Vissaria Sakka

Early alterations of the innate and adaptive immune statuses in sepsis according to the type of underlying infection

IntroductionAlthough major changes of the immune system have been described in sepsis, it has never been studied whether these may differ in relation to the type of underlying infection or not. This was studied for the first time.MethodsThe statuses of the innate and adaptive immune systems were prospectively compared in 505 patients. Whole blood was sampled within less than 24 hours of advent of sepsis; white blood cells were stained with monoclonal antibodies and analyzed though a flow cytometer.ResultsExpression of HLA-DR was significantly decreased among patients with severe sepsis/shock due to acute pyelonephritis and intraabdominal infections compared with sepsis. The rate of apoptosis of natural killer (NK) cells differed significantly among patients with severe sepsis/shock due to ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) compared with sepsis. The rate of apoptosis of NKT cells differed significantly among patients with severe sepsis/shock due to acute pyelonephritis, primary bacteremia and VAP/HAP compared with sepsis. Regarding adaptive immunity, absolute counts of CD4-lymphocytes were significantly decreased among patients with severe sepsis/shock due to community-acquired pneumonia (CAP) and intraabdominal infections compared with sepsis. Absolute counts of B-lymphocytes were significantly decreased among patients with severe sepsis/shock due to CAP compared with sepsis.ConclusionsMajor differences of the early statuses of the innate and adaptive immune systems exist between sepsis and severe sepsis/shock in relation to the underlying type of infection. These results may have a major impact on therapeutics.

Effect of the Novel Influenza A (H1N1) Virus in the Human Immune System

Background The pandemic by the novel H1N1 virus has created the need to study any probable effects of that infection in the immune system of the host. Methodology/Principal Findings Blood was sampled within the first two days of the presentation of signs of infection from 10 healthy volunteers; from 18 cases of flu-like syndrome; and from 31 cases of infection by H1N1 confirmed by reverse RT-PCR. Absolute counts of subtypes of monocytes and of lymphocytes were determined after staining with monoclonal antibodies and analysis by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were isolated from patients and stimulated with various bacterial stimuli. Concentrations of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-18, interferon (FN)-alpha and of IFN-gamma were estimated in supernatants by an enzyme immunoassay. Infection by H1N1 was accompanied by an increase of monocytes. PBMCs of patients evoked strong cytokine production after stimulation with most of bacterial stimuli. Defective cytokine responses were shown in response to stimulation with phytohemagglutin and with heat-killed Streptococcus pneumoniae. Adaptive immune responses of H1N1-infected patients were characterized by decreases of CD4-lymphocytes and of B-lymphocytes and by increase of T-regulatory lymphocytes (Tregs). Conclusions/Significance Infection by the H1N1 virus is accompanied by a characteristic impairment of the innate immune responses characterized by defective cytokine responses to S.pneumoniae. Alterations of the adaptive immune responses are predominated by increase of Tregs. These findings signify a predisposition for pneumococcal infections after infection by H1N1 influenza.

Association of Toll-Like Receptor 4 Asp299Gly and Thr399Ile Polymorphisms with Increased Infection Risk in Patients with Advanced HIV-1 Infection

BACKGROUND. The Toll-like receptor 4 (TLR4) is an essential component of the innate immune response to various microorganisms. We investigated the association between TLR4 polymorphism and the risk of acquiring severe infections, in patients with human immunodeficiency virus (HIV)-1 infection. METHODS. The presence of TLR4 Asp299Gly and Thr399Ile single nucleotide polymorphisms (SNPs) was determined in a cohort of 199 HIV-1 infected patients and evaluated in relation to the occurrence of various infections. RESULTS. One hundred seventy-two patients were homozygous for the wild-type genotype; 22 patients (11%) were heterozygous for both SNPs; 4 were heterozygous for 1 polymorphism; 1 patient was heterozygous for the Asp299Gly SNP and homozygous for the Thr399Ile SNP. Of individuals with a nadir CD4 cell count of <100 cells/mm(3), those who carried both SNPs, compared with those who carried the wild-type genotype, demonstrated a >3-fold increase in the odds ratio (OR) of any serious infection (OR, 6.33 vs OR, 1.83, P = .043). CONCLUSIONS. This study suggests an association between the presence of TLR4 Asp299Gly and Thr399Ile polymorphisms and the occurrence of serious infections in HIV-1 infected patients with a history of nadir CD4 cell count of <100 cells/mm(3).

