Clinical symptoms cannot predict influenza infection during the 2013 influenza season in Bavaria, Germany.

For influenza surveillance and diagnosis typical clinical symptoms are traditionally used to discriminate influenza virus infections from infections by other pathogens. During the 2013 influenza season we performed a multiplex assay for 16 different viruses in 665 swabs from patients with acute respiratory infections (ARIs) to display the variety of different pathogens causing ARI and to test the diagnostic value of both the commonly used case definitions [ARI, and influenza like illness (ILI)] as well as the clinical judgement of physicians, respectively, to achieve a laboratory-confirmed influenza diagnosis. Fourteen different viruses were identified as causing ARI/ILI. Influenza diagnosis based on clinical signs overestimated the number of laboratory-confirmed influenza cases and misclassified cases. Furthermore, ILI case definition and physicians agreed in only 287/651 (44%) cases with laboratory confirmation. Influenza case management has to be supported by laboratory confirmation to allow evidence-based decisions. Epidemiological syndromic surveillance data should be supported by laboratory confirmation for reasonable interpretation.

Effectiveness of trivalent and monovalent influenza vaccines against laboratory-confirmed influenza infection in persons with medically attended influenza-like illness in Bavaria, Germany, 2010/2011 season.

We estimated the vaccine effectiveness (VE) of trivalent and monovalent influenza vaccines,respectively, against laboratory-confirmed influenza infections in patients with influenza-likeillness who visited physicians participating in the Bayern Influenza Sentinel in Bavaria, Germany during 2010/2011. Swab specimens were analysed for influenza A(H1N1)pdm09, A(H3) andB by PCR. VE was estimated using the test-negative case-control study design and logistic regression. In total, 1866 patients (790 cases, 1076 controls) were included. The VE of trivalentvaccines administered in season 2010/2011 against laboratory-confirmed infection with any influenza virus, adjusted for age group, sex, chronic illness and week of arrival of the specimen,was 67.8% [95% confidence interval (CI) 39.2­82.9)]. The adjusted VE of monovalent influenza vaccines administered in season 2009/2010 against laboratory-confirmed influenza A(H1N1)pdm09 infection in 2010/2011 was 38.6% (95% CI x 70.0 to 77 . 8). This is the first VE study conducted in Bavaria. We concluded that the trivalent influenza vaccines were effective in our study population

A multiplex one-step real-time RT-PCR assay for influenza surveillance.

For surveillance purposes real-time PCR assays for influenza viruses had to be adapted to the pandemic influenza A(H1N1)2009 strain. We combined published primers and probes for influenza A, influenza B and an internal amplification control with a detection system for influenza A(H1N1)2009 to set up a rapid, reliable, simple and cost-effective high-throughput multiplex one-step real-time RT-PCR. The workflow also includes automated sample preparation for high-throughput screening. The lower limit of detection of the multiplex assay was 3.5x10(2) RNA copies per PCR reaction. The diagnostic sensitivity of the multiplex assay was 87.7%, but increased to 99.4% for influenza-positive samples yielding C(t) values of less than 34 cycles in the respective diagnostic assay. High specificity was confirmed by sequencing and correct detection of 15 reference samples from two quality assurance studies. The multiplex PCR was introduced for surveillance of samples from a network of general practitioners and paediatricians in Bavaria, Germany during the influenza pandemic of 2009. Comparison with surveillance data from reported cases proved the reliability of the multiplex assay for influenza surveillance programmes.

SARS - Pandemie und Emerging Disease.

The SARS-epidemic of 2002/2003 with worldwide 8.096 cases and 774 fatalities was the first pandemia of the 21st century. SARS, the severe acute respiratory syndrome, arose in southern China and spread from Southeast-Asia finally over all five continents. It caused heavy pneumonia with pulmonal failure and enteric involvement in man. The causative agent was a novel coronavirus (SARS-CoV), which was transmitted from bats to small carnivores and from them to man. The mutations of the viral receptor gene thus allowed the infection of man and the transmission from man to man. The SARS-pandemia can therefore be regarded as a model of an emerging disease.

Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission--experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG).

