Maternal Filarial Infection Influences the Development of Regulatory T Cells in Children from Infancy to Early Childhood

PubMed Central

Bal, Madhusmita; Ranjit, Manoranjan; Achary, K. Gopinath; Satapathy, Ashok K.

2016-01-01

Background Children born from filarial infected mothers are comparatively more susceptible to filarial infection than the children born to uninfected mothers. But the mechanism of such increased susceptibility to infection in early childhood is not exactly known. Several studies have shown the association of active filarial infection with T cell hypo-responsiveness which is mediated by regulatory T cells (Tregs). Since the Tregs develop in the thymus from CD4+ CD25hi thymocytes at an early stage of the human fetus, it can be hypothesized that the maternal infection during pregnancy affects the development of Tregs in children at birth as well as early childhood. Hence the present study was designed to test the hypothesis by selecting a cohort of pregnant mothers and children born to them subsequently in a filarial endemic area of Odisha, India. Methodology and Principal finding A total number of 49 pregnant mothers and children born to them subsequently have been followed up (mean duration 4.4 years) in an area where the microfilariae (Mf) rate has come down to <1% after institution of 10 rounds of annual mass drug administration (MDA). The infection status of mother, cord and children were assessed through detection of microfilariae (Mf) and circulating filarial antigen (CFA). Expression of Tregs cells were measured by flow cytometry. The levels of IL-10 were evaluated by using commercially available ELISA kit. A significantly high level of IL-10 and Tregs have been observed in children born to infected mother compared to children of uninfected mother at the time of birth as well as during early childhood. Moreover a positive correlation between Tregs and IL-10 has been observed among the children born to infected mother. Significance From these observations we predict that early priming of the fetal immune system by filarial antigens modulate the development of Tregs, which ultimately scale up the production of IL-10 in neonates and creates a milieu for high rate

Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection.

PubMed

Rossenkhan, Raabya; MacLeod, Iain J; Brumme, Zabrina L; Magaret, Craig A; Sebunya, Theresa K; Musonda, Rosemary; Gashe, Berhanu A; Edlefsen, Paul T; Novitsky, Vlad; Essex, M

Viral variants that predominate during early infection may exhibit constrained diversity compared with those found during chronic infection and could contain amino acid signature patterns that may enhance transmission, establish productive infection, and influence early events that modulate the infection course. We compared amino acid distributions in 17 patients recently infected with HIV-1C with patients with chronic infection. We found significantly lower entropy in inferred transmitted/founder (t/f) compared with chronic viruses and identified signature patterns in Vif and Vpr from inferred t/f viruses. We investigated sequence evolution longitudinally up to 500 days postseroconversion and compared the impact of selected substitutions on predicted human leukocyte antigen (HLA) binding affinities of published and predicted cytotoxic T-lymphocyte epitopes. Polymorphisms in Vif and Vpr during early infection occurred more frequently at epitope-HLA anchor residues and significantly decreased predicted epitope-HLA binding. Transmission-associated sequence signatures may have implications for novel strategies to prevent HIV-1 transmission.

Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection

PubMed Central

Rossenkhan, Raabya; MacLeod, Iain J.; Brumme, Zabrina L.; Magaret, Craig A.; Sebunya, Theresa K.; Musonda, Rosemary; Gashe, Berhanu A.; Edlefsen, Paul T.; Novitsky, Vlad

2016-01-01

Abstract Viral variants that predominate during early infection may exhibit constrained diversity compared with those found during chronic infection and could contain amino acid signature patterns that may enhance transmission, establish productive infection, and influence early events that modulate the infection course. We compared amino acid distributions in 17 patients recently infected with HIV-1C with patients with chronic infection. We found significantly lower entropy in inferred transmitted/founder (t/f) compared with chronic viruses and identified signature patterns in Vif and Vpr from inferred t/f viruses. We investigated sequence evolution longitudinally up to 500 days postseroconversion and compared the impact of selected substitutions on predicted human leukocyte antigen (HLA) binding affinities of published and predicted cytotoxic T-lymphocyte epitopes. Polymorphisms in Vif and Vpr during early infection occurred more frequently at epitope-HLA anchor residues and significantly decreased predicted epitope-HLA binding. Transmission-associated sequence signatures may have implications for novel strategies to prevent HIV-1 transmission. PMID:27349335

Diagnostic and prognostic value of procalcitonin for early intracranial infection after craniotomy

PubMed Central

Yu, Y.; Li, H.J.

2017-01-01

Intracranial infection is a common clinical complication after craniotomy. We aimed to explore the diagnostic and prognostic value of dynamic changing procalcitonin (PCT) in early intracranial infection after craniotomy. A prospective study was performed on 93 patients suspected of intracranial infection after craniotomy. Routine peripheral venous blood was collected on the day of admission, and C reactive protein (CRP) and PCT levels were measured. Cerebrospinal fluid (CSF) was collected for routine biochemical, PCT and culture assessment. Serum and CSF analysis continued on days 1, 2, 3, 5, 7, 9, and 11. The patients were divided into intracranial infection group and non-intracranial infection group; intracranial infection group was further divided into infection controlled group and infection uncontrolled group. Thirty-five patients were confirmed with intracranial infection after craniotomy according to the diagnostic criteria. The serum and cerebrospinal fluid PCT levels in the infected group were significantly higher than the non-infected group on day 1 (P<0.05, P<0.01). The area under curve of receiver operating characteristics was 0.803 for CSF PCT in diagnosing intracranial infection. The diagnostic sensitivity and specificity of CSF PCT was superior to other indicators. The serum and CSF PCT levels have potential value in the early diagnosis of intracranial infection after craniotomy. Since CSF PCT levels have higher sensitivity and specificity, dynamic changes in this parameter could be used for early detection of intracranial infection after craniotomy, combined with other biochemical indicators. PMID:28443989

Exploiting persistent infection for selection of bovine herpesvirus 4 recombinants.

PubMed

Donofrio, G; Martignani, E; Cavirani, S; Flammini, C F

2005-09-01

Bovine herpesvirus 4 (BoHV-4) is a gamma-herpesvirus with no clear disease association, and due to its biological characteristics, has been suggested as a gene delivery vector. It was demonstrated previously that recombinant BoHV-4 carrying a neomycin-resistance gene was able to infect a human rhabdomyosarcoma cell line (RD-4), resulting in no detectable cytopathic effect (CPE) and allowing selection of G418-resistant persistently-infected cells containing circular episomal viral DNA [Donofrio, G., Cavirani, S., van Santen, V.L., 2000a. Establishment of a cell line persistently infected with recombinant BoHV-4. J. Gen. Virol. 81, 1807-1814.]. Those cells produce infectious virus and infection is predominantly non-permissive and non-cytopathic. Starting from these results, the ability of RD-4 cells to sustain persistent infection was combined with positive selection activity conferred by the neomycin-expression cassette insert, as an easier way to select recombinants of BoHV-4 following homologous recombination in permissive cells. A tool for selecting BoHV-4 recombinants was developed by drug positive selection.

Demographic processes affect HIV-1 evolution in primary infection before the onset of selective processes.

PubMed

Herbeck, Joshua T; Rolland, Morgane; Liu, Yi; McLaughlin, Sherry; McNevin, John; Zhao, Hong; Wong, Kim; Stoddard, Julia N; Raugi, Dana; Sorensen, Stephanie; Genowati, Indira; Birditt, Brian; McKay, Angela; Diem, Kurt; Maust, Brandon S; Deng, Wenjie; Collier, Ann C; Stekler, Joanne D; McElrath, M Juliana; Mullins, James I

2011-08-01

HIV-1 transmission and viral evolution in the first year of infection were studied in 11 individuals representing four transmitter-recipient pairs and three independent seroconverters. Nine of these individuals were enrolled during acute infection; all were men who have sex with men (MSM) infected with HIV-1 subtype B. A total of 475 nearly full-length HIV-1 genome sequences were generated, representing on average 10 genomes per specimen at 2 to 12 visits over the first year of infection. Single founding variants with nearly homogeneous viral populations were detected in eight of the nine individuals who were enrolled during acute HIV-1 infection. Restriction to a single founder variant was not due to a lack of diversity in the transmitter as homogeneous populations were found in recipients from transmitters with chronic infection. Mutational patterns indicative of rapid viral population growth dominated during the first 5 weeks of infection and included a slight contraction of viral genetic diversity over the first 20 to 40 days. Subsequently, selection dominated, most markedly in env and nef. Mutants were detected in the first week and became consensus as early as day 21 after the onset of symptoms of primary HIV infection. We found multiple indications of cytotoxic T lymphocyte (CTL) escape mutations while reversions appeared limited. Putative escape mutations were often rapidly replaced with mutually exclusive mutations nearby, indicating the existence of a maturational escape process, possibly in adaptation to viral fitness constraints or to immune responses against new variants. We showed that establishment of HIV-1 infection is likely due to a biological mechanism that restricts transmission rather than to early adaptive evolution during acute infection. Furthermore, the diversity of HIV strains coupled with complex and individual-specific patterns of CTL escape did not reveal shared sequence characteristics of acute infection that could be harnessed for

Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease

PubMed Central

Weiner, Zachary P.; Crew, Rebecca M.; Brandt, Kevin S.; Ullmann, Amy J.; Schriefer, Martin E.; Molins, Claudia R.

2015-01-01

Laboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of Borrelia burgdorferi proteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additional in vivo-expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing. PMID:26376927

Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease.

PubMed

Weiner, Zachary P; Crew, Rebecca M; Brandt, Kevin S; Ullmann, Amy J; Schriefer, Martin E; Molins, Claudia R; Gilmore, Robert D

2015-11-01

Laboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of Borrelia burgdorferi proteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additional in vivo-expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Early-life Infection is a Vulnerability Factor for Aging-Related Glial Alterations and Cognitive Decline

PubMed Central

Bilbo, Staci D.

2010-01-01

There is significant individual variability in cognitive decline during aging, suggesting the existence of “vulnerability factors” for eventual deficits. Neuroinflammation may be one such factor; increased glial reactivity is a common outcome of aging, which in turn is associated with numerous neurodegenerative conditions. Early-life infection leads to cognitive impairment in conjunction with an inflammatory challenge in young adulthood, which led us to explore whether it might also accelerate the cognitive decline associated with aging. Rats were treated on postnatal day 4 with PBS or E. coli, and then tested for learning & memory at 2 or 16 month of age, using 2 fear conditioning tasks (context pre-exposure and ambiguous cue), and a spatial water maze task. Neonatally-infected rats exhibited memory impairments in both the ambiguous cue fear-conditioning task and in the water maze, but only at 16 month. There were no differences in anxiety between groups. Neonatally-infected rats also exhibited greater aging-induced increases in glial markers (CD11b and MHC II on microglia, and GFAP on astrocytes), as well as selective changes in NMDA receptor subunit expression within the hippocampus, but not in amygdala or parietal cortex compared to controls. Taken together, these data suggest that early-life infection leads to less successful cognitive aging, which may be linked to changes in glial reactivity. PMID:20388544

Early-life infection is a vulnerability factor for aging-related glial alterations and cognitive decline.

PubMed

Bilbo, Staci D

2010-07-01

There is significant individual variability in cognitive decline during aging, suggesting the existence of "vulnerability factors" for eventual deficits. Neuroinflammation may be one such factor; increased glial reactivity is a common outcome of aging, which in turn is associated with numerous neurodegenerative conditions. Early-life infection leads to cognitive impairment in conjunction with an inflammatory challenge in young adulthood, which led us to explore whether it might also accelerate the cognitive decline associated with aging. Rats were treated on postnatal day 4 with PBS or Escherichia coli, and then tested for learning and memory at 2 or 16months of age, using two fear-conditioning tasks (context pre-exposure and ambiguous cue), and a spatial water maze task. Neonatally-infected rats exhibited memory impairments in both the ambiguous cue fear-conditioning task and in the water maze, but only at 16months. There were no differences in anxiety between groups. Neonatally-infected rats also exhibited greater aging-induced increases in glial markers (CD11b and MHCII on microglia, and GFAP on astrocytes), as well as selective changes in NMDA receptor subunit expression within the hippocampus, but not in amygdala or parietal cortex compared to controls. Taken together, these data suggest that early-life infection leads to less successful cognitive aging, which may be linked to changes in glial reactivity.

Flavivirus Infection Impairs Peroxisome Biogenesis and Early Antiviral Signaling

PubMed Central

You, Jaehwan; Hou, Shangmei; Malik-Soni, Natasha; Xu, Zaikun; Kumar, Anil; Rachubinski, Richard A.; Frappier, Lori

2015-01-01

ABSTRACT Flaviviruses are significant human pathogens that have an enormous impact on the global health burden. Currently, there are very few vaccines against or therapeutic treatments for flaviviruses, and our understanding of how these viruses cause disease is limited. Evidence suggests that the capsid proteins of flaviviruses play critical nonstructural roles during infection, and therefore, elucidating how these viral proteins affect cellular signaling pathways could lead to novel targets for antiviral therapy. We used affinity purification to identify host cell proteins that interact with the capsid proteins of West Nile and dengue viruses. One of the cellular proteins that formed a stable complex with flavivirus capsid proteins is the peroxisome biogenesis factor Pex19. Intriguingly, flavivirus infection resulted in a significant loss of peroxisomes, an effect that may be due in part to capsid expression. We posited that capsid protein-mediated sequestration and/or degradation of Pex19 results in loss of peroxisomes, a situation that could result in reduced early antiviral signaling. In support of this hypothesis, we observed that induction of the lambda interferon mRNA in response to a viral RNA mimic was reduced by more than 80%. Together, our findings indicate that inhibition of peroxisome biogenesis may be a novel mechanism by which flaviviruses evade the innate immune system during early stages of infection. IMPORTANCE RNA viruses infect hundreds of millions of people each year, causing significant morbidity and mortality. Chief among these pathogens are the flaviviruses, which include dengue virus and West Nile virus. Despite their medical importance, there are very few prophylactic or therapeutic treatments for these viruses. Moreover, the manner in which they subvert the innate immune response in order to establish infection in mammalian cells is not well understood. Recently, peroxisomes were reported to function in early antiviral signaling, but

Cytomegalovirus infection in HIV-infected versus non-infected infants and HIV disease progression in Cytomegalovirus infected versus non infected infants early treated with cART in the ANRS 12140-Pediacam study in Cameroon.

PubMed

Kfutwah, Anfumbom K W; Ngoupo, Paul Alain T; Sofeu, Casimir Ledoux; Ndongo, Francis Ateba; Guemkam, Georgette; Ndiang, Suzie Tetang; Owona, Félicité; Penda, Ida Calixte; Tchendjou, Patrice; Rouzioux, Christine; Warszawski, Josiane; Faye, Albert; Tejiokem, Mathurin Cyrille

2017-03-23

The outcome of CMV/HIV co-infection in infants treated early with combined antiretroviral therapy (cART) in resource-limited settings has not been described. We aimed to estimate the prevalence and identify factors associated with early CMV infection in HIV-infected and non-infected infants included in a study in Cameroon, and to compare HIV disease progression and survival after 1 year of early cART, following infants' CMV status. HIV-infected infants followed from birth or from HIV diagnosis before 7 months old and HIV-uninfected infants born to HIV-infected or uninfected mothers were tested for CMV at a median age of 4.0 months [Interquartile range (IQR): 3.4-4.9]. Multivariable logistic regression was performed to identify factors associated with CMV infection. Early cART was offered to HIV-infected infants: mortality, immunological and virological outcomes were assessed. Three hundred and sixty-nine infants were tested. The proportion of infants infected with CMV at baseline was significantly higher in HIV-infected than in HIV-uninfected groups (58.9% (86/146) vs 30.0% (67/223), p < 0.001). At baseline, median CMV viral load was higher in HIV-infected (3.7 log copies/ml [IQR; 3.1-4.3]) than in HIV-uninfected infants (2.8 log copies [IQR; 2.1-3.4], p < 0.001). cART was initiated in 90% of HIV-infected infants (132/146) at a median age of 4.0 months (IQR; 3.2-5.9); in this sub-group CMV infection was independently associated with being followed from the time of HIV diagnosis rather than from birth (aOR = 3.1, 95%CI [1.2-8.0]), born to a non-single mother (aOR = 3.4[1.4-8.1]), and breastfeeding (aOR = 7.3 [2.7-19.4]). HIV-infected infants were retested after a median of 7.1 months [4.8-9.5]: CMV was undetectable in 37 of the 61 (60.7%) initially CMV-infected cases and became detectable in 8 of the 38 (21.1%) initially CMV-negative cases. After 1 year of cART, the probability of death (0.185 vs 0.203; p = 0.75), the proportion of

Lassa and Marburg viruses elicit distinct host transcriptional responses early after infection.

PubMed

Caballero, Ignacio S; Yen, Judy Y; Hensley, Lisa E; Honko, Anna N; Goff, Arthur J; Connor, John H

2014-11-06

Lassa virus and Marburg virus are two causative agents of viral hemorrhagic fever. Their diagnosis is difficult because patients infected with either pathogen present similar nonspecific symptoms early after infection. Current diagnostic tests are based on detecting viral proteins or nucleic acids in the blood, but these cannot be found during the early stages of disease, before the virus starts replicating in the blood. Using the transcriptional response of the host during infection can lead to earlier diagnoses compared to those of traditional methods. In this study, we use RNA sequencing to obtain a high-resolution view of the in vivo transcriptional dynamics of peripheral blood mononuclear cells (PBMCs) throughout both types of infection. We report a subset of host mRNAs, including heat-shock proteins like HSPA1B, immunoglobulins like IGJ, and cell adhesion molecules like SIGLEC1, whose differences in expression are strong enough to distinguish Lassa infection from Marburg infection in non-human primates. We have validated these infection-specific expression differences by using microarrays on a larger set of samples, and by quantifying the expression of individual genes using RT-PCR. These results suggest that host transcriptional signatures are correlated with specific viral infections, and that they can be used to identify highly pathogenic viruses during the early stages of disease, before standard detection methods become effective.

Early Weight Development of Goats Experimentally Infected with Mycobacterium avium subsp. paratuberculosis

PubMed Central

Malone, Alyssa N.; Fletcher, Darcy M.; Vogt, Megan B.; Meyer, Stephen K.; Hess, Ann M.; Eckstein, Torsten M.

2013-01-01

Johne’s disease is an infectious chronic inflammatory bowel disease in ruminants. The key factor for the management of this disease is an early positive diagnosis. Unfortunately, most diagnostics detect animals with Johne’s disease in the clinical stage with positive serology and/or positive fecal cultures. However, for effective management of the disease within herds, it is important to detect infected animals as early as possible. This might only be possible with the help of parameters not specific for Johne’s disease but that give an early indication for chronic infections such as weight development. Here we report our findings on the development of total body weight and weight gain during the first six months of goats experimentally infected to induce Johne’s disease. Twenty dairy goat kids age 2 to 5 days were included in this study. Goats were divided into two groups: a negative control group and a positive infected group. The weight was obtained weekly throughout the study. Goats of the positive group were infected at the age of seven weeks. We detected significant changes in weight gain and total body weight as early as one week after infection. Differences are significant throughout the six month time period. Weight as a non-specific parameter should be used to monitor infection especially in studies on Johne’s disease using the goat model. Our study suggests that goats with Johne’s disease have a reduced weight gain and reduced weight when compared with healthy goats of the same age. PMID:24349564

T Cell Immunosenescence after Early Life Adversity: Association with Cytomegalovirus Infection.

PubMed

Elwenspoek, Martha M C; Sias, Krystel; Hengesch, Xenia; Schaan, Violetta K; Leenen, Fleur A D; Adams, Philipp; Mériaux, Sophie B; Schmitz, Stephanie; Bonnemberger, Fanny; Ewen, Anouk; Schächinger, Hartmut; Vögele, Claus; Muller, Claude P; Turner, Jonathan D

2017-01-01

Early life adversity (ELA) increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences. However, it is unclear what drives ELA-associated immunosenescence and which cells are primarily affected. We investigated different biomarkers of immunosenescence in a healthy subset of the EpiPath cohort. Participants were either parent-reared (Ctrl, n  = 59) or had experienced separation from their parents in early childhood and were subsequently adopted (ELA, n  = 18). No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood, containing a heterogeneous mixture of immune cells. However, when specifically investigating T cells, we found a higher expression of senescence markers (CD57) in ELA. In addition, senescent T cells (CD57 + ) in ELA had an increased cytolytic potential compared to senescent cells in controls. With a mediation analysis we demonstrated that cytomegalovirus (CMV) infection, which is an important driving force of immunosenescence, largely accounted for elevated CD57 expression observed in ELA. Leukocyte telomere length may obscure cell-specific immunosenescence; here, we demonstrated that the use of cell surface markers of senescence can be more informative. Our data suggest that ELA may increase the risk of CMV infection in early childhood, thereby mediating the effect of ELA on T cell-specific immunosenescence. Thus, future studies should include CMV as a confounder or selectively investigate CMV seronegative cohorts.

T Cell Immunosenescence after Early Life Adversity: Association with Cytomegalovirus Infection

PubMed Central

Elwenspoek, Martha M. C.; Sias, Krystel; Hengesch, Xenia; Schaan, Violetta K.; Leenen, Fleur A. D.; Adams, Philipp; Mériaux, Sophie B.; Schmitz, Stephanie; Bonnemberger, Fanny; Ewen, Anouk; Schächinger, Hartmut; Vögele, Claus; Muller, Claude P.; Turner, Jonathan D.

2017-01-01

Early life adversity (ELA) increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences. However, it is unclear what drives ELA-associated immunosenescence and which cells are primarily affected. We investigated different biomarkers of immunosenescence in a healthy subset of the EpiPath cohort. Participants were either parent-reared (Ctrl, n = 59) or had experienced separation from their parents in early childhood and were subsequently adopted (ELA, n = 18). No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood, containing a heterogeneous mixture of immune cells. However, when specifically investigating T cells, we found a higher expression of senescence markers (CD57) in ELA. In addition, senescent T cells (CD57+) in ELA had an increased cytolytic potential compared to senescent cells in controls. With a mediation analysis we demonstrated that cytomegalovirus (CMV) infection, which is an important driving force of immunosenescence, largely accounted for elevated CD57 expression observed in ELA. Leukocyte telomere length may obscure cell-specific immunosenescence; here, we demonstrated that the use of cell surface markers of senescence can be more informative. Our data suggest that ELA may increase the risk of CMV infection in early childhood, thereby mediating the effect of ELA on T cell-specific immunosenescence. Thus, future studies should include CMV as a confounder or selectively investigate CMV seronegative cohorts. PMID:29089944

Explaining the apparent paradox of persistent selection for early flowering.

PubMed

Austen, Emily J; Rowe, Locke; Stinchcombe, John R; Forrest, Jessica R K

2017-08-01

Decades of observation in natural plant populations have revealed pervasive phenotypic selection for early flowering onset. This consistent pattern seems at odds with life-history theory, which predicts stabilizing selection on age and size at reproduction. Why is selection for later flowering rare? Moreover, extensive evidence demonstrates that flowering time can and does evolve. What maintains ongoing directional selection for early flowering? Several non-mutually exclusive processes can help to reconcile the apparent paradox of selection for early flowering. We outline four: selection through other fitness components may counter observed fecundity selection for early flowering; asymmetry in the flowering-time-fitness function may make selection for later flowering hard to detect; flowering time and fitness may be condition-dependent; and selection on flowering duration is largely unaccounted for. In this Viewpoint, we develop these four mechanisms, and highlight areas where further study will improve our understanding of flowering-time evolution. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Early-season avian deaths from West Nile virus as warnings of human infection

USGS Publications Warehouse

Guptill, S.C.; Julian, K.G.; Campbell, G.L.; Price, S.D.; Marfin, A.A.

2003-01-01

An analysis of 2001 and 2002 West Nile virus (WNV) surveillance data shows that counties that report WNV-infected dead birds early in the transmission season are more likely to report subsequent WNV disease cases in humans than are counties that do not report early WNV-infected dead birds.

Mountain lions prey selectively on prion-infected mule deer

PubMed Central

Krumm, Caroline E.; Conner, Mary M.; Hobbs, N. Thompson; Hunter, Don O.; Miller, Michael W.

2010-01-01

The possibility that predators choose prey selectively based on age or condition has been suggested but rarely tested. We examined whether mountain lions (Puma concolor) selectively prey upon mule deer (Odocoileus hemionus) infected with chronic wasting disease, a prion disease. We located kill sites of mountain lions in the northern Front Range of Colorado, USA, and compared disease prevalence among lion-killed adult (≥2 years old) deer with prevalence among sympatric deer taken by hunters in the vicinity of kill sites. Hunter-killed female deer were less likely to be infected than males (odds ratios (OR) = 0.2, 95% confidence intervals (CI) = 0.1–0.6; p = 0.015). However, both female (OR = 8.5, 95% CI = 2.3–30.9) and male deer (OR = 3.2, 95% CI = 1–10) killed by a mountain lion were more likely to be infected than same-sex deer killed in the vicinity by a hunter (p < 0.001), suggesting that mountain lions in this area actively selected prion-infected individuals when targeting adult mule deer as prey items. PMID:19864271

The Importance of First Impressions: Early Events in Mycobacterium tuberculosis Infection Influence Outcome.

PubMed

Cadena, Anthony M; Flynn, JoAnne L; Fortune, Sarah M

2016-04-05

Tuberculosis remains a major health threat in much of the world. New vaccines against Mycobacterium tuberculosis are essential for preventing infection, disease, and transmission. However, the host immune responses that need to be induced by an effective vaccine remain unclear. Increasingly, it has become clear that early events in infection are of major importance in the eventual outcome of the infection. Studying such events in humans is challenging, as they occur within the lung and thoracic lymph nodes, and any clinical signs of early infection are relatively nonspecific. Nonetheless, clinical studies and animal models of tuberculosis have provided new insights into the local events that occur in the first few weeks of tuberculosis. Development of an effective vaccine requires a clear understanding of the successful (and detrimental) early host responses against M. tuberculosis, with the goal to improve upon natural immune responses and prevent infection or disease. Copyright © 2016 Cadena et al.

Cytokine expression during early and late phase of acute Puumala hantavirus infection

PubMed Central

2011-01-01

Background Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. Results We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa . Conclusion High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection

Health Selection, Migration, and HIV Infection in Malawi.

PubMed

Anglewicz, Philip; VanLandingham, Mark; Manda-Taylor, Lucinda; Kohler, Hans-Peter

2018-04-27

Despite its importance in studies of migrant health, selectivity of migrants-also known as migration health selection-has seldom been examined in sub-Saharan Africa (SSA). This neglect is problematic because several features of the context in which migration occurs in SSA-very high levels of HIV, in particular-differ from contextual features in regions that have been studied more thoroughly. To address this important gap, we use longitudinal panel data from Malawi to examine whether migrants differ from nonmigrants in pre-migration health, assessed via SF-12 measures of mental and physical health. In addition to overall health selection, we focus on three more-specific factors that may affect the relationship between migration and health: (1) whether migration health selection differs by destination (rural-rural, rural-town, and rural-urban), (2) whether HIV infection moderates the relationship between migration and health, and (3) whether circular migrants differ in pre-migration health status. We find evidence of the healthy migrant phenomenon in Malawi, where physically healthier individuals are more likely to move. This relationship varies by migration destination, with healthier rural migrants moving to urban and other rural areas. We also find interactions between HIV-infected status and health: HIV-infected women moving to cities are physically healthier than their nonmigrant counterparts.

Repression of inflammasome by Francisella tularensis during early stages of infection.

PubMed

Dotson, Rachel J; Rabadi, Seham M; Westcott, Elizabeth L; Bradley, Stephen; Catlett, Sally V; Banik, Sukalyani; Harton, Jonathan A; Bakshi, Chandra Shekhar; Malik, Meenakshi

2013-08-16

Francisella tularensis is an important human pathogen responsible for causing tularemia. F. tularensis has long been developed as a biological weapon and is now classified as a category A agent by the Centers for Disease Control because of its possible use as a bioterror agent. F. tularensis represses inflammasome; a cytosolic multi-protein complex that activates caspase-1 to produce proinflammatory cytokines IL-1β and IL-18. However, the Francisella factors and the mechanisms through which F. tularensis mediates these suppressive effects remain relatively unknown. Utilizing a mutant of F. tularensis in FTL_0325 gene, this study investigated the mechanisms of inflammasome repression by F. tularensis. We demonstrate that muted IL-1β and IL-18 responses generated in macrophages infected with F. tularensis live vaccine strain (LVS) or the virulent SchuS4 strain are due to a predominant suppressive effect on TLR2-dependent signal 1. Our results also demonstrate that FTL_0325 of F. tularensis impacts proIL-1β expression as early as 2 h post-infection and delays activation of AIM2 and NLRP3-inflammasomes in a TLR2-dependent fashion. An enhanced activation of caspase-1 and IL-1β observed in FTL_0325 mutant-infected macrophages at 24 h post-infection was independent of both AIM2 and NLRP3. Furthermore, F. tularensis LVS delayed pyroptotic cell death of the infected macrophages in an FTL_0325-dependent manner during the early stages of infection. In vivo studies in mice revealed that suppression of IL-1β by FTL_0325 early during infection facilitates the establishment of a fulminate infection by F. tularensis. Collectively, this study provides evidence that F. tularensis LVS represses inflammasome activation and that F. tularensis-encoded FTL_0325 mediates this effect.

Repression of Inflammasome by Francisella tularensis during Early Stages of Infection*

PubMed Central

Dotson, Rachel J.; Rabadi, Seham M.; Westcott, Elizabeth L.; Bradley, Stephen; Catlett, Sally V.; Banik, Sukalyani; Harton, Jonathan A.; Bakshi, Chandra Shekhar; Malik, Meenakshi

2013-01-01

Francisella tularensis is an important human pathogen responsible for causing tularemia. F. tularensis has long been developed as a biological weapon and is now classified as a category A agent by the Centers for Disease Control because of its possible use as a bioterror agent. F. tularensis represses inflammasome; a cytosolic multi-protein complex that activates caspase-1 to produce proinflammatory cytokines IL-1β and IL-18. However, the Francisella factors and the mechanisms through which F. tularensis mediates these suppressive effects remain relatively unknown. Utilizing a mutant of F. tularensis in FTL_0325 gene, this study investigated the mechanisms of inflammasome repression by F. tularensis. We demonstrate that muted IL-1β and IL-18 responses generated in macrophages infected with F. tularensis live vaccine strain (LVS) or the virulent SchuS4 strain are due to a predominant suppressive effect on TLR2-dependent signal 1. Our results also demonstrate that FTL_0325 of F. tularensis impacts proIL-1β expression as early as 2 h post-infection and delays activation of AIM2 and NLRP3-inflammasomes in a TLR2-dependent fashion. An enhanced activation of caspase-1 and IL-1β observed in FTL_0325 mutant-infected macrophages at 24 h post-infection was independent of both AIM2 and NLRP3. Furthermore, F. tularensis LVS delayed pyroptotic cell death of the infected macrophages in an FTL_0325-dependent manner during the early stages of infection. In vivo studies in mice revealed that suppression of IL-1β by FTL_0325 early during infection facilitates the establishment of a fulminate infection by F. tularensis. Collectively, this study provides evidence that F. tularensis LVS represses inflammasome activation and that F. tularensis-encoded FTL_0325 mediates this effect. PMID:23821549

Identification of new antigen candidates for the early diagnosis of Mycobacterium avium subsp. paratuberculosis infection in goats.

PubMed

Souriau, Armel; Freret, Sandrine; Foret, Benjamin; Willemsen, Peter T J; Bakker, Douwe; Guilloteau, Laurence A

2017-12-01

Currently Mycobacterium avium subsp. paratuberculosis (MAP) infection is diagnosed through indirect tests based on the immune response induced by the infection. The antigens commonly used in IFN-γ release assays (IGRA) are purified protein derivative tuberculins (PPD). However, PPDs, lack both specificity (Sp) and sensitivity (Se) in the early phase of infection. This study investigated the potential of 16 MAP recombinant proteins and five lipids to elicit the release of IFN-γ in goats from herds with or without a history of paratuberculosis. Ten recombinant proteins were selected as potential candidates for the detection of MAP infection in young goats. They were found to detect 25 to 75% of infected shedder (IS) and infected non-shedder (INS) kids younger than 10months of age. In comparison, PPD was shown to detect only 10% of INS and no IS kids. For seven antigens, Se (21-33%) and Sp (≥90%) of IGRA were shown to be comparable with PPD at 20months old. Only three antigens were suitable candidates to detect IS adult goats, although Se was lower than that obtained with PPD. In paratuberculosis-free herds, IGRA results were negative in 97% of indoor goats and 86% of outdoor goats using the 10 antigens. However, 22 to 44% of one-year-old outdoor goats were positive suggesting that they may be infected. In conclusion, this study showed that ten MAP recombinant proteins are potential candidates for early detection of MAP infected goats. Combining these antigens could form a possible set of MAP antigens to optimize the Se of caprine IGRA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Infections complicating cirrhosis.

PubMed

Piano, Salvatore; Brocca, Alessandra; Mareso, Sara; Angeli, Paolo

2018-02-01

Patients with cirrhosis have a high risk of bacterial infections. Bacterial infections induce systemic inflammation that may lead to organ failure and acute-on-chronic liver failure (ACLF) resulting in a high risk of short term mortality. The early diagnosis and treatment of bacterial infections is essential to improve the patient's prognosis. However, in recent years, the spread of multidrug resistant (MDR) bacterial infections has reduced the efficacy of commonly used antibiotics such as third generation cephalosporins. In patients at high risk of MDR bacteria, such as those with nosocomial infections, the early administration of broad spectrum antibiotics has been shown to improve the prognosis. However, early de-escalation of antibiotics is recommended to reduce a further increase in antibiotic resistance. Strategies to prevent acute kidney injury and other organ failures should be implemented. Although prophylaxis of bacterial infections with antibiotics improves the prognosis in selected patients, their use should be limited to patients at high risk of developing infections. In this article, we review the pathogenesis and management of bacterial infections in patients with cirrhosis. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease

PubMed Central

Panas, Michael W.; Mao, Rong; Delanoy, Michelle; Flanagan, John J.; Binder, Steven R.; Rebman, Alison W.; Montoya, Jose G.; Soloski, Mark J.; Steere, Allen C.; Dattwyler, Raymond J.; Arnaboldi, Paul M.; Aucott, John N.

2015-01-01

The current standard for laboratory diagnosis of Lyme disease in the United States is serologic detection of antibodies against Borrelia burgdorferi. The Centers for Disease Control and Prevention recommends a two-tiered testing algorithm; however, this scheme has limited sensitivity for detecting early Lyme disease. Thus, there is a need to improve diagnostics for Lyme disease at the early stage, when antibiotic treatment is highly efficacious. We examined novel and established antigen markers to develop a multiplex panel that identifies early infection using the combined sensitivity of multiple markers while simultaneously maintaining high specificity by requiring positive results for two markers to designate a positive test. Ten markers were selected from our initial analysis of 62 B. burgdorferi surface proteins and synthetic peptides by assessing binding of IgG and IgM to each in a training set of Lyme disease patient samples and controls. In a validation set, this 10-antigen panel identified a higher proportion of early-Lyme-disease patients as positive at the baseline or posttreatment visit than two-tiered testing (87.5% and 67.5%, respectively; P < 0.05). Equivalent specificities of 100% were observed in 26 healthy controls. Upon further analysis, positivity on the novel 10-antigen panel was associated with longer illness duration and multiple erythema migrans. The improved sensitivity and comparable specificity of our 10-antigen panel compared to two-tiered testing in detecting early B. burgdorferi infection indicates that multiplex analysis, featuring the next generation of markers, could advance diagnostic technology to better aid clinicians in diagnosing and treating early Lyme disease. PMID:26447113

A parapoxviral virion protein inhibits NF-κB signaling early in infection

PubMed Central

Khatiwada, Sushil; Delhon, Gustavo; Nagendraprabhu, Ponnuraj; Chaulagain, Sabal; Luo, Shuhong; Diel, Diego G.; Flores, Eduardo F.

2017-01-01

Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. Infection with ORFV073 gene deletion virus (OV-IA82Δ073) led to increased accumulation of NF-κB essential modulator (NEMO), marked phosphorylation of IκB kinase (IKK) subunits IKKα and IKKβ, IκBα and NF-κB subunit p65 (NF-κB-p65), and to early nuclear translocation of NF-κB-p65 in virus-infected cells (≤ 30 min post infection). Expression of ORFV073 alone was sufficient to inhibit TNFα induced activation of the NF-κB signaling in uninfected cells. Consistent with observed inhibition of IKK complex activation, ORFV073 interacted with the regulatory subunit of the IKK complex NEMO. Infection of sheep with OV-IA82Δ073 led to virus attenuation, indicating that ORFV073 is a virulence determinant in the natural host. Notably, ORFV073 represents the first poxviral virion-associated NF-κB inhibitor described, highlighting the significance of viral inhibition of NF-κB signaling very early in infection. PMID:28787456

Media ideals and early adolescents' body image: Selective avoidance or selective exposure?

PubMed

Rousseau, Ann; Eggermont, Steven

2018-06-05

The present study combines selective exposure theory with body image coping literature to study effects of media internalization in early adolescence. The main objective was to explore how early adolescents selectively internalize media body ideals to manage their body image. To examine the role of media internalization in early adolescents' body image management, we used two-wave panel data (N Wave1  = 1986) gathered among 9- to 14-year-olds. Structural equation analyses indicated that media internalization (Wave 1) positively related to body surveillance (Wave 2). Body surveillance (Wave 2), in turn, was associated with more body image self-discrepancy (Wave 2). In addition, body image self-discrepancy (Wave 1) related to higher body surveillance (Wave 1). Body surveillance, in turn, related to more media internalization cross-sectionally, but less media internalization six months later. Taken together, these results suggest a role for media internalization in early adolescents' body image management. Theoretical and practical implications are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Changes in plasma protein levels as an early indication of a bloodstream infection

PubMed Central

Joenväärä, Sakari; Kaartinen, Johanna; Järvinen, Asko; Renkonen, Risto

2017-01-01

Blood culture is the primary diagnostic test performed in a suspicion of bloodstream infection to detect the presence of microorganisms and direct the treatment. However, blood culture is slow and time consuming method to detect blood stream infections or separate septic and/or bacteremic patients from others with less serious febrile disease. Plasma proteomics, despite its challenges, remains an important source for early biomarkers for systemic diseases and might show changes before direct evidence from bacteria can be obtained. We have performed a plasma proteomic analysis, simultaneously at the time of blood culture sampling from ten blood culture positive and ten blood culture negative patients, and quantified 172 proteins with two or more unique peptides. Principal components analysis, Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) and ROC curve analysis were performed to select protein(s) features which can classify the two groups of samples. We propose a number of candidates which qualify as potential biomarkers to select the blood culture positive cases from negative ones. Pathway analysis by two methods revealed complement activation, phagocytosis pathway and alterations in lipid metabolism as enriched pathways which are relevant for the condition. Data are available via ProteomeXchange with identifier PXD005022. PMID:28235076

Early life socioeconomic position and immune response to persistent infections among elderly Latinos.

PubMed

Meier, Helen C S; Haan, Mary N; Mendes de Leon, Carlos F; Simanek, Amanda M; Dowd, Jennifer B; Aiello, Allison E

2016-10-01

Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T. gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age. Copyright © 2016 Elsevier Ltd. All rights

Examination of the early infection stages of koi herpesvirus (KHV) in experimentally infected carp, Cyprinus carpio L. using in situ hybridization.

PubMed

Monaghan, S J; Thompson, K D; Adams, A; Kempter, J; Bergmann, S M

2015-05-01

Koi herpesvirus (KHV) causes a highly infectious disease afflicting common carp and koi, Cyprinus carpio L. Various molecular and antibody-based detection methods have been used to elucidate the rapid attachment and dissemination of the virus throughout carp tissues, facilitating ongoing development of effective diagnostic approaches. In situ hybridization (ISH) was used here to determine the target tissues of KHV during very early infection, after infecting carp with a highly virulent KHV isolate. Analysis of paraffin-embedded tissues (i.e. gills, skin, spleen, kidney, gut, liver and brain) during the first 8 h and following 10 days post-infection (hpi; dpi) revealed positive signals in skin mucus, gills and gut sections after only 1 hpi. Respiratory epithelial cells were positive as early as 2 hpi. Viral DNA was also detected within blood vessels of various tissues early in the infection. Notable increases in signal abundance were observed in the gills and kidney between 5 and 10 dpi, and viral DNA was detected in all tissues except brain. This study suggests that the gills and gut play an important role in the early pathogenesis of this Alloherpesvirus, in addition to skin, and demonstrates ISH as a useful diagnostic tool for confirmation of acutely infected carp. © 2014 John Wiley & Sons Ltd.

HIV Trafficking Between Blood and Semen During Early Untreated HIV Infection.

PubMed

Chaillon, Antoine; Smith, Davey M; Vanpouille, Christophe; Lisco, Andrea; Jordan, Parris; Caballero, Gemma; Vargas, Milenka; Gianella, Sara; Mehta, Sanjay R

2017-01-01

Understanding the dynamics of HIV across anatomic compartments is important to design effective eradication strategies. In this study, we evaluated viral trafficking between blood and semen during primary HIV infection in 6 antiretroviral-naive men who have sex with men. Deep sequencing data of HIV env were generated from longitudinal blood plasma, peripheral blood mononuclear cells, and seminal plasma samples. The presence or absence of viral compartmentalization was assessed using tree-based Slatkin-Maddison and distance-based Fst methods. Phylogeographic analyses were performed using a discrete Bayesian asymmetric approach of diffusion with Markov jump count estimation to evaluate the gene flow between blood and semen during primary HIV infection. Levels of DNA from human herpesviruses and selected inflammatory cytokines were also measured on genital secretions collected at baseline to evaluate potential correlates of increased viral migration between anatomic compartments. We detected varying degrees of compartmentalization in all 6 individuals evaluated. None of them maintained viral compartmentalization between blood and seminal plasma throughout the analyzed time points. Phylogeographic analyses revealed that the HIV population circulating in blood plasma populated the seminal compartment during the earliest stages of infection. In our limited data set, we found no association between local inflammation or herpesvirus shedding at baseline and viral trafficking between semen and blood. The early spread of virus from blood plasma to genital tract and the complex viral interplay between these compartments suggest that viral eradication efforts will require monitoring viral subpopulations in anatomic sites and viral trafficking during the course of infection.

The neutralizing role of IgM during early Chikungunya virus infection

PubMed Central

Chua, Chong-Long; Chiam, Chun-Wei; Chan, Yoke-Fun

2017-01-01

The antibody isotype IgM appears earlier than IgG, within days of onset of symptoms, and is important during the early stages of the adaptive immune response. Little is known about the functional role of IgM during infection with chikungunya virus (CHIKV), a recently reemerging arbovirus that has caused large global outbreaks. In this study, we studied antibody responses in 102 serum samples collected during CHIKV outbreaks in Malaysia. We described the neutralizing role of IgM at different times post-infection and examined the independent contributions of IgM and IgG towards the neutralizing capacity of human immune sera during the early phase of infection, including the differences in targets of neutralizing epitopes. Neutralizing IgM starts to appear as early as day 4 of symptoms, and their appearance from day 6 is associated with a reduction in viremia. IgM acts in a complementary manner with the early IgG, but plays the main neutralizing role up to a point between days 4 and 10 which varies between individuals. After this point, total neutralizing capacity is attributable almost entirely to the robust neutralizing IgG response. IgM preferentially binds and targets epitopes on the CHIKV surface E1-E2 glycoproteins, rather than individual E1 or E2. These findings provide insight into the early antibody responses to CHIKV, and have implications for design of diagnostic serological assays. PMID:28182795

Plasma Viral Loads During Early HIV-1 Infection Are Similar in Subtype C– and Non-Subtype C–Infected African Seroconverters

PubMed Central

Campbell, Mary S.; Kahle, Erin M.; Celum, Connie; Lingappa, Jairam R.; Kapiga, Saidi; Mujugira, Andrew; Mugo, Nelly R.; Fife, Kenneth H.; Mullins, James I.; Baeten, Jared M.; Celum, Connie; Wald, Anna; Lingappa, Jairam; Baeten, Jared M.; Campbell, Mary S.; Corey, Lawrence; Coombs, Robert W.; Hughes, James P.; Magaret, Amalia; McElrath, M. Juliana; Morrow, Rhoda; Mullins, James I.; Coetzee, David; Fife, Kenneth; Were, Edwin; Essex, Max; Makhema, Joseph; Katabira, Elly; Ronald, Allan; Allen, Susan; Kayitenkore, Kayitesi; Karita, Etienne; Bukusi, Elizabeth; Cohen, Craig; Allen, Susan; Kanweka, William; Allen, Susan; Vwalika, Bellington; Kapiga, Saidi; Manongi, Rachel; Farquhar, Carey; John-Stewart, Grace; Kiarie, James; Allen, Susan; Inambao, Mubiana; Farm, Orange; Delany-Moretlwe, Sinead; Rees, Helen; de Bruyn, Guy; Gray, Glenda; McIntyre, James; Mugo, Nelly Rwamba

2013-01-01

Recent data suggest that infection with human immunodeficiency virus type 1 (HIV-1) subtype C results in prolonged high-level viremia (>5 log10 copies/mL) during early infection. We examined the relationship between HIV-1 subtype and plasma viremia among 153 African seroconverters. Mean setpoint viral loads were similar for C and non-C subtypes: 4.36 vs 4.42 log10 copies/mL (P = .61). The proportion of subtype C–infected participants with viral loads >5 log10 copies/mL was not greater than the proportion for those with non-C infection. Our data do not support the hypothesis that higher early viral load accounts for the rapid spread of HIV-1 subtype C in southern Africa. PMID:23315322

Innate Immunity to Respiratory Infection in Early Life

PubMed Central

Lambert, Laura; Culley, Fiona J.

2017-01-01

Early life is a period of particular susceptibility to respiratory infections and symptoms are frequently more severe in infants than in adults. The neonatal immune system is generally held to be deficient in most compartments; responses to innate stimuli are weak, antigen-presenting cells have poor immunostimulatory activity and adaptive lymphocyte responses are limited, leading to poor immune memory and ineffective vaccine responses. For mucosal surfaces such as the lung, which is continuously exposed to airborne antigen and to potential pathogenic invasion, the ability to discriminate between harmless and potentially dangerous antigens is essential, to prevent inflammation that could lead to loss of gaseous exchange and damage to the developing lung tissue. We have only recently begun to define the differences in respiratory immunity in early life and its environmental and developmental influences. The innate immune system may be of relatively greater importance than the adaptive immune system in the neonatal and infant period than later in life, as it does not require specific antigenic experience. A better understanding of what constitutes protective innate immunity in the respiratory tract in this age group and the factors that influence its development should allow us to predict why certain infants are vulnerable to severe respiratory infections, design treatments to accelerate the development of protective immunity, and design age specific adjuvants to better boost immunity to infection in the lung. PMID:29184555

Lack of viral selection in human immunodeficiency virus type 1 mother-to-child transmission with primary infection during late pregnancy and/or breastfeeding.

PubMed

Ceballos, Ana; Andreani, Guadalupe; Ripamonti, Chiara; Dilernia, Dario; Mendez, Ramiro; Rabinovich, Roberto D; Cárdenas, Patricia Coll; Zala, Carlos; Cahn, Pedro; Scarlatti, Gabriella; Martínez Peralta, Liliana

2008-11-01

Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) as described for women with an established infection is, in most cases, associated with the transmission of few maternal variants. This study analysed virus variability in four cases of maternal primary infection occurring during pregnancy and/or breastfeeding. Estimated time of seroconversion was at 4 months of pregnancy for one woman (early seroconversion) and during the last months of pregnancy and/or breastfeeding for the remaining three (late seroconversion). The C2V3 envelope region was analysed in samples of mother-child pairs by molecular cloning and sequencing. Comparisons of nucleotide and amino acid sequences as well as phylogenetic analysis were performed. The results showed low variability in the virus population of both mother and child. Maximum-likelihood analysis showed that, in the early pregnancy seroconversion case, a minor viral variant with further evolution in the child was transmitted, which could indicate a selection event in MTCT or a stochastic event, whereas in the late seroconversion cases, the mother's and child's sequences were intermingled, which is compatible with the transmission of multiple viral variants from the mother's major population. These results could be explained by the less pronounced selective pressure exerted by the immune system in the early stages of the mother's infection, which could play a role in MTCT of HIV-1.

Operative treatment of early infection after internal fixation of limb fractures (exclusive of severe open fractures).

PubMed

Bonnevialle, P

2017-02-01

Early infection after open reduction and internal fixation (ORIF) of a limb bone is defined as bacteriologically documented, deep and/or superficial surgical-site infection (SSI) diagnosed within 6months after the surgical procedure. This interval is arbitrarily considered sufficient to obtain fracture healing. The treatment of early infection after ORIF should be decided by a multidisciplinary team. The principles are the same as for revision arthroplasty. Superficial SSIs should be differentiated from deep SSIs, based on the results of bacteriological specimens collected using flawless technique. A turning point in the local microbial ecology occurs around the third or fourth week, when a biofilm develops around metallic implants. This biofilm protects the bacteria. The treatment relies on both non-operative and operative measures, which are selected based on the time to occurrence of the infection, condition of the soft tissues, and stage of bone healing. Both the surgical strategy and the antibiotic regimen should be determined during a multidisciplinary discussion. When treating superficial SSIs after ORIF, soft-tissue management is the main challenge. The treatment differs according to whether the hardware is covered or exposed. Defects in the skin and/or fascia can be managed using reliable reconstructive surgery techniques, either immediately or after a brief period of vacuum-assisted closure. In deep SSIs, deciding whether to leave or to remove the hardware is difficult. If the hardware is removed, the fracture site can be stabilised provisionally using either external fixation or a cement rod. Once infection control is achieved, several measures can be taken to stimulate bone healing before the end of the classical 6-month interval. If the hardware was removed, then internal fixation must be performed once the infection is eradicated. Copyright © 2016. Published by Elsevier Masson SAS.

Early HIV Infections Among Men Who Have Sex with Men in Five Cities in the United States

PubMed Central

Smith, A.; Masciotra, S.; Zhang, W.; Bingham, T.; Flynn, C.; German, D.; Al-Tayyib, A.; Magnus, M.; LaLota, M.; Rose, C. E.; Owen, S. M.

2016-01-01

We tested blood samples from men who have sex with men (MSM) to detect early HIV infection. Early HIV included both acute (infected past 30 days) and recent (estimated recency past 240 days). Acute infections were defined as screen immunoassay (IA) negative/NAAT-positive or IA-positive/Multispot-negative/NAAT-positive. Recent infections were defined as avidity index cutoff <30 % on an avidity-based IA and, (1) not reporting antiretroviral therapy use or, (2) HIV RNA >150 copies/mL. Of 937 samples, 26 % (244) were HIV-infected and of these 5 % (12) were early. Of early infections, 2 were acute and 10 recent; most (8/12) were among black MSM. Early infection was associated with last partner of black race [adjusted relative risk (ARR) = 4.6, confidence intervals (CI) 1.2–17.3], receptive anal sex at last sex (ARR = 4.3, CI 1.2–15.0), and daily Internet use to meet partners/ friends (ARR = 3.3, CI 1.1–9.7). Expanding prevention and treatment for black MSM will be necessary for reducing incidence in the United States. PMID:25680518

Cytomegalovirus infection in early childhood may be protective against glioblastoma multiforme, while later infection is a risk factor.

PubMed

Lehrer, Steven

2012-05-01

Glioblastoma multiforme is the most common and most aggressive type of primary brain tumor, accounting for 52% of all primary brain tumor cases and 20% of all intracranial tumors. Recently, evidence for a viral cause has been postulated, possibly cytomegalovirus (CMV). In one report, 80% of patients with newly diagnosed glioblastoma multiforme had detectable cytomegalovirus DNA in their peripheral blood, while sero-positive normal donors and other surgical patients did not exhibit detectable virus. However, another study reported that five glioblastoma patients showed no circulating CMV detected either with RT-PCR or blood culture. But CMV could still be a factor in the genesis of glioblastoma multiforme, if age at infection is taken into account, since the incidence of both glioblastoma multiforme and CMV infection are inversely related to socioeconomic status. CMV infection in early childhood, more common in lower socioeconomic groups, may be protective against glioblastoma multiforme, whereas CMV infection in later childhood or adulthood may be a risk factor for glioblastoma. If so, glioblastoma multiforme occurrence would resemble paralytic polio, where low socioeconomic status, poor hygiene and early infection are protective. Copyright © 2012 Elsevier Ltd. All rights reserved.

Selectivity in early prosocial behavior

PubMed Central

Kuhlmeier, Valerie A.; Dunfield, Kristen A.; O’Neill, Amy C.

2014-01-01

Prosocial behavior requires expenditure of personal resources for the benefit of others, a fact that creates a “problem” when considering the evolution of prosociality. Models that address this problem have been developed, with emphasis typically placed on reciprocity. One model considers the advantages of being selective in terms of one’s allocation of prosocial behavior so as to improve the chance that one will be benefitted in return. In this review paper, we first summarize this “partner choice” model and then focus on prosocial development in the preschool years, where we make the case for selective partner choice in early instances of human prosocial behavior. PMID:25120526

Breastfeeding and early infection in the aetiology of childhood leukaemia in Down syndrome.

PubMed

Flores-Lujano, J; Perez-Saldivar, M L; Fuentes-Pananá, E M; Gorodezky, C; Bernaldez-Rios, R; Del Campo-Martinez, M A; Martinez-Avalos, A; Medina-Sanson, A; Paredes-Aguilera, R; De Diego-Flores Chapa, J; Bolea-Murga, V; Rodriguez-Zepeda, M C; Rivera-Luna, R; Palomo-Colli, M A; Romero-Guzman, L; Perez-Vera, P; Alvarado-Ibarra, M; Salamanca-Gómez, F; Fajardo-Gutierrez, A; Mejía-Aranguré, J M

2009-09-01

For a child to develop acute leukaemia (AL), environmental exposure may not be sufficient: interaction with a susceptibility factor to the disease, such as Down syndrome (DS), may also be necessary. We assessed whether breastfeeding and early infection were associated with the risk of developing AL in children with DS. Children with DS in Mexico City, and either with or without AL, were the cases (N=57) and controls (N=218), respectively. Population was divided in children with AL and with acute lymphoblastic leukaemia (ALL) and also in children < or = 6 and >6 years old. Breastfeeding and early infections showed moderate (but not significant) association for AL, whereas hospitalisation by infection during the first year of life increased the risk: odds ratios (confidence interval 95%) were 0.84 (0.43-1.61), 1.70 (0.82-3.52); and 3.57 (1.59-8.05), respectively. A similar result was obtained when only ALL was analysed. We found that breastfeeding was a protective factor for developing AL and ALL, and during the first year of life, infections requiring hospitalisation were related to a risk for developing the disease in those children with DS >6 years of age. These data do not support the Greaves's hypothesis of early infection being protective for developing ALL.

Alternate promoter selection within a human cytomegalovirus immediate-early and early transcription unit (UL119-115) defines true late transcripts containing open reading frames for putative viral glycoproteins.

PubMed Central

Leatham, M P; Witte, P R; Stinski, M F

1991-01-01

The human cytomegalovirus open reading frames (ORFs) UL119 through UL115 (UL119-115) are located downstream of the immediate-early 1 and 2 transcription units. The promoter upstream of UL119 is active at all times after infection and drives the synthesis of a spliced 3.1-kb mRNA. The viral mRNA initiates in UL119, contains UL119-117 and UL116, and terminates just downstream of UL115. True late transcripts that are detected only after viral DNA synthesis originate from this transcription unit. True late mRNAs of 2.1 kb, containing ORFs UL116 and UL115, and 1.2 kb, containing ORF UL115 only, are synthesized. The true late viral mRNAs are 3' coterminal with the 3.1-kb mRNA. This transcription unit is an example of late promoters nested within an immediate-early-early transcription unit. The gene products of UL119-117, UL116, and UL115 are predicted to be glycoproteins. Efficient expression of the downstream ORFs at late times after infection may be related to alternate promoter usage and downstream cap site selection. Images PMID:1717716

The bradykinin B2 receptor in the early immune response against Listeria infection.

PubMed

Kaman, Wendy E; Wolterink, Arthur F W M; Bader, Michael; Boele, Linda C L; van der Kleij, Desiree

2009-02-01

The endogenous danger signal bradykinin was recently found implicated in the development of immunity against parasites via dendritic cells. We here report an essential role of the B(2) (B(2)R) bradykinin receptor in the early immune response against Listeria infection. Mice deficient in B(2)R (B(2)R(-/-) mice) were shown to suffer from increased hepatic bacterial burden and concomitant dramatic weight loss during infection with Listeria monocytogenes. Levels of cytokines known to play a pivotal role in the early phase immune response against L. monocytogenes, IL-12p70 and IFN-gamma, were reduced in B(2)R(-/-) mice. To extend these findings to the human system, we show that bradykinin potentiates the production of IL-12p70 in human monocyte-derived dendritic cells. Thus, we show that bradykinin and the B(2)R play a role in early innate immune functions during bacterial infection.

CHANGES IN HUMORAL IMMUNITY OCCURRING DURING THE EARLY STAGES OF EXPERIMENTAL PNEUMOCOCCUS INFECTION

PubMed Central

Terrell, Edward E.

1930-01-01

A study was made of the changes in humoral immunity occurring during the early phases of experimental pneumococcus infection in the dog and cat. The methods devised by Robertson and Sia were employed to demonstrate the presence of anti-pneumococcus properties in the serum of animals naturally resistant to this micro-organism. It was found that with a generalized and overwhelming infection accompanied by early blood invasion, there was a prompt and rapid decrease in the concentration of natural humoral immune bodies which frequently disappeared entirely by the time of death. This same early diminution of humoral immune substances, opsonins, agglutinins, and pneumococcidal-promoting bodies was observed in animals that survived a moderately severe generalized infection but the concentration of immune bodies rose again with the onset of recovery. The decrease in concentration of humoral immune substances during a severe generalized infection appeared to be due to the combination of "S" substance with the normal immune bodies. When the pneumococcus infection was more localized as in the case of true lobar pneumonia a quite different sequence of events was observed to occur. Several animals, in which extensive lobar pneumonia was produced, showed the presence in quantity of humoral immune bodies in the blood throughout the course of an infection terminating fatally. These findings suggest that after the inception of pneumococcus infection in the dog and cat the chief function of natural anti-pneurnococcus substances in the blood is to limit or prevent blood invasion. When pneumococcic infection is localized these circulating antibodies appear to have little effect either in preventing the spread of the process or determining the outcome of the disease. PMID:19869701

Risk of Early-Onset Neonatal Infection with Maternal Infection or Colonization: A Global Systematic Review and Meta-Analysis

PubMed Central

Chan, Grace J.; Lee, Anne CC; Baqui, Abdullah H.; Tan, Jingwen; Black, Robert E.

2013-01-01

Background Neonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections) in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period. Methods and Findings We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4%) were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9–11.2). Newborns of mothers with colonization had a 9.4 (95% CI 3.1–28.5) times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM) had a 2.3 (95% CI 1.0–5.4) times higher odds of infection than newborns of mothers without risk factors. Conclusions Neonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high

T-DNA-genome junctions form early after infection and are influenced by the chromatin state of the host genome

PubMed Central

Tripathi, Pooja; Muth, Theodore R.

2017-01-01

Agrobacterium tumefaciens mediated T-DNA integration is a common tool for plant genome manipulation. However, there is controversy regarding whether T-DNA integration is biased towards genes or randomly distributed throughout the genome. In order to address this question, we performed high-throughput mapping of T-DNA-genome junctions obtained in the absence of selection at several time points after infection. T-DNA-genome junctions were detected as early as 6 hours post-infection. T-DNA distribution was apparently uniform throughout the chromosomes, yet local biases toward AT-rich motifs and T-DNA border sequence micro-homology were detected. Analysis of the epigenetic landscape of previously isolated sites of T-DNA integration in Kanamycin-selected transgenic plants showed an association with extremely low methylation and nucleosome occupancy. Conversely, non-selected junctions from this study showed no correlation with methylation and had chromatin marks, such as high nucleosome occupancy and high H3K27me3, that correspond to three-dimensional-interacting heterochromatin islands embedded within euchromatin. Such structures may play a role in capturing and silencing invading T-DNA. PMID:28742090

Early Epstein-Barr Virus Genomic Diversity and Convergence toward the B95.8 Genome in Primary Infection.

PubMed

Weiss, Eric R; Lamers, Susanna L; Henderson, Jennifer L; Melnikov, Alexandre; Somasundaran, Mohan; Garber, Manuel; Selin, Liisa; Nusbaum, Chad; Luzuriaga, Katherine

2018-01-15

populations is a key step in this process, as is the expansion of intrahost genomic variation during infection. We report full-length EBV genomes sequenced from the blood and oral wash of 10 individuals early in primary infection and during convalescence. Our data demonstrate considerable diversity within the pool of circulating EBV strains, as well as within individual patients. Overall viral diversity decreased from early to persistent infection, particularly in latently infected B cells, which serve as the viral reservoir. Reduction in B cell-associated viral genome diversity coincided with a convergence toward a reference-like EBV genotype. Greater convergence positively correlated with time after infection, suggesting that the reference-like genome is the result of selection. Copyright © 2018 American Society for Microbiology.

Identifying Early Target Cells of Nipah Virus Infection in Syrian Hamsters

PubMed Central

Baseler, Laura; Scott, Dana P.; Saturday, Greg; Horne, Eva; Rosenke, Rebecca; Thomas, Tina; Meade-White, Kimberly; Haddock, Elaine; Feldmann, Heinz

2016-01-01

Background Nipah virus causes respiratory and neurologic disease with case fatality rates up to 100% in individual outbreaks. End stage lesions have been described in the respiratory and nervous systems, vasculature and often lymphoid organs in fatal human cases; however, the initial target organs of Nipah virus infection have not been identified. Here, we detected the initial target tissues and cells of Nipah virus and tracked virus dissemination during the early phase of infection in Syrian hamsters inoculated with a Nipah virus isolate from Malaysia (NiV-M) or Bangladesh (NiV-B). Methodology/Principal Findings Syrian hamsters were euthanized between 4 and 48 hours post intranasal inoculation and tissues were collected and analyzed for the presence of viral RNA, viral antigen and infectious virus. Virus replication was first detected at 8 hours post inoculation (hpi). Nipah virus initially targeted type I pneumocytes, bronchiolar respiratory epithelium and alveolar macrophages in the lung and respiratory and olfactory epithelium lining the nasal turbinates. By 16 hpi, virus disseminated to epithelial cells lining the larynx and trachea. Although the pattern of viral dissemination was similar for both virus isolates, the rate of spread was slower for NiV-B. Infectious virus was not detected in the nervous system or blood and widespread vascular infection and lesions within lymphoid organs were not observed, even at 48 hpi. Conclusions/Significance Nipah virus initially targets the respiratory system. Virus replication in the brain and infection of blood vessels in non-respiratory tissues does not occur during the early phase of infection. However, virus replicates early in olfactory epithelium and may serve as the first step towards nervous system dissemination, suggesting that development of vaccines that block virus dissemination or treatments that can access the brain and spinal cord and directly inhibit virus replication may be necessary for preventing central

Identifying Early Target Cells of Nipah Virus Infection in Syrian Hamsters.

