Susceptibility of group A beta-hemolytic streptococci in the lower St Lawrence region, Quebec

A DesRosiers, P Dolcé, P Jutras, LP Jetté. Susceptibility of group A beta-hemolytic streptococci in the lower St Lawrence region, Quebec, Canada. Can J Infect Dis 1999;10(4):279-285. OBJECTIVE: To determine the susceptibility of group A beta-hemolytic streptococci (GABHS) in the lower St Lawrence region, Quebec to different antibiotics, particularly macrolides, and to compare different antibiogram methods (disk diffusion, E-test and microdilution) and incubation atmospheres (ambient air and 5% carbon dioxide). METHODS: A total of 384 strains of GABHS isolated from 377 patients (throat 335; other sites 49) from three hospitals in the lower St Lawrence region were analyzed for their susceptibility to erythromycin, clarithromycin, azithromycin, penicillin, clindamycin, cephalothin, rifampin and vancomycin by disk diffusion on Mueller-Hinton (MH) agar supplemented with 5% defibrinated sheep blood (MHB) at 35ºC in 5% carbon dioxide. Strains that were found to be intermediately resistant or resistant to one of the antibiotics by disc diffusion, strains from sites other than throat, and a sample of 97 pharyngeal strains were evaluated by E-test on MHB (35ºC, 5% carbon dioxide) for their susceptibility to the antibiotics erythromycin, clarithromycin, azithromycin, penicillin, clindamycin and ceftriaxone. In addition, minimum inhibitory concentrations (MICs) were determined for erythromycin and azithromycin by broth microdilution using MH broth supplemented with 2.5 % of lysed horse blood (35ºC, ambient air) on strains that were resistant or intermediately resistant to the macrolides (erythromycin, clarithromycin, azithromycin). An evaluation was also carried out on these strains to determine the influence of the incubating atmosphere (ambient air versus 5% carbon dioxide) on susceptibility results obtained by disk diffusion (erythromycin, clarithromycin and azithromycin) and E-test (erythromycin and azithromycin) methods. RESULTS: Nine strains (2%) from nine patients (throat eight, pus one) were resistant to all macrolides as tested by three different techniques (disk diffusion, E-test and microdilution). All strains were susceptible to all the other antibiotics tested. For the strains intermediately resistant or resistant to macrolides, incubation in a 5% carbon dioxide atmosphere was associated with a reduction in the diameter of inhibition determined by disk diffusion (P<0.001) with frequent minor variations in interpretation, and with an increase in the MIC by E-test (P<0.001), which had no impact on interpretation. CONCLUSIONS: Resistance of GABHS to macrolides was not common (2%) in the lower St Lawrence Region. GABHS susceptibility to erythromycin seemed to predict the susceptibility to the other macrolides. Significant variation in antibiogram results (disk diffusion and E-test) of GABHS susceptibility to macrolides was related to the incubation atmosphere and may have an impact on the interpretation of disk diffusion results. I n the past few years with the resurgence of invasive infections, group A beta-hemolytic streptococci (GABHS) have become a public health threat (1-8). Surveillance programs have been implemented in many countries. In Canada, in the province of Quebec, GABHS invasive infections became a notifiable disease in 1995 (unpublished data). In 1995, 11 cases of invasive GABHS infections occurred in the lower St Lawrence region (LSLR) of Quebec. This region, with a population of approximately 215,000 people, had an incidence rate of 5.1/100 000 cases/year, the highest in the province of Quebec. The overall incidence rate in Quebec was 1.4/100,000 cases/year (unpublished data). Pharyngitis is the most frequent clinical manifestation of GABHS infections, and it is believed that pharyngitis usually precedes invasive infections. Penicillin is the antibiotic of choice in the treatment of pharyngitis. Erythromycin is recommended as an alternative for patients allergic to penicillin (9,110). Recently, increasing resistance of GABHS to erythromycin and its derivatives has been observed in several countries. In Japan, the frequency of GABHS erythromycin resistance rose from 2% in 1971 to 50% to 70% in the 1990s (11-13). A resistance of nearly 40% was reported in certain areas of Finland in 1990 (14-16) and was associated with the level of regional erythromycin consumption. Erythromycin resistance dropped to 8.6% after a successful nationwide information and education program to reduce erythromycin consumption (17). Such high levels of resistance have not been reported in North America. For instance, the rate of erythromycin resistance is low in the United States: 5% and less, for studies published between 1968 and 1997 (11,18,19). Very few Canadian studies have addressed the issue of GABHS resistance to macrolides. In 1992, Knowles et al (20) found 2% erythromycin resistance among 492 GABHS isolates from clinical specimens gathered from in a children's hospital in Montreal. They also reported that, in comparison with ambient air, incubation