Bakgrund: Luftvägarna inkluderar flera olika delar bland annat näsa, bihålor, svalg, struphuvudet, luftstrupen och lungor. Luftvägarna kan infekteras av virus eller bakterier och kan leda till inflammation. De olika varianter av virus som kan orsaka luftvägsinfektion är rhinoviruset, influensavirus (RS-virus), coronavirus samt bakterier av streptokocker eller pneumokocker. En variant av coronavirus med namnet, SARS-CoV-2 har orsakat utbrott i världen och förklarades som pandemi 11 mars 2020. I genomsnitt brukar vuxna insjukna i luftvägsinfektion ca 2-4 gånger per år, medan barn insjuknar oftare, 6-8 gånger om året. Immunförsvaret består av komponenter som samverkar för att angripa bakterier, svamp samt virus och skydda kroppen mot infektioner. Vitamin-D har en väsentlig påverkan på immunförsvaret, både det medfödda och adaptiva. Kroppen kan få i sig Vitamin-D genom kost och via UV-strålningen från solen.Vitamin-D har påverkan på immunförsvaret som leder till uppreglering av immunförsvarets väsentliga komponenter samt bidrar till att bekämpa infektion och skada cellmembran hos mikrober. Syfte: att undersöka om d-vitamin har skyddande effekt mot luftvägsinfektion. Metod: Följande litteraturstudie utgår från fem vetenskapliga artiklar från databasen, PubMed. Följande sökord var ”vitamin-D”, ”covid-19” och ”respiratory infection”.Resultat: Samtliga fem studier påvisade att tillskott av vitamin-D minskade förekomst av luftvägsinfektion samt att sjukdomsförloppet förkortades. I studie 5 minskade sannolikheten för covid-19 patienter med tillskott av vitamin-D att placeras i intensivvården. Det fanns signifikant skillnad i dosering av vitamin-D i studie 2 som jämfördes med en högre dos och en rekommenderad dos. Slutsats: Samtliga studier påvisar att vitamin-D har en viss skyddande effekt mot luftvägsinfektioner samt hjälper förkorta sjukdomsförloppet genom att stärka immunförsvaret. Studiernas resultat har varit varierande utifrån dess olika syfte samt behandlings tillvägagångssätt, således förekommit svårigheter att dra konkreta slutsatser. Doseringarna tolererades bra och orsakade inte allvarliga biverkningar som kunde kopplas till behandlingen. Det krävs ytterligare studier för att faställa vitamin-D:s skyddande effekter på luftvägsinfektion samtidigt om det förekommer individuella skillnader i upptag av vitamin-D samt metabolism. / Background: The respiratory tract includes several different parts including; nose, sinuses, pharynx, larynx, trachea and lungs. The respiratory tract can be infected by viruses or bacteria, which can lead to inflammation. The respiratory infection can be caused by rhinovirus, influenza virus, coronavirus or bacteria, such as streptococci or pneumococci. A variant of the coronavirus with the name, SARS-CoV-2 caused outbreaks over the entire world and was declared as a pandemic on 11th March 2020. On average, adults get a respiratory infection about 2-4 times a year, while children get sick more often, approximately 6-8 times a year. The immune system consists of components that work together to attack bacteria, fungi and viruses to protect the body against infections. Vitamin D has a significant effect on the innate and adaptive immune system. The body can absorb vitamin D through diet and from UV-radiation from the sun. Vitamin D has an effect on the immune system, which leads to upregulation of the immune system´s essential components and helps to fight infections as well as damaging cell membrane of microbes.  Objective: The purpose of the study was to investigate whether vitamin D has a protective effect in the fight against respiratory infections.  Method: The following literature study was based on five scientific articles from the databasePubMed. The following keywords were “vitamin d” and “respiratory infection”.Results: All five studies showed that vitamin D supplementation reduced the incidence of respiratory infections and the course of the disease was shortened. In study 5, the probability of covid-19 patients with vitamin D supplementation to be placed in intensive care decreased. There was a significant difference in the dosage of vitamin D in study 2, where higher dose was compared to a recommended dose.  Conclusion: All studies show that vitamin D has a certain protective effect against respiratory infections and helps shorten the course of the disease by strengthening the immune system. The results of the studies have varied depending on different aims and treatment approaches. Therefore it has been difficult to draw concrete conclusions. The dosages where well tolerated and didn’t cause serious side effects that could be linked to the treatment. Further studies are needed to determine the protective effects of vitamin D on respiratory tract infections and also toinvestigate whether there are individual differences in vitamin D uptake and metabolismthereby being able to draw concrete and general conclusions.