Patients with CLL responding to initial chemotherapy with fludarabine alone (F) or in combination with cyclophosphamide (FC) were randomized for treatment with alemtuzumab (30 mg i.v. TIW, 12 weeks) or observation. Of 21 evaluable patients, 11 were randomized to alemtuzumab before the study was stopped due to severe infections in seven of 11 patients. These infections (one life-threatening pulmonary aspergillosis IV; four CMV reactivations III requiring i.v. ganciclovir; one pulmonary tuberculosis III; one herpes zoster III) were successfully treated and not associated with cumulative dose of alemtuzumab. In the observation arm, one herpes zoster infection II and one sinusitis I were documented. At 6 months after randomization, two patients in the alemtuzumab arm converted to CR, while three patients in the observation arm progressed. After alemtuzumab treatment, five of six patients achieved a molecular remission in peripheral blood while all patients in the observation arm remained MRD-positive (P=0.048). At 21.4 months median follow-up, patients receiving alemtuzumab showed a significant longer progression-free survival (no progression vs mean 24.7 months; P=0.036). In conclusion, a consolidation therapy with alemtuzumab is able to achieve molecular remissions and longer survival in CLL, but a safe treatment regimen needs to be determined.

[Adult T-cell lymphoma/leukemia: a very rare disease in Europe]. / Das adulte T-Zell Lymphom/Leukämie--eine in Europa sehr seltene Erkrankung.

HISTORY AND CLINICAL FINDINGS: A 45-year-old man was admitted with generalized itchy papules. He was originally from the Carribean island of Grenada. The disease had started two years before and was diagnosed as lupus erythematosus, polymorphic light eruption and atopic eczema. Physical examination showed skin-colored papules all over the integument, sebostasis and enlarged supraclavicular and inguinal lymph nodes. INVESTIGATIONS: Lymphocyte count was elevated with 58% as well as LDH (322 U/l) and gamma GT (133 U/l). In a blood smear characteristic pleomorphic lymphoid cells (flower cells) could be obtained. Histopathologic evaluation demonstrated a subepidermally located infiltrate of pleomorphic lymphocytes with epidermal involvement. HTLV-I/II serology (ELISA-screening test) was positive. Polymerase chain reaction analysis revealed HTLV-specific sequences. DIAGNOSIS, TREATMENT AND COURSE: Diagnosis of adult T-cell lymphoma/leukemia was obtained. Treatment consisted of interferon alpha 2b and zidovudine which resulted in a rapid response. However, as a result of an increased loss of weight (12 kg) this therapy was stopped. Two weeks later generalized lymphadenopathy and disseminated skin lesions were observed. Chemotherapy (CHOP-scheme) was initiated. The patient deceased with signs of an acute leukemia after a short period. CONCLUSIONS: Adult T-cell lymphoma/leukemia is a rare disease in Europe. However, in patients with skin rashes, and lymphadenopathy, which are originally from HTLV-I endemic areas, adult T-cell lymphoma/leukemia should be considered.

Urine desmosine is unrelated to cigarette smoking or to spirometric function.

We measured urine desmosine by radioimmunoassay in 157 subjects. Desmosine excretion (expressed as desmosine/creatinine ratio) did not correlate with ventilatory function (assessed by spirometry) or with current smoking status or total lifetime cigarette consumption. We conclude that measurement of urine desmosine may not be useful as an indirect measurement of elastolysis in cigarette smokers.

Mechanisms of airway smooth muscle response to isoproterenol and theophylline.

Airway smooth muscle preparations from various sites and species exhibit a range of sensitivities to the same beta-adrenergic agonist. This variability has been attributed to beta-receptor function but the exact mechanism determining the response has not been identified. After first inducing contraction with acetylcholine, we measured isoproterenol and theophylline relaxation responses in five separate airway smooth muscle preparations in vitro. The order of sensitivity was identical for both drugs: guinea pig trachea greater than dog lung strip greater than dog bronchiole greater than rat trachea greater than dog trachea. Because of evidence that both drugs act by increasing adenosine 3',5'-cyclic monophosphate (cAMP) concentrations, we utilized a kinetic model of cAMP metabolism to investigate the possibility that the identical order of sensitivity to both drugs could be explained by a common mechanism. Relaxation responses to both drugs are in accord with known kinetic data. Small differences in the velocity constants of enzymes affecting cAMP metabolism or differences in the relaxation response to the same concentrations of cAMP can fully explain the variable muscle responses to both drugs.