under a 5% carbon dioxide atmosphere was associated with a significant increase in minimal inhibition concentration (MIC) for GABHS isolates to erythromycin and clarithromycin. A similar effect of incubation atmosphere was described by Brorson and Larsson (21). The aim of the present study was to determine the susceptibility level of GABHS to different antibiotics, particularly macrolides, in the LSLR. In addition, the study compared different antibiogram methods (disk diffusion, E-test and microdilution) and two incubation atmospheres (ambient air and 5% carbon dioxide) in a subset of isolates. MATERIALS AND METHODS GABHS strains: GABHS isolates were collected between March 1995 and February 1996 from three hospitals in the LSLR: the Centre Hospitalier Régional de Rimouski, the Centre Hospitalier d'Amqui and the Centre Hospitalier du Grand Portage. A maximum of two strains per patient were admissible: one strain from the throat and the other from a normally sterile site. 280 Can J Infect Dis Vol 10 No 4 July/August 1999 MÉTHODES : En tout, on a analysé 384 isolats de SBHGA provenant de 377 patients (gorge, 335; autres foyers, 49) de trois hôpitaux du Bas Saint-Laurent pour vérifier leur sensibilité à l'érythromycine, à la clarithromycine, à l'azithromycine, à la pénicilline, à la clindamicyne, à la céphalothine, au rifampim et à la vancomycine, par diffusion en gélose de Mueller-Hinton (MH) enrichie de sang de mouton à 5 % défibriné (SMD), à 35°C, dans du dioxyde de carbone à 5 %. Les souches qui se sont révélées résistantes ou moyennement résistantes à l'un des antibiotiques par la méthode de diffusion en gélose, les souches provenant d'autres foyers que la gorge et un échantillon de 97 isolats pharyngés ont été éva-lués par test E sur SMD (35°C, dioxyde de carbone à 5 %) pour en mesurer la sensibilité à l'endroit des antibiotiques érythromycine, clarithromycine, azithromycine, pénicilline, clindamycine et ceftriaxone. De plus, les concentrations minimales inhibitrices (CMI) ont été calculées pour l'érythromycine et l'azithromycine par microdilution sur bouillon de culture, à l'aide de solutions MH auxquelles a été ajouté du sang de cheval à 2,5 % lysé (35°C, air ambiant), sur des souches qui se sont révélées résistantes ou moyennement résistantes à l'endroit des macrolides (érythromycine, clarithromycine, azithromycine). Une évaluation a en outre été effectuée sur ces souches afin de déterminer l'influence de l'atmosphère d'incubation (air ambiant vs dioxyde de carbone à 5 %) sur les résultats d'antibiogrammes obtenus par diffusion en gélose (érythromycine, clarithromycine et azithromycine) et test E (érythromycine et azithromycine). RÉSULTATS : Neuf souches (2 %) provenant de neuf patients (8 prélèvements de gorge, 1 spécimen de pus) se sont révé-lées résistantes à tous les macrolides testés au moyen des trois techniques (diffusion en gélose, test E et microdilution). La totalité des souches se sont révélées sensibles à tous les autres antibiotiques testés. Pour les souches résistantes ou moyennement résistantes aux macrolides, l'incubation dans une atmosphère de dioxyde de carbone à 5 % a été associée à une réduction du diamètre d'inhibition, déterminée par la méthode de diffusion en gélose (p < 0,001), avec fréquentes variations mineures des interprétations et augmentation de la CMI selon le test E (p < 0,001), qui n'ont eu aucun impact sur l'interprétation de ces résultats. CONCLUSIONS : La résistance des SBHGA à l'endroit des macrolides n'a pas été fréquente (2 %) dans le Bas Saint-Laurent. Leur sensibilité à l'érythromycine a semblé être un facteur de prévisibilité de leur sensibilité aux autres macrolides. La variabilité significative des résultats d'antibiogrammes (diffusion en gélose et test E), du degré de sensibilité des SBHGA à l'endroit des macrolides a été jugée en lien avec l'atmosphère d'incubation et pourrait exercer un impact sur l'interprétation des résultats obtenus au moyen de la technique par diffusion en gélose. Statistical analysis: Data were analyzed on EPI INFO, version 6.0 (Atlanta, Georgia). The influence of the incubation atmosphere (ambient air versus carbon dioxide) was determined by ANOVA with a significance level of P<0.05 using SYSTAT software, version 5.02 (Systat Inc, Evanston, Illinois). Conservation and reidentification: Review of the medical files: The medical files of patients with strains resistant or intermediately resistant to macrolides were reviewed to obtain any pertinent clinical data. RESULTS A total of 384 GABHS strains isolated from 377 patients (throat 335 [87%], other sites 49 [13%]) were examined (Table 1). Seven patients had two isolates: one from the throat and the second from another site (wound four, fascia two, joint liquid one). Fifteen of the 49 nonpharyngeal strains were isolated in patients with invasive infections. The re-identification of all 384 strains confirmed them to be S pyogenes. Only six isolates yielded unexpected results; all exhibited trimethoprim/sulphamethoxazole susceptibility. In these cases, seroagglutination with group A antigen gave positive results