In this thesis, we have studied the immunological processes of joint inflammation that may be targets for future treatment of patients with arthritis. We focus on the immune-modulating properties of interferon-α (IFN-α) and uridine in experimental arthritis. The nucleoside uridine, which is regarded a safe treatment has anti-inflammatory properties notably by inhibiting tumor necrosis factor (TNF) release. Because the inflamed synovium in rheumatoid arthritis (RA) is characterised by pathogenic TNF-production, uridine could potentially be away to ameliorate arthritis. Systemic administration of uridine had no effect on antigeninduced arthritis (AIA), which is a T-cell dependent model where animals are immunized twice (sensitization) with bovine serum albumin (mBSA), before local triggering of arthritis by intra-articular antigen (mBSA) re-challenge. In contrast, intra-articular administration of uridine clearly down modulated development of AIA in a dose dependent manner and inhibited the expression of synovial adhesion molecules, influx of inflammatory leukocytes and synovial expression of TNF and interleukin 6, but did not affect systemic levels of proinflammatory cytokines or antigen-specific T-cell responses. Local administration of uridine may thus be a viable therapeutic option for treatment of arthritis in the future. Viral double-stranded deoxyribonucleic acid (dsRNA), a common nucleic acid found in most viruses, can be found in the joints of RA patients and local deposition of such viral dsRNA induces arthritis by activating IFN-α. Here we show that arthritis induced by dsRNA can be mediated by IFN-producing dendritic cells in the joint and this may thus explain why viral infections are sometimes associated with arthritis. Earlier, to study the effect of dsRNA and IFN-α in an arthritis model, that like RA, is dependent on adaptive immunity, dsRNA and IFN-α were administered individually during the development of AIA. Both molecules clearly protected against AIA in a type I IFN receptor-dependent manner but were only effective if administered in the sensitization phase of AIA. Here we show that the anti-inflammatory effect of IFN-α is critically dependent on signalling via transforming growth factor β (TGF-β) and the enzymatic activity of indoleamine 2,3 dioxygenase 1 (IDO). The IDO enzyme is produced by plasmacytoid DC and this cell type was critically required both during antigen sensitization and in the arthritis phase of AIA for the protective effect of IFN-α against AIA. In contrast, TGF-β and the enzymatic activity of IDO were only required during sensitization, which indicate that they are involved in initial steps of tolerogenic antigen sensitization. In this scenario, IFN- α first activates the enzymatic activity of IDO in pDC, which converts Tryptophan to Kynurenine, which thereafter activates TGF-β. Common for IDO-expressing pDC, Kyn and TGF-β is their ability to induce development of regulatory T cells (Tregs). We found that Tregs were crucial for IFN-α-mediated protection against AIA, but only in the arthritis phase. In line with this, adoptive transfer of Tregs isolated from IFN-α treated mice to recipient animals in the arthritis phase clearly protected against AIA. The numbers of Tregs were not significantly altered by IFN-α but IFN-α increased the suppressive capacity of Tregs against antigen-induced proliferation. This enhanced suppressive activity of Tregs in the arthritis phase was dependent on the earlier activated enzyme IDO1 during the sensitization phase of AIA. Thus, presence of IFN-α at the time of antigen sensitization activates the enzymatic activity of IDO, which generates Tregs with enhanced suppressive capacity that upon antigen re-challenge prevents inflammation. We have thus identified one example of how immune tolerance can be developed, that may be a future way to combat autoimmunity.

