Erik Bäck

Non‐Hodgkin's lymphoma and other nonhepatic malignancies in Swedish patients with hepatitis C virus infection

The aim of this study was to evaluate the association between hepatitis C virus (HCV) infection and non‐Hodgkins lymphoma (NHL), multiple myeloma (MM), thyroid cancer (TC), chronic lymphatic leukemia (CLL), acute lymphatic leukemia (ALL), and Hodgkins lymphoma (HL). A Swedish cohort of 27,150 HCV‐infected persons notified during 1990‐2000 was included in the study. The database was linked to other national registers to calculate the observation time, expressed as person‐years, and to identify all incident malignancies in the cohort. The patients were stratified according to assumed time of previous HCV infection. The relative risk of malignancy was expressed as a standardized incidence ratio (SIR)—the observed number compared to the expected number. During 1990‐2000 there were 50 NHL, 15 MM, 14 ALL, 8 TC, 6 CLL, and 4 HL diagnoses in the cohort. Altogether, 20 NHL, 7 MM, 5 TC, 4 CLL, 1 ALL, and 1 HL patient fulfilled the criteria to be included in the statistical analysis. The observation time was 122,272 person‐years. The risk of NHL and MM was significantly increased in the stratum with more than 15 years of infection (SIR 1.89 [95% CI, 1.10‐3.03] and 2.54 [95% CI, 1.11‐5.69], respectively). The association was not significant in TC or CLL. In conclusion, we report the incidence of several malignancies in a nationwide cohort of HCV‐infected persons. Although the delayed diagnosis of HCV probably has resulted in an underestimation of the risk, this study showed a significantly increased risk of NHL and MM. (HEPATOLOGY 2005;41:652–659.)

Landscape Epidemiology of Tularemia Outbreaks in Sweden

Transmission sites of specific Francisella tularensis genotypes were highly localized during natural outbreaks of human tularemia.

Tularaemia in an emergent area in Sweden: an analysis of 234 cases in five years.

A retrospective study of clinical tularaemia in an emergent area in Sweden is presented. 234 patients seen during the y 2000–2004 were studied, using case files and a questionnaire. There was a predominance of ulceroglandular tularaemia (89%), occurring in late summer and early autumn, reflecting the dominance of mosquito-borne transmission. The incubation period varied from a few hours to 11 d, with a median of 3 d. Cutaneous manifestations of tularaemia, apart from primary lesions, were noted in 43% of the cases. Coughing was common, even in patients with ulceroglandular tularaemia, supporting the view that haematogenous spread to the respiratory system occurs. Regular laboratory tests, such as WBC, ESR and C-reactive protein, were in general only moderately elevated. In the earlier y studied, the Doctors Delay was substantial as was the misdiagnosis and prescription of inadequate antibiotics. In the later y, however, the delay and misdiagnosis were significantly lower, reflecting the increased recognition of the disease by the physicians in the area. A few relapses occurred, all in patients treated with doxycycline. No lethality was seen, reflecting the benign course of tularaemia type B infection.

Cause of death in individuals with chronic HBV and/or HCV infection, a nationwide community‐based register study

Summary.  Studies on chronic viral hepatitis and mortality have often been made on selected populations or in high‐endemic countries. The aim of this study was to investigate the causes of death and the mortality rates in the nationwide cohorts of people chronically infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) in Sweden, a low‐endemic country. All notifications on chronic HBV infection and HCV infection 1990–2003 were linked to the Cause of Death Register. A total of 9517 people with chronic HBV infection, 34 235 people with HCV infection and 1601 with chronic HBV–HCV co‐infection were included, and the mean observation times were 6.4, 6.3 and 7.9 years, respectively. The mortality in the cohorts was compared with age‐ and gender‐specific mortality in the general population and standardized mortality ratios (SMR) were calculated. All‐cause mortality was significantly increased, SMR 2.3 (HBV), 5.8 (HCV) and 8.5 (HBV–HCV), with a great excess liver‐related mortality in all cohorts, SMR 21.7, 35.5 and 46.2, respectively. In HCV and HBV–HCV infected there was an increased mortality due to drug‐related psychiatric diagnoses (SMR: 20.7 and 27.6) and external causes (SMR: 12.4 and 11.4), predominantly at younger age. To conclude, this study demonstrated an increased all‐cause mortality, with a great excess mortality from liver disease, in all cohorts. In people with HCV infection the highest excess mortality in younger ages was from drug‐related and external reasons.