PubMed

Baseler, Laura; Scott, Dana P; Saturday, Greg; Horne, Eva; Rosenke, Rebecca; Thomas, Tina; Meade-White, Kimberly; Haddock, Elaine; Feldmann, Heinz; de Wit, Emmie

2016-11-01

Nipah virus causes respiratory and neurologic disease with case fatality rates up to 100% in individual outbreaks. End stage lesions have been described in the respiratory and nervous systems, vasculature and often lymphoid organs in fatal human cases; however, the initial target organs of Nipah virus infection have not been identified. Here, we detected the initial target tissues and cells of Nipah virus and tracked virus dissemination during the early phase of infection in Syrian hamsters inoculated with a Nipah virus isolate from Malaysia (NiV-M) or Bangladesh (NiV-B). Syrian hamsters were euthanized between 4 and 48 hours post intranasal inoculation and tissues were collected and analyzed for the presence of viral RNA, viral antigen and infectious virus. Virus replication was first detected at 8 hours post inoculation (hpi). Nipah virus initially targeted type I pneumocytes, bronchiolar respiratory epithelium and alveolar macrophages in the lung and respiratory and olfactory epithelium lining the nasal turbinates. By 16 hpi, virus disseminated to epithelial cells lining the larynx and trachea. Although the pattern of viral dissemination was similar for both virus isolates, the rate of spread was slower for NiV-B. Infectious virus was not detected in the nervous system or blood and widespread vascular infection and lesions within lymphoid organs were not observed, even at 48 hpi. Nipah virus initially targets the respiratory system. Virus replication in the brain and infection of blood vessels in non-respiratory tissues does not occur during the early phase of infection. However, virus replicates early in olfactory epithelium and may serve as the first step towards nervous system dissemination, suggesting that development of vaccines that block virus dissemination or treatments that can access the brain and spinal cord and directly inhibit virus replication may be necessary for preventing central nervous system pathology.

Arsenic and Immune Response to Infection During Pregnancy and Early Life.

PubMed

Attreed, Sarah E; Navas-Acien, Ana; Heaney, Christopher D

2017-06-01

Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity-including the specific mechanisms in humans-is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines.

Breastfeeding and early infection in the aetiology of childhood leukaemia in Down syndrome

PubMed Central

Flores-Lujano, J; Perez-Saldivar, M L; Fuentes-Pananá, E M; Gorodezky, C; Bernaldez-Rios, R; Del Campo-Martinez, M A; Martinez-Avalos, A; Medina-Sanson, A; Paredes-Aguilera, R; De Diego-Flores Chapa, J; Bolea-Murga, V; Rodriguez-Zepeda, M C; Rivera-Luna, R; Palomo-Colli, M A; Romero-Guzman, L; Perez-Vera, P; Alvarado-Ibarra, M; Salamanca-Gómez, F; Fajardo-Gutierrez, A; Mejía-Aranguré, J M

2009-01-01

Background: For a child to develop acute leukaemia (AL), environmental exposure may not be sufficient: interaction with a susceptibility factor to the disease, such as Down syndrome (DS), may also be necessary. We assessed whether breastfeeding and early infection were associated with the risk of developing AL in children with DS. Methods: Children with DS in Mexico City, and either with or without AL, were the cases (N=57) and controls (N=218), respectively. Population was divided in children with AL and with acute lymphoblastic leukaemia (ALL) and also in children ⩽6 and >6 years old. Results: Breastfeeding and early infections showed moderate (but not significant) association for AL, whereas hospitalisation by infection during the first year of life increased the risk: odds ratios (confidence interval 95%) were 0.84 (0.43–1.61), 1.70 (0.82–3.52); and 3.57 (1.59–8.05), respectively. A similar result was obtained when only ALL was analysed. Conclusion: We found that breastfeeding was a protective factor for developing AL and ALL, and during the first year of life, infections requiring hospitalisation were related to a risk for developing the disease in those children with DS >6 years of age. These data do not support the Greaves's hypothesis of early infection being protective for developing ALL. PMID:19707206

Microaspiration of Solanum tuberosum root cells at early stages of infection by Globodera pallida.

PubMed

Kooliyottil, Rinu; Dandurand, Louise-Marie; Kuhl, Joseph C; Caplan, Allan; Xiao, Fangming

2017-01-01

Sedentary endoparasitic cyst nematodes form a feeding structure in plant roots, called a syncytium. Syncytium formation involves extensive transcriptional modifications, which leads to cell modifications such as increased cytoplasmic streaming, enlarged nuclei, increased numbers of organelles, and replacement of a central vacuole by many small vacuoles. When whole root RNA is isolated and analyzed, transcript changes manifested in the infected plant cells are overshadowed by gene expression from cells of the entire root system. Use of microaspiration allows isolation of the content of nematode infected cells from a heterogeneous cell population. However, one challenge with this method is identifying the nematode infected cells under the microscope at early stages of infection. This problem was addressed by staining nematode juveniles with a fluorescent dye prior to infection so that the infected cells could be located and microaspirated. In the present study, we used the fluorescent vital stain PKH26 coupled with a micro-rhizosphere chamber to locate the infected nematode Globodera pallida in Solanum tuberosum root cells. This enabled microaspiration of nematode-infected root cells during the early stages of parasitism. To study the transcriptional events occurring in these cells, an RNA isolation method from microaspirated samples was optimized, and subsequently the RNA was purified using magnetic beads. With this method, we obtained an RNA quality number of 7.8. For transcriptome studies, cDNA was synthesized from the isolated RNA and assessed by successfully amplifying several pathogenesis related protein coding genes. The use of PKH26 stained nematode juveniles enabled early detection of nematode infected cells for microaspiration. To investigate transcriptional changes in low yielding RNA samples, bead-based RNA extraction procedures minimized RNA degradation and provided high quality RNA. This protocol provides a robust procedure to analyze gene expression in

Eradication of early P. aeruginosa infection in children <7 years of age with cystic fibrosis: The early study.

PubMed

Ratjen, Felix; Moeller, Alexander; McKinney, Martha L; Asherova, Irina; Alon, Nipa; Maykut, Robert; Angyalosi, Gerhild

2018-04-20

Antibiotic eradication treatment is the standard-of-care for cystic fibrosis (CF) patients with early Pseudomonas aeruginosa (Pa)-infection; however, evidence from placebo-controlled trials is limited. This double-blind, placebo-controlled trial randomised CF patients <7 years (N = 51) with early Pa-infection to tobramycin inhalation solution (TOBI 300 mg) or placebo (twice daily) for 28 days with an optional cross-over on Day 35. Primary endpoint was proportion of patients having throat swabs/sputum free of Pa on Day 29. On Day 29, 84.6% patients in the TOBI versus 24.0% in the placebo group were Pa-free (p < 0.001). At the end of the cross-over period, 76.0% patients receiving TOBI in the initial 28 days were Pa-free compared to 47.8% receiving placebo initially. Adverse events were consistent with the TOBI safety profile with no differences between TOBI and placebo. TOBI was effective in eradicating early Pa-infection with a favourable safety profile in young CF patients. NCT01082367. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection.

PubMed

Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu

2017-03-01

Little research focuses on the association between immune thrombocytopenic purpura and human immunodeficiency virus infection in Taiwan. This study investigated whether immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection in Taiwan. We conducted a retrospective population-based cohort study using data of individuals enrolled in Taiwan National Health Insurance Program. There were 5472 subjects aged 1-84 years with a new diagnosis of immune thrombocytopenic purpura as the purpura group since 1998-2010 and 21,887 sex-matched and age-matched, randomly selected subjects without immune thrombocytopenic purpura as the non-purpura group. The incidence of human immunodeficiency virus infection at the end of 2011 was measured in both groups. We used the multivariable Cox proportional hazards regression model to measure the hazard ratio and 95 % confidence interval (CI) for the association between immune thrombocytopenic purpura and human immunodeficiency virus infection. The overall incidence of human immunodeficiency virus infection was 6.47-fold higher in the purpura group than that in the non-purpura group (3.78 vs. 0.58 per 10,000 person-years, 95 % CI 5.83-7.18). After controlling for potential confounding factors, the adjusted HR of human immunodeficiency virus infection was 6.3 (95 % CI 2.58-15.4) for the purpura group, as compared with the non-purpura group. We conclude that individuals with immune thrombocytopenic purpura are 6.47-fold more likely to have human immunodeficiency virus infection than those without immune thrombocytopenic purpura. We suggest not all patients, but only those who have risk factors for human immunodeficiency virus infection should receive testing for undiagnosed human immunodeficiency virus infection when they develop immune thrombocytopenic purpura.

Performances of fourth generation HIV antigen/antibody assays on filter paper for detection of early HIV infections.

PubMed

Kania, Dramane; Truong, Tam Nguyen; Montoya, Ana; Nagot, Nicolas; Van de Perre, Philippe; Tuaillon, Edouard

2015-01-01

Point-of-care testing and diagnosis of HIV acute infections play important roles in preventing transmission, but HIV rapid diagnosis tests have poor capacity to detect early infections. Filter paper can be used for capillary blood collection and HIV testing using 4th generation immunoassays. Antigen/antibody combined immunoassays were evaluated for their capacity to identify early HIV infections using filter paper in comparison with rapid test. Thirty nine serum samples collected from HIV seroconverters were spotted onto filter paper and tested by the Roche Elecsys(®) HIV Combi PT test and the DiaSorin Liaison XL Murex HIV Ab/Ag assay. Fourth generation immunoassays identified 34 out of 39 HIV early infections using dried serum spot, whereas the Determine™ HIV-1/2 rapid test detected 24 out of 39 HIV positive serum (87.2% vs 61.5% respectively, p = 0.009). p24 antigen was detected by the Liaison XL in 19 dried serum samples (48.7%). In the group characterized by a negative western blot, 7 out of 8 (87.5%) and 6 out of 8 (75.0%) samples were found positive for HIV using the Elecsys and the Liaison XL, respectively. None of these eight samples classified in this group of early acute infections were found positive by the rapid test. Fourth generation Ag/Ab immunoassays performed on dried serum spot had good performance for HIV testing during the early phases of HIV infection. This method may be useful to detect HIV early infections in hard-to-reach populations and individuals living in remote areas before rapid tests become positive. Copyright © 2014 Elsevier B.V. All rights reserved.

Early infection risk with primary versus staged Hemodialysis Reliable Outflow (HeRO) graft implantation.

PubMed

Griffin, Andrew S; Gage, Shawn M; Lawson, Jeffrey H; Kim, Charles Y

2017-01-01

This study evaluated whether the use of a staged Hemodialysis Reliable Outflow (HeRO; Merit Medical, South Jordan, Utah) implantation strategy incurs increased early infection risk compared with conventional primary HeRO implantation. A retrospective review was performed of 192 hemodialysis patients who underwent HeRO graft implantation: 105 patients underwent primary HeRO implantation in the operating room, and 87 underwent a staged implantation where a previously inserted tunneled central venous catheter was used for guidewire access for the venous outflow component. Within the staged implantation group, 32 were performed via an existing tunneled hemodialysis catheter (incidentally staged), and 55 were performed via a tunneled catheter inserted across a central venous occlusion in an interventional radiology suite specifically for HeRO implantation (intentionally staged). Early infection was defined as episodes of bacteremia or HeRO infection requiring resection ≤30 days of HeRO implantation. For staged HeRO implantations, the median interval between tunneled catheter insertion and conversion to a HeRO graft was 42 days. The overall HeRO-related infection rate ≤30 days of implantation was 8.6% for primary HeRO implantation and 2.3% for staged implantations (P = .12). The rates of early bacteremia and HeRO resection requiring surgical resection were not significantly different between groups (P = .19 and P = .065, respectively), nor were age, gender, laterality, anastomosis to an existing arteriovenous access, human immunodeficiency virus status, diabetes, steroids, chemotherapy, body mass index, or graft location. None of the patient variables, techniques, or graft-related variables correlated significantly with the early infection rate. The staged HeRO implantation strategy did not result in an increased early infection risk compared with conventional primary implantation and is thus a reasonable strategy for HeRO insertion in hemodialysis patients

[Aging affects early stage direction selectivity of MT cells in rhesus monkeys].

PubMed

Liang, Zhen; Chen, Yue-Ming; Meng, Xue; Wang, Yi; Zhou, Bao-Zhuo; Xie, Ying-Ying; He, Wen-Sheng

2012-10-01

The middle temporal area (MT/V5) plays an important role in motion processing. Neurons in this area have a strongly selective response to the moving direction of objects and as such, the selectivity of MT neurons was proposed to be a neural mechanism for the perception of motion. Our previous studies have found degradation in direction selectivity of MT neurons in old monkeys, but this direction selectivity was calculated during the whole response time and the results were not able to uncover the mechanism of motion perception over a time course. Furthermore, experiments have found that direction selectivity was enhanced by attention at a later stage. Therefore, the response should be excluded in experiments with anesthesia. To further characterize the neural mechanism over a time course, we investigated the age-related changes of direction selectivity in the early stage by comparing the proportions of direction selective MT cells in old and young macaque monkeys using in vivo single-cell recording techniques. Our results show that the proportion of early-stage-direction-selective cells is lower in old monkeys than in young monkeys, and that the early stage direction bias (esDB) of old MT cells decreased relative to young MT cells. Furthermore, the proportion of MT cells having strong early stage direction selectivity in old monkeys was decreased. Accordingly, the functional degradation in the early stage of MT cells may mediate perceptual declines of old primates in visual motion tasks.

Impact of pretransplant rifaximin therapy on early post-liver transplant infections.

PubMed

Esfeh, Jamak Modaresi; Hanouneh, Ibrahim A; Koval, Christine E; Kovacs, Christopher; Dalal, Deepan S; Ansari-Gilani, Kianoush; Confer, Bradley D; Eghtesad, Bijan; Zein, Nizar N; Menon, K V Narayanan

2014-05-01

Bacterial and fungal infections are major causes of morbidity and mortality after liver transplantation (LT). The role of intestinal decontamination in the prevention of post-LT infections is controversial. Rifaximin is widely used for the treatment of hepatic encephalopathy. The effect of rifaximin on post-LT infections is unknown. The aim of our study was to determine the effect of rifaximin therapy in the pretransplant period on early bacterial infections (EBIs) and fungal infections within the first 30 days after LT. All adult patients who underwent LT at our institution (January 2009 to July 2011) were included in this retrospective cohort study. Patients receiving antibiotics other than pretransplant protocol antibiotics were excluded. Patients were stratified into 2 groups based on the presence or absence of rifaximin therapy for at least 2 days before LT. Infections were defined by the isolation of any bacterial or fungal organisms within 30 days of LT. Multivariate regression analysis, Student t tests, and Pearson's chi-square tests were used to compare the 2 groups. Two hundred sixty-eight patients were included, and 71 of these patients (26.5%) were on rifaximin at the time of LT. The 2 groups were comparable with respect to age, sex, race, and Model for End-Stage Liver Disease score. There were no significant differences in the rates of EBIs (30% for the non-rifaximin group and 25% for the rifaximin group, P = 0.48) or fungal infections between the 2 groups. There was no increase in antimicrobial resistance among the infecting organisms. There was no difference in survival between the rifaximin and non-rifaximin groups (98% versus 97%, P = 0.36). In conclusion, the use of rifaximin in the pre-LT period was not associated with an increased risk of bacterial or fungal infections in the early post-LT period. © 2014 American Association for the Study of Liver Diseases.

Presence of archaea and selected bacteria in infected root canal systems.

PubMed

Brzezińska-Błaszczyk, Ewa; Pawłowska, Elżbieta; Płoszaj, Tomasz; Witas, Henryk; Godzik, Urszula; Agier, Justyna

2018-05-01

Infections of the root canal have polymicrobial etiology. The main group of microflora in the infected pulp is bacteria. There is limited data that archaea may be present in infected pulp tissue. The aim of this study was to check the prevalence of archaea in necrotic root canal samples obtained from patients with primary or post-treatment infection. The prevalence of selected bacteria species (Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Synergistes sp.) in necrotic samples was evaluated as well. Sixty-four samples from root canal were collected for DNA and RNA extraction. A PCR assay based on the 16S rRNA gene was used to determine the presence of archaea and selected bacteria. Of the 64 samples, 6 were analyzed by semiquantitative reverse transcription PCR to estimate expression profiles of 16S rRNA, and another 9 were selected for direct sequencing. Archaea were detected in 48.4% samples. Statistical analysis indicated a negative association in coexistence between archaea and Treponema denticola (P < 0.05; Pearson's χ 2 test). The main representative of the Archaea domain found in infected pulp tissue was Methanobrevibacter oralis. Archaea 16S rRNA gene expression was significantly lower than Synergistes sp., Porphyromonas gingivalis, and Tannerella forsythia (P < 0.05; Student's t test). Thus, it can be hypothesized that archaea may participate in the endodontic microbial community.

HMGCR inhibits the early stage of PCV2 infection, while PKC enhances the infection at the late stage.

PubMed

Ma, Teng; Chen, Xinrong; Ouyang, Hongsheng; Liu, Xiaohui; Ouyang, Ting; Peng, Zhiyuan; Yang, Xin; Chen, Fuwang; Pang, Daxin; Bai, Jieying; Ren, Linzhu

2017-02-02

Porcine circovirus type 2 (PCV2) is the smallest DNA virus, which causes porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD). Due the small size of viral genomic DNA, PCV2 replication predominantly relies on the host factors. In this study, effects of PKC and HMGCR on PCV2 infection were evaluated using real time PCR and western blot. We found that PKC and HMGCR participated in different stages of PCV2 infection. HMGCR works on the early stage of the infection to inhibit the virus infection, while PKC enhances the infection at the late stage. Furthermore, PKC enhances PCV2 replication by activating JNK1/2 and inactivating HMGCR via regulating phosphorylation of these two proteins, while HMGCR can suppress phosphorylation of JNK1/2. The results in the present study will provide new sights in the pathogenesis of PCV2 infection, as well as interactions between host factors during PCV2 infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical Prediction and Diagnosis of Neurosyphilis in HIV-Infected Patients with Early Syphilis

PubMed Central

Langevin, Stéphanie; Gagnon, Simon; Serhir, Bouchra; Deligne, Benoît; Tremblay, Cécile; Tsang, Raymond S. W.; Fortin, Claude; Coutlée, François; Roger, Michel

2013-01-01

The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected patients, and the criteria for deciding when to perform a lumbar puncture (LP) in HIV-infected patients with syphilis are controversial. We retrospectively reviewed demographic, clinical, and laboratory data from 122 cases of HIV-infected patients with documented early syphilis who underwent an LP to rule out NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the Treponema pallidum particle agglutination (TPPA) assay, the fluorescent treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white blood cell (WBC) count of >20 cells/μl. Thirty of the 122 patients (24.6%) had early NS. Headache, visual symptoms, a CD4 cell count of <500 cells/μl, and viremia, as defined by an HIV-1 RNA count of ≥50 copies/ml, were associated with NS in multivariate analysis (P = <0.001 for each factor). Blood serum rapid plasma reagin (RPR) titers were not associated with early NS (P = 0.575). For the diagnosis of NS, the PCR, FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of 58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances, headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/μl were predictors of NS in HIV-infected patients with early syphilis, while blood serum RPR titers were not; therefore, RPR titers should not be used as the sole criterion for deciding whether to perform an LP in early syphilis. When applied to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS. PMID:24088852

Clinical prediction and diagnosis of neurosyphilis in HIV-infected patients with early Syphilis.

PubMed

Dumaresq, Jeannot; Langevin, Stéphanie; Gagnon, Simon; Serhir, Bouchra; Deligne, Benoît; Tremblay, Cécile; Tsang, Raymond S W; Fortin, Claude; Coutlée, François; Roger, Michel

2013-12-01

The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected patients, and the criteria for deciding when to perform a lumbar puncture (LP) in HIV-infected patients with syphilis are controversial. We retrospectively reviewed demographic, clinical, and laboratory data from 122 cases of HIV-infected patients with documented early syphilis who underwent an LP to rule out NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the Treponema pallidum particle agglutination (TPPA) assay, the fluorescent treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white blood cell (WBC) count of >20 cells/μl. Thirty of the 122 patients (24.6%) had early NS. Headache, visual symptoms, a CD4 cell count of <500 cells/μl, and viremia, as defined by an HIV-1 RNA count of ≥50 copies/ml, were associated with NS in multivariate analysis (P = <0.001 for each factor). Blood serum rapid plasma reagin (RPR) titers were not associated with early NS (P = 0.575). For the diagnosis of NS, the PCR, FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of 58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances, headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/μl were predictors of NS in HIV-infected patients with early syphilis, while blood serum RPR titers were not; therefore, RPR titers should not be used as the sole criterion for deciding whether to perform an LP in early syphilis. When applied to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS.

Arsenic and Immune Response to Infection During Pregnancy and Early Life

PubMed Central

Attreed, Sarah E.; Navas-Acien, Ana

2017-01-01

Purpose of Review Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity—including the specific mechanisms in humans—is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. Recent Findings The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Summary Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines. PMID:28488132

The association between maternal cervicovaginal proinflammatory cytokines concentrations during pregnancy and subsequent early-onset neonatal infection.

PubMed

Kalinka, Jarosław; Krajewski, Paweł; Sobala, Wojciech; Wasiela, Małgorzata; Brzezińska-Błaszczyk, Ewa

2006-01-01

The aim of this study was to investigate the relationship between the concentration of selected proinflammatory cytokines (IL-1alpha, IL-1beta, IL-6 and IL-8) in cervicovaginal fluid, as measured in midgestation, and the risk of early-onset neonatal infection (EONI). Cervicovaginal fluids were obtained from a cohort of 114 pregnant women at 22 to 34 weeks' gestation. The samples were analyzed for the concentrations of selected proinflammatory cytokines using standard enzyme-linked immunosorbent assay technique (ELISA). Lower genital tract microbiology was diagnosed using Gram stain method according to Spiegel's criteria and by culture. Mean gestational age at the time of sampling was 29.0 weeks. Mean time between sampling and delivery was 9.3 (SD 4.7) weeks. Bacterial vaginosis (BV) was diagnosed in 27.2% of subjects and M. hominis and U. urealyticum in 22.8% and 26.3%, respectively. Out of 114 women examined, 20 (17.5%) delivered newborns with EONI. Median cervicovaginal concentrations of IL-1alpha, IL-1beta, IL-6 and IL-8 did not differ between women who delivered newborns with EONI as compared to women who delivered newborns without EONI. Women with pathological lower genital tract microflora and low IL-8 concentration (below 25(th) percentile) during pregnancy presented a significant risk of delivering newborns with EONI (OR=4.9; 95% CI, 1.1-22.8). Subjects with pathological lower genital tract microflora and a low concentration of more than one cytokine had the highest risk of delivering a newborn with EONI, OR=16.2, 95% CI, 1.1-234.0. Cytokine measurement in cervicovaginal fluid in early gestation could be useful for predicting subsequent EONI only among pregnant women with lower genital tract infection. Maternal genital tract immune hyporesponsiveness as represented by low concentrations of proinflammatory cytokines may create a permissive environment for ascending infection and may lead to subsequent EONI.

Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs.

PubMed

Alaoui, Lamine; Palomino, Gustavo; Zurawski, Sandy; Zurawski, Gerard; Coindre, Sixtine; Dereuddre-Bosquet, Nathalie; Lecuroux, Camille; Goujard, Cecile; Vaslin, Bruno; Bourgeois, Christine; Roques, Pierre; Le Grand, Roger; Lambotte, Olivier; Favier, Benoit

2018-05-01

Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response.

Discovery of Cellular Proteins Required for the Early Steps of HCV Infection Using Integrative Genomics

PubMed Central

Yang, Jae-Seong; Kwon, Oh Sung; Kim, Sanguk; Jang, Sung Key

2013-01-01

Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets. PMID:23593195

Early detection of Trichinella spiralis DNA in the feces of experimentally infected mice by using PCR.

PubMed

Liu, Xiao Lin; Ren, Hua Nan; Shi, Ya Li; Hu, Chen Xi; Song, Yan Yan; Duan, Jiang Yang; Zhang, Hui Ping; Du, Xin Rui; Liu, Ruo Dan; Jiang, Peng; Wang, Zhong Quan; Cui, Jing

2017-02-01

The aim of this study was to detect Trichinella spiralis DNA in mouse feces during the early stages of infection using PCR. The target gene fragment, a 1.6kb repetitive sequence of T. spiralis genome, was amplified by PCR from feces of mice infected with 100 or 300 larvae at 3-24h post infection (hpi) and 2-28dpi. The sensitivity of PCR was 0.016 larvae in feces. The primers used were highly specific for T. spiralis. No cross-reactivity was observed with the DNA of other intestinal helminths. T. spiralis DNA was detected in 100% (12/12) of feces of mice infected with 100 or 300 larvae as early as 3hpi, with the peak detection lasting to 12-24hpi, and then fluctuating before declining gradually. By 28dpi, the detection rate of T. spiralis DNA in feces of the two groups of infected mice decreased to 8.33% and 25%, respectively. PCR detection of T. spiralis DNA in feces is simple and specific; it might be useful for the early diagnosis of Trichinella infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Rapidly-growing mycobacterial infection: a recognized cause of early-onset prosthetic joint infection.

PubMed

Jitmuang, Anupop; Yuenyongviwat, Varah; Charoencholvanich, Keerati; Chayakulkeeree, Methee

2017-12-28

Prosthetic joint infection (PJI) is a major complication of total hip and total knee arthroplasty (THA, TKA). Although mycobacteria are rarely the causative pathogens, it is important to recognize and treat them differently from non-mycobacterial infections. This study aimed to compare the clinical characteristics, associated factors and long-term outcomes of mycobacterial and non-mycobacterial PJI. We conducted a retrospective case-control study of patients aged ≥18 years who were diagnosed with PJI of the hip or knee at Siriraj Hospital from January 2000 to December 2012. Patient characteristics, clinical data, treatments and outcomes were evaluated. A total of 178 patients were included, among whom 162 had non-mycobacterial PJI and 16 had mycobacterial PJI. Rapidly growing mycobacteria (RGM) (11) and M. tuberculosis (MTB) (5) were the causative pathogens of mycobacterial PJI. PJI duration and time until onset were significantly different between mycobacterial and non-mycobacterial PJI. Infection within 90 days of arthroplasty was significantly associated with RGM infection (OR 21.86; 95% CI 4.25-112.30; p < .001). Implant removal was associated with improved favorable outcomes at 6 months (OR 5.96; 95% CI 1.88-18.88; p < .01) and 12 months (OR 3.96; 95% CI 1.15-13.71; p = .03) after the infection. RGM were the major pathogens of early onset PJI after THA and TKA. Both a high clinical index of suspicion and mycobacterial cultures are recommended when medically managing PJI with negative cultures or non-response to antibiotics. Removal of infected implants was associated with favorable outcomes.

R5 human immunodeficiency virus type 1 with efficient DC-SIGN use is not selected for early after birth in vertically infected children.

PubMed

Borggren, Marie; Navér, Lars; Casper, Charlotte; Ehrnst, Anneka; Jansson, Marianne

2013-04-01

The binding of human immunodeficiency virus (HIV) to C-type lectin receptors may result in either enhanced trans-infection of T-cells or virus degradation. We have investigated the efficacy of HIV-1 utilization of DC-SIGN, a C-type lectin receptor, in the setting of intrauterine or intrapartum mother-to-child transmission (MTCT). Viruses isolated from HIV-1-infected mothers at delivery and from their vertically infected children both shortly after birth and later during the progression of the disease were analysed for their use of DC-SIGN, binding and ability to trans-infect. DC-SIGN use of a child's earlier virus isolate tended to be reduced as compared with that of the corresponding maternal isolate. Furthermore, the children's later isolate displayed enhanced DC-SIGN utilization compared with that of the corresponding earlier virus. These results were also supported in head-to-head competition assays and suggest that HIV-1 variants displaying efficient DC-SIGN use are not selected for during intrauterine or intrapartum MTCT. However, viruses with increased DC-SIGN use may evolve later in paediatric HIV-1 infections.

Eosinophils contribute to early clearance of Pneumocystis murina infection

PubMed Central

Eddens, Taylor; Elsegeiny, Waleed; Nelson, Michael P.; Horne, William; Campfield, Brian T.; Steele, Chad; Kolls, Jay K.

2015-01-01

Pneumocystis pneumonia remains a common opportunistic infection in the diverse immunosuppressed population. One clear risk factor for susceptibility to Pneumocystis is a declining CD4+ T-cell counts in the setting of HIV/AIDS or primary immunodeficiency. Non-HIV infected individuals taking immunosuppressive drug regimens targeting T-cell activation are also susceptible. Given the crucial role of CD4+ T-cells in host defense against Pneumocystis, we used RNA-sequencing of whole lung early in infection in wild type and CD4-depleted animals as an unbiased approach to examine mechanisms of fungal clearance. In wild type mice, a strong eosinophil signature was observed at day 14 post-Pneumocystis challenge and eosinophils were increased in the bronchoalveolar lavage fluid of wild type mice. Furthermore, eosinophilopoiesis-deficient Gata1tm6Sho/J mice were more susceptible to Pneumocystis infection when compared to BALB/c controls and bone marrow derived eosinophils had in vitro Pneumocystis killing activity. To drive eosinophilia in vivo, Rag1−/− mice were treated with a plasmid expressing IL-5 (pIL5) or an empty plasmid control via hydrodynamic injection. pIL5 treated mice had increased serum IL-5 and eosinophilia in the lung, as well as reduced Pneumocystis burden compared to mice treated with control plasmid. Additionally, pIL5 treatment could induce eosinophilia and reduce Pneumocystis burden in CD4-depleted C57Bl/6 and BALB/c mice, but not eosinophilopoiesis-deficient Gata1tm6Sho/J mice. Taken together, these results demonstrate that an early role of CD4+ T-cells is to recruit eosinophils to the lung and that eosinophils are a novel candidate for future therapeutic development for Pneumocystis pneumonia in the immunosuppressed population. PMID:25994969

Dynamic range of Nef-mediated evasion of HLA class II-restricted immune responses in early HIV-1 infection.

PubMed

Mahiti, Macdonald; Brumme, Zabrina L; Jessen, Heiko; Brockman, Mark A; Ueno, Takamasa

2015-07-31

HLA class II-restricted CD4(+) T lymphocytes play an important role in controlling HIV-1 replication, especially in the acute/early infection stage. But, HIV-1 Nef counteracts this immune response by down-regulating HLA-DR and up-regulating the invariant chain associated with immature HLA-II (Ii). Although functional heterogeneity of various Nef activities, including down-regulation of HLA class I (HLA-I), is well documented, our understanding of Nef-mediated evasion of HLA-II-restricted immune responses during acute/early infection remains limited. Here, we examined the ability of Nef clones from 47 subjects with acute/early progressive infection and 46 subjects with chronic progressive infection to up-regulate Ii and down-regulate HLA-DR and HLA-I from the surface of HIV-infected cells. HLA-I down-regulation function was preserved among acute/early Nef clones, whereas both HLA-DR down-regulation and Ii up-regulation functions displayed relatively broad dynamic ranges. Nef's ability to down-regulate HLA-DR and up-regulate Ii correlated positively at this stage, suggesting they are functionally linked in vivo. Acute/early Nef clones also exhibited higher HLA-DR down-regulation and lower Ii up-regulation functions compared to chronic Nef clones. Taken together, our results support enhanced Nef-mediated HLA class II immune evasion activities in acute/early compared to chronic infection, highlighting the potential importance of these functions following transmission. Copyright © 2015 Elsevier Inc. All rights reserved.

Early Admissions at Selective Colleges. NBER Working Paper No. 14844

ERIC Educational Resources Information Center

Avery, Christopher; Levin, Jonathan D.

2009-01-01

Early admissions is widely used by selective colleges and universities. We identify some basic facts about early admissions policies, including the admissions advantage enjoyed by early applicants and patterns in application behavior, and propose a game-theoretic model that matches these facts. The key feature of the model is that colleges want to…

West nile virus infections suppress early viral RNA synthesis and avoid inducing the cell stress granule response.

PubMed

Courtney, S C; Scherbik, S V; Stockman, B M; Brinton, M A

2012-04-01

West Nile virus (WNV) recently became endemic in the United States and is a significant cause of human morbidity and mortality. Natural WNV strain infections do not induce stress granules (SGs), while W956IC (a lineage 2/1 chimeric WNV infectious clone) virus infections produce high levels of early viral RNA and efficiently induce SGs through protein kinase R (PKR) activation. Additional WNV chimeric viruses made by replacing one or more W956IC genes with the lineage 1 Eg101 equivalent in the W956IC backbone were analyzed. The Eg-NS4b+5, Eg-NS1+3+4a, and Eg-NS1+4b+5 chimeras produced low levels of viral RNA at early times of infection and inefficiently induced SGs, suggesting the possibility that interactions between viral nonstructural proteins and/or between viral nonstructural proteins and cell proteins are involved in suppressing early viral RNA synthesis and membrane remodeling during natural WNV strain infections. Detection of exposed viral double-stranded RNA (dsRNA) in W956IC-infected cells suggested that the enhanced early viral RNA synthesis surpassed the available virus-induced membrane protection and allowed viral dsRNA to activate PKR.

Early Detection of Infection in Pigs through an Online Monitoring System.

PubMed

Martínez-Avilés, M; Fernández-Carrión, E; López García-Baones, J M; Sánchez-Vizcaíno, J M

2017-04-01

Late detection of emergency diseases causes significant economic losses for pig producers and governments. As the first signs of animal infection are usually fever and reduced motion that lead to reduced consumption of water and feed, we developed a novel smart system to monitor body temperature and motion in real time, facilitating the early detection of infectious diseases. In this study, carried out within the framework of the European Union research project Rapidia Field, we tested the smart system on 10 pigs experimentally infected with two doses of an attenuated strain of African swine fever. Biosensors and an accelerometer embedded in an eartag captured data before and after infection, and video cameras were used to monitor the animals 24 h per day. The results showed that in 8 of 9 cases, the monitoring system detected infection onset as an increase in body temperature and decrease in movement before or simultaneously with fever detection based on rectal temperature measurement, observation of clinical signs, the decrease in water consumption or positive qPCR detection of virus. In addition, this decrease in movement was reliably detected using automatic analysis of video images therefore providing an inexpensive alternative to direct motion measurement. The system can be set up to alert staff when high fever, reduced motion or both are detected in one or more animals. This system may be useful for monitoring sentinel herds in real time, considerably reducing the financial and logistical costs of periodic sampling and increasing the chances of early detection of infection. © 2015 Blackwell Verlag GmbH.

Use of digital PCR to improve early detection of CLas infection

USDA-ARS?s Scientific Manuscript database

Huanglongbing is a devastating disease of citrus caused by the bacterium Candidatus Liberibacter asiaticus. Huanglongbing has devastated the Florida citrus industry and is threatening citrus in Texas and California. Detection of Candidatus Liberibacter asiaticus infections as early as possible is ...

Discovery and Validation of Prognostic Biomarker Models to Guide Triage among Adult Dengue Patients at Early Infection

PubMed Central

Tolfvenstam, Thomas; Thein, Tun-Linn; Naim, Ahmad Nazri Mohamed; Ling, Ling; Chow, Angelia; Chen, Mark I-Cheng; Ooi, Eng Eong; Leo, Yee Sin; Hibberd, Martin L.

2016-01-01

Background Dengue results in a significant public health burden in endemic regions. The World Health Organization (WHO) recommended the use of warning signs (WS) to stratify patients at risk of severe dengue disease in 2009. However, WS is limited in stratifying adult dengue patients at early infection (Day 1–3 post fever), who require close monitoring in hospitals to prevent severe dengue. The aim of this study is to identify and validate prognostic models, built with differentially expressed biomarkers, that enable the early identification of those with early dengue infection that require close clinical monitoring. Methods RNA microarray and protein assays were performed to identify differentially expressed biomarkers of severity among 92 adult dengue patients recruited at early infection from years 2005–2008. This comprised 47 cases who developed WS after first presentation and required hospitalization (WS+Hosp), as well as 45 controls who did not develop WS after first presentation and did not require hospitalization (Non-WS+Non-Hosp). Independent validation was conducted with 80 adult dengue patients recruited from years 2009–2012. Prognostic models were developed based on forward stepwise and backward elimination estimation, using multiple logistic regressions. Prognostic power was estimated by the area under the receiver operating characteristic curve (AUC). Results The WS+Hosp group had significantly higher viral load (P<0.001), lower platelet (P<0.001) and lymphocytes counts (P = 0.004) at early infection compared to the Non-WS+Non-Hosp group. From the RNA microarray and protein assays, the top single RNA and protein prognostic models at early infection were CCL8 RNA (AUC:0.73) and IP-10 protein (AUC:0.74), respectively. The model with CCL8, VPS13C RNA, uPAR protein, and with CCL8, VPS13C RNA and platelets were the best biomarker models for stratifying adult dengue patients at early infection, with sensitivity and specificity up to 83% and 84

Evaluation of intrapartum antibiotic prophylaxis for the prevention of early-onset group B streptococcal infection.

PubMed

Sakata, Hiroshi

2012-12-01

We retrospectively assessed the medical records of pregnant women who delivered at Asahikawa Kosei Hospital during a period of 3 years between January 2009 and December 2011 and their neonates. Our prophylactic measures against group B Streptococcus (GBS) infection are based on the Japanese guidelines. More specifically, we performed screening by examining bacterial cultures of vaginal-perianal swabs from pregnant women between gestational weeks 33 and 37. Then, sulbactam/ampicillin (SBT/ABPC) was given at a dose of 1.5 g through a drip intravenous infusion at delivery if pregnant women were screened positive for GBS. For neonates born to GBS carrier women, bacterial cultures of pharyngeal swabs, vernix caseosa, stool, and gastric juice were performed at birth. There were 2,399 deliveries and 2,499 births at our hospital. In 169 of the deliveries (175 of the births), GBS was isolated from specimens obtained from gestational weeks 33-37. According to delivery mode, there were 42 cases of cesarean section (45 births) and 127 cases of vaginal delivery (130 births). The GBS-positive neonates accounted for 4.1 % of all deliveries in pregnant women who tested positive for GBS at gestational weeks 33-37. In neonates born by vaginal delivery, the GBS-positive rate was 5.5 %. Of the 2,499 neonates born at our hospital during a period of 3 years, early-onset GBS infection occurred in 1 neonate. The incidence of early-onset GBS infection was 0.40 per 1,000 live births. From 1997 to 2001 (routine GBS screening of mothers was not performed), there were 2,097 deliveries and 2,166 births. Early-onset GBS infection occurred in 1 neonate during this period; thus, the incidence of early-onset GBS infection was 0.46 per 1,000 live births. There were no significant differences in the two periods. The present prophylactic measures such as screening of maternal GBS carriers and intrapartum antibiotic administration are inadequate to decrease the occurrence of early-onset GBS

Optimal timing for early surgery in infective endocarditis: a meta-analysis†

PubMed Central

Liang, Fuxiang; Song, Bing; Liu, Ruisheng; Yang, Liu; Tang, Hanbo; Li, Yuanming

2016-01-01

To systematically review early surgery and the optimal timing of surgery in patients with infective endocarditis (IE), a search for foreign and domestic articles on cohort studies about the association between early surgery and infective endocarditis published from inception to January 2015 was conducted in the PubMed, EMBASE, Chinese Biomedical Literature (CBM), Wanfang and Chinese National Knowledge Infrastructure (CNKI) databases. The studies were screened according to the inclusion and exclusion criteria, the data were extracted and the quality of the method of the included studies was assessed. Then, the meta-analysis was performed using the Stata 12.0 software. Sixteen cohort studies, including 8141 participants were finally included. The results of the meta-analysis revealed that, compared with non-early surgery, early surgery in IE lowers the incidence of in-hospital mortality [odds ratio (OR) = 0.57, 95% confidence interval (CI) (0.42, 0.77); P = 0.000, I2 = 73.1%] and long-term mortality [OR = 0.57, 95% CI (0.43, 0.77); P = 0.001, I2 = 67.4%]. Further, performing operation within 2 weeks had a more favourable effect on long-term mortality [OR = 0.63, 95% CI (0.41, 0.97); P = 0.192, I2 = 39.4%] than non-early surgery. In different kinds of IE, we found that early surgery for native valve endocarditis (NVE) had a lower in-hospital [OR = 0.46, 95% CI (0.31, 0.69); P = 0.001, I2 = 73.0%] and long-term [OR = 0.57, 95% CI (0.40, 0.81); P = 0.001, I2 = 68.9%] mortality than the non-early surgery group. However, for prosthetic valve endocarditis (PVE), in-hospital mortality did not differ significantly [OR = 0.83, 95% CI (0.65, 1.06); P = 0.413, I2 = 0.0%] between early and non-early surgery. We concluded that early surgery was associated with lower in-hospital and long-term mortality compared with non-early surgical treatment for IE, especially in NVE. However, the optimal timing of surgery remains unclear. Additional larger prospective clinical trials will be

HIV Clade-C Infection and Cognitive Impairment, Fatigue, Depression, and Quality of Life in Early-Stage Infection in Northern Indians

PubMed Central

Cook, R.; Jones, D. L.; Nehra, R.; Kumar, A. M.; Prabhakar, S.; Waldrop-Valverde, D.; Sharma, S.; Kumar, M.

2017-01-01

HIV disease progression is associated with declining quality of life and overall health status, although most research in this domain has been conducted among Western populations where B is the infecting clade. This study sought to determine the effects of early-stage clade-C HIV infection (CD4 count ≥400 cells/mm3) on neurocognitive functioning, cognitive depression, and fatigue by comparing a matched sample of HIV-positive and HIV-negative Northern Indians. This study also examined the impact of these factors on quality of life within the HIV-positive individuals. HIV-positive participants demonstrated reduced cognitive functioning, increased fatigue, and lower quality of life. Fatigue and cognitive impairment interacted to negatively impact quality of life. Results suggest that early-stage HIV clade-C-infected individuals may experience subclinical symptoms, and further research is needed to explore the benefit of therapeutic interventions to ensure optimal clinical outcomes and maintain quality of life in this vulnerable population. PMID:23722088

HIV Clade-C Infection and Cognitive Impairment, Fatigue, Depression, and Quality of Life in Early-Stage Infection in Northern Indians.

PubMed

Cook, R; Jones, D L; Nehra, R; Kumar, A M; Prabhakar, S; Waldrop-Valverde, D; Sharma, S; Kumar, M

2016-07-01

HIV disease progression is associated with declining quality of life and overall health status, although most research in this domain has been conducted among Western populations where B is the infecting clade. This study sought to determine the effects of early-stage clade-C HIV infection (CD4 count ≥400 cells/mm(3)) on neurocognitive functioning, cognitive depression, and fatigue by comparing a matched sample of HIV-positive and HIV-negative Northern Indians. This study also examined the impact of these factors on quality of life within the HIV-positive individuals. HIV-positive participants demonstrated reduced cognitive functioning, increased fatigue, and lower quality of life. Fatigue and cognitive impairment interacted to negatively impact quality of life. Results suggest that early-stage HIV clade-C-infected individuals may experience subclinical symptoms, and further research is needed to explore the benefit of therapeutic interventions to ensure optimal clinical outcomes and maintain quality of life in this vulnerable population. © The Author(s) 2013.

Decreased sensitivity of early imaging with In-111 oxine-labeled leukocytes in detection of occult infection: concise communication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Datz, F.L.; Jacobs, J.; Baker, W.

1984-03-01

Imaging with leukocytes labeled with indium-111 oxine is a sensitive technique for detecting sites of occult infection. Traditionally, imaging is performed 24 hr after injection. The authors undertook a prospective study of 35 patients (40 studies) with possible occult infection to see whether a 24-hr delay in imaging is really necessary. Patients were imaged at 1-4 hr and again at 24 hr after injection. The early images had a sensitivity of only 33%, compared with 95% for the 24-hr images. Of the seven studies that were positive on both early and delayed images, 71% had more intense uptake at 24more » hr. There were no false-positive early images. It was concluded that imaging 1-4 hr after injection with In-111 oxine-labeled leukocytes has a low sensitivity for detecting occult infection. However, a positive early image is specific for a site of infection.« less

Selection occurs within linear fruit and during the early stages of reproduction in Robinia pseudoacacia

PubMed Central

2014-01-01

Background Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Results Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Conclusions Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low

Selection occurs within linear fruit and during the early stages of reproduction in Robinia pseudoacacia.

PubMed

Yuan, Cun-Quan; Sun, Yu-Han; Li, Yun-Fei; Zhao, Ke-Qi; Hu, Rui-Yang; Li, Yun

2014-03-21

Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low seed set in R. pseudoacacia.

Low prevalence of neurocognitive impairment in early diagnosed and managed HIV-infected persons

PubMed Central

Moore, David J.; Letendre, Scott; Poehlman Roediger, Mollie; Eberly, Lynn; Weintrob, Amy; Ganesan, Anuradha; Johnson, Erica; Del Rosario, Raechel; Agan, Brian K.; Hale, Braden R.

2013-01-01

Objective: To describe the prevalence of neurocognitive impairment (NCI) among early diagnosed and managed HIV-infected persons (HIV+) compared to HIV-negative controls. Methods: We performed a cross-sectional study among 200 HIV+ and 50 matched HIV-uninfected (HIV−) military beneficiaries. HIV+ patients were categorized as earlier (<6 years of HIV, no AIDS-defining conditions, and CD4 nadir >200 cells/mm3) or later stage patients (n = 100 in each group); both groups were diagnosed early and had access to care. NCI was diagnosed using a comprehensive battery of standardized neuropsychological tests. Results: HIV+ patients had a median age of 36 years, 91% were seroconverters (median window of 1.2 years), had a median duration of HIV of 5 years, had a CD4 nadir of 319, had current CD4 of 546 cells/mm3, and 64% were on highly active antiretroviral therapy (initiated 1.3 years after diagnosis at a median CD4 of 333 cells/mm3). NCI was diagnosed among 38 (19%, 95% confidence interval 14%–25%) HIV+ patients, with a similar prevalence of NCI among earlier and later stage patients (18% vs 20%, p = 0.72). The prevalence of NCI among HIV+ patients was similar to HIV− patients. Conclusions: HIV+ patients diagnosed and managed early during the course of HIV infection had a low prevalence of NCI, comparable to matched HIV-uninfected persons. Early recognition and management of HIV infection may be important in limiting neurocognitive impairment. PMID:23303852

Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

PubMed

Campbell, Jennifer H; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J; Tse, Samantha; Miller, Andrew D; González, R Gilberto; Salemi, Marco; Burdo, Tricia H; Williams, Kenneth C

2014-12-01

Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection.

PubMed

Wang, Kun; Langevin, Stanley; O'Hern, Corey S; Shattuck, Mark D; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G; Kirby, Michael

2016-01-01

Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical

Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection

PubMed Central

O’Hern, Corey S.; Shattuck, Mark D.; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G.

2016-01-01

Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical

Early-life enteric infections: relation between chronic systemic inflammation and poor cognition in children

PubMed Central

Murray-Kolb, Laura E.; Scharf, Rebecca J.; Pendergast, Laura L.; Lang, Dennis R.; Kolling, Glynis L.; Guerrant, Richard L.

2016-01-01

The intestinal microbiota undergoes active remodeling in the first 6 to 18 months of life, during which time the characteristics of the adult microbiota are developed. This process is strongly influenced by the early diet and enteric pathogens. Enteric infections and malnutrition early in life may favor microbiota dysbiosis and small intestinal bacterial overgrowth, resulting in intestinal barrier dysfunction and translocation of intestinal bacterial products, ultimately leading to low-grade, chronic, subclinical systemic inflammation. The leaky gut–derived low-grade systemic inflammation may have profound consequences on the gut–liver–brain axis, compromising normal growth, metabolism, and cognitive development. This review examines recent data suggesting that early-life enteric infections that lead to intestinal barrier disruption may shift the intestinal microbiota toward chronic systemic inflammation and subsequent impaired cognitive development. PMID:27142301

FDA-Approved Selective Estrogen Receptor Modulators Inhibit Ebola Virus Infection

PubMed Central

Johansen, Lisa M.; Brannan, Jennifer M.; Delos, Sue E.; Shoemaker, Charles J.; Stossel, Andrea; Lear, Calli; Hoffstrom, Benjamin G.; DeWald, Lisa Evans; Schornberg, Kathryn L.; Scully, Corinne; Lehár, Joseph; Hensley, Lisa E.; White, Judith M.; Olinger, Gene G.

2014-01-01

Ebola viruses remain a substantial threat to both civilian and military populations as bioweapons, during sporadic outbreaks, and from the possibility of accidental importation from endemic regions by infected individuals. Currently, no approved therapeutics exist to treat or prevent infection by Ebola viruses. Therefore, we performed an in vitro screen of Food and Drug Administration (FDA)– and ex–US-approved drugs and selected molecular probes to identify drugs with antiviral activity against the type species Zaire ebolavirus (EBOV). From this screen, we identified a set of selective estrogen receptor modulators (SERMs), including clomiphene and toremifene, which act as potent inhibitors of EBOV infection. Anti-EBOV activity was confirmed for both of these SERMs in an in vivo mouse infection model. This anti-EBOV activity occurred even in the absence of detectable estrogen receptor expression, and both SERMs inhibited virus entry after internalization, suggesting that clomiphene and toremifene are not working through classical pathways associated with the estrogen receptor. Instead, the response appeared to be an off-target effect where the compounds interfere with a step late in viral entry and likely affect the triggering of fusion. These data support the screening of readily available approved drugs to identify therapeutics for the Ebola viruses and other infectious diseases. The SERM compounds described in this report are an immediately actionable class of approved drugs that can be repurposed for treatment of filovirus infections. PMID:23785035

Alterations in early cytokine-mediated immune responses to Plasmodium falciparum infection in Tanzanian children with mineral element deficiencies: a cross-sectional survey

PubMed Central

2010-01-01

Background Deficiencies in vitamins and mineral elements are important causes of morbidity in developing countries, possibly because they lead to defective immune responses to infection. The aim of the study was to assess the effects of mineral element deficiencies on early innate cytokine responses to Plasmodium falciparum malaria. Methods Peripheral blood mononuclear cells from 304 Tanzanian children aged 6-72 months were stimulated with P. falciparum-parasitized erythrocytes obtained from in vitro cultures. Results The results showed a significant increase by 74% in geometric mean of TNF production in malaria-infected individuals with zinc deficiency (11% to 240%; 95% CI). Iron deficiency anaemia was associated with increased TNF production in infected individuals and overall with increased IL-10 production, while magnesium deficiency induced increased production of IL-10 by 46% (13% to 144%) in uninfected donors. All donors showed a response towards IL-1β production, drawing special attention for its possible protective role in early innate immune responses to malaria. Conclusions In view of these results, the findings show plasticity in cytokine profiles of mononuclear cells reacting to malaria infection under conditions of different micronutrient deficiencies. These findings lay the foundations for future inclusion of a combination of precisely selected set of micronutrients rather than single nutrients as part of malaria vaccine intervention programmes in endemic countries. PMID:20470442

Severity of Disease in Humanized Mice Infected With Ebola Virus or Reston Virus Is Associated With Magnitude of Early Viral Replication in Liver.

PubMed

Spengler, Jessica R; Saturday, Greg; Lavender, Kerry J; Martellaro, Cynthia; Keck, James G; Nichol, Stuart T; Spiropoulou, Christina F; Feldmann, Heinz; Prescott, Joseph

2017-12-27

Both Ebola virus (EBOV) and Reston virus (RESTV) cause disease in nonhuman primates, yet only EBOV causes disease in humans. To investigate differences in viral pathogenicity, humanized mice (hu-NSG-SGM3) were inoculated with EBOV or RESTV. Consistent with differences in disease in human infection, pronounced weight loss and markers of hepatic damage and disease were observed exclusively in EBOV-infected mice. These abnormalities were associated with significantly higher EBOV replication in the liver but not in the spleen, suggesting that in this model, efficiency of viral replication in select tissues early in infection may contribute to differences in viral pathogenicity. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Herpes zoster could be an early manifestation of undiagnosed human immunodeficiency virus infection.

PubMed

Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu; Chen, Wen-Chi

2016-05-01

No formal epidemiological research based on systematic analysis has focused on the relationship between herpes zoster and immunodeficiency virus (HIV) infection in Taiwan. Our aim was to explore whether herpes zoster is an early manifestation of undiagnosed human HIV infection in Taiwan. This was a retrospective cohort study using the database of the Taiwan National Health Insurance Program. A total of 35,892 individuals aged ≤ 84 years with newly diagnosed herpes zoster from 1998 to 2010 were assigned to the herpes zoster group, whereas 143,568 sex-matched and age-matched, randomly selected individuals without herpes zoster served as the non-herpes zoster group. The incidence of HIV diagnosis at the end of 2011 was estimated in both groups. The multivariable Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence interval (CI) for risk of HIV diagnosis associated with herpes zoster and other comorbidities including drug dependence and venereal diseases. The overall incidence of HIV diagnosis was 4.19-fold greater in the herpes zoster group than that in the non-herpes zoster group (3.33 per 10,000 person-years vs. 0.80 per 10,000 person-years, 95% CI 4.04-4.35). The multivariable Cox proportional hazards regression analysis revealed that the adjusted hazard ratio of HIV diagnosis was 4.37 (95% CI 3.10-6.15) for individuals with herpes zoster and without comorbidities, as compared with individuals without herpes zoster and without comorbidities. Herpes zoster is associated with HIV diagnosis. Patients who have risk behaviors of HIV infection should receive regular surveillance for undiagnosed HIV infection when they present with herpes zoster. Copyright © 2015. Published by Elsevier B.V.

Prophylactic antibiotics for preventing early Gram-positive central venous catheter infections in oncology patients, a Cochrane systematic review.

PubMed

van de Wetering, M D; van Woensel, J B M; Kremer, L C M; Caron, H N

2005-05-01

Long-term tunnelled central venous catheters (TCVC) are increasingly used in oncology patients. Infections are a frequent complication of TCVC, mostly caused by Gram-positive bacteria. The objective of this review is to evaluate the efficacy of antibiotics in the prevention of early Gram-positive TCVC infections, in oncology patients. We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register up to July 2003. We selected randomised controlled trials (RCT) evaluating prophylactic antibiotics prior to insertion of the TCVC, and the combination of an antibiotic and heparin to flush the TCVC, in paediatric and adult oncology patients. The primary outcome was documented Gram-positive bacteraemia in patients with a TCVC. All trials identified were assessed and the data extracted independently by two reviewers. There were nine trials included. Four trials reported on vancomycin/teicoplanin prior to insertion of the TCVC compared to no antibiotics. There was no reduction in the number of Gram-positive TCVC infections with an Odds ratio of 0.42 (95% confidence interval 0.13-1.31). Five trials studied flushing of the TCVC with a vancomycin/heparin solution compared to heparin flushing only. This method decreased the number of TCVC infections significantly with an Odds ratio of 0.43 (95% CI 0.21-0.87). Flushing the TCVC with a vancomycin/heparin solution reduced the incidence of Gram-positive infections.

Esmolol reduces apoptosis and inflammation in early sepsis rats with abdominal infection.

PubMed

Lu, Yang; Yang, Yang; He, Xin; Dong, Shangwen; Wang, Wanhua; Wang, Donghao; Zhang, Peng

2017-10-01

Esmolol is a highly selective beta 1 receptor blocker with various effects such as slowing heart rate, lowering blood pressure and reducing myocardial oxygen consumption. However, few studies have reported the use of beta blockers in sepsis with multiple organ dysfunctions. This study aimed to investigate the effects of esmolol on reducing apoptosis and inflammation in early sepsis rats with abdominal infection. Rats were randomly divided into sham operation group, sepsis group, antibiotic group, Esmolol + antibiotic group with low, median and high dose Esmolol (L group, M group and H group). Values between two or more groups were compared by independent t-tests. In the liver and kidney, we found inflammatory infiltration in sepsis group while pathological aspects reduced in L, M and H groups. Bcl-2 mRNA and protein levels increased while Bax mRNA and protein levels decreased in the liver and kidney of L, M and H groups. Serum IL-6, HMGB-1 and TNF-α levels decreased but IL-10 level increased in L, M and H groups, compared to sepsis group. Compared to sepsis and antibiotic groups, the levels of myocardial enzymes were lower in L, M and H groups. The administration of esmolol in early sepsis may reduce inflammation, inhibit apoptosis and protect key organs. Copyright © 2017 Elsevier Inc. All rights reserved.

Optimal timing for early surgery in infective endocarditis: a meta-analysis.

PubMed

Liang, Fuxiang; Song, Bing; Liu, Ruisheng; Yang, Liu; Tang, Hanbo; Li, Yuanming

2016-03-01

To systematically review early surgery and the optimal timing of surgery in patients with infective endocarditis (IE), a search for foreign and domestic articles on cohort studies about the association between early surgery and infective endocarditis published from inception to January 2015 was conducted in the PubMed, EMBASE, Chinese Biomedical Literature (CBM), Wanfang and Chinese National Knowledge Infrastructure (CNKI) databases. The studies were screened according to the inclusion and exclusion criteria, the data were extracted and the quality of the method of the included studies was assessed. Then, the meta-analysis was performed using the Stata 12.0 software. Sixteen cohort studies, including 8141 participants were finally included. The results of the meta-analysis revealed that, compared with non-early surgery, early surgery in IE lowers the incidence of in-hospital mortality [odds ratio (OR) = 0.57, 95% confidence interval (CI) (0.42, 0.77); P = 0.000, I(2) = 73.1%] and long-term mortality [OR = 0.57, 95% CI (0.43, 0.77); P = 0.001, I(2) = 67.4%]. Further, performing operation within 2 weeks had a more favourable effect on long-term mortality [OR = 0.63, 95% CI (0.41, 0.97); P = 0.192, I(2) = 39.4%] than non-early surgery. In different kinds of IE, we found that early surgery for native valve endocarditis (NVE) had a lower in-hospital [OR = 0.46, 95% CI (0.31, 0.69); P = 0.001, I(2) = 73.0%] and long-term [OR = 0.57, 95% CI (0.40, 0.81); P = 0.001, I(2) = 68.9%] mortality than the non-early surgery group. However, for prosthetic valve endocarditis (PVE), in-hospital mortality did not differ significantly [OR = 0.83, 95% CI (0.65, 1.06); P = 0.413, I(2) = 0.0%] between early and non-early surgery. We concluded that early surgery was associated with lower in-hospital and long-term mortality compared with non-early surgical treatment for IE, especially in NVE. However, the optimal timing of surgery remains unclear. Additional larger prospective clinical

Early life rhinovirus infection exacerbates house-dust-mite induced lung disease more severely in female mice.

PubMed

Phan, Jennifer A; Kicic, Anthony; Berry, Luke J; Sly, Peter D; Larcombe, Alexander N

2016-01-01

Recent studies have employed animal models to investigate links between rhinovirus infection and allergic airways disease, however, most do not involve early life infection, and none consider the effects of sex on responses. Here, we infected male and female mice with human rhinovirus 1B (or control) on day 7 of life. Mice were then subjected to 7 weeks of exposure to house-dust-mite prior to assessment of bronchoalveolar inflammation, serum antibodies, lung function, and responsiveness to methacholine. There were significant differences in responses between males and females in most outcomes. In males, chronic house-dust-mite exposure increased bronchoalveolar inflammation, house-dust-mite specific IgG1 and responsiveness of the lung parenchyma, however, there was no additional impact of rhinovirus infection. Conversely, in females, there were additive and synergistic effects of rhinovirus infection and house-dust-mite exposure on neutrophilia, airway resistance, and responsiveness of the lung parenchyma. We conclude that early life rhinovirus infection influences the development of house-dust-mite induced lung disease in female, but not male mice.

Early divergent host responses in SHIVsf162P3 and SIVmac251 infected macaques correlate with control of viremia.

PubMed

Xu, Huanbin; Wang, Xiaolei; Morici, Lisa A; Pahar, Bapi; Veazey, Ronald S

2011-03-25

We previously showed intravaginal inoculation with SHIVsf162p3 results in transient viremia followed by undetectable viremia in most macaques, and some displayed subsequent immunity to superinfection with pathogenic SIVmac251. Here we compare early T cell activation, proliferation, and plasma cytokine/chemokine responses in macaques intravaginally infected with either SHIVsf162p3 or SIVmac251 to determine whether distinct differences in host responses may be associated with early viral containment. The data show SIVmac251 infection results in significantly higher levels of T cell activation, proliferation, and a mixed cytokine/chemokine "storm" in plasma in primary infection, whereas infection with SHIVsf162p3 resulted in significantly lower levels of T cell activation, proliferation, and better preservation of memory CD4+ T cells in early infection which immediately preceded control of viremia. These results support the hypothesis that early systemic immune activation, T cell proliferation, and a more prominent and broader array of cytokine/chemokine responses facilitate SIV replication, and may play a key role in persistence of infection, and the progression to AIDS. In contrast, immune unresponsiveness may be associated with eventual clearance of virus, a concept that may have key significance for therapy and vaccine design.

Feed resource selection of Criollo goats artificially infected with Haemonchus contortus: nutritional wisdom and prophylactic self-medication.

PubMed

Ventura-Cordero, J; González-Pech, P G; Jaimez-Rodriguez, P R; Ortiz-Ocampo, G I; Sandoval-Castro, C A; Torres-Acosta, J F J

2018-06-01

Previous cafeteria studies suggested that a moderate natural gastrointestinal nematode (GIN) infection did not modify the resource selection of adult Criollo goats towards tannin-rich plants compared with worm-free goats. A higher infection with Haemonchus contortus could trigger a change in the resource selection behaviour towards tannin-rich foliage. Alternatively, goats might select plant species solely to meet their nutritional requirements. A cafeteria study investigated the effect of a high artificial infection with H. contortus on the feed resource selection of goats. Adult Criollo goats (37.5±4.8 kg BW) with browsing experience were distributed in two groups: the infected group (IG) with six animals artificially infected with H. contortus (6000 L3/animal); and the non-infected group (NIG) with six animals maintained worm-free. The experiment included two 5-day periods with additional 5-day adaptation period. In the first period, animals were offered foliage of five plant species with a decreasing gradient of condensed tannins (CT) (Mimosa bahamensis, Gymnopodium floribundum, Havardia albicans, Acacia pennatula, Lysiloma latisiliqum), and three plant species with negligible CT content (Leucaena leucocephala, Piscidia piscipula and Brosimum alicastrum). In the second period the foliage of B. alicastrum was withdrawn. A grain-based concentrate feed was offered daily at 1% BW in DM basis. Dry matter and nutrient intake was determined. Foliage selection of each experimental group was determined using the Chesson selection index. The H. contortus egg count per gram of faeces (EPG) was determined for infected goats twice daily. Chesson index showed a similar pattern of foliage selection on periods 1 and 2. Mean EPG of goats in IG was 2028±259 EPG during period 1 and 1 293±198 EPG during period 2 (P>0.05). During period 1, the selection pattern was highest for B. alicastrum (tannin-free), followed by a tannin-rich plant (M. bahamensis). These two plants remained

Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection

PubMed Central

2012-01-01

Background Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection. Methods Using TaqMan Low-Density Array (TLDA) analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP), varicella-zoster virus (VZV) and enterovirus (EV) were analyzed. Results The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated). Following qRT-PCR confirmation and receiver operational curve (ROC) analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p) were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC) value range, 0.711-0.848). Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Conclusions Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection. PMID:23272999

Selective isolation of Yersinia pestis from plague-infected fleas

PubMed Central

Sarovich, Derek S.; Colman, Rebecca E.; Price, Erin P.; Chung, Wai Kwan; Lee, Judy; Schupp, James M.; Alexander, James; Keim, Paul; Wagner., David M.

