Characterization of two Achromobacter xylosoxidans isolates from patients with pertussis-like symptoms

[email protected]: To characterize two Achromobacter xylosoxidans recovered from 2 patients diagnosed with pertussis during a Bordetella pertussis surveillance program. Methods: Nasopharyngeal swabs from 2 children under 1 year of age with clinical suspicion of pertussis were analyzed by culture and PCR. Results: Two Achromobacter xylosoxidans A8, closely related to Bordetella spp. were recovered from 2 patients diagnosed of pertussis, both carrying the ptxA gene and IS418 the pertussis toxin encoding gene. Subsequently, antibiotic susceptibility was evaluated by disk-diffusion method and by PCR. Conclusions: Although more detailed studies are needed, the present data highlight the possibility that Achromobacter xylosoxidans, closely related Bordetella pertussis microorganisms and not covered under the vaccine umbrella, might also result in cases of whooping cough. Thereby further surveillance is necessary to determine the extension and relevance of their pathogenic role in order to discriminate their real public health implication.This work has been supported by Sanofi Aventis del Peru. JR has a fellowship from the program I3, of the ISCIII (grant number: CES11/012), CG has a PhD fellowship of the ISCIII (FI12/00561). MJP has a fellowship from CONCYTEC/FONDECYT.Revisión por pare

Oropouche infection a neglected arbovirus in patients with acute febrile illness from the Peruvian coast

Objective: To evaluate the frequency of infection caused by the Oropouche virus (OROV) in 496 patients with acute febrile disease (AFI), whose samples were obtained for the analysis of endemic arboviruses in a previous investigation carried out in 2016. Results: OROV was detected in 26.4% (131/496) of serum samples from patients with AFI. Co-infections with Dengue virus (7.3%), Zika virus (1.8%) and Chikungunya (0.2%) were observed. The most common clinical symptoms reported among the patients with OROV infections were headache 85.5% (112/131), myalgia 80.9% (106/131), arthralgia 72.5% (95/131) and loss of appetite 67.9% (89/131). Headache and myalgia were predominant in all age groups. Both OROV infections and co-infections were more frequent in May, June and July corresponding to the dry season of the region.Revisión por pare

Characterization of two Achromobacter xylosoxidans isolates from patients with pertussis-like symptoms

OBJECTIVE: To characterize two Achromobacter xylosoxidans recovered from 2 patients diagnosed with pertussis during a Bordetella pertussis surveillance program. METHODS: Nasopharyngeal swabs from 2 children under 1 year of age with clinical suspicion of pertussis were analyzed by culture and PCR. RESULTS: Two Achromobacter xylosoxidans A8, closely related to Bordetella spp. were recovered from 2 patients diagnosed of pertussis, both carrying the ptxA gene and IS418 the pertussis toxin encoding gene. Subsequently, antibiotic susceptibility was evaluated by disk-diffusion method and by PCR. CONCLUSIONS: Although more detailed studies are needed, the present data highlight the possibility that Achromobacter xylosoxidans, closely related Bordetella pertusssis microorganisms and not covered under the vaccine umbrella, might also result in cases of whooping cough. Thereby further surveillance is necessary to determine the extension and relevance of their pathogenic role in order to discriminate their real public health implication

Dengue diagnosis in an endemic area of Peru: Clinical characteristics and positive frequencies by RT-PCR and serology for NS1, IgM, and IgG

This work was supported by Cienciativa of CONCYTEC Peru, under contract number 164-2016-FONDECYT, and the Programa Nacional de Innovación para la Competitividad y Productividad (Innóvate Perú), under contract number 116-PNICP-PIAP-2015.Background: Huánuco is a central eastern region of Peru whose geography includes high forest and low jungle, as well as a mountain range that constitutes the inter-Andean valleys. It is considered a region endemic for dengue due to the many favorable conditions that facilitate transmission of the virus. Methods: A total of 268 serum samples from patients in Huánuco, Peru with an acute febrile illness were assessed for the presence of dengue virus (DENV) via RT-PCR and NS1, IgM, and IgG ELISA during December 2015 and March 2016. Results: DENV was detected in 25% of samples via RT-PCR, 19% of samples by NS1 antigen ELISA, and 10.5% of samples by IgM ELISA. DENV IgG was detected in 15.7% of samples by ELISA. The most frequent symptoms associated with fever across all groups were headache, myalgia, and arthralgia, with no significant difference between the four test methods Conclusions: In this study, DENV was identified in up to 25% of the samples using the standard laboratory method. In addition, a correlation was established between the frequency of positive results and the serological tests that determine NS1, IgM, and IgG. There is an increasing need for point-of-care tests to strengthen epidemiological surveillance in Peru.Revisión por paresRevisión por pare

Genotype-specific prevalence of human papillomavirus infection in asymptomatic Peruvian women: a community-based study