Discomfort and agitation in older adults with dementia

<p>Abstract</p> <p>Background</p> <p>A majority of patients with dementia present behavioral and psychological symptoms, such as agitation, which may increase their suffering, be difficult to manage by caregivers, and precipitate institutionalization. Although internal factors, such as discomfort, may be associated with agitation in patients with dementia, little research has examined this question. The goal of this study is to document the relationship between discomfort and agitation (including agitation subtypes) in older adults suffering from dementia.</p> <p>Methods</p> <p>This correlational study used a cross-sectional design. Registered nurses (RNs) provided data on forty-nine residents from three long-term facilities. Discomfort, agitation, level of disability in performing activities of daily living (ADL), and severity of dementia were measured by RNs who were well acquainted with the residents, using the Discomfort Scale for patients with Dementia of the Alzheimer Type, the Cohen-Mansfield Agitation Inventory, the ADL subscale of the Functional Autonomy Measurement System, and the Functional Assessment Staging, respectively. RNs were given two weeks to complete and return all scales (i.e., the Cohen-Mansfield Agitation Inventory was completed at the end of the two weeks and all other scales were answered during this period). Other descriptive variables were obtained from the residents' medical file or care plan.</p> <p>Results</p> <p>Hierarchical multiple regression analyses controlling for residents' characteristics (sex, severity of dementia, and disability) show that discomfort explains a significant share of the variance in overall agitation (28%, <it>p </it>< 0.001), non aggressive physical behavior (18%, <it>p </it>< 0.01) and verbally agitated behavior (30%, <it>p </it>< 0.001). No significant relationship is observed between discomfort and aggressive behavior but the power to detect this specific relationship was low.</p> <p>Conclusion</p> <p>Our findings provide further evidence of the association between discomfort and agitation in persons with dementia and reveal that this association is particularly strong for verbally agitated behavior and non aggressive physical behavior.</p

The reliability of side to side measurements of upper extremity activity levels in healthy subjects

<p>Abstract</p> <p>Background</p> <p>In both clinical and occupational settings, ambulatory sensors are becoming common for assessing all day measurements of arm motion. In order for the motion of a healthy, contralateral side to be used as a control for the involved side, the inherent side to side differences in arm usage must be minimal. The goal of the present study was to determine the reliability of side to side measurements of upper extremity activity levels in healthy subjects.</p> <p>Methods</p> <p>Thirty two subjects with no upper extremity pathologies were studied. Each subject wore a triaxial accelerometer on both arms for three and a half hours. Motion was assessed using parameters previously reported in the literature. Side to side differences were compared with the intraclass correlation coefficient, standard error of the mean, minimal detectable change scores and a projected sample size analysis.</p> <p>Results</p> <p>The variables were ranked based on their percentage of minimal detectable change scores and sample sizes needed for paired t-tests. The order of these rankings was found to be identical and the top ranked parameters were activity counts per hour (MDC% = 9.5, n = 5), jerk time (MDC% = 15.8, n = 8) and percent time above 30 degrees (MDC% = 34.7, n = 9).</p> <p>Conclusions</p> <p>In general, the mean activity levels during daily activities were very similar between dominant and non-dominant arms. Specifically, activity counts per hour, jerk time, and percent time above 30 degrees were found to be the variables most likely to reveal significant difference or changes in both individuals and groups of subjects. The use of ambulatory measurements of upper extremity activity has very broad uses for occupational assessments, musculoskeletal injuries of the shoulder, elbow, wrist and hand as well as neurological pathologies.</p

