Abstract
This thesis contains clinical studies on 2009 pandemic influenza A (H1N1) and other respiratory pathogens. Chapter 1 is a general introduction. Chapter 2 comprises three studies on epidemiology. The first describes epidemiological characteristics of 964 adult outpatients who presented with influenza-like signs and symptoms during the 2009 H1N1 pandemic. Respiratory
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pathogens were detected in 41% and pandemic influenza A (H1N1) in 16%. Sensitivity, specificity, positive and negative predictive value of 4 investigated clinical case definitions were rather poor (66%, 70%, 34% and 90%, respectively). The second study characterizes the pandemic in a population of 412 symptomatic children. One third proved positive for influenza A (H1N1) and another one third for various other respiratory pathogens. H1N1-positive children were significantly older than H1N1-negatives (6.8 versus 4.2 years) and all showed a relatively mild clinical illness. In the third study a total of 334 neonates admitted to a medium care unit in the period 2010-2011 were screened for respiratory pathogens which were detected in 10.2%. Increasing age (OR 1.21 for each day older) and symptoms of rhinorrhea (OR 6.71) were identified as significant predictor variables.Chapter 3 includes one study on hospital prevention. Sixty-six healthcare workers with different occupational exposure risks (26 high-risk, 20 intermediate-risk and 20 low-risk) were intensively monitored throughout the pandemic outbreak, during which preventive hygiene standards were strictly followed. Only one participant from the high-risk group proved positive once for active H1N1 infection, which corresponds with a low incidence rate of 5.7/1,000 person weeks. Chapter 4 involves two studies on diagnostic testing. One study evaluated the performance of an influenza rapid-test for the detection of 2009 pandemic influenza A (H1N1). Overall sensitivity of the test was poor (20%). The other study explores the capacity of procalcitonin, a novel biomarker of inflammation, to differentiate bacterial from viral infection in febrile children during the pandemic outbreak. PCT levels were below the lower cut-off value (<0.71 ng/mL) in 22 of 25 children with viral diseases (88%), suggesting added diagnostic value. Chapter 5 considers cardiovascular complications. The first study investigates the association between respiratory virus infection and acute coronary syndrome. From 41 cases with a myocardial infarction and 41 matched controls it was shown that the adjusted odds ratio of acute coronary syndrome for patients who had laboratory proven recent respiratory viral infection was not significantly increased (OR 1.1; 95% CI 0.3-4.0). In the other study hemostatic changes after 2009 H1N1 vaccination in 94 healthy volunteers were assessed. After a follow-up of two weeks only D-dimer showed a significant decreasefrom 0.30 to 0.26 μg/L, which might indicate a slightly impaired fibrinolysis following vaccination. Finally, chapter 6 reviews the clinical effectiveness and safety of oseltamivir for treatment and prophylaxis of influenza. From 66 comparative studies it was shown that treatment reduces duration of illness by 0.5-1.5 days and secondary complications by 40-50% in otherwise healthy individuals. There is moderate evidence that treatment reduces secondary complications in those with chronic pulmonary or cardiovascular disease. Prophylaxis in general offers a 64-75% protection rate
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