Antibodies passively administered together with their specific antigen can enhance or suppress the specific antibody response. This phenomenon is known as antibody feedback regulation. Whether this modulation causes up- or downregulation of the antibody response depends both on the antibody isotype and the antigen used. IgG antibodies passively administered together with particulate antigens, e.g. erythrocytes, can completely prevent the induction of an antibody response to the antigen. The suppressive capacity of IgG has been routinely used in the clinic since the 1960’s in RhD-prophylaxis to prevent hemolytic disease of the fetus and newborn. Although studied for decades, the underlying mechanism of IgG-suppression has remained elusive. The main focus of this thesis has been to elucidate the mechanism behind IgG-suppression of antibody responses in vivo in mouse models using intravenous immunization with specific IgG together with native or haptenated sheep red blood cells, SRBC. We show that IgG-suppression of IgM and long-term serum IgG-responses operates independently of activating FcγRI, III, IV, or the inhibitory FcγRIIB, thus confirming and extending previous findings. Moreover, we demonstrate for the first time that C1q, C3 and CR1/2 are dispensable for IgG-suppression of antibody responses. These findings strongly argue against the involvement of Fc-dependent mechanisms as the explanation for IgG-suppression. Interestingly, GC formation occurs in IgG-suppressed mice although the antibody response to surface SRBC epitopes are completely suppressed. The data suggests that these GCs develop in response to intracellular SRBC epitopes as well as to the passively administered suppressive IgG. Moreover, we demonstrate that passively administered IgG suppresses several parameters of an antibody/B cell response including antigen specific GC and non-GC B cells, extra-follicular antibody secreting cells, long-lived plasma cells and induction of immunological memory. Before the onset of the present study, two mechanisms appeared compatible with the majority of experimental findings: IgG-mediated antigen clearance and epitope masking. Herein we show that the contribution of IgG-mediated antigen clearance is negligible and that suppression of IgG-responses is strictly epitope specific. This provides compelling evidence that a very important mechanism underlying IgG-suppression is epitope masking.

A sophisticated evolutionary conserved innate immune system has evolved in insects to fight pathogens and to restrict damage in harmful (danger) situations including cancer. A significant amount of knowledge about different infection models in Drosophila has been generated in past decades, which revealed functional resemblances and implications for vertebrate systems. However, how Drosophila responds towards multicellular parasitic nematodes and in danger situations is still little understood. Therefore, the aim of the thesis was to characterize multiple aspects of the host defense in the two important contexts mentioned above. We analyzed the transcriptome profiles of nematode-infected Drosophila larvae with uninfected samples. For this we employed the entomopathogenic nematode Heterorhabditis bacteriophora with its symbiont Photorhabdus luminescence to infect Drosophila larvae. We found 642 genes were differentially regulated upon infection. Among them a significant portion belonged to immune categories. Further functional analysis identified a thioester containing protein TEP3, a recognition protein GNBP-like 3, the basement membrane component protein Glutactin and several other small peptides. Upon loss or reduced expression of these genes hosts showed mortality during nematode infections. This study uncovers a novel function for several of the genes in immunity. Furthermore, we investigated the cellular response towards nematodes. When we eliminated hemocytes genetically (referred to as hml-apo) in Drosophila, we found hml-apo larvae are resistant to nematodes. Subsequent characterization of hml-apo larvae showed massive lamellocyte differentiation (another blood cell type which is rare in naïve larvae), emergence of melanotic masses, up- and down-regulation of Toll and Imd signaling respectively suggesting a pro-inflammatory response. Moreover, a striking defective leg phenotype in adult escapers from pupal lethality was observed. We identified nitric oxide (NO) as a key regulator of these processes. We also showed that imaginal disc growth factors 3 (IDGF3): (a) protects hosts against nematodes, (b) is a clotting component and (c) negatively regulates Wnt and JAK/STAT signaling. To follow larval behavior in the presence or absence of nematodes we monitored Drosophila larval locomotion behaviors using FIMtrack (a recently devised automated method) to elucidate evasive strategies of hosts. Finally, we characterized host defenses in three Drosophila leukemia models with and without nematode infection. Taken together, these studies shed light on host responses in two crucial circumstances, nematode infections and danger situations. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: Manuscript. Paper 3: Manuscript.</p>