Association Pattern of Interleukin-1 Receptor-Associated Kinase-4 Gene Polymorphisms with Allergic Rhinitis in a Han Chinese Population

Interleukin-1 receptor-associated kinase-4 (IRAK-4) encodes a kinase that is essential for NF-kB activation in Toll-like receptor and T-cell receptor signaling pathways, indicating a possible crosstalk between innate and acquired immunities. We attempted to determine whether the polymorphisms in the Interleukin-1 receptor-associated kinase-4 (IRAK-4) gene are associated with allergic rhinitis (AR) in the Han Chinese population.A population of 379 patients with AR and 333 healthy controls was studied. Blood was drawn for DNA extraction and total serum immunoglobulin E (IgE). A total of 11 single nucleotide polymorphisms (SNPs) in IRAK-4 were selected and individually genotyped.Significant allelic differences between cases and controls were obtained for the SNP of rs3794262 in the IRAK-4 gene. In the stratified analysis for gender, two SNPs (rs4251431 and rs6582484) in males appeared as significant associations. Subgroup analysis for the presence of different allergen sensitivities displayed associations only in the house dust mite-allergic cohorts (rs3794262, rs4251481). None of the selected SNPs in IRAK-4 was associated with total IgE level. The haplotype analysis indicated GCCTGCGA was significantly associated with AR. The SNP-SNP interaction information analysis indicated that the selected sets of polymorphisms had no synergistic effect.Our findings did not support the potential contribution of the IRAK-4 gene to serum IgE levels. However, the results demonstrated a gender- and allergen-dependant association pattern between polymorphisms in IRAK-4 and AR in Chinese population

Role of Occult and Post-acute Phase Replication in Protective Immunity Induced with a Novel Live Attenuated SIV Vaccine

In order to evaluate the role of persisting virus replication during occult phase immunisation in the live attenuated SIV vaccine model, a novel SIVmac239Δnef variant (SIVrtTA) genetically engineered to replicate in the presence of doxycycline was evaluated for its ability to protect against wild-type SIVmac239. Indian rhesus macaques were vaccinated either with SIVrtTA or with SIVmac239Δnef. Doxycycline was withdrawn from 4 of 8 SIVrtTA vaccinates before challenge with wild-type virus. Unvaccinated challenge controls exhibited ~107 peak plasma viral RNA copies/ml persisting beyond the acute phase. Six vaccinates, four SIVmac239Δnef and two SIVrtTA vaccinates exhibited complete protection, defined by lack of wild-type viraemia post-challenge and virus-specific PCR analysis of tissues recovered post-mortem, whereas six SIVrtTA vaccinates were protected from high levels of viraemia. Critically, the complete protection in two SIVrtTA vaccinates was associated with enhanced SIVrtTA replication in the immediate post-acute vaccination period but was independent of doxycycline status at the time of challenge. Mutations were identified in the LTR promoter region and rtTA gene that do not affect doxycycline-control but were associated with enhanced post-acute phase replication in protected vaccinates. High frequencies of total circulating CD8+T effector memory cells and a higher total frequency of SIV-specific CD8+ mono and polyfunctional T cells on the day of wild-type challenge were associated with complete protection but these parameters were not predictive of outcome when assessed 130 days after challenge. Moreover, challenge virus-specific Nef CD8+ polyfunctional T cell responses and antigen were detected in tissues post mortem in completely-protected macaques indicating post-challenge control of infection. Within the parameters of the study design, on-going occult-phase replication may not be absolutely required for protective immunity