Molecular Detection of Persistent Francisella tularensis Subspecies holarctica in Natural Waters

Tularemia, caused by the bacterium Francisella tularensis, where F. tularensis subspecies holarctica has long been the cause of endemic disease in parts of northern Sweden. Despite this, our understanding of the natural life-cycle of the organism is still limited. During three years, we collected surface water samples (n = 341) and sediment samples (n = 245) in two areas in Sweden with endemic tularemia. Real-time PCR screening demonstrated the presence of F. tularenis lpnA sequences in 108 (32%) and 48 (20%) of the samples, respectively. The 16S rRNA sequences from those samples all grouped to the species F. tularensis. Analysis of the FtM19InDel region of lpnA-positive samples from selected sampling points confirmed the presence of F. tularensis subspecies holarctica-specific sequences. These sequences were detected in water sampled during both outbreak and nonoutbreak years. Our results indicate that diverse F. tularensis-like organisms, including F. tularensis subsp. holarctica, persist in natural waters and sediments in the investigated areas with endemic tularemia.

Transcriptional profiling of the peripheral blood response during tularemia

Tularemia is a febrile disease caused by the highly contagious bacterium Francisella tularensis. We undertook an analysis of the transcriptional response in peripheral blood during the course of ulceroglandular tularemia by use of Affymetrix microarrays comprising 14 500 genes. Samples were obtained from seven individuals at five occasions during 2 weeks after the first hospital visit and convalescent samples 3 months later. In total, 265 genes were differentially expressed, 95 of which at more than one time point. The differential expression was verified with real-time quantitative polymerase chain reaction for 36 genes (R2=0.590). The most prominent changes were noted in samples drawn on days 2–3 and a considerable proportion of the upregulated genes appeared to represent an interferon-γ-induced response and also a proapoptotic response. Genes involved in the generation of innate and acquired immune responses were found to be downregulated, presumably a pathogen-induced event. A logistic regression analysis revealed that seven genes were good predictors of the early phase of tularemia. This is the first description of the transcriptional host response to ulceroglandular tularemia and the study has identified gene subsets relevant to the pathogenesis of the disease and subsets that may serve as early diagnostic biomarkers.

Antibiotic Therapy in Pneumonia: A Comparative Study of Parenteral and Oral Administration of Penicillin

An open, randomized study of treatment of radiologically verified community-acquired pneumonia is described. 33 patients were treated with phenoxymethylpenicillin orally in an average dose of 2 g every 8 h, and 36 patients were treated intravenously with benzylpenicillin 3 g every 8 h. When temperature was normalized the antibiotic dose was reduced in both groups to oral phenoxymethylpenicillin in an average dose of 1 g every 8 h. 24 and 26 patients in respective groups completed 10 days of therapy. No statistically significant differences between the two groups were found when compared for duration of fever, hospital stay, CRP, ESR, leukocyte counts and X-ray normalization. In spite of the low number of patients included in this study it gives a clear indication that treatment of pneumonia with penicillin by the oral route results in the same outcome as parenteral treatment when patients suffering from vomiting, diarrhoea and severe illness with respiratory distress are excluded. In addition, oral treatment is cheaper than parenteral and more simple to manage.

Clinical use of a diagnostic PCR for Francisella tularensis in patients with suspected ulceroglandular tularaemia

A retrospective analysis to evaluate the clinical use of a diagnostic PCR for Francisella tularensis in patients with suspected ulceroglandular tularaemia was performed. 154 samples, 129 from patients with definitive tularaemia and 25 from patients where tularaemia could be ruled out, were analysed. The diagnostic PCR had a specificity of 96%, a sensitivity of 78.3%, and a Positive Predictive Value of 99%. Especially samples from encrusted lesions, even up to 4 weeks old, in patients with tularaemia, were PCR positive to a high degree when taken properly. The diagnostic PCR is useful in suspected ulceroglandular tularaemia, giving a fast and accurate diagnosis.

Water-Melon as a Vehicle of Transmission of Shigellosis

An epidemic of Shigella sonnei infection is described in which the only common source of infection was the ingestion of water-melon. Bacteriological studies demonstrated that S. sonnei bacteria injected into water-melons could multiply to infective doses. Therefore water-melons should not be excluded as a possible source of S. sonnei infection.

Non-efficacy of low-dose intradermal vaccination against hepatitis B in Down's syndrome

Persons with Downs syndrome (DS) constitute a risk group for hepatitis B (HB) and are recommended to be immunized. Of 123 persons with DS in Orebro county screened for markers of HB, 31% had such markers; 16% were potentially contagious. 83 persons without markers participated in a comparative trial of the immunogenicity of a recombinant HB vaccine given either intramuscularly (IM) or in a lower dose intradermally (ID). Immunity developed in 73% after IM vaccination as compared to 29% of those given ID vaccination (p < 0.005). At 3-year follow-up half and two-thirds of the immune persons, respectively, had lost their immunity. Those > 30 years had a poor immunization response compared to the younger ones (p < 0.01). Only 19% of the non-responders developed immunity after an IM booster dose given 10 months after the third injection. Intradermal vaccination is not warranted in persons with DS, especially not in middle aged and older persons. A booster dose of vaccine does not ascertain immunity in those who do not respond with immunity to the ordinary immunization schedule. Post-vaccination immunity should therefore be controlled.