2010-01-01

We evaluated Yersinia CIN agar for the isolation of Yersinia pestis from infected fleas. CIN media is effective for the differentiation of Y. pestis from flea commensal flora and is sufficiently inhibitory to other bacteria that typically outcompete Y. pestis after 48 hours of growth using less selective media. PMID:20385178

Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at early and late times after infection.

PubMed

Price, Alexander M; Dai, Joanne; Bazot, Quentin; Patel, Luv; Nikitin, Pavel A; Djavadian, Reza; Winter, Peter S; Salinas, Cristina A; Barry, Ashley Perkins; Wood, Kris C; Johannsen, Eric C; Letai, Anthony; Allday, Martin J; Luftig, Micah A

2017-04-20

Latent Epstein-Barr virus (EBV) infection is causally linked to several human cancers. EBV expresses viral oncogenes that promote cell growth and inhibit the apoptotic response to uncontrolled proliferation. The EBV oncoprotein LMP1 constitutively activates NFκB and is critical for survival of EBV-immortalized B cells. However, during early infection EBV induces rapid B cell proliferation with low levels of LMP1 and little apoptosis. Therefore, we sought to define the mechanism of survival in the absence of LMP1/NFκB early after infection. We used BH3 profiling to query mitochondrial regulation of apoptosis and defined a transition from uninfected B cells (BCL-2) to early-infected (MCL-1/BCL-2) and immortalized cells (BFL-1). This dynamic change in B cell survival mechanisms is unique to virus-infected cells and relies on regulation of MCL-1 mitochondrial localization and BFL-1 transcription by the viral EBNA3A protein. This study defines a new role for EBNA3A in the suppression of apoptosis with implications for EBV lymphomagenesis.

[Surgical treatment for incisions fat colliquation or infections at early stage after operation of lumbar disc herniation].

PubMed

Guan, Ting-Jin; Zheng, Liang-Guo; Sun, Peng; Li, Xing-Xue

2014-05-01

To explore the reason, key diagnosic point and therapeutic method of the incisions fat colliquation or infections at early stage after operation of lumbar disc herniation. From July 2007 to May 2012, clinical data of 11 patients with incision fat liquefaction or early infection after lumbar discectomy were retrospectively analyzed. There were 5 males and 6 females with an average age of 43.1 years, and the mean time of incisions fat colliquation or infection was 5 days and a half after operation. The main clinical features included local wound pain aggravating, fervescence, fresh seepage in the wound, and blood inflammatory index increased, etc. The wound could heal at the first treatment stage or not was an evaluation standard of curative effect. All patients were followed up with an average period of 21 months. The wounds of 10 cases healed at the first stage without recurrence and complications. In 1 case infected by staphylococcus aureus, distal part of the wound present local red, swelling and with wave motion at 2 months after operation, staphylococcus aureus infection was confirmed after puncture and bacterial culture, and 1 thrum was found after local incision. The wound healed after change dressings for 1 week, without recurrence after followed up for 13 months. Preventing the risk factors before operation, minimizing invasive technique during operation reasonable antibiotics application for the lumbar operation reguiring placement objects, and correctly handling with wound after operation could prevent and reduce the incidence of incisions fat liquefaction or infection after operation of lumbar disc herniation. For incision fat liquefaction or infection, early diagnosis, debridement, VSD negative pressure irrigation and drainage, to choosing sensitive antibiotics according to the results of drug sensitivity, may contribute to wound early healing and decrease complication.

Accuracy of different diagnostic tests for early, delayed and late prosthetic joint infection.

PubMed

Fernández-Sampedro, M; Fariñas-Alvarez, C; Garces-Zarzalejo, C; Alonso-Aguirre, M A; Salas-Venero, C; Martínez-Martínez, L; Fariñas, M C

2017-08-25

A combination of laboratory, histopathological and microbiological tests for diagnosis of prosthetic joint infection (PJI) have been strongly recommended. This study aims to characterize the accuracy of individual or group tests, such as culture of sonicate fluid, synovial fluid and peri-implant tissue, C-reactive protein (CRP) and histopathology for detection of early, delayed and late PJI. A prospective study of patients undergoing hip or knee arthroplasty from February 2009 to February 2014 was performed in a Spanish tertiary health care hospital. The diagnostic accuracy of the different methods was evaluated constructing receiver-operating-characteristic (ROC) curve areas. One hundred thirty consecutive patients were included: 18 (13.8%) early PJI, 35 (27%) delayed PJI and 77 (59.2%) late PJI. For individual parameters, the area under the ROC curve for peri-implant tissue culture was larger for early (0.917) than for delayed (0.829) and late PJI (0.778), p = 0.033. There was a significantly larger difference for ROC area in the synovial fluid culture for delayed (0.803) than for early (0.781) and late infections (0.679), p = 0.039. The comparison of the areas under the ROC curves for the two microbiological tests showed that sonicate fluid was significantly different from peri-implant tissue in delayed (0.951 vs 0.829, p = 0.005) and late PJI (0.901 vs 0.778, p = 0.000). The conjunction of preoperative parameters, synovial fluid culture and CRP, improved the accuracy for late PJI (p = 0.01). The conjunction of histopathology and sonicate fluid culture increased the area under ROC curve of sonication in early (0.917 vs 1.000); p = 0.06 and late cases (0.901 vs 0.999); p < 0.001. For early PJI, sonicate fluid and peri-implant tissue cultures achieve the same best sensitivity. For delayed and late PJI, sonicate fluid culture is the most sensitive individual diagnostic method. By combining histopathology and peri-implant tissue, all early, 97% of

Reflections on Teaching Literacy: Selected Speeches of Margaret J. Early

ERIC Educational Resources Information Center

Wolcott, Willa, Ed.

2011-01-01

The late Margaret J. Early was a nationally renowned educator in the field of English education and reading, a past president of the National Council of Teachers of English, an author and an editor herself, and the recipient of many awards. The book Reflections on Teaching Literacy: Selected Speeches of Margaret J. Early, edited by Willa Wolcott,…

Selection and Validation of Model Early Childhood Projects: Final Report.

ERIC Educational Resources Information Center

Stock, John R.; And Others

Presented is the final report of a research program to select and describe outstanding Handicapped Children's Early Education Program (HCEEP) projects. Projects were analyzed in terms of 14 components of an HCEEP program (such as screening, programing, and inservice training). A detailed discussion of model selection and validation is appendixed.)…

Impacts of early viability selection on management of inbreeding and genetic diversity in conservation.

PubMed

Grueber, Catherine E; Hogg, Carolyn J; Ivy, Jamie A; Belov, Katherine

2015-04-01

Maintaining genetic diversity is a crucial goal of intensive management of threatened species, particularly for those populations that act as sources for translocation or re-introduction programmes. Most captive genetic management is based on pedigrees and a neutral theory of inheritance, an assumption that may be violated by selective forces operating in captivity. Here, we explore the conservation consequences of early viability selection: differential offspring survival that occurs prior to management or research observations, such as embryo deaths in utero. If early viability selection produces genotypic deviations from Mendelian predictions, it may undermine management strategies intended to minimize inbreeding and maintain genetic diversity. We use empirical examples to demonstrate that straightforward approaches, such as comparing litter sizes of inbred vs. noninbred breeding pairs, can be used to test whether early viability selection likely impacts estimates of inbreeding depression. We also show that comparing multilocus genotype data to pedigree predictions can reveal whether early viability selection drives systematic biases in genetic diversity, patterns that would not be detected using pedigree-based statistics alone. More sophisticated analysis combining genomewide molecular data with pedigree information will enable conservation scientists to test whether early viability selection drives deviations from neutrality across wide stretches of the genome, revealing whether this form of selection biases the pedigree-based statistics and inference upon which intensive management is based. © 2015 John Wiley & Sons Ltd.

Multispecific T cell response and negative HCV RNA tests during acute HCV infection are early prognostic factors of spontaneous clearance

PubMed Central

Spada, E; Mele, A; Berton, A; Ruggeri, L; Ferrigno, L; Garbuglia, A R; Perrone, M P; Girelli, G; Del Porto, P; Piccolella, E; Mondelli, M U; Amoroso, P; Cortese, R; Nicosia, A; Vitelli, A; Folgori, A

2004-01-01

Background/Aims: Hepatitis C virus (HCV) infection results in a high frequency of chronic disease. The aim of this study was to identify early prognostic markers of disease resolution by performing a comprehensive analysis of viral and host factors during the natural course of acute HCV infection. Methods: The clinical course of acute hepatitis C was determined in 34 consecutive patients. Epidemiological and virological parameters, as well as cell mediated immunity (CMI) and distribution of human leukocyte antigens (HLA) alleles were analysed. Results: Ten out of 34 patients experienced self-limiting infection, with most resolving patients showing fast kinetics of viral clearance: at least one negative HCV RNA test during this phase predicted a favourable outcome. Among other clinical epidemiological parameters measured, the self-limiting course was significantly associated with higher median peak bilirubin levels at the onset of disease, and with the female sex, but only the latter parameter was independently associated after multivariate analysis. No significant differences between self-limiting or chronic course were observed for the distribution of DRB1 and DQB1 alleles. HCV specific T cell response was more frequently detected during acute HCV infection, than in patients with chronic HCV disease. A significantly broader T cell response was found in patients with self-limiting infection than in those with chronic evolving acute hepatitis C. Conclusion: The results suggest that host related factors, in particular sex and CMI, play a crucial role in the spontaneous clearance of this virus. Most importantly, a negative HCV RNA test and broad CMI within the first month after onset of the symptoms represent very efficacious predictors of viral clearance and could thus be used as criteria in selecting candidates for early antiviral treatment. PMID:15479691

c-Myc Represses Transcription of Epstein-Barr Virus Latent Membrane Protein 1 Early after Primary B Cell Infection.

PubMed

Price, Alexander M; Messinger, Joshua E; Luftig, Micah A

2018-01-15

Recent evidence has shown that the Epstein-Barr virus (EBV) oncogene LMP1 is not expressed at high levels early after EBV infection of primary B cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (LCLs). In this study, we found that expression of LMP1 increased 50-fold between 7 days postinfection and the LCL state. Metabolic labeling of nascent transcribed mRNA indicated that this was primarily a transcription-mediated event. EBNA2, the key viral transcription factor regulating LMP1, and CTCF, an important chromatin insulator, were recruited to the LMP1 locus similarly early and late after infection. However, the activating histone H3K9Ac mark was enriched at the LMP1 promoter in LCLs relative to that in infected B cells early after infection. We found that high c-Myc activity in EBV-infected lymphoma cells as well as overexpression of c-Myc in an LCL model system repressed LMP1 transcription. Finally, we found that chemical inhibition of c-Myc both in LCLs and early after primary B cell infection increased LMP1 expression. These data support a model in which high levels of endogenous c-Myc activity induced early after primary B cell infection directly repress LMP1 transcription. IMPORTANCE EBV is a highly successful pathogen that latently infects more than 90% of adults worldwide and is also causally associated with a number of B cell malignancies. During the latent life cycle, EBV expresses a set of viral oncoproteins and noncoding RNAs with the potential to promote cancer. Critical among these is the viral latent membrane protein LMP1. Prior work suggests that LMP1 is essential for EBV to immortalize B cells, but our recent work indicates that LMP1 is not produced at high levels during the first few weeks after infection. Here we show that transcription of the LMP1 gene can be negatively regulated by a host transcription factor, c-Myc. Ultimately, understanding the regulation of EBV oncogenes will allow us

Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.

PubMed

Ferns, R Bridget; Tarr, Alexander W; Hue, Stephane; Urbanowicz, Richard A; McClure, C Patrick; Gilson, Richard; Ball, Jonathan K; Nastouli, Eleni; Garson, Jeremy A; Pillay, Deenan

2016-05-01

HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization. Copyright © 2016 Elsevier Inc. All rights reserved.

Selective Attention in Early Dementia of Alzheimer Type

ERIC Educational Resources Information Center

Fernandez-Duque, Diego; Black, Sandra E.

2008-01-01

This study explored possible deficits in selective attention brought about by Dementia of Alzheimer Type (DAT). In three experiments, we tested patients with early DAT, healthy elderly, and young adults under low memory demands to assess perceptual filtering, conflict resolution, and set switching abilities. We found no evidence of impaired…

Early Immune Responses in Rainbow Trout Liver upon Viral Hemorrhagic Septicemia Virus (VHSV) Infection

PubMed Central

Castro, Rosario; Abós, Beatriz; Pignatelli, Jaime; von Gersdorff Jørgensen, Louise; González Granja, Aitor; Buchmann, Kurt; Tafalla, Carolina

2014-01-01

Among the essential metabolic functions of the liver, in mammals, a role as mediator of systemic and local innate immunity has also been reported. Although the presence of an important leukocyte population in mammalian liver is well documented, the characterization of leukocyte populations in the teleost liver has been only scarcely addressed. In the current work, we have confirmed the presence of IgM+, IgD+, IgT+, CD8α+, CD3+ cells, and cells expressing major histocompatibility complex (MHC-II) in rainbow trout (Oncorhynchus mykiss) liver by flow cytometry and/or immunohistochemistry analysis. Additionally, the effect of viral hemorrhagic septicemia virus (VHSV) on the liver immune response was assessed. First, we studied the effect of viral intraperitoneal injection on the transcription of a wide selection of immune genes at days 1, 2 and 5 post-infection. These included a group of leukocyte markers genes, pattern recognition receptors (PRRs), chemokines, chemokine receptor genes, and other genes involved in the early immune response and in acute phase reaction. Our results indicate that T lymphocytes play a key role in the initial response to VHSV in the liver, since CD3, CD8, CD4, perforin, Mx and interferon (IFN) transcription levels were up-regulated in response to VHSV. Consequently, flow cytometry analysis of CD8α+ cells in liver and spleen at day 5 post-infection revealed a decrease in the number of CD8α+ cells in the spleen and an increased population in the liver. No differences were found however in the percentages of B lymphocyte (IgM+ or IgD+) populations. In addition, a strong up-regulation in the transcription levels of several PRRs and chemokines was observed from the second day of infection, indicating an important role of these factors in the response of the liver to viral infections. PMID:25338079

Are Sunflower chlorotic mottle virus infection symptoms modulated by early increases in leaf sugar concentration?

PubMed

Rodríguez, Marianela; Taleisnik, Edith; Lenardon, Sergio; Lascano, Ramiro

2010-09-15

Symptom development in a susceptible sunflower line inoculated with Sunflower chlorotic mottle virus (SuCMoV) was followed in the second pair of leaves at different post-inoculation times: before symptom expression (BS), at early (ES) and late (LS) symptom expression. Sugar and starch increases and photoinhibition were observed as early effects BS, and were maintained or enhanced later on, however, chlorophyll loss was detected only at LS. Photoinhibition correlated with a drastic decrease in D1 protein level. The progress of infection was accompanied by decreasing levels of apoplastic reactive oxygen species (ROS). In infected leaves, higher antioxidant enzyme activities (superoxide dismutase, SOD; ascorbate peroxidase, APX; glutathione reductase, GR) were observed from BS. The purpose of this work was to evaluate whether the early increases in carbohydrate accumulation may participate in SuCMoV symptom expression. Similar effects on photoinhibition, apoplastic ROS generation and antioxidant activity were generated when healthy leaves were treated with sugars. These results suggest that photoinhibitory processes and lower apoplastic superoxide levels induced by SuCMoV infection may be modulated by sugar increases. Copyright 2010 Elsevier GmbH. All rights reserved.

Some Limitations for Early Diagnosis of Congenital Chagas Infection by PCR.

PubMed

Volta, Bibiana Julieta; Perrone, Alina Elizabet; Rivero, Rocío; Scollo, Karenina; Bustos, Patricia Laura; Bua, Jacqueline

2018-04-01

Trypanosoma cruzi , the causing agent of Chagas disease, can be transmitted to the offspring of infected pregnant women, thus being an epidemiologically important way of parasite transmission in humans. In addition, the migration of infected women from endemic areas to nonendemic countries may export this parasite infection. The diagnosis of congenital Chagas disease relies on the detection of the parasite because maternal antibodies are passively transferred to infants during pregnancy. The diagnosis of congenital infection can also be confirmed by detection of infant-specific anti- T cruzi antibodies at 10 months after delivery. Because early detection of T cruzi infection in newborns allows an efficient trypanocidal treatment and cure, more sensitive molecular techniques such as DNA amplification are being used for a prompt parasitological diagnosis of children born to seropositive mothers. In this report, we describe a diagnosis case of a child congenitally infected with T cruzi who tested negative for parasite detection both by microscopic observation and DNA amplification at 20 days and 6 months after delivery. However, at 7 months of age, a hemoculture was made from the infant's blood, and the infective parasite was finally isolated and classified as T cruzi discrete typing unit I. In a retrospective study, real-time polymerase chain reaction also allowed detecting the parasite but failed to detect any parasite load in earlier control samples. This case report stresses that even when molecular techniques are negative, a long-term follow-up is necessary for the diagnosis of infants congenitally infected with T cruzi . Copyright © 2018 by the American Academy of Pediatrics.

Loop-mediated isothermal amplification (LAMP): early detection of Toxoplasma gondii infection in mice.

PubMed

Kong, Qing-Ming; Lu, Shao-Hong; Tong, Qun-Bo; Lou, Di; Chen, Rui; Zheng, Bin; Kumagai, Takashi; Wen, Li-Yong; Ohta, Nobuo; Zhou, Xiao-Nong

2012-01-03

Toxoplasmosis is a widespread zoonotic parasitic disease that occurs in both animals and humans. Traditional molecular assays are often difficult to perform, especially for the early diagnosis of Toxoplasma gondii infections. Here, we established a novel loop-mediated isothermal amplification targeting the 529 bp repeat element (529 bp-LAMP) to detect T. gondii DNA in blood samples of experimental mice infected with tachyzoites of the RH strain. The assay was performed with Bst DNA polymerase at 65°C for 1 h. The detection limit of the 529 bp-LAMP assay was as low as 0.6 fg of T. gondii DNA. The sensitivity of this assay was 100 and 1000 fold higher than that of the LAMP targeting B1 gene (B1-LAMP) and nested PCR targeting 529 bp repeat element (529 bp-nested PCR), respectively. The specificity of the 529 bp-LAMP assay was determined using the DNA samples of Trypanosoma evansi, Plasmodium falciparum, Paragonimus westermani, Schistosoma japonicum, Fasciola hepatica and Angiostrongylus cantonensis. No cross-reactivity with the DNA of any parasites was found. The assay was able to detect T. gondii DNA in all mouse blood samples at one day post infection (dpi). We report the following findings: (i) The detection limit of the 529 bp-LAMP assay is 0.6 fg of T. gondii DNA; (ii) The assay does not involve any cross-reactivity with the DNA of other parasites; (iii) This is the first report on the application of the LAMP assay for early diagnosis of toxoplasmosis in blood samples from experimentally infected mice. Due to its simplicity, sensitivity and cost-effectiveness for common use, we suggest that this assay should be used as an early diagnostic tool for health control of toxoplasmosis.

Experimental Infection of Plants with an Herbivore-Associated Bacterial Endosymbiont Influences Herbivore Host Selection Behavior

PubMed Central

Davis, Thomas Seth; Horton, David R.; Munyaneza, Joseph E.; Landolt, Peter J.

2012-01-01

Although bacterial endosymbioses are common among phloeophagous herbivores, little is known regarding the effects of symbionts on herbivore host selection and population dynamics. We tested the hypothesis that plant selection and reproductive performance by a phloem-feeding herbivore (potato psyllid, Bactericera cockerelli) is mediated by infection of plants with a bacterial endosymbiont. We controlled for the effects of herbivory and endosymbiont infection by exposing potato plants (Solanum tuberosum) to psyllids infected with “Candidatus Liberibacter solanacearum” or to uninfected psyllids. We used these treatments as a basis to experimentally test plant volatile emissions, herbivore settling and oviposition preferences, and herbivore population growth. Three important findings emerged: (1) plant volatile profiles differed with respect to both herbivory and herbivory plus endosymbiont infection when compared to undamaged control plants; (2) herbivores initially settled on plants exposed to endosymbiont-infected psyllids but later defected and oviposited primarily on plants exposed only to uninfected psyllids; and (3) plant infection status had little effect on herbivore reproduction, though plant flowering was associated with a 39% reduction in herbivore density on average. Our experiments support the hypothesis that plant infection with endosymbionts alters plant volatile profiles, and infected plants initially recruited herbivores but later repelled them. Also, our findings suggest that the endosymbiont may not place negative selection pressure on its host herbivore in this system, but plant flowering phenology appears correlated with psyllid population performance. PMID:23166641

Temporally selective attention modulates early perceptual processing: event-related potential evidence.

PubMed

Sanders, Lisa D; Astheimer, Lori B

2008-05-01

Some of the most important information we encounter changes so rapidly that our perceptual systems cannot process all of it in detail. Spatially selective attention is critical for perception when more information than can be processed in detail is presented simultaneously at distinct locations. When presented with complex, rapidly changing information, listeners may need to selectively attend to specific times rather than to locations. We present evidence that listeners can direct selective attention to time points that differ by as little as 500 msec, and that doing so improves target detection, affects baseline neural activity preceding stimulus presentation, and modulates auditory evoked potentials at a perceptually early stage. These data demonstrate that attentional modulation of early perceptual processing is temporally precise and that listeners can flexibly allocate temporally selective attention over short intervals, making it a viable mechanism for preferentially processing the most relevant segments in rapidly changing streams.

Early generation selection results from a two year, six location study

USDA-ARS?s Scientific Manuscript database

In potato breeding programs, early generation selections are rarely evaluated in multiple environments because of limited seed quantities. By the time seed quantities are available, few clones remain from the original population. The purpose of this study was to allow multiple locations to select ...

Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.

PubMed

Benton, Tami; Lynch, Kevin; Dubé, Benoit; Gettes, David R; Tustin, Nancy B; Ping Lai, Jian; Metzger, David S; Blume, Joshua; Douglas, Steven D; Evans, Dwight L

2010-11-01

To test the hypothesis that the selective serotonin reuptake inhibitor (SSRI) citalopram would down-regulate human immunodeficiency virus (HIV) infectivity and that the greatest effects would be seen in people with depression. Depression is a risk factor for morbidity and mortality in HIV/acquired immune deficiency syndrome. Serotonin (5-HT) neurotransmission has been implicated in the pathobiology of depression, and pharmacologic therapies for depression target this system. The 5-HT transporter and 5-HT receptors are widely distributed throughout the central nervous and immune systems. Depression has been associated with suppression of natural killer cells and CD8(+) lymphocytes, key regulators of HIV infection. Ex vivo models for acute and chronic HIV infection were used to study the effects of citalopram on HIV viral infection and replication in 48 depressed and nondepressed women. For both the acute and chronic infection models, HIV reverse transcriptase activity was measured in the citalopram treatment condition and the control condition. The SSRI significantly down-regulated the reverse transcriptase response in both the acute and chronic infection models. Specifically, citalopram significantly decreased the acute HIV infectivity of macrophages. Citalopram also significantly decreased HIV viral replication in the latently infected T-cell line and in the latently infected macrophage cell line. There was no difference in down-regulation by depression status. These studies suggest that an SSRI enhances natural killer/CD8 noncytolytic HIV suppression in HIV/acquired immune deficiency syndrome and decreases HIV viral infectivity of macrophages, ex vivo, suggesting the need for in vivo studies to determine a potential role for agents targeting serotonin in the host defense against HIV.

Early diagnosis of hantavirus infection by family doctors can reduce inappropriate antibiotic use and hospitalization.

PubMed

Brorstad, Alette; Oscarsson, Kristina Bergstedt; Ahlm, Clas

2010-09-01

Hantavirus infections are emerging infections that cause either Hantavirus pulmonary syndrome or haemorrhagic fever with renal syndrome (HFRS). A recent Swedish outbreak of nephropathia epidemica, a European HFRS, was analysed to study the patient flow and clinical picture and to investigate the value of an early diagnosis in general practice. Design. In a retrospective design, medical records of verified cases of Hantavirus infection were studied. The study was conducted in the county of Norrbotten, Sweden. Data from Hantavirus patients diagnosed between 2006 and 2008 were analysed. Demographic data, level of care, treatment, clinical symptoms, and laboratory findings were obtained. In total, 456 cases were included (58% males and 42% females). The majority of patients first saw their general practitioner and were exclusively treated in general practice (83% and 56%, respectively). When diagnosed correctly at the first visit, antibiotics and hospitalization were significantly lowered compared with delayed diagnosis (14% vs. 53% and 30% vs. 54%, respectively; p < 0.0001). The clinical picture was diverse. Early thrombocytopenia was found in 65% of the patients, and haemorrhagic manifestations were documented in a few cases. Signs of renal involvement--haematuria, proteinuria, and raised levels of serum creatinine--were found in a majority of patients. Raised awareness in general practice regarding emerging infections and better diagnostic tools are desirable. This study of a Hantavirus outbreak shows that general practitioners are frontline doctors during outbreaks and through early and correct diagnosis they can reduce antibiotic treatment and hospitalization.

Acute and chronic neurological consequences of early-life Zika virus infection in mice.

PubMed

Nem de Oliveira Souza, Isis; Frost, Paula S; França, Julia V; Nascimento-Viana, Jéssica B; Neris, Rômulo L S; Freitas, Leandro; Pinheiro, Daniel J L L; Nogueira, Clara O; Neves, Gilda; Chimelli, Leila; De Felice, Fernanda G; Cavalheiro, Ésper A; Ferreira, Sergio T; Assunção-Miranda, Iranaia; Figueiredo, Claudia P; Da Poian, Andrea T; Clarke, Julia R

2018-06-06

Although congenital Zika virus (ZIKV) exposure has been associated with microcephaly and other neurodevelopmental disorders, long-term consequences of perinatal infection are largely unknown. We evaluated short- and long-term neuropathological and behavioral consequences of neonatal ZIKV infection in mice. ZIKV showed brain tropism, causing postnatal-onset microcephaly and several behavioral deficits in adulthood. During the acute phase of infection, mice developed frequent seizures, which were reduced by tumor necrosis factor-α (TNF-α) inhibition. During adulthood, ZIKV replication persisted in neonatally infected mice, and the animals showed increased susceptibility to chemically induced seizures, neurodegeneration, and brain calcifications. Altogether, the results show that neonatal ZIKV infection has long-term neuropathological and behavioral complications in mice and suggest that early inhibition of TNF-α-mediated neuroinflammation might be an effective therapeutic strategy to prevent the development of chronic neurological abnormalities. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Viral reprogramming of the Daxx histone H3.3 chaperone during early Epstein-Barr virus infection.

PubMed

Tsai, Kevin; Chan, Lilian; Gibeault, Rebecca; Conn, Kristen; Dheekollu, Jayaraju; Domsic, John; Marmorstein, Ronen; Schang, Luis M; Lieberman, Paul M

2014-12-01

Host chromatin assembly can function as a barrier to viral infection. Epstein-Barr virus (EBV) establishes latent infection as chromatin-assembled episomes in which all but a few viral genes are transcriptionally silent. The factors that control chromatin assembly and guide transcription regulation during the establishment of latency are not well understood. Here, we demonstrate that the EBV tegument protein BNRF1 binds the histone H3.3 chaperone Daxx to modulate histone mobility and chromatin assembly on the EBV genome during the early stages of primary infection. We demonstrate that BNRF1 substitutes for the repressive cochaperone ATRX to form a ternary complex of BNRF1-Daxx-H3.3-H4, using coimmunoprecipitation and size-exclusion chromatography with highly purified components. FRAP (fluorescence recovery after photobleaching) assays were used to demonstrate that BNRF1 promotes global mobilization of cellular histone H3.3. Mutation of putative nucleotide binding motifs on BNRF1 attenuates the displacement of ATRX from Daxx. We also show by immunofluorescence combined with fluorescence in situ hybridization that BNRF1 is important for the dissociation of ATRX and Daxx from nuclear bodies during de novo infection of primary B lymphocytes. Virion-delivered BNRF1 suppresses Daxx-ATRX-mediated H3.3 loading on viral chromatin as measured by chromatin immunoprecipitation assays and enhances viral gene expression during early infection. We propose that EBV tegument protein BNRF1 replaces ATRX to reprogram Daxx-mediated H3.3 loading, in turn generating chromatin suitable for latent gene expression. Epstein-Barr Virus (EBV) is a human herpesvirus that efficiently establishes latent infection in primary B lymphocytes. Cellular chromatin assembly plays an important role in regulating the establishment of EBV latency. We show that the EBV tegument protein BNRF1 functions to regulate chromatin assembly on the viral genome during early infection. BNRF1 alters the host cellular

Gastrointestinal nematode infection does not affect selection of tropical foliage by goats in a cafeteria trial.

PubMed

Ventura-Cordero, J; González-Pech, P G; Jaimez-Rodriguez, P R; Ortíz-Ocampo, G I; Sandoval-Castro, C A; Torres-Acosta, J F J

2017-01-01

It is important to determine whether gastrointestinal nematodes (GINs) affect foliage choice of goats leading to confirm the expression of a self-medication behavior. This study investigated the effect of GIN infection on tropical foliage selection by goats. During experimental stage 1 (10 days), goats had a natural mixed GIN infection, and at stage 2 (10 days), goats were treated with effective anthelmintics to maintain them free of GIN infection. During stage 1 the twelve adult goats (32 ± 2.3 kg live weight [LW]) were assigned to three groups (n = 4) according to their initial GIN infection status: HI group, with fecal egg count (FEC) between 1450 and 2150 eggs per g/feces (EPG); MI group, medium FEC (592-1167 EPG); and the NI group, free from GIN infection. Fresh foliage of four tropical plants were offered to goats ad libitum for 1 h daily: Gymnopodium floribundum (high condensed tannin [CT] content, 37-40 %), Mimosa bahamensis (medium CT content, 16-17 %), Leucaena leucocephala (low CT content, 3-5 %), and Viguiera dentata (negligible CT content, 0.6-0.9 %). Jacobs' selection indexes (JSIs) were estimated for the experimental foliage based on dry matter (DM), CT, or crude protein (CP) intake. During both study stages, individual fecal egg counts were estimated. The JSI patterns of different plant species, based on DM, CT, or CP, were similar irrespective of infection level during stage 1 (HI, MI, and NI) or no GIN infection (stage 2). Thus, irrespective of GIN infection, goats actively selected M. bahamensis (high CT, low CP content) and V. dentata (negligible CT, high CP content) but avoided G. floribundum (high CT, low CP content) and L. leucocephala (medium CT and high CP content). Thus, natural GIN infection did not influence goats' foliage selection.

Functional selectivity for face processing in the temporal voice area of early deaf individuals

PubMed Central

van Ackeren, Markus J.; Rabini, Giuseppe; Zonca, Joshua; Foa, Valentina; Baruffaldi, Francesca; Rezk, Mohamed; Pavani, Francesco; Rossion, Bruno; Collignon, Olivier

2017-01-01

Brain systems supporting face and voice processing both contribute to the extraction of important information for social interaction (e.g., person identity). How does the brain reorganize when one of these channels is absent? Here, we explore this question by combining behavioral and multimodal neuroimaging measures (magneto-encephalography and functional imaging) in a group of early deaf humans. We show enhanced selective neural response for faces and for individual face coding in a specific region of the auditory cortex that is typically specialized for voice perception in hearing individuals. In this region, selectivity to face signals emerges early in the visual processing hierarchy, shortly after typical face-selective responses in the ventral visual pathway. Functional and effective connectivity analyses suggest reorganization in long-range connections from early visual areas to the face-selective temporal area in individuals with early and profound deafness. Altogether, these observations demonstrate that regions that typically specialize for voice processing in the hearing brain preferentially reorganize for face processing in born-deaf people. Our results support the idea that cross-modal plasticity in the case of early sensory deprivation relates to the original functional specialization of the reorganized brain regions. PMID:28652333

Specific Selection of Essential Oil Compounds for Treatment of Children’s Infection Diseases

PubMed Central

Pauli, Alexander; Schilcher, Heinz

2004-01-01

Preparations with essential oils and their dosages applied in the therapy of children’s infectious diseases are well documented. In contrast, information is only sparingly available about uses of isolated pure essential oil compounds for the treatment of such infections. To find out safe antimicrobials from essential oils, microbiological inhibitory data of children pathogens were combined with oral and dermal acute toxicity data to calculate oral and dermal therapeutical indices (TI). The superiority of antibiotic drugs became obvious following calculating oral TIs of antimicrobials from higher plants, which suggests that oral administrations of essential oil compounds are not suitable to cure severe infections. A few selected compounds from higher plants show moderate effectiveness against gram-positive bacteria, yeast and fungi, but not gram-negative bacteria. Topical application or inhalation of selected compounds for the treatment or additional treatment of mild infections is reasonable.

Effects of Perinatal HIV Infection and Early Institutional Rearing on Physical and Cognitive Development of Children in Ukraine

ERIC Educational Resources Information Center

Dobrova-Krol, Natasha A.; van IJzendoorn, Marinus H.; Bakermans-Kranenburg, Marian J.; Juffer, Femmie

2010-01-01

To study the effects of perinatal HIV-1 infection and early institutional rearing on the physical and cognitive development of children, 64 Ukrainian uninfected and HIV-infected institutionalized and family-reared children were examined (mean age = 50.9 months). Both HIV infection and institutional care were related to delays in physical and…

A susceptible-infected model of early detection of respiratory infection outbreaks on a background of influenza

PubMed Central

Mohtashemi, Mojdeh; Szolovits, Peter; Dunyak, James; Mandl, Kenneth D.

2013-01-01

The threat of biological warfare and the emergence of new infectious agents spreading at a global scale have highlighted the need for major enhancements to the public health infrastructure. Early detection of epidemics of infectious diseases requires both real-time data and real-time interpretation of data. Despite moderate advancements in data acquisition, the state of the practice for real-time analysis of data remains inadequate. We present a nonlinear mathematical framework for modeling the transient dynamics of influenza, applied to historical data sets of patients with influenza-like illness. We estimate the vital time-varying epidemiological parameters of infections from historical data, representing normal epidemiological trends. We then introduce simulated outbreaks of different shapes and magnitudes into the historical data, and estimate the parameters representing the infection rates of anomalous deviations from normal trends. Finally, a dynamic threshold-based detection algorithm is devised to assess the timeliness and sensitivity of detecting the irregularities in the data, under a fixed low false-positive rate. We find that the detection algorithm can identify such designated abnormalities in the data with high sensitivity with specificity held at 97%, but more importantly, early during an outbreak. The proposed methodology can be applied to a broad range of influenza-like infectious diseases, whether naturally occurring or a result of bioterrorism, and thus can be an integral component of a real-time surveillance system. PMID:16556450

[Different wavelengths selection methods for identification of early blight on tomato leaves by using hyperspectral imaging technique].

PubMed

Cheng, Shu-Xi; Xie, Chuan-Qi; Wang, Qiao-Nan; He, Yong; Shao, Yong-Ni

2014-05-01

Identification of early blight on tomato leaves by using hyperspectral imaging technique based on different effective wavelengths selection methods (successive projections algorithm, SPA; x-loading weights, x-LW; gram-schmidt orthogonaliza-tion, GSO) was studied in the present paper. Hyperspectral images of seventy healthy and seventy infected tomato leaves were obtained by hyperspectral imaging system across the wavelength range of 380-1023 nm. Reflectance of all pixels in region of interest (ROI) was extracted by ENVI 4. 7 software. Least squares-support vector machine (LS-SVM) model was established based on the full spectral wavelengths. It obtained an excellent result with the highest identification accuracy (100%) in both calibration and prediction sets. Then, EW-LS-SVM and EW-LDA models were established based on the selected wavelengths suggested by SPA, x-LW and GSO, respectively. The results showed that all of the EW-LS-SVM and EW-LDA models performed well with the identification accuracy of 100% in EW-LS-SVM model and 100%, 100% and 97. 83% in EW-LDA model, respectively. Moreover, the number of input wavelengths of SPA-LS-SVM, x-LW-LS-SVM and GSO-LS-SVM models were four (492, 550, 633 and 680 nm), three (631, 719 and 747 nm) and two (533 and 657 nm), respectively. Fewer input variables were beneficial for the development of identification instrument. It demonstrated that it is feasible to identify early blight on tomato leaves by using hyperspectral imaging, and SPA, x-LW and GSO were effective wavelengths selection methods.

Association Between Early Idiopathic Neonatal Jaundice and Urinary Tract Infections

PubMed Central

Özcan, Murat; Sarici, S Ümit; Yurdugül, Yüksel; Akpinar, Melis; Altun, Demet; Özcan, Begüm; Serdar, Muhittin A; Sarici, Dilek

2017-01-01

Background and purpose: Etiologic role, incidence, demographic, and response-to-treatment characteristics of urinary tract infection (UTI) among neonates, its relationship with significant neonatal hyperbilirubinemia, and abnormalities of the urinary system were studied in a prospective investigation in early (≤10 days) idiopathic neonatal jaundice in which all other etiologic factors of neonatal hyperbilirubinemia were ruled out. Patients and methods: Urine samples for microscopic and bacteriologic examination were obtained with bladder catheterization from 155 newborns with early neonatal jaundice. Newborns with a negative urine culture and with a positive urine culture were defined as group I and group II, respectively, and the 2 groups were compared with each other. Results: The incidence of UTI in whole of the study group was 16.7%. Serum total and direct bilirubin levels were statistically significantly higher in group II when compared with group I (P = .005 and P = .001, respectively). Decrease in serum total bilirubin level at the 24th hour of phototherapy was statistically significantly higher in group I compared with group II (P = .022). Conclusions: Urinary tract infection should be investigated in the etiologic evaluation of newborns with significant hyperbilirubinemia. The possibility of UTI should be considered in jaundiced newborns who do not respond to phototherapy well or have a prolonged duration of phototherapy treatment. PMID:28469520

[Determination of nosocomial infection incidence in mothers and newborns during the early postpartum period].

PubMed

Malavaud, S; Bou-Segonds, E; Berrebi, A; Castagno, R; Assouline, C; Connan, L

2003-04-01

We wished to determine the incidence of nosocomial infections in the mother and the newborn during the early postpartum period. Over a three-month period, the same investigator collected 50 different clinical and microbiological, standardized data related to infectious diseases in parturients and their newborns. Data were collected on 804 deliveries. The overall rate of nosocomial infection was 2.9% (23/804). For vaginal deliveries, the rate was 1.9% (12/615) and for deliveries by Cesarean section, the rate was 5.8% (11/189). Of 745 newborns followed until discharge from hospital, 0.7% (5/745) had a nosocomial infection. These results are in line with previously published rates of nosocomial infections, which varied between 0.2% to 2.3% for vaginal deliveries, 1.6% to 18.9% for Cesarean section, and 0.2 to 4% in newborns. Regular surveys of the incidence or the prevalence of nosocomial infections are necessary to monitor the effectiveness of educational programs, aimed to reduce hospital acquired infections.

Decision-support models for empiric antibiotic selection in Gram-negative bloodstream infections.

PubMed

MacFadden, D R; Coburn, B; Shah, N; Robicsek, A; Savage, R; Elligsen, M; Daneman, N

2018-04-25

Early empiric antibiotic therapy in patients can improve clinical outcomes in Gram-negative bacteraemia. However, the widespread prevalence of antibiotic-resistant pathogens compromises our ability to provide adequate therapy while minimizing use of broad antibiotics. We sought to determine whether readily available electronic medical record data could be used to develop predictive models for decision support in Gram-negative bacteraemia. We performed a multi-centre cohort study, in Canada and the USA, of hospitalized patients with Gram-negative bloodstream infection from April 2010 to March 2015. We analysed multivariable models for prediction of antibiotic susceptibility at two empiric windows: Gram-stain-guided and pathogen-guided treatment. Decision-support models for empiric antibiotic selection were developed based on three clinical decision thresholds of acceptable adequate coverage (80%, 90% and 95%). A total of 1832 patients with Gram-negative bacteraemia were evaluated. Multivariable models showed good discrimination across countries and at both Gram-stain-guided (12 models, areas under the curve (AUCs) 0.68-0.89, optimism-corrected AUCs 0.63-0.85) and pathogen-guided (12 models, AUCs 0.75-0.98, optimism-corrected AUCs 0.64-0.95) windows. Compared to antibiogram-guided therapy, decision-support models of antibiotic selection incorporating individual patient characteristics and prior culture results have the potential to increase use of narrower-spectrum antibiotics (in up to 78% of patients) while reducing inadequate therapy. Multivariable models using readily available epidemiologic factors can be used to predict antimicrobial susceptibility in infecting pathogens with reasonable discriminatory ability. Implementation of sequential predictive models for real-time individualized empiric antibiotic decision-making has the potential to both optimize adequate coverage for patients while minimizing overuse of broad-spectrum antibiotics, and therefore requires

Distinct expression patterns of CD69 in mucosal and systemic lymphoid tissues in primary SIV infection of rhesus macaques.

PubMed

Wang, Xiaolei; Xu, Huanbin; Alvarez, Xavier; Pahar, Bapi; Moroney-Rasmussen, Terri; Lackner, Andrew A; Veazey, Ronald S

2011-01-01

Although the intestinal tract plays a major role in early human immunodeficiency virus (HIV) infection, the role of immune activation and viral replication in intestinal tissues is not completely understood. Further, increasing evidence suggests the early leukocyte activation antigen CD69 may be involved in the development or regulation of important T cell subsets, as well as a major regulatory molecule of immune responses. Using the simian immunodeficiency virus (SIV) rhesus macaque model, we compared expression of CD69 on T cells from the intestine, spleen, lymph nodes, and blood of normal and SIV-infected macaques throughout infection. In uninfected macaques, the majority of intestinal lamina propria CD4+ T cells had a memory (CD95+) phenotype and co-expressed CD69, and essentially all intestinal CCR5+ cells co-expressed CD69. In contrast, systemic lymphoid tissues had far fewer CD69+ T cells, and many had a naïve phenotype. Further, marked, selective depletion of intestinal CD4+CD69+ T cells occurred in early SIV infection, and this depletion persisted throughout infection. Markedly increased levels of CD8+CD69+ T cells were detected after SIV infection in virtually all tissues, including the intestine. Further, confocal microscopy demonstrated selective, productive infection of CD3+CD69+ T cells in the intestine in early infection. Combined, these results indicate CD69+CD4+ T cells are a major early target for viral infection, and their rapid loss by direct infection may have profound effects on intestinal immune regulation in HIV infected patients.

EARLY DIAGNOSIS IN POST RENAL TRANSPLANT OPPORTUNISTIC INFECTIONS: A FRESH LOOK.

PubMed

Chopra, G S; Narula, A S; Reddy, P S; Bhardwaj, J R

1999-04-01

A total of 86 renal transplant patients who were transplanted with live related donor (LRD) and live unrelated donor (LURD) kidneys were studied for opportunistic infections. Immune diagnosis of Toxoplasma, Cytomegalovirus (CMV), Herpes-simplex virus type II (HSV-2), Aspergillosis and Tuberculosis was carried out in these patients along with sputum examination, CSF studies and biopsy of lymphnode and other tissues in few cases. A high degree of Toxoplasma, CMV & HSV-2 positivity was seen in transplanted patients. However sensitivity of serological diagnosis of tuberculos was found to be low with standard criteria, which increased significantly when modified criteria were used. It is concluded that regular immunological monitoring should be carried out in transplanted patients so as to reach an early diagnosis and management of opportunistic infections.

Association Between Parental Hospital-Treated Infection and the Risk of Schizophrenia in Adolescence and Early Adulthood

PubMed Central

Nielsen, Philip R.; Laursen, Thomas M.; Mortensen, Preben B.

2013-01-01

It has been suggested that infection during perinatal life may lie at the etiological root of schizophrenia. It has thus been hypothesized that the origin of schizophrenia may lie either in direct fetal infection and/or in a generally increased familial susceptibility to infections, some of which may occur during pregnancy. We explored these 2 hypotheses by assessing maternal infection during pregnancy and maternal as well as paternal infection in general as predictors of schizophrenia in their offspring. We found a slightly increased risk to be associated with prenatal infection exposure. However, the effect of prenatal infection exposure was not statistically significantly different from the effect of infection exposure in general. Parental infection appeared to be associated with development of schizophrenia in adolescence and early adulthood. Our study does not exclude a specific effect of infection during fetal life; yet, it does suggest that schizophrenia is associated with an increased familial liability to develop severe infection. PMID:22021661

Intestinal Integrity Biomarkers in Early Antiretroviral-Treated Perinatally HIV-1-Infected Infants.

PubMed

Koay, Wei Li A; Lindsey, Jane C; Uprety, Priyanka; Bwakura-Dangarembizi, Mutsa; Weinberg, Adriana; Levin, Myron J; Persaud, Deborah

2018-05-12

Biomarkers of intestinal integrity (intestinal fatty acid binding protein (iFABP) and zonulin), were compared in early antiretroviral-treated, HIV-1-infected (HIV+; n=56) African infants and HIV-exposed but uninfected (HEU; n=53) controls. Despite heightened inflammation and immune activation in HIV+ infants, iFABP and zonulin levels at three months of age were not different from those in HEU infants, and largely not correlated with inflammatory and immune activation biomarkers. However, zonulin levels increased, and became significantly higher in HIV+ compared to HEU infants by five months of age despite ART-suppression. These findings have implications for intestinal integrity biomarker profiling in perinatal HIV-1 infection.

Prediction of early postoperative infections in pediatric liver transplantation by logistic regression

NASA Astrophysics Data System (ADS)

Uzunova, Yordanka; Prodanova, Krasimira; Spassov, Lubomir

2016-12-01

Orthotopic liver transplantation (OLT) is the only curative treatment for end-stage liver disease. Early diagnosis and treatment of infections after OLT are usually associated with improved outcomes. This study's objective is to identify reliable factors that can predict postoperative infectious morbidity. 27 children were included in the analysis. They underwent liver transplantation in our department. The correlation between two parameters (the level of blood glucose at 5th postoperative day and the duration of the anhepatic phase) and postoperative infections was analyzed, using univariate analysis. In this analysis, an independent predictive factor was derived which adequately identifies patients at risk of infectious complications after a liver transplantation.

Identification of immunodominant Leishmania major antigenic markers of the early C57BL/6 and BALB/c mice infection stages.

PubMed

Sassi, Atfa; Kaak, Olfa; Elgaaied, Amel Benammar

2015-08-24

The C57BL/6 mouse strain is resistant to Leishmania (L.) major infection and, unlike susceptible BALB/c, develops small self healing cutaneous lesions. The specific antibody responses of C57BL/6 and BALB/c mice were previously characterized by the predominance of IgG2a ("resistant" isotype associated with Th1) and IgG1 ("pathogenic" isotype associated with Th2) antibodies, respectively. In this study, we looked for the presence of antigens able to elicit an exclusive or predominant IgG1 production during the early stages of C57BL/6 lesion development and checked whether they are recognized or not by BALB/c mice. We demonstrate first that IgG2a predominance in C57BL/6 sera occurs only late after infection whereas in BALB/c, IgG1 antibodies dominate mostly in the early stages. Interestingly, soon after inoculation of live amastigotes, C57BL/6 displayed an exclusive IgG1 reactivity against particular L. major antigens but with MWs different from those identified in BALB/c. Furthermore, mice immunized with killed amastigotes displayed striking differences in their immunodetection profiles, particularly for the IgG1 isotype. Taken together, the observed differences in the specific antibody repertoires between infected mice resulted, at least in part, from immunological events independent from those triggered by the replicating parasite, and bring new insights into the selection of future vaccine candidates. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The roles of early surgery and comorbid conditions on outcomes of severe necrotizing soft-tissue infections.

PubMed

Latifi, Rifat; Patel, Apar S; Samson, David J; Tilley, Elizabeth H; Gashi, Saranda; Bergamaschi, Roberto; El-Menyar, Ayman

2018-05-22

Severe necrotizing soft-tissue infections (NSTIs) require immediate early surgical treatment to avoid adverse outcomes. This study aims to determine the impact of early surgery and comorbid conditions on the outcomes of NSTIs. A retrospective cohort study was performed on all subjects presenting with NSTI at an academic medical center between 2005 and 2016. Patients were identified based on ICD codes. Those under the age of 18 or with intraoperative findings not consistent with NSTI diagnosis were excluded. There were 115 patients with a confirmed diagnosis of NSTI with a mean age of 55 ± 18 years; 41% were females and 55% were diabetics. Thirty percent of patients underwent early surgery (< 6 h). There were no significant differences between groups in baseline characteristics. The late group (≥ 6 h) had prolonged hospital stay (38 vs. 23 days, p < 0.008) in comparison to the early group (< 6 h). With every 1 h delay in time to surgery, there is a 0.268 day increase in length of stay, adjusted for these other variables: alcohol abuse, number of debridements, peripheral vascular disease, previous infection and clinical necrosis. Mortality was 16.5%. Multivariable analysis revealed that alcohol abuse, peripheral vascular disease, diabetes, obesity, hypothyroidism, and presence of COPD were associated with an increase in mortality. Early surgical intervention in patients with severe necrotizing soft-tissue infections reduces length of hospital stay. Presence of comorbid conditions such as alcohol abuse, peripheral vascular disease, diabetes, obesity and hypothyroidism were associated with increased mortality.

Early primary cytomegalovirus infection in pregnancy: maternal hyperimmunoglobulin therapy improves outcomes among infants at 1 year of age.

PubMed

Visentin, Silvia; Manara, Renzo; Milanese, Laura; Da Roit, Anna; Forner, Gabriella; Salviato, Eleonora; Citton, Valentina; Magno, Fioretta Marciani; Orzan, Eva; Morando, Carla; Cusinato, Riccardo; Mengoli, Carlo; Palu, Giorgio; Ermani, Mario; Rinaldi, Roberto; Cosmi, Erich; Gussetti, Nadia

2012-08-01

Primary cytomegalovirus (CMV) infection during pregnancy is the leading infectious cause of congenital neurological disabilities. Early CMV infection carries a higher risk of adverse neonatal outcome (sensorineural hearing loss or neurological deficits). Intravenous hyperimmunoglobulin (HIG) therapy seems to be promising, but its efficacy needs further investigation. Since 2002, we have enrolled consecutively all pregnant women with early (ie, before gestational week 17) CMV infection. Beginning in 2007, all women were offered treatment with HIG (200 UI per kilogram of maternal weight, in a single intravenous administration). Outcome of infants was evaluated at the age of 1 year. Of the 592 women with early primary CMV infection, amniocentesis for CMV DNA detection was performed for 446. Of the 92 CMV-positive fetuses, pregnancy was terminated for 24, HIG was administered to mothers of 31, and no treatment was received by mothers of 37. Fetuses of treated mothers did not differ from fetuses of nontreated mothers according to mother's age, gestational week of infection, CMV load, or detection of abnormal ultrasonography findings. At the 1-year evaluation, 4 of 31 infants with treated mothers (13%; 95% confidence interval [CI], 1%-25%) and 16 of 37 infants with nontreated mothers (43%; 95% CI, 27%-59%) presented with poor outcomes (P < .01, by the 2-tailed Fisher exact test). HIG treatment improved the outcome of fetuses from women who had primary CMV infection before gestational week 17.

Long-Term Evolution of Burkholderia multivorans during a Chronic Cystic Fibrosis Infection Reveals Shifting Forces of Selection

PubMed Central

Silva, Inês N.; Santos, Mário R.; Zlosnik, James E. A.; Speert, David P.; Buskirk, Sean W.; Bruger, Eric L.; Waters, Christopher M.

2016-01-01

ABSTRACT Burkholderia multivorans is an opportunistic pathogen capable of causing severe disease in patients with cystic fibrosis (CF). Patients may be chronically infected for years, during which the bacterial population evolves in response to unknown forces. Here we analyze the genomic and functional evolution of a B. multivorans infection that was sequentially sampled from a CF patient over 20 years. The population diversified into at least four primary, coexisting clades with distinct evolutionary dynamics. The average substitution rate was only 2.4 mutations/year, but notably, some lineages evolved more slowly, whereas one diversified more rapidly by mostly nonsynonymous mutations. Ten loci, mostly involved in gene expression regulation and lipid metabolism, acquired three or more independent mutations and define likely targets of selection. Further, a broad range of phenotypes changed in association with the evolved mutations; they included antimicrobial resistance, biofilm regulation, and the presentation of lipopolysaccharide O-antigen repeats, which was directly caused by evolved mutations. Additionally, early isolates acquired mutations in genes involved in cyclic di-GMP (c-di-GMP) metabolism that associated with increased c-di-GMP intracellular levels. Accordingly, these isolates showed lower motility and increased biofilm formation and adhesion to CFBE41o− epithelial cells than the initial isolate, and each of these phenotypes is an important trait for bacterial persistence. The timing of the emergence of this clade of more adherent genotypes correlated with the period of greatest decline in the patient’s lung function. All together, our observations suggest that selection on B. multivorans populations during long-term colonization of CF patient lungs either directly or indirectly targets adherence, metabolism, and changes in the cell envelope related to adaptation to the biofilm lifestyle. IMPORTANCE Bacteria may become genetically and

Domestic dengue infection with hemophagocytic lymphohistiocytosis successfully treated by early steroid therapy.

PubMed

Yoshifuji, Kota; Oshina, Takahiro; Sonokawa, Saeko; Noguchi, Yuma; Suzuki, Sayaka; Tanaka, Keisuke; Kumagai, Takashi

2016-07-01

A 34-year-old man, working at a park in Tokyo, Japan, was repeatedly bitten by mosquitoes while cutting grass. He was hospitalized with sudden fever, fatigue, and weakness. He was eventually diagnosed with dengue virus infection, detected using reverse transcription polymerase chain reaction for the genome and by the presence of nonstructural protein 1 in his peripheral blood. Symptomatic treatments such as acetaminophen for the fever were not effective. Moreover, peripheral blood examination showed drastically decreased white blood cells and platelets, as well as marked elevations of ferritin and soluble interleukin 2 receptor. Furthermore, bone marrow examination revealed increased macrophages with hemophagocytosis. Dengue infection with hemophagocytic lymphohistiocytosis (HLH) was ultimately diagnosed. Half-dose steroid pulse therapy for three days dramatically reduced his temperature, thereby ameliorating physical symptoms and restoring normal peripheral blood data. He was discharged 12 days after admission. Dengue infection with HLH is rare and this is the first report, to our knowledge, of domestic dengue infection with HLH in Japan. Early steroid therapy may be effective in such cases.

Critical potential of early cardiac surgery for infective endocarditis with cardio-embolic strokes.

PubMed

Suzuki, Makoto; Takanashi, Shuichiro; Ohshima, Yutaro; Nagatomo, Yuji; Seki, Atsushi; Takamisawa, Itaru; Tobaru, Tetsuya; Naito, Kazuhiro; Kin, Hajime; Umemura, Jun; Takayama, Morimasa; Sumiyoshi, Tetsuya; Tomoike, Hitonobu

2017-01-15

Early cardiac surgery may have a trade-off between stabilized hemodynamics with controlled infection and a risk of peri-operative death in patients with infective endocarditis (IE) complicated with cardio-embolic strokes. We retrospectively studied clinical characteristics and outcomes in 68 consecutive patients with IE (mean age, 58±3years, 62% male) who admitted in our institute during June 2013 and August 2015. Cardio-embolic strokes were noted in 37% of patients (n=25) with IE and overall in-hospital mortality was 4 times higher in IE with cardio-embolic strokes than IE with an absence of strokes (n=43) (20% vs. 4.7%, p=0.045). Bacteremia of Staphylococcus aureus (p=0.021) and a complication of cardio-embolic strokes (p=0.031) were independently associated with in-hospital death in those with IE. However, in-hospital mortality was quite low in 19 with early cardiac surgery compared with 6 with conventional treatment in those with cardio-embolic strokes (11% vs. 50%, p=0.035). Multivariate logistic analysis demonstrated that lack of early cardiac surgery (p=0.014), a complication of cerebral hemorrhage (p=0.002), and a presence of refractory heart failure (p=0.047) were independently associated with in-hospital death in those with IE complicated with cardio-embolic strokes. Early cardiac surgery may provide clinical advantages overcoming peri-operative risks in those with IE complicated with cardio-embolic strokes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib.

PubMed

Ghez, David; Calleja, Anne; Protin, Caroline; Baron, Marine; Ledoux, Marie-Pierre; Damaj, Gandhi; Dupont, Mathieu; Dreyfus, Brigitte; Ferrant, Emmanuelle; Herbaux, Charles; Laribi, Kamel; Le Calloch, Ronan; Malphettes, Marion; Paul, Franciane; Souchet, Laetitia; Truchan-Graczyk, Malgorzata; Delavigne, Karen; Dartigeas, Caroline; Ysebaert, Loïc

2018-04-26

Ibrutinib has revolutionized the management of chronic lymphocytic leukemia and is now being increasingly used. Although considered to be less immunosuppressive than conventional immunochemotherapy, the observation of a few cases of invasive fungal infections in patients treated with ibrutinib prompted us to conduct a retrospective survey. We identified 33 cases of invasive fungal infections in patients receiving ibrutinib alone or in combination. Invasive aspergillosis (IA) was overrepresented (27/33) and was associated with cerebral localizations in 40% of the cases. Remarkably, most cases of invasive fungal infections occurred with a median of 3 months after starting ibrutinib. In 18/33 cases, other conditions that could have contributed to decreased antifungal responses, such as corticosteroids, neutropenia, or combined immunochemotherapy, were present. These observations indicate that ibrutinib may be associated with early-onset invasive fungal infections, in particular IA with frequent cerebral involvement, and that patients on ibrutinib should be closely monitored in particular when other risk factors of fungal infections are present. © 2018 by The American Society of Hematology.

[Osteosynthesis-associated infections : Epidemiology, definition and diagnosis].

PubMed

Renz, N; Feihl, S; Dlaska, C E; Schütz, M A; Trampuz, A

2017-06-01

Osteosynthesis-associated infections occur in 1-5% after closed and in up to 30% after open fractures. There are three different descriptions of implant-associated infections after fracture fixation, which are crucial for the selection of the adequate treatment strategy; temporal appearance from the index surgery (early versus late), pathogenesis of the infection (exogenous, hematogenous and contiguous from an adjacent focus), duration of infection symptoms (acute versus chronic). Diagnosis of osteosynthesis-associated infection is challenging, as chronic low-grade infections often present only with unspecific and subtle clinical symptoms. History, clinical evaluation, imaging, histopathlogical and microbiological examination build the cornerstones of diagnostics in implant-associated infections. A new onset of rest pain, early loosening of the prosthesis or mechanically unexplained, nonunion should raise suspicion for infection and prompt further evaluation. Percutaneous sinus tracts, purulent wound secretion and skin erosions with visibility of the implant confirm the implant-associated infection. Elevated C‑reactive protein value in blood is a supportive argument for infection, but is neither sensitive nor specific for infection. Imaging plays a key role to detect nonunions, infectious callus, sequester, peri-implant osteolysis and extraosseous and intramedullary involvement. Through microbiological and histopathological examination of intraoperative tissue samples, as well as sonication of explanted implants the causative pathogen is identified in most cases.

Selection is stronger in early-versus-late stages of divergence in a Neotropical livebearing fish.

PubMed

Ingley, Spencer J; Johnson, Jerald B

2016-03-01

How selection acts to drive trait evolution at different stages of divergence is of fundamental importance in our understanding of the origins of biodiversity. Yet, most studies have focused on a single point along an evolutionary trajectory. Here, we provide a case study evaluating the strength of divergent selection acting on life-history traits at early-versus-late stages of divergence in Brachyrhaphis fishes. We find that the difference in selection is stronger in the early-diverged population than the late-diverged population, and that trait differences acquired early are maintained over time. © 2016 The Author(s).

Incidence of infection after early intramedullary nailing of open tibial shaft fractures stabilized with pinless external fixators

PubMed Central

Kulshrestha, Vikas

2008-01-01

Background: A major drawback of conventional fixator system is the penetration of fixator pins into the medullary canal. The pins create a direct link between the medullary cavity and outer environment, leading to higher infection rates on conversion to intramedullary nailing. This disadvantage is overcome by the AO pinless fixator, in which the trocar points are clamped onto the outer cortex without penetrating it. This study was designed to evaluate the role of AO pinless fixators in primary stabilization of open diaphyseal tibial fractures that received staged treatment because of delayed presentation or poor general condition. We also analyzed the rate of infection on early conversion to intramedullary nail. Materials and Methods: This study is a retrospective review of 30 open diaphyseal fractures of tibia, which were managed with primary stabilization with pinless fixator and early exchange nailing. Outcome was evaluated in terms of fracture union and rate of residual infection. The data were compared with that available in the literature. Results: All the cases were followed up for a period of 2 years. The study includes Gustilo type 1 (n=10), 14 Gustilo type 2 (n=14), and type3 (n=6) cases. 6 cases (20%) had clamp site infection, 2 cases (6.7%) had deep infection, and in 28 cases (93%) the fracture healed and consolidated well. Conclusion: This study has highlighted the valuable role of pinless external fixator in the management of open tibial fractures in terms of safety and ease of application as well as the advantage of early conversion to intramedullary implant without the risk of deep infection. PMID:19753227

The 2013 Frank Stinchfield Award: Diagnosis of infection in the early postoperative period after total hip arthroplasty.

PubMed

Yi, Paul H; Cross, Michael B; Moric, Mario; Sporer, Scott M; Berger, Richard A; Della Valle, Craig J

2014-02-01

Diagnosis of periprosthetic joint infection (PJI) can be difficult in the early postoperative period after total hip arthroplasty (THA) because normal cues from the physical examination often are unreliable, and serological markers commonly used for diagnosis are elevated from the recent surgery. The purposes of this study were to determine the optimal cutoff values for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), synovial fluid white blood cell (WBC) count, and differential for diagnosing PJI in the early postoperative period after primary THA. We reviewed 6033 consecutive primary THAs and identified 73 patients (1.2%) who underwent reoperation for any reason within the first 6 weeks postoperatively. Thirty-six of these patients were infected according to modified Musculoskeletal Infection Society criteria. Mean values for the diagnostic tests were compared between groups and receiver operating characteristic curves generated along with an area under the curve (AUC) to determine test performance and optimal cutoff values to diagnose infection. The best test for the diagnosis of PJI was the synovial fluid WBC count (AUC = 98%; optimal cutoff value 12,800 cells/μL) followed by the CRP (AUC = 93%; optimal cutoff value 93 mg/L), and synovial fluid differential (AUC = 91%; optimal cutoff value 89% PMN). The mean ESR (infected = 69 mm/hr, not infected = 46 mm/hr), CRP (infected = 192 mg/L, not infected = 30 mg/L), synovial fluid WBC count (infected = 84,954 cells/μL, not infected = 2391 cells/μL), and differential (infected = 91% polymorphonuclear cells [PMN], not infected = 63% PMN) all were significantly higher in the infected group. Optimal cutoff values for the diagnosis of PJI in the acute postoperative period were higher than those traditionally used for the diagnosis of chronic PJI. The serum CRP is an excellent screening test, whereas the synovial fluid WBC count is more specific.

