Michael Kundi

Herd immunity after two years of the universal mass vaccination program against rotavirus gastroenteritis in Austria

Austria was the first country in Europe implementing a universal mass vaccination program against rotavirus gastroenteritis (RV-GE) for all infants nationwide. Epidemiological data from a hospital based surveillance system show that incidence rates of children hospitalized with RV-GE decreased in 2009 compared to 2008 and compared to the prevaccination period 2001-2005. Decreasing hospitalization-rates from RV-GE were observed in children of all age groups, even in those not eligible for vaccination according to their age, suggesting herd immunity induced by universal mass vaccination against RV-GE. In 2009 the disease burden was highest in children below three months of age stressing the importance of the early start of the immunization course.

Prognostic factors for intensive care unit admission, intensive care outcome, and post-intensive care survival in patients with de novo acute myeloid leukemia: a single center experience

Background Acute myeloid leukemia is a life-threatening disease associated with high mortality rates. A substantial number of patients require intensive care. This investigation analyzes risk factors predicting admission to the intensive care unit in patients with acute myeloid leukemia eligible for induction chemotherapy, the outcome of these patients, and prognostic factors predicting their survival. Design and Methods A total of 406 consecutive patients with de novo acute myeloid leukemia (15–89 years) were analyzed retrospectively. Markers recorded at the time of diagnosis included karyotype, fibrinogen, C-reactive protein, and Charlson comorbidity index. In patients requiring critical care, the value of the Simplified Acute Physiology Score II, the need for mechanical ventilation, and vasopressor support were recorded at the time of intensive care unit admission. The independent prognostic relevance of the parameters was tested by multivariate analysis. Results Sixty-two patients (15.3%) required intensive care, primarily due to respiratory failure (50.0%) or life-threatening bleeding (22.6%). Independent risk factors predicting intensive care unit admission were lower fibrinogen concentration, the presence of an infection, and comorbidity. The survival rate was 45%, with the Simplified Acute Physiology Score II being the only independent prognostic parameter (P<0.05). Survival was inferior in intensive care patients compared to patients not admitted to an intensive care unit. However, no difference between intensive care and non-intensive care patients was found concerning continuous complete remission at 6 years or survival at 6 years in patients who survived the first 30 days after diagnosis (non-intensive care patients: 28%; intensive care patients: 20%, P>0.05). Conclusions Ongoing infections, low fibrinogen and comorbidity are predictive for intensive care unit admission in acute myeloid leukemia. Although admission was a risk factor for survival, continuous complete remission and survival of patients alive at day 30 were similar in patients who were admitted or not admitted to an intensive care unit.

Portal Pressure Predicts Outcome and Safety of Antiviral Therapy in Cirrhotic Patients With Hepatitis C Virus Infection

BACKGROUND & AIMSnThere are limited data on the efficacy and safety of antiviral therapy in patients with hepatitis C virus (HCV)-related cirrhosis, particularly on the impact of portal hypertension.nnnMETHODSnWe assessed hepatovenous pressure gradient (HVPG), liver stiffness (transient elastography), and interleukin (IL)-28B polymorphisms (rs12979860) in 90 cirrhotic patients with HCV infection (82% genotype 1 or 4) before antiviral therapy with pegylated interferon and ribavirin. Efficacy and safety were evaluated.nnnRESULTSnRates of sustained virologic response were significantly lower among patients with clinically significant portal hypertension (CSPH; HVPG ≥ 10 mm Hg; n = 50) than among patients without CSPH (HVPG <10 mm Hg; n = 40): 14% vs 51% (P = .0007). Seventy-nine percent and 83% of patients with CSPH and without CSPH, respectively, received more than 80% of planned dose (P = .647). The predictive value of HVPG (area under the curve [AUC], 0.743) was greater than that of liver stiffness (AUC, 0.647) or of baseline HCV RNA levels (AUC, 0.620). The IL-28B polymorphism was not associated significantly with a sustained virologic response. Multivariate analysis revealed that HVPG (odds ratio [OR], 14.3; P = .009), baseline HCV RNA levels (OR, 5.3; P = .019), and HCV genotype (OR, 6.5; P = .046) were independent risk factors for treatment failure. A trend toward higher incidence of anemia and neutropenia was observed for patients with CSPH. The incidence and grade of thrombocytopenia were significantly higher among patients with than without CSPH (94% vs 75%; P = .006).nnnCONCLUSIONSnHVPG is an independent predictor of response to antiviral therapy, with better predictive value than liver stiffness, baseline HCV RNA levels, HCV genotype, or IL-28B polymorphism. The incidence and grade of thrombocytopenia during antiviral therapy are higher among patients with CSPH. In evaluating cirrhotic HCV patients for antiviral treatment, measurement of HVPG should be considered.