An intact complement system is essential for the initiation of a normal antibody response. Antibodies can regulate their own production against the antigens that they are specific for. Both IgG3 and IgM are able to enhance the antibody response via complement. Here, we have compared the fate of OVA-TNP (ovalbumin-2,4,6-trinitrophenyl) administered intravenously to mice either alone or in complex with monoclonal IgG3 anti-TNP. IgG3-antigen complexes bind to marginal zone (MZ) B cells via complement receptors 1 and 2 (CR1/2) and are transported into splenic follicles. The majority (50% - 90%) of the antigens is deposited on follicular dendritic cells (FDC) and the antigen distribution pattern is strikingly similar to peripheral dendrites/processes of FDC already 2 h after immunization. The development of germinal centers (GC) induced by IgG3-antigen complexes is impaired in mice lacking CR1/2. Experiments on bone marrow chimeric mice show that CR1/2 expression on both MZ B cells and FDC is required for optimal IgG3-mediated enhancement of antibody responses. Complement factors C3 and C1q are essential for OVA-TNP delivery and deposition on splenic FDC. The production of IgG anti-OVA is abrogated in mice lacking CR1/2, C1q, and C3. Further, IgG3-antigen complexes dramatically upregulate the memory response against OVA-TNP by inducing OVA-specific memory cells. Besides small protein OVA, IgG3 can also upregulate humoral responses against large soluble keyhole limpet hemocyanin. To further study the role of MZ B-cells and CR1/2 in enhancement of antibody responses, a knock-in mouse strain, Cμ13, was used. IgM in this mouse strain is unable to activate complement due to a point mutation in the constant µ-heavy chain. Cμ13 mice have a higher proportion of MZ B cells, with higher CR1/2 expression, than wild-type mice. More IgG3-immune complexes are captured by MZ B cells and deposited on FDC in Cμ13 than in WT mice. In spite of this, IgG3 did not enhance the primary antibody response more efficiently in Cμ13 mice. The existence of endogenous IgM-mediated feedback regulation was suggested by the observation that GC development and antibody responses, after priming and boosting with suboptimal doses of SRBC, was lower in Cμ13 than in WT mice.

Chronic Lymphocytic Leukemia (CLL) is a type of cancer that affects the B cells of the immune system causing problems in the process of producing antibodies. It can be sorted into mutated and unmutated CLL based on the percentage of somatic mutations in the Immunoglobulin Heavy chain Variable region (IgHV). The B cells of healthy individuals can be sorted into three groups; CD27dull memory B cells (MBCs), CD27bright MBCs and naïve B cells. The hypothesis for the project was that the unmutated CLL subset originates from CD27dull MBCs and the mutated CLL subset originates from CD27bright MBCs. RNA-sequencing data from healthy individuals were acquired from a collaboration partner in Rome and CLL-patients were collected from public datasets available online. Several bioinformatic tools were used to analyze the data. First, the quality of the data files was checked, then adapter sequence from the sequencing process and low-quality bases were removed (trimming). Good quality of the files was confirmed after the trimming. Secondly, these files were mapped against the human reference genome (GRCh38/hg38) for alignment, then the resulted data was used to check for genes that showed differential expression between the different groups. Results were analyzed and visualized using Venn diagrams, Principal Component Analysis (PCA) and heatmap plots and random forest. A list of 85 genes was generated based on the different comparisons and was used in one PCA plot that showed clear separation between the different groups. The SWAP70 gene was analyzed for single nucleotide polymorphisms (SNPs). The study concluded five genes that could be used as biomarkers for CLL and the diagnosis of its subtypes where some of them were discussed in previous studies. Also, the mutated CLL subset showed a similar behavior to the healthy individuals and this could validate the original hypothesis and justifies the better disease prognosis for this subtype.