Developments in early diagnosis and therapy of HIV infection in newborns.

PubMed

Canals, Francisco; Masiá, Mar; Gutiérrez, Félix

2018-01-01

Infants who acquire HIV have an exceptionally high risk of morbidity and mortality if they do not receive antiretroviral therapy (ART). Areas covered: This review aims to summarize the currently available evidence on ART in HIV-infected neonates. Data were obtained from literature searches from PubMed, abstracts from International Conferences (2000-2017), and authors' files. Expert opinion: Current evidence favors early diagnosis and prompt ART of HIV infection in newborns. The precise timing of initiation of ART remains undetermined. Very early (close to birth) ART appears to limit the size of the viral reservoir and may restrict replication-competent virus, but the clinical benefit remains unproven. Among the current options for initial therapy, in full term neonates from 2 weeks of life onwards, a lopinavir/ritonavir-based three-drug regimen is preferred. In term infants, younger than 2 weeks a nevirapine-based regimen is recommended, although there are no clinical trial data supporting that initiating treatment before 2 weeks improves outcome compared to starting afterwards. Existing safety information is insufficient to recommend ART in preterm infants, with pharmacokinetic data available for zidovudine only. If ART is considered in this setting, an individual case assessment of the risk/benefit ratio of treatment should be made.

Translating Translations: Selecting and Using Translated Early Childhood Materials.

ERIC Educational Resources Information Center

Santos, Rosa Milagros; Lee, Sung Yoon; Valdivia, Rebeca; Zhang, Chun

2001-01-01

This article provides early intervention professionals with strategies for selecting and using translated materials. It stresses the importance of considering both the intended audience of the material and the quality of the translation itself. The article notes that many Web-based translator programs fail to capture the idiomatic usage or…

Dissociating early- and late-selection processes in recall: the mixed blessing of categorized study lists.

PubMed

Guzel, Mehmet A; Higham, Philip A

2013-07-01

Two experiments are reported in which we used type-2 signal detection theory to separate the effects of semantic categorization on early- and late-selection processes in free and cued recall. In Experiment 1, participants studied cue-target pairs for which the targets belonged to two, six, or 24 semantic categories, and later the participants were required to recall the targets either with (cued recall) or without (free recall) the studied cues. A confidence rating and a report decision were also required, so that we could compute both forced-report quantity and metacognitive resolution (type-2 discrimination), which served as our estimates of early- and late-selection processes, respectively. Consistent with prior research, having fewer categories enhanced the early-selection process (in performance, two > six > 24 categories). However, in contrast, the late-selection process was impaired (24 > six = two categories). In Experiment 2, encoding of paired associates, for which the targets belonged to either two or 20 semantic categories, was manipulated by having participants either form interactive images or engage in rote repetition. Having fewer categories again was associated with enhanced early selection (two > 20 categories); this effect was greater for rote repetition than for interactive imagery, and greater for free recall than for cued recall. However, late selection again showed the opposite pattern (20 > two categories), even with interactive-imagery encoding, which formed distinctive, individuated memory traces. The results are discussed in terms of early- and late-selection processes in retrieval, as well as overt versus covert recognition.

Education Inequality in Slovakia: The Effects of Early Selection

ERIC Educational Resources Information Center

Zelmanova, Olga; Korsnakova, Paulina; Tramonte, Lucia; Willms, J. Douglas

2006-01-01

Like many other countries in Central and Eastern Europe, children in Slovakia are allocated to different types of schools at an early age based upon their perceived aptitude. Part of the selection process includes an attempt to identify those children who are particularly academic-oriented. Primary and secondary education in Slovakia is divided…

Constitutively Expressed IFITM3 Protein in Human Endothelial Cells Poses an Early Infection Block to Human Influenza Viruses

PubMed Central

Sun, Xiangjie; Zeng, Hui; Kumar, Amrita; Belser, Jessica A.; Maines, Taronna R.

2016-01-01

ABSTRACT A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza viruses were capable of binding to host cellular receptors, becoming internalized and initiating hemifusion but failing to uncoat the viral nucleocapsid and to replicate in host nuclei. Unlike numerous cell types, including epithelial cells, we found that pulmonary endothelial cells constitutively express a high level of the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by small interfering RNA (siRNA) could partially rescue H1N1 virus infection in HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus infection in endothelial cells. In contrast, selected avian influenza viruses were able to escape IFITM3 restriction in endothelial cells, possibly by fusing in early endosomes at higher pH or by other, unknown mechanisms. Collectively, our study demonstrates that the human pulmonary endothelium possesses intrinsic immunity to human influenza viruses, in part due to the constitutive expression of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to escape this restriction, possibly contributing to virus-induced pneumonia and severe lung disease in humans. IMPORTANCE Avian influenza viruses, including H5N1 and H7N9, have been associated with severe respiratory disease and fatal outcomes in humans. Although acute respiratory distress syndrome (ARDS) and progressive pulmonary

Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques

PubMed Central

Moukambi, Félicien; Rabezanahary, Henintsoa; Rodrigues, Vasco; Racine, Gina; Robitaille, Lynda; Krust, Bernard; Andreani, Guadalupe; Soundaramourty, Calayselvy; Silvestre, Ricardo; Laforge, Mireille; Estaquier, Jérôme

2015-01-01

Follicular T helper cells (Tfh), a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs) during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs) during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies. PMID:26640894

Early Spatial and Temporal Events of Human T-Lymphotropic Virus Type 1 Spread following Blood-Borne Transmission in a Rabbit Model of Infection ▿

PubMed Central

Haynes, Rashade A. H.; Zimmerman, Bevin; Millward, Laurie; Ware, Evan; Premanandan, Christopher; Yu, Lianbo; Phipps, Andrew J.; Lairmore, Michael D.

2010-01-01

Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell leukemia/lymphoma (ATL) and is associated with a variety of lymphocyte-mediated disorders. HTLV-1 transmission occurs by transmission of infected cells via breast-feeding by infected mothers, sexual intercourse, and contaminated blood products. The route of exposure and early virus replication events are believed to be key determinants of virus-associated spread, antiviral immune responses, and ultimately disease outcomes. The lack of knowledge of early events of HTLV-1 spread following blood-borne transmission of the virus in vivo hinders a more complete understanding of the immunopathogenesis of HTLV-1 infections. Herein, we have used an established animal model of HTLV-1 infection to study early spatial and temporal events of the viral infection. Twelve-week-old rabbits were injected intravenously with cell-associated HTLV-1 (ACH-transformed R49). Blood and tissues were collected at defined intervals throughout the study to test the early spread of the infection. Antibody and hematologic responses were monitored throughout the infection. HTLV-1 intracellular Tax and soluble p19 matrix were tested from ex vivo cultured lymphocytes. Proviral copy numbers were measured by real-time PCR from blood and tissue mononuclear leukocytes. Our data indicate that intravenous infection with cell-associated HTLV-1 targets lymphocytes located in both primary lymphoid and gut-associated lymphoid compartments. A transient lymphocytosis that correlated with peak virus detection parameters was observed by 1 week postinfection before returning to baseline levels. Our data support emerging evidence that HTLV-1 promotes lymphocyte proliferation preceding early viral spread in lymphoid compartments to establish and maintain persistent infection. PMID:20219918

Interleukin-10 production at the early stage of infection with foot-and-mouth disease virus related to the likelihood of persistent infection in cattle.

PubMed

Zhang, Zhidong; Doel, Claudia; Bashiruddin, John B

2015-11-19

The factors leading to persistent infection of foot-and-mouth disease (FMD) virus in ruminants are not well defined. This paper provides evidence of the presence of interleukin-10 (IL-10) early in the course of infection (1-4 days) as a factor in the development of persistence of FMD virus in cattle. Results showed that serum IL-10 in carrier cattle infected with FMD virus type O (n = 4) was detected and peaked at 1 or 2 days post infection and rapidly declined thereafter. In contract, serum IL-10 levels in non-carrier cattle (n = 21) were very low or undetectable during the same period.

Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization.

PubMed

Anand, Sarah; Thomas, Samantha; Hyslop, Terry; Adcock, Janet; Corbet, Kelly; Gasparetto, Cristina; Lopez, Richard; Long, Gwynn D; Morris, Ashley K; Rizzieri, David A; Sullivan, Keith M; Sung, Anthony D; Sarantopoulos, Stefanie; Chao, Nelson J; Horwitz, Mitchell E

2017-07-01

Delayed hematopoietic recovery contributes to increased infection risk following umbilical cord blood (UCB) transplantation. In a Phase 1 study, adult recipients of UCB stem cells cultured ex vivo for 3 weeks with nicotinamide (NiCord) had earlier median neutrophil recovery compared with historical controls. To evaluate the impact of faster neutrophil recovery on clinically relevant early outcomes, we reviewed infection episodes and hospitalization during the first 100 days in an enlarged cohort of 18 NiCord recipients compared with 86 standard UCB recipients at our institution. The median time to neutrophil engraftment was shorter in NiCord recipients compared with standard UCB recipients (12.5 days versus 26 days; P < .001). Compared with standard UCB recipients, NiCord recipients had a significantly reduced risk for total infection (RR, 0.69; P = .01), grade 2-3 (moderate to severe) infection (RR, 0.36; P < .001), bacterial infection (RR, 0.39; P = .003), and grade 2-3 bacterial infection (RR, 0.21; P = .003) by Poisson regression analysis; this effect persisted after adjustment for age, disease stage, and grade II-IV acute GVHD. NiCord recipients also had significantly more time out of the hospital in the first 100 days post-transplantation after adjustment for age and Karnofsky Performance Status (69.9 days versus 49.7 days; P = .005). Overall, transplantation of NiCord was associated with faster neutrophil engraftment, fewer total and bacterial infections, and shorter hospitalization in the first 100 days compared with standard UCB transplantation. In conclusion, rapid hematopoietic recovery from an ex vivo expanded UCB transplantation approach is associated with early clinical benefit. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Five year neurodevelopment outcomes of perinatally HIV-infected children on early limited or deferred continuous antiretroviral therapy.

PubMed

Laughton, Barbara; Cornell, Morna; Kidd, Martin; Springer, Priscilla Estelle; Dobbels, Els Françoise Marie-Thérèse; Rensburg, Anita Janse Van; Otwombe, Kennedy; Babiker, Abdel; Gibb, Diana M; Violari, Avy; Kruger, Mariana; Cotton, Mark Fredric

2018-05-01

Early antiretroviral therapy (ART) has improved neurodevelopmental outcomes of HIV-infected (HIV-positive) children; however, little is known about the longer term outcomes in infants commencing early ART or whether temporary ART interruption might have long-term consequences. In the children with HIV early antiretroviral treatment (CHER) trial, HIV-infected infants ≤12 weeks of age with CD4 ≥25% were randomized to deferred ART (ART-Def); immediate time-limited ART for 40 weeks (ART-40W) or 96 weeks (ART-96W). ART was restarted in the time-limited arms for immunologic/clinical progression. Our objective was to compare the neurodevelopmental profiles in all three arms of Cape Town CHER participants. A prospective, longitudinal observational study was used. The Griffiths mental development scales (GMDS), which includes six subscales and a global score, were performed at 11, 20, 30, 42 and 60 months, and the Beery-Buktenica developmental tests for visual motor integration at 60 months. HIV-exposed uninfected (HEU) and HIV-unexposed (HU) children were enrolled for comparison. Mixed model repeated measures were used to compare groups over time, using quotients derived from standardized British norms. In this study, 28 ART-Def, 35 ART-40W, 33 ART-96W CHER children, and 34 HEU and 39 HU controls were enrolled. GMDS scores over five years were similar between the five groups in all subscales except locomotor and general Griffiths (interaction p < 0.001 and p = 0.02 respectively), driven by early lower scores in the ART-Def arm. At 60 months, scores for all groups were similar in each GMDS scale. However, Beery visual perception scores were significantly lower in HIV-infected children (mean standard scores: 75.8 ART-Def, 79.8 ART-40W, 75.9 ART-96W) versus 84.4 in HEU and 90.5 in HU (p < 0.01)). Early locomotor delay in the ART-Def arm resolved by five years. Neurodevelopmental outcomes at five years in HIV-infected children on early time-limited ART were

Initiation of ART during Early Acute HIV Infection Preserves Mucosal Th17 Function and Reverses HIV-Related Immune Activation

PubMed Central

Schuetz, Alexandra; Deleage, Claire; Sereti, Irini; Rerknimitr, Rungsun; Phanuphak, Nittaya; Phuang-Ngern, Yuwadee; Estes, Jacob D.; Sandler, Netanya G.; Sukhumvittaya, Suchada; Marovich, Mary; Jongrakthaitae, Surat; Akapirat, Siriwat; Fletscher, James L. K.; Kroon, Eugene; Dewar, Robin; Trichavaroj, Rapee; Chomchey, Nitiya; Douek, Daniel C.; O′Connell, Robert J.; Ngauy, Viseth; Robb, Merlin L.; Phanuphak, Praphan; Michael, Nelson L.; Excler, Jean-Louis; Kim, Jerome H.; de Souza, Mark S.; Ananworanich, Jintanat

2014-01-01

Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation. PMID:25503054

Gene expression profiling at birth characterizing the preterm infant with early onset infection.

PubMed

Hilgendorff, Anne; Windhorst, Anita; Klein, Manuel; Tchatalbachev, Svetlin; Windemuth-Kieselbach, Christine; Kreuder, Joachim; Heckmann, Matthias; Gkatzoflia, Anna; Ehrhardt, Harald; Mysliwietz, Josef; Maier, Michael; Izar, Benjamin; Billion, Andre; Gortner, Ludwig; Chakraborty, Trinad; Hossain, Hamid

2017-02-01

Early onset infection (EOI) in preterm infants <32 weeks gestational age (GA) is associated with a high mortality rate and the development of severe acute and long-term complications. The pathophysiology of EOI is not fully understood and clinical and laboratory signs of early onset infections in this patient cohort are often not conclusive. Thus, the aim of this study was to identify signatures characterizing preterm infants with EOI by using genome-wide gene expression (GWGE) analyses from umbilical arterial blood of preterm infants. This prospective cohort study was conducted in preterm infants <32 weeks GA. GWGE analyses using CodeLink human microarrays were performed from umbilical arterial blood of preterm infants with and without EOI. GWGE analyses revealed differential expression of 292 genes in preterm infants with EOI as compared to infants without EOI. Infants with EOI could be further differentiated into two subclasses and were distinguished by the magnitude of the expression of genes involved in both neutrophil and T cell activation. A hallmark activity for both subclasses of EOI was a common suppression of genes involved in natural killer (NK) cell function, which was independent from NK cell numbers. Significant results were recapitulated in an independent validation cohort. Gene expression profiling may enable early and more precise diagnosis of EOI in preterm infants. Gene expression (GE) profiling at birth characterizes preterm infants with EOI. GE analysis indicates dysregulation of NK cell activity. NK cell activity at birth may be a useful marker to improve early diagnosis of EOI.

Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4+ T-cell Count?

PubMed Central

Ghiglione, Yanina; Hormanstorfer, Macarena; Coloccini, Romina; Salido, Jimena; Trifone, César; Ruiz, María Julia; Falivene, Juliana; Caruso, María Paula; Figueroa, María Inés; Salomón, Horacio; Giavedoni, Luis D.; Pando, María de los Ángeles; Gherardi, María Magdalena; Rabinovich, Roberto Daniel; Sued, Omar

2018-01-01

Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4+ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1β correlated directly with CD4+ T-cell activation (p < 0.05). However, none of these cytokines had good predictive values to distinguish “progressors” from “non-progressors”. Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85). Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied. PMID:29342870

Early sex work initiation independently elevates odds of HIV infection and police arrest among adult sex workers in a Canadian setting.

PubMed

Goldenberg, Shira M; Chettiar, Jill; Simo, Annick; Silverman, Jay G; Strathdee, Steffanie A; Montaner, Julio S G; Shannon, Kate

2014-01-01

To explore factors associated with early sex work initiation and model the independent effect of early initiation on HIV infection and prostitution arrests among adult sex workers (SWs). Baseline data (2010-2011) were drawn from a cohort of SWs who exchanged sex for money within the last month and were recruited through time location sampling in Vancouver, Canada. Analyses were restricted to adults ≥18 years old. SWs completed a questionnaire and HIV/sexually transmitted infection testing. Using multivariate logistic regression, we identified associations with early sex work initiation (<18 years old) and constructed confounder models examining the independent effect of early initiation on HIV and prostitution arrests among adult SWs. Of 508 SWs, 193 (38.0%) reported early sex work initiation, with 78.53% primarily street-involved SWs and 21.46% off-street SWs. HIV prevalence was 11.22%, which was 19.69% among early initiates. Early initiates were more likely to be Canadian born [adjusted odds ratio (AOR): 6.8, 95% confidence interval (CI): 2.42 to 19.02], inject drugs (AOR: 1.6, 95% CI: 1.0 to 2.5), and to have worked for a manager (AOR: 2.22, 95% CI: 1.3 to 3.6) or been coerced into sex work (AOR: 2.3, 95% CI: 1.14 to 4.44). Early initiation retained an independent effect on increased risk of HIV infection (AOR: 2.5, 95% CI: 1.3 to 3.2) and prostitution arrests (AOR: 2.0, 95% CI: 1.3 to 3.2). Adolescent sex work initiation is concentrated among marginalized, drug, and street-involved SWs. Early initiation holds an independent increased effect on HIV infection and criminalization of adult SWs. Findings suggest the need for evidence-based approaches to reduce harm among adult and youth SWs.

Differences in Early Cytokine Production Are Associated With Development of a Greater Number of Symptoms Following West Nile Virus Infection.

PubMed

Hoffman, Kevin W; Sachs, David; Bardina, Susana V; Michlmayr, Daniela; Rodriguez, Carlos A; Sum, Janet; Foster, Gregory A; Krysztof, David; Stramer, Susan L; Lim, Jean K

2016-08-15

West Nile virus (WNV) is an emerging cause of meningitis and encephalitis in the United States. Although severe neuroinvasive disease and death can occur in rare instances, the majority of infected individuals remain asymptomatic or present with a range of clinical manifestations associated with West Nile fever. To better understand the interindividual variability associated with the majority of WNV infections, we evaluated the association of cytokine/chemokine production and outcome of infection among 115 WNV-positive US blood donors identified in 2008-2011. All subjects self-reported symptoms as having occurred during the 2 weeks following blood donation, using a standardized questionnaire. We discovered that, prior to seroconversion, an early potent, largely type I interferon-mediated response correlated with development of a greater number of symptoms in WNV-infected individuals. Interestingly, individuals who developed fewer symptoms had not only a more modest type I interferon response initially, but also a protracted cytokine response after seroconversion, marked by the production of monocyte and T-cell-associated chemokines. Collectively, our data suggest that, although an early type I interferon response appears to be crucial to control WNV infection, successful immunity may require a modest early response that is maintained during the course of infection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Cyclooxygenase activity is important for efficient replication of mouse hepatitis virus at an early stage of infection

PubMed Central

Raaben, Matthijs; Einerhand, Alexandra WC; Taminiau, Lucas JA; van Houdt, Michel; Bouma, Janneke; Raatgeep, Rolien H; Büller, Hans A; de Haan, Cornelis AM; Rossen, John WA

2007-01-01

Cyclooxygenases (COXs) play a significant role in many different viral infections with respect to replication and pathogenesis. Here we investigated the role of COXs in the mouse hepatitis coronavirus (MHV) infection cycle. Blocking COX activity by different inhibitors or by RNA interference affected MHV infection in different cells. The COX inhibitors reduced MHV infection at a post-binding step, but early in the replication cycle. Both viral RNA and viral protein synthesis were affected with subsequent loss of progeny virus production. Thus, COX activity appears to be required for efficient MHV replication, providing a potential target for anti-coronaviral therapy. PMID:17555580

Pharmacological intervention for dengue virus infection.

PubMed

Lai, Jenn-Haung; Lin, Yi-Ling; Hsieh, Shie-Liang

2017-04-01

Dengue virus (DENV) infection has a considerable health impact in tropical and subtropical countries worldwide. Escalation of infection rates greatly increases morbidity and mortality, most commonly from deaths due to dengue hemorrhagic fever and dengue shock syndrome. Although the development of an effective, long-lasting vaccine has been a major aim for control and prevention of DENV infection, the currently licensed vaccine has limitations and is less than satisfactory. Thus, there remains an important need to identify effective and tolerable medications for treatment of DENV-infected patients both in the early phase, to prevent progression to fatal outcomes, and to minimize deaths after patients develop severe complications. This review will address several specific points, including (1) approaches to identify anti-DENV medications, (2) recent advances in the development of potential compounds targeting DENV infection, (3) experience with clinical trials of regimens for DENV infection, (4) some available medications of potential for clinical trials against DENV infection, (5) reasons for unsuccessful outcomes and challenges of anti-DENV treatments, and (6) directions for developing or selecting better anti-DENV strategies. This review provides useful guidance for clinicians selecting drugs for DENV-infected patients with severe manifestations or potential fatal disease progression, and for basic researchers seeking to develop effective anti-DENV regimens. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigating the Consequences of Interference between Multiple CD8+ T Cell Escape Mutations in Early HIV Infection

PubMed Central

Garcia, Victor; Feldman, Marcus W.; Regoes, Roland R.

2016-01-01

During early human immunodeficiency virus (HIV) infection multiple CD8+ T cell responses are elicited almost simultaneously. These responses exert strong selective pressures on different parts of HIV’s genome, and select for mutations that escape recognition and are thus beneficial to the virus. Some studies reveal that the later these escape mutations emerge, the more slowly they go to fixation. This pattern of escape rate decrease(ERD) can arise by distinct mechanisms. In particular, in large populations with high beneficial mutation rates interference among different escape strains –an effect that can emerge in evolution with asexual reproduction and results in delayed fixation times of beneficial mutations compared to sexual reproduction– could significantly impact the escape rates of mutations. In this paper, we investigated how interference between these concurrent escape mutations affects their escape rates in systems with multiple epitopes, and whether it could be a source of the ERD pattern. To address these issues, we developed a multilocus Wright-Fisher model of HIV dynamics with selection, mutation and recombination, serving as a null-model for interference. We also derived an interference-free null model assuming initial neutral evolution before immune response elicitation. We found that interference between several equally selectively advantageous mutations can generate the observed ERD pattern. We also found that the number of loci, as well as recombination rates substantially affect ERD. These effects can be explained by the underexponential decline of escape rates over time. Lastly, we found that the observed ERD pattern in HIV infected individuals is consistent with both independent, interference-free mutations as well as interference effects. Our results confirm that interference effects should be considered when analyzing HIV escape mutations. The challenge in estimating escape rates and mutation-associated selective coefficients posed by

Early Whole Blood Transcriptional Signatures Are Associated with Severity of Lung Inflammation in Cynomolgus Macaques with Mycobacterium tuberculosis Infection.

PubMed

Gideon, Hannah P; Skinner, Jason A; Baldwin, Nicole; Flynn, JoAnne L; Lin, Philana Ling

2016-12-15

Whole blood transcriptional profiling offers great diagnostic and prognostic potential. Although studies identified signatures for pulmonary tuberculosis (TB) and transcripts that predict the risk for developing active TB in humans, the early transcriptional changes immediately following Mycobacterium tuberculosis infection have not been evaluated. We evaluated the gene expression changes in the cynomolgus macaque model of TB, which recapitulates all clinical aspects of human M. tuberculosis infection, using a human microarray and analytics platform. We performed genome-wide blood transcriptional analysis on 38 macaques at 11 postinfection time points during the first 6 mo of M. tuberculosis infection. Of 6371 differentially expressed transcripts between preinfection and postinfection, the greatest change in transcriptional activity occurred 20-56 d postinfection, during which fluctuation of innate and adaptive immune response-related transcripts was observed. Modest transcriptional differences between active TB and latent infection were observed over the time course with substantial overlap. The pattern of module activity previously published for human active TB was similar in macaques with active disease. Blood transcript activity was highly correlated with lung inflammation (lung [ 18 F]fluorodeoxyglucose [FDG] avidity) measured by positron emission tomography and computed tomography at early time points postinfection. The differential signatures between animals with high and low lung FDG were stronger than between clinical outcomes. Analysis of preinfection signatures of macaques revealed that IFN signatures could influence eventual clinical outcomes and lung FDG avidity, even before infection. Our data support that transcriptional changes in the macaque model are translatable to human M. tuberculosis infection and offer important insights into early events of M. tuberculosis infection. Copyright © 2016 by The American Association of Immunologists, Inc.

Relationship between Functional Profile of HIV-1 Specific CD8 T Cells and Epitope Variability with the Selection of Escape Mutants in Acute HIV-1 Infection

PubMed Central

Goonetilleke, Nilu; Liu, Michael K. P.; Turnbull, Emma L.; Salazar-Gonzalez, Jesus F.; Hawkins, Natalie; Self, Steve; Watson, Sydeaka; Betts, Michael R.; Gay, Cynthia; McGhee, Kara; Pellegrino, Pierre; Williams, Ian; Tomaras, Georgia D.; Haynes, Barton F.; Gray, Clive M.; Borrow, Persephone; Roederer, Mario; McMichael, Andrew J.; Weinhold, Kent J.

2011-01-01

In the present study, we analyzed the functional profile of CD8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus escape mutations. Seven anti-retroviral therapy-naïve subjects were studied in detail between 1 and 87 weeks following onset of symptoms of acute HIV-1 infection. Synthetic peptides representing the autologous transmitted/founder HIV-1 sequences were used in multiparameter flow cytometry assays to determine the functionality of HIV-1-specific CD8+ T memory cells. In all seven patients, the earliest T cell responses were predominantly oligofunctional, although the relative contribution of multifunctional cell responses increased significantly with time from infection. Interestingly, only the magnitude of the total and not of the poly-functional T-cell responses was significantly associated with the selection of escape mutants. However, the high contribution of MIP-1β-producing CD8+ T-cells to the total response suggests that mechanisms not limited to cytotoxicity could be exerting immune pressure during acute infection. Lastly, we show that epitope entropy, reflecting the capacity of the epitope to tolerate mutational change and defined as the diversity of epitope sequences at the population level, was also correlated with rate of emergence of escape mutants. PMID:21347345

Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections

PubMed Central

Wisniewska, Monika; Cremer, Malte; Wiehe, Lennart; Becker, Niels-Peter; Rijntjes, Eddy; Martitz, Janine; Renko, Kostja; Bührer, Christoph; Schomburg, Lutz

2017-01-01

Copper (Cu) and zinc (Zn) are essential trace elements for regular development. Acute infections alter their metabolism, while deficiencies increase infection risks. A prospective observational case-control study was conducted with infected (n = 21) and control (n = 23) term and preterm newborns. We analyzed trace element concentrations by X-ray fluorescence, and ceruloplasmin (CP) by Western blot. Median concentration of Cu at birth (day 1) was 522.8 [387.1–679.7] μg/L, and Zn was 1642.4 ± 438.1 μg/L. Cu and Zn correlated positively with gestational age in control newborns. Cu increased in infected newborns from day 1 to day 3. CP correlated positively to Cu levels at birth in both groups and on day 3 in the group of infected neonates. The Cu/Zn ratio was relatively high in infected newborns. Interleukin (IL)-6 concentrations on day 1 were unrelated to Cu, Zn, or the Cu/Zn ratio, whereas C-reactive protein (CRP) levels on day 3 correlated positively to the Cu/Zn -ratio at both day 1 and day 3. We conclude that infections affect the trace element homeostasis in newborns: serum Zn is reduced, while Cu and CP are increased. The Cu/Zn ratio combines both alterations, independent of gestational age. It may, thus, constitute a meaningful diagnostic biomarker for early-onset infections. PMID:28358335

Human immunodeficiency virus infection of helper T cell clones. Early proliferative defects despite intact antigen-specific recognition and interleukin 4 secretion.

PubMed Central

Laurence, J; Friedman, S M; Chartash, E K; Crow, M K; Posnett, D N

1989-01-01

HIV selectively inhibited the proliferative response of clonal CD4+ T lymphocytes to alloantigen while other alloantigen-dependent responses were unperturbed. Specifically, impaired blastogenesis could be dissociated from alloantigen-specific induction of the B cell activation molecule CD23, IL-4 release, and inositol lipid hydrolysis. In addition, membrane expression of pertinent T cell receptor molecules, including CD2, CD3, and T cell antigen receptor (Ti), remained intact. Using two MHC class II-specific human CD4+ helper T cell clones, the proliferative defect was shown to be an early consequence of HIV infection, occurring within 4 d of viral inoculation and preceding increases in mature virion production. It was generalizable to three distinct methods of T cell activation, all independent of antigen-presenting cells: anti-CD3 mediated cross-linking of the CD3/Ti complex; anti-CD2 and phorbol 12-myristic 13-acetate (PMA); and anti-CD28 plus PMA. These abnormalities were not mitigated by addition of exogenous IL-2, even though expression of the IL-2 receptor (CD25) was unaltered. These studies define a selective blockade in T cell function early after HIV exposure that could serve as a model for certain in vivo manifestations of AIDS. PMID:2470786

Effect of Unshaven Hair with Absorbable Sutures and Early Postoperative Shampoo on Cranial Surgery Site Infection.

PubMed

Oh, Won-Oak; Yeom, Insun; Kim, Dong-Seok; Park, Eun-Kyung; Shim, Kyu-Won

2018-01-01

Cranial surgical site infection is a significant cause of morbidity and mortality in hospitals. Preoperative hair shaving for cranial neurosurgical procedures is performed traditionally in an attempt to protect patients against complications from infections at cranial surgical sites. However, preoperative shaving of surgical incision sites using traditional surgical blades without properly washing the head after surgery can cause infections at surgical sites. Therefore, a rapid protocol in which the scalp remains unshaven and absorbable sutures are used for scalp closure with early postoperative shampooing is examined in this study. A retrospective comparative study was conducted from January 2008 to December 2012. A total of 2,641 patients who underwent unshaven cranial surgery with absorbable sutures for scalp closure were enrolled in this study. Data of 1,882 patients who underwent surgery with the traditional protocol from January 2005 to December 2007 were also analyzed for comparison. Of 2,641 patients who underwent cranial surgery with the rapid protocol, all but 2 (0.07%) patients experienced satisfactory wound healing. Of 1,882 patients who underwent cranial surgery with the traditional protocol, 3 patients (0.15%) had infections. Each infection occurred at the superficial incisional surgical site. Unshaven cranial surgery using absorbable sutures for scalp closure with early postoperative shampooing is safe and effective in the cranial neurosurgery setting. This protocol has a positive psychological effect. It can help patients accept neurosurgical procedures and improve their self-image after the operation. © 2017 S. Karger AG, Basel.

Depletion of Neutrophils Exacerbates the Early Inflammatory Immune Response in Lungs of Mice Infected with Paracoccidioides brasiliensis

PubMed Central

Lopera, Damaris; Urán-Jiménez, Martha Eugenia

2016-01-01

Neutrophils predominate during the acute phase of the Paracoccidioides brasiliensis infection. Herein, we determined the role of the neutrophil during the early stages of experimental pulmonary paracoccidioidomycosis using a monoclonal antibody (mAb) specific for neutrophils. Male BALB/c mice were inoculated intranasally with 1.5 × 106 or 2 × 106 P. brasiliensis yeast cells. The mAb was administered 24 h before infection, followed by doses every 48 h until mice were sacrificed. Survival time was evaluated and mice were sacrificed at 48 h and 96 h after inoculation to assess cellularity, fungal load, cytokine/chemokine levels, and histopathological analysis. Neutrophils from mAb-treated mice were efficiently depleted (99.04%). Eighty percent of the mice treated with the mAb and infected with 1.5 × 106 yeast cells died during the first two weeks after infection. When mice were treated and infected with 2 × 106 yeast cells, 100% of them succumbed by the first week after infection. During the acute inflammatory response significant increases in numbers of eosinophils, fungal load and levels of proinflammatory cytokines/chemokines were observed in the mAb-treated mice. We also confirmed that neutrophils are an important source of IFN-γ and IL-17. These results indicate that neutrophils are essential for protection as well as being important for regulating the early inflammatory immune response in experimental pulmonary paracoccidioidomycosis. PMID:27642235

Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

PubMed Central

Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

2014-01-01

The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initial control of MCMV, although at later time points, CD70-/- mice became more susceptible to MCMV infection. The heightened cytokine response during the early phase of MCMV infection in CD70-/- mice was paralleled by a reduction in regulatory T cells (Treg). Treg from naïve CD70-/- mice were not as efficient at suppressing T cell proliferation compared to Treg from naïve WT mice and depletion of Treg during MCMV infection in Foxp3-DTR mice or in WT mice recapitulated the phenotype observed in CD70-/- mice. Our study demonstrates that while CD70 is required for the activation of the antiviral adaptive response, it has a regulatory role in early cytokine responses to viruses such as MCMV, possibly through maintenance of Treg survival and function. PMID:24913981

Constitutively Expressed IFITM3 Protein in Human Endothelial Cells Poses an Early Infection Block to Human Influenza Viruses.

PubMed

Sun, Xiangjie; Zeng, Hui; Kumar, Amrita; Belser, Jessica A; Maines, Taronna R; Tumpey, Terrence M

2016-12-15

A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza viruses were capable of binding to host cellular receptors, becoming internalized and initiating hemifusion but failing to uncoat the viral nucleocapsid and to replicate in host nuclei. Unlike numerous cell types, including epithelial cells, we found that pulmonary endothelial cells constitutively express a high level of the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by small interfering RNA (siRNA) could partially rescue H1N1 virus infection in HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus infection in endothelial cells. In contrast, selected avian influenza viruses were able to escape IFITM3 restriction in endothelial cells, possibly by fusing in early endosomes at higher pH or by other, unknown mechanisms. Collectively, our study demonstrates that the human pulmonary endothelium possesses intrinsic immunity to human influenza viruses, in part due to the constitutive expression of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to escape this restriction, possibly contributing to virus-induced pneumonia and severe lung disease in humans. Avian influenza viruses, including H5N1 and H7N9, have been associated with severe respiratory disease and fatal outcomes in humans. Although acute respiratory distress syndrome (ARDS) and progressive pulmonary endothelial damage

Selective HDAC Inhibition for the Disruption of Latent HIV-1 Infection

PubMed Central

Barton, Kirston M.; Archin, Nancie M.; Keedy, Kara S.; Espeseth, Amy S.; Zhang, Yan-ling; Gale, Jennifer; Wagner, Florence F.; Holson, Edward B.; Margolis, David M.

2014-01-01

Selective histone deacetylase (HDAC) inhibitors have emerged as a potential anti-latency therapy for persistent human immunodeficiency virus type 1 (HIV-1) infection. We utilized a combination of small molecule inhibitors and short hairpin (sh)RNA-mediated gene knockdown strategies to delineate the key HDAC(s) to be targeted for selective induction of latent HIV-1 expression. Individual depletion of HDAC3 significantly induced expression from the HIV-1 promoter in the 2D10 latency cell line model. However, depletion of HDAC1 or −2 alone or in combination did not significantly induce HIV-1 expression. Co-depletion of HDAC2 and −3 resulted in a significant increase in expression from the HIV-1 promoter. Furthermore, concurrent knockdown of HDAC1, −2, and −3 resulted in a significant increase in expression from the HIV-1 promoter. Using small molecule HDAC inhibitors of differing selectivity to ablate the residual HDAC activity that remained after (sh)RNA depletion, the effect of depletion of HDAC3 was further enhanced. Enzymatic inhibition of HDAC3 with the selective small-molecule inhibitor BRD3308 activated HIV-1 transcription in the 2D10 cell line. Furthermore, ex vivo exposure to BRD3308 induced outgrowth of HIV-1 from resting CD4+ T cells isolated from antiretroviral-treated, aviremic HIV+ patients. Taken together these findings suggest that HDAC3 is an essential target to disrupt HIV-1 latency, and inhibition of HDAC2 may also contribute to the effort to purge and eradicate latent HIV-1 infection. PMID:25136952

Early Changes by 18Fluorodeoxyglucose Positron Emission Tomography Coregistered with Computed Tomography Predict Outcome after Mycobacterium tuberculosis Infection in Cynomolgus Macaques

PubMed Central

Coleman, M. Teresa; Maiello, Pauline; Tomko, Jaime; Frye, Lonnie James; Fillmore, Daniel; Janssen, Christopher; Klein, Edwin

2014-01-01

Cynomolgus macaques infected with low-dose Mycobacterium tuberculosis develop both active tuberculosis and latent infection similar to those of humans, providing an opportunity to study the clinically silent early events in infection. 18Fluorodeoxyglucose radiotracer with positron emission tomography coregistered with computed tomography (FDG PET/CT) provides a noninvasive method to measure disease progression. We sought to determine temporal patterns of granuloma evolution that distinguished active-disease and latent outcomes. Macaques (n = 10) were infected with low-dose M. tuberculosis with FDG PET/CT performed during infection. At 24 weeks postinfection, animals were classified as having active disease (n = 3) or latent infection (n = 6), with one “percolator” monkey. Imaging characteristics (e.g., lesion number, metabolic activity, size, mineralization, and distribution of lesions) were compared among active and latent groups. As early as 3 weeks postinfection, more pulmonary granulomas were observed in animals that would later develop active disease than in those that would develop latent infection. Over time, new lesions developed in active-disease animals but not in latent animals. Granulomas and mediastinal lymph nodes from active-disease but not latent animals consistently increased in metabolic activity at early time points. The presence of fewer lesions at 3 weeks and the lack of new lesion development in animals with latent infection suggest that innate and rapid adaptive responses are critical to preventing active tuberculosis. A greater emphasis on innate responses and/or rapid recruitment of adaptive responses, especially in the airway, should be emphasized in newer vaccine strategies. PMID:24664509

Early Gag Immunodominance of the HIV-Specific T-Cell Response during Acute/Early Infection Is Associated with Higher CD8+ T-Cell Antiviral Activity and Correlates with Preservation of the CD4+ T-Cell Compartment

PubMed Central

Ghiglione, Yanina; Falivene, Juliana; Socias, María Eugenia; Laufer, Natalia; Coloccini, Romina Soledad; Rodriguez, Ana María; Ruiz, María Julia; Pando, María Ángeles; Giavedoni, Luis David; Cahn, Pedro; Sued, Omar; Salomon, Horacio; Gherardi, María Magdalena

2013-01-01

The important role of the CD8+ T-cell response on HIV control is well established. Moreover, the acute phase of infection represents a proper scenario to delineate the antiviral cellular functions that best correlate with control. Here, multiple functional aspects (specificity, ex vivo viral inhibitory activity [VIA] and polyfunctionality) of the HIV-specific CD8+ T-cell subset arising early after infection, and their association with disease progression markers, were examined. Blood samples from 44 subjects recruited within 6 months from infection (primary HIV infection [PHI] group), 16 chronically infected subjects, 11 elite controllers (EC), and 10 healthy donors were obtained. Results indicated that, although Nef dominated the anti-HIV response during acute/early infection, a higher proportion of early anti-Gag T cells correlated with delayed progression. Polyfunctional HIV-specific CD8+ T cells were detected at early time points but did not associate with virus control. Conversely, higher CD4+ T-cell set points were observed in PHI subjects with higher HIV-specific CD8+ T-cell VIA at baseline. Importantly, VIA levels correlated with the magnitude of the anti-Gag cellular response. The advantage of Gag-specific cells may result from their enhanced ability to mediate lysis of infected cells (evidenced by a higher capacity to degranulate and to mediate VIA) and to simultaneously produce IFN-γ. Finally, Gag immunodominance was associated with elevated plasma levels of interleukin 2 (IL-2) and macrophage inflammatory protein 1β (MIP-1β). All together, this study underscores the importance of CD8+ T-cell specificity in the improved control of disease progression, which was related to the capacity of Gag-specific cells to mediate both lytic and nonlytic antiviral mechanisms at early time points postinfection. PMID:23616666

Host and Bacterial Proteins That Repress Recruitment of LC3 to Shigella Early during Infection

PubMed Central

Baxt, Leigh A.; Goldberg, Marcia B.

2014-01-01

Shigella spp. are intracytosolic gram-negative pathogens that cause disease by invasion and spread through the colonic mucosa, utilizing host cytoskeletal components to form propulsive actin tails. We have previously identified the host factor Toca-1 as being recruited to intracellular S. flexneri and being required for efficient bacterial actin tail formation. We show that at early times during infection (40 min.), the type three-secreted effector protein IcsB recruits Toca-1 to intracellular bacteria and that recruitment of Toca-1 is associated with repression of recruitment of LC3, as well as with repression of recruitment of the autophagy marker NDP52, around these intracellular bacteria. LC3 is best characterized as a marker of autophagosomes, but also marks phagosomal membranes in the process LC3-associated phagocytosis. IcsB has previously been demonstrated to be required for S. flexneri evasion of autophagy at late times during infection (4–6 hr) by inhibiting binding of the autophagy protein Atg5 to the Shigella surface protein IcsA (VirG). Our results suggest that IcsB and Toca-1 modulation of LC3 recruitment restricts LC3-associated phagocytosis and/or LC3 recruitment to vacuolar membrane remnants. Together with published results, our findings suggest that IcsB inhibits innate immune responses in two distinct ways, first, by inhibiting LC3-associated phagocytosis and/or LC3 recruitment to vacuolar membrane remnants early during infection, and second, by inhibiting autophagy late during infection. PMID:24722587

IgG avidity test for the diagnosis of acute Toxoplasma gondii infection in early pregnancy.

PubMed

Pour Abolghasem, Shabnam; Bonyadi, Mohammad Reza; Babaloo, Zohre; Porhasan, Abolfazl; Nagili, Behroz; Gardashkhani, Omid Ali; Salehi, Parviz; Hashemi, Mohammad; Varshoghi, Mojtaba; Gaffari, Gafar Olade

2011-12-01

Toxoplasmosis is well known as an important infection in pregnant women. Although many serologic methods are available, diagnosis of early Toxoplasmosis may be extremely difficult. To detect the Toxoplasma IgG antibodies developed at the early stage of infection in pregnant women. 225 pregnant women, who were in the 2nd to 4th month of their pregnancy, enrolled in this study. Anti-toxoplasma IgG, IgM and IgG avidity were evaluated by ELISA method. The patients were categorized into three groups as follows: Group A, 124 cases; IgG+, IgM+, 55.1%; group B, 99 cases; IgG+, IgM-, 44%; and group C, 2 cases; IgG -, IgM +, 0.9%. Fifty five percent of the pregnant women had positive IgG and IgM among which 7.1% had low avidity which revealed an active infection in the pregnant women. In the current study, 44% of pregnant women had positive IgG and negative IgM, all of which had high avidity, which is an indication that in our population the level of toxoplasmosis infection is high and most women have had contacts with this parasite before pregnancy. In this study, the low avidity test was 7.1% showing that the occurrence of toxoplasmosis infection is still a serious issue. Observation of 45.8% high avidity among group A suggests that either IgM has a high half-life or there is a false positive IgM as a result of rheumatologic disorders. Therefore, avidity test is important in predicting maternal toxoplasmosis which is of value in disease treatment.

Selective Cooperation in Early Childhood – How to Choose Models and Partners

PubMed Central

Hermes, Jonas; Behne, Tanya; Studte, Kristin; Zeyen, Anna-Maria; Gräfenhain, Maria; Rakoczy, Hannes

2016-01-01

Cooperation is essential for human society, and children engage in cooperation from early on. It is unclear, however, how children select their partners for cooperation. We know that children choose selectively whom to learn from (e.g. preferring reliable over unreliable models) on a rational basis. The present study investigated whether children (and adults) also choose their cooperative partners selectively and what model characteristics they regard as important for cooperative partners and for informants about novel words. Three- and four-year-old children (N = 64) and adults (N = 14) saw contrasting pairs of models differing either in physical strength or in accuracy (in labeling known objects). Participants then performed different tasks (cooperative problem solving and word learning) requiring the choice of a partner or informant. Both children and adults chose their cooperative partners selectively. Moreover they showed the same pattern of selective model choice, regarding a wide range of model characteristics as important for cooperation (preferring both the strong and the accurate model for a strength-requiring cooperation tasks), but only prior knowledge as important for word learning (preferring the knowledgeable but not the strong model for word learning tasks). Young children’s selective model choice thus reveals an early rational competence: They infer characteristics from past behavior and flexibly consider what characteristics are relevant for certain tasks. PMID:27505043

Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection.

PubMed

Wang, Xiaolei; Rasmussen, Terri; Pahar, Bapi; Poonia, Bhawna; Alvarez, Xavier; Lackner, Andrew A; Veazey, Ronald S

2007-02-01

Rapid, profound, and selective depletion of memory CD4+ T cells has now been confirmed to occur in simian immunodeficiency virus (SIV)-infected adult macaques and human immunodeficiency virus (HIV)-infected humans. Within days of infection, marked depletion of memory CD4+ T cells occurs primarily in mucosal tissues, the major reservoir for memory CD4+ T cells in adults. However, HIV infection in neonates often results in higher viral loads and rapid disease progression, despite the paucity of memory CD4+ T cells in the peripheral blood. Here, we examined the immunophenotype of CD4+ T cells in normal and SIV-infected neonatal macaques to determine the distribution of naive and memory T-cell subsets in tissues. We demonstrate that, similar to adults, neonates have abundant memory CD4+ T cells in the intestinal tract and spleen and that these are selectively infected and depleted in primary SIV infection. Within 12 days of SIV infection, activated (CD69+), central memory (CD95+CD28+) CD4+ T cells are marked and persistently depleted in the intestine and other tissues of neonates compared with controls. The results in dicate that "activated" central memory CD4+ T cells are the major target for early SIV infection and CD4+ T cell depletion in neonatal macaques.

Intrapartum antibiotics and early onset neonatal sepsis caused by group B Streptococcus and by other organisms in Australia. Australasian Study Group for Neonatal Infections.

PubMed

Isaacs, D; Royle, J A

1999-06-01

Early onset group B streptococcal (EOGBS) infection, the major neonatal infection in industrialized countries, can be prevented by intrapartum antibiotics, but population studies are lacking. This study aimed to determine the incidence of early onset infections caused by group B Streptococcus (GBS) and other organisms in Australia and to assess intrapartum antibiotic use. Longitudinal, prospective surveillance of neonatal infections in Australian neonatal units from 1991 to 1997. Early onset infection defined as clinical sepsis in first 48 h after birth, with positive cultures of blood or cerebrospinal fluid or positive urine GBS antigen detection. The incidence of EOGBS sepsis fell from 2.0 per 1000 live births (95% confidence interval, 1.4, 2.5) in 1991 to 1993, to 1.3 (1.2, 1.4) in 1993 to 1995, to 0.5 (0.4, 0.7) in 1995 to 1997 (P < 0.0001). The incidence in Aboriginal babies was 5.2 (1.8, 8.6) in 1991 to 1993, 5.1 (3.0, 7.2) in 1993 to 1995 and 1.8 (1.1, 2.5) in 1995 to 1997 (P < 0.05). The incidence of early onset infections caused by organisms other than GBS also fell, from 1.2 per 1000 live births (0.8, 1.7) in 1991 to 1993, to 0.8 (0.7, 0.9) in 1993 to 1995 and 0.5 (0.3, 0.7) in 1995 to 1997 (P < 0.0001). In 1991, 3 of 9 study hospitals had a formal policy on intrapartum antibiotic use, whereas in 1997 all 11 hospitals had a formal policy (P=0.002). A steady fall in EOGBS infections in Australia from 1991 to 1997 has been associated with increasing use of intrapartum antibiotics. Increased antibiotic use is probably causal in the fall in GBS, because the incidence of early onset infections caused by other organisms has also fallen.

Chronic restraint stress during early Theiler’s virus infection exacerbates the subsequent demyelinating disease in SJL mice: II. CNS disease severity

PubMed Central

Young, Erin E.; Sieve, Amy N.; Vichaya, Elisabeth G.; Carcoba, Luis M.; Young, Colin R.; Ambrus, Andrew; Storts, Ralph; Welsh, C. Jane R.; Meagher, Mary W.

2010-01-01

Theiler’s murine encephalomyelitis virus (TMEV) infection is a well-characterized model of multiple sclerosis (MS). Previous research has shown that chronic restraint stress (RS) during early TMEV infection exacerbates behavioral signs of disease. The present data suggest RS-induced increases in CNS inflammation, demyelination, and axonal degeneration may underlie this exacerbation. In addition, we report that males exhibit greater CNS inflammation and higher numbers of demyelinating lesions while females show greater susceptibility to RS-induced exacerbation. These findings indicate RS during early TMEV infection increases CNS lesion formation during the late phase and suggest the effects of RS are sex-dependent. PMID:20167380

Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection

PubMed Central

Muir, Roshell; Metcalf, Talibah; Tardif, Virginie; Takata, Hiroshi; Phanuphak, Nittaya; Kroon, Eugene; Colby, Donn J.; Trichavaroj, Rapee; Valcour, Victor; Robb, Merlin L.; Michael, Nelson L.; Ananworanich, Jintanat; Trautmann, Lydie; Haddad, Elias K.

2016-01-01

The RV254 cohort of HIV-infected very early acute (4thG stage 1 and 2) (stage 1/2) and late acute (4thG stage 3) (stage 3) individuals was used to study T helper- B cell responses in acute HIV infection and the impact of early antiretroviral treatment (ART) on T and B cell function. To investigate this, the function of circulating T follicular helper cells (cTfh) from this cohort was examined, and cTfh and memory B cell populations were phenotyped. Impaired cTfh cell function was observed in individuals treated in stage 3 when compared to stage 1/2. The cTfh/B cell cocultures showed lower B cell survival and IgG secretion at stage 3 compared to stage 1/2. This coincided with lower IL-10 and increased RANTES and TNF-α suggesting a role for inflammation in altering cTfh and B cell responses. Elevated plasma viral load in stage 3 was found to correlate with decreased cTfh-mediated B cell IgG production indicating a role for increased viremia in cTfh impairment and dysfunctional humoral response. Phenotypic perturbations were also evident in the mature B cell compartment, most notably a decrease in resting memory B cells in stage 3 compared to stage 1/2, coinciding with higher viremia. Our coculture assay also suggested that intrinsic memory B cell defects could contribute to the impaired response despite at a lower level. Overall, cTfh-mediated B cell responses are significantly altered in stage 3 compared to stage 1/2, coinciding with increased inflammation and a reduction in memory B cells. These data suggest that early ART for acutely HIV infected individuals could prevent immune dysregulation while preserving cTfh function and B cell memory. PMID:27463374

Early allelic selection in maize as revealed by ancient DNA.

PubMed

Jaenicke-Després, Viviane; Buckler, Ed S; Smith, Bruce D; Gilbert, M Thomas P; Cooper, Alan; Doebley, John; Pääbo, Svante

2003-11-14

Maize was domesticated from teosinte, a wild grass, by approximately 6300 years ago in Mexico. After initial domestication, early farmers continued to select for advantageous morphological and biochemical traits in this important crop. However, the timing and sequence of character selection are, thus far, known only for morphological features discernible in corn cobs. We have analyzed three genes involved in the control of plant architecture, storage protein synthesis, and starch production from archaeological maize samples from Mexico and the southwestern United States. The results reveal that the alleles typical of contemporary maize were present in Mexican maize by 4400 years ago. However, as recently as 2000 years ago, allelic selection at one of the genes may not yet have been complete.

Monitoring chicken flock behaviour provides early warning of infection by human pathogen Campylobacter

PubMed Central

Colles, Frances M.; Cain, Russell J.; Nickson, Thomas; Smith, Adrian L.; Roberts, Stephen J.; Maiden, Martin C. J.; Lunn, Daniel; Dawkins, Marian Stamp

2016-01-01

Campylobacter is the commonest bacterial cause of gastrointestinal infection in humans, and chicken meat is the major source of infection throughout the world. Strict and expensive on-farm biosecurity measures have been largely unsuccessful in controlling infection and are hampered by the time needed to analyse faecal samples, with the result that Campylobacter status is often known only after a flock has been processed. Our data demonstrate an alternative approach that monitors the behaviour of live chickens with cameras and analyses the ‘optical flow’ patterns made by flock movements. Campylobacter-free chicken flocks have higher mean and lower kurtosis of optical flow than those testing positive for Campylobacter by microbiological methods. We show that by monitoring behaviour in this way, flocks likely to become positive can be identified within the first 7–10 days of life, much earlier than conventional on-farm microbiological methods. This early warning has the potential to lead to a more targeted approach to Campylobacter control and also provides new insights into possible sources of infection that could transform the control of this globally important food-borne pathogen. PMID:26740618

Virulence evolution in response to anti-infection resistance: toxic food plants can select for virulent parasites of monarch butterflies.

PubMed

de Roode, J C; de Castillejo, C Lopez Fernandez; Faits, T; Alizon, S

2011-04-01

Host resistance to parasites can come in two main forms: hosts may either reduce the probability of parasite infection (anti-infection resistance) or reduce parasite growth after infection has occurred (anti-growth resistance). Both resistance mechanisms are often imperfect, meaning that they do not fully prevent or clear infections. Theoretical work has suggested that imperfect anti-growth resistance can select for higher parasite virulence by favouring faster-growing and more virulent parasites that overcome this resistance. In contrast, imperfect anti-infection resistance is thought not to select for increased parasite virulence, because it is assumed that it reduces the number of hosts that become infected, but not the fitness of parasites in successfully infected hosts. Here, we develop a theoretical model to show that anti-infection resistance can in fact select for higher virulence when such resistance reduces the effective parasite dose that enters a host. Our model is based on a monarch butterfly-parasite system in which larval food plants confer resistance to the monarch host. We carried out an experiment and showed that this environmental resistance is most likely a form of anti-infection resistance, through which toxic food plants reduce the effective dose of parasites that initiates an infection. We used these results to build a mathematical model to investigate the evolutionary consequences of food plant-induced resistance. Our model shows that when the effective infectious dose is reduced, parasites can compensate by evolving a higher per-parasite growth rate, and consequently a higher intrinsic virulence. Our results are relevant to many insect host-parasite systems, in which larval food plants often confer imperfect anti-infection resistance. Our results also suggest that - for parasites where the infectious dose affects the within-host dynamics - vaccines that reduce the effective infectious dose can select for increased parasite virulence. �

Sustained live poultry market surveillance contributes to early warnings for human infection with avian influenza viruses.

PubMed

Fang, Shisong; Bai, Tian; Yang, Lei; Wang, Xin; Peng, Bo; Liu, Hui; Geng, Yijie; Zhang, Renli; Ma, Hanwu; Zhu, Wenfei; Wang, Dayan; Cheng, Jinquan; Shu, Yuelong

2016-08-03

Sporadic human infections with the highly pathogenic avian influenza (HPAI) A (H5N6) virus have been reported in different provinces in China since April 2014. From June 2015 to January 2016, routine live poultry market (LPM) surveillance was conducted in Shenzhen, Guangdong Province. H5N6 viruses were not detected until November 2015. The H5N6 virus-positive rate increased markedly beginning in December 2015, and viruses were detected in LPMs in all districts of the city. Coincidently, two human cases with histories of poultry exposure developed symptoms and were diagnosed as H5N6-positive in Shenzhen during late December 2015 and early January 2016. Similar viruses were identified in environmental samples collected in the LPMs and the patients. In contrast to previously reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or H7N9 viruses were detected in the present study. The increased H5N6 virus-positive rate in the LPMs and the subsequent human infections demonstrated that sustained LPM surveillance for avian influenza viruses provides an early warning for human infections. Interventions, such as LPM closures, should be immediately implemented to reduce the risk of human infection with the H5N6 virus when the virus is widely detected during LPM surveillance.

Interferon-γ Inhibits Ebola Virus Infection.

PubMed

Rhein, Bethany A; Powers, Linda S; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A; Monick, Martha M; Maury, Wendy

2015-01-01

Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila.

PubMed

Kuo, Tzu-Hsing; Williams, Julie A

2014-05-01

Sleep is known to increase as an acute response to infection. However, the function of this behavioral response in host defense is not well understood. To address this problem, we evaluated the effect of acute sleep deprivation on post-infection sleep and immune function in Drosophila. Laboratory. Drosophila melanogaster. Flies were subjected to sleep deprivation before (early DEP) or after (late DEP) bacterial infection. Relative to a non-deprived control, flies subjected to early DEP had enhanced sleep after infection as well as increased bacterial clearance and survival outcome. Flies subjected to late DEP experienced enhanced sleep following the deprivation period, and showed a modest improvement in survival outcome. Continuous DEP (early and late DEP) throughout infection also enhanced sleep later during infection and improved survival. However, improved survival in flies subjected to late or continuous DEP did not occur until after flies had experienced sleep. During infection, both early and late DEP enhanced NFκB transcriptional activity as measured by a luciferase reporter (κB-luc) in living flies. Early DEP also increased NFκB activity prior to infection. Flies that were deficient in expression of either the Relish or Dif NFκB transcription factors showed normal responses to early DEP. However, the effect of early DEP on post-infection sleep and survival was abolished in double mutants, which indicates that Relish and Dif have redundant roles in this process. Acute sleep deprivation elevated NFκB-dependent activity, increased post-infection sleep, and improved survival during bacterial infection.

Identifying the Target Cell in Primary Simian Immunodeficiency Virus (SIV) Infection: Highly Activated Memory CD4+ T Cells Are Rapidly Eliminated in Early SIV Infection In Vivo

PubMed Central

Veazey, Ronald S.; Tham, Irene C.; Mansfield, Keith G.; DeMaria, MaryAnn; Forand, Amy E.; Shvetz, Daniel E.; Chalifoux, Laura V.; Sehgal, Prabhat K.; Lackner, Andrew A.

2000-01-01

It has recently been shown that rapid and profound CD4+ T-cell depletion occurs almost exclusively within the intestinal tract of simian immunodeficiency virus (SIV)-infected macaques within days of infection. Here we demonstrate (by three- and four-color flow cytometry) that this depletion is specific to a definable subset of CD4+ T cells, namely, those having both a highly and/or acutely activated (CD69+ CD38+ HLA-DR+) and memory (CD45RA− Leu8−) phenotype. Moreover, we demonstrate that this subset of helper T cells is found primarily within the intestinal lamina propria. Viral tropism for this particular cell type (which has been previously suggested by various studies in vitro) could explain why profound CD4+ T-cell depletion occurs in the intestine and not in peripheral lymphoid tissues in early SIV infection. Furthermore, we demonstrate that an acute loss of this specific subset of activated memory CD4+ T cells may also be detected in peripheral blood and lymph nodes in early SIV infection. However, since this particular cell type is present in such small numbers in circulation, its loss does not significantly affect total CD4+ T cell counts. This finding suggests that SIV and, presumably, human immunodeficiency virus specifically infect, replicate in, and eliminate definable subsets of CD4+ T cells in vivo. PMID:10590091

Comprehensive evaluation of Streptococcus sanguinis cell wall-anchored proteins in early infective endocarditis.

PubMed

Turner, Lauren Senty; Kanamoto, Taisei; Unoki, Takeshi; Munro, Cindy L; Wu, Hui; Kitten, Todd

2009-11-01

Streptococcus sanguinis is a member of the viridans group of streptococci and a leading cause of the life-threatening endovascular disease infective endocarditis. Initial contact with the cardiac infection site is likely mediated by S. sanguinis surface proteins. In an attempt to identify the proteins required for this crucial step in pathogenesis, we searched for surface-exposed, cell wall-anchored proteins encoded by S. sanguinis and then used a targeted signature-tagged mutagenesis (STM) approach to evaluate their contributions to virulence. Thirty-three predicted cell wall-anchored proteins were identified-a number much larger than those found in related species. The requirement of each cell wall-anchored protein for infective endocarditis was assessed in the rabbit model. It was found that no single cell wall-anchored protein was essential for the development of early infective endocarditis. STM screening was also employed for the evaluation of three predicted sortase transpeptidase enzymes, which mediate the cell surface presentation of cell wall-anchored proteins. The sortase A mutant exhibited a modest (approximately 2-fold) reduction in competitiveness, while the other two sortase mutants were indistinguishable from the parental strain. The combined results suggest that while cell wall-anchored proteins may play a role in S. sanguinis infective endocarditis, strategies designed to interfere with individual cell wall-anchored proteins or sortases would not be effective for disease prevention.

Acute Sleep Deprivation Enhances Post-Infection Sleep and Promotes Survival during Bacterial Infection in Drosophila

PubMed Central

Kuo, Tzu-Hsing; Williams, Julie A.

2014-01-01

Study Objectives: Sleep is known to increase as an acute response to infection. However, the function of this behavioral response in host defense is not well understood. To address this problem, we evaluated the effect of acute sleep deprivation on post-infection sleep and immune function in Drosophila. Setting: Laboratory. Participants: Drosophila melanogaster. Methods and Results: Flies were subjected to sleep deprivation before (early DEP) or after (late DEP) bacterial infection. Relative to a non-deprived control, flies subjected to early DEP had enhanced sleep after infection as well as increased bacterial clearance and survival outcome. Flies subjected to late DEP experienced enhanced sleep following the deprivation period, and showed a modest improvement in survival outcome. Continuous DEP (early and late DEP) throughout infection also enhanced sleep later during infection and improved survival. However, improved survival in flies subjected to late or continuous DEP did not occur until after flies had experienced sleep. During infection, both early and late DEP enhanced NFκB transcriptional activity as measured by a luciferase reporter (κB-luc) in living flies. Early DEP also increased NFκB activity prior to infection. Flies that were deficient in expression of either the Relish or Dif NFκB transcription factors showed normal responses to early DEP. However, the effect of early DEP on post-infection sleep and survival was abolished in double mutants, which indicates that Relish and Dif have redundant roles in this process. Conclusions: Acute sleep deprivation elevated NFκB-dependent activity, increased post-infection sleep, and improved survival during bacterial infection. Citation: Kuo TH, Williams JA. Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila. SLEEP 2014;37(5):859-869. PMID:24790264

Early Initial Antibiotics and Debridement Independently Reduce Infection in an Open Fracture Model

DTIC Science & Technology

2012-01-01

infection in those Gustilo-Anderson grade III fractures whose surgery was delayed until return to the US, compared with those who underwent early...LEAP) included a prospective observational study of 315 patients with Gustilo-Anderson grade III open fractures of the tibia, foot and ankle and, in...6. Ashford RU, Mehta JA, Cripps R. Delayed presentation is no barrier to satisfactory outcome in the management of open tibial fractures . Injury

Early increase of peripheral B cell levels in kidney transplant recipients with CMV infection or reactivation.