Long term immunity following a booster dose of the inactivated Japanese Encephalitis vaccine IXIARO®, IC51

INTRODUCTIONnIXIARO (IC51), a recently approved inactivated Japanese Encephalitis vaccine, is immunogenic and safe in a 0/28 days primary immunization schedule. Neutralizing antibody titers decline with time and booster doses are likely needed to enhance persistence of immunity.nnnOBJECTIVESnTo assess the effect of a booster dose on neutralizing JE antibody titers for up to 12 months after boostering.nnnMETHODSnIn this phase III trial, 198 subjects, who had received primary immunization in a preceding randomized trial, were boosted with IXIARO 15 months after the primary immunization. Neutralizing antibody titers were assessed by plaque-reduction neutralisation test, PRNT.nnnRESULTSnPrior to the booster dose, 69.2% (137/198) of subjects had PRNT50 titers ≥ 1:10. One month after the booster, the rate of subjects with PRNT50 ≥ 1:10 (recognized as a protective titer) was 100%. This rate remained high at 98.5% at 6 and 12 months; GMTs were 22.5 before the booster and 900, 487 and 361 at 1, 6 and 12 months after the booster, respectively.nnnCONCLUSIONnA booster dose of IXIARO at 15 months after primary immunization was highly immunogenic with GMTs >5-fold higher than those seen immediately after primary immunization, and remained at high levels for at least 12 months after the booster.

Impact of smoking on the frequencies of micronuclei and other nuclear abnormalities in exfoliated oral cells: a comparative study with different cigarette types

The primary aim of the study was to investigate the impact of tar and nicotine contents of cigarettes on chromosomal damage in oral mucosa cells of smokers. We monitored the effect of smoking different cigarette types (i.e., of ultralight filter, light filter, medium filter and unfiltered cigarettes) on induction of nuclear anomalies including micronuclei (MN), broken eggs (BE), binucleates (BN), condensed chromatin (CC), karyorrhexis (KR), karyolysis (KL) and pyknosis (P) in exfoliated buccal cells. The cells were collected from 83 healthy heavy smokers (n=15-25/group) consuming a similar number of cigarettes (26-33) per day and from never smokers as controls (n=20). The frequencies of KR, CC, KL, BE and BN were increased significantly only in smokers of medium (MF) and non-filtered (NF) types of cigarettes while MN levels were only elevated (p < 0.0001) in the group that smoked NF cigarettes. Since BN and BE were increased (p < 00001) as a consequence of exposure to lower levels of toxic constituents in tobacco, it suggests that these endpoints, which both reflect DNA damage, are more sensitive than MN, which is the only parameter scored in most earlier studies. The induction of MN, BN, KR and KL increased significantly with daily tar exposure and decreased simultaneously with daily nicotine uptake (in all cases, P was < 0.0001). These findings also suggest that nicotine potentially protects cells against DNA reactive carcinogens contained in tobacco smoke although earlier in vitro and animal studies showed that the alkaloid induces DNA damage per se. A significant inverse correlation between the frequencies of endpoints such as cells with MN (- 1.56), MN (-1.69), BN (-1.36), KR (-1.10) and KL (-1.87) with the nicotine levels in cigarettes was found. However, this observation requires further verification by a controlled intervention study. In case it can be substantiated it will have an impact on the ongoing discussion of the health risks associated with nicotine replacement therapy.

Considerable under-treatment of chronic HCV infection in HIV patients despite acceptable sustained virological response rates in a real-life setting.

BACKGROUNDnAccording to guidelines, treatment of HCV infection should be considered a priority in HIV-HCV-coinfected patients.nnnMETHODSnThis multicentre study includes HIV-HCV-coinfected patients diagnosed since 2001 in 14 participating centres in Austria and Germany. Demographic and virological data were recorded. Factors associated with non-initiation of HCV treatment were identified.nnnRESULTSnAmong 9,524 HIV patients screened, 1,033 HIV-HCV-coinfected patients were identified (male/female: 760/273; age: 43±9 years; weight: 71±12 kg; CD4(+) T-cell nadir: 255±189 cells/μl; HCV RNA: 3.79×10(6) IU/ml; HIV RNA: 65×10(3) copies/ml). HCV genotype (GT) was predominantly GT-1 (62%). A total of 416 (40%) patients received HCV treatment, whereas 617 (60%) patients remained untreated. The main reasons for deferral of HCV treatment were patient refusal (20%), adherence/compliance (18%), active intravenous drug abuse (14%) and advanced immunodeficiency/AIDS (9%). Patients starting HCV treatment had significantly lower fibrosis stage (F2 versus F4; P<0.0001), higher CD4(+) T-cell count (530 cells/μl versus 430 cells/μl; P<0.0001), lower HIV RNA levels (18×10(3) copies/ml versus 47×10(3) copies/ml; P=0.0008) and higher alanine aminotransferase (ALT; 113 IU/ml versus 75 IU/ml; P<0.0001) than patients without initiation of HCV treatment. Age, HCV GTs, HCV RNA, haemoglobin levels, platelet count and white blood cell count were similar in patients receiving and in patients not receiving antiviral therapy. Multivariate analysis identified ALT levels (P<0.0001) and CD4(+) T-cell count (P<0.0001) as independent predictors of treatment uptake. The overall sustained virological response (SVR) was 41% (155/416), with GT-1 and non-GT1 patients achieving SVR rates of 29% and 48%, respectively.nnnCONCLUSIONSnThis large cohort study provides evidence for considerable under-treatment of chronic HCV infection in HIV patients. Despite acceptable treatment success in this real-life setting, HCV remains untreated in the majority of patients and often owing to potentially modifiable reasons.