The inflammasome complex is a multiprotein complex that may play a role in the pathogenesis of inflammatory bowel disease (IBD) by secreting the inflammatory cytokines interleukin (IL)-1β and IL-18, and inducing pyroptosis, as a response to signals through several inflammasome sensors. This study looked at the expression of several inflammasome components in the ileum and colon of patients suffering from IBD. The inflammasome sensors NLRP1, NLRP3, AIM2 and pyrin were upregulated in whole intestinal tissue of IBD patients, particularly in the colon. NLRP6 expression was increased in the colon of Crohn's disease patients, but not ulcerative colitis patients relative to colon of controls, and was reduced in the ileum of Crohn's disease patients compared to control ileum. Expression of caspase-1 and IL-1β, but not IL-18, were also increased in ileum and colon tissue from Crohn's patients. To identify the cell type where inflammasome expression was altered in Crohn’s disease, transcription of inflammasome subunits in intestinal tissue enriched for epithelial cells or lamina propria (LP) cells was analysed. These analyses indicated that LP cells have greater expression of the inflammasome sensors NLRP1, NLRP3, AIM2 and pyrin relative to epithelial cells, both during disease and in control tissue. Moreover, LP cells from Crohn’s patients have higher expression level of NLRP1, AIM2 and pyrin than LP cells from controls. In contrast the inflammasome sensor NLRP6 was more highly expressed by epithelial cells relative to LP cells in general, and NLRP6 expression in LP cells from IBD patients was lower than that observed in LP cells from controls. The observed differential expression of inflammasome components in controls versus IBD intestine and in different cellular fractions of intestinal tissue highlight the importance of understanding the role of the inflammasome in IBD and hints at the possibility of targeting the inflammasome pathway as a future treatment strategy.

<p>Ribosomes are the universal ribonucleoprotein organelles that translate the genetic message from mRNA to protein. In prokaryotes, the ribosomal subunits are 30S and 50S subunit, which bind together during the translation process forming 70S ribosome. The ribosome is a highly dynamic structure, and acts as a working platform for the different factors involved in the process of converting the genetic information into protein.</p><p>Cryo-electron tomography (cryo-ET) is an emerging imaging technology that combines the potential of three-dimensional (3D) reconstruction at molecular resolution with a close-to-native preservation of the specimen. Here, we have applied this method to reconstruct rifampicin-treated <i>Escherichia coli</i> individual 30S subunits in vitro and in situ, and individual 50S subunits in situ. In the 30S subunit, the head, the platform and the body show large conformational movements relative to each other. The particles are grouped into three conformational groups according to the width/height ratios. Also, an S15 fusion protein derivative has been used as a physical reporter to localize S15 in the 30S subunit. In the 50S subunit, the L1 stalk, the L7/L12 stalk, the central protuberance (CP), and the peptidyl transferase center (PTC) cleft are the most dynamic and flexible parts in the reconstructed structures with clear movements indicated. Different locations of the tunnel in the central cross-sections through the in situ 50S subunits indicate a flexible pathway inside the large subunit. In addition, gross morphological changes were also been observed in our reconstructions. Our results demonstrate a considerable conformational flexibility among individual ribosomal subunits, both in vitro and in situ.</p><p>Translation is an essential process for all cells and organisms. Translation initiation is the rate-limiting step and the most highly regulated phase of translation process. Several regions along the mRNA have been reported to influence translation initiation. The Shine-Dalgarno (SD) sequence located 5-9 bases upstream of the initiation codon supports translation initiation by complementary binding to the Anti-Shine-Dalgarno (ASD) sequence on the 16S rRNA.