PubMed

Besançon-Watelet, C; De March, A K; Renoult, E; Kessler, M; Béné, M C; Faure, G C; Sarda, M N

2000-02-15

Cytomegalovirus (CMV) infection or reactivation is a frequent complication of renal transplantation. Diagnosis of these conditions relies on the detection of circulating antigen, or of specific IgM and/or IgG, which develop over several weeks. Evocative clinical features may be detected earlier, but lack specificity. Rapid and early changes in the partition of lymphocyte subsets could be an additional indication of pending CMV infection. A systematic follow-up of peripheral B lymphocytes identified immunophenotypically by the determination of surface immunoglobulins (sIg), performed in 97 kidney transplant recipients, allowed to identify transient increases apparently predictive of CMV primo-infection or reactivation over the next 3 months. To better define the nature of these B cells, an extended investigation was performed for 14 prospective patients. In addition to surface Ig, membrane CD19, HLA-DR, and CD80 expression were explored. The cytoplasmic presence of mu, kappa, and lambda chains was also examined. B cell function was investigated using the ELISPOT technique, which allows an enumeration of the populations of IgG, IgA, and IgM secreting B cells. Retrospective analysis of the clinical outcome of the cohort of 97 patients evidenced that early transient increases in B cell levels were significantly (P<0.0001) associated with CMV infection. The same trend was noted in the smaller series of patients who benefited from a more extensive investigation of B cells, 10 of whom presented clinical or biological signs of CMV infection. Mature B cells, expressing surface Ig, CD19, DR, and CD80 are those presenting transient increases. No significant variation of preB (cmu+/kappalambda-) or activated (spot-forming) cells was evidenced in these patients. Individual examination of each patient's immune reconstitution profile allows to detect transient peaks of mature B cell during the initial immunosuppressive therapy, that appear to be predictive of oncoming CMV

Genetic inheritance of pulp colour and selected traits of cassava (Manihot esculenta Crantz) at early generation selection.

PubMed

Nduwumuremyi, Athanase; Melis, Rob; Shanahan, Paul; Theodore, Asiimwe

2018-06-01

The early generation selection of cassava quantitative and qualitative traits saves breeding resources as it can shorten breeding schemes. Inheritance analysis provides important breeding information for developing new improved varieties. This study aimed at developing an F1 segregating cassava population and determining mode of gene action of pulp colour and selected traits at early generation selection (F1 seedling and clones). The 15 families exhibited significant (P < 0.05) phenotypic variation between offspring. The general combining ability (GCA) was significant for all traits except cassava brown streak disease on leaves, whereas specific combining ability (SCA) was significant for all evaluated traits. The Garukansubire and Gitamisi genotypes were the best general combiners for improving fresh storage root yield, while G1 and G2 were the best general combiners for improved carotenoid (yellow/orange pulp colour) and delayed physiological postharvest deterioration. The pulp colour had the highest GCA/SCA ratio and percent sum of squares due to GCA. The 15 F1 families exhibited essential genetic diversity for cassava improvement. The expression of most cassava traits was controlled by both additive and non-additive gene action. The study elucidated the role of dominance effects over the additive effects for the evaluated traits. However, the pulp colour was predominantly controlled by additive gene action. This implies the possibility of improving cassava through conventional breeding using recurrent selection for most traits. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Nucleosome positioning in the regulatory region of SV40 chromatin correlates with the activation and repression of early and late transcription during infection

PubMed Central

Kumar, Meera Ajeet; Christensen, Kendra; Woods, Benjamin; Dettlaff, Ashley; Perley, Danielle; Scheidegger, Adam; Balakrishnan, Lata; Milavetz, Barry

2017-01-01

The location of nucleosomes in SV40 virions and minichromosomes isolated during infection were determined by next generation sequencing (NGS). The patterns of reads within the regulatory region of chromatin from wild-type virions indicated that micrococcal nuclease-resistant nucleosomes were specifically positioned at nt 5223 and nt 363, while in minichromosomes isolated 48 h post-infection we observed nuclease-resistant nucleosomes at nt 5119 and nt 212. The nucleosomes at nt 5223 and nt 363 in virion chromatin would be expected to repress early and late transcription, respectively. In virions from the mutant cs1085, which does not repress early transcription, we found that these two nucleosomes were significantly reduced compared to wild-type virions confirming a repressive role for them. In chromatin from cells infected for only 30 min with wild-type virus, we observed a significant reduction in the nucleosomes at nt 5223 and nt 363 indicating that the potential repression by these nucleosomes appeared to be relieved very early in infection. PMID:28126638

Herpesvirus tegument and immediate early proteins are pioneers in the battle between viral infection and nuclear domain 10-related host defense.

PubMed

Zhang, Kuan; van Drunen Littel-van den Hurk, Sylvia

2017-06-15

The sophisticated anti-viral functions of nuclear domain 10 (ND10) are revealed by identifying the role of each component and the countermeasures applied by viruses. Several ND10 proteins suppress herpesviruses at initial and early phases of infection. Herpesviruses need to antagonize these anti-viral proteins to start a productive infection. In this review the recently identified similarities and differences among the strategies adopted by the three subfamilies of herpesviruses are discussed, highlighting that one of the significant purposes of incorporating tegument proteins into the viral particles might be to counteract ND10 proteins immediately after the viral genome enters the host nucleus. Once the infection progresses, a sufficient amount of immediate early proteins is expressed to disperse and hydrolyze ND10 proteins, accelerating the development of infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Early versus late surgical intervention or medical management for infective endocarditis: a systematic review and meta-analysis.

PubMed

Anantha Narayanan, Mahesh; Mahfood Haddad, Toufik; Kalil, Andre C; Kanmanthareddy, Arun; Suri, Rakesh M; Mansour, George; Destache, Christopher J; Baskaran, Janani; Mooss, Aryan N; Wichman, Tammy; Morrow, Lee; Vivekanandan, Renuga

2016-06-15

Infective endocarditis is associated with high morbidity and mortality and optimal timing for surgical intervention is unclear. We performed a systematic review and meta-analysis to compare early surgical intervention with conservative therapy in patients with infective endocarditis. PubMed, Cochrane, EMBASE, CINAHL and Google-scholar databases were searched from January 1960 to April 2015. Randomised controlled trials, retrospective cohorts and prospective observational studies comparing outcomes between early surgery at 20 days or less and conservative management for infective endocarditis were analysed. A total of 21 studies were included. OR of all-cause mortality for early surgery was 0.61 (95% CI 0.50 to 0.74, p<0.001) in unmatched groups and 0.41 (95% CI 0.31 to 0.54, p<0.001) in the propensity-matched groups (matched for baseline variables). For patients who had surgical intervention at 7 days or less, OR of all-cause mortality was 0.61 (95% CI 0.39 to 0.96, p=0.034) and in those who had surgical intervention within 8-20 days, the OR of mortality was 0.64 (95% CI 0.48 to 0.86, p=0.003) compared with conservative management. In propensity-matched groups, the OR of mortality in patients with surgical intervention at 7 days or less was 0.30 (95% CI 0.16 to 0.54, p<0.001) and in the subgroup of patients who underwent surgery between 8 and 20 days was 0.51 (95% CI 0.35 to 0.72, p<0.001). There was no significant difference in in-hospital mortality, embolisation, heart failure and recurrence of endocarditis between the overall unmatched cohorts. The results of our meta-analysis suggest that early surgical intervention is associated with significantly lower risk of mortality in patients with infective endocarditis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Cost-Effectiveness of Early Versus Standard Antiretroviral Therapy in HIV-Infected Adults in Haiti

PubMed Central

Koenig, Serena P.; Bang, Heejung; Severe, Patrice; Jean Juste, Marc Antoine; Ambroise, Alex; Edwards, Alison; Hippolyte, Jessica; Fitzgerald, Daniel W.; McGreevy, Jolion; Riviere, Cynthia; Marcelin, Serge; Secours, Rode; Johnson, Warren D.; Pape, Jean W.; Schackman, Bruce R.

2011-01-01

Background In a randomized clinical trial of early versus standard antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial. Methods and Findings Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS), including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART patients had higher mean costs for ART (US$398 versus US$81) but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS–US$9,979/YLS) including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS–US$5,537/YLS). Conclusions Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita) after a maximum of 3 years, after excluding research-related laboratory tests. Trial registration ClinicalTrials.gov NCT00120510 Please see

Early Assessment of Pancreatic Infections and Overall Prognosis in Severe Acute Pancreatitis by Procalcitonin (PCT)

PubMed Central

Rau, Bettina M.; Kemppainen, Esko A.; Gumbs, Andrew A.; Büchler, Markus W.; Wegscheider, Karl; Bassi, Claudio; Puolakkainen, Pauli A.; Beger, Hans G.

2007-01-01

Background: Pancreatic infections and sepsis are major complications in severe acute pancreatitis (AP) with significant impact on management and outcome. We investigated the value of Procalcitonin (PCT) for identifying patients at risk to develop pancreatic infections in severe AP. Methods: A total of 104 patients with predicted severe AP were enrolled in five European academic surgical centers within 96 hours of symptom onset. PCT was measured prospectively by a semi-automated immunoassay in each center, C-reactive protein (CRP) was routinely assessed. Both parameters were monitored over a maximum of 21 consecutive days and in weekly intervals thereafter. Results: In contrast to CRP, PCT concentrations were significantly elevated in patients with pancreatic infections and associated multiorgan dysfunction syndrome (MODS) who all required surgery (n = 10) and in nonsurvivors (n = 8) early after onset of symptoms. PCT levels revealed only a moderate increase in patients with pancreatic infections in the absence of MODS (n = 7), all of whom were managed nonoperatively without mortality. A PCT value of ≥3.5 ng/mL on 2 consecutive days was superior to CRP ≥430 mg/L for the assessment of infected necrosis with MODS or nonsurvival as determined by ROC analysis with a sensitivity and specificity of 93% and 88% for PCT and 40% and 100% for CRP, respectively (P < 0.01). The single or combined prediction of the two major complications was already possible on the third and fourth day after onset of symptoms with a sensitivity and specificity of 79% and 93% for PCT ≥3.8 ng/mL compared with 36% and 97% for CRP ≥430 mg/L, respectively (P = 0.002). Conclusion: Monitoring of PCT allows early and reliable assessment of clinically relevant pancreatic infections and overall prognosis in AP. This single test parameter significantly contributes to an improved stratification of patients at risk to develop major complications. PMID:17457167

Early childhood growth failure and the developmental origins of adult disease: Do enteric infections and malnutrition increase risk for the metabolic syndrome?

PubMed Central

DeBoer, Mark D.; Lima, Aldo A. M.; Oría, Reinaldo B.; Scharf, Rebecca J.; Moore, Sean R.; Luna, Max A.; Guerrant, Richard L.

2012-01-01

Hypotheses regarding the developmental origins of health and disease postulate that developing fetuses–and potentially young children—undergo adaptive epigenetic changes with longstanding effects on metabolism and other processes. Ongoing research explores whether these adaptations occur during early life following malnutrition. In the developing world there remains a high degree of nutritional stunting—linear growth failure due to inadequate calories that may be exacerbated by inflammation from ongoing infections. In areas with poor sanitation children experience vicious cycles of enteric infections and malnutrition, resulting in poor nutrient absorption from intestinal mucosa changes now termed “environmental enteropathy.” Emerging evidence links early childhood diarrhea and/or growth failure with increased CVD risk factors in later life, including dyslipidemia, hypertension and glucose intolerance. The mechanisms for these associations remain poorly understood and may relate to epigenetic responses to poor nutrition, increased inflammation or both. Given increases in CVD in developing areas of the world, associations between childhood malnutrition, early life infections and increased CVD risk factors underscore further reasons to improve nutrition and infection-related outcomes for young children worldwide. PMID:23110643

Early signs of cardiac failure: a clue for parvovirus infection screening in the first trimester?

PubMed

Carraca, Teresa; Matias, Alexandra; Brandão, Otília; Montenegro, Nuno

2011-01-01

Parvovirus B19 is a small single-stranded DNA virus and a potent inhibitor of erythropoiesis due to its cytotoxicity to erythroid progenitor cells. Although adult disease is generally mild, fetal parvovirus B19 infection can cause spontaneous abortion in early pregnancy and aplastic anemia, nonimmune hydrops fetalis and in utero fetal demise. The prevalence of parvovirus B19 maternal infection during pregnancy is about 1-2%. The vertical transmission occurs in 10-35%, being highest in the first and second trimesters. The risk of adverse fetal outcome is 10%. In contrast to the second or third trimester, in pregnancies affected by increased nuchal translucency (NT) in the late first trimester, the prevalence of maternal infection was not higher than in the general population. We report a case of first-trimester parvovirus B19 infection with increased NT and reversed a-wave in the ductus venosus (DV) at 11 weeks, with fetal demise 2 weeks later. 2011 S. Karger AG, Basel.

Development of an Infection-Responsive Fluorescent Sensor for the Early Detection of Urinary Catheter Blockage.

PubMed

Milo, Scarlet; Acosta, Florianne B; Hathaway, Hollie J; Wallace, Laura A; Thet, Naing T; Jenkins, A Toby A

2018-03-23

Formation of crystalline biofilms following infection by Proteus mirabilis can lead to encrustation and blockage of long-term indwelling catheters, with serious clinical consequences. We describe a simple sensor, placed within the catheter drainage bag, to alert of impending blockage via a urinary color change. The pH-responsive sensor is a dual-layered polymeric "lozenge", able to release the self-quenching dye 5(6)-carboxyfluorescein in response to the alkaline urine generated by the expression of bacterial urease. Sensor performance was evaluated within a laboratory model of the catheterized urinary tract, infected with both urease positive and negative bacterial strains under conditions of established infection, achieving an average "early warning" of catheter blockage of 14.5 h. Signaling only occurred following infection with urease positive bacteria. Translation of these sensors into a clinical environment would allow appropriate intervention before the occurrence of catheter blockage, a problem for which there is currently no effective control method.

Selective Targeting of Antiviral and Immunomodulating Agents in the Treatment of Arenavirus Infections

DTIC Science & Technology

1987-10-01

observed with free MTP-PE. In addition to our observations on peritoneal and alveolar macrophages, we also examined the effect of MTP-PE treatment on liver...Ir OIC FILE COPY C2 ILn 00 NM AD _____ N SELECTIVE TARGETING OF ANTIVIRAL AND IMMUNOMODULATING AGENTS IN THE TREATMENT OF ARENAVIRUS INFECTIONS "Kc...Selective Targeting of Antiviral and Immunomodulating Agents in the Treatment of Arenavirus Injections 12. PERSONAL AUTHOR(S) J. David Gangemi 13a. TYPE OF

Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4⁺ T-cell Count?

PubMed

Turk, Gabriela; Ghiglione, Yanina; Hormanstorfer, Macarena; Laufer, Natalia; Coloccini, Romina; Salido, Jimena; Trifone, César; Ruiz, María Julia; Falivene, Juliana; Holgado, María Pía; Caruso, María Paula; Figueroa, María Inés; Salomón, Horacio; Giavedoni, Luis D; Pando, María de Los Ángeles; Gherardi, María Magdalena; Rabinovich, Roberto Daniel; Pury, Pedro A; Sued, Omar

2018-01-13

Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4⁺ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1β correlated directly with CD4⁺ T-cell activation ( p < 0.05). However, none of these cytokines had good predictive values to distinguish "progressors" from "non-progressors". Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85). Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied.

Early age at time of primary Epstein-Barr virus infection results in poorly controlled viral infection in infants from Western Kenya: clues to the etiology of endemic Burkitt lymphoma.

PubMed

Piriou, Erwan; Asito, Amolo S; Sumba, Peter O; Fiore, Nancy; Middeldorp, Jaap M; Moormann, Ann M; Ploutz-Snyder, Robert; Rochford, Rosemary

2012-03-15

Infection with Epstein-Barr virus (EBV) early in life and repeated malaria exposure have been proposed as risk factors for endemic Burkitt lymphoma (eBL). Infants were enrolled from 2 rural sites in Kenya: the Kisumu District, where malaria transmission is holoendemic and risk for eBL is high, and the Nandi District, where malaria transmission is limited and the risk for eBL is low. Blood samples were taken from infants through 2 years of age to measure EBV viral load, EBV antibodies, and malaria parasitemia. We observed a significantly younger age at time of primary EBV infection in children from Kisumu compared with children from Nandi (mean age, 7.28 months [±0.33 SEM] in Kisumu vs 8.39 months [±0.26 SEM] in Nandi), with 35.3% of children in Kisumu infected before 6 months of age. To analyze how different predictors affected EBV viral load over time, we performed multilevel mixed modeling. This modeling revealed that residence in Kisumu and younger age at first EBV infection were significant predictors for having a higher EBV viral load throughout the period of observation. Children from a region at high risk for eBL were infected very early in life with EBV, resulting in higher viral loads throughout infancy.

Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection

PubMed Central

Wang, Xiaolei; Rasmussen, Terri; Pahar, Bapi; Poonia, Bhawna; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S.

2007-01-01

Rapid, profound, and selective depletion of memory CD4+ T cells has now been confirmed to occur in simian immunodeficiency virus (SIV)–infected adult macaques and human immunodeficiency virus (HIV)–infected humans. Within days of infection, marked depletion of memory CD4+ T cells occurs primarily in mucosal tissues, the major reservoir for memory CD4+ T cells in adults. However, HIV infection in neonates often results in higher viral loads and rapid disease progression, despite the paucity of memory CD4+ T cells in the peripheral blood. Here, we examined the immunophenotype of CD4+ T cells in normal and SIV-infected neonatal macaques to determine the distribution of naive and memory T-cell subsets in tissues. We demonstrate that, similar to adults, neonates have abundant memory CD4+ T cells in the intestinal tract and spleen and that these are selectively infected and depleted in primary SIV infection. Within 12 days of SIV infection, activated (CD69+), central memory (CD95+CD28+) CD4+ T cells are marked and persistently depleted in the intestine and other tissues of neonates compared with controls. The results in dicate that “activated” central memory CD4+ T cells are the major target for early SIV infection and CD4+ T cell depletion in neonatal macaques. PMID:17047153

Viral FGARAT ORF75A promotes early events in lytic infection and gammaherpesvirus pathogenesis in mice

PubMed Central

Hogan, Chad H.; Oldenburg, Darby G.; Kara, Mehmet

2018-01-01

Gammaherpesviruses encode proteins with homology to the cellular purine metabolic enzyme formyl-glycinamide-phosphoribosyl-amidotransferase (FGARAT), but the role of these viral FGARATs (vFGARATs) in the pathogenesis of a natural host has not been investigated. We report a novel role for the ORF75A vFGARAT of murine gammaherpesvirus 68 (MHV68) in infectious virion production and colonization of mice. MHV68 mutants with premature stop codons in orf75A exhibited a log reduction in acute replication in the lungs after intranasal infection, which preceded a defect in colonization of multiple host reservoirs including the mediastinal lymph nodes, peripheral blood mononuclear cells, and the spleen. Intraperitoneal infection rescued splenic latency, but not reactivation. The 75A.stop virus also exhibited defective replication in primary fibroblast and macrophage cells. Viruses produced in the absence of ORF75A were characterized by an increase in the ratio of particles to PFU. In the next round of infection this led to the alteration of early events in lytic replication including the deposition of the ORF75C tegument protein, the accelerated kinetics of viral gene expression, and induction of TNFα release and cell death. Infecting cells to deliver equivalent genomes revealed that ORF75A was required for initiating early events in infection. In contrast with the numerous phenotypes observed in the absence of ORF75A, ORF75B was dispensable for replication and pathogenesis. These studies reveal that murine rhadinovirus vFGARAT family members ORF75A and ORF75C have evolved to perform divergent functions that promote replication and colonization of the host. PMID:29390024

Viral FGARAT ORF75A promotes early events in lytic infection and gammaherpesvirus pathogenesis in mice.

PubMed

Van Skike, Nick D; Minkah, Nana K; Hogan, Chad H; Wu, Gary; Benziger, Peter T; Oldenburg, Darby G; Kara, Mehmet; Kim-Holzapfel, Deborah M; White, Douglas W; Tibbetts, Scott A; French, Jarrod B; Krug, Laurie T

2018-02-01

Gammaherpesviruses encode proteins with homology to the cellular purine metabolic enzyme formyl-glycinamide-phosphoribosyl-amidotransferase (FGARAT), but the role of these viral FGARATs (vFGARATs) in the pathogenesis of a natural host has not been investigated. We report a novel role for the ORF75A vFGARAT of murine gammaherpesvirus 68 (MHV68) in infectious virion production and colonization of mice. MHV68 mutants with premature stop codons in orf75A exhibited a log reduction in acute replication in the lungs after intranasal infection, which preceded a defect in colonization of multiple host reservoirs including the mediastinal lymph nodes, peripheral blood mononuclear cells, and the spleen. Intraperitoneal infection rescued splenic latency, but not reactivation. The 75A.stop virus also exhibited defective replication in primary fibroblast and macrophage cells. Viruses produced in the absence of ORF75A were characterized by an increase in the ratio of particles to PFU. In the next round of infection this led to the alteration of early events in lytic replication including the deposition of the ORF75C tegument protein, the accelerated kinetics of viral gene expression, and induction of TNFα release and cell death. Infecting cells to deliver equivalent genomes revealed that ORF75A was required for initiating early events in infection. In contrast with the numerous phenotypes observed in the absence of ORF75A, ORF75B was dispensable for replication and pathogenesis. These studies reveal that murine rhadinovirus vFGARAT family members ORF75A and ORF75C have evolved to perform divergent functions that promote replication and colonization of the host.

Early respiratory infection is associated with reduced spirometry in children with cystic fibrosis.

PubMed

Ramsey, Kathryn A; Ranganathan, Sarath; Park, Judy; Skoric, Billy; Adams, Anne-Marie; Simpson, Shannon J; Robins-Browne, Roy M; Franklin, Peter J; de Klerk, Nick H; Sly, Peter D; Stick, Steve M; Hall, Graham L

2014-11-15

Pulmonary inflammation, infection, and structural lung disease occur early in life in children with cystic fibrosis. We hypothesized that the presence of these markers of cystic fibrosis lung disease in the first 2 years of life would be associated with reduced lung function in childhood. Lung function (forced expiratory volume in the first three-quarters of a second [FEV0.75], FVC) was assessed in individuals with cystic fibrosis diagnosed after newborn screening and healthy subjects during infancy (0-2 yr) and again at early school age (4-8 yr). Individuals with cystic fibrosis underwent annual bronchoalveolar lavage fluid examination, and chest computed tomography. We examined which clinical outcomes (pulmonary inflammation, infection, structural lung disease, respiratory hospitalizations, antibiotic prophylaxis) measured in the first 2 years of life were associated with reduced lung function in infants and young children with cystic fibrosis, using a mixed effects model. Children with cystic fibrosis (n = 56) had 8.3% (95% confidence interval [CI], -15.9 to -6.6; P = 0.04) lower FEV0.75 compared with healthy subjects (n = 18). Detection of proinflammatory bacterial pathogens (Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Aspergillus species, Streptococcus pneumoniae) in bronchoalveolar lavage fluid was associated with clinically significant reductions in FEV0.75 (ranging between 11.3 and 15.6%). The onset of lung disease in infancy, specifically the occurrence of lower respiratory tract infection, is associated with low lung function in young children with cystic fibrosis. Deficits in lung function measured in infancy persist into childhood, emphasizing the need for targeted therapeutic interventions in infancy to maximize functional outcomes later in life.

A novel double recognition enzyme-linked immunosorbent assay based on the nucleocapsid protein for early detection of European porcine reproductive and respiratory syndrome virus infection.

PubMed

Venteo, A; Rebollo, B; Sarraseca, J; Rodriguez, M J; Sanz, A

2012-04-01

Precise and rapid detection of porcine reproductive respiratory syndrome virus (PRRSV) infection in swine farms is critical. Improvement of control procedures, such as testing incoming gilt and surveillance of seronegative herds requires more rapid and sensitive methods. However, standard serological techniques detect mainly IgG antibodies. A double recognition enzyme-linked immunosorbent assay (DR-ELISA) was developed for detection of antibodies specific to European PRRSV. This new assay can recognize both IgM and IgG antibodies to PRSSV which might be useful for detecting in routine surveillance assays pigs that are in the very early stages of infection and missed by conventional assays detecting only IgG antibodies. DR-ELISA is based on the double recognition of antigen by antibody. In this study, the recombinant nucleocapsid protein (N) of PRRSV was used both as the coating and the enzyme-conjugated antigen. To evaluate the sensitivity of the assay at early stages of the infection, sera from 69 pigs infected with PRRSV were collected during successive days post infection (pi) and tested. While standard methods showed low sensitivity rates before day 14 pi, DR-ELISA detected 88.4% seropositive samples at day 7 showing greater sensitivity at early stages of the infection. Further studies were carried out to assess the efficiency of the new assay, and the results showed DR-ELISA to be a sensitive and accurate method for early diagnosis of EU-PRRSV infection. Copyright © 2012 Elsevier B.V. All rights reserved.

Early Selection versus Late Correction: Age-Related Differences in Controlling Working Memory Contents

PubMed Central

Schwarzkopp, Tina; Mayr, Ulrich; Jost, Kerstin

2016-01-01

We examined whether a reduced ability to ignore irrelevant information is responsible for the age-related decline of working-memory (WM) functions. By means of event-related brain potentials we will show that filtering is not out of service in older adults but shifted to a later processing stage. Participants performed a visual short-term memory task (change-detection task) in which targets were presented along with distractors. To allow early selection, a cue was presented in advance of each display, indicating where the targets were to appear. Despite this relatively easy selection criterion, older adults’ filtering was delayed as indicated by the amplitude pattern of the contralateral delay activity. Importantly, WM-equated younger adults did not show a delay indicating that the delay is specific to older adults and not a general phenomenon that comes with low WM capacity. Moreover, the analysis of early visual potentials revealed qualitatively different perceptual/attentional processing between the age groups. Young adults exhibited stronger distractor sensitivity that in turn facilitated filtering. Older adults, in contrast, seemed to initially store distractors and to suppress them after the fact. These early-selection versus late-correction modes suggest an age-related shift in the strategy to control the contents of WM. PMID:27253867

Early sex work initiation independently elevates odds of HIV infection and police arrest among adult sex workers in a Canadian setting

PubMed Central

GOLDENBERG, Shira M.; CHETTIAR, Jill; SIMO, Annick; SILVERMAN, Jay G.; STRATHDEE, Steffanie A.; MONTANER, Julio; SHANNON, Kate

2014-01-01

Objectives To explore factors associated with early sex work initiation, and model the independent effect of early initiation on HIV infection and prostitution arrests among adult sex workers (SWs). Design Baseline data (2010–2011) were drawn from a cohort of SWs who exchanged sex for money within the last month and were recruited through time-location sampling in Vancouver, Canada. Analyses were restricted to adults ≥18 years old. Methods SWs completed a questionnaire and HIV/STI testing. Using multivariate logistic regression, we identified associations with early sex work initiation (<18 years old) and constructed confounder models examining the independent effect of early initiation on HIV and prostitution arrests among adult SWs. Results Of 508 SWs, 193 (38.0%) reported early sex work initiation, with 78.53% primarily street-involved SWs and 21.46% off-street SWs. HIV prevalence was 11.22%, which was 19.69% among early initiates. Early initiates were more likely to be Canadian-born (Adjusted Odds Ratio (AOR): 6.8, 95% Confidence Interval (CI): 2.42–19.02), inject drugs (AOR: 1.6, 95%CI: 1.0–2.5), and to have worked for a manager (AOR: 2.22, 95%CI: 1.3–3.6) or been coerced into sex work (AOR: 2.3, 95%CI: 1.14–4.44). Early initiation retained an independent effect on increased risk of HIV infection (AOR: 2.5, 95% CI: 1.3–3.2) and prostitution arrests (AOR: 2.0, 95%CI: 1.3–3.2). Conclusions Adolescent sex work initiation is concentrated among marginalized, drug and street-involved SWs. Early initiation holds an independent increased effect on HIV infection and criminalization of adult SWs. Findings suggest the need for evidence-based approaches to reduce harm among adult and youth SWs. PMID:23982660

Huntingtons Disease Mice Infected with Toxoplasma gondii Demonstrate Early Kynurenine Pathway Activation, Altered CD8+ T-Cell Responses, and Premature Mortality.

PubMed

Donley, David W; Olson, Andrew R; Raisbeck, Merl F; Fox, Jonathan H; Gigley, Jason P

2016-01-01

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine-repeat expansion in the huntingtin protein. Activation of the kynurenine pathway of tryptophan degradation is implicated in the pathogenesis of HD. Indoleamine-2,3-dioxygenase (IDO) catalyzes the oxidation of tryptophan to kynurenine, the first step in this pathway. The prevalent, neuroinvasive protozoal pathogen Toxoplasma gondii (T. gondii) results in clinically silent life-long infection in immune-competent individuals. T. gondii infection results in activation of IDO which provides some protection against the parasite by depleting tryptophan which the parasite cannot synthesize. The kynurenine pathway may therefore represent a point of synergism between HD and T. gondii infection. We show here that IDO activity is elevated at least four-fold in frontal cortex and striata of non-infected N171-82Q HD mice at 14-weeks corresponding to early-advanced HD. T. gondii infection at 5 weeks resulted in elevation of cortical IDO activity in HD mice. HD-infected mice died significantly earlier than wild-type infected and HD control mice. Prior to death, infected HD mice demonstrated decreased CD8+ T-lymphocyte proliferation in brain and spleen compared to wild-type infected mice. We demonstrate for the first time that HD mice have an altered response to an infectious agent that is characterized by premature mortality, altered immune responses and early activation of IDO. Findings are relevant to understanding how T. gondii infection may interact with pathways mediating neurodegeneration in HD.

Odor, Not Performance, Dictates Bemisia tabaci's Selection between Healthy and Virus Infected Plants

PubMed Central

Chen, Gong; Su, Qi; Shi, Xiaobin; Liu, Xin; Peng, Zhengke; Zheng, Huixin; Xie, Wen; Xu, Baoyun; Wang, Shaoli; Wu, Qingjun; Zhou, Xuguo; Zhang, Youjun

2017-01-01

Although, insect herbivores are generally thought to select hosts that favor the fitness of their progeny, this “mother-knows-best” hypothesis may be challenged by the presence of a plant virus. Our previous study showed that the whitefly, Bemisia tabaci, the obligate vector for transmitting Tomato yellow leaf curl virus (TYLCV), preferred to settle and oviposit on TYLCV-infected rather than healthy host plant, Datura stramonium. The performances of B. tabaci larvae and adults were indeed improved on virus-infected D. stramonium, which is consistent with “mother-knows-best” hypothesis. In this study, B. tabaci Q displayed the same preference to settle and oviposit on Tomato spotted wilt virus (TSWV)-infected host plants, D. stramonium and Capsicum annuum, respectively. As a non-vector of TSWV, however, insect performance was impaired since adult body size, longevity, survival, and fecundity were reduced in TSWV infected D. stramonium. This appears to be an odor-mediated behavior, as plant volatile profiles are modified by viral infection. Infected plants have reduced quantities of o-xylene and α-pinene, and increased levels of phenol and 2-ethyl-1-hexanol in their headspace. Subsequent behavior experiments showed that o-xylene and α-pinene are repellant, while phenol and 2-ethyl-1-hexanol are attractive. This indicates that the preference of B. tabaci for virus-infected plants is modulated by the dynamic changes in the volatile profiles rather than the subsequent performances on virus-infected plants. PMID:28360861

Fungal infections in children in the early postoperative period after cardiac surgery for congenital heart disease: a single-centre experience.

PubMed

Jaworski, Radoslaw; Haponiuk, Ireneusz; Irga-Jaworska, Ninela; Chojnicki, Maciej; Steffens, Mariusz; Paczkowski, Konrad; Zielinski, Jacek

2016-09-01

Postoperative infections are still an important problem in cardiac surgery, especially in the paediatric population, and may influence the final outcome of congenital heart disease treatment. Postoperative infections with fungi are uncommon. The aetiology is poorly understood, and the proper diagnosis and treatment is unclear. In this single-centre study, the frequency of invasive fungal disease in children who underwent surgical management of congenital heart diseases was determined along with the risk factors for infection, treatment options and outcomes. All consecutive paediatric patients (<18 years of age) who underwent cardiac surgery for congenital heart disease between September 2008 and December 2015 in a paediatric cardiac centre in Poland were identified. Those who developed invasive fungal disease in the early postoperative period (30 days) were identified. Of the 1540 cardiosurgical procedures for congenital heart disease, 6 were complicated by fungal infection (0.39%). One patient had a high probability of fungal infection, but the diagnosis was unproved. Nevertheless, the patient was successfully treated with antifungal treatment. Five had proven invasive fungal disease. Of these, 3 were diagnosed with candidaemia. All had undergone cardiopulmonary bypass. Of the remaining 2 patients, 1 was a preterm newborn with complete atrioventricular septal defect who developed rib fungal invasion. The remaining patient had pulmonary atresia with ventricular septal defect and developed Fournier's gangrene after surgery. None of the patients died due to infection in the early postoperative period. However, the child with rib fungal invasion died 39 days after surgery as a result of multiorgan failure. Fungal infections in paediatric patients after cardiac surgery may markedly influence morbidity and mortality. Fungal infection prophylaxis in this specific group of children may reduce morbidity, whereas early empirical treatment followed by a targeted approach may

The selection system of silviculture in spruce-fir stands - procedures, early results, and comparisons with unmanaged stands

Treesearch

Robert M. Frank; Barton M. Blum

1978-01-01

Early results after 20 years of record keeping indicate that spruce-fir stands will respond to the selection system of silviculture. Stand quality is improved, species composition can be altered, diameter-class distribution approaches a stated goal, stand density is controlled, and yields are increased. Selection silviculture in spruce-fir can now be compared to early...

Protist predation can select for bacteria with lowered susceptibility to infection by lytic phages.

PubMed

Örmälä-Odegrip, Anni-Maria; Ojala, Ville; Hiltunen, Teppo; Zhang, Ji; Bamford, Jaana K H; Laakso, Jouni

2015-05-07

Consumer-resource interactions constitute one of the most common types of interspecific antagonistic interaction. In natural communities, complex species interactions are likely to affect the outcomes of reciprocal co-evolution between consumers and their resource species. Individuals face multiple enemies simultaneously, and consequently they need to adapt to several different types of enemy pressures. In this study, we assessed how protist predation affects the susceptibility of bacterial populations to infection by viral parasites, and whether there is an associated cost of defence on the competitive ability of the bacteria. As a study system we used Serratia marcescens and its lytic bacteriophage, along with two bacteriovorous protists with distinct feeding modes: Tetrahymena thermophila (particle feeder) and Acanthamoeba castellanii (surface feeder). The results were further confirmed with another study system with Pseudomonas and Tetrahymena thermophila. We found that selection by protist predators lowered the susceptibility to infections by lytic phages in Serratia and Pseudomonas. In Serratia, concurrent selection by phages and protists led to lowered susceptibility to phage infections and this effect was independent from whether the bacteria shared a co-evolutionary history with the phage population or not. Bacteria that had evolved with phages were overall more susceptible to phage infection (compared to bacteria with history with multiple enemies) but they were less vulnerable to the phages they had co-evolved with than ancestral phages. Selection by bacterial enemies was costly in general and was seen as a lowered fitness in absence of phages, measured as a biomass yield. Our results show the significance of multiple species interactions on pairwise consumer-resource interaction, and suggest potential overlap in defending against predatory and parasitic enemies in microbial consumer-resource communities. Ultimately, our results could have larger scale

Transcriptome Analysis of Early Responsive Genes in Rice during Magnaporthe oryzae Infection.

PubMed

Wang, Yiming; Kwon, Soon Jae; Wu, Jingni; Choi, Jaeyoung; Lee, Yong-Hwan; Agrawal, Ganesh Kumar; Tamogami, Shigeru; Rakwal, Randeep; Park, Sang-Ryeol; Kim, Beom-Gi; Jung, Ki-Hong; Kang, Kyu Young; Kim, Sang Gon; Kim, Sun Tae

2014-12-01

Rice blast disease caused by Magnaporthe oryzae is one of the most serious diseases of cultivated rice (Oryza sativa L.) in most rice-growing regions of the world. In order to investigate early response genes in rice, we utilized the transcriptome analysis approach using a 300 K tilling microarray to rice leaves infected with compatible and incompatible M. oryzae strains. Prior to the microarray experiment, total RNA was validated by measuring the differential expression of rice defense-related marker genes (chitinase 2, barwin, PBZ1, and PR-10) by RT-PCR, and phytoalexins (sakuranetin and momilactone A) with HPLC. Microarray analysis revealed that 231 genes were up-regulated (>2 fold change, p < 0.05) in the incompatible interaction compared to the compatible one. Highly expressed genes were functionally characterized into metabolic processes and oxidation-reduction categories. The oxidative stress response was induced in both early and later infection stages. Biotic stress overview from MapMan analysis revealed that the phytohormone ethylene as well as signaling molecules jasmonic acid and salicylic acid is important for defense gene regulation. WRKY and Myb transcription factors were also involved in signal transduction processes. Additionally, receptor-like kinases were more likely associated with the defense response, and their expression patterns were validated by RT-PCR. Our results suggest that candidate genes, including receptor-like protein kinases, may play a key role in disease resistance against M. oryzae attack.

Selective predation on hantavirus-infected voles by owls and confounding effects from landscape properties.

PubMed

Khalil, Hussein; Ecke, Frauke; Evander, Magnus; Hörnfeldt, Birger

2016-06-01

It has been suggested that predators may protect human health through reducing disease-host densities or selectively preying on infected individuals from the population. However, this has not been tested empirically. We hypothesized that Tengmalm's owl (Aegolius funereus) selectively preys on hantavirus-infected individuals of its staple prey, the bank vole (Myodes glareolus). Bank voles are hosts of Puumala hantavirus, which causes a form of hemorrhagic fever in humans. Selective predation by owls on infected voles may reduce human disease risk. We compared the prevalence of anti-Puumala hantavirus antibodies (seroprevalence), in bank voles cached by owls in nest boxes to seroprevalence in voles trapped in closed-canopy forest around each nest box. We found no general difference in seroprevalence. Forest landscape structure could partly account for the observed patterns in seroprevalence. Only in more connected forest patches was seroprevalence in bank voles cached in nest boxes higher than seroprevalence in trapped voles. This effect disappeared with increasing forest patch isolation, as seroprevalence in trapped voles increased with forest patch isolation, but did not in cached voles. Our results suggest a complex relationship between zoonotic disease prevalence in hosts, their predators, and landscape structure. Some mechanisms that may have caused the seroprevalence patterns in our results include higher bank vole density in isolated forest patches. This study offers future research potential to shed further light on the contribution of predators and landscape properties to human health.

Testing the mutant selection window hypothesis with Escherichia coli exposed to levofloxacin in a rabbit tissue cage infection model.

PubMed

Ni, W; Song, X; Cui, J

2014-03-01

The purpose of this study was to test the mutant selection window (MSW) hypothesis with Escherichia coli exposed to levofloxacin in a rabbit model and to compare in vivo and in vitro exposure thresholds that restrict the selection of fluoroquinolone-resistant mutants. Local infection with E. coli was established in rabbits, and the infected animals were treated orally with various doses of levofloxacin once a day for five consecutive days. Changes in levofloxacin concentration and levofloxacin susceptibility were monitored at the site of infection. The MICs of E. coli increased when levofloxacin concentrations at the site of infection fluctuated between the lower and upper boundaries of the MSW, defined in vitro as the minimum inhibitory concentration (MIC99) and the mutant prevention concentration (MPC), respectively. The pharmacodynamic thresholds at which resistant mutants are not selected in vivo was estimated as AUC24/MPC > 20 h or AUC24/MIC > 60 h, where AUC24 is the area under the drug concentration time curve in a 24-h interval. Our finding demonstrated that the MSW existed in vivo. The AUC24/MPC ratio that prevented resistant mutants from being selected estimated in vivo is consistent with that observed in vitro, indicating it might be a reliable index for guiding the optimization of antimicrobial treatment regimens for suppression of the selection of antimicrobial resistance.

Selective alterations of the host cell architecture upon infection with parvovirus minute virus of mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nueesch, Juerg P.F.; Lachmann, Sylvie; Rommelaere, Jean

During a productive infection, the prototype strain of parvovirus minute virus of mice (MVMp) induces dramatic morphological alterations to the fibroblast host cell A9, resulting in cell lysis and progeny virus release. In order to understand the mechanisms underlying these changes, we characterized the fate of various cytoskeletal filaments and investigated the nuclear/cytoplasmic compartmentalization of infected cells. While most pronounced effects could be seen on micro- and intermediate filaments, manifest in dramatic rearrangements and degradation of filamentous (F-)actin and vimentin structures, only little impact could be seen on microtubules or the nuclear envelope during the entire monitored time of infection.more » To further analyze the disruption of the cytoskeletal structures, we investigated the viral impact on selective regulatory pathways. Thereby, we found a correlation between microtubule stability and MVM-induced phosphorylation of {alpha}/{beta} tubulin. In contrast, disassembly of actin filaments late in infection could be traced back to the disregulation of two F-actin associated proteins gelsolin and Wiscott-Aldrich Syndrome Protein (WASP). Thereby, an increase in the amount of gelsolin, an F-actin severing protein was observed during infection, accounting for the disruption of stress fibers upon infection. Concomitantly, the actin polymerization activity also diminished due to a loss of WASP, the activator protein of the actin polymerization machinery the Arp2/3 complex. No effects could be seen in amount and distribution of other F-actin regulatory factors such as cortactin, cofilin, and profilin. In summary, the selective attack of MVM towards distinct host cell cytoskeletal structures argues for a regulatory feature during infection, rather than a collapse of the host cell as a mere side effect of virus production.« less

Environmental Suitability of Vibrio Infections in a Warming Climate: An Early Warning System.

PubMed

Semenza, Jan C; Trinanes, Joaquin; Lohr, Wolfgang; Sudre, Bertrand; Löfdahl, Margareta; Martinez-Urtaza, Jaime; Nichols, Gordon L; Rocklöv, Joacim

2017-10-10

Some Vibrio spp. are pathogenic and ubiquitous in marine waters with low to moderate salinity and thrive with elevated sea surface temperature (SST). Our objective was to monitor and project the suitability of marine conditions for Vibrio infections under climate change scenarios. The European Centre for Disease Prevention and Control (ECDC) developed a platform (the ECDC Vibrio Map Viewer) to monitor the environmental suitability of coastal waters for Vibrio spp. using remotely sensed SST and salinity. A case-crossover study of Swedish cases was conducted to ascertain the relationship between SST and Vibrio infection through a conditional logistic regression. Climate change projections for Vibrio infections were developed for Representative Concentration Pathway (RCP) 4.5 and RCP 8.5. The ECDC Vibrio Map Viewer detected environmentally suitable areas for Vibrio spp. in the Baltic Sea in July 2014 that were accompanied by a spike in cases and one death in Sweden. The estimated exposure-response relationship for Vibrio infections at a threshold of 16°C revealed a relative risk (RR)=1.14 (95% CI: 1.02, 1.27; p=0.024) for a lag of 2 wk; the estimated risk increased successively beyond this SST threshold. Climate change projections for SST under the RCP 4.5 and RCP 8.5 scenarios indicate a marked upward trend during the summer months and an increase in the relative risk of these infections in the coming decades. This platform can serve as an early warning system as the risk of further Vibrio infections increases in the 21st century due to climate change. https://doi.org/10.1289/EHP2198.

Environmental Suitability of Vibrio Infections in a Warming Climate: An Early Warning System

PubMed Central

Trinanes, Joaquin; Lohr, Wolfgang; Sudre, Bertrand; Löfdahl, Margareta; Martinez-Urtaza, Jaime; Nichols, Gordon L.; Rocklöv, Joacim

2017-01-01

Background: Some Vibrio spp. are pathogenic and ubiquitous in marine waters with low to moderate salinity and thrive with elevated sea surface temperature (SST). Objectives: Our objective was to monitor and project the suitability of marine conditions for Vibrio infections under climate change scenarios. Methods: The European Centre for Disease Prevention and Control (ECDC) developed a platform (the ECDC Vibrio Map Viewer) to monitor the environmental suitability of coastal waters for Vibrio spp. using remotely sensed SST and salinity. A case-crossover study of Swedish cases was conducted to ascertain the relationship between SST and Vibrio infection through a conditional logistic regression. Climate change projections for Vibrio infections were developed for Representative Concentration Pathway (RCP) 4.5 and RCP 8.5. Results: The ECDC Vibrio Map Viewer detected environmentally suitable areas for Vibrio spp. in the Baltic Sea in July 2014 that were accompanied by a spike in cases and one death in Sweden. The estimated exposure–response relationship for Vibrio infections at a threshold of 16°C revealed a relative risk (RR)=1.14 (95% CI: 1.02, 1.27; p=0.024) for a lag of 2 wk; the estimated risk increased successively beyond this SST threshold. Climate change projections for SST under the RCP 4.5 and RCP 8.5 scenarios indicate a marked upward trend during the summer months and an increase in the relative risk of these infections in the coming decades. Conclusions: This platform can serve as an early warning system as the risk of further Vibrio infections increases in the 21st century due to climate change. https://doi.org/10.1289/EHP2198 PMID:29017986

Transcriptomic analysis of two Beauveria bassiana strains grown on cuticle extracts of the silkworm uncovers their different metabolic response at early infection stage.

PubMed

Wang, Jing-Jie; Bai, Wen-Wen; Zhou, Wei; Liu, Jing; Chen, Jie; Liu, Xiao-Yuan; Xiang, Ting-Ting; Liu, Ren-Hua; Wang, Wen-Hui; Zhang, Bao-Ling; Wan, Yong-Ji

2017-05-01

Beauveria bassiana is an important entomopathogenic fungus which not only widely distributes in the environment but also shows phenotypic diversity. However, the mechanism of pathogenic differences among natural B. bassiana strains has not been revealed at transcriptome-wide level. In the present study, in order to explore the mechanism, two B. bassiana strains with different pathogenicity were isolated from silkworms (Bombyx mori L.) and selected to analyze the gene expression of early stage by culturing on cuticle extracts of the silkworm and using RNA-sequencing technique. A total of 2108 up-regulated and 1115 down-regulated genes were identified in B. bassiana strain GXsk1011 (hyper-virulent strain) compared with B. bassiana strain GXtr1009 (hypo-virulent strain), respectively. The function categorization of differential expressed genes (DEGs) showed that most of them involved in metabolic process, biosynthesis of secondary metabolites, catalytic activity, and some involved in nutrition uptake, adhesion and host defense were also noted. Based on our data, distinct pathogenicity among different strains of B. bassiana may largely attribute to unique gene expression pattern which differed at very early infection process. Most of the genes involved in conidia adhesion, cuticle degradation and fungal growth were up-regulated in hyper-virulent B. bassiana strain GXsk1011. Furthermore, in combination with fungal growth analysis, our research provided a clue that fungal growth may also play an important role during early infection process. The results will help to explain why different B. bassiana strains show distinct pathogenicity on the same host even under same condition. Moreover, the transcriptome data were also useful for screening potential virulence factors. Copyright © 2017 Elsevier Inc. All rights reserved.

The control of sea lice in Atlantic salmon by selective breeding.

PubMed

Gharbi, Karim; Matthews, Louise; Bron, James; Roberts, Ron; Tinch, Alan; Stear, Michael

2015-09-06

Sea lice threaten the welfare of farmed Atlantic salmon and the sustainability of fish farming across the world. Chemical treatments are the major method of control but drug resistance means that alternatives are urgently needed. Selective breeding can be a cheap and effective alternative. Here, we combine experimental trials and diagnostics to provide a practical protocol for quantifying resistance to sea lice. We then combined quantitative genetics with epidemiological modelling to make the first prediction of the response to selection, quantified in terms of reduced need for chemical treatments. We infected over 1400 young fish with Lepeophtheirus salmonis, the most important species in the Northern Hemisphere. Mechanisms of resistance were expressed early in infection. Consequently, the number of lice per fish and the ranking of families were very similar at 7 and 17 days post infection, providing a stable window for assessing susceptibility to infection. The heritability of lice numbers within this time window was moderately high at 0.3, confirming that selective breeding is viable. We combined an epidemiological model of sea lice infection and control on a salmon farm with genetic variation in susceptibility among individuals. We simulated 10 generations of selective breeding and examined the frequency of treatments needed to control infection. Our model predicted that substantially fewer chemical treatments are needed to control lice outbreaks in selected populations and chemical treatment could be unnecessary after 10 generations of selection. Selective breeding for sea lice resistance should reduce the impact of sea lice on fish health and thus substantially improve the sustainability of Atlantic salmon production. © 2015 The Author(s).

Socio-economic status and time trends associated with early ART initiation following primary HIV infection in Montreal, Canada: 1996 to 2015.

PubMed

Mehraj, Vikram; Cox, Joseph; Lebouché, Bertrand; Costiniuk, Cecilia; Cao, Wei; Li, Taisheng; Ponte, Rosalie; Thomas, Réjean; Szabo, Jason; Baril, Jean-Guy; Trottier, Benoit; Côté, Pierre; LeBlanc, Roger; Bruneau, Julie; Tremblay, Cécile; Routy, Jean-Pierre

2018-02-01

Guidelines regarding antiretroviral therapy (ART) initiation in HIV infection have varied over time, with the 2015 World Health Organization recommendation suggesting ART initiation at the time of diagnosis regardless of CD4 T-cell counts. Herein, we investigated the influence of socio-demographic and clinical factors in addition to time trends on early ART initiation among participants of the Montreal Primary HIV Infection Study. The Montreal Primary HIV Infection Study is a prospective cohort established in three community medical centres (CMCs) and two university medical centres (UMCs). Recently diagnosed HIV-infected adults were categorized as receiving early (vs. delayed) ART if ART was initiated within 180 days of the baseline visit. Associations between early ART initiation and socio-demographic, socio-economic and behavioural information were examined. Independent associations of factors linked with early ART initiation were determined using multivariable binary logistic regression analysis. A total of 348 participants had a documented date of HIV acquisition of <180 days. The median interquartile range (IQR) age of participants was 35 (28; 42) years and the majority were male (96%), having paid employment (63%), men who have sex with men (MSM) (78%) and one to four sexual partners in the last three months (70%). Participants presented with a median IQR HIV plasma viral load of 4.6 (3.7; 5.3) log 10 copies/ml, CD4 count of 510 (387; 660) cells/μl and were recruited in CMCs (52%) or UMCs (48%). Early ART initiation was observed in 47% of the participants and the trend followed a V-shaped curve with peaks in 1996 to 1997 (89%) and 2013 to 2015 (88%) with a dip in 2007 to 2009 (22%). Multivariable analyses showed that having a paid employment adjusted odds ratio (aOR: 2.43; 95% CI: 1.19, 4.95), lower CD4 count (aOR per 50 cell increase: 0.93; 95% CI: 0.87, 0.99) and care at UMCs (aOR: 2.03; 95% CI: 1.06 to 3.90) were independently associated with early ART

Early molecular diagnosis of acute Chagas disease after transplantation with organs from Trypanosoma cruzi-infected donors.

PubMed

Cura, C I; Lattes, R; Nagel, C; Gimenez, M J; Blanes, M; Calabuig, E; Iranzo, A; Barcan, L A; Anders, M; Schijman, A G

2013-12-01

Organ transplantation (TX) is a novel transmission modality of Chagas disease. The results of molecular diagnosis and characterization of Trypanosoma cruzi acute infection in naïve TX recipients transplanted with organs from infected deceased donors are reported. Peripheral blood and cerebrospinal fluid samples from the TX recipients of organs from infected donors were prospectively and sequentially studied for detection of T. cruzi by means of kinetoplastid DNA polymerase chain reaction (kDNA-PCR). In positive blood samples, a PCR algorithm for identification of T. cruzi Discrete Typing Units (DTUs) and quantitative real-time PCR (qPCR) to quantify parasitic loads were performed. Minicircle signatures of T. cruzi infecting populations were also analyzed using restriction fragment length polymorphism (RFLP)-PCR. Eight seronegative TX recipients from four infected donors were studied. In five, the infection was detected at 68.4 days post-TX (36-98 days). In one case, it was transmitted to two of three TX recipients. The comparison of the minicircle signatures revealed nearly identical RFLP-PCR profiles, confirming a common source of infection. The five cases were infected by DTU TcV. This report reveals the relevance of systematic monitoring of TX recipients using PCR strategies in order to provide an early diagnosis allowing timely anti-trypanosomal treatment. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Simian immunodeficiency virus selectively infects proliferating CD4+ T cells in neonatal rhesus macaques.

PubMed

Wang, Xiaolei; Xu, Huanbin; Pahar, Bapi; Alvarez, Xavier; Green, Linda C; Dufour, Jason; Moroney-Rasmussen, Terri; Lackner, Andrew A; Veazey, Ronald S

2010-11-18

Infants infected with HIV have a more severe course of disease and persistently higher viral loads than HIV-infected adults. However, the underlying pathogenesis of this exacerbation remains obscure. Here we compared the rate of CD4(+) and CD8(+) T-cell proliferation in intestinal and systemic lymphoid tissues of neonatal and adult rhesus macaques, and of normal and age-matched simian immunodeficiency virus (SIV)-infected neonates. The results demonstrate infant primates have much greater rates of CD4(+) T-cell proliferation than adult macaques, and that these proliferating, recently "activated" CD4(+) T cells are infected in intestinal and other lymphoid tissues of neonates, resulting in selective depletion of proliferating CD4(+) T cells in acute infection. This depletion is accompanied by a marked increase in CD8(+) T-cell activation and production, particularly in the intestinal tract. The data indicate intestinal CD4(+) T cells of infant primates have a markedly accelerated rate of proliferation and maturation resulting in more rapid and sustained production of optimal target cells (activated memory CD4(+) T cells), which may explain the sustained "peak" viremia characteristic of pediatric HIV infection. Eventual failure of CD4(+) T-cell turnover in intestinal tissues may indicate a poorer prognosis for HIV-infected infants.

Disappointing performance of literature-derived selective screening criteria for asymptomatic Chlamydia trachomatis infection in an inner-city population.

PubMed

van Valkengoed, I G; Boeke, A J; Morré, S A; van den Brule, A J; Meijer, C J; Devillé, W; Bouter, L M

2000-10-01

In an inner-city population with a low prevalence of Chlamydia trachomatis infection, selective screening may be indicated to increase the efficiency of screening. To evaluate the performance of sets of selective screening criteria for asymptomatic Chlamydia trachomatis infection in an inner-city population. The criteria were derived from reports of studies carried out in various settings. A total of 5714 women age 15 to 40 years living in Amsterdam were invited for a screening based on home-obtained urine specimens. Criteria identified from the literature were applied to the screening population. A calculated area under the receiver-operator characteristic curve (AUC) of greater than 0.75 was considered a good measure of diagnostic accuracy. Of the four sets of criteria, selection based on the following determinants showed the highest diagnostic accuracy: younger than 25 years, being unmarried, number of partners during the previous 6 months, Surinam or Antillean origin (black), and vaginal douching (AUC, 0.67; 95% CI, 0.65-0.69). Selection based on age alone showed an AUC of 0.57 (95% CI, 0.55-0.69). The performance of selective screening criteria for asymptomatic C trachomatis infection in an inner-city population in Amsterdam was insufficient to recommend its implementation in practice.

A population-based prospective cohort study examining the influence of early-life respiratory tract infections on school-age lung function and asthma.

PubMed

van Meel, Evelien R; den Dekker, Herman T; Elbert, Niels J; Jansen, Pauline W; Moll, Henriëtte A; Reiss, Irwin K; de Jongste, Johan C; Jaddoe, Vincent W V; Duijts, Liesbeth

2018-02-01

Early-life respiratory tract infections could affect airway obstruction and increase asthma risk in later life. However, results from previous studies are inconsistent. We examined the associations of early-life respiratory tract infections with lung function and asthma in school-aged children. This study among 5197 children born between April 2002 and January 2006 was embedded in a population-based prospective cohort study. Information on physician-attended upper and lower respiratory tract infections until age 6 years (categorised into ≤ 3 and >3-6 years) was obtained by annual questionnaires. Spirometry measures and physician-diagnosed asthma were assessed at age 10 years. Upper respiratory tract infections were not associated with adverse respiratory outcomes. Compared with children without lower respiratory tract infections ≤3 years, children with lower respiratory tract infections ≤3 years had a lower FEV 1 , FVC, FEV 1 :FVC and forced expiratory flow at 75% of FVC (FEF 75 ) (Z-score (95% CI): ranging from -0.22 (-0.31 to -0.12) to -0.12 (-0.21 to -0.03)) and an increased risk of asthma (OR (95% CI): 1.79 (1.19 to 2.59)). Children with lower respiratory tract infections >3-6 years had an increased risk of asthma (3.53 (2.37 to 5.17)) only. Results were not mediated by antibiotic or paracetamol use and not modified by inhalant allergic sensitisation. Cross-lagged modelling showed that results were not bidirectional and independent of preschool wheezing patterns. Early-life lower respiratory tract infections ≤3 years are most consistently associated with lower lung function and increased risk of asthma in school-aged children. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comprehensive Evaluation of Streptococcus sanguinis Cell Wall-Anchored Proteins in Early Infective Endocarditis▿ †

PubMed Central

Turner, Lauren Senty; Kanamoto, Taisei; Unoki, Takeshi; Munro, Cindy L.; Wu, Hui; Kitten, Todd

2009-01-01

Streptococcus sanguinis is a member of the viridans group of streptococci and a leading cause of the life-threatening endovascular disease infective endocarditis. Initial contact with the cardiac infection site is likely mediated by S. sanguinis surface proteins. In an attempt to identify the proteins required for this crucial step in pathogenesis, we searched for surface-exposed, cell wall-anchored proteins encoded by S. sanguinis and then used a targeted signature-tagged mutagenesis (STM) approach to evaluate their contributions to virulence. Thirty-three predicted cell wall-anchored proteins were identified—a number much larger than those found in related species. The requirement of each cell wall-anchored protein for infective endocarditis was assessed in the rabbit model. It was found that no single cell wall-anchored protein was essential for the development of early infective endocarditis. STM screening was also employed for the evaluation of three predicted sortase transpeptidase enzymes, which mediate the cell surface presentation of cell wall-anchored proteins. The sortase A mutant exhibited a modest (∼2-fold) reduction in competitiveness, while the other two sortase mutants were indistinguishable from the parental strain. The combined results suggest that while cell wall-anchored proteins may play a role in S. sanguinis infective endocarditis, strategies designed to interfere with individual cell wall-anchored proteins or sortases would not be effective for disease prevention. PMID:19703977

Selective dentate gyrus disruption causes memory impairment at the early stage of experimental multiple sclerosis.

PubMed

Planche, Vincent; Panatier, Aude; Hiba, Bassem; Ducourneau, Eva-Gunnel; Raffard, Gerard; Dubourdieu, Nadège; Maitre, Marlène; Lesté-Lasserre, Thierry; Brochet, Bruno; Dousset, Vincent; Desmedt, Aline; Oliet, Stéphane H; Tourdias, Thomas

2017-02-01

Memory impairment is an early and disabling manifestation of multiple sclerosis whose anatomical and biological substrates are still poorly understood. We thus investigated whether memory impairment encountered at the early stage of the disease could be explained by a differential vulnerability of particular hippocampal subfields. By using experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, we identified that early memory impairment was associated with selective alteration of the dentate gyrus as pinpointed in vivo with diffusion-tensor-imaging (DTI). Neuromorphometric analyses and electrophysiological recordings confirmed dendritic degeneration, alteration in glutamatergic synaptic transmission and impaired long-term synaptic potentiation selectively in the dentate gyrus, but not in CA1, together with a more severe pattern of microglial activation in this subfield. Systemic injections of the microglial inhibitor minocycline prevented DTI, morphological, electrophysiological and behavioral impairments in EAE-mice. Furthermore, daily infusions of minocycline specifically within the dentate gyrus were sufficient to prevent memory impairment in EAE-mice while infusions of minocycline within CA1 were inefficient. We conclude that early memory impairment in EAE is due to a selective disruption of the dentate gyrus associated with microglia activation. These results open new pathophysiological, imaging, and therapeutic perspectives for memory impairment in multiple sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells

PubMed Central

Spiess, Katja; Jeppesen, Mads G.; Malmgaard-Clausen, Mikkel; Krzywkowski, Karen

2017-01-01

Immunotoxins as antiviral therapeutics are largely unexplored but have promising prospective due to their high selectivity potential and their unparalleled efficiency. One recent example targeted the virus-encoded G protein-coupled receptor US28 as a strategy for specific and efficient treatment of human cytomegalovirus (HCMV) infections. US28 is expressed on virus-infected cells and scavenge chemokines by rapid internalization. The chemokine-based fusion-toxin protein (FTP) consisted of a variant (F49A) of CX3CL1 specifically targeting US28 linked to the catalytic domain of Pseudomonas exotoxin A (PE). Here, we systematically seek to improve F49A-FTP by modifications in its three structural domains; we generated variants with (1) altered chemokine sequence (K14A, F49L, and F49E), (2) shortened and elongated linker region, and (3) modified toxin domain. Only F49L-FTP displayed higher selectivity in its binding to US28 versus CX3CR1, the endogenous receptor for CX3CL1, but this was not matched by a more selective killing of US28-expressing cells. A longer linker and different toxin variants decreased US28 affinity and selective killing. Thereby, F49A-FTP represents the best candidate for HCMV treatment. Many viruses encode internalizing receptors suggesting that not only HCMV but also, for instance, Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus may be targeted by FTPs. PMID:28251165

Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells.

PubMed

Spiess, Katja; Jeppesen, Mads G; Malmgaard-Clausen, Mikkel; Krzywkowski, Karen; Kledal, Thomas N; Rosenkilde, Mette M

2017-01-01

Immunotoxins as antiviral therapeutics are largely unexplored but have promising prospective due to their high selectivity potential and their unparalleled efficiency. One recent example targeted the virus-encoded G protein-coupled receptor US28 as a strategy for specific and efficient treatment of human cytomegalovirus (HCMV) infections. US28 is expressed on virus-infected cells and scavenge chemokines by rapid internalization. The chemokine-based fusion-toxin protein (FTP) consisted of a variant (F49A) of CX 3 CL1 specifically targeting US28 linked to the catalytic domain of Pseudomonas exotoxin A (PE). Here, we systematically seek to improve F49A-FTP by modifications in its three structural domains; we generated variants with (1) altered chemokine sequence (K14A, F49L, and F49E), (2) shortened and elongated linker region, and (3) modified toxin domain. Only F49L-FTP displayed higher selectivity in its binding to US28 versus CX 3 CR1, the endogenous receptor for CX 3 CL1, but this was not matched by a more selective killing of US28-expressing cells. A longer linker and different toxin variants decreased US28 affinity and selective killing. Thereby, F49A-FTP represents the best candidate for HCMV treatment. Many viruses encode internalizing receptors suggesting that not only HCMV but also, for instance, Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus may be targeted by FTPs.

Development and validation of the San Diego Early Test Score to predict acute and early HIV infection risk in men who have sex with men.

PubMed

Hoenigl, Martin; Weibel, Nadir; Mehta, Sanjay R; Anderson, Christy M; Jenks, Jeffrey; Green, Nella; Gianella, Sara; Smith, Davey M; Little, Susan J

2015-08-01

Although men who have sex with men (MSM) represent a dominant risk group for human immunodeficiency virus (HIV), the risk of HIV infection within this population is not uniform. The objective of this study was to develop and validate a score to estimate incident HIV infection risk. Adult MSM who were tested for acute and early HIV (AEH) between 2008 and 2014 were retrospectively randomized 2:1 to a derivation and validation dataset, respectively. Using the derivation dataset, each predictor associated with an AEH outcome in the multivariate prediction model was assigned a point value that corresponded to its odds ratio. The score was validated on the validation dataset using C-statistics. Data collected at a single HIV testing encounter from 8326 unique MSM were analyzed, including 200 with AEH (2.4%). Four risk behavior variables were significantly associated with an AEH diagnosis (ie, incident infection) in multivariable analysis and were used to derive the San Diego Early Test (SDET) score: condomless receptive anal intercourse (CRAI) with an HIV-positive MSM (3 points), the combination of CRAI plus ≥5 male partners (3 points), ≥10 male partners (2 points), and diagnosis of bacterial sexually transmitted infection (2 points)-all as reported for the prior 12 months. The C-statistic for this risk score was >0.7 in both data sets. The SDET risk score may help to prioritize resources and target interventions, such as preexposure prophylaxis, to MSM at greatest risk of acquiring HIV infection. The SDET risk score is deployed as a freely available tool at http://sdet.ucsd.edu. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection.