Patients suffering from non-IgE-mediated cow’s milk protein intolerance cannot be diagnosed based on IgG subclass or IgA responses to milk allergens

To cite this article: Hochwallner H, Schulmeister U, Swoboda I, Twaroch TE, Vogelsang H, Kazemi‐Shirazi L, Kundi M, Balic N, Quirce S, Rumpold H, Fröschl R, Horak F, Tichatschek B, Stéfanescu CL, Szépfalusi Z, Papadopoulos NG, Mari A, Ebner C, Pauli G, Valenta R, Spitzauer S. Patients suffering from non‐IgE‐mediated cow’s milk protein intolerance cannot be diagnosed based on IgG subclass or IgA responses to milk allergens. Allergy 2011; 66: 1201–1207.

Potent protection of gallic acid against DNA oxidation: results of human and animal experiments.

Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a constituent of plant derived foods, beverages and herbal remedies. We investigated its DNA protective properties in a placebo controlled human intervention trial in single cell gel electrophoresis experiments. Supplementation of drinking water with GA (12.8 mg/person/d) for three days led to a significant reduction of DNA migration attributable to oxidised pyrimidines (endonuclease III sensitive sites) and oxidised purines (formamidopyrimidine glycosylase sensitive sites) in lymphocytes of healthy individuals by 75% and 64% respectively. Also DNA damage caused by treatment of the cells with reactive oxygen species (ROS) was reduced after GA consumption (by 41%). These effects were paralleled by an increase of the activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase and glutathion-S-transferase-π) and a decrease of intracellular ROS concentrations in lymphocytes, while no alterations of the total antioxidant capacity (TAC), of malondialdehyde levels in serum and of the urinary excretion of isoprostanes were found. Experiments with rats showed that GA reduces oxidatively damaged DNA in lymphocytes, liver, colon and lungs and protects these organs against γ-irradiation-induced strand breaks and formation of oxidatively damaged DNA-bases. Furthermore, the number of radiation-induced preneoplastic hepatic foci was decreased by 43% after oral administration of the phenolic. Since we did not find alterations of the TAC in plasma and lipid peroxidation of cell membranes but intracellular effects it is likely that the antioxidant properties of GA seen in vivo are not due to direct scavenging of radicals but rather to indirect mechanisms (e.g. protection against ROS via activation of transcription factors). As the amount of GA used in the intervention trial is similar to the daily intake in Middle Europe (18 mg/person/day), our findings indicate that it may contribute to prevention of formation of oxidatively damaged DNA in humans.

Recombinant allergen-based monitoring of antibody responses during injection grass pollen immunotherapy and after 5 years of discontinuation.

To cite this article: Gadermaier E, Staikuniene J, Scheiblhofer S, Thalhamer J, Kundi M, Westritschnig K, Swoboda I, Flicker S, Valenta R. Recombinant allergen–based monitoring of antibody responses during injection grass pollen immunotherapy and after 5u2003years of discontinuation. Allergy 2011; 66: 1174–1182.

Socioeconomic Factors and Suicide: An Analysis of 18 Industrialized Countries for the Years 1983 Through 2007

Objective: To evaluate the association between socioeconomic factors and suicide rates. Methods: Analysis of time series of suicide rates, gross domestic product, unemployment rates, labor force participation, and divorce rates of 18 countries are analyzed by the application of panel-vector error correction models. Main outcome measures are the association between the socioeconomic factors and suicide rates. Results: Decreasing economic growth and increasing divorce rates are significantly associated with increasing suicide rates in men. For women, increasing economic growth, increasing unemployment, and increasing divorce rates are significantly associated with increasing suicides. Increasing female labor force participation is associated with decreasing suicides. Conclusion: Socioeconomic factors are associated with suicide rates. However, this relationship differs by sex. The current results provide a strong argument that suicide prevention strategies must include the monitoring of socioeconomic development.