Objective: To determine the general and genotype-specific prevalence of HPV and to identify potential risk factors for the infection in a population-based screening of Peruvian women. Results: A total of 524 samples were analyzed by PCR and a total of 100 HPV positive samples were found, of which 89 were high-risk, 19 were probably oncogenic, 9 were low-risk and 27 other HPV types. The 26–35 and 36–45 age groups showed the highest proportion of HPV positive samples with a total of 37% (37/100) and 30% (30/100), respectively. Moreover, high-risk HPV was found in 33.7% of both groups and probably oncogenic HPV in 52.6% and 31.6%, respectively. High-risk HPV were the most frequent types identified in the population studied, being HPV-52, HPV-31 and HPV-16 the most commonly detected with 17.6%, 15.7% y 12.9%, respectively. Demographic characteristics and habits were assessed in the studied population. A total of 62% high-risk HPV were detected in married/cohabiting women. Women with two children showed the highest proportion (33.8%) of high-risk HPV, followed by women with only one child (26.9%). Those women without history of abortion had a higher frequency of high-risk HPV (71.9%), followed by those with one abortion (25.8%).Revisión por pare

Determination of neuronal antibodies in suspected and definite Creutzfeldt-Jakob disease

IMPORTANCE Creutzfeldt-Jakob disease (CJD) and autoimmune encephalitis with antibodies against neuronal surface antigens (NSA-abs) may present with similar clinical features. Establishing the correct diagnosis has practical implications in the management of care for these patients. OBJECTIVE To determine the frequency of NSA-abs in the cerebrospinal fluid of patients with suspected CJD and in patients with pathologically confirmed (ie, definite) CJD. DESIGN, SETTING, AND PARTICIPANTS A mixed prospective (suspected) and retrospective (definite) CJD cohort study was conducted in a reference center for detection of NSA-abs. The population included 346 patients with suspected CJD and 49 patients with definite CJD. MAIN OUTCOMES AND MEASURES Analysis of NSA-abs in cerebrospinal fluid with brain immunohistochemistry optimized for cell-surface antigens was performed. Positive cases in the suspected CJD group were further studied for antigen specificity using cell-based assays. All definite CJD cases were comprehensively tested for NSA-abs, with cell-based assays used for leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), N-methyl-D-aspartate (NMDA), and glycine (GlY) receptors. RESULTS Neuronal surface antigens were detected in 6 of 346 patients (1.7%) with rapid neurologic deterioration suggestive of CJD. None of these 6 patients fulfilled the diagnostic criteria for probable or possible CJD. The target antigens included CASPR2, LGI1, NMDAR, aquaporin 4, Tr (DNER [δ/notch-like epidermal growth factor-related receptor]), and an unknown protein. Four of the patients developed rapidly progressive dementia, and the other 2 patients had cerebellar ataxia or seizures that were initially considered to be myoclonus without cognitive decline. The patient with Tr-abs had a positive 14-3-3 test result. Small cell lung carcinoma was diagnosed in the patient with antibodies against an unknown antigen. All patients improved or stabilized after appropriate treatment. None of the 49 patients with definite CJD had NSA-abs. CONCLUSIONS AND RELEVANCE A low, but clinically relevant, number of patients with suspected CJD had potentially treatable disorders associated with NSA-abs. In contrast, none of 49 patients with definite CJD had NSA-abs, including NMDAR-abs, GlyR-abs, LGI1-abs, or CASPR2-abs. These findings suggest that cerebrospinal fluid NSA-abs analysis should be included in the diagnostic workup of patients with rapidly progressive central nervous system syndromes, particularly when they do not fulfill the diagnostic criteria of probable or possible CJD

Dengue Virus Inhibits Immune Responses in Aedes aegypti Cells

The ability of many viruses to manipulate the host antiviral immune response often results in complex host-pathogen interactions. In order to study the interaction of dengue virus (DENV) with the Aedes aegypti immune response, we have characterized the DENV infection-responsive transcriptome of the immune-competent A. aegypti cell line Aag2. As in mosquitoes, DENV infection transcriptionally activated the cell line Toll pathway and a variety of cellular physiological systems. Most notably, however, DENV infection down-regulated the expression levels of numerous immune signaling molecules and antimicrobial peptides (AMPs). Functional assays showed that transcriptional induction of AMPs from the Toll and IMD pathways in response to bacterial challenge is impaired in DENV-infected cells. In addition, Escherichia coli, a Gram-negative bacteria species, grew better when co-cultured with DENV-infected cells than with uninfected cells, suggesting a decreased production of AMPs from the IMD pathway in virus-infected cells. Pre-stimulation of the cell line with Gram-positive bacteria prior to DENV infection had no effect on DENV titers, while pre-stimulation with Gram-negative bacteria resulted in an increase in DENV titers. These results indicate that DENV is capable of actively suppressing immune responses in the cells it infects, a phenomenon that may have important consequences for virus transmission and insect physiology