Detection of delirium by nurses among long-term care residents with dementia

<p>Abstract</p> <p>Background</p> <p>Delirium is a prevalent problem in long-term care (LTC) facilities where advanced age and cognitive impairment represent two important risk factors for this condition. Delirium is associated with numerous negative outcomes including increased morbidity and mortality. Despite its clinical importance, delirium often goes unrecognized by nurses. Although rates of nurse-detected delirium have been studied among hospitalized older patients, this issue has been largely neglected among demented older residents in LTC settings. The goals of this study were to determine detection rates of delirium and delirium symptoms by nurses among elderly residents with dementia and to identify factors associated with undetected cases of delirium.</p> <p>Methods</p> <p>In this prospective study (N = 156), nurse ratings of delirium were compared to researcher ratings of delirium. This procedure was repeated for 6 delirium symptoms. Sensitivity, specificity, positive and negative predictive values were computed. Logistic regressions were conducted to identify factors associated with delirium that is undetected by nurses.</p> <p>Results</p> <p>Despite a high prevalence of delirium in this cohort (71.5%), nurses were able to detect the delirium in only a minority of cases (13%). Of the 134 residents not identified by nurses as having delirium, only 29.9% of them were correctly classified. Detection rates for the 6 delirium symptoms varied between 39.1% and 58.1%, indicating an overall under-recognition of symptoms of delirium. Only the age of the residents (≥ 85 yrs) was associated with undetected delirium (OR: 4.1; 90% CI: [1.5–11.0]).</p> <p>Conclusion</p> <p>Detection of delirium is a major issue for nurses that clearly needs to be addressed. Strategies to improve recognition of delirium could result in a reduction of adverse outcomes for this very vulnerable population.</p

Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine

BACKGROUND: The generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infective but non-replicative virions able to elicit broad and strong cellular immune responses in HIV-1 seropositive individuals. RESULTS: Viral particles were generated through transient transfection in producer cells (293-T) of a full length HIV-1 DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the sequence that codes for the reverse transcriptase (NL4-3/ΔRT clone). The viral particles generated were able to enter target cells, but due to the absence of reverse transcriptase no replication was detected. The immunogenic capacity of these particles was assessed by ELISPOT to determine γ-interferon production in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals. Surprisingly, defective particles produced from NL4-3/ΔRT triggered stronger cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT-2) and in a larger proportion of individuals (55% versus 23% seropositive individuals tested). Electron microscopy showed that NL4-3/ΔRT virions display immature morphology. Interestingly, wild-type viruses treated with Amprenavir (APV) to induce defective core maturation also induced stronger responses than the same viral particles generated in the absence of protease inhibitors. CONCLUSIONS: We propose that immature HIV-1 virions generated from NL4-3/ΔRT viral clones may represent new prototypes of immunogens with a safer profile and stronger capacity to induce cellular immune responses than wild-type inactivated viral particles.This study was supported by grants FIS PI050265, FIS PI040503, FIS PI070291, FIS Intrasalud 080752, FIS PS09/01297, FIS PI10/02984, SAF2006-26667-E, FIT 09-010-205-9, FIPSE 36780/08, Fundación Mútua Madrileña, TRA-094, EC10-153, ISCIII-RETIC RD06/0006, HIVACAT–HIV Development Program in Catalonia, FIPSE 36630/07, UE Program Health 2009 CHAARM. Spanish Health Institute Carlos III (ISCIII) and the Health Department of the Catalan Government (Generalitat de Catalunya). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Determinants of social participation of visually impaired older adults

PURPOSE: To assess determinants of social participation among visually impaired older adults. METHODS: This cross-sectional study included visually impaired persons (>/=55 years; n = 173) who were referred to a low-vision rehabilitation center. Determinants (i.e., sociodemographic, physical, social and psychological factors, and personal values) of participation were identified in four domains of participation: (1) domestic life; (2) interpersonal interactions and relationships; (3) major life areas; and (4) community, social, and civic life. Study participants completed telephone interviews. RESULTS: Age, physical fitness, and helplessness were determinants of participation in domestic life. Social network size was associated with participation in major life areas. The personal value attached to participation (i.e., perceived importance) was a determinant of participation in interpersonal interactions and relationships, major life areas, and community, social and civic life. Vision-related characteristics (i.e., self-perceived vision and degree of visual impairment) were not associated with participation. CONCLUSIONS: Across the participation domains, perceived importance is a major determinant of social participation among visually impaired older adults. Physical health along with social and psychological status, also affect participation. Knowing how participation is determined can be used to develop rehabilitation interventions to enhance participation of visually impaired older adults