PubMed

Geisbert, Thomas W; Hensley, Lisa E; Larsen, Tom; Young, Howard A; Reed, Douglas S; Geisbert, Joan B; Scott, Dana P; Kagan, Elliott; Jahrling, Peter B; Davis, Kelly J

2003-12-01

Ebola virus (EBOV) infection causes a severe and fatal hemorrhagic disease that in many ways appears to be similar in humans and nonhuman primates; however, little is known about the development of EBOV hemorrhagic fever. In the present study, 21 cynomolgus monkeys were experimentally infected with EBOV and examined sequentially over a 6-day period to investigate the pathological events of EBOV infection that lead to death. Importantly, dendritic cells in lymphoid tissues were identified as early and sustained targets of EBOV, implicating their important role in the immunosuppression characteristic of EBOV infections. Bystander lymphocyte apoptosis, previously described in end-stage tissues, occurred early in the disease-course in intravascular and extravascular locations. Of note, apoptosis and loss of NK cells was a prominent finding, suggesting the importance of innate immunity in determining the fate of the host. Analysis of peripheral blood mononuclear cell gene expression showed temporal increases in tumor necrosis factor-related apoptosis-inducing ligand and Fas transcripts, revealing a possible mechanism for the observed bystander apoptosis, while up-regulation of NAIP and cIAP2 mRNA suggest that EBOV has evolved additional mechanisms to resist host defenses by inducing protective transcripts in cells that it infects. The sequence of pathogenetic events identified in this study should provide new targets for rational prophylactic and chemotherapeutic interventions.

Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

NASA Astrophysics Data System (ADS)

Chu, Li-Wei; Huang, Yi-Lung; Lee, Jin-Hui; Huang, Long-Ying; Chen, Wei-Jun; Lin, Ya-Hsuan; Chen, Jyun-Yu; Xiang, Rui; Lee, Chau-Hwang; Ping, Yueh-Hsin

2014-01-01

Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.

Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection.

PubMed

Keele, Brandon F; Giorgi, Elena E; Salazar-Gonzalez, Jesus F; Decker, Julie M; Pham, Kimmy T; Salazar, Maria G; Sun, Chuanxi; Grayson, Truman; Wang, Shuyi; Li, Hui; Wei, Xiping; Jiang, Chunlai; Kirchherr, Jennifer L; Gao, Feng; Anderson, Jeffery A; Ping, Li-Hua; Swanstrom, Ronald; Tomaras, Georgia D; Blattner, William A; Goepfert, Paul A; Kilby, J Michael; Saag, Michael S; Delwart, Eric L; Busch, Michael P; Cohen, Myron S; Montefiori, David C; Haynes, Barton F; Gaschen, Brian; Athreya, Gayathri S; Lee, Ha Y; Wood, Natasha; Seoighe, Cathal; Perelson, Alan S; Bhattacharya, Tanmoy; Korber, Bette T; Hahn, Beatrice H; Shaw, George M

2008-05-27

The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathematical model of random viral evolution and, together with phylogenetic tree construction, used it to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection. Viral env genes evolving from individual transmitted or founder viruses generally exhibited a Poisson distribution of mutations and star-like phylogeny, which coalesced to an inferred consensus sequence at or near the estimated time of virus transmission. Overall, 78 of 102 subjects had evidence of productive clinical infection by a single virus, and 24 others had evidence of productive clinical infection by a minimum of two to five viruses. Phenotypic analysis of transmitted or early founder Envs revealed a consistent pattern of CCR5 dependence, masking of coreceptor binding regions, and equivalent or modestly enhanced resistance to the fusion inhibitor T1249 and broadly neutralizing antibodies compared with Envs from chronically infected subjects. Low multiplicity infection and limited viral evolution preceding peak viremia suggest a finite window of potential vulnerability of HIV-1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense.

Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection

PubMed Central

Keele, Brandon F.; Giorgi, Elena E.; Salazar-Gonzalez, Jesus F.; Decker, Julie M.; Pham, Kimmy T.; Salazar, Maria G.; Sun, Chuanxi; Grayson, Truman; Wang, Shuyi; Li, Hui; Wei, Xiping; Jiang, Chunlai; Kirchherr, Jennifer L.; Gao, Feng; Anderson, Jeffery A.; Ping, Li-Hua; Swanstrom, Ronald; Tomaras, Georgia D.; Blattner, William A.; Goepfert, Paul A.; Kilby, J. Michael; Saag, Michael S.; Delwart, Eric L.; Busch, Michael P.; Cohen, Myron S.; Montefiori, David C.; Haynes, Barton F.; Gaschen, Brian; Athreya, Gayathri S.; Lee, Ha Y.; Wood, Natasha; Seoighe, Cathal; Perelson, Alan S.; Bhattacharya, Tanmoy; Korber, Bette T.; Hahn, Beatrice H.; Shaw, George M.

2008-01-01

The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathematical model of random viral evolution and, together with phylogenetic tree construction, used it to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection. Viral env genes evolving from individual transmitted or founder viruses generally exhibited a Poisson distribution of mutations and star-like phylogeny, which coalesced to an inferred consensus sequence at or near the estimated time of virus transmission. Overall, 78 of 102 subjects had evidence of productive clinical infection by a single virus, and 24 others had evidence of productive clinical infection by a minimum of two to five viruses. Phenotypic analysis of transmitted or early founder Envs revealed a consistent pattern of CCR5 dependence, masking of coreceptor binding regions, and equivalent or modestly enhanced resistance to the fusion inhibitor T1249 and broadly neutralizing antibodies compared with Envs from chronically infected subjects. Low multiplicity infection and limited viral evolution preceding peak viremia suggest a finite window of potential vulnerability of HIV-1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense. PMID:18490657

Understanding the link between early sexual initiation and later sexually transmitted infection: test and replication in two longitudinal studies.

PubMed

Epstein, Marina; Bailey, Jennifer A; Manhart, Lisa E; Hill, Karl G; Hawkins, J David; Haggerty, Kevin P; Catalano, Richard F

2014-04-01

Age at sexual initiation is strongly associated with sexually transmitted infections (STI); yet, prevention programs aiming to delay sexual initiation have shown mixed results in reducing STI. This study tested three explanatory mechanisms for the relationship between early sexual debut and STI: number of sexual partners, individual characteristics, and environmental antecedents. A test-and-replicate strategy was employed using two longitudinal studies: the Seattle Social Development Project (SSDP) and Raising Healthy Children (RHC). Childhood measures included pubertal age, behavioral disinhibition, and family, school, and peer influences. Alcohol use and age of sexual debut were measured during adolescence. Lifetime number of sexual partners and having sex under the influence were measured during young adulthood. Sexually transmitted infection diagnosis was self-reported at age 24. Early sex was defined as debut at <15 years. Path models were developed in SSDP evaluating relationships between measures, and were then tested in RHC. The relationship between early sex and STI was fully mediated by lifetime sex partners in SSDP, but only partially in RHC, after accounting for co-occurring factors. Behavioral disinhibition predicted early sex, early alcohol use, number of sexual partners, and sex under the influence, but had no direct effect on STI. Family management protected against early sex and early alcohol use, whereas antisocial peers exacerbated the risk. Early sexual initiation, a key mediator of STI, is driven by antecedents that influence multiple risk behaviors. Targeting co-occurring individual and environmental factors may be more effective than discouraging early sexual debut and may concomitantly improve other risk behaviors. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Cervical Lymph Nodes as a Selective Niche for Brucella during Oral Infections

PubMed Central

von Bargen, Kristine; Gagnaire, Aurélie; Arce-Gorvel, Vilma; de Bovis, Béatrice; Baudimont, Fannie; Chasson, Lionel; Bosilkovski, Mile; Papadopoulos, Alexia; Martirosyan, Anna; Henri, Sandrine; Mège, Jean-Louis; Malissen, Bernard; Gorvel, Jean-Pierre

2015-01-01

Cervical lymph nodes (CLN) are the first lymph nodes encountered by material taking the oral route. To study their role in orally acquired infections, we analyzed 307 patients of up to 14 years treated in the university clinic of Skopje, Macedonia, for brucellosis, a zoonotic bacterial disease frequently acquired by ingestion of contaminated dairy products. From these children, 36% had lymphadenopathy. Among orally infected children, lymphadenopathy with CLN being the only lymph nodes affected was significantly more frequent as compared to those infected by contact with animals (83% vs. 63%), suggesting a possible involvement of CLN during orally acquired human brucellosis. Using a murine model where bacteria are delivered into the oral cavity, we show that Brucella quickly and selectively colonize the CLN where they proliferate and persist over long periods of time for up to 50 days post-infection. A similar efficient though less specific drainage to CLN was found for Brucella, Salmonella typhimurium and fluorescent microspheres delivered by gavage, a pathway likely representing a mixed infection mode of intragastric and oral infection, suggesting a central pathway of drained material. Microspheres as well as bacteria drained to CLN predominately reside in cells expressing CD68 and no or low levels of CD11c. Even though no systemic response could be detected, Brucella induced a locally restricted inflammatory reaction with increased expression levels of interferon γ, interleukin (IL)-6, IL-12, granzyme B and a delayed induction of Nos2. Inflammation led to pronounced lymphadenopathy, infiltration of macrophages/monocytes expressing high levels of major histocompatibility complex II and to formation of epitheloid granulomas. Together, these results highlight the role of CLN in oral infections as both, an initial and efficient trap for bacterial invaders and as possible reservoir for chronic pathogens. They likewise cast a new light on the significance of oral

Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection.

PubMed

Borges, Álvaro H; Neuhaus, Jacqueline; Babiker, Abdel G; Henry, Keith; Jain, Mamta K; Palfreeman, Adrian; Mugyenyi, Peter; Domingo, Pere; Hoffmann, Christian; Read, Tim R H; Pujari, Sanjay; Meulbroek, Michael; Johnson, Margaret; Wilkin, Timothy; Mitsuyasu, Ronald

2016-12-15

 In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts and human immunodeficiency virus (HIV) RNA between the study arms.  Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART.  There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated); hazard ratios of immediate vs deferred cART initiation were 0.26 (95% confidence interval [CI], .11-.64) for infection-related and 0.49 (95% CI, .21-1.15) for infection-unrelated cancer. Independent predictors of infection-related cancer were older age, higher body mass index, low- to middle-income region, HIV RNA, and baseline CD8 cell count. Older age and baseline CD8 cell count were independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level had little impact on the protective effect of immediate cART on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4 cell count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer.  Immediate cART initiation significantly reduces risk of cancer. Although limited by small sample size, this benefit does not appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights

Anticipating persistent infection

NASA Astrophysics Data System (ADS)

Moitra, Promit; Jain, Kanishk; Sinha, Sudeshna

2018-03-01

We explore the emergence of persistent infection in a closed region where the disease progression of the individuals is given by the SIRS model, with an individual becoming infected on contact with another infected individual within a given range. We focus on the role of synchronization in the persistence of contagion. Our key result is that higher degree of synchronization, both globally in the population and locally in the neighbourhoods, hinders persistence of infection. Importantly, we find that early short-time asynchrony appears to be a consistent precursor to future persistence of infection, and can potentially provide valuable early warnings for sustained contagion in a population patch. Thus, transient synchronization can help anticipate the long-term persistence of infection. Further we demonstrate that when the range of influence of an infected individual is wider, one obtains lower persistent infection. This counterintuitive observation can also be understood through the relation between synchronization and infection burn-out.

Predictors of Early Readmission in Patients With Cirrhosis After the Resolution of Bacterial Infections.

PubMed

Piano, Salvatore; Morando, Filippo; Carretta, Giovanni; Tonon, Marta; Vettore, Elia; Rosi, Silvia; Stanco, Marialuisa; Pilutti, Chiara; Romano, Antonietta; Brocca, Alessandra; Sticca, Antonietta; Donato, Daniele; Angeli, Paolo

2017-10-01

In patients with cirrhosis, infections represent a frequent trigger for complications, increasing frequency of hospitalizations and mortality rate. This study aimed to identify predictors of early readmission (30 days) and of mid-term mortality (6 months) in patients with liver cirrhosis discharged after a hospitalization for bacterial and/or fungal infection. A total of 199 patients with cirrhosis discharged after an admission for a bacterial and/or fungal infection were included in the study and followed up for a least 6 months. During follow-up, 69 patients (35%) were readmitted within 30 days from discharge. C-reactive protein (CRP) value at discharge (odds ratio (OR)=1.91; P=0.022), diagnosis of acute-on-chronic liver failure during the hospital stay (OR=2.48; P=0.008), and the hospitalization in the last 30 days previous to the admission/inclusion in the study (OR=1.50; P=0.042) were found to be independent predictors of readmission. During the 6-month follow-up, 47 patients (23%) died. Age (hazard ratio (HR)=1.05; P=0.001), model of end-stage liver disease (MELD) score (HR=1.13; P<0.001), CRP (HR=1.85; P=0.001), refractory ascites (HR=2.22; P=0.007), and diabetes (HR=2.41; P=0.010) were found to be independent predictors of 6-month mortality. Patients with a CRP >10 mg/l at discharge had a significantly higher probability of being readmitted within 30 days (44% vs. 24%; P=0.007) and a significantly lower probability of 6-month survival (62% vs. 88%; P<0.001) than those with a CRP ≤10 mg/l. CRP showed to be a strong predictor of early hospital readmission and 6-month mortality in patients with cirrhosis after hospitalization for bacterial and/or fungal infection. CRP values could be used both in the stewardship of antibiotic treatment and to identify fragile patients who deserve a strict surveillance program.

Raman spectroscopy based investigation of molecular changes associated with an early stage of dengue virus infection

NASA Astrophysics Data System (ADS)

Bilal, Maria; Bilal, Muhammad; Saleem, Muhammad; Khurram, Muhammad; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, Mushtaq; Shahzada, Shaista; Ullah Khan, Ehsan

2017-04-01

Raman spectroscopy based investigations of the molecular changes associated with an early stage of dengue virus infection (DENV) using a partial least squares (PLS) regression model is presented. This study is based on non-structural protein 1 (NS1) which appears after three days of DENV infection. In total, 39 blood sera samples were collected and divided into two groups. The control group contained samples which were the negative for NS1 and antibodies and the positive group contained those samples in which NS1 is positive and antibodies were negative. Out of 39 samples, 29 Raman spectra were used for the model development while the remaining 10 were kept hidden for blind testing of the model. PLS regression yielded a vector of regression coefficients as a function of Raman shift, which were analyzed. Cytokines in the region 775-875 cm-1, lectins at 1003, 1238, 1340, 1449 and 1672 cm-1, DNA in the region 1040-1140 cm-1 and alpha and beta structures of proteins in the region 933-967 cm-1 have been identified in the regression vector for their role in an early stage of DENV infection. Validity of the model was established by its R-square value of 0.891. Sensitivity, specificity and accuracy were 100% each and the area under the receiver operator characteristic curve was found to be 1.

Early Invasive Versus Selective Strategy for Non-ST-Segment Elevation Acute Coronary Syndrome: The ICTUS Trial.

PubMed

Hoedemaker, Niels P G; Damman, Peter; Woudstra, Pier; Hirsch, Alexander; Windhausen, Fons; Tijssen, Jan G P; de Winter, Robbert J

2017-04-18

The ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes) trial compared early invasive strategy with a selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and an elevated cardiac troponin T. No long-term benefit of an early invasive strategy was found at 1 and 5 years. The aim of this study was to determine the 10-year clinical outcomes of an early invasive strategy versus a selective invasive strategy in patients with NSTE-ACS and an elevated cardiac troponin T. The ICTUS trial was a multicenter, randomized controlled clinical trial that included 1,200 patients with NSTE-ACS and an elevated cardiac troponin T. Enrollment was from July 2001 to August 2003. We collected 10-year follow-up of death, myocardial infarction (MI), and revascularization through the Dutch population registry, patient phone calls, general practitioners, and hospital records. The primary outcome was the 10-year composite of death or spontaneous MI. Additional outcomes included the composite of death or MI, death, MI (spontaneous and procedure-related), and revascularization. Ten-year death or spontaneous MI was not statistically different between the 2 groups (33.8% vs. 29.0%, hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.97 to 1.46; p = 0.11). Revascularization occurred in 82.6% of the early invasive group and 60.5% in the selective invasive group. There were no differences in additional outcomes, except for a higher rate of death or MI in the early invasive group compared with the rates for the selective invasive group (37.6% vs. 30.5%; HR: 1.30; 95% CI: 1.07 to 1.58; p = 0.009), driven by a higher rate of procedure-related MI in the early invasive group (6.5% vs. 2.4%; HR: 2.82; 95% CI: 1.53 to 5.20; p = 0.001). In patients with NSTE-ACS and elevated cardiac troponin T levels, an early invasive strategy has no benefit over a selective invasive strategy in reducing the 10-year composite outcome of

Effects of Antiretroviral Therapy on Autonomic Function in Early HIV Infection: A Preliminary Report

PubMed Central

Chow, Dominic; Kocher, Morgan; Shikuma, Cecilia; Parikh, Nisha; Grandinetti, Andrew; Nakamoto, Beau; Seto, Todd; Low, Phillip

2012-01-01

Background: A prospective study was conducted in human immunodeficiency virus (HIV)-infected patients as they undergo alterations in their antiretroviral therapy (ART) to determine the effect of ART on autonomic function. Methods: HIV-infected subjects who were either 1) naïve to ART and initiating ART, or 2) receiving ART and in HIV virologic failure for at least 4 months and were about to switch ART were enrolled in this study. Autonomic function assessment (cardiovagal, adrenergic, and sudomotor tests) was performed prior to and 4 months after initiating the new ART. Changes in clinical autonomic symptoms and virologic assessment were assessed. Results: Twelve subjects completed the study: 92% male; median age (Q1, Q3) was 41.0 (28.0, 48.2) years; and 50% White/Non-Hispanic. Seventy-five percent were ART naïve while 25% were failing their ART regimen. The median CD4 count was 336.5 (245.3, 372.3) cells/mm3. All subjects achieved an undetectable HIV viral load by the 4-month follow-up visit. The majority of naïve subjects were started on an ART regimen of tenofovir / emtricitabine / efavirenz. There were no significant differences in autonomic function assessment, as measured by cardiovagal, adrenergic, and sudomotor tests, with regards to ART initiation. Conclusion: This is the first study to examine the effects of initiating ART on autonomic function in early HIV infection. This study found no appreciable differences of ART on the autonomic nervous system when ART is initiated early in the course of HIV disease. ART may not contribute to short-term changes in autonomic function. PMID:22859899

Low pretransplant IgA level is associated with early post-lung transplant seromucous infection.

PubMed

Murthy, Sudish C; Avery, Robin K; Budev, Marie; Gupta, Sandeep; Pettersson, Gösta B; Nowicki, Edward R; Mehta, Atul; Chapman, Jeffrey T; Rajeswaran, Jeevanantham; Blackstone, Eugene H

2018-04-13

Infection is an important cause of morbidity and mortality after lung transplantation. Immunoglobulins are part of both seromucous (IgA) and serum (IgG) infection defense mechanisms. We therefore hypothesized that lower pretransplant IgA levels would be associated with more early post-lung transplant seromucous infections and greater mortality independent of IgG. From January 2000 to July 2010, 538 patients undergoing primary lung transplantation had pretransplant IgA (n = 429) and IgG (n = 488) measured as a clinical routine. Median IgA was 200 mg·dL -1 (2% < 70 mg·dL -1 , lower limit of normal); median IgG was 970 mg·dL -1 (5% < 600 mg·dL -1 ). Intensive microbiology review was used to categorize infections and their causative organisms within the first posttransplant year. In total, 397 seromucous infections were observed in 247 patients, most bacterial. Although IgA and IgG were moderately correlated (r = 0.5, P < .0001), low pretransplant IgA was a strong risk factor (P = .01) for seromucous infections, but pretransplant IgG was not (P ≥ .6). As pretransplant IgA levels fell below 200 mg·dL -1 , the risk of these posttransplant infections rose nearly linearly. Lower pretransplant levels of IgA were associated with greater posttransplant mortality to end of follow-up (P = .004), but pretransplant IgG was not (P ≥ .3). Low levels of preoperative IgA, an important immunoglobulin involved in mucosal immunologic defense, but not IgG, are associated with seromucous infections in the year after lung transplantation and increased follow-up mortality. It would appear prudent to identify patients with relative IgA deficiency at listing and to increase vigilance of monitoring for, and prophylaxis against, seromucous infection in this high-risk population. Copyright © 2018. Published by Elsevier Inc.

Early Salmonella Typhimurium infection in pigs disrupts Microbiome composition and functionality principally at the ileum mucosa.

PubMed

Argüello, Héctor; Estellé, Jordi; Zaldívar-López, Sara; Jiménez-Marín, Ángeles; Carvajal, Ana; López-Bascón, Mª Asunción; Crispie, Fiona; O'Sullivan, Orla; Cotter, Paul D; Priego-Capote, Feliciano; Morera, Luis; Garrido, Juan J

2018-05-17

Salmonella is a major foodborne pathogen which successfully infects animal species for human consumption such as swine. The pathogen has a battery of virulence factors which it uses to colonise and persist within the host. The host microbiota may play a role in resistance to, and may also be indirectly responsible from some of the consequences of, Salmonella infection. To investigate this, we used 16S rRNA metagenomic sequencing to determine the changes in the gut microbiota of pigs in response to infection by Salmonella Typhimurium at three locations: ileum mucosa, ileum content and faeces. Early infection (2 days post-infection) impacted on the microbiome diversity at the mucosa, reflected in a decrease in representatives of the generally regarded as desirable genera (i.e., Bifidobacterium and Lactobacillus). Severe damage in the epithelium of the ileum mucosa correlated with an increase in synergistic (with respect to Salmonella infection; Akkermansia) or opportunistically pathogenic bacteria (Citrobacter) and a depletion in anaerobic bacteria (Clostridium spp., Ruminococcus, or Dialliser). Predictive functional analysis, together with metabolomic analysis revealed changes in glucose and lipid metabolism in infected pigs. The observed changes in commensal healthy microbiota, including the growth of synergistic or potentially pathogenic bacteria and depletion of beneficial or competing bacteria, could contribute to the pathogen's ability to colonize the gut successfully. The findings from this study could be used to form the basis for further research aimed at creating intervention strategies to mitigate the effects of Salmonella infection.

Cost-Effectiveness of Early Infant HIV Diagnosis of HIV-Exposed Infants and Immediate Antiretroviral Therapy in HIV-Infected Children under 24 Months in Thailand

PubMed Central

Collins, Intira Jeannie; Cairns, John; Ngo-Giang-Huong, Nicole; Sirirungsi, Wasna; Leechanachai, Pranee; Le Coeur, Sophie; Samleerat, Tanawan; Kamonpakorn, Nareerat; Mekmullica, Jutarat; Jourdain, Gonzague; Lallemant, Marc

2014-01-01

Background HIV-infected infants have high risk of death in the first two years of life if untreated. WHO guidelines recommend early infant HIV diagnosis (EID) of all HIV-exposed infants and immediate antiretroviral therapy (ART) in HIV-infected children under 24-months. We assessed the cost-effectiveness of this strategy in HIV-exposed non-breastfed children in Thailand. Methods A decision analytic model of HIV diagnosis and disease progression compared: EID using DNA PCR with immediate ART (Early-Early); or EID with deferred ART based on immune/clinical criteria (Early-Late); vs. clinical/serology based diagnosis and deferred ART (Reference). The model was populated with survival and cost data from a Thai observational cohort and the literature. Incremental cost-effectiveness ratio per life-year gained (LYG) was compared against the Reference strategy. Costs and outcomes were discounted at 3%. Results Mean discounted life expectancy of HIV-infected children increased from 13.3 years in the Reference strategy to 14.3 in the Early-Late and 17.8 years in Early-Early strategies. The mean discounted lifetime cost was $17,335, $22,583 and $29,108, respectively. The cost-effectiveness ratio of Early-Late and Early-Early strategies was $5,149 and $2,615 per LYG, respectively as compared to the Reference strategy. The Early-Early strategy was most cost-effective at approximately half the domestic product per capita per LYG ($4,420 in Thailand 2011). The results were robust in deterministic and probabilistic sensitivity analyses including varying perinatal transmission rates. Conclusion In Thailand, EID and immediate ART would lead to major survival benefits and is cost- effective. These findings strongly support the adoption of WHO recommendations as routine care. PMID:24632750

Intramammary infections in heifers during early lactation following intramammary infusion of pirlimycin hydrochloride or penicillin-novobiocin at the first milking after parturition.

PubMed

Oliver, Stephen P; Headrick, Susan I; Gillespie, Barbara E; Lewis, Mark J; Johnson, David L; Lamar, Kenneth C; Moorehead, Hugh; Dowlen, Henry H; Hallberg, John W

2007-05-01

A study was conducted to determine whether intramammary antibiotic treatment of heifer mammary glands following the first milking after calving was effective for reducing the percentage of mammary quarters infected during early lactation. Jersey and Holstein heifers from two research herds were assigned to one of three treatment groups: (1) no intramammary infusion following the first milking after parturition, (2) intramammary infusion of all quarters with pirlimycin hydrochloride following the first milking after parturition and (3) intramammary infusion of all quarters with novobiocin sodium plus penicillin G procaine following the first milking after parturition. Almost 93% of Jersey heifers (40/43) and 73.1% of quarters (125/171) were infected at the first milking. Almost 77% of quarters (33/43) were cured following treatment with pirlimycin, 61.8% (21/34) were cured following treatment with penicillin-novobiocin and 39.6% (19/48) of infections were eliminated spontaneously in the untreated control group. Significantly fewer infections were observed in pirlimycin or penicillin-novobiocin treated mammary glands of Jersey heifers during early lactation than in untreated control mammary glands. Almost 89% of Holstein heifers (32/36) and 52.8% of quarters (76/144) were infected at the first milking. About 57% (12/21) of quarters were cured following treatment with pirlimycin, 41.4% (12/29) were cured following treatment with penicillin-novobiocin and 23.1% (6/26) of infections were eliminated spontaneously in the untreated negative control group. Significantly fewer infections were observed in pirlimycin treated mammary glands of Holstein heifers during early lactation than in untreated control mammary glands. However, no significant differences were observed following penicillin-novobiocin treatment of Holstein heifers after the first milking of lactation compared with untreated control quarters. Coagulase-negative staphylococci, Streptococcus uberis and

Nonencapsulated Trichinella pseudospiralis Infection Impairs Follicular Helper T Cell Differentiation with Subclass-Selective Decreases in Antibody Responses

PubMed Central

Asano, Kazunobu; Wu, Zhiliang; Srinontong, Piyarat; Ikeda, Takahide; Nagano, Isao; Morita, Hirokuyi

2016-01-01

Infectious microorganisms often modify host immunity to escape from immune elimination. Trichinella is a unique nematode of the helminth family, whose members parasitize the muscle cells inside the host without robust eliminative reactions. There are several species of Trichinella; some develop in muscle cells that become encapsulated (e.g., Trichinella spiralis) and others in cells that do not encapsulate (e.g., Trichinella pseudospiralis). It has already been established that Trichinella infection affects host immune responses in several experimental immune diseases in animal models; however, most of those studies were done using T. spiralis infection. As host immune responses to T. spiralis and T. pseudospiralis infections have been reported to be different, it is necessary to clarify how T. pseudospiralis infection influences the host immune responses. In this study, we investigated the influence on host humoral immunity in T. pseudospiralis-infected mice. We demonstrated that T. pseudospiralis infection decreased antigen-specific IgG2a and IgG2b antibody (Ab) production in mice immunized with a model antigen. This selective decrease in gamma interferon (IFN-γ)-dependent Ab production was not due to a decrease in IFN-γ production, and we instead found impaired follicular helper T (Tfh) cell differentiation. The affinity maturation of antigen-specific Ab tended to be delayed but was not significant in T. pseudospiralis-infected mice. We also observed that CD11b+ spleen cells in T. pseudospiralis-infected mice expressed CD206 and PD-L2, the phenotype of which was M2 macrophages with weak production of interleukin-6 (IL-6), possibly resulting in impaired Tfh differentiation. Taken together, our results indicate that nonencapsulated Trichinella infection induces selective dampening in humoral immunity with the suppression of Tfh differentiation. PMID:27736779

Nonencapsulated Trichinella pseudospiralis Infection Impairs Follicular Helper T Cell Differentiation with Subclass-Selective Decreases in Antibody Responses.

PubMed

Asano, Kazunobu; Wu, Zhiliang; Srinontong, Piyarat; Ikeda, Takahide; Nagano, Isao; Morita, Hirokuyi; Maekawa, Yoichi

2016-12-01

Infectious microorganisms often modify host immunity to escape from immune elimination. Trichinella is a unique nematode of the helminth family, whose members parasitize the muscle cells inside the host without robust eliminative reactions. There are several species of Trichinella; some develop in muscle cells that become encapsulated (e.g., Trichinella spiralis) and others in cells that do not encapsulate (e.g., Trichinella pseudospiralis). It has already been established that Trichinella infection affects host immune responses in several experimental immune diseases in animal models; however, most of those studies were done using T. spiralis infection. As host immune responses to T. spiralis and T. pseudospiralis infections have been reported to be different, it is necessary to clarify how T. pseudospiralis infection influences the host immune responses. In this study, we investigated the influence on host humoral immunity in T. pseudospiralis-infected mice. We demonstrated that T. pseudospiralis infection decreased antigen-specific IgG2a and IgG2b antibody (Ab) production in mice immunized with a model antigen. This selective decrease in gamma interferon (IFN-γ)-dependent Ab production was not due to a decrease in IFN-γ production, and we instead found impaired follicular helper T (Tfh) cell differentiation. The affinity maturation of antigen-specific Ab tended to be delayed but was not significant in T. pseudospiralis-infected mice. We also observed that CD11b + spleen cells in T. pseudospiralis-infected mice expressed CD206 and PD-L2, the phenotype of which was M2 macrophages with weak production of interleukin-6 (IL-6), possibly resulting in impaired Tfh differentiation. Taken together, our results indicate that nonencapsulated Trichinella infection induces selective dampening in humoral immunity with the suppression of Tfh differentiation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Early age at start of antiretroviral therapy associated with better virologic control after initial suppression in HIV-infected infants.

PubMed

Shiau, Stephanie; Strehlau, Renate; Technau, Karl-Günter; Patel, Faeezah; Arpadi, Stephen M; Coovadia, Ashraf; Abrams, Elaine J; Kuhn, Louise

2017-01-28

The report of the 'Mississippi baby' who was initiated on antiretroviral therapy (ART) within 30 h of birth and maintained viral suppression off ART for 27 months has increased interest in the timing of ART initiation early in life. We examined associations between age at ART initiation and virologic outcomes in five cohorts of HIV-infected infants and young children who initiated ART before 2 years of age in Johannesburg, South Africa. We compared those who initiated ART early (<6 months of age) and those who started ART late (6-24 months of age). Two primary outcomes were examined: initial response to ART in three cohorts and later sustained virologic control after achieving suppression on ART in two cohorts. We did not observe consistent differences in initial viral suppression rates by age at ART initiation. Overall, initial viral suppression rates were low. Only 31, 40.1, and 26.5% of early-treated infants (<6 months of age) in the three cohorts, respectively, were suppressed less than 50 copies/ml of HIV RNA 6 months after starting ART. We did observe better sustained virologic control after achieving suppression on ART among infants starting ART early compared with late. Children who started ART early were less likely to experience viral rebound (>50 copies/ml or >1000 copies/ml) than children who started late in both cohorts. These findings provide additional support for early initiation of ART in HIV-infected infants.

The Features of Fecal and Ileal Mucosa-Associated Microbiota in Dairy Calves during Early Infection with Mycobacterium avium Subspecies paratuberculosis.

PubMed

Derakhshani, Hooman; De Buck, Jeroen; Mortier, Rienske; Barkema, Herman W; Krause, Denis O; Khafipour, Ehsan

2016-01-01

Current diagnostic tests for Johne's disease (JD), a chronic granulomatous inflammation of the gastrointestinal tract of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), lack the sensitivity to identify infected animals at early (asymptomatic) stages of the disease. The objective was to determine the pattern of MAP-associated dysbiosis of intestinal microbiota as a potential biomarker for early detection of infected cattle. To that end, genomic DNA was extracted from ileal mucosa and fecal samples collected from 28 MAP-positive and five control calves. High-throughput Illumina sequencing of the V4 hypervariable region of the 16S rRNA gene was used for community profiling of ileal mucosa-associated (MAM) or fecal microbiota. The PERMANOVA analysis of unweighted UniFrac distances revealed distinct clustering of ileal MAM (P = 0.049) and fecal microbiota (P = 0.068) in MAP-infected vs. control cattle. Microbiota profile of MAP-infected animals was further investigated by linear discriminant analysis effective size (LEfSe); several bacterial taxa within the phylum Proteobacteria were overrepresented in ileal MAM of control calves. Moreover, based on reconstructed metagenomes (PICRUSt) of ileal MAM, functional pathways associated with MAP infection were inferred. Enrichment of lysine and histidine metabolism pathways, and underrepresentation of glutathione metabolism and leucine and isoleucine degradation pathways in MAP-infected calves suggested potential contributions of ileal MAM in development of intestinal inflammation. Finally, simultaneous overrepresentation of families Planococcaceae and Paraprevotellaceae, as well as underrepresentation of genera Faecalibacterium and Akkermansia in the fecal microbiota of infected cattle, served as potential biomarker for identifying infected cattle during subclinical stages of JD. Collectively, based on compositional and functional shifts in intestinal microbiota of infected cattle, we inferred that

The Features of Fecal and Ileal Mucosa-Associated Microbiota in Dairy Calves during Early Infection with Mycobacterium avium Subspecies paratuberculosis

PubMed Central

Derakhshani, Hooman; De Buck, Jeroen; Mortier, Rienske; Barkema, Herman W.; Krause, Denis O.; Khafipour, Ehsan

2016-01-01

Current diagnostic tests for Johne's disease (JD), a chronic granulomatous inflammation of the gastrointestinal tract of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), lack the sensitivity to identify infected animals at early (asymptomatic) stages of the disease. The objective was to determine the pattern of MAP-associated dysbiosis of intestinal microbiota as a potential biomarker for early detection of infected cattle. To that end, genomic DNA was extracted from ileal mucosa and fecal samples collected from 28 MAP-positive and five control calves. High-throughput Illumina sequencing of the V4 hypervariable region of the 16S rRNA gene was used for community profiling of ileal mucosa-associated (MAM) or fecal microbiota. The PERMANOVA analysis of unweighted UniFrac distances revealed distinct clustering of ileal MAM (P = 0.049) and fecal microbiota (P = 0.068) in MAP-infected vs. control cattle. Microbiota profile of MAP-infected animals was further investigated by linear discriminant analysis effective size (LEfSe); several bacterial taxa within the phylum Proteobacteria were overrepresented in ileal MAM of control calves. Moreover, based on reconstructed metagenomes (PICRUSt) of ileal MAM, functional pathways associated with MAP infection were inferred. Enrichment of lysine and histidine metabolism pathways, and underrepresentation of glutathione metabolism and leucine and isoleucine degradation pathways in MAP-infected calves suggested potential contributions of ileal MAM in development of intestinal inflammation. Finally, simultaneous overrepresentation of families Planococcaceae and Paraprevotellaceae, as well as underrepresentation of genera Faecalibacterium and Akkermansia in the fecal microbiota of infected cattle, served as potential biomarker for identifying infected cattle during subclinical stages of JD. Collectively, based on compositional and functional shifts in intestinal microbiota of infected cattle, we inferred that

Development of a quantitative NS1-capture enzyme-linked immunosorbent assay for early detection of yellow fever virus infection.

PubMed

Ricciardi-Jorge, Taissa; Bordignon, Juliano; Koishi, Andrea; Zanluca, Camila; Mosimann, Ana Luiza; Duarte Dos Santos, Claudia Nunes

2017-11-24

Yellow fever is an arboviral disease that causes thousands of deaths every year in Africa and the Americas. However, few commercial diagnostic kits are available. Non-structural protein 1 (NS1) is an early marker of several flavivirus infections and is widely used to diagnose dengue virus (DENV) infection. Nonetheless, little is known about the dynamics of Yellow fever virus (YFV) NS1 expression and secretion, to encourage its use in diagnosis. To tackle this issue, we developed a quantitative NS1-capture ELISA specific for YFV using a monoclonal antibody and recombinant NS1 protein. This test was used to quantify NS1 in mosquito and human cell line cultures infected with vaccine and wild YFV strains. Our results showed that NS1 was detectable in the culture supernatants of both cell lines; however, a higher concentration was maintained as cell-associated rather than secreted into the extracellular milieu. A panel of 73 human samples was used to demonstrate the suitability of YFV NS1 as a diagnostic tool, resulting in 80% sensitivity, 100% specificity, a 100% positive predictive value and a 95.5% negative predictive value compared with RT-PCR. Overall, the developed NS1-capture ELISA showed potential as a promising assay for the detection of early YF infection.

Early Virological and Immunological Events in Asymptomatic Epstein-Barr Virus Infection in African Children

PubMed Central

Jayasooriya, Shamanthi; de Silva, Thushan I.; Njie-jobe, Jainaba; Sanyang, Chilel; Leese, Alison M.; Bell, Andrew I.; McAulay, Karen A.; Yanchun, Peng; Long, Heather M.; Dong, Tao; Whittle, Hilton C.; Rickinson, Alan B.; Rowland-Jones, Sarah L.; Hislop, Andrew D.; Flanagan, Katie L.

2015-01-01

Epstein-Barr virus (EBV) infection often occurs in early childhood and is asymptomatic. However, if delayed until adolescence, primary infection may manifest as acute infectious mononucleosis (AIM), a febrile illness characterised by global CD8+ T-cell lymphocytosis, much of it reflecting a huge expansion of activated EBV-specific CD8+ T-cells. While the events of AIM have been intensely studied, little is known about how these relate to asymptomatic primary infection. Here Gambian children (14–18 months old, an age at which many acquire the virus) were followed for the ensuing six months, monitoring circulating EBV loads, antibody status against virus capsid antigen (VCA) and both total and virus-specific CD8+ T-cell numbers. Many children were IgG anti-VCA-positive and, though no longer IgM-positive, still retained high virus loads comparable to AIM patients and had detectable EBV-specific T-cells, some still expressing activation markers. Virus loads and the frequency/activation status of specific T-cells decreased over time, consistent with resolution of a relatively recent primary infection. Six children with similarly high EBV loads were IgM anti-VCA-positive, indicating very recent infection. In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells. That response was culled and the cells lost activation markers over time, just as seen in AIM. However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers. Thus asymptomatic EBV infection in children elicits a virus-specific CD8+ T-cell response that can control the infection without over-expansion; conversely, in AIM it appears the CD8 over-expansion, rather than virus load per se, is the cause of disease symptoms. PMID:25816224

Effect of Poor Access to Water and Sanitation As Risk Factors for Soil-Transmitted Helminth Infection: Selectiveness by the Infective Route.

PubMed

Echazú, Adriana; Bonanno, Daniela; Juarez, Marisa; Cajal, Silvana P; Heredia, Viviana; Caropresi, Silvia; Cimino, Ruben O; Caro, Nicolas; Vargas, Paola A; Paredes, Gladys; Krolewiecki, Alejandro J

2015-09-01

Soil-transmitted helminth (STH) infections are a public health problem in resource-limited settings worldwide. Chronic STH infection impairs optimum learning and productivity, contributing to the perpetuation of the poverty-disease cycle. Regular massive drug administration (MDA) is the cardinal recommendation for its control; along with water, sanitation and hygiene (WASH) interventions. The impact of joint WASH interventions on STH infections has been reported; studies on the independent effect of WASH components are needed to contribute with the improvement of current recommendations for the control of STH. The aim of this study is to assess the association of lacking access to water and sanitation with STH infections, taking into account the differences in route of infection among species and the availability of adequate water and sanitation at home. Cross-sectional study, conducted in Salta province, Argentina. During a deworming program that enrolled 6957 individuals; 771 were randomly selected for stool/serum sampling for parasitological and serological diagnosis of STH. Bivariate stratified analysis was performed to explore significant correlations between risk factors and STH infections grouped by mechanism of entry as skin-penetrators (hookworms and Strongyloides stercoralis) vs. orally-ingested (Ascaris lumbricoides and Trichuris trichiura). After controlling for potential confounders, unimproved sanitation was significantly associated with increased odds of infection of skin-penetrators (adjusted odds ratio [aOR] = 3.9; 95% CI: 2.6-5.9). Unimproved drinking water was significantly associated with increased odds of infection of orally-ingested (aOR = 2.2; 95% CI: 1.3-3.7). Lack of safe water and proper sanitation pose a risk of STH infections that is distinct according to the route of entry to the human host used by each of the STH species. Interventions aimed to improve water and sanitation access should be highlighted in the recommendations for the

Effect of Poor Access to Water and Sanitation As Risk Factors for Soil-Transmitted Helminth Infection: Selectiveness by the Infective Route

PubMed Central

Echazú, Adriana; Bonanno, Daniela; Juarez, Marisa; Cajal, Silvana P.; Heredia, Viviana; Caropresi, Silvia; Cimino, Ruben O.; Caro, Nicolas; Vargas, Paola A.; Paredes, Gladys; Krolewiecki, Alejandro J.

2015-01-01

Background Soil-transmitted helminth (STH) infections are a public health problem in resource-limited settings worldwide. Chronic STH infection impairs optimum learning and productivity, contributing to the perpetuation of the poverty-disease cycle. Regular massive drug administration (MDA) is the cardinal recommendation for its control; along with water, sanitation and hygiene (WASH) interventions. The impact of joint WASH interventions on STH infections has been reported; studies on the independent effect of WASH components are needed to contribute with the improvement of current recommendations for the control of STH. The aim of this study is to assess the association of lacking access to water and sanitation with STH infections, taking into account the differences in route of infection among species and the availability of adequate water and sanitation at home. Methods and Findings Cross-sectional study, conducted in Salta province, Argentina. During a deworming program that enrolled 6957 individuals; 771 were randomly selected for stool/serum sampling for parasitological and serological diagnosis of STH. Bivariate stratified analysis was performed to explore significant correlations between risk factors and STH infections grouped by mechanism of entry as skin-penetrators (hookworms and Strongyloides stercoralis) vs. orally-ingested (Ascaris lumbricoides and Trichuris trichiura). After controlling for potential confounders, unimproved sanitation was significantly associated with increased odds of infection of skin-penetrators (adjusted odds ratio [aOR] = 3.9; 95% CI: 2.6–5.9). Unimproved drinking water was significantly associated with increased odds of infection of orally-ingested (aOR = 2.2; 95% CI: 1.3–3.7). Conclusions Lack of safe water and proper sanitation pose a risk of STH infections that is distinct according to the route of entry to the human host used by each of the STH species. Interventions aimed to improve water and sanitation access should

Predictors of human immunodeficiency virus (HIV) infection in primary care: a systematic review protocol.

PubMed

Rumbwere Dube, Benhildah N; Marshall, Tom P; Ryan, Ronan P

2016-09-20

Antiretroviral therapies for human immunodeficiency virus are more effective if infected individuals are diagnosed early, before they have irreversible immunologic damage. A large proportion of patients that are diagnosed with HIV, in United Kingdom, would have seen a general practitioner (GP) within the previous year. Determining the demographic and clinical characteristics of HIV-infected patients prior to diagnosis of HIV may be useful in identifying patients likely to be HIV positive in primary care. This could help inform a strategy of early HIV testing in primary care. This systematic review aims to identify characteristics of HIV-infected adults prior to diagnosis that could be used in a prediction model for early detection of HIV in primary care. The systematic review will search for literature, mainly observational (cohort and case-control) studies, with human participants aged 18 years and over. The exposures are demographic, socio-economic or clinical risk factors or characteristics associated with HIV infection. The comparison group will be patients with no risk factors or no comparison group. The outcome is laboratory-confirmed HIV/AIDS infection. Evidence will be identified from electronic searches of online databases of EMBASE, MEDLINE, The Cochrane Library and grey literature search engines of Open Grey, Web of Science Conference Proceedings Citation Index and examination of reference lists from selected studies (reference searching). Two reviewers will be involved in quality assessment and data extraction of the review. A data extraction form will be developed to collate data from selected studies. A checklist for quality assessment will be adapted from the Scottish Intercollegiate Guidelines Network (SIGN). This systematic review will identify and consolidate existing scientific evidence on characteristics of HIV infected individuals that could be used to inform decision-making in prognostic model development. PROSPERO CRD42016042427.

Infection of Brachypodium distachyon by Formae Speciales of Puccinia graminis: Early Infection Events and Host-Pathogen Incompatibility

PubMed Central

Figueroa, Melania; Alderman, Stephen; Garvin, David F.; Pfender, William F.

2013-01-01

Puccinia graminis causes stem rust, a serious disease of cereals and forage grasses. Important formae speciales of P. graminis and their typical hosts are P. graminis f. sp. tritici (Pg-tr) in wheat and barley, P. graminis f. sp. lolii (Pg-lo) in perennial ryegrass and tall fescue, and P. graminis f. sp. phlei-pratensis (Pg-pp) in timothy grass. Brachypodium distachyon is an emerging genetic model to study fungal disease resistance in cereals and temperate grasses. We characterized the P. graminis-Brachypodium pathosystem to evaluate its potential for investigating incompatibility and non-host resistance to P. graminis. Inoculation of eight Brachypodium inbred lines with Pg-tr, Pg-lo or Pg-pp resulted in sporulating lesions later accompanied by necrosis. Histological analysis of early infection events in one Brachypodium inbred line (Bd1-1) indicated that Pg-lo and Pg-pp were markedly more efficient than Pg-tr at establishing a biotrophic interaction. Formation of appressoria was completed (60–70% of germinated spores) by 12 h post-inoculation (hpi) under dark and wet conditions, and after 4 h of subsequent light exposure fungal penetration structures (penetration peg, substomatal vesicle and primary infection hyphae) had developed. Brachypodium Bd1-1 exhibited pre-haustorial resistance to Pg-tr, i.e. infection usually stopped at appressorial formation. By 68 hpi, only 0.3% and 0.7% of the Pg-tr urediniospores developed haustoria and colonies, respectively. In contrast, development of advanced infection structures by Pg-lo and Pg-pp was significantly more common; however, Brachypodium displayed post-haustorial resistance to these isolates. By 68 hpi the percentage of urediniospores that only develop a haustorium mother cell or haustorium in Pg-lo and Pg-pp reached 8% and 5%, respectively. The formation of colonies reached 14% and 13%, respectively. We conclude that Brachypodium is an apt grass model to study the molecular and genetic components of incompatiblity

Roles of Macrophages and Neutrophils in the Early Host Response to Bacillus anthracis Spores in a Mouse Model of Infection

PubMed Central

Cote, Christopher K.; Van Rooijen, Nico; Welkos, Susan L.

2006-01-01

The development of new approaches to combat anthrax requires that the pathogenesis and host response to Bacillus anthracis spores be better understood. We investigated the roles that macrophages and neutrophils play in the progression of infection by B. anthracis in a mouse model. Mice were treated with a macrophage depletion agent (liposome-encapsulated clodronate) or with a neutrophil depletion agent (cyclophosphamide or the rat anti-mouse granulocyte monoclonal antibody RB6-8C5), and the animals were then infected intraperitoneally or by aerosol challenge with fully virulent, ungerminated B. anthracis strain Ames spores. The macrophage-depleted mice were significantly more susceptible to the ensuing infection than the saline-pretreated mice, whereas the differences observed between the neutropenic mice and the saline-pretreated controls were generally not significant. We also found that augmenting peritoneal neutrophil populations before spore challenge did not increase resistance of the mice to infection. In addition, the bacterial load in macrophage-depleted mice was significantly greater and appeared significantly sooner than that observed with the saline-pretreated mice. However, the bacterial load in the neutropenic mice was comparable to that of the saline-pretreated mice. These data suggest that, in our model, neutrophils play a relatively minor role in the early host response to spores, whereas macrophages play a more dominant role in early host defenses against infection by B. anthracis spores. PMID:16369003

GP50 as a promising early diagnostic antigen for Taenia multiceps infection in goats by indirect ELISA.

PubMed

Huang, Xing; Xu, Jing; Wang, Yu; Guo, Cheng; Chen, Lin; Gu, Xiaobin; Lai, Weimin; Peng, Xuerong; Yang, Guangyou

2016-12-01

Coenurosis is caused by coenurus, the metacestode of Taenia multiceps, which mainly parasitizes the brain and spinal cord of cattle, sheep and goats. To date, no widely-approved methods are available to identify early coenurus infection. In this study, we identified a full-length cDNA that encodes GP50 (TmGP50) from the transcriptome of T. multiceps, and then cloned and expressed in E. coli. The native proteins in adult stage and coenurus were located via immunofluorescence assays, while the potential of recombinant TmGP50 protein (rTmGP50) for indirect ELISA-based serodiagnostics was assessed using native goat sera. In addition, we orally infected 20 goats with mature T. multiceps eggs. Praziquantel (10%) was given to 10 of the goats 45 days post-infection (p.i.). Blood samples were collected for 17 weeks p.i. from the 20 goats and anti-rTmGP50 antibodies were evaluated using the indirect ELISA established here. The TmGP50 contains an 897 bp open reading frame, in which signal sequence resides in 1 ~ 48 sites and mature polypeptide consists of 282 amino acid residues. Immunofluorescence staining showed that native TmGP50 was localized to the microthrix and parenchymatous zone of the adult parasite and coenurus, and the coenurus cystic wall. The indirect ELISA based on rTmGP50 exhibited a sensitivity of 95.0% and a specificity of 92.6% when detecting GP50 antibodies in sera of naturally infected goats and sheep. In goats experimentally infected with T. multiceps, anti-TmGP50 antibody was detectable from 2 to 17 weeks p.i. in the control group, while the antibody fell below the cut-off value about 3 weeks after praziquantel treatment. Our results indicate that recombinant TmGP50 is a suitable early diagnostic antigen for coenurus infection in goats.

Endogenous attention modulates early selective attention in psychopathy: An ERP investigation.

PubMed

Krusemark, Elizabeth A; Kiehl, Kent A; Newman, Joseph P

2016-10-01

Psychopathic individuals are prone to act on urges without adequate consideration of future consequences or the rights of other individuals. One interpretation of this behavior is that it reflects abnormal selective attention (i.e., a failure to process information that is incongruent with their primary focus of attention; Hiatt, Schmitt, & Newman, Neuropsychology, 18, 50-59, 2004). Unfortunately, it is unclear whether this selective attention abnormality reflects top-down endogenous influences, such as the strength or specificity of attention focus (i.e., top-down set) apart from other, more exogenous (bottom-up), effects on attention. To explore this question, we used an early visual event-related potential (N2pc) in combination with a modified visual search task designed to assess the effect of early endogenous (i.e., top-down) attention on the processing of set-congruent information. The task was administered to a sample of 70 incarcerated adult males, who were assigned to high, intermediate, and low psychopathy groups using Hare's Psychopathy Checklist-Revised (Hare, 2003). Based on the assumption that their failure to process set-incongruent information reflects the exaggerated effects of endogenous attention, we predicted that participants with high psychopathy scores would show an exaggerated N2pc response to set-congruent information. The results supported the hypothesis and provide novel electrophysiological evidence that psychopathy is associated with exaggerated endogenous attention effects during early stages of processing. Further research is needed to examine the implications of this finding for the well-established failure of psychopathic individuals to process set-incongruent information and inhibit inappropriate responses.

Early life traumatic stressors and the mediating role of PTSD in incident HIV infection among US men, comparisons by sexual orientation and race/ethnicity: results from the NESARC, 2004-2005.

PubMed

Reisner, Sari L; Falb, Kathryn L; Mimiaga, Matthew J

2011-08-01

Stressful life events in childhood during critical periods of development have long-term psychological and neurobiological sequelae, which may affect risk for HIV infection across the life course. Data were from a nationally representative sample of 13,274 US men (National Epidemiologic Survey on Alcohol and Related Conditions, 2004-2005). Weighted multivariable logistic regression models examined (1) the association of childhood violent events before age 18 on 12-month incident HIV infection and (2) whether posttraumatic stress disorder (PTSD) diagnosis (clinical interview) mediated the association between early life events and HIV. Overall, the 12-month HIV incidence was <1% (0.35%); 44% of new infections were among racial/ethnic minorities and 31% among men who have sex with men). One-third of the sample (33.5%) reported one or more early life stressors (physical abuse, sexual abuse, neglect, verbal violence, or witnessed violence). In a weighted multivariable logistic regression model adjusted for age, education, family's socioeconomic position, and sexual behaviors, each additional early life violent event was associated with an elevated odds of HIV infection [adjusted odds ratio (aOR) = 1.32; 95% confidence interval (CI): 1.16 to 1.50]. Adding PTSD to this adjusted model, PTSD was highly associated with incident HIV infection (aOR = 5.75; 95% CI: 4.76 to 6.95). There was evidence that PTSD partially mediated the relationship between early life events and HIV (aOR = 1.14; 95% CI: 1.02 to 1.28). Experiencing early life violent family stressors was associated with HIV infection among men. Early life events and HIV infection were mediated by PTSD, which has implications for understanding disparities in HIV infection. Interventions are urgently needed that address the long-term sequelae of childhood violence.

Artificial selection on ant female caste ratio uncovers a link between female-biased sex ratios and infection by Wolbachia endosymbionts.

PubMed

Pontieri, L; Schmidt, A M; Singh, R; Pedersen, J S; Linksvayer, T A

2017-02-01

Social insect sex and caste ratios are well-studied targets of evolutionary conflicts, but the heritable factors affecting these traits remain unknown. To elucidate these factors, we carried out a short-term artificial selection study on female caste ratio in the ant Monomorium pharaonis. Across three generations of bidirectional selection, we observed no response for caste ratio, but sex ratios rapidly became more female-biased in the two replicate high selection lines and less female-biased in the two replicate low selection lines. We hypothesized that this rapid divergence for sex ratio was caused by changes in the frequency of infection by the heritable bacterial endosymbiont Wolbachia, because the initial breeding stock varied for Wolbachia infection, and Wolbachia is known to cause female-biased sex ratios in other insects. Consistent with this hypothesis, the proportions of Wolbachia-infected colonies in the selection lines changed rapidly, mirroring the sex ratio changes. Moreover, the estimated effect of Wolbachia on sex ratio (~13% female bias) was similar in colonies before and during artificial selection, indicating that this Wolbachia effect is likely independent of the effects of artificial selection on other heritable factors. Our study provides evidence for the first case of endosymbiont sex ratio manipulation in a social insect. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Corticosteroid therapy in Epstein-Barr virus infection. Effect on lymphocyte class, subset, and response to early antigen.

PubMed

Brandfonbrener, A; Epstein, A; Wu, S; Phair, J

1986-02-01

Corticosteroid treatment of impending upper airway obstruction due to Epstein-Barr virus (EBV) infectious mononucleosis did not alter the pattern of lymphocyte changes induced by this viral infection during the first two weeks following administration of prednisone. By 12 weeks, 11 treated students had significantly fewer lymphocytes, including B, total T, helper, and T-suppressor cell numbers, than 11 untreated EBV-infected students, and values were closer to those noted in uninfected controls. Corticosteroid therapy did not alter the serologic response to early antigens of EBV. Fever and lymphadenopathy resolved somewhat more quickly in treated students.

The alternative Medicago truncatula defense proteome of ROS—defective transgenic roots during early microbial infection

PubMed Central

Kiirika, Leonard M.; Schmitz, Udo; Colditz, Frank

2014-01-01

ROP-type GTPases of plants function as molecular switches within elementary signal transduction pathways such as the regulation of ROS synthesis via activation of NADPH oxidases (RBOH-respiratory burst oxidase homolog in plants). Previously, we reported that silencing of the Medicago truncatula GTPase MtROP9 led to reduced ROS production and suppressed induction of ROS-related enzymes in transgenic roots (MtROP9i) infected with pathogenic (Aphanomyces euteiches) and symbiotic microorganisms (Glomus intraradices, Sinorhizobium meliloti). While fungal infections were enhanced, S. meliloti infection was drastically impaired. In this study, we investigate the temporal proteome response of M. truncatula MtROP9i transgenic roots during the same microbial interactions under conditions of deprived potential to synthesize ROS. In comparison with control roots (Mtvector), we present a comprehensive proteomic analysis using sensitive MS protein identification. For four early infection time-points (1, 3, 5, 24 hpi), 733 spots were found to be different in abundance: 213 spots comprising 984 proteins (607 unique) were identified after S. meliloti infection, 230 spots comprising 796 proteins (580 unique) after G. intraradices infection, and 290 spots comprising 1240 proteins (828 unique) after A. euteiches infection. Data evaluation by GelMap in combination with a heatmap tool allowed recognition of key proteome changes during microbial interactions under conditions of hampered ROS synthesis. Overall, the number of induced proteins in MtROP9i was low as compared with controls, indicating a dual function of ROS in defense signaling as well as alternative response patterns activated during microbial infection. Qualitative analysis of induced proteins showed that enzymes linked to ROS production and scavenging were highly induced in control roots, while in MtROP9i the majority of proteins were involved in alternative defense pathways such as cell wall and protein degradation. PMID

Monitoring of early humoral immunity to identify lung recipients at risk for development of serious infections: A multicenter prospective study.

PubMed

Sarmiento, Elizabeth; Cifrian, Jose; Calahorra, Leticia; Bravo, Carles; Lopez, Sonia; Laporta, Rosalia; Ussetti, Piedad; Sole, Amparo; Morales, Carmen; de Pablos, Alicia; Jaramillo, Maria; Ezzahouri, Ikram; García, Sandra; Navarro, Joaquin; Lopez-Hoyos, Marcos; Carbone, Javier

2018-04-06

Infection is still a leading cause of death during the first year after lung transplantation. We performed a multicenter study among teaching hospitals to assess monitoring of early humoral immunity as a means of identifying lung recipients at risk of serious infections. We prospectively analyzed 82 adult lung recipients at 5 centers in Spain. Data were collected before transplantation and at 7 and 30 days after transplantation. Biomarkers included IgG, IgM, IgA, complement factors C3 and C4, titers of antibodies to pneumococcal polysaccharide antigens (IgG, IgA, IgM) and antibodies to cytomegalovirus (IgG), and serum B-cell activating factor (BAFF) levels. The clinical follow-up period lasted 6 months. Clinical outcomes were bacterial infections requiring intravenous anti-microbial agents, cytomegalovirus (CMV) disease, and fungal infections requiring therapy. We found that 33 patients (40.2%) developed at least 1 serious bacterial infection, 8 patients (9.8%) had CMV disease, and 10 patients (12.2%) had fungal infections. Lower IgM antibody levels against pneumococcal polysaccharide antigens at Day 7 (defined as <5 mg/dl) were a risk factor for serious bacterial infection (adjusted odds ratio [OR] 3.96; 95% confidence interval [CI] 1.39 to 11.26; p = 0.0099). At Day 7 after transplantation, IgG hypogammaglobulinemia (defined as IgG <600 mg/dl) was associated with a higher risk of CMV disease (after adjustment for CMV mismatch: OR 8.15; 95% CI 1.27 to 52.55; p = 0.028) and fungal infection (adjusted OR 8.03, 95% CI 1.51 to 42.72; p = 0.015). Higher BAFF levels before transplantation were associated with a higher rate of development of serious bacterial infection and acute cellular rejection. Early monitoring of specific humoral immunity parameters proved useful for the identification of lung recipients who are at risk of serious infections. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights

A predictive model for early mortality after surgical treatment of heart valve or prosthesis infective endocarditis. The EndoSCORE.

PubMed

Di Mauro, Michele; Dato, Guglielmo Mario Actis; Barili, Fabio; Gelsomino, Sandro; Santè, Pasquale; Corte, Alessandro Della; Carrozza, Antonio; Ratta, Ester Della; Cugola, Diego; Galletti, Lorenzo; Devotini, Roger; Casabona, Riccardo; Santini, Francesco; Salsano, Antonio; Scrofani, Roberto; Antona, Carlo; Botta, Luca; Russo, Claudio; Mancuso, Samuel; Rinaldi, Mauro; De Vincentiis, Carlo; Biondi, Andrea; Beghi, Cesare; Cappabianca, Giangiuseppe; Tarzia, Vincenzo; Gerosa, Gino; De Bonis, Michele; Pozzoli, Alberto; Nicolini, Francesco; Benassi, Filippo; Rosato, Francesco; Grasso, Elena; Livi, Ugolino; Sponga, Sandro; Pacini, Davide; Di Bartolomeo, Roberto; De Martino, Andrea; Bortolotti, Uberto; Onorati, Francesco; Faggian, Giuseppe; Lorusso, Roberto; Vizzardi, Enrico; Di Giammarco, Gabriele; Marinelli, Daniele; Villa, Emmanuel; Troise, Giovanni; Picichè, Marco; Musumeci, Francesco; Paparella, Domenico; Margari, Vito; Tritto, Francesco; Damiani, Girolamo; Scrascia, Giuseppe; Zaccaria, Salvatore; Renzulli, Attilio; Serraino, Giuseppe; Mariscalco, Giovanni; Maselli, Daniele; Foschi, Massimiliano; Parolari, Alessandro; Nappi, Giannantonio

2017-08-15

The aim of this large retrospective study was to provide a logistic risk model along an additive score to predict early mortality after surgical treatment of patients with heart valve or prosthesis infective endocarditis (IE). From 2000 to 2015, 2715 patients with native valve endocarditis (NVE) or prosthesis valve endocarditis (PVE) were operated on in 26 Italian Cardiac Surgery Centers. The relationship between early mortality and covariates was evaluated with logistic mixed effect models. Fixed effects are parameters associated with the entire population or with certain repeatable levels of experimental factors, while random effects are associated with individual experimental units (centers). Early mortality was 11.0% (298/2715); At mixed effect logistic regression the following variables were found associated with early mortality: age class, female gender, LVEF, preoperative shock, COPD, creatinine value above 2mg/dl, presence of abscess, number of treated valve/prosthesis (with respect to one treated valve/prosthesis) and the isolation of Staphylococcus aureus, Fungus spp., Pseudomonas Aeruginosa and other micro-organisms, while Streptococcus spp., Enterococcus spp. and other Staphylococci did not affect early mortality, as well as no micro-organisms isolation. LVEF was found linearly associated with outcomes while non-linear association between mortality and age was tested and the best model was found with a categorization into four classes (AUC=0.851). The following study provides a logistic risk model to predict early mortality in patients with heart valve or prosthesis infective endocarditis undergoing surgical treatment, called "The EndoSCORE". Copyright © 2017. Published by Elsevier B.V.

Herpes zoster in African patients: an early manifestation of HIV infection.