Linezolid in Prophylaxis against Experimental Aortic Valve Endocarditis Due to Streptococcus oralis or Enterococcus faecalis

ABSTRACT There are no experimental studies regarding the prophylactic efficacy of linezolid against infective endocarditis. Nonbacterial thrombotic endocarditis of the aortic valve was induced in rabbits by the insertion of a polyethylene catheter. Twenty-four hours later, animals were randomly assigned to a control group, and groups receiving either ampicillin (two doses of 40 mg/kg of body weight each, given intravenously, 2 h apart) or linezolid (a single per os dose of 75 mg/kg). The first dose of ampicillin and the single dose of linezolid were administered 0.5 and 1 h, respectively, prior to the intravenous inoculation of ∼107 CFU of Streptococcus oralis or Enterococcus faecalis. Linezolid peak levels in rabbit serum were similar to the peak serum levels in humans following a 600-mg oral dose of linezolid. Linezolid prevented endocarditis in 87% of S. oralis-challenged rabbits (P < 0.001 versus controls; P = 0.026 versus ampicillin). In rabbits challenged with E. faecalis, linezolid prevented endocarditis in 73% (P = 0.003 versus controls; P = 0.049 versus ampicillin). Ampicillin prevented endocarditis due to S. oralis or due to E. faecalis in 47% (P = 0.005 versus controls) and in 30% (P = not significant versus controls) of the challenged animals, respectively. In conclusion, linezolid was effective as prophylaxis against endocarditis caused by a strain of S. oralis and to a lesser degree against that caused by a strain of E. faecalis. Its prophylactic efficacy was superior to that of ampicillin.

Promoting prudent use of antibiotics: the experience from a multifaceted regional campaign in Greece

BackgroundAntibiotic resistance, a major public health problem, has been linked to antibiotic consumption. In Greece both consumption and resistance rates are among the highest in Europe. A multifaceted campaign targeting both physicians and parents of school children was implemented for the first time in order to educate the public and update doctors, aiming to promote judicious use of antibiotics and hopefully decrease its consumption.MethodsThe programme consisted of a public education campaign and academic detailing of primary care physicians in the district of Corinth in Peloponnese. The experience and perceptions of parents were recorded in the meetings in the form of course evaluation and assessment, anonymous questionnaires. The use of Rapid Antigen Detection Test (RADT) for streptococcal pharyngitis by primary care physicians was also assessed by use of anonymous questionnaires. Antibiotic consumption was compared before and after the programme between the district of Corinth and the other districts of Peloponnese, as well as at a national level.ResultsAntibiotic consumption remained unaltered at 26 Defined daily doses per 1000 Inhabitants per Day (DID) in accordance with the trend in other regions and at a national level. However, the utilization of Amoxycillin and Penicillin was increased by 34.3%, while the use of other antimicrobial classes including macrolides, cephalosporins and fluoroquinolones decreased by 6.4-21.9%. The use of RADT did not lead to a significantly decreased antimicrobial consumption.ConclusionsA multifaceted educational programme targeting both the general public and primary care physicians was associated with rationalization in the choice of antimicrobial. A reduction in the total antimicrobial consumption was not achieved.

Association of Mal/TIRAP S180L variant polymorphism with decreased infection risk in patients with advanced HIV-1 infection

OBJECTIVES MyD88 adaptor-like (Mal/TIRAP) is an adaptor protein bridging activation of Toll-like receptors 2 and 4 after stimulation by exogenous and endogenous ligands. We investigated the association between the presence of the S180L SNP of Mal and the risk of severe infection in individuals with human immunodeficiency virus (HIV)-1 infection. METHODS The SNP S180L was determined in a cohort of 179 HIV-1 infected Greek patients. Analysis of the prevalence of this SNP in relation to the infectious complications was evaluated. RESULTS One hundred and thirty-two (73.3%) patients were bearing the wild type haplotype, 43 (24%) were heterozygous for the SNP, and four (2.2%) were homozygous for the variant allele. The individuals with a nadir CD4 count <200 cells/mm(3) who carried the 180L variant demonstrated a 4-fold decrease in the odds ratio (OR) for any serious infection compared with those who carried the wild-type 180S genotype (OR 0.58 vs OR 2.6, p=0.016). CONCLUSIONS This study suggest a protection effect of the Mal S180L SNP against serious infections in HIV-1 infected individuals with low CD4 cell counts.