</p><p>We have here compared how an SD⁺ sequence influences gene expression, if located upstream or downstream of an initiation codon. The positive effect of an upstream SD⁺ is confirmed. A downstream SD⁺ gives decreased gene expression. If an SD⁺ is placed between two potential initiation codons, initiation takes place predominantly at the second start site. The first start site is activated if the distance between this site and the downstream SD⁺ is enlarged and/or if the second start site is weakened. Upstream initiation is eliminated if a stable stem-loop structure is placed between this SD⁺ and the upstream start site. The results suggest that the two start sites compete for ribosomes that bind to an SD⁺ located between them. A minor positive contribution to upstream initiation resulting from 3’ to 5’ ribosomal diffusion along the mRNA is suggested. Since the location of SD⁺or SD-like sequences can strongly influence gene expression, this should be of significant evolutionary importance.</p>

<p>Upon an inflammation the immune system signals the brain by secreted cytokines to elicit central nervous responses such as fever, loss of appetite and secretion of stress hormones. Since the blood brain barrier, (BBB) protects the brain from unwanted material, molecules like cytokines are not allowed to cross the barrier and enter the brain. However, it is clear that they in some way can signal the brain upon an inflammation. Many suggestions concerning this signaling has been made, one being that cytokines bind to receptors on the endothelial cells of the blood vessels of the brain and trigger the production of prostaglandins that can cross the BBB. This conversion is catalyzed by the enzyme cyclooxygenase-2, (COX-2), which is induced by transcription factors like NF-κB in response to cytokines. One of the central nervous responses to inflammatory stimuli is activation of the HPA-axis whose main purpose is glucocorticoid production. Glucocorticoids inhibit the inflammatory response by suppressing gene transcription of pro-inflammatory genes including those producing prostaglandins through direct interference with transcription factors such as NF-κB or initiation of transcription of anti-inflammatory genes like IκB or IL-10. It has however not been clear if glucocorticoids can target the endothelial cells of the brain in order to provide negative feed-back on the immune-to-brain signaling, and in that way inhibit central nervous inflammatory symptoms. An anatomical prerequisite for such a mechanism would be that the induced prostaglandin production occurs in cells expressing GR. This has however never been demonstrated. Here I show that a majority of the brain endothelial cells expressing the prostaglandin synthesizing enzyme COX-2 in response to immune challenge also express the glucocorticoid receptor, (GR). This indicates that immune-to-brain signaling is a target for negative regulation of inflammatory signaling executed by glucocorticoids and identifies brain endothelial GR as a possible future drug target for treatment of central nervous responses to inflammation such as fever and pain.</p>

<p><strong>Abstract</strong></p><p><strong>Introduction</strong></p><p>Occurrence of bacteraemia and fungemia is a serious condition with high mortality and the incidence is increasing worldwide. The aim of this study was to survey the occurrence of bacteria and fungi in blood cultures from adult patients domiciled in the county of Gävleborg during one year and also to calculate the incidence and mortality in the same geographical area.</p><p><strong>Method</strong></p><p>This is a descriptive epidemiologic study, based on all episodes of blood cultures analyzed at the Microbiology laboratory, Gävle hospital during 2005. Patients from 20 years of age, domiciled in the county of Gävleborg at the date of drawing the blood culture, where included in the study. Criteria of exclusion were negative blood cultures and cultures which were classified as contaminants.