PubMed

Van de Perre, P; Bakkers, E; Batungwanayo, J; Kestelyn, P; Lepage, P; Nzaramba, D; Bogaerts, J; Serufilira, A; Rouvroy, D; Uwimana, A

1988-01-01

During a 3-month period, 131 cases of herpes zoster were diagnosed in Kigali, Rwanda. There were 46 female and 85 male patients. Mean age was 29 years (range 1-66). An unusually high proportion of patients presented with cranial and sacral nerve localisation of their cutaneous lesions. 55/131 patients (42%) had involvement of more than one dermatome. None of the patients had an underlying condition known to favour herpes zoster. 120/131 (92%) had antibodies to HIV detected by an immunoenzymatic assay (EIA) and indirect immunofluorescence. 92/125 adult patients (74%) had no sign or symptom related to HIV infection other than herpes zoster. This study suggests that herpes zoster in Central Africa is an early and readily detectable manifestation of HIV-induced immunosuppression.

Rapid down-regulation of γc on T cells in early SIV infection correlates with impairment of T-cell function

PubMed Central

Xu, Huanbin; Wang, Xiaolei; Pahar, Bapi; Alvarez, Xavier; Rasmussen, Kelsi K.; Lackner, Andrew A.; Veazey, Ronald S.

2012-01-01

The common γc subunit molecule is shared among all γc cytokines and clearly involved in T-cell function, but its role in HIV infection and immunity is not well understood. Here, we examined expression and function of γc on T cells during SIV infection in Rhesus macaques. Surface γc distribution was differentially expressed on CD4+ and CD8+ T cells, and CD4+ naive/memory cell populations in various lymphoid tissues of normal macaques. However, surface γc expression was rapidly and significantly down-regulated on T cells in acute infection with pathogenic SIV, compared to infection with a less virulent SHIV or controls and did not recover on CD8+ T cells in the chronic stage. Moreover, the peripheral and CD4+T cell loss was inversely correlated with γc+ CD8+ T cells in individual tissues. γc+ T cells were mainly functional as evidenced by higher cytokine secretion and proliferative capacity. Further in vitro experiments found that surface γc expression could be down-regulated following high level of IL-7 treatment by both internalization and shedding. Down-regulation of γc during early HIV/SIV infection may inhibit T-cell function, particularly of CD8+ T cells, and, may be linked with immune failure and loss of viral containment.—Xu, H., Wang, X., Pahar, B., Alvarez, X., Rasmussen, K. K., Lackner, A. A., Veazey, R. S. Rapid down-regulation of γc on T cells in early SIV infection correlates with impairment of T-cell function. PMID:22375017

Prediction of Multiple Infections After Severe Burn Trauma: a Prospective Cohort Study

PubMed Central

Yan, Shuangchun; Tsurumi, Amy; Que, Yok-Ai; Ryan, Colleen M.; Bandyopadhaya, Arunava; Morgan, Alexander A.; Flaherty, Patrick J.; Tompkins, Ronald G.; Rahme, Laurence G.

2014-01-01

Objective To develop predictive models for early triage of burn patients based on hyper-susceptibility to repeated infections. Background Infection remains a major cause of mortality and morbidity after severe trauma, demanding new strategies to combat infections. Models for infection prediction are lacking. Methods Secondary analysis of 459 burn patients (≥16 years old) with ≥20% total body surface area burns recruited from six US burn centers. We compared blood transcriptomes with a 180-h cut-off on the injury-to-transcriptome interval of 47 patients (≤1 infection episode) to those of 66 hyper-susceptible patients (multiple [≥2] infection episodes [MIE]). We used LASSO regression to select biomarkers and multivariate logistic regression to built models, accuracy of which were assessed by area under receiver operating characteristic curve (AUROC) and cross-validation. Results Three predictive models were developed covariates of: (1) clinical characteristics; (2) expression profiles of 14 genomic probes; (3) combining (1) and (2). The genomic and clinical models were highly predictive of MIE status (AUROCGenomic = 0.946 [95% CI, 0.906–0.986]); AUROCClinical = 0.864 [CI, 0.794–0.933]; AUROCGenomic/AUROCClinical P = 0.044). Combined model has an increased AUROCCombined of 0.967 (CI, 0.940–0.993) compared to the individual models (AUROCCombined/AUROCClinical P = 0.0069). Hyper-susceptible patients show early alterations in immune-related signaling pathways, epigenetic modulation and chromatin remodeling. Conclusions Early triage of burn patients more susceptible to infections can be made using clinical characteristics and/or genomic signatures. Genomic signature suggests new insights into the pathophysiology of hyper-susceptibility to infection may lead to novel potential therapeutic or prophylactic targets. PMID:24950278

[Early kinetics of Toxoplasma gondii infection in mice infected intragastrically with tachyzoites by chromogenic in situ hybridization targeting SAG2 mRNA].

PubMed

Meng, Xiao-li; Ma, Xiao-ming; Yin, Guo-rong; Liu, Hong-li; Yin, Li-tian; Shen, Jin-yan; Wang, Hai-long

2010-04-01

To observe the early kinetics of Toxoplasma gondii infection in mice inoculated with tachyzoites of RH strain. Twenty BALB/c mice were administered intragastrically with tachyzoites of RH strain (2 x 10(4)/mice). Parasite burdens in mesenteric lymph node (MLN), liver, spleen, lung and brain were determined by chromogenic in situ hybridization targeting SAG2 mRNA at 1, 2, 4, 6 and 8 days postinfection. Five mice were inoculated with PBS as blank control. The MLN, liver and spleen were the first organs where tachyzoites were found on the first day after infection, followed by the lungs on the 4th day and the brain on the 6th day. On days 6 to 8 after infection, there was a significant difference on parasite load among the tissues (P < 0.05), and the parasite load in MLN was highest, followed by that of liver, spleen, lungs and brain. The number of tachyzoites in various tissues was time-dependent. T. gondii tachyzoites were first detected in MLN, liver and spleen, then in the lungs, and finally in the brain. The number of tachyzoites in the MLNs increased more rapidly.

Novel Mahalanobis-based feature selection improves one-class classification of early hepatocellular carcinoma.

PubMed

Thomaz, Ricardo de Lima; Carneiro, Pedro Cunha; Bonin, João Eliton; Macedo, Túlio Augusto Alves; Patrocinio, Ana Claudia; Soares, Alcimar Barbosa

2018-05-01

Detection of early hepatocellular carcinoma (HCC) is responsible for increasing survival rates in up to 40%. One-class classifiers can be used for modeling early HCC in multidetector computed tomography (MDCT), but demand the specific knowledge pertaining to the set of features that best describes the target class. Although the literature outlines several features for characterizing liver lesions, it is unclear which is most relevant for describing early HCC. In this paper, we introduce an unconstrained GA feature selection algorithm based on a multi-objective Mahalanobis fitness function to improve the classification performance for early HCC. We compared our approach to a constrained Mahalanobis function and two other unconstrained functions using Welch's t-test and Gaussian Data Descriptors. The performance of each fitness function was evaluated by cross-validating a one-class SVM. The results show that the proposed multi-objective Mahalanobis fitness function is capable of significantly reducing data dimensionality (96.4%) and improving one-class classification of early HCC (0.84 AUC). Furthermore, the results provide strong evidence that intensity features extracted at the arterial to portal and arterial to equilibrium phases are important for classifying early HCC.

Early detection of foot-and-mouth disease virus from infected cattle using a dry filter air sampling system

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease (FMD) is a highly contagious livestock disease of high economic impact. Early detection of FMD virus (FMDV) is fundamental for rapid outbreak control. Air sampling collection has been demonstrated as a useful technique for detection of FMDV RNA in infected animals, related to ...

Antimicrobial prophylaxis in acute pancreatitis: selective decontamination versus antibiotics.

PubMed

Luiten, E J; Bruining, H A

1999-07-01

The results of several controlled clinical trials, published during the last 5 years, provide evidence of a beneficial role for early antimicrobial prophylaxis in severe acute pancreatitis. Pancreatic infections, especially gram-negative, which are of major importance with regard to morbidity and mortality, are gut-derived. Early enteral administration of antibiotics therefore seems the most logical measure to nip the danger in the bud. Intravenous antibiotics should adequately penetrate (peri)pancreatic tissues, i.e. necrotic tissues, and should be effective against the prevalent flora in infected necrotic tissues. However, the optimal route of administration is still a matter of debate. In contrast to one clinical trial using selective decontamination (SD) (i.e. enteral antibiotics combined with short systemic prophylaxis until SD is established), no clinical trial using intravenous antibiotics has been reported in which both pancreatic infections as well as mortality were reduced. Although the evidence supporting enteral administration, i.e. SD, is not unimpressive, further controlled clinical trials, in which the different ways of administration are compared, are warranted.

Impact of early cART on HIV blood and semen compartments at the time of primary infection.

PubMed

Chéret, Antoine; Durier, Christine; Mélard, Adeline; Ploquin, Mickaël; Heitzmann, Julia; Lécuroux, Camille; Avettand-Fenoël, Véronique; David, Ludivine; Pialoux, Gilles; Chennebault, Jean-Marie; Müller-Trutwin, Michaela; Goujard, Cécile; Rouzioux, Christine; Meyer, Laurence

2017-01-01

HIV-infected cells in semen facilitate viral transmission. We studied the establishment of HIV reservoirs in semen and blood during PHI, along with systemic immune activation and the impact of early cART. Patients in the ANRS-147-OPTIPRIM trial received two years of early cART. Nineteen patients of the trial were analyzed, out of which 8 had acute PHI (WB ≤1 Ab). We quantified total cell-associated (ca) HIV-DNA in blood and semen and HIV-RNA in blood and semen plasma samples, collected during PHI and at 24 months of treatment. At enrollment, HIV-RNA load was higher in blood than in semen (median 5.66 vs 4.22 log10 cp/mL, p<0.0001). Semen HIV-RNA load correlated strongly with blood HIV-RNA load (r = 0.81, p = 0.02, the CD4 cell count (r = -0.98, p<0.0001), and the CD4/CD8 ratio (r = -0.85, p<0.01) in acute infection but not in later stages of PHI. Median blood and seminal cellular HIV-DNA levels were 3.59 and 0.31 log10cp/106 cells, respectively. HIV-DNA load peaked in semen later than in blood and then correlated with blood IP10 level (r = 0.62, p = 0.04). HIV-RNA was undetectable in blood and semen after two years of effective cART. Semen HIV-DNA load declined similarly, except in one patient who had persistently high IP-10 and IL-6 levels and used recreational drugs. HIV reservoir cells are found in semen during PHI, with gradual compartmentalization. Its size was linked to the plasma IP-10 level. Early treatment purges both the virus and infected cells, reducing the high risk of transmission during PHI. NCT01033760.

Early Childhood Intervention-Infancy: A Selective Bibliography. Exceptional Child Bibliography Series No. 670.

ERIC Educational Resources Information Center

ERIC Clearinghouse on Handicapped and Gifted Children, Reston, VA.

The annotated bibliography on early childhood intervention in infancy contains approximately 65 abstracts and associated indexing information for documents published from 1968 to 1974 and selected from the computer files of the Council for Exceptional Children's Information Services and the Education Resources Information Center (ERIC). It is…

Natural Selection on Individual Variation in Tolerance of Gastrointestinal Nematode Infection

PubMed Central

Hayward, Adam D.; Nussey, Daniel H.; Wilson, Alastair J.; Berenos, Camillo; Pilkington, Jill G.; Watt, Kathryn A.; Pemberton, Josephine M.; Graham, Andrea L.

2014-01-01

Hosts may mitigate the impact of parasites by two broad strategies: resistance, which limits parasite burden, and tolerance, which limits the fitness or health cost of increasing parasite burden. The degree and causes of variation in both resistance and tolerance are expected to influence host–parasite evolutionary and epidemiological dynamics and inform disease management, yet very little empirical work has addressed tolerance in wild vertebrates. Here, we applied random regression models to longitudinal data from an unmanaged population of Soay sheep to estimate individual tolerance, defined as the rate of decline in body weight with increasing burden of highly prevalent gastrointestinal nematode parasites. On average, individuals lost weight as parasite burden increased, but whereas some lost weight slowly as burden increased (exhibiting high tolerance), other individuals lost weight significantly more rapidly (exhibiting low tolerance). We then investigated associations between tolerance and fitness using selection gradients that accounted for selection on correlated traits, including body weight. We found evidence for positive phenotypic selection on tolerance: on average, individuals who lost weight more slowly with increasing parasite burden had higher lifetime breeding success. This variation did not have an additive genetic basis. These results reveal that selection on tolerance operates under natural conditions. They also support theoretical predictions for the erosion of additive genetic variance of traits under strong directional selection and fixation of genes conferring tolerance. Our findings provide the first evidence of selection on individual tolerance of infection in animals and suggest practical applications in animal and human disease management in the face of highly prevalent parasites. PMID:25072883

Infant anthropometry, early life infection, and subsequent risk of type 1 diabetes mellitus: a prospective birth cohort study.

PubMed

Ponsonby, Anne-Louise; Pezic, Angela; Cochrane, Jennifer; Cameron, Fergus J; Pascoe, Mark; Kemp, Andrew; Dwyer, Terence

2011-06-01

Higher birthweight is associated with increased type 1 diabetes mellitus (T1DM) risk, but the contribution of higher adiposity or lean mass is unclear. In this Tasmanian infant cohort, early upper respiratory infection has been associated with higher asthma risk. Eligible infants represented one-fifth of live births in Tasmania, 1988-1995. Hospital interview data (day 6) were obtained on 96.3% (10 628/11 040), home (5 wk) visit data (38 d) on 92.9% (9876/10 628) of those, then a phone (12 wk) interview (87 d). Tricep and subscapular skinfold measures and upper arm circumference were recorded at the first two interviews. T1DM cases (n = 26) arising from the age of 16 or under in Tasmania from 1988 to 2006 were ascertained. Higher birthweight [adjusted odds ratio (AOR) 2.82 (95% CI 1.31-6.09)], lean mid-upper arm circumference [AOR 1.76 (95% CI 1.16-2.66)], not skinfold measures, were associated with T1DM risk. Children with an early upper respiratory tract infection by 5-wk visit [AOR 2.74 (95% CI 1.19-6.32)] or ear infection by 12-wk interview [AOR 3.44 (95% CI 1.00-11.79)] were also at higher risk. Putative markers of altered microbial exposure such as resident density were not associated with T1DM risk but the effect of increasing birth order on T1DM risk differed for older (AOR 0.41, p = 0.02) than young mother (AOR 2.45, p = 0.01); difference in effect, p = 0.001. In this cohort, early upper respiratory tract infection was associated with T1DM risk, as had been previously found for asthma, consistent with immunoinflammatory upregulation. Using the detailed anthropometric measures available, the link between higher birthweight and T1DM did not appear to reflect increased adiposity. © 2011 John Wiley & Sons A/S.

Reduced lymphocyte count as an early marker for predicting infected pancreatic necrosis.

PubMed

Shen, Xiao; Sun, Jing; Ke, Lu; Zou, Lei; Li, Baiqiang; Tong, Zhihui; Li, Weiqin; Li, Ning; Li, Jieshou

2015-10-26

Early occurrence of immunosuppression is a risk factor for infected pancreatic necrosis (IPN) in the patients with acute pancreatitis (AP). However, current measures for the immune systems are too cumbersome and not widely available. Significantly decreased lymphocyte count has been shown in patients with severe but not mild type of AP. Whereas, the correlation between the absolute lymphocyte count and IPN is still unknown. We conduct this study to reveal the exact relationship between early lymphocyte count and the development of IPN in the population of AP patients. One hundred and fifty-three patients with acute pancreatitis admitted to Jinling Hospital during the period of January 2012 to July 2014 were included in this retrospective study. The absolute lymphocyte count and other relevant parameters were measured on admission. The diagnosis of IPN was based on the definition of the revised Atlanta classification. Patients were divided into two groups according to the presence of IPN. Thirty patients developed infected necrotizing pancreatitis during the disease course. The absolute lymphocyte count in patients with IPN was significantly lower on admission (0.62 × 10(9)/L, interquartile range [IQR]: 0.46-0.87 × 10(9)/L vs. 0.91 × 10(9)/L, IQR: 0.72-1.27 × 10(9)/L, p < 0.001) and throughout the whole clinical course than those without IPN. Logistic regression indicated that reduced lymphocyte count was an independent risk factor for IPN. The optimal cut-offs from ROC curve was 0.66 × 10(9)/L giving sensitivity of 83.7 % and specificity of 66.7 %. Reduced lymphocyte count within 48 h of AP onset is significantly and independently associated with the development of IPN.

ASSOCIATION OF KIDNEY FUNCTION AND EARLY KIDNEY INJURY WITH INCIDENT HYPERTENSION IN HIV-INFECTED WOMEN

PubMed Central

Ascher, Simon B.; Scherzer, Rebecca; Peralta, Carmen A.; Tien, Phyllis C.; Grunfeld, Carl; Estrella, Michelle M.; Abraham, Alison; Gustafson, Deborah R.; Nowicki, Marek; Sharma, Anjali; Cohen, Mardge H.; Butch, Anthony W.; Young, Mary A.; Bennett, Michael R.; Shlipak, Michael G.

2016-01-01

Subclinical kidney disease is associated with developing hypertension in the general population, but data are lacking among HIV-infected persons. We examined associations of kidney function and injury with incident hypertension in 823 HIV-infected and 267 HIV-uninfected women in the Women’s Interagency HIV Study, a multicenter, prospective cohort of HIV-infected and uninfected women in the United States. Baseline kidney biomarkers included estimated glomerular filtration rate using cystatin C (eGFR), urine albumin-to-creatinine ratio (ACR), and seven urine biomarkers of tubular injury: alpha-1-microglobulin, interleukin-18 (IL-18), kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, liver fatty acid binding protein, N-acetyl-beta-D-glucosaminidase (NAG), and alpha1-acid-glycoprotein (AAG). We used multivariable Poisson regression to evaluate associations of kidney biomarkers with incident hypertension, defined as two consecutive visits of anti-hypertensive medication use. Over a median follow-up of 9.6 years, 288 HIV-infected women (35%) developed hypertension. Among the HIV-infected women, higher ACR was independently associated with incident hypertension (RR=1.13 per ACR doubling, 95%CI: 1.07, 1.20), as was lower eGFR (RR=1.10 per 10 ml/min/1.73m2 lower eGFR, CI: 1.04, 1.17). No tubular injury and dysfunction biomarkers were independently associated with incident hypertension in HIV-infected women. In contrast, among the HIV-uninfected women, ACR was not associated with incident hypertension, whereas higher IL-18, AAG and NAG were significantly associated with incident hypertension. These findings suggest that early glomerular injury and kidney dysfunction may be involved in the pathogenesis of hypertension in HIV-infected persons. The associations of the tubular markers with hypertension in HIV-uninfected women should be validated in other studies. PMID:27993956

Magnetic resonance imaging of appendicular musculoskeletal infection.

PubMed

Lalam, Radhesh K; Cassar-Pullicino, Victor N; Tins, Bernhard J

2007-06-01

Appendicular skeletal infection includes osseous and extraosseous infections. Skeletal infection needs early diagnosis and appropriate management to prevent long-term morbidity. Magnetic resonance imaging is the best imaging modality to diagnose skeletal infection early in most circumstances. This article describes the role of magnetic resonance imaging in relation to the other available imaging modalities in the diagnosis of skeletal infection. Special circumstances such as diabetic foot, postoperative infection, and chronic recurrent multifocal osteomyelitis are discussed separately.

Serodiagnosis of Echinococcus spp. Infection: Explorative Selection of Diagnostic Antigens by Peptide Microarray

PubMed Central

List, Claudia; Qi, Weihong; Maag, Eva; Gottstein, Bruno; Müller, Norbert; Felger, Ingrid

2010-01-01

Background Production of native antigens for serodiagnosis of helminthic infections is laborious and hampered by batch-to-batch variation. For serodiagnosis of echinococcosis, especially cystic disease, most screening tests rely on crude or purified Echinococcus granulosus hydatid cyst fluid. To resolve limitations associated with native antigens in serological tests, the use of standardized and highly pure antigens produced by chemical synthesis offers considerable advantages, provided appropriate diagnostic sensitivity and specificity is achieved. Methodology/Principal Findings Making use of the growing collection of genomic and proteomic data, we applied a set of bioinformatic selection criteria to a collection of protein sequences including conceptually translated nucleotide sequence data of two related tapeworms, Echinococcus multilocularis and Echinococcus granulosus. Our approach targeted alpha-helical coiled-coils and intrinsically unstructured regions of parasite proteins potentially exposed to the host immune system. From 6 proteins of E. multilocularis and 5 proteins of E. granulosus, 45 peptides between 24 and 30 amino acids in length were designed. These peptides were chemically synthesized, spotted on microarrays and screened for reactivity with sera from infected humans. Peptides reacting above the cut-off were validated in enzyme-linked immunosorbent assays (ELISA). Peptides identified failed to differentiate between E. multilocularis and E. granulosus infection. The peptide performing best reached 57% sensitivity and 94% specificity. This candidate derived from Echinococcus multilocularis antigen B8/1 and showed strong reactivity to sera from patients infected either with E. multilocularis or E. granulosus. Conclusions/Significance This study provides proof of principle for the discovery of diagnostically relevant peptides by bioinformatic selection complemented with screening on a high-throughput microarray platform. Our data showed that a single

Towards functional antibody-based vaccines to prevent pre-erythrocytic malaria infection.

PubMed

Sack, Brandon; Kappe, Stefan H I; Sather, D Noah

2017-05-01

An effective malaria vaccine would be considered a milestone of modern medicine, yet has so far eluded research and development efforts. This can be attributed to the extreme complexity of the malaria parasites, presenting with a multi-stage life cycle, high genome complexity and the parasite's sophisticated immune evasion measures, particularly antigenic variation during pathogenic blood stage infection. However, the pre-erythrocytic (PE) early infection forms of the parasite exhibit relatively invariant proteomes, and are attractive vaccine targets as they offer multiple points of immune system attack. Areas covered: We cover the current state of and roadblocks to the development of an effective, antibody-based PE vaccine, including current vaccine candidates, limited biological knowledge, genetic heterogeneity, parasite complexity, and suboptimal preclinical models as well as the power of early stage clinical models. Expert commentary: PE vaccines will need to elicit broad and durable immunity to prevent infection. This could be achievable if recent innovations in studying the parasites' infection biology, rational vaccine selection and design as well as adjuvant formulation are combined in a synergistic and multipronged approach. Improved preclinical assays as well as the iterative testing of vaccine candidates in controlled human malaria infection trials will further accelerate this effort.

Screening for chlamydial infection.

PubMed

Nelson, H D; Helfand, M

2001-04-01

To examine data on the effectiveness of screening for chlamydial infection by a physician or other health care professional. Specifically, we examine the evidence that early treatment of chlamydial infection improves health outcomes, as well as evidence of the effectiveness of screening strategies in nonpregnant women, pregnant women, and men, and the accuracy of tests used for screening. This review updates the literature since the last recommendation of the U.S. Preventive Services Task Force published in 1996. We searched the topic of chlamydia in the MEDLINE, HealthSTAR, and Cochrane Library databases from January 1994 to July 2000, supplemented by reference lists of relevant articles and from experts in the field. Articles published prior to 1994 and research abstracts were cited if particularly important to the key questions or to the interpretation of included articles. A single reader reviewed all English abstracts. Articles were selected for full review if they were about Chlamydia trachomatis genitourinary infections in nonpregnant women, pregnant women, or men and were relevant to key questions in the analytic framework. Investigators read the full-text version of the retrieved articles and applied additional eligibility criteria. For all topics, we excluded articles if they did not provide sufficient information to determine the methods for selecting subjects and for analyzing data. We systematically reviewed three types of studies about screening in nonpregnant women that relate to three key questions: (1) studies about the effectiveness of screening programs in reducing prevalence rates of infection, (2) studies about risk factors for chlamydial infection in women, and (3) studies about chlamydial screening tests in women. Our search found too few studies on pregnant women to systematically review, although pertinent studies are described. We systematically reviewed two types of studies about screening in men: (1) studies about prevalence rates and

Human Neutrophil Clearance of Bacterial Pathogens Triggers Anti-Microbial γδ T Cell Responses in Early Infection

PubMed Central

Roberts, Gareth W.; Heuston, Sinéad; Brown, Amanda C.; Chess, James A.; Toleman, Mark A.; Gahan, Cormac G. M.; Hill, Colin; Parish, Tanya; Williams, John D.; Davies, Simon J.; Johnson, David W.; Topley, Nicholas; Moser, Bernhard; Eberl, Matthias

2011-01-01

Human blood Vγ9/Vδ2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vγ9/Vδ2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vγ9/Vδ2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vγ9/Vδ2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-α dependent proliferation of Vγ9/Vδ2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting γδ T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vγ9/Vδ2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The γδ T cell-driven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of γδ T cells and TNF-α and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive γδ T cells in early

Induction of immune response in macaque monkeys infected with simian-human immunodeficiency virus having the TNF-{alpha} gene at an early stage of infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shimizu, Yuya; Miyazaki, Yasuyuki; Ibuki, Kentaro

2005-12-20

TNF-{alpha} has been implicated in the pathogenesis of, and the immune response against, HIV-1 infection. To clarify the roles of TNF-{alpha} against HIV-1-related virus infection in an SHIV-macaque model, we genetically engineered an SHIV to express the TNF-{alpha} gene (SHIV-TNF) and characterized the virus's properties in vivo. After the acute viremic stage, the plasma viral loads declined earlier in the SHIV-TNF-inoculated monkeys than in the parental SHIV (SHIV-NI)-inoculated monkeys. SHIV-TNF induced cell death in the lymph nodes without depletion of circulating CD4{sup +} T cells. SHIV-TNF provided some immunity in monkeys by increasing the production of the chemokine RANTES andmore » by inducing an antigen-specific proliferation of lymphocytes. The monkeys immunized with SHIV-TNF were partly protected against a pathogenic SHIV (SHIV-C2/1) challenge. These findings suggest that TNF-{alpha} contributes to the induction of an effective immune response against HIV-1 rather than to the progression of disease at the early stage of infection.« less

Peripheral B cells latently infected with Epstein–Barr virus display molecular hallmarks of classical antigen-selected memory B cells

PubMed Central

Souza, Tatyana A.; Stollar, B. David; Sullivan, John L.; Luzuriaga, Katherine; Thorley-Lawson, David A.

2005-01-01

Epstein–Barr virus (EBV) establishes a lifelong persistent infection within peripheral blood B cells with the surface phenotype of memory cells. To date there is no proof that these cells have the genotype of true germinal-center-derived memory B cells. It is critical to understand the relative contribution of viral mimicry versus antigen signaling to the production of these cells because EBV encodes proteins that can affect the surface phenotype of infected cells and provide both T cell help and B cell receptor signals in the absence of cognate antigen. To address these questions we have developed a technique to identify single EBV-infected cells in the peripheral blood and examine their expressed Ig genes. The genes were all isotype-switched and somatically mutated. Furthermore, the mutations do not cause stop codons and display the pattern expected for antigen-selected memory cells based on their frequency, type, and location within the Ig gene. We conclude that latently infected peripheral blood B cells display the molecular hallmarks of classical antigen-selected memory B cells. Therefore, EBV does not disrupt the normal processing of latently infected cells into memory, and deviations from normal B cell biology are not tolerated in the infected cells. This article provides definitive evidence that EBV in the peripheral blood persists in true memory B cells. PMID:16330748

Prognostic importance of gram-negative intestinal colonization preceding pancreatic infection in severe acute pancreatitis. Results of a controlled clinical trial of selective decontamination.

PubMed

Luiten, E J; Hop, W C; Endtz, H P; Bruining, H A

1998-05-01

To establish, firstly, whether gram-negative (re)-colonization of the gut leads to an increased risk of gram-negative pancreatic infections and whether this event is time-related and, secondly, whether the difference in the quantity and quality of micro-organisms colonizing the digestive tract influences morbidity and mortality. Prospective analysis of the results of systematic semi-quantitative cultures of several body areas taken from patients with severe acute pancreatitis, during a controlled multicenter trial of adjuvant selective decontamination. Surgical intensive care units of 16 hospitals. A total of 2,159 semi-quantitative cultures from the oropharynx, rectum and pancreatic tissues taken from 90 patients were analyzed. Surveillance cultures from the oropharynx and rectum were taken on admission and repeated twice weekly and from the (peri)-pancreatic devitalized tissues (i. e. necrosis) at every relaparotomy and from drainage. All gram-negative pancreatic infections were preceded by intestinal colonization with the same micro-organisms. The risk of developing a pancreatic infection following gram-negative intestinal colonization (15/42 patients) was significantly higher as compared to patients without gram-negative colonization (0/10 patients) (p < 0.001) or to patients in whom E. coli was the only intestinal micro-organism cultured (0/30 patients) (p < 0.001). The occurrence of intestinal E. coli did not increase the risk of pancreatic infection. Gram-negative colonization of the rectum and oropharynx significantly correlated with the later development of pancreatic infection: relative risks 73.7 (p < 0.001) and 13.6 (p < 0.001), respectively. However, when both areas were evaluated simultaneously, the rectum was more significant (p < 0.001). The severity of intestinal intestinal colonization until the moment of pancreatic infection showed an increase in time in all 15 patients. In 11 of 15 patients (73%) these infections occurred within 1 week following

Active and separate secretion of fiber and penton base during the early phase of Ad2 or Ad5 infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Yuhua; Zhang, Bo; Hou, Weihong

Fiber and penton base overproduced in adenovirus (Ad) infected cells can be secreted prior to progeny release and thereby regulate progeny spread. We aimed to investigate the mechanisms of fiber and penton base secretion in Ad2- or Ad5-infected A549 cells. Our flow cytometry analyses detected abundant surface fiber molecules, but little penton base molecules at 12 h post infection. Immunogold staining combined with transmission electron microscopic analyses revealed separate, non-co-localized release of fiber and penton base in the proximity of the plasma membrane. Depolymerization of microtubule and actin cytoskeletons, and inhibition of Rock kinase and myosin II activity together demonstratedmore » cytoskeletal network-dependent fiber secretion. Inhibition of intracellular calcium [Ca{sup 2+}]{sub i} signaling caused diminished fiber secretion, which was associated with diminished progeny production. Thus, fiber and penton base are actively and separately secreted during the early stages of Ad2 or Ad5 infection, their secretion may play important role in Ad life cycle. - Highlights: •Excessive production of structural proteins is common to viral infection, which may regulate the host-virus equilibrium and the spreading of viruses. •The adenovirus (Ad) structural proteins, fiber and penton base, are respectively important for Ad binding to its receptor and subsequent internalization in host cells. In Ad infected cells, these two structural proteins are excessively produced. •The mechanisms underlying the release of fiber and penton base molecules at the early phase of Ad infection is yet poorly understood. •Our studies show that in Ad5 or Ad2 infected A549 cells, fiber and penton base molecules are actively and separately secreted. •Fiber secretion is dependent on cytoskeleton-mediated protein traffic. •Inhibition of myosin II motor and Ca{sup 2+} signaling activity significantly diminishes fiber secretion. •These findings could contribute to our

Early-shared Mycobacterium bovis bacillus Calmette-Guérin sub-strains induce Th1 cytokine production in vivo.

PubMed

Taniguchi, Keiichi; Miyatake, Yuuji; Hayashi, Daisuke; Takami, Atsuro; Itoh, Saotomo; Yamamoto, Saburo; Hida, Shigeaki; Onozaki, Kikuo; Takii, Takemasa

2015-11-01

Interleukin-12 is one of the cytokines that induce acquired immunity by progressing the differentiation of T cells. When antigens are presented by APCs, including macrophages and DCs, T cells are activated and produce the Th1 cytokines IL-2 and IFN-γ. We have previously reported greater IL-12 production from macrophages infected with early-shared BCG sub-strains (ex. BCG-Japan, -Sweden) than from those infected with late-shared BCG (ex. BCG-Pasteur and -Connaught) . In this study, we investigated the Th1 cytokine-inducing activity of splenocytes co-cultured with BCG-infected DCs. Early-shared BCG-infected DCs produced IL-12 and TNF-α⋅ Furthermore, when they were co-cultured with purified protein derivative-stimulated DCs, the splenocytes of mice immunized with BCG-Tokyo/Japan produced more Th1 cytokine than did those of mice immunized with BCG-Connaught. In conclusion, early-shared BCG sub-strains more strongly induce Th1 cytokine production in vivo. This study provides basic information to inform the selection of candidates for primary vaccination. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

Multifaceted antibiotic treatment analysis of methicillin-sensitive Staphylococcus aureus bloodstream infections.

PubMed

Weber, Zhanni; Ariano, Robert; Lagacé-Wiens, Philippe; Zelenitsky, Sheryl

2016-12-01

Given the overall prevalence and poor prognosis of Staphylococcus aureus bloodstream infections (BSIs), the study of treatment strategies to improve patient outcomes is important. The aim of this study was to conduct a multifaceted antibiotic treatment analysis of methicillin-sensitive S. aureus (MSSA) BSI and to characterise optimal early antibiotic therapy (within the first 7 days of drawing the index blood culture) for this serious infection. Antibiotic selection was categorised as optimal targeted (intravenous cloxacillin or cefazolin), optimal broad (piperacillin/tazobactam or meropenem), adequate (vancomycin) or inadequate (other antibiotics or oral therapy). A TSE (timing, selection, exposure) score was developed to comprehensively characterise early antibiotic therapy, where higher points corresponded to prompt initiation, optimal antibiotic selection and longer exposure (duration). Amongst 71 cases of complicated MSSA-BSI, end-of-treatment (EOT) response (i.e. clinical cure) was improved when at least adequate antibiotic therapy was initiated within 24 h [71.7% (33/46) vs. 48.0% (12/25); P = 0.047]. Clinical cure was also more likely when therapy included ≥4 days of optimal targeted antibiotics within the first 7 days [74.4% (29/39) vs. 50.0% (16/32); P = 0.03]. The TSE score was an informative index of early antibiotic therapy, with EOT cure documented in 72.0% (36/50) compared with 42.9% (9/21) of cases with scores above and below 15.2, respectively (P = 0.02). In multivariable analysis, lower Charlson comorbidity index, presence of BSI on admission, and optimising early antibiotic therapy, as described above, were associated with clinical cure in patients with MSSA-BSI. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations.

PubMed

Marchandeau, Stéphane; Pontier, Dominique; Guitton, Jean-Sébastien; Letty, Jérôme; Fouchet, David; Aubineau, Jacky; Berger, Francis; Léonard, Yves; Roobrouck, Alain; Gelfi, Jacqueline; Peralta, Brigitte; Bertagnoli, Stéphane

2014-03-04

The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen.

Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations

PubMed Central

2014-01-01

The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen. PMID:24589193

Toxicity associated with high dosage 9-[(2R,5R-2,5-dihydro-5-phosphonomethoxy)-2-furanyl]adenine therapy off attempts to abort early FIV infection.

PubMed

Hartmann, K; Ferk, G; North, T W; Pedersen, N C

1997-09-01

9-[(2R,5R-2,5-dihydro-5-phosphonomethoxy)-2-furanyl]adenine, or D4API, was tested in the feline immunodeficiency virus (FIV) infection model and found to be significantly more inhibitory in vitro than its parent compound 9-phosphonylmethoxethyl adenine (PMEA). Cytotoxicity was less than for PMEA or azidothymidine (AZT) for culture periods of 7 days, but more toxic after 10 days. D4API was rapidly absorbed by cats following subcutaneous inoculation, with a plasma half-life of less than 1 h after intravenous inoculation and between 2 and 3 h after subcutaneous injection. Peripheral blood mononuclear cells collected from cats given a single dose of D4API were refractory, however, to FIV infection in vitro for up to 24 h. Given its prolonged intracellular phase and high selectivity index, high dose D4API therapy was tested for its ability to abort an acute (i.e. 2 week) FIV infection. A divided daily dose of D4API, which was one-fourth the toxic dose and 125 times the concentration that would totally inhibit virus replication in vitro, completely abrogated the anticipated viremia and antibody responses. Unfortunately, a majority of treated/uninfected and treated/infected test cats died acutely of drug toxicity after 47 days of treatment. Toxicity in vivo mirrored what was observed in vitro, being precipitous and cumulative in nature. Toxic signs included widespread hepatic and lymphoid necrosis. A surviving treated/FIV infected cat remained healthy to day 175 when the study was terminated; antibodies appeared 2 months later than in untreated/infected cats and virus was only detectable at low levels on day 175. In contrast, untreated/infected cats were viremic and antibody positive from 3 to 4 weeks post-infection onwards. Therefore, it was possible to alter, but not abort, an early FIV infection with prolonged, high-dose D4API treatment.

Dipole source localization of event-related brain activity indicative of an early visual selective attention deficit in ADHD children.

PubMed

Jonkman, L M; Kenemans, J L; Kemner, C; Verbaten, M N; van Engeland, H

2004-07-01

This study was aimed at investigating whether attention-deficit hyperactivity disorder (ADHD) children suffer from specific early selective attention deficits in the visual modality with the aid of event-related brain potentials (ERPs). Furthermore, brain source localization was applied to identify brain areas underlying possible deficits in selective visual processing in ADHD children. A two-channel visual color selection task was administered to 18 ADHD and 18 control subjects in the age range of 7-13 years and ERP activity was derived from 30 electrodes. ADHD children exhibited lower perceptual sensitivity scores resulting in poorer target selection. The ERP data suggested an early selective-attention deficit as manifested in smaller frontal positive activity (frontal selection positivity; FSP) in ADHD children around 200 ms whereas later occipital and fronto-central negative activity (OSN and N2b; 200-400 ms latency) appeared to be unaffected. Source localization explained the FSP by posterior-medial equivalent dipoles in control subjects, which may reflect the contribution of numerous surrounding areas. ADHD children have problems with selective visual processing that might be caused by a specific early filtering deficit (absent FSP) occurring around 200 ms. The neural sources underlying these problems have to be further identified. Source localization also suggested abnormalities in the 200-400 ms time range, pertaining to the distribution of attention-modulated activity in lateral frontal areas.

Predictors of early infection in cerebral ischemic stroke.

PubMed

Ashour, Wmr; Al-Anwar, A D; Kamel, A E; Aidaros, M A

2016-01-01

Infection is the most common complication of stroke. To determine the risk factors and predictors of post-stroke infection (PSI), which developed within 7 days from the onset of acute ischemic stroke. The study included 60 ischemic stroke patients admitted in the Neurology Department of Zagazig University, Egypt, who were subdivided into: [Non Stroke Associated Infection group (nSAI); 30 patients having stroke without any criteria of infection within 7 days from the onset and Stroke Associated Infection group (SAI); 30 patients having stroke with respiratory tract infection (RTI) or urinary tract infection within 7 days], in addition to 30 healthy sex and age-matching subjects as control. All the patients had a detailed history taking, thorough clinical general and neurological examination, laboratory tests (Urine analysis & urine culture, blood sugar, lipid profile and serum tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10), a chest radiography to assess RTI and brain computed tomography (CT) to exclude the hemorrhagic stroke and to confirm the ischemic stroke. SAI patients were found to be significantly older with higher baseline blood glucose level. Also the number of patients with tube feeding, lower conscious level, more stroke severity and more large size infarcts were significantly higher in SAI patients. There was a significant elevation in the IL-10, a significant decrease in the TNF-α and a significant decrease in the TNF-α/ IL-10 ratio, in the SAI group. The baseline serum level of IL-10 ≥ 14.5 pg/ ml and size of infarct area > 3.5 cm3 were found to be the independent predictors of PSI. Patients with older age, tube feeding, lower conscious level, worse baseline stroke severity, large cerebral infarcts in CT scan, and increased IL-10 serum level were more susceptible to infection. The baseline serum level of IL-10 ≥ 14.5 pg/ ml and the size of infarct area > 3.5 cm3 were the independent predictors of PSI.

Predictors of early infection in cerebral ischemic stroke

PubMed Central

Ashour, WMR; Al-Anwar, AD; Kamel, AE; Aidaros, MA

2016-01-01

Background: Infection is the most common complication of stroke. Aim: To determine the risk factors and predictors of post-stroke infection (PSI), which developed within 7 days from the onset of acute ischemic stroke. Subjects: The study included 60 ischemic stroke patients admitted in the Neurology Department of Zagazig University, Egypt, who were subdivided into: [Non Stroke Associated Infection group (nSAI); 30 patients having stroke without any criteria of infection within 7 days from the onset and Stroke Associated Infection group (SAI); 30 patients having stroke with respiratory tract infection (RTI) or urinary tract infection within 7 days], in addition to 30 healthy sex and age-matching subjects as control. Methods: All the patients had a detailed history taking, thorough clinical general and neurological examination, laboratory tests (Urine analysis & urine culture, blood sugar, lipid profile and serum tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10), a chest radiography to assess RTI and brain computed tomography (CT) to exclude the hemorrhagic stroke and to confirm the ischemic stroke. Results: SAI patients were found to be significantly older with higher baseline blood glucose level. Also the number of patients with tube feeding, lower conscious level, more stroke severity and more large size infarcts were significantly higher in SAI patients. There was a significant elevation in the IL-10, a significant decrease in the TNF-α and a significant decrease in the TNF-α/ IL-10 ratio, in the SAI group. The baseline serum level of IL-10 ≥ 14.5 pg/ ml and size of infarct area > 3.5 cm3 were found to be the independent predictors of PSI. Conclusion: Patients with older age, tube feeding, lower conscious level, worse baseline stroke severity, large cerebral infarcts in CT scan, and increased IL-10 serum level were more susceptible to infection. The baseline serum level of IL-10 ≥ 14.5 pg/ ml and the size of infarct area > 3.5 cm3 were the

Improved outcome with early rifampicin combination treatment in methicillin-sensitive Staphylococcus aureus bacteraemia with a deep infection focus - a retrospective cohort study.

PubMed

Forsblom, Erik; Ruotsalainen, Eeva; Järvinen, Asko

2015-01-01

Rifampicin has been used as adjunctive therapy in Staphylococcus aureus bacteraemia (SAB) with a deep infection focus. However, data for prognostic impact of rifampicin therapy is unestablished including the optimal initiation time point. We studied the impact of rifampicin therapy and the optimal initiation time for rifampicin treatment on prognosis in methicillin-sensitive S. aureus bacteraemia with a deep infection. Retrospective, multicentre study in Finland including 357 SAB patients with a deep infection focus. Patients with alcoholism, liver disease or patients who died within 3 days were excluded. Patients were categorised according to duration of rifampicin therapy and according to whether rifampicin was initiated early (within 7 days) or late (7 days after) after the positive blood cultures. Primary end point was 90 days mortality. Twenty-seven percent of patients received no rifampicin therapy, 14% received rifampicin for 1-13 days whereas 59% received rifampicin ≥14 days. The 90 day mortality was; 26% for patients treated without rifampicin, 16% for rifampicin therapy of any length and 10% for early onset rifampicin therapy ≥14 days. Lack of rifampicin therapy increased (OR 1.89, p=0.026), rifampicin of any duration decreased (OR 0.53, p=0.026) and rifampicin therapy ≥14 days with early onset lowered the risk for a fatal outcome (OR 0.33, p<0.01) during 90 days follow-up. Rifampicin adjunctive therapy for at least 14 days and initiated within 7 days of positive blood culture associated with improved outcome among SAB patients with a deep infection.

Host-cell interaction of attenuated and wild-type strains of yellow fever virus can be differentiated at early stages of hepatocyte infection.

PubMed

Lefeuvre, Anabelle; Contamin, Hugues; Decelle, Thierry; Fournier, Christophe; Lang, Jean; Deubel, Vincent; Marianneau, Philippe

2006-05-01

Yellow fever (YF) virus is currently found in tropical Africa and South America, and is responsible for a febrile to severe illness characterized by organ failure and shock. The attenuated YF 17D strain, used in YF vaccine, was derived from the wild-type strain Asibi. Although studies have been done on genetic markers of YF virulence, differentiation of the two strains in terms of host-cell interaction during infection remains elusive. As YF wild-type strains are hepatotropic, we chose a hepatic cell line (HepG2) to study YF virus-host cell interaction. HepG2 cells rapidly produced high titres of infectious viral particles for 17D and Asibi YF strains. However, HepG2 cells were more susceptible to the attenuated 17D virus infection, and only this virus strain induced early apoptosis in these cells. Molecular markers specific for the 17D virus were identified by microarray analysis and confirmed by quantitative RT-PCR analysis. As early as 1h postinfection, three genes, (IEX-1, IRF-1, DEC-1) all implicated in apoptosis pathways, were upregulated. Later in infection (48 h) two other genes (HSP70-1A and 1B), expressed in cases of cellular stress, were highly upregulated in 17D-infected HepG2 cells. The early specific upregulation of these cellular genes in HepG2 cells may be considered markers of the 17D virus. This study on the YF attenuated strain gives a new approach to the analysis of the factors involved in virus attenuation.

Staphylococcus aureus infections in Australasian neonatal nurseries.

PubMed

Isaacs, D; Fraser, S; Hogg, G; Li, H Y

2004-07-01

To study the incidence and outcome of systemic infections with methicillin sensitive (MSSA) and methicillin resistant Staphylococcus aureus (MRSA) infections in Australasian neonatal nurseries. Prospective longitudinal study of systemic infections (clinical sepsis plus positive cultures of blood and/or cerebrospinal fluid) in 17 Australasian neonatal nurseries. The incidence of early onset sepsis with S aureus, mainly MSSA, was 19 cases per 244 718 live births or 0.08 per 1000. From 1992 to 1994, MRSA infections caused only 8% of staphylococcal infections. From 1995 to 1998, there was an outbreak of MRSA infection, in two Melbourne hospitals. The outbreak resolved, after the use of topical mupirocin and improved handwashing. Babies with MRSA sepsis were significantly smaller than babies with MSSA sepsis (mean birth weight 1093 v 1617 g) and more preterm (mean gestation 27.5 v 30.3 weeks). The mortality of MRSA sepsis was 24.6% compared with 9.9% for MSSA infections. The mortality of early onset MSSA sepsis, however, was 39% (seven of 18) compared with 7.3% of late onset MSSA infection presenting more than two days after birth. S aureus is a rare but important cause of early onset sepsis. Late onset MRSA infections carried a higher mortality than late onset MSSA infections, but babies with early onset MSSA sepsis had a particularly high mortality.

γδ T Cells Regulate the Early Inflammatory Response to Bordetella pertussis Infection in the Murine Respiratory Tract

PubMed Central

Zachariadis, O.; Cassidy, J. P.; Brady, J.; Mahon, B. P.

2006-01-01

The role of γδ T cells in the regulation of pulmonary inflammation following Bordetella pertussis infection was investigated. Using a well-characterized murine aerosol challenge model, inflammatory events in mice with targeted disruption of the T-cell receptor δ-chain gene (γδ TCR−/− mice) were compared with those in wild-type animals. Early following challenge with B. pertussis, γδ TCR−/− mice exhibited greater pulmonary inflammation, as measured by intra-alveolar albumin leakage and lesion histomorphometry, yet had lower contemporaneous bacterial lung loads. The larger numbers of neutrophils and macrophages and the greater concentration of the neutrophil marker myeloperoxidase in bronchoalveolar lavage fluid from γδ TCR−/− mice at this time suggested that differences in lung injury were mediated through increased leukocyte trafficking into infected alveoli. Furthermore, flow cytometric analysis found the pattern of recruitment of natural killer (NK) and NK receptor+ T cells into airspaces differed between the two mouse types over the same time period. Taken together, these findings suggest a regulatory influence for γδ T cells over the early pulmonary inflammatory response to bacterial infection. The absence of γδ T cells also influenced the subsequent adaptive immune response to specific bacterial components, as evidenced by a shift from a Th1 to a Th2 type response against the B. pertussis virulence factor filamentous hemagglutinin in γδ TCR−/− mice. The findings are relevant to the study of conditions such as neonatal B. pertussis infection and acute respiratory distress syndrome where γδ T cell dysfunction has been implicated in the inflammatory process. PMID:16495558

Early Adolescent Friendship Selection Based on Externalizing Behavior: the Moderating Role of Pubertal Development. The SNARE Study.

PubMed

Franken, Aart; Prinstein, Mitchell J; Dijkstra, Jan Kornelis; Steglich, Christian E G; Harakeh, Zeena; Vollebergh, Wilma A M

2016-11-01

This study examined friendship (de-)selection processes in early adolescence. Pubertal development was examined as a potential moderator. It was expected that pubertal development would be associated with an increased tendency for adolescents to select their friends based on their similarities in externalizing behavior engagement (i.e., delinquency, alcohol use, and tobacco use). Data were used from the first three waves of the SNARE (Social Network Analysis of Risk behavior in Early adolescence) study (N = 1144; 50 % boys; M age  = 12.7; SD = 0.47), including students who entered the first year of secondary school. The hypothesis was tested using Stochastic Actor-Based Modeling in SIENA. While taking the network structure into account, and controlling for peer influence effects, the results supported this hypothesis. Early adolescents with higher pubertal development were as likely as their peers to select friends based on similarity in externalizing behavior and especially likely to remain friends with peers who had a similar level of externalizing behavior, and thus break friendship ties with dissimilar friends in this respect. As early adolescents are actively engaged in reorganizing their social context, adolescents with a higher pubertal development are especially likely to lose friendships with peers who do not engage in externalizing behavior, thus losing an important source of adaptive social control (i.e., friends who do not engage in externalizing behavior).

Detection of autoimmunity in early primary Epstein-Barr virus infection by Western blot analysis.

PubMed

Mascia, M T; Sandri, G; Guerzoni, C; Roncaglia, R; Mantovani, G; Ferri, C

2008-01-01

The Epstein-Barr virus (EBV) represents a potentially important factor in the pathogenesis of certain autoimmune disorders such as systemic lupus erythematosus (SLE), and Sjögren's syndrome, probably through a molecular mimicry mechanism. Several studies have focused on the relationship between previous EBV infection and clinically overt connective tissue diseases (CTDs), while the aim of this study was to investigate the immunological alterations during the early phase of primary acute EBV infection by means of ENA Western blotting (WB) analysis. This technique is able to detect a wide spectrum of anti-ENA autoantibodies, potentially directed against diverse epitopes of the same antigen. Sera from 54 subjects (F/M=24/30, mean age 17+/-6 SD years) with primary acute EBV infection were analysed using indirect immunofluorescence (IF) on Hep-2 cells for ANA, and both ELISA and WB for ENA. Only 8 ANA+ and no ENA+ were found by means of IF and ELISA techniques, respectively; however, one or more ENA autoantibodies were detected in 24/54 (44%) sera using WB. The autoantibodies were no longer present at the second evaluation. Subjects with immunological alterations had not developed any significant clinical manifestations at a 5-year follow-up. This study demonstrated the appearance of autoantibody production in a high proportion of individuals with primary acute EBV infection; interestingly, the observed serological subsets are quite similar to clinical SLE clusters. Moreover, the absence of immunological disorders during the follow-up reinforces the role of multiple genetic and/or environmental co-factors in the pathogenesis of CTDs.

Usefulness of quantitative polymerase chain reaction in amniotic fluid as early prognostic marker of fetal infection with Toxoplasma gondii.

PubMed

Romand, Stéphane; Chosson, Muriel; Franck, Jacqueline; Wallon, Martine; Kieffer, François; Kaiser, Karine; Dumon, Henri; Peyron, François; Thulliez, Philippe; Picot, Stéphane

2004-03-01

Our purpose was to evaluate Toxoplasma gondii concentration in amniotic fluid (AF) samples as a prognostic marker of congenital toxoplasmosis. A retrospective study was carried out in 88 consecutive AF samples from 86 pregnant women, which were found positive by prospective polymerase chain reaction (PCR) testing. Parasite AF concentrations were estimated by real-time quantitative PCR and analyzed in relation to the clinical outcome of infected fetuses during pregnancy and at birth, taking into account the gestational age at maternal infection. A significant negative linear regression was observed between gestational age at maternal infection and T gondii DNA loads in AF. After adjusting for time at maternal seroconversion by multivariate analysis, higher parasite concentrations were significantly associated with a severe outcome of congenital infection (odds ratio [OR]=15.38/log (parasites/mL AF) [95% CI=2.45-97.7]). PCR quantification of T gondii in AF can be highly contributive for early prognosis of congenital toxoplasmosis. Maternal infections acquired before 20 weeks with a parasite load greater than 100/mL of AF have the highest risk of severe fetal outcome.

Fluidity of HIV-1-Specific T-Cell Responses during Acute and Early Subtype C HIV-1 Infection and Associations with Early Disease Progression ▿

PubMed Central

Mlotshwa, Mandla; Riou, Catherine; Chopera, Denis; de Assis Rosa, Debra; Ntale, Roman; Treunicht, Florette; Woodman, Zenda; Werner, Lise; van Loggerenberg, Francois; Mlisana, Koleka; Abdool Karim, Salim; Williamson, Carolyn; Gray, Clive M.

2010-01-01

Deciphering immune events during early stages of human immunodeficiency virus type 1 (HIV-1) infection is critical for understanding the course of disease. We characterized the hierarchy of HIV-1-specific T-cell gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay responses during acute subtype C infection in 53 individuals and associated temporal patterns of responses with disease progression in the first 12 months. There was a diverse pattern of T-cell recognition across the proteome, with the recognition of Nef being immunodominant as early as 3 weeks postinfection. Over the first 6 months, we found that there was a 23% chance of an increased response to Nef for every week postinfection (P = 0.0024), followed by a nonsignificant increase to Pol (4.6%) and Gag (3.2%). Responses to Env and regulatory proteins appeared to remain stable. Three temporal patterns of HIV-specific T-cell responses could be distinguished: persistent, lost, or new. The proportion of persistent T-cell responses was significantly lower (P = 0.0037) in individuals defined as rapid progressors than in those progressing slowly and who controlled viremia. Almost 90% of lost T-cell responses were coincidental with autologous viral epitope escape. Regression analysis between the time to fixed viral escape and lost T-cell responses (r = 0.61; P = 0.019) showed a mean delay of 14 weeks after viral escape. Collectively, T-cell epitope recognition is not a static event, and temporal patterns of IFN-γ-based responses exist. This is due partly to viral sequence variation but also to the recognition of invariant viral epitopes that leads to waves of persistent T-cell immunity, which appears to associate with slower disease progression in the first year of infection. PMID:20826686

MHC-driven HIV-1 control on the long run is not systematically determined at early times post-HIV-1 infection.

PubMed

Antoni, Guillemette; Guergnon, Julien; Meaudre, Céline; Samri, Assia; Boufassa, Faroudy; Goujard, Cécile; Lambotte, Olivier; Autran, Brigitte; Rouzioux, Christine; Costagliola, Dominique; Meyer, Laurence; Theodorou, Ioannis

2013-07-17

Human leukocyte antigen (HLA) class I-driven long-term protection against HIV-1 is mainly associated with HLA-B*27 and HLA-B*57. This effect is observed early after infection. Clarification needs to be established concerning the moment of action for the other HLA-B or HLA-C alleles. HLA-B and HLA-C alleles from 111 individuals that control HIV-1 disease for over 8 years and from 747 seroconverters frequencies were compared. Also, HLA-B and HLA-C influence on early levels of plasma HIV-RNA, cellular HIV-DNA, CD4, CD8 and CD4/CD8 ratio was evaluated among the seroconverters. We performed univariate, multivariate and haplotypic analyses in order to disentangle the respective contribution of the HLA-B and HLA-C genes. The haplotypes analysis shows three patterns of protective effects of HLA-B and HLA-C alleles or haplotypes. First, the HLA B*57, HLA-B*27, HLA-B*13 and HLA-C*14 alleles, which have a strong effect on long-term disease control, also influence at least one of the early infection phenotypes. Second, HLA-B*52 has a strong effect during early time points on HIV-RNA without significant effect on the long-term control of HIV-1. Finally, the HLA-B*14-C*08 haplotype has a strong effect on the long-term protection, without influencing early viral control. Our study highlighted independent effects of HLA-B and HLA-C alleles on HIV-disease progression. Furthermore, some alleles appeared to be specifically associated with either long-term control or early virological parameters, suggesting different immunological mechanisms according to the disease stages.

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

PubMed Central

Feldman, Amy S.; He, Yuan; Moore, Martin L.; Hershenson, Marc B.

2015-01-01

A first step in primary disease prevention is identifying common, modifiable risk factors that contribute to a significant proportion of disease development. Infant respiratory viral infection and childhood asthma are the most common acute and chronic diseases of childhood, respectively. Common clinical features and links between these diseases have long been recognized, with early-life respiratory syncytial virus (RSV) and rhinovirus (RV) lower respiratory tract infections (LRTIs) being strongly associated with increased asthma risk. However, there has long been debate over the role of these respiratory viruses in asthma inception. In this article, we systematically review the evidence linking early-life RSV and RV LRTIs with asthma inception and whether they could therefore be targets for primary prevention efforts. PMID:25369458

Impact of operative time on early joint infection and deep vein thrombosis in primary total hip arthroplasty.

PubMed

Wills, B W; Sheppard, E D; Smith, W R; Staggers, J R; Li, P; Shah, A; Lee, S R; Naranje, S M

2018-03-22

Infections and deep vein thrombosis (DVT) after total hip arthroplasty (THA) are challenging problems for both the patient and surgeon. Previous studies have identified numerous risk factors for infections and DVT after THA but have often been limited by sample size. We aimed to evaluate the effect of operative time on early postoperative infection as well as DVT rates following THA. We hypothesized that an increase in operative time would result in increased odds of acquiring an infection as well as a DVT. We conducted a retrospective analysis of prospectively collected data using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database from 2006 to 2015 for all patients undergoing primary THA. Associations between operative time and infection or DVT were evaluated with multivariable logistic regressions controlling for demographics and several known risks factors for infection. Three different types of infections were evaluated: (1) superficial surgical site infection (SSI), an infection involving the skin or subcutaneous tissue, (2) deep SSI, an infection involving the muscle or fascial layers beneath the subcutaneous tissue, and (3) organ/space infection, an infection involving any part of the anatomy manipulated during surgery other than the incisional components. In total, 103,044 patients who underwent THA were included in our study. Our results suggested a significant association between superficial SSIs and operative time. Specifically, the adjusted odds of suffering a superficial SSI increased by 6% (CI=1.04-1.08, p<0.0001) for every 10-minute increase of operative time. When using dichotomized operative time (<90minutes or >90minutes), the adjusted odds of suffering a superficial SSI was 56% higher for patients with prolonged operative time (CI=1.05-2.32, p=0.0277). The adjusted odds of suffering a deep SSI increased by 7% for every 10-minute increase in operative time (CI=1.01-1.14, p=0.0335). No significant

Th1/Th2 balance and humoral immune response to potential antigens as early diagnostic method of equine Strongylus nematode infection.

PubMed

Abo-Aziza, Faten A M; Hendawy, Seham H M; Namaky, Amira H El; Ashry, Heba M

2017-06-01

The aim of this study was to investigate the early diagnosis of strongyle infection based on early changes in Th1 and Th2 cytokines beside the diagnostic accuracy values and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting profiles using prepared strongyles antigens. A total of 73 donkeys had a mean age of 4-32 years old were parasitologically examined for strongyle infection. The early changes in Th1 and Th2 cytokines were determined, and the diagnostic accuracy values and SDS-PAGE and western blotting profiles were performed using prepared strongyles antigens; crude somatic Strongylus vulgaris (CSS), excretory-secretory S. vulgaris (ESS), crude somatic Cyathostomins (CSC), and excretory-secretory Cyathostomins (ESC). The results revealed highest 437.04% and lowest 37.81% immunoglobulin G (IgG) in high and low egg shedder groups when using ESC and CSS antigens, respectively. Antibodies index for ESS and CSC were significantly higher in moderate egg shedder group while that for ESS and CSC, ESC was significantly higher in high egg shedder group. Tumor necrosis factor alpha (TNF-α)/interleukin-4 (IL-4) balance in S. vulgaris infected donkeys was approximately equal in apparently healthy, low and high egg shedder groups while TNF-α < IL-4 in moderate egg shedder. In Cyathostomins infected animals, TNF-α/IL-4 balance was approximately equal in apparently healthy group while it was low in moderate and high egg shedder groups. The diagnostic accuracy showed that the higher specificity (46.6%) and prevalence (95.40%) were recorded by CSS and ESC antigens, respectively. However, SDS-PAGE and western blotting profiling proved that the band at molecular weight 25 kDa is exhibited by CSS antigen. Combination of detecting level of TNF-α/IL-4 balance, CSS antigen and IgG concentration is good tool for appropriate diagnosis of such infection. More advancement research must be done concerning Th1/Th2 balance and cross-reactivity of S

Th1/Th2 balance and humoral immune response to potential antigens as early diagnostic method of equine Strongylus nematode infection

PubMed Central

Abo-Aziza, Faten A. M.; Hendawy, Seham H. M.; Namaky, Amira H. El; Ashry, Heba M.

2017-01-01

Aim:: The aim of this study was to investigate the early diagnosis of strongyle infection based on early changes in Th1 and Th2 cytokines beside the diagnostic accuracy values and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting profiles using prepared strongyles antigens. Materials and Methods:: A total of 73 donkeys had a mean age of 4-32 years old were parasitologically examined for strongyle infection. The early changes in Th1 and Th2 cytokines were determined, and the diagnostic accuracy values and SDS-PAGE and western blotting profiles were performed using prepared strongyles antigens; crude somatic Strongylus vulgaris (CSS), excretory-secretory S. vulgaris (ESS), crude somatic Cyathostomins (CSC), and excretory-secretory Cyathostomins (ESC). Results:: The results revealed highest 437.04% and lowest 37.81% immunoglobulin G (IgG) in high and low egg shedder groups when using ESC and CSS antigens, respectively. Antibodies index for ESS and CSC were significantly higher in moderate egg shedder group while that for ESS and CSC, ESC was significantly higher in high egg shedder group. Tumor necrosis factor alpha (TNF-α)/interleukin-4 (IL-4) balance in S. vulgaris infected donkeys was approximately equal in apparently healthy, low and high egg shedder groups while TNF-α < IL-4 in moderate egg shedder. In Cyathostomins infected animals, TNF-α/IL-4 balance was approximately equal in apparently healthy group while it was low in moderate and high egg shedder groups. The diagnostic accuracy showed that the higher specificity (46.6%) and prevalence (95.40%) were recorded by CSS and ESC antigens, respectively. However, SDS-PAGE and western blotting profiling proved that the band at molecular weight 25 kDa is exhibited by CSS antigen. Conclusion:: Combination of detecting level of TNF-α/IL-4 balance, CSS antigen and IgG concentration is good tool for appropriate diagnosis of such infection. More advancement research must be done

Reduced mortality associated with breast-feeding-acquired HIV infection and breast-feeding among HIV-infected children in Zambia.

