Curacao over a period of 16 months. Four patients carried KPC-2 positive Klebsiella pneumoniae, ST11. Two patients carried KPC-3 positive Klebsiella pneumoniae ST258 and one patient carried a KPC-3 positive Citrobacter freundii. Furthermore, our Klebsiella pneumoniae KPC-2 ST11 strain was matched to the Klebsiella pneumoniae KPC-2 ST11 strain in the United Kingdom. CONCLUSIONS: Introduction of new laboratory methods, and adoption of new guidelines and breakpoints led to the first detection of CPE in Curacao. By matching our Klebsiella pneumoniae KPC-2 ST11 strain to a Klebsiella pneumoniae KPC-2 ST11 strain in the United Kingdom, we suggest that carbapenemase-producing Enterobacteriaceae are probably more prevalent in Curacao than previously recognized.

Predominant association of Raoultella bacteremia with diseases of the biliary tract.

A case series of 14 patients with Raoultella bacteremia was compared with 28 Klebsiella oxytoca and 28 Klebsiella pneumoniae bacteremia cases. Forty-three percent of Raoultella bacteremia cases were associated with biliary tract disease, compared to 32% and 22% of patients with K. oxytoca and K. pneumoniae bacteremia, respectively.

Saffold virus, a human Theiler's-like cardiovirus, is ubiquitous and causes infection early in life.

The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus). In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV) and Theiler's murine encephalomyelits virus (TMEV). The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV). The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3) isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months) and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible role in acute and/or chronic disease.

Cutting edge: activity of human adult microglia in response to CC chemokine ligand 21.

The approximately 50 known chemokines are classified in distinct subfamilies: CXC, CC, CX3C, and C. Although the signaling of chemokines often is promiscuous, signaling events between members of these distinct chemokine classes are hardly observed. The only known exception so far is the murine CC chemokine ligand (CCL)21 (secondary lymphoid tissue chemokine, Exodus-2, 6Ckine), which binds and activates the murine CXC chemokine receptor CXCR3. However, this exception has not been found in humans. In this study, we provide evidence that human CCL21 is a functional ligand for endogenously expressed CXCR3 in human adult microglia. In absence of CCR7 expression, CCL21 induced chemotaxis of human microglia with efficiency similar to the CXCR3 ligands CXC chemokine ligand 9 (monokine induced by IFN-gamma) and CXC chemokine ligand 10 (IFN-gamma-inducible protein-10). Because human CCL21 did not show any effects in CXCR3-transfected HEK293 cells, it is indicated that CXCR3 signaling depends on the cellular background in which the CXCR3 is expressed.

CX3CL1 and CX3CR1 expression in human brain tissue: noninflammatory control versus multiple sclerosis.

An important role for CX3CL1 in neuroinflammation and neurodegeneration has been suggested in recent publications. In this study, we compared the expression of CX3CL1 and its receptor CX3CR1 in human brain tissue derived from control patients without neurological complications and in multiple sclerosis (MS) patients. Results from this study demonstrate that CX3CL1 is constitutively expressed in human central nervous system (CNS) astrocytes in vivo and under basal conditions in human adult astrocyte cultures. CX3CR1 is expressed on astrocytes and microglial cells both in vivo and in vitro. Chemotaxis assay shows a functional response upon CX3CR1 signaling in microglial cells. Although CX3CL1 expression is upregulated in cultured astrocytes in response to proinflammatory cytokines, no evidence for expression differences of CX3CL1 between control patients and MS patients was found. Our data suggest that CX3CL1 has more general physiological functions, which occur also in the absence of proinflammatory conditions.

Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance.

BACKGROUND: Various types of pathologic mechanisms in multiple sclerosis (MS) can alter magnetic resonance imaging (MRI) signals, and the appearance of remyelinated lesions on MRI is largely unknown. OBJECTIVE: To describe the MRI appearance of remyelinated lesions in MS. DESIGN: Comparison of postmortem MRI findings with histopathologic findings. SETTING: Brain donations from a general community. Patients Magnetic resonance images from 36 rapid autopsies yielded 161 areas that could be matched with histologic characteristics, including 149 focal T2-weighted abnormalities, with a range of signal intensities on T1-weighted images. In a subset of 49 lesions, magnetization transfer ratio could be determined. MAIN OUTCOME MEASURES: An observer blinded to the MRI findings assessed the presence of remyelination using light microscopic criteria; in 25 areas, in situ hybridization was used to assess the presence of oligodendrocytes expressing proteolipid protein messenger RNA. RESULTS: Remyelinated areas were found in 67 lesions (42%): partial remyelination was present in 30 lesions (19%), whereas 37 lesions (23%) were fully remyelinated. Remyelinated lesions contained enhanced numbers of oligodendrocytes containing proteolipid protein messenger RNA. All areas with remyelination shown histopathologically were hyperintense on T2-weighted images. Strong hypointensity on T1-weighted images was significantly associated (chi2 = 29.8, P<.001) with demyelinated and partially remyelinated lesions compared with fully remyelinated lesions. The magnetization transfer ratio of remyelinated lesions (mean [SD], 27.6% [41%]) differed (F = 46.3, P<.001) from both normal-appearing white matter (35.2% [32%]) and demyelinated lesions (22.3% [48%]). CONCLUSIONS: Remyelinated lesions return an abnormal signal on T2-weighted images. Both T1-weighted images and magnetization transfer ratio may have (limited) additional value in separating lesions with and without remyelination.

Cellular localization and expression patterns of interleukin-10, interleukin-4, and their receptors in multiple sclerosis lesions.

Cytokines have been shown to play a crucial role in the pathogenesis of multiple sclerosis (MS). However, still limited data are available on the expression of anti-inflammatory cytokines within the central nervous system (CNS) during MS lesion development. Therefore, we have examined the expression of the anti-inflammatory cytokines, interleukin-10 (IL-10) and IL-4, and their specific receptors, IL-10R and IL-4R, in postmortem human brain tissue obtained from MS patients. Specific patterns of protein localization and expression for both proteins could be observed within active and chronic MS lesions. Strongest IL-10 immunoreactivity was observed in reactive astrocytes within active demyelinating lesions and the hypercellular rim of chronic active MS lesions. Moreover, perivascular macrophages were immunoreactive for IL-10 in (chronic) active MS lesions. Most intense IL-4 immunoreactivity was detected in reactive fibrillary astrocytes within the hypocellular regions of chronic active and chronic inactive MS lesions. Strong immunoreactivity for IL-10R and IL-4R was detected on macrophages in both parenchymal and perivascular areas and on reactive astrocytes in active and chronic MS lesions. Our results indicate that IL-10 and IL-4 have an active role in CNS immune responses. The specific patterns of protein localization and protein expression for both IL-10 and IL-4 in MS lesions at different stages of development suggest that these anti-inflammatory cytokines and their receptors participate in processes leading to the formation of chronic MS lesions.