LabKey Server: An open source platform for scientific data integration, analysis and collaboration

<p>Abstract</p> <p>Background</p> <p>Broad-based collaborations are becoming increasingly common among disease researchers. For example, the Global HIV Enterprise has united cross-disciplinary consortia to speed progress towards HIV vaccines through coordinated research across the boundaries of institutions, continents and specialties. New, end-to-end software tools for data and specimen management are necessary to achieve the ambitious goals of such alliances. These tools must enable researchers to organize and integrate heterogeneous data early in the discovery process, standardize processes, gain new insights into pooled data and collaborate securely.</p> <p>Results</p> <p>To meet these needs, we enhanced the LabKey Server platform, formerly known as CPAS. This freely available, open source software is maintained by professional engineers who use commercially proven practices for software development and maintenance. Recent enhancements support: (i) Submitting specimens requests across collaborating organizations (ii) Graphically defining new experimental data types, metadata and wizards for data collection (iii) Transitioning experimental results from a multiplicity of spreadsheets to custom tables in a shared database (iv) Securely organizing, integrating, analyzing, visualizing and sharing diverse data types, from clinical records to specimens to complex assays (v) Interacting dynamically with external data sources (vi) Tracking study participants and cohorts over time (vii) Developing custom interfaces using client libraries (viii) Authoring custom visualizations in a built-in R scripting environment.</p> <p>Diverse research organizations have adopted and adapted LabKey Server, including consortia within the Global HIV Enterprise. Atlas is an installation of LabKey Server that has been tailored to serve these consortia. It is in production use and demonstrates the core capabilities of LabKey Server. Atlas now has over 2,800 active user accounts originating from approximately 36 countries and 350 organizations. It tracks roughly 27,000 assay runs, 860,000 specimen vials and 1,300,000 vial transfers.</p> <p>Conclusions</p> <p>Sharing data, analysis tools and infrastructure can speed the efforts of large research consortia by enhancing efficiency and enabling new insights. The Atlas installation of LabKey Server demonstrates the utility of the LabKey platform for collaborative research. Stable, supported builds of LabKey Server are freely available for download at <url>http://www.labkey.org</url>. Documentation and source code are available under the Apache License 2.0.</p

HIV-1 Nef Induces Proinflammatory State in Macrophages through Its Acidic Cluster Domain: Involvement of TNF Alpha Receptor Associated Factor 2

Background: HIV-1 Nef is a virulence factor that plays multiple roles during HIV replication. Recently, it has been described that Nef intersects the CD40 signalling in macrophages, leading to modification in the pattern of secreted factors that appear able to recruit, activate and render T lymphocytes susceptible to HIV infection. The engagement of CD40 by CD40L induces the activation of different signalling cascades that require the recruitment of specific tumor necrosis factor receptor-associated factors (i.e. TRAFs). We hypothesized that TRAFs might be involved in the rapid activation of NF-kappa B, MAPKs and IRF-3 that were previously described in Nef-treated macrophages to induce the synthesis and secretion of proinflammatory cytokines, chemokines and IFN beta to activate STAT1, -2 and -3. Methodology/Principal Findings: Searching for possible TRAF binding sites on Nef, we found a TRAF2 consensus binding site in the AQEEEE sequence encompassing the conserved four-glutamate acidic cluster. Here we show that all the signalling effects we observed in Nef treated macrophages depend on the integrity of the acidic cluster. In addition, Nef was able to interact in vitro with TRAF2, but not TRAF6, and this interaction involved the acidic cluster. Finally silencing experiments in THP-1 monocytic cells indicate that both TRAF2 and, surprisingly, TRAF6 are required for the Nef-induced tyrosine phosphorylation of STAT1 and STAT2. Conclusions: Results reported here revealed TRAF2 as a new possible cellular interactor of Nef and highlighted that in monocytes/macrophages this viral protein is able to manipulate both the TRAF/NF-kappa B and TRAF/IRF-3 signalling axes, thereby inducing the synthesis of proinflammatory cytokines and chemokines as well as IFN beta