Successful treatment with moxifloxacin of experimental aortic valve endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA)

Moxifloxacin (MXF) is an 8-methoxyquinolone with high activity against Gram-positive bacteria. In an experimental model of aortic valve endocarditis (EAVE), the efficacy of MXF was evaluated against a strain of methicillin-resistant Staphylococcus aureus (MRSA). Rabbits with catheter-induced aortic valve vegetations were randomly assigned to a control group or to groups receiving MXF 20 mg/kg intravenous (i.v.) twice a day (bid) or vancomycin (VAN) 30 mg/kg i.v. bid for a total of eight doses (4 days). Rabbits were sacrificed 15 h after the last dose of antibiotics. In another group, treatment with MXF was extended to 5 days and rabbits were sacrificed 5 days after the last dose (10th dose) of MXF in order to detect possible relapses of endocarditis after the end of treatment (test-of-cure (TOC) study). Both MXF and VAN significantly reduced the bacterial load in vegetations (P < 0.001 vs. controls). All animals in the MXF-TOC group had sterile vegetations. MXF given at a dose of 20 mg/kg i.v. bid for 4 days was equally effective as VAN in the treatment of EAVE due to MRSA. When treatment with MXF was extended to 5 days, the cure rate reached 100% and no relapses of endocarditis were observed.

Reliability, validity and psychometric properties of the Greek translation of the posttraumatic stress disorder scale

The Greek version of the Davidson Trauma Scale (DTS) was developed to respond to the need of Greek-speaking individuals. The translated questionnaire was administered to 128 HIV outpatients (aged 37.1±9.1) and 166 control patients (aged 32.4±13.4). In addition to the DTS Greek scale, subjects were assessed with two other scales useful for assessing validity. For each factor analyses two components were extracted, based on Cattell’s scree test. The two components solution accounted for 55.34% of the total variation in case of frequency variables and 61.45% in case of severity variables. The Cronbach’s alpha coefficient and Guttman split-half coefficient of the DTS scale were 0.93 and 0.88 respectively. The test-retest reliability of the Greek version of DTS scale proved to be satisfactory. Individual items had good intra-class correlation coefficients higher than 0.5, which means that all questions have high levels of external validity. The psychometric strength of interview for posttraumatic stress disorder-Greek version it’s reliable for its future use, particularly for screening subjects with possible diagnosis of posttraumatic stress disorder.

Reliability, Validity, and Psychometric Properties of the Greek Translation of the Cambridge Depersonalization Scale (CDS) -

Introduction: The Cambridge Depersonalisation Scale is meant to capture the frequency and duration of depersonalisation symptoms over the ‘last 6 months’. Methods: In order to develop a Greek version of CDS scale, the CDS scale was translated in Greek by 2 psychiatrists. Then, the Greek version of CDS scale was back-translated by a person who did not knew the original English version. The back-translated version was reviewed in order to establish whether is consistent with the original English version. After this procedure we administered the Greek version of CDS scale to a sample of 294 Greeks in order to assess the reliability and the validity of the Greek version of scale. Results: The five components solution accounted for 58.204% of the total variation. Initial eigenvalues of the five components were: factor 1=11.555, factor 2=1.564, factor 3=1.356, factor 4=1.247 and factor 5=1.157. Six items did not load on any factor. Correlations between factors were low ranged from 0.134 to 0.314 and no complex variables were found. Cronbach’s alpha and Guttman split-half coefficient were used to evaluate interval consistency of CDS scale in 294 individuals. The alpha coefficients and Guttman split-half coefficient of the CDS scale were 0.938 and 0.921, respectively. The test-retest reliability proved to be satisfactory. The intraclass correlation coefficients for the total CDS score was very good and equal to 0,883. The CDS scale correlated highly with the SCL-90 and all subscales (p-value<0.0001). Conclusion: The psychometric strength of CDS – Greek its reliable for its future use, particularly for screening for subjects with possible diagnosis of CDS.