The Soluble Recombinant Neisseria meningitidis Adhesin NadAΔ351–405 Stimulates Human Monocytes by Binding to Extracellular Hsp90

The adhesin NadA favors cell adhesion/invasion by hypervirulent Neisseria meningitidis B (MenB). Its recombinant form NadAΔ351–405, devoid of the outer membrane domain, is an immunogenic candidate for an anti-MenB vaccine able to stimulate monocytes, macrophages and dendritic cells. In this study we investigated the molecular mechanism of NadAΔ351–405 cellular effects in monocytes. We show that NadAΔ351–405 (against which we obtained polyclonal antibodies in rabbits), binds to hsp90, but not to other extracellular homologous heat shock proteins grp94 and hsp70, in vitro and on the surface of monocytes, in a temperature dependent way. Pre-incubation of monocytes with the MenB soluble adhesin interfered with the binding of anti-hsp90 and anti-hsp70 antibodies to hsp90 and hsp70 at 37°C, a condition in which specific cell-binding occurs, but not at 0°C, a condition in which specific cell-binding is very diminished. Conversely, pre-incubation of monocytes with anti-hsp90 and anti-hsp70 antibodies did not affected NadAΔ351–405 cell binding in any temperature condition, indicating that it associates to another receptor on their plasma membrane and then laterally diffuses to encounter hsp90. Consistently, polymixin B interfered with NadAΔ351–405 /hsp90 association, abrogated the decrease of anti-hsp90 antibodies binding to the cell surface due to NadAΔ351–405 and inhibited adhesin-induced cytokine/chemokine secretion without affecting monocyte-adhesin binding. Co-stimulation of monocytes with anti-hsp90 antibodies and NadAΔ351–405 determined a stronger but polymixin B insensitive cell activation. This indicated that the formation of a recombinant NadA/hsp90/hsp70 complex, although essential for full monocyte stimulation, can be replaced by anti-hsp90 antibody/hsp90 binding. Finally, the activation of monocytes by NadAΔ351–405 alone or in the presence of anti-hsp90 antibodies were both inhibited by neutralizing anti-TLR4 antibodies, but not by anti-TLR2 antibodies. We propose that hsp90-dependent recruitment into an hsp90/hsp70/TLR4 transducing signal complex is necessary for the immune-stimulating activity of NadAΔ351–405 anti-MenB vaccine candidate

Charge separation relative to the reaction plane in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}}= 2.76 TeV

Measurements of charge dependent azimuthal correlations with the ALICE detector at the LHC are reported for Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV. Two- and three-particle charge-dependent azimuthal correlations in the pseudo-rapidity range $|\eta| < 0.8$ are presented as a function of the collision centrality, particle separation in pseudo-rapidity, and transverse momentum. A clear signal compatible with a charge-dependent separation relative to the reaction plane is observed, which shows little or no collision energy dependence when compared to measurements at RHIC energies. This provides a new insight for understanding the nature of the charge dependent azimuthal correlations observed at RHIC and LHC energies.Comment: 12 pages, 3 captioned figures, authors from page 2 to 6, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/286

Mactinin, a fragment of cytoskeletal α-actinin, is a novel inducer of heat shock protein (Hsp)-90 mediated monocyte activation

<p>Abstract</p> <p>Background</p> <p>Monocytes, their progeny such as dendritic cells and osteoclasts and products including tumor necrosis factor (TNF)-α, interleukin (IL)-1α and IL-1β play important roles in cancer, inflammation, immune response and atherosclerosis. We previously showed that mactinin, a degradative fragment of the cytoskeletal protein α-actinin, is present at sites of monocytic activation in vivo, has chemotactic activity for monocytes and promotes monocyte/macrophage maturation. We therefore sought to determine the mechanism by which mactinin stimulates monocytes.</p> <p>Results</p> <p>Radiolabeled mactinin bound to a heterocomplex on monocytes comprised of at least 3 proteins of molecular weight 88 kD, 79 kD and 68 kD. Affinity purification, mass spectroscopy and Western immunoblotting identified heat shock protein (Hsp)-90 as the 88 kD component of this complex. Hsp90 was responsible for mediating the functional effects of mactinin on monocytes, since Hsp90 inhibitors (geldanamycin and its analogues 17-allylamino-17-demethoxygeldanamycin [17-AAG] and 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin [17-DMAG]) almost completely abrogated the stimulatory activity of mactinin on monocytes (production of the pro-inflammatory cytokines IL-1α, IL-1β and TNF-α, as well as monocyte chemotaxis).</p> <p>Conclusion</p> <p>Mactinin is a novel inducer of Hsp90 activity on monocytes and may serve to perpetuate and augment monocytic activation, thereby functioning as a "matrikine." Blockage of this function of mactinin may be useful in diseases where monocyte/macrophage activation and/or Hsp90 activity are detrimental.</p