</p><p><strong>Results</strong></p><p>Altogether there were 4 564 blood cultures analyzed, resulting in 524 (11 %) positive cultures for further study. There were 442 patients (48 % women) involved in 499 episodes with confirmed bacteraemia or fungemia. Gram positive bacteria represented 52 %, gram negative 45 % and fungi 3 %. The most frequently isolated bacterium was <em>Escherichia coli </em>followed by <em>Staphylococcus aureus. </em>In women, <em>Escherichia coli </em>was the most common bacterium, and there was a significant difference between the genders (<em>p= </em>0.004). In men, <em>Staphylococcus </em><em>aureus </em>was the dominant species (<em>p= </em>0.027<em>)</em>. <em>Streptococcus pneumoniae </em>was more common in women (<em>p= </em>0.005). The incidence of bacteraemia and fungemia in the county of Gävleborg was 235/100 000 inhabitants above the age of 20 (women, 223/100 000 men, 247/100 000). The incidence increased with age and the mean age was 70.2 years. The mortality within 30 days after the last positive blood culture was 22 % (97 patients). <em>Escherichia coli </em>was the most common bacteria diagnosed among those who died. The mortality in fungemia was 66 %. There was no significant difference in incidence or mortality between the two provinces Gästrikland and Hälsingland. Patients with bacteraemia and fungemia were initially cared for at all medical care units at the three hospitals in the county.</p><p><strong>Conclusion</strong></p><p>The incidence of bacteraemia/fungemia in the county of Gävleborg was 235/100 000 inhabitants. The most common bacteria in patients with confirmed bacteraemia were <em>Escherichia coli </em>and <em>Staphylococcus aureus. </em>Increasing age was a contributing risk factor. Patients with fungemia had considerably higher mortality compared to patients with bacteraemia. There where no significant differences in mortality between the two provinces.</p> / <p><strong>Introduktion</strong></p><p>Fynd av bakterier, bakteriemi, och svampar, fungemi, i blodbanan är ett allvarligt tillstånd med hög mortalitet och incidensen ökar i världen. Syftet med denna studie var att kartlägga vilka bakterier och svampar som förekom i alla blododlingar tagna under ett år från vuxna patienter i Gävleborgs län, samt att analysera incidens och mortalitet för bakteriemi och fungemi i länet.</p><p><strong>Metod</strong></p><p>Det är en deskriptiv epidemiologisk studie som utgår från analyserade blododlingar under år 2005 vid Enheten för Klinisk Mikrobiologi Laboratoriemedicin vid Gävle sjukhus. Till studien inkluderades personer från 20 års ålder som var mantalsskrivna i Gävleborgs län det datum som blododlingen utfördes. Exklusionskriterierna var negativa odlingssvar och svar som bedömdes som kontamination.</p><p><strong>Resultat</strong></p><p>Totalt analyserades 4 564 blododlingar, av vilka 524 (11 %) var positiva och bearbetades i denna studie. Det blev 442 patienter (48 % kvinnor) med 499 episoder av säkerställd bakteriemi eller fungemi. De grampositiva bakterierna stod för 52 %, gramnegativa bakterier 45 % och svampar 3 %. De enskilt vanligaste bakterierna var <em>Escherichia coli </em>och <em>Staphylococcus aureus. </em>För kvinnorna var <em>Escherichia coli </em>vanligast och det fanns en signifikant skillnad mellan könen (<em>p= </em>0,004 ), för männen var <em>Staphylococcus aureus </em>vanligast (<em>p= </em>0,027<em>)</em>. <em>Streptococcus pneumoniae </em>visade högre förekomst bland kvinnorna än männen (<em>p= </em>0,005). Incidensen för bakteriemi och fungemi i Gävleborgs län var 235/100 000 invånare äldre än 20 år (kvinnor, 223/100 000 och män, 247/100 000). Incidensen ökade med åldern och medelåldern var 70,2 år. Mortaliteten inom 30 dagar efter utförd blododling var 22 % (97 patienter). <em>Escherichia coli </em>var vanligast hos de avlidna. För patienter med fungemi var mortaliteten 66 %. Det påvisades ingen signifikant skillnad beträffande incidens eller mortalitet mellan länets båda landskap Gästrikland och Hälsingland. Patienter med bakteriemi och fungemi vårdades initialt på samtliga vårdenheter på länets tre sjukhus.</p><p><strong>Konklusion</strong></p><p>Incidensen för bakteriemi/fungemi i Gävleborgs län var 235/100 000 invånare. De vanligaste fynden vid säkerställd bakteriemi var <em>Escherichia coli </em>och <em>Staphylococcus aureus</em>. Ökande ålder var en riskfaktor. Patienter med fungemi hade avsevärt högre mortalitet än de med bakteriemi. Ingen skillnad påvisades mellan de två landskapen beträffande mortalitet.</p>