PubMed

Fox, Matthew P; Brooks, Daniel; Kuhn, Louise; Aldrovandi, Grace; Sinkala, Moses; Kankasa, Chipepo; Mwiya, Mwiya; Horsburgh, Robert; Thea, Donald M

2008-05-01

In developing countries, where mother-to-child transmission of HIV through breast-feeding is common, little is known about the impact of postpartum transmission on child survival. This study assessed whether children infected postpartum have longer survival from time of infection versus those infected during gestation or delivery. We used a prospective cohort study to analyze data from 213 HIV-infected children enrolled in a breast-feeding intervention trial in Lusaka, Zambia (2001 to 2004). We compared mortality 1 year after HIV infection in children stratified by age of infection: 0 to 3 days (intrauterine [IU] group), 4 to 40 days (intrapartum/early postpartum [IP/EPP] group), and >40 days (postpartum [PP] group). A total of 61, 71, and 81 children were infected in the IU, IP/EPP, and PP groups, respectively. Children with intrauterine or intrapartum/early postpartum transmission had higher mortality over the first 12 months after infection than children with postpartum transmission (P = 0.001 and P = 0.006, respectively); no differences were detected between children with intrauterine and intrapartum/early postpartum transmission. Nearly 20% of the IU and IP/EPP groups died by 100 days after infection, whereas nearly 10% of the PP group had died by this time. After adjusting for birth weight, maternal CD4 cell count, breast-feeding, and maternal death, children infected postpartum had one quarter the mortality rate (hazard ratio [HR] = 0.27, 95% confidence interval [CI]: 0.15 to 0.50) of those infected in utero. Stopping breast-feeding increased mortality in infected children (HR = 3.1, 95% CI: 1.8 to 5.3). This study demonstrates a survival benefit among children infected postpartum versus children infected during pregnancy or delivery and a benefit to increased breast-feeding duration among infected children. Testing children for HIV early may provide a means to allow for earlier intervention.

Characterization of Early-Phase Neutrophil Extracellular Traps in Urinary Tract Infections

PubMed Central

Yu, Yanbao; Kwon, Keehwan; Tsitrin, Tamara; Sikorski, Patricia; Nelson, Karen E.; Pieper, Rembert

2017-01-01

Neutrophils have an important role in the antimicrobial defense and resolution of urinary tract infections (UTIs). Our research suggests that a mechanism known as neutrophil extracellular trap (NET) formation is a defense strategy to combat pathogens that have invaded the urinary tract. A set of human urine specimens with very high neutrophil counts had microscopic evidence of cellular aggregation and lysis. Deoxyribonuclease I (DNase) treatment resulted in disaggregation of such structures, release of DNA fragments and a proteome enriched in histones and azurophilic granule effectors whose quantitative composition was similar to that of previously described in vitro-formed NETs. The effector proteins were further enriched in DNA-protein complexes isolated in native PAGE gels. Immunofluorescence microscopy revealed a flattened morphology of neutrophils associated with decondensed chromatin, remnants of granules in the cell periphery, and myeloperoxidase co-localized with extracellular DNA, features consistent with early-phase NETs. Nuclear staining revealed that a considerable fraction of bacterial cells in these structures were dead. The proteomes of two pathogens, Staphylococcus aureus and Escherichia coli, were indicative of adaptive responses to early-phase NETs, specifically the release of virulence factors and arrest of ribosomal protein synthesis. Finally, we discovered patterns of proteolysis consistent with widespread cleavage of proteins by neutrophil elastase, proteinase 3 and cathepsin G and evidence of citrullination in many nuclear proteins. PMID:28129394

Proteomic Profile of Brucella abortus-Infected Bovine Chorioallantoic Membrane Explants

PubMed Central

Mol, Juliana P. S.; Pires, Simone F.; Chapeaurouge, Alexander D.; Perales, Jonas; Santos, Renato L.; Andrade, Hélida M.; Lage, Andrey P.

2016-01-01

Brucella abortus is the etiological agent of bovine brucellosis, a zoonotic disease that causes significant economic losses worldwide. The differential proteomic profile of bovine chorioallantoic membrane (CAM) explants at early stages of infection with B. abortus (0.5, 2, 4, and 8 h) was determined. Analysis of CAM explants at 0.5 and 4 h showed the highest differences between uninfected and infected CAM explants, and therefore were used for the Differential Gel Electrophoresis (DIGE). A total of 103 spots were present in only one experimental group and were selected for identification by mass spectrometry (MALDI/ToF-ToF). Proteins only identified in extracts of CAM explants infected with B. abortus were related to recognition of PAMPs by TLR, production of reactive oxygen species, intracellular trafficking, and inflammation. PMID:27104343

Host and bacterial factors that regulate LC3 recruitment to Listeria monocytogenes during the early stages of macrophage infection.

PubMed

Lam, Grace Y; Cemma, Marija; Muise, Aleixo M; Higgins, Darren E; Brumell, John H

2013-07-01

Listeria monocytogenes is a bacterial pathogen that can escape the phagosome and replicate in the cytosol of host cells during infection. We previously observed that a population (up to 35%) of L. monocytogenes strain 10403S colocalize with the macroautophagy marker LC3 at 1 h postinfection. This is thought to give rise to spacious Listeria-containing phagosomes (SLAPs), a membrane-bound compartment harboring slow-growing bacteria that is associated with persistent infection. Here, we examined the host and bacterial factors that mediate LC3 recruitment to bacteria at 1 h postinfection. At this early time point, LC3(+) bacteria were present within single-membrane phagosomes that are LAMP1(+). Protein ubiquitination is known to play a role in targeting cytosolic L. monocytogenes to macroautophagy. However, we found that neither protein ubiquitination nor the ubiquitin-binding adaptor SQSTM1/p62 are associated with LC3(+) bacteria at 1 h postinfection. Reactive oxygen species (ROS) production by the CYBB/NOX2 NADPH oxidase was also required for LC3 recruitment to bacteria at 1 h postinfection and for subsequent SLAP formation. Diacylglycerol is an upstream activator of the CYBB/NOX2 NADPH oxidase, and its production by both bacterial and host phospholipases was required for LC3 recruitment to bacteria. Our data suggest that the LC3-associated phagocytosis (LAP) pathway, which is distinct from macroautophagy, targets L. monocytogenes during the early stage of infection within host macrophages and allows establishment of an intracellular niche (SLAPs) associated with persistent infection.

Improved Variable Selection Algorithm Using a LASSO-Type Penalty, with an Application to Assessing Hepatitis B Infection Relevant Factors in Community Residents

PubMed Central

Guo, Pi; Zeng, Fangfang; Hu, Xiaomin; Zhang, Dingmei; Zhu, Shuming; Deng, Yu; Hao, Yuantao

2015-01-01

Objectives In epidemiological studies, it is important to identify independent associations between collective exposures and a health outcome. The current stepwise selection technique ignores stochastic errors and suffers from a lack of stability. The alternative LASSO-penalized regression model can be applied to detect significant predictors from a pool of candidate variables. However, this technique is prone to false positives and tends to create excessive biases. It remains challenging to develop robust variable selection methods and enhance predictability. Material and methods Two improved algorithms denoted the two-stage hybrid and bootstrap ranking procedures, both using a LASSO-type penalty, were developed for epidemiological association analysis. The performance of the proposed procedures and other methods including conventional LASSO, Bolasso, stepwise and stability selection models were evaluated using intensive simulation. In addition, methods were compared by using an empirical analysis based on large-scale survey data of hepatitis B infection-relevant factors among Guangdong residents. Results The proposed procedures produced comparable or less biased selection results when compared to conventional variable selection models. In total, the two newly proposed procedures were stable with respect to various scenarios of simulation, demonstrating a higher power and a lower false positive rate during variable selection than the compared methods. In empirical analysis, the proposed procedures yielding a sparse set of hepatitis B infection-relevant factors gave the best predictive performance and showed that the procedures were able to select a more stringent set of factors. The individual history of hepatitis B vaccination, family and individual history of hepatitis B infection were associated with hepatitis B infection in the studied residents according to the proposed procedures. Conclusions The newly proposed procedures improve the identification of

Association of Kidney Function and Early Kidney Injury With Incident Hypertension in HIV-Infected Women.

PubMed

Ascher, Simon B; Scherzer, Rebecca; Peralta, Carmen A; Tien, Phyllis C; Grunfeld, Carl; Estrella, Michelle M; Abraham, Alison; Gustafson, Deborah R; Nowicki, Marek; Sharma, Anjali; Cohen, Mardge H; Butch, Anthony W; Young, Mary A; Bennett, Michael R; Shlipak, Michael G

2017-02-01

Subclinical kidney disease is associated with developing hypertension in the general population, but data are lacking among HIV-infected people. We examined associations of kidney function and injury with incident hypertension in 823 HIV-infected and 267 HIV-uninfected women in the Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-infected and uninfected women in the United States. Baseline kidney biomarkers included estimated glomerular filtration rate using cystatin C, urine albumin-to-creatinine ratio, and 7 urine biomarkers of tubular injury: α-1-microglobulin, interleukin-18, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, liver fatty acid-binding protein, N-acetyl-β-d-glucosaminidase, and α1-acid-glycoprotein. We used multivariable Poisson regression to evaluate associations of kidney biomarkers with incident hypertension, defined as 2 consecutive visits of antihypertensive medication use. During a median follow-up of 9.6 years, 288 HIV-infected women (35%) developed hypertension. Among the HIV-infected women, higher urine albumin-to-creatinine ratio was independently associated with incident hypertension (relative risk =1.13 per urine albumin-to-creatinine ratio doubling, 95% confidence interval, 1.07-1.20), as was lower estimated glomerular filtration rate (relative risk =1.10 per 10 mL/min/1.73 m 2 lower estimated glomerular filtration rate; 95% confidence interval, 1.04-1.17). No tubular injury and dysfunction biomarkers were independently associated with incident hypertension in HIV-infected women. In contrast, among the HIV-uninfected women, urine albumin-to-creatinine ratio was not associated with incident hypertension, whereas higher urine interleukin-18, α1-acid-glycoprotein, and N-acetyl-β-d-glucosaminidase levels were significantly associated with incident hypertension. These findings suggest that early glomerular injury and kidney dysfunction may be involved in the pathogenesis of hypertension in

Early-Life Exposure to Outdoor Air Pollution and Respiratory Health, Ear Infections, and Eczema in Infants from the INMA Study

PubMed Central

Pedersen, Marie; Garcia-Esteban, Raquel; Ballester, Ferran; Basterrechea, Mikel; Esplugues, Ana; Fernández-Somoano, Ana; Lertxundi, Aitana; Tardón, Adonina; Sunyer, Jordi

2012-01-01

Background: Prenatal and early-life periods may be critical windows for harmful effects of air pollution on infant health. Objectives: We studied the association of air pollution exposure during pregnancy and the first year of life with respiratory illnesses, ear infections, and eczema during the first 12–18 months of age in a Spanish birth cohort of 2,199 infants. Methods: We obtained parentally reported information on doctor-diagnosed lower respiratory tract infections (LRTI) and parental reports of wheezing, eczema, and ear infections. We estimated individual exposures to nitrogen dioxide (NO2) and benzene with temporally adjusted land use regression models. We used log-binomial regression models and a combined random-effects meta-analysis to estimate the effects of air pollution exposure on health outcomes across the four study locations. Results: A 10-µg/m3 increase in average NO2 during pregnancy was associated with LRTI [relative risk (RR) = 1.05; 95% CI: 0.98, 1.12] and ear infections (RR = 1.18; 95% CI: 0.98, 1.41). The RRs for an interquartile range (IQR) increase in NO2 were 1.08 (95% CI: 0.97, 1.21) for LRTI and 1.31 (95% CI: 0.97, 1.76) for ear infections. Compared with NO2, the association for an IQR increase in average benzene exposure was similar for LRTI (RR = 1.06; 95% CI: 0.94, 1.19) and slightly lower for ear infections (RR = 1.17; 95% CI: 0.93, 1.46). Associations were slightly stronger among infants whose mothers spent more time at home during pregnancy. Air pollution exposure during the first year was highly correlated with prenatal exposure, so we were unable to discern the relative importance of each exposure period. Conclusions: Our findings support the hypothesis that early-life exposure to ambient air pollution may increase the risk of upper and lower respiratory tract infections in infants. PMID:23221880

Selective testing strategies for diagnosing group A streptococcal infection in children with pharyngitis: a systematic review and prospective multicentre external validation study

PubMed Central

Cohen, Jérémie F.; Cohen, Robert; Levy, Corinne; Thollot, Franck; Benani, Mohamed; Bidet, Philippe; Chalumeau, Martin

2015-01-01

Background: Several clinical prediction rules for diagnosing group A streptococcal infection in children with pharyngitis are available. We aimed to compare the diagnostic accuracy of rules-based selective testing strategies in a prospective cohort of children with pharyngitis. Methods: We identified clinical prediction rules through a systematic search of MEDLINE and Embase (1975–2014), which we then validated in a prospective cohort involving French children who presented with pharyngitis during a 1-year period (2010–2011). We diagnosed infection with group A streptococcus using two throat swabs: one obtained for a rapid antigen detection test (StreptAtest, Dectrapharm) and one obtained for culture (reference standard). We validated rules-based selective testing strategies as follows: low risk of group A streptococcal infection, no further testing or antibiotic therapy needed; intermediate risk of infection, rapid antigen detection for all patients and antibiotic therapy for those with a positive test result; and high risk of infection, empiric antibiotic treatment. Results: We identified 8 clinical prediction rules, 6 of which could be prospectively validated. Sensitivity and specificity of rules-based selective testing strategies ranged from 66% (95% confidence interval [CI] 61–72) to 94% (95% CI 92–97) and from 40% (95% CI 35–45) to 88% (95% CI 85–91), respectively. Use of rapid antigen detection testing following the clinical prediction rule ranged from 24% (95% CI 21–27) to 86% (95% CI 84–89). None of the rules-based selective testing strategies achieved our diagnostic accuracy target (sensitivity and specificity > 85%). Interpretation: Rules-based selective testing strategies did not show sufficient diagnostic accuracy in this study population. The relevance of clinical prediction rules for determining which children with pharyngitis should undergo a rapid antigen detection test remains questionable. PMID:25487666

Urinary Tract Infections: Leading Initiatives in Selecting Empiric Outpatient Treatment (UTILISE)

PubMed Central

Landry, Eric; Sulz, Linda; Bell, Ali; Rathgeber, Lane; Balogh, Heather

2014-01-01

change in overall antibiotic selection (OR 0.25, 95% CI 0.11–0.58; p < 0.001). Further analysis suggested that this significant change was driven by a decrease in use of ciprofloxacin, from 32% (31/96) to 11% (8/76). Conclusion: Creation of a best-practice algorithm and education focused on emergency physicians significantly increased adherence to best practice and optimized antibiotic prescribing for outpatients with uncomplicated urinary tract infection by limiting overuse of fluoroquinolones, primarily ciprofloxacin. PMID:24799721

Field levels of infection of progenies of western white pines selected for blister rust resistance

Treesearch

R. J. Steinhoff

1971-01-01

Western white pine trees resulting from crosses of parents selected for phenotypic resistance to Cronartium ribicola J. C. Fisch. ex Rabenh., the white pine blister rust, were inspected for rust infection after 11 to 15 years in two field plots. When compared to controls and to natural reproduction, the progenies of crosses involving trees that exhibited general...

Resistance to gastrointestinal nematodes in dairy sheep: Genetic variability and relevance of artificial infection of nucleus rams to select for resistant ewes on farms.

PubMed

Aguerre, S; Jacquiet, P; Brodier, H; Bournazel, J P; Grisez, C; Prévot, F; Michot, L; Fidelle, F; Astruc, J M; Moreno, C R

2018-05-30

Breeding sheep for enhanced resistance to gastrointestinal parasites is a promising strategy to limit the use of anthelmintics due to the now widespread resistance of parasites to these molecules. This paper reports the genetic parameters estimated for parasite resistance and resilience traits in the Blond-faced Manech dairy sheep breed and the putative impacts of the selection for resistance to gastrointestinal nematodes (GIN) on farms. Two datasets were used. First, the rams of the selection scheme were artificially infected twice with L3 Haemonchus contortus larvae. Faecal egg counts (FEC) and packed cell volume (PCV) loss were measured 30 days after each infection. Secondly, the FEC, PCV and body condition score (BCS) (1-6 measures per ewe) of naturally infected ewes on farms were measured in the spring, summer and autumn over a two-year period. Genetic parameters were estimated for each dataset independently but also globally based on the pedigree connections between the two datasets. For the experimentally infected sires, the FEC following the second infection was moderately heritable (heritability: 0.35) and strongly correlated with FEC after the first infection (genetic correlation: 0.92). For the naturally infected ewes, FEC was also heritable (0.18). Using the two datasets together, a genetic correlation of 0.56-0.71 was estimated between the FEC values of the experimentally infected rams and naturally infected ewes. Consequently, the genetic variability of parasite resistance is similar whatever the physiological status (males or milking/pregnant ewes) and the infection conditions (experimental infection with one parasite or natural infection with several parasites). In practice, when the sire population is divided into two groups based on their genetic value, the FEC of the ewes born to the 50% most resistant sires is half that of the ewes born to the 50% most susceptible sires. Our study shows the feasibility and efficiency of genetic selection for

Biomarker Discovery for Early Detection of Hepatocellular Carcinoma in Hepatitis C–infected Patients*

PubMed Central

Mustafa, Mehnaz G.; Petersen, John R.; Ju, Hyunsu; Cicalese, Luca; Snyder, Ned; Haidacher, Sigmund J.; Denner, Larry; Elferink, Cornelis

2013-01-01

Chronic hepatic disease damages the liver, and the resulting wound-healing process leads to liver fibrosis and the subsequent development of cirrhosis. The leading cause of hepatic fibrosis and cirrhosis is infection with hepatitis C virus (HCV), and of the patients with HCV-induced cirrhosis, 2% to 5% develop hepatocellular carcinoma (HCC), with a survival rate of 7%. HCC is one of the leading causes of cancer-related death worldwide, and the poor survival rate is largely due to late-stage diagnosis, which makes successful intervention difficult, if not impossible. The lack of sensitive and specific diagnostic tools and the urgent need for early-stage diagnosis prompted us to discover new candidate biomarkers for HCV and HCC. We used aptamer-based fractionation technology to reduce serum complexity, differentially labeled samples (six HCV and six HCC) with fluorescent dyes, and resolved proteins in pairwise two-dimensional difference gel electrophoresis. DeCyder software was used to identify differentially expressed proteins and spots picked, and MALDI-MS/MS was used to determine that ApoA1 was down-regulated by 22% (p < 0.004) in HCC relative to HCV. Differential expression quantified via two-dimensional difference gel electrophoresis was confirmed by means of 18O/16O stable isotope differential labeling with LC-MS/MS zoom scans. Technically independent confirmation was demonstrated by triple quadrupole LC-MS/MS selected reaction monitoring (SRM) assays with three peptides specific to human ApoA1 (DLATVYVDVLK, WQEEMELYR, and VSFLSALEEYTK) using 18O/16O-labeled samples and further verified with AQUA peptides as internal standards for quantification. In 50 patient samples (24 HCV and 26 HCC), all three SRM assays yielded highly similar differential expression of ApoA1 in HCC and HCV patients. These results validated the SRM assays, which were independently confirmed by Western blotting. Thus, ApoA1 is a candidate member of an SRM biomarker panel for early diagnosis

Does a regular Wessex Head Injury Matrix assessment identify early signs of infections in people with Prolonged Disorders of Consciousness?

PubMed

Dhamapurkar, Samira Kashinath; Wilson, Barbara A; Rose, Anita; Florschutz, Gerhard; Watson, Peter; Shiel, Agnes

2018-06-12

Patients with brain injury are at high risk for infections. Although infection and cognitive deterioration are established for people with dementia, this has not been shown for patients with a prolonged disorder of consciousness (PDOC). This study determines whether regular Wessex Head Injury Matrix (WHIM) assessments can identify early signs of infections in patients with PDOC. Retrospective and prospective approaches were used to assess the WHIM scores of patients with a PDOC (N = 21 in the retrospective study and 22 in the prospective study). The WHIM total scores decreased due to infections in 17 of the 21 cases of infection (p < 0.001) in the retrospective study and 15 (p = 0.001) of the 22 prospective cases of infection. Patients in a minimally conscious state (MCS) showed a bigger proportion of change between their baseline score and the scores taken in the pre-infection stage in both the retrospective and prospective studies when compared to patients in a vegetative state (VS). The findings suggest the importance of serial WHIM assessments throughout the period of recovery, not only to measure cognitive changes but also to highlight underlying physical changes such as infections that will impact the response to rehabilitation and recovery.

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

PubMed

Richardson, Simone I; Chung, Amy W; Natarajan, Harini; Mabvakure, Batsirai; Mkhize, Nonhlanhla N; Garrett, Nigel; Abdool Karim, Salim; Moore, Penny L; Ackerman, Margaret E; Alter, Galit; Morris, Lynn

2018-04-01

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

[Predictive value of interleukin 6 from the umbilical cord blood in early neonatal infection].

PubMed

Cosićkić, Almira; Skokić, Fahrija

2009-01-01

We have analyzed diagnostic value of interleukin 6 (IL-6) from the umbilical cord blood in recognition of early neonatal infection (ENI) of newborns whose mothers have obstetrical risks. The study included 120 newborns with birth weight <2500 gr., gestational age from 37 to 42 weeks, which mothers had some of the obstetrical risks. We established three groups: group A (newborns with microbiological proof of ENI), group B (clinical signs and hematological parameters of ENI) and group C (newborns without ENI). Median of IL-6 value in group A was 48.5 pg/ml with sensitivity, specificity and diagnostic value in recognition of ENI 78%, 81% and 80%. In group B median of IL-6 was 49 pg/ml with sensitivity, specificity and diagnostic value 65%, 80% and 77%. In group C median of IL-6 was 9.7 pg/ml. We noticed significant connection between value of IL-6 and mother's urinary tract infection; group A (p=0.023), group B (p = 0.007). Also there was a remarkable relationship between mother's colpitis and level of IL-6 in newborn with ENI in group A (p=0.011) and group B (p = 0.012). High levels of IL-6 in umbilical cord blood can help us in recognition of newborns that are endangered by infection and they are clearly connected with some of mother's obstetrical risks.

Species distribution in human immunodeficiency virus-related mycobacterial infections: implications for selection of initial treatment.

PubMed

Montessori, V; Phillips, P; Montaner, J; Haley, L; Craib, K; Bessuille, E; Black, W

1996-06-01

Management of mycobacterial infection is species specific; however, treatment is prompted by positive smears or cultures, often several weeks before species identification. The objective of this study was to determine the species distribution of mycobacterial isolates from various body sites in patients infected with human immunodeficiency virus (HIV). All mycobacterial isolates recovered at St. Paul's Hospital (Vancouver, British Columbia, Canada) from April 1989 to March 1993 were reviewed. Among 357 HIV-positive patients with mycobacterial infections, 64% (96) of the sputum isolates were Mycobacterium avium complex (MAC), 18% were Mycobacterium tuberculosis, and 17% were Mycobacterium kansasii. Lymph node involvement (25 patients) was due to either MAC (72%) or M. tuberculosis (24%). Two hundred ninety-eight episodes of mycobacteremia were due to MAC (98%), M. tuberculosis (1%), and M. kansasii (1%). Similarly, cultures of 84 bone marrow biopsy specimens (99%), 19 intestinal biopsy specimens (100%), and 30 stool specimens (97%) yielded predominantly MAC. These results have implications for initial therapy, particularly in areas where rapid methods for species identification are not readily available. Because of considerable geographic variation, development of guidelines for selection of initial therapy depends on regional determination of species distribution in HIV-related mycobacterial infections.

Selective pre-priming of HA-specific CD4 T cells restores immunological reactivity to HA on heterosubtypic influenza infection.

PubMed

Alam, Shabnam; Chan, Cory; Qiu, Xing; Shannon, Ian; White, Chantelle L; Sant, Andrea J; Nayak, Jennifer L

2017-01-01

A hallmark of the immune response to influenza is repeated encounters with proteins containing both genetically conserved and variable components. Therefore, the B and T cell repertoire is continually being remodeled, with competition between memory and naïve lymphocytes. Our previous work using a mouse model of secondary heterosubtypic influenza infection has shown that this competition results in a focusing of CD4 T cell response specificity towards internal virion proteins with a selective decrease in CD4 T cell reactivity to the novel HA epitopes. Strikingly, this shift in CD4 T cell specificity was associated with a diminished anti-HA antibody response. Here, we sought to determine whether the loss in HA-specific reactivity that occurs as a consequence of immunological memory could be reversed by selectively priming HA-specific CD4 T cells prior to secondary infection. Using a peptide-based priming strategy, we found that selective expansion of the anti-HA CD4 T cell memory repertoire enhanced HA-specific antibody production upon heterosubtypic infection. These results suggest that the potentially deleterious consequences of repeated exposure to conserved influenza internal virion proteins could be reversed by vaccination strategies that selectively arm the HA-specific CD4 T cell compartment. This could be a potentially useful pre-pandemic vaccination strategy to promote accelerated neutralizing antibody production on challenge with a pandemic influenza strain that contains few conserved HA epitopes.

Fiber array based hyperspectral Raman imaging for chemical selective analysis of malaria-infected red blood cells.

PubMed

Brückner, Michael; Becker, Katja; Popp, Jürgen; Frosch, Torsten

2015-09-24

A new setup for Raman spectroscopic wide-field imaging is presented. It combines the advantages of a fiber array based spectral translator with a tailor-made laser illumination system for high-quality Raman chemical imaging of sensitive biological samples. The Gaussian-like intensity distribution of the illuminating laser beam is shaped by a square-core optical multimode fiber to a top-hat profile with very homogeneous intensity distribution to fulfill the conditions of Koehler. The 30 m long optical fiber and an additional vibrator efficiently destroy the polarization and coherence of the illuminating light. This homogeneous, incoherent illumination is an essential prerequisite for stable quantitative imaging of complex biological samples. The fiber array translates the two-dimensional lateral information of the Raman stray light into separated spectral channels with very high contrast. The Raman image can be correlated with a corresponding white light microscopic image of the sample. The new setup enables simultaneous quantification of all Raman spectra across the whole spatial area with very good spectral resolution and thus outperforms other Raman imaging approaches based on scanning and tunable filters. The unique capabilities of the setup for fast, gentle, sensitive, and selective chemical imaging of biological samples were applied for automated hemozoin analysis. A special algorithm was developed to generate Raman images based on the hemozoin distribution in red blood cells without any influence from other Raman scattering. The new imaging setup in combination with the robust algorithm provides a novel, elegant way for chemical selective analysis of the malaria pigment hemozoin in early ring stages of Plasmodium falciparum infected erythrocytes. Copyright © 2015 Elsevier B.V. All rights reserved.

Early detection and classification of powdery mildew-infected rose leaves using ANFIS based on extracted features of thermal images

NASA Astrophysics Data System (ADS)

Jafari, Mehrnoosh; Minaei, Saeid; Safaie, Naser; Torkamani-Azar, Farah

2016-05-01

Spatial and temporal changes in surface temperature of infected and non-infected rose plant (Rosa hybrida cv. 'Angelina') leaves were visualized using digital infrared thermography. Infected areas exhibited a presymptomatic decrease in leaf temperature up to 2.3 °C. In this study, two experiments were conducted: one in the greenhouse (semi-controlled ambient conditions) and the other, in a growth chamber (controlled ambient conditions). Effect of drought stress and darkness on the thermal images were also studied in this research. It was found that thermal histograms of the infected leaves closely follow a standard normal distribution. They have a skewness near zero, kurtosis under 3, standard deviation larger than 0.6, and a Maximum Temperature Difference (MTD) more than 4. For each thermal histogram, central tendency, variability, and parameters of the best fitted Standard Normal and Laplace distributions were estimated. To classify healthy and infected leaves, feature selection was conducted and the best extracted thermal features with the largest linguistic hedge values were chosen. Among those features independent of absolute temperature measurement, MTD, SD, skewness, R2l, kurtosis and bn were selected. Then, a neuro-fuzzy classifier was trained to recognize the healthy leaves from the infected ones. The k-means clustering method was utilized to obtain the initial parameters and the fuzzy "if-then" rules. Best estimation rates of 92.55% and 92.3% were achieved in training and testing the classifier with 8 clusters. Results showed that drought stress had an adverse effect on the classification of healthy leaves. More healthy leaves under drought stress condition were classified as infected causing PPV and Specificity index values to decrease, accordingly. Image acquisition in the dark had no significant effect on the classification performance.

Early-life inflammation, immune response and ageing.

PubMed

Khan, Imroze; Agashe, Deepa; Rolff, Jens

2017-03-15

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. © 2017 The Author(s).

Early-life inflammation, immune response and ageing

PubMed Central

2017-01-01

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. PMID:28275145

On the Origin of the Canonical Nucleobases: An Assessment of Selection Pressures across Chemical and Early Biological Evolution

PubMed Central

Rios, Andro C.

2014-01-01

The native bases of RNA and DNA are prominent examples of the narrow selection of organic molecules upon which life is based. How did nature “decide” upon these specific heterocycles? Evidence suggests that many types of heterocycles could have been present on the early Earth. It is therefore likely that the contemporary composition of nucleobases is a result of multiple selection pressures that operated during early chemical and biological evolution. The persistence of the fittest heterocycles in the prebiotic environment towards, for example, hydrolytic and photochemical assaults, may have given some nucleobases a selective advantage for incorporation into the first informational polymers. The prebiotic formation of polymeric nucleic acids employing the native bases remains, however, a challenging problem to reconcile. Hypotheses have proposed that the emerging RNA world may have included many types of nucleobases. This is supported by the extensive utilization of non-canonical nucleobases in extant RNA and the resemblance of many of the modified bases to heterocycles generated in simulated prebiotic chemistry experiments. Selection pressures in the RNA world could have therefore narrowed the composition of the nucleic acid bases. Two such selection pressures may have been related to genetic fidelity and duplex stability. Considering these possible selection criteria, the native bases along with other related heterocycles seem to exhibit a certain level of fitness. We end by discussing the strength of the N-glycosidic bond as a potential fitness parameter in the early DNA world, which may have played a part in the refinement of the alphabetic bases. PMID:25284884

Regulation of early mRNA synthesis after bacteriophage T4 infection of Escherichia coli.

PubMed Central

Linder, C H; Fast, R

1975-01-01

Regulation of T4-specific mRNA synthesis was studied during leucine starvation of a leucine-requiring stringent Escherichia coli B strain. This was done by imposing starvation prior to T4 infection and then letting RNA synthesis proceed for different time periods. Rifampin or streptolydigin was added to stop further RNA synthesis, and protein synthesis was restored by addition of leucine. Samples were withdrawn at different times, and the enzyme-forming capacities found that, during conditions which elicit the stringent response in uninfected bacteria, immediate early mRNA is not stringently regulated. This conclusion contradicts the earlier conclusion of others, obtained by measuring incorporation of radioactive uracil; this is explained by the observation of Edlin and Neuhard (1967), confirmed and extended by us to the T4-infected cell, that the incorporation of uracil into RNA of a stringent strain is virtually blocked by amino acid starvation, whereas that of adenine continues at 30 to 50% of the rate seen in the presence of the required amino acid. PMID:1099229

Polymer-attached zanamivir inhibits synergistically both early and late stages of influenza virus infection

PubMed Central

Lee, Chia Min; Weight, Alisha K.; Haldar, Jayanta; Wang, Ling; Klibanov, Alexander M.; Chen, Jianzhu

2012-01-01

Covalently conjugating multiple copies of the drug zanamivir (ZA; the active ingredient in Relenza) via a flexible linker to poly-l-glutamine (PGN) enhances the anti-influenza virus activity by orders of magnitude. In this study, we investigated the mechanisms of this phenomenon. Like ZA itself, the PGN-attached drug (PGN-ZA) binds specifically to viral neuraminidase and inhibits both its enzymatic activity and the release of newly synthesized virions from infected cells. Unlike monomeric ZA, however, PGN-ZA also synergistically inhibits early stages of influenza virus infection, thus contributing to the markedly increased antiviral potency. This inhibition is not caused by a direct virucidal effect, aggregation of viruses, or inhibition of viral attachment to target cells and the subsequent endocytosis; rather, it is a result of interference with intracellular trafficking of the endocytosed viruses and the subsequent virus-endosome fusion. These findings both rationalize the great anti-influenza potency of PGN-ZA and reveal that attaching ZA to a polymeric chain confers a unique mechanism of antiviral action potentially useful for minimizing drug resistance. PMID:23185023

Immune reactivity in early life stages of sea-cage cultured Pacific bluefin tuna naturally infected with blood flukes from genus Cardicola (Trematoda: Aporocotylidae).

PubMed

Pennacchi, Ylenia; Shirakashi, Sho; Nowak, Barbara F; Bridle, Andrew R

2016-11-01

Pacific bluefin tuna (PBT), Thunnus orientalis, due to its high average price on the market is an economically valuable fish species. Infections by blood flukes from the genus Cardicola (Trematoda: Aporocotylidae) represent a growing concern for the cage culture of bluefin tuna in Japan, Australia and Southern Europe. The accumulation of numerous Cardicola eggs in the fish gills causes severe pathology that has been linked to mortality in PBT juveniles up to one year old. The only effective treatment used to mitigate the infection is the oral administration of the antihelminthic drug praziquantel (PZQ) to the affected fish. However, with the need to minimise therapeutic drug use in aquaculture it is hoped that immunoprophylaxis can provide a future alternative to protect the PBT juveniles against Cardicola infection. Currently, little is known of the host immune response to these parasites and of their infection dynamics. In this study, using real-time qPCR we aimed to quantitatively detect C. orientalis and C. opisthorchis DNA within the gills and heart of cultured PBT juveniles and to investigate the host immune response at the transcriptional level in the gills. The research focused mainly during early stages of infection soon after young PBT were transferred to culture cages (from 14 to 77 days post-transfer). An increase (up to 11-fold) of immune-related genes, namely IgM, MHC-I, TCR-β and IL-1β was observed in the PBT gills infected with Cardicola spp. (28-77 days post-transfer). Furthermore, IgM (19-fold increase) and MHC-I (11.5-fold increase) transcription was strongly up-regulated in gill samples of PBT infected with C. orientalis relative to uninfected fish but not in fish infected with C. opisthorchis. Cardicola-specific DNA was first detected in the host 14 days post-transfer (DPT) to sea-cages which was 55 days earlier than the first detection of parasite eggs and adults by microscopy. Oral administration of PZQ did not have an immediate effect

Persistent poliovirus infection of human fetal brain cells.

PubMed

Pavio, N; Buc-Caron, M H; Colbère-Garapin, F

1996-09-01

It has been suggested that poliovirus (PV), the causative agent of poliomyelitis, could persist in surviving patients. We have previously shown that PV can persistently infect some human cell lines in vitro, particularly neuroblastoma cell lines. We report here an ex vivo model in which PV can persistently infect primary cultures of human fetal brain cells. Two mutations involving capsid residues 142 of VP2 and 95 of VP1 were repeatedly selected during the persistent infections. These residues are located in capsid regions known to be involved in interactions between PV and its receptor. During the first week after infection, viral antigens were found in cells of both the neuronal and glial lineages. In contrast, 2 weeks after infection, viral antigens were detected almost exclusively in cells of the neuronal lineage. They were detected predominantly in cells expressing a marker of early commitment to the neuronal lineage, MAP-5, particularly in neuroblasts. Viral antigens were also found in immature progenitors expressing a neuroepithelium marker, nestin, and in cells expressing a marker of postmitotic neurons, MAP-2. The presence of viral antigens in postmitotic neurons suggests that PV can persist in neurons of patients who have survived poliomyelitis.

Time interval between infective endocarditis first symptoms and diagnosis: relationship to infective endocarditis characteristics, microorganisms and prognosis.

PubMed

N'Guyen, Yohan; Duval, Xavier; Revest, Matthieu; Saada, Matthieu; Erpelding, Marie-Line; Selton-Suty, Christine; Bouchiat, Coralie; Delahaye, François; Chirouze, Catherine; Alla, François; Strady, Christophe; Hoen, Bruno

2017-03-01

To analyze the characteristics and outcome of infective endocarditis (IE) according to the time interval between IE first symptoms and diagnosis. Among the IE cases of a French population-based epidemiological survey, patients having early-diagnosed IE (diagnosis of IE within 1 month of first symptoms) were compared with those having late-diagnosed IE (diagnosis of IE more than 1 month after first symptoms). Among the 486 definite-IE, 124 (25%) had late-diagnosed IE whereas others had early-diagnosed IE. Early-diagnosed IE were independently associated with female gender (OR = 1.8; 95% CI [1.0-3.0]), prosthetic valve (OR= 2.6; 95% CI [1.4-5.0]) and staphylococci as causative pathogen (OR = 3.7; 95% CI [2.2-6.2]). Cardiac surgery theoretical indication rates were not different between early and late-diagnosed IE (56.3% vs 58.9%), whereas valve surgery performance was lower in early-diagnosed IE (41% vs 53%; p = .03). In-hospital mortality rates were higher in early-diagnosed IE than in late-diagnosed IE (25.1% vs 16.1%; p < .001). The time interval between IE first symptoms and diagnosis is closely related to the IE clinical presentation, patient characteristics and causative microorganism. Better prognosis reported in late-diagnosed IE may be related to a higher rate of valvular surgery. KEY MESSAGES Infective endocarditis, which time interval between first symptoms and diagnosis was less than one month, were mainly due to Staphylococcus aureus in France. Staphylococcus aureus infective endocarditis were associated with septic shock, transient ischemic attack or stroke and higher mortality rates than infective endocarditis due to other bacteria or infective endocarditis, which time interval between first symptoms and diagnosis was more than one month. Infective endocarditis, which time interval between first symptoms and diagnosis was more than one month, were accounting for one quarter of all infective endocarditis in our study and were

Impact of Early Initiation of Antiretroviral Therapy in Patients with Acute HIV Infection in Vienna, Austria

PubMed Central

Herout, Sandra; Mandorfer, Mattias; Breitenecker, Florian; Reiberger, Thomas; Grabmeier-Pfistershammer, Katharina; Rieger, Armin; Aichelburg, Maximilian C.

2016-01-01

Background It is unclear whether antiretroviral therapy (ART) should be initiated during acute HIV infection. Most recent data provides evidence of benefits of early ART. Methods We retrospectively compared the clinical and immunological course of individuals with acute HIV infection, who received ART within 3 months (group A) or not (group B) after diagnosis. Results Among the 84 individuals with acute HIV infection, 57 (68%) received ART within 3 months (A) whereas 27 (32%) did not receive ART within 3 months (B), respectively. Clinical progression to CDC stadium B or C within 5 years after the diagnosis of HIV was less common in (A) when compared to (B) (P = 0.002). After twelve months, both the mean increase in CD4+ T cell count and the mean decrease in viral load was more pronounced in (A), when compared to (B) (225 vs. 87 cells/μl; P = 0.002 and -4.19 vs. -1.14 log10 copies/mL; P<0.001). Twenty-four months after diagnosis the mean increase from baseline of CD4+ T cells was still higher in group A compared to group B (251 vs. 67 cells/μl, P = 0.004). Conclusions Initiation of ART during acute HIV infection is associated with a lower probability of clinical progression to more advanced CDC stages and significant immunological benefits. PMID:27065239

Preventing urinary tract infections in early childhood.

PubMed

Williams, Gabrielle J; Craig, Jonathan C; Carapetis, Jonathan R

2013-01-01

Urinary tract infection (UTI) is common in children, causes them considerable discomfort, as well as distress to parents and has a tendency to recur. Approximately 20% of those children who experience one infection will have a repeat episode. Since 1975, 11 trials of long-term antibiotics compared with placebo or no treatment in 1,550 children have been published. Results have been heterogeneous, but the largest trial demonstrated a small reduction (6% absolute risk reduction, risk ratio 0.65) in the risk of repeat symptomatic UTI over 12 months of treatment. This effect was consistent across sub groups of children based upon age, gender, vesicoureteric reflux status and number of prior infections. Trials involving re-implantation surgery (and antibiotics compared with antibiotics alone) for the sub-group of children with vesicoureteric reflux have not shown a reduction in repeat UTI, with the possible exception of a very small benefit for febrile UTI. Systematic reviews have shown that circumcision reduces the risk of repeat infection but 111 circumcisions would need to be performed to prevent one UTI in unpredisposed boys. Given the need for anaesthesia and the risk of surgical complication, net clinical benefit is probably restricted to those who are predisposed (such as those with recurrent infection). Many small trials in complementary therapies have been published and many suggest some benefit, however inclusion of children is limited. Only three trials involving 394 children for cranberry products, two trials with a total of 252 children for probiotics and one trial with 24 children for vitamin A are published. Estimates of efficacy vary widely and imprecision is evident. Multiple interventions to prevent UTI in children exist. Of those, long-term low dose antibiotics has the strongest evidence base, but the benefit is small. Circumcision in boys reduces the risk substantially, but should be restricted to those at risk. There is little evidence of benefit of

Role of HIV-specific CD8+ T cells in pediatric HIV cure strategies after widespread early viral escape.

PubMed

Leitman, Ellen M; Thobakgale, Christina F; Adland, Emily; Ansari, M Azim; Raghwani, Jayna; Prendergast, Andrew J; Tudor-Williams, Gareth; Kiepiela, Photini; Hemelaar, Joris; Brener, Jacqui; Tsai, Ming-Han; Mori, Masahiko; Riddell, Lynn; Luzzi, Graz; Jooste, Pieter; Ndung'u, Thumbi; Walker, Bruce D; Pybus, Oliver G; Kellam, Paul; Naranbhai, Vivek; Matthews, Philippa C; Gall, Astrid; Goulder, Philip J R

2017-11-06

Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-infected slow-progressor children to play an effective role in "shock-and-kill" cure strategies. Two distinct subgroups of children were identified on the basis of viral load. Unexpectedly, in both groups, as in adults, HIV-specific CTL drove the selection of escape variants across a range of epitopes within the first weeks of infection. However, in HIV-infected children, but not adults, de novo autologous variant-specific CTL responses were generated, enabling the pediatric immune system to "corner" the virus. Thus, even when escape variants are selected in early infection, the capacity in children to generate variant-specific anti-HIV CTL responses maintains the potential for CTL to contribute to effective shock-and-kill cure strategies in pediatric HIV infection. © 2017 Leitman et al.

[Urinary tract infection in pregnancy].

PubMed

Herráiz, Miguel Angel; Hernández, Antonio; Asenjo, Eloy; Herráiz, Ignacio

2005-12-01

Urinary tract infections, asymptomatic bacteriuria (AB), acute cystitis (AC) and acute pyelonephritis (AP), are favored by the morphological and functional changes involved in pregnancy. AB increases the risk of preterm labor, low birth weight and AP. AB should be detected by uroculture (other methods are not sufficiently effective) and treated early. Approximately 80% of cases are caused by Escherichia coli. The risks and effectiveness of the distinct antibiotic regimens should be evaluated: fosfomycin trometamol in monotherapy or as short course therapy is safe and effective for the treatment of AB and AC. AP is the most frequent cause of hospital admission for medical reasons in pregnant women and can lead to complications in 10% of cases, putting the lives of the mother and fetus at risk. Currently outpatient treatment of AP is recommended in selected cases. Adequate follow-up of pregnant women with urinary tract infections is required due to frequent recurrence.

Lessons from acute HIV infection.

PubMed

Robb, Merlin L; Ananworanich, Jintanat

2016-11-01

Understanding the characteristics of transmission during acute HIV infection (AHI) may inform targets for vaccine-induced immune interdiction. Individuals treated in AHI with a small HIV reservoir size may be ideal candidates for therapeutic HIV vaccines aiming for HIV remission (i.e. viremic control after treatment interruption). The AHI period is brief and peak viremia predicts a viral set point that occurs 4-5 weeks following infection. Robust HIV-specific CD8 T-cell responses lower viral set points. Phylogenetic analyses of founder viruses demonstrated unique bottleneck selections and specific genetic signatures to optimize for high-fitness variants and successful transmission events. HIV clades, route of transmission and the presence of minor variants may affect vaccine protection. Antiretroviral treatment in AHI results in smaller HIV reservoir size, better CD4 T-cell recovery and fewer virus escapes. The knowledge of untreated and treated AHI informs the development of vaccines, in that preventive vaccines will require broad coverage for multiple clades and antigenic variants associated with unique bottleneck selections. Vaccines that help the host to control viremia could minimize onward transmission. Therapeutic HIV vaccines aimed at HIV remission should be studied in early-treated individuals who have few or no viral escape mutants and a more preserved immune system.

Divergent kinetics of proliferating T cell subsets in simian immunodeficiency virus (SIV) infection: SIV eliminates the "first responder" CD4+ T cells in primary infection.

PubMed

Wang, Xiaolei; Xu, Huanbin; Pahar, Bapi; Lackner, Andrew A; Veazey, Ronald S

2013-06-01

Although increased lymphocyte turnover in chronic human immunodeficiency virus and simian immunodeficiency virus (SIV) infection has been reported in blood, there is little information on cell turnover in tissues, particularly in primary SIV infection. Here we examined the levels of proliferating T cell subsets in mucosal and peripheral lymphoid tissues of adult macaques throughout SIV infection. To specifically label cells in S-phase division, all animals were inoculated with bromodeoxyuridine 24 h prior to sampling. In healthy macaques, the highest levels of proliferating CD4(+) and CD8(+) T cells were in blood and, to a lesser extent, in spleen. Substantial percentages of proliferating cells were also found in intestinal tissues, including the jejunum, ileum, and colon, but very few proliferating cells were detected in lymph nodes (axillary and mesenteric). Moreover, essentially all proliferating T cells in uninfected animals coexpressed CD95 and many coexpressed CCR5 in the tissues examined. Confocal microscopy also demonstrated that proliferating cells were substantial viral target cells for SIV infection and viral replication. After acute SIV infection, percentages of proliferating CD4(+) and CD8(+) T cells were significantly higher in tissues of chronically infected macaques and macaques with AIDS than in those of the controls. Surprisingly, however, we found that proliferating CD4(+) T cells were selectively decreased in very early infection (8 to 10 days postinoculation [dpi]). In contrast, levels of proliferating CD8(+) T cells rapidly increased after SIV infection, peaked by 13 to 21 dpi, and thereafter remained significantly higher than those in the controls. Taken together, these findings suggest that SIV selectively infects and destroys dividing, nonspecific CD4(+) T cells in acute infection, resulting in homeostatic changes and perhaps continuing loss of replication capacity to respond to nonspecific and, later, SIV-specific antigens.

Perceptual learning selectively refines orientation representations in early visual cortex.

PubMed

Jehee, Janneke F M; Ling, Sam; Swisher, Jascha D; van Bergen, Ruben S; Tong, Frank

2012-11-21

Although practice has long been known to improve perceptual performance, the neural basis of this improvement in humans remains unclear. Using fMRI in conjunction with a novel signal detection-based analysis, we show that extensive practice selectively enhances the neural representation of trained orientations in the human visual cortex. Twelve observers practiced discriminating small changes in the orientation of a laterally presented grating over 20 or more daily 1 h training sessions. Training on average led to a twofold improvement in discrimination sensitivity, specific to the trained orientation and the trained location, with minimal improvement found for untrained orthogonal orientations or for orientations presented in the untrained hemifield. We measured the strength of orientation-selective responses in individual voxels in early visual areas (V1-V4) using signal detection measures, both before and after training. Although the overall amplitude of the BOLD response was no greater after training, practice nonetheless specifically enhanced the neural representation of the trained orientation at the trained location. This training-specific enhancement of orientation-selective responses was observed in the primary visual cortex (V1) as well as higher extrastriate visual areas V2-V4, and moreover, reliably predicted individual differences in the behavioral effects of perceptual learning. These results demonstrate that extensive training can lead to targeted functional reorganization of the human visual cortex, refining the cortical representation of behaviorally relevant information.

Risk of Vaginal Infections at Early Gestation in Patients with Diabetic Conditions during Pregnancy: A Retrospective Cohort Study.

PubMed

Marschalek, Julian; Farr, Alex; Kiss, Herbert; Hagmann, Michael; Göbl, Christian S; Trofaier, Marie-Louise; Kueronya, Verena; Petricevic, Ljubomir

2016-01-01

Pregnant women with gestational diabetes mellitus (GDM) are reported to be at increased risk for infections of the genital tract. This study aimed to compare the prevalence of asymptomatic bacterial vaginosis (BV) and Candida colonization at early gestation between pregnant women with and without diabetic conditions during pregnancy. We included data from 8, 486 singleton pregnancies that underwent an antenatal infection screen-and-treat programme at our department. All women with GDM or pre-existing diabetes were retrospectively assigned to the diabetic group (DIAB), whereas non-diabetic women served as controls (CON). Prevalence for BV and Candida colonization was 9% and 14% in the DIAB group, and 9% and 13% in the CON group, respectively (n.s.). No significant difference regarding stillbirth and preterm delivery (PTD), defined as a delivery earlier than 37 + 0 (37 weeks plus 0 days) weeks of gestation was found. We could not find an increased risk of colonization with vaginal pathogens at early gestation in pregnant women with diabetes, compared to non-diabetic women. Large prospective studies are needed to evaluate the long-term risk of colonization with vaginal pathogens during the course of pregnancy in these women.

STAT6 inhibitory peptide given during RSV infection of neonatal mice reduces exacerbated airway responses upon adult reinfection.

PubMed

Srinivasa, Bharat T; Restori, Katherine H; Shan, Jichuan; Cyr, Louis; Xing, Li; Lee, Soojin; Ward, Brian J; Fixman, Elizabeth D

2017-02-01

Respiratory syncytial virus (RSV)-related hospitalization during infancy is strongly associated with the subsequent development of asthma. Early life RSV infection results in a Th2-biased immune response, which is also typical of asthma. Murine models of neonatal RSV infection have been developed to examine the possible contribution of RSV-driven Th2 responses to the development of airway hyper-responsiveness later in childhood. We have investigated the ability of a cell-penetrating STAT6 inhibitory peptide (STAT6-IP), when delivered selectively during neonatal RSV infection, to modify pathogenesis induced upon secondary RSV reinfection of adults 6 wk later. Neonatal STAT6-IP treatment inhibited the development of airway hyper-responsiveness (AHR) and significantly reduced lung eosinophilia and collagen deposition in adult mice following RSV reinfection. STAT6-IP-treated, RSV-infected neonates had reduced levels of both IL-4 and alternatively activated macrophages (AAMs) in the lungs. Our findings suggest that targeting STAT6 activity at the time of early-life RSV infection may effectively reduce the risk of subsequent asthma development. © Society for Leukocyte Biology.

Risk Behavior and Sexually Transmitted Infections Among Transgender Women and Men Undergoing Community-Based Screening for Acute and Early HIV Infection in San Diego.

PubMed

Green, Nella; Hoenigl, Martin; Morris, Sheldon; Little, Susan J

2015-10-01

The transgender community represents an understudied population in the literature. The objective of this study was to compare risk behavior, and HIV and sexually transmitted infection (STI) rates between transgender women and transgender men undergoing community-based HIV testing.With this retrospective analysis of a cohort study, we characterize HIV infection rates as well as reported risk behaviors and reported STI in 151 individual transgender women and 30 individual transgender men undergoing community based, voluntary screening for acute and early HIV infection (AEH) in San Diego, California between April 2008 and July 2014.HIV positivity rate was low for both, transgender women and transgender men undergoing AEH screening (2% and 3%, respectively), and the self-reported STI rate for the prior 12 months was 13% for both. Although transgender women appeared to engage in higher rates of risk behavior overall, with 69% engaged in condomless receptive anal intercourse (CRAI) and 11% engaged in sex work, it is important to note that 91% of transgender women reported recent sexual intercourse, 73% had more than 1 sexual partner, 63% reported intercourse with males, 37% intercourse with males and females, and 30% had CRAI.Our results indicate that in some settings rates of HIV infection, as well as rates of reported STIs and sexual risk behavior in transgender men may resemble those found in transgender women. Our findings support the need for comprehensive HIV prevention in both, transgender women and men.

Linkage and retention in HCV care for HIV-infected populations: early data from the DAA era.

PubMed

Sacks-Davis, Rachel; Doyle, Joseph S; Rauch, Andri; Beguelin, Charles; Pedrana, Alisa E; Matthews, Gail V; Prins, Maria; van der Valk, Marc; Klein, Marina B; Saeed, Sahar; Lacombe, Karine; Chkhartishvili, Nikoloz; Altice, Frederick L; Hellard, Margaret E

2018-04-01

There is currently no published data on the effectiveness of DAA treatment for elimination of HCV infection in HIV-infected populations at a population level. However, a number of relevant studies and initiatives are emerging. This research aims to report cascade of care data for emerging HCV elimination initiatives and studies that are currently being evaluated in HIV/HCV co-infected populations in the context of implementation science theory. HCV elimination initiatives and studies in HIV co-infected populations that are currently underway were identified. Context, intervention characteristics and cascade of care data were synthesized in the context of implementation science frameworks. Seven HCV elimination initiatives and studies were identified in HIV co-infected populations, mainly operating in high-income countries. Four were focused mainly on HCV elimination in HIV-infected gay and bisexual men (GBM), and three included a combination of people who inject drugs (PWID), GBM and other HIV-infected populations. None were evaluating treatment delivery in incarcerated populations. Overall, HCV RNA was detected in 4894 HIV-infected participants (range within studies: 297 to 994): 48% of these initiated HCV treatment (range: 21% to 85%; within studies from a period where DAAs were broadly available the total is 57%, range: 36% to 74%). Among studies with treatment completion data, 96% of 1109 initiating treatment completed treatment (range: 94% to 99%). Among those who could be assessed for sustained virological response at 12 weeks (SVR12), 1631 of 1757 attained SVR12 (93%, range: 86% to 98%). Early results from emerging research on HCV elimination in HIV-infected populations suggest that HCV treatment uptake is higher than reported levels prior to DAA treatment availability, but approximately half of patients remain untreated. These results are among diagnosed populations and additional effort is required to increase diagnosis rates. Among those who have

Early detection of neuropathophysiology using diffusion-weighted magnetic resonance imaging in asymptomatic cats with feline immunodeficiency viral infection.

PubMed

Bucy, Daniel S; Brown, Mark S; Bielefeldt-Ohmann, Helle; Thompson, Jesse; Bachand, Annette M; Morges, Michelle; Elder, John H; Vandewoude, Sue; Kraft, Susan L

2011-08-01

HIV infection results in a highly prevalent syndrome of cognitive and motor disorders designated as HIV-associated dementia (HAD). Neurologic dysfunction resembling HAD has been documented in cats infected with strain PPR of the feline immunodeficiency virus (FIV), whereas another highly pathogenic strain (C36) has not been known to cause neurologic signs. Animals experimentally infected with equivalent doses of FIV-C36 or FIV-PPR, and uninfected controls were evaluated by magnetic resonance diffusion-weighted imaging (DW-MRI) and spectroscopy (MRS) at 17.5-18 weeks post-infection, as part of a study of viral clade pathogenesis in FIV-infected cats. The goals of the MR imaging portion of the project were to determine whether this methodology was capable of detecting early neuropathophysiology in the absence of outward manifestation of neurological signs and to compare the MR imaging results for the two viral strains expected to have differing degrees of neurologic effects. We hypothesized that there would be increased diffusion, evidenced by the apparent diffusion coefficient as measured by DW-MRI, and altered metabolite ratios measured by MRS, in the brains of FIV-PPR-infected cats relative to C36-infected cats and uninfected controls. Increased apparent diffusion coefficients were seen in the white matter, gray matter, and basal ganglia of both the PPR and C36-infected (asymptomatic) cats. Thalamic MRS metabolite ratios did not differ between groups. The equivalently increased diffusion by DW-MRI suggests similar indirect neurotoxicity mechanisms for the two viral genotypes. DW-MRI is a sensitive tool to detect neuropathophysiological changes in vivo that could be useful during longitudinal studies of FIV.

Identification of Owl Monkey CD4 Receptors Broadly Compatible with Early-Stage HIV-1 Isolates

PubMed Central

Meyerson, Nicholas R.; Sharma, Amit; Wilkerson, Gregory K.

2015-01-01

ABSTRACT Most HIV-1 variants isolated from early-stage human infections do not use nonhuman primate versions of the CD4 receptor for cellular entry, or they do so poorly. We and others have previously shown that CD4 has experienced strong natural selection over the course of primate speciation, but it is unclear whether this selection has influenced the functional characteristics of CD4 as an HIV-1 receptor. Surprisingly, we find that selection on CD4 has been most intense in the New World monkeys, animals that have never been found to harbor lentiviruses related to HIV-1. Based on this, we sampled CD4 genetic diversity within populations of individuals from seven different species, including five species of New World monkeys. We found that some, but not all, CD4 alleles found in Spix's owl monkeys (Aotus vociferans) encode functional receptors for early-stage human HIV-1 isolates representing all of the major group M clades (A, B, C, and D). However, only some isolates of HIV-1 subtype C can use the CD4 receptor encoded by permissive Spix's owl monkey alleles. We characterized the prevalence of functional CD4 alleles in a colony of captive Spix's owl monkeys and found that 88% of surveyed individuals are homozygous for permissive CD4 alleles, which encode an asparagine at position 39 of the receptor. We found that the CD4 receptors encoded by two other species of owl monkeys (Aotus azarae and Aotus nancymaae) also serve as functional entry receptors for early-stage isolates of HIV-1. IMPORTANCE Nonhuman primates, particularly macaques, are used for preclinical evaluation of HIV-1 vaccine candidates. However, a significant limitation of the macaque model is the fact that most circulating HIV-1 variants cannot use the macaque CD4 receptor to enter cells and have to be adapted to these species. This is particularly true for viral variants from early stages of infection, which represent the most relevant vaccine targets. In this study, we found that some individuals

Evaluation of Elecsys Syphilis Assay for Routine and Blood Screening and Detection of Early Infection

PubMed Central

Kremastinou, J.; Polymerou, V.; Lavranos, D.; Aranda Arrufat, A.; Harwood, J.; Martínez Lorenzo, M. J.; Ng, K. P.; Queiros, L.; Vereb, I.

2016-01-01

Treponema pallidum infections can have severe complications if not diagnosed and treated at an early stage. Screening and diagnosis of syphilis require assays with high specificity and sensitivity. The Elecsys Syphilis assay is an automated treponemal immunoassay for the detection of antibodies against T. pallidum. The performance of this assay was investigated previously in a multicenter study. The current study expands on that evaluation in a variety of diagnostic settings and patient populations, at seven independent laboratories. The samples included routine diagnostic samples, blood donation samples, samples from patients with confirmed HIV infections, samples from living organ or bone marrow donors, and banked samples, including samples previously confirmed as syphilis positive. This study also investigated the seroconversion sensitivity of the assay. With a total of 1,965 syphilis-negative routine diagnostic samples and 5,792 syphilis-negative samples collected from blood donations, the Elecsys Syphilis assay had specificity values of 99.85% and 99.86%, respectively. With 333 samples previously identified as syphilis positive, the sensitivity was 100% regardless of disease stage. The assay also showed 100% sensitivity and specificity with samples from 69 patients coinfected with HIV. The Elecsys Syphilis assay detected infection in the same bleed or earlier, compared with comparator assays, in a set of sequential samples from a patient with primary syphilis. In archived serial blood samples collected from 14 patients with direct diagnoses of primary syphilis, the Elecsys Syphilis assay detected T. pallidum antibodies for 3 patients for whom antibodies were not detected with the Architect Syphilis TP assay, indicating a trend for earlier detection of infection, which may have the potential to shorten the time between infection and reactive screening test results. PMID:27358468

Early adolescent friendships and academic adjustment: examining selection and influence processes with longitudinal social network analysis.

PubMed

Shin, Huiyoung; Ryan, Allison M

2014-11-01

This study investigated early adolescent friendship selection and social influence with regard to academic motivation (self-efficacy and intrinsic value), engagement (effortful and disruptive behavior), and achievement (GPA calculated from report card grades) among 6th graders (N = 587, 50% girls at Wave 1; N = 576, 52% girls at Wave 2) followed from fall to spring within 1 academic year. A stochastic actor-based model of social network analysis was used to overcome methodological limitations of prior research on friends, peer groups, and academic adjustment. Evidence that early adolescents sought out friends who were similar to themselves (selection) was found in regard to academic self-efficacy, and a similar trend was found for achievement. Evidence that friends became more similar to their friends over time (influence) was found for all aspects of academic adjustment except academic self-efficacy. Collectively, results indicate that selection effects were not as pervasive as influence effects in explaining similarity among friends in academic adjustment. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies

PubMed Central

Richardson, Simone I.; Mabvakure, Batsirai; Mkhize, Nonhlanhla N.; Moore, Penny L.; Alter, Galit

2018-01-01

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies. PMID:29630668

Stunting and helminth infection in early preschool-age children in a resource-poor community in the Amazon lowlands of Peru.

PubMed

Gyorkos, Theresa W; Maheu-Giroux, Mathieu; Casapía, Martín; Joseph, Serene A; Creed-Kanashiro, Hilary

2011-04-01

The World Health Organization recommends deworming of children aged 12-24 months in highly endemic areas. Our research objectives were to: 1) examine prevalence patterns of helminth infection in early childhood; 2) assess the association between helminth infection and socio-demographic characteristics; and 3) examine the effect of the intensity of helminth infection on stunting and anemia. A survey of children (7-9 and 12-14 months) living in Belén (Peru) was undertaken between July 2007 and February 2008. A questionnaire was administered to obtain socio-demographic characteristics, blood and stool samples were collected, and length-for-age Z scores were calculated. The Kato-Katz method was used to determine the prevalence and intensity of Ascaris, Trichuris, and hookworm infections. Of 370 participating children, 349 had parasitological results. Infections first appeared in children at 8 months of age. The prevalence of any helminth infection increased linearly to approximately 37.0% (95%CI: 24.3-51.3%) by 14 months of age. Multivariate analysis showed that age, female sex, and residing in the floodplain were significant determinants of helminth infection. Among infected children, moderate-to-heavy infection of any helminth was associated with stunting (βadjusted=-0.84; 95%CI: -1.48, -0.20). These results support the implementation of deworming programs aimed at young children in highly endemic areas. Copyright © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Reactivation of Latent Tuberculosis in Cynomolgus Macaques Infected with SIV Is Associated with Early Peripheral T Cell Depletion and Not Virus Load

PubMed Central

Klein, Edwin; Janssen, Chris; Phuah, Jiayao; Sturgeon, Timothy J.; Montelaro, Ronald C.; Lin, Philana Ling; Flynn, JoAnne L.

2010-01-01

HIV-infected individuals with latent Mycobacterium tuberculosis (Mtb) infection are at significantly greater risk of reactivation tuberculosis (TB) than HIV-negative individuals with latent TB, even while CD4 T cell numbers are well preserved. Factors underlying high rates of reactivation are poorly understood and investigative tools are limited. We used cynomolgus macaques with latent TB co-infected with SIVmac251 to develop the first animal model of reactivated TB in HIV-infected humans to better explore these factors. All latent animals developed reactivated TB following SIV infection, with a variable time to reactivation (up to 11 months post-SIV). Reactivation was independent of virus load but correlated with depletion of peripheral T cells during acute SIV infection. Animals experiencing reactivation early after SIV infection (<17 weeks) had fewer CD4 T cells in the periphery and airways than animals reactivating in later phases of SIV infection. Co-infected animals had fewer T cells in involved lungs than SIV-negative animals with active TB despite similar T cell numbers in draining lymph nodes. Granulomas from these animals demonstrated histopathologic characteristics consistent with a chronically active disease process. These results suggest initial T cell depletion may strongly influence outcomes of HIV-Mtb co-infection. PMID:20224771