BackgroundAn outbreak of Legionnaires’ Disease took place in the Swedish town Lidköping on Lake Vänern in August 2004 and the number of pneumonia cases at the local hospital increased markedly. As soon as the first patients were diagnosed, health care providers were informed and an outbreak investigation was launched.MethodsClassical epidemiological investigation, diagnostic tests, environmental analyses, epidemiological typing and meteorological methods.ResultsThirty-two cases were found. The median age was 62 years (range 36 – 88) and 22 (69%) were males. No common indoor exposure was found. Legionella pneumophila serogroup 1 was found at two industries, each with two cooling towers. In one cooling tower exceptionally high concentrations, 1.2 × 109 cfu/L, were found. Smaller amounts were also found in the other tower of the first industry and in one tower of the second plant. Sero- and genotyping of isolated L. pneumophila serogroup 1 from three patients and epidemiologically suspected environmental strains supported the cooling tower with the high concentration as the source. In all, two L. pneumophila strains were isolated from three culture confirmed cases and both these strains were detected in the cooling tower, but one strain in another cooling tower as well. Meteorological modelling demonstrated probable spread from the most suspected cooling tower towards the town centre and the precise location of four cases that were stray visitors to Lidköping.ConclusionsClassical epidemiological, environmental and microbiological investigation of an LD outbreak can be supported by meteorological modelling methods.The broad competence and cooperation capabilities in the investigation team from different authorities were of paramount importance in stopping this outbreak.
An outbreak of Legionnaires' disease (LD) occurred in Lidköping, Sweden, in August 2004. A cooling tower was identified as the probable source of infection. During the outbreak period an unexpected 3-6-fold increase in pneumonia patients was noted at the local hospital. During 7 weeks LD was diagnosed in 15 patients by urinary antigen and/or sputum culture. Additionally, 15 LD patients were diagnosed later by serology. Patients with LD were generally younger, more healthy, and more often smokers compared to other pneumonia patients. On admittance they had more severe symptoms with high fever and raised CRP levels, and more often hyponatraemia, gastrointestinal and CNS symptoms. A causative agent besides Legionella was found in 2 patients only. A significant titre rise for Mycoplasma and/or Chlamydophila pneumoniae was found in 13 of 29 tested patients with confirmed LD. We conclude that the clinical diagnosis of LD is difficult and that available diagnostic methods detect only a minority of patients in the acute phase. Therefore in severe pneumonia, empirically targeted therapy should be instituted on clinical grounds irrespective of the results of diagnostic tests. The observation of increased antibody levels for M. and C. pneumoniae suggests an unspecific immune reaction and merits further study.
Background In myeloproliferative neoplasms (MPN), Interferon-α (IFN-α) has been shown effective in inducing hematologic and molecular responses and in reducing vascular events. In clinical practice its use is mainly limited by intolerance due to side effects. Aim We sought to evaluate the tolerability of IFN-α therapy, the thromboembolic incidence and the causes of termination of therapy in a cohort of MPN, treated outside of clinical trials. Methods One hundred patients (M/F 41/59, median age 48 years, range 15-73) with a diagnosis of polycythemia vera (PV, n=47), essential thrombocythemia (ET, n=43) and myelofibrosis (MF, n=10) according to the WHO 2008 criteria, on current or previous treatment with IFN-α (IFN-α-2b, Peg-IFN-α-2b, Peg-IFN-α-2a) were included. The patients, diagnosed 1987-2012, were recruited from 9 centers in Sweden and Norway, and retrospectively analyzed. Hematologic response in PV and ET was assessed according to ELN criteria from 2009. Response to treatment in MF was defined as platelets ² 400x109 /L, white blood counts ² 10x109/L and transfusion independency. Results IFN-α treatment characteristics are displayed in Table 1. The median treatment duration for IFN-α was 34 months. Treatment prior to IFN-α had been received by 44 pts including hydroxyurea (n=34), anagrelide (n=19), busulphan (n=2), radioactive phosphorus (n=1), 10 pts having received more than one cytoreductive agent. Complete hematologic response (CR) was observed in 58 pts (PV=28/47, ET=30/43) and partial hematologic response (PR) in 15 pts (PV=2, ET=13). In MF, hematologic response was noted in 8 out of 10 patients. IFN-α related adverse events (AE) were recorded in 76 pts (76/100, 76%) with similar rates between genders (M 30/41, 73%, F 45/59, 76%). AE were generally of low grade. Twenty pts experienced multiple (³ 3) side effects (M/F 6/14), females reporting a total of 96 AE compared to 53 in males. Hematologic toxicity was low with 4 pts presenting with anemia, 4 with leukopenia and 3 with thrombocytopenia. Most common non-hematologic toxicities were fatigue in 30 pts (M/F 11/19), myalgia in 28 (M/F 11/17) and depression in 21 (M/F 4/17), followed by liver function test elevation (n=9), headache (n=9), alopecia (n=8) and skin reaction (n=7). In two pts with autoimmune co-morbidities (rheumatoid arthritis, psoriasis), flare-up of symptoms related to autoimmune activity were seen, leading to discontinuation of therapy. Only one vascular event occurred in a 64 year old woman with PV, in CR since 92 months, who developed a myocardial infarction after 94 months of IFN-α-2b treatment. A total of 43 pts (M 16/41, 39%, F 27/59, 46%) discontinued therapy, of whom 34 (M 13/41, 32%, F 21/59, 36%) due to side effects. The most common cause of discontinuation of therapy due to side effects was depression (15/21), followed by fatigue (12/30) and myalgia (9/28). Nineteen (19/34, 58%) of the pts who discontinued therapy due to side effects were in CR. Discontinuation due to other reasons than side effects were lack of efficacy/progression of disease (n=5), co-morbidities (n=2), CR including molecular response (n=2) and pregnancy (n=1). Out of the 53 pts with ET and MF, 25 were JAK2V617F mutated and 14 had a CALR-mutation. No significant differences between these two groups were seen regarding side effects or discontinuation rate. Out of the 57 pts remaining on IFN-α, 19 still received IFN-α-2b (19/35, 54%), 7 PegIFN-α-2b (7/12, 58%) and 31 PegIFN-α-2a (31/53, 58%). Conclusion In this retrospective cohort study, the treatment discontinuation rate due to side effects was higher than in previous reports. This may be explained by the relatively long median duration of treatment in this cohort, reflecting a poor tolerance of low-grade toxicity over time. Depression was frequent and the most common reported side effect when therapy was discontinued. Gender difference, with females reporting a higher incidence of depression and a larger total burden of AE, was noted. The frequency of thromboembolic events was very low in this IFN-α treated cohort. Table 1. IFN-α treatment characteristics. Type of Interferon Patiens (n) Dose per week–median (range) Treatment time-median IFN α-2b 35 9 MIE (1,2-20) 58 PegIFN α-2b 12 40 μg (30-80) 46 PegIFN α-2a 53 90 μg (30-135) 15 Disclosures No relevant conflicts of interest to declare.
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