ABSTRACT
On 6 June 2019, the Norwegian Institute of Public Health was notified of more than 50 cases of gastroenteritis in Askøy. A reservoir in a water supply system was suspected as the source of the outbreak because of the acute onset and geographical distribution of cases. We investigated the outbreak to confirm the source, extent of the outbreak and effect of control measures. A case was defined as a person in a household served by Water Supply System A (WSS-A) who had gastroenteritis for more than 24 h between 1 and 19 June 2019. We conducted pilot interviews, a telephone survey and an SMS-based cohort study of residents served by WSS-A. System information of WSS-A was collected. Whole genome sequencing on human and environmental isolates was performed. Among 6,108 individuals, 1,573 fulfilled the case definition. Residents served by the reservoir had a 4.6× higher risk of illness than others. Campylobacter jejuni isolated from cases (n = 24) and water samples (n = 4) had identical core genome MLST profiles. Contamination through cracks in the reservoir most probably occurred during heavy rainfall. Water supply systems are susceptible to contamination, particularly to certain weather conditions. This highlights the importance of water safety planning and risk-based surveillance to mitigate risks.
Subject(s)
Campylobacter Infections/epidemiology , Campylobacter jejuni/isolation & purification , Disease Outbreaks/statistics & numerical data , Drinking Water/microbiology , Water Supply , Abdominal Pain/etiology , Campylobacter Infections/diagnosis , Campylobacter jejuni/genetics , Child , Child, Preschool , Cohort Studies , Diarrhea/etiology , Female , Gastroenteritis/epidemiology , Headache/etiology , Humans , Incidence , Male , Multilocus Sequence Typing , Norway/epidemiology , Retrospective Studies , Surveys and Questionnaires , Whole Genome SequencingABSTRACT
Cytokines act as chemical mediators during the inflammatory process. Measurements of cytokine levels in tissue have previously been performed in homogenized tissue, but the true concentrations in native interstitial fluid (ISF), i.e., the compartment where cytokines exert their biologically active role, have remained unknown. The role of skeletal muscle myocytes as a source for cytokines during endotoxemia was explored by collecting muscle ISF using a wick method, and the levels of 14 cytokines in ISF and plasma were related to the corresponding changes in mRNA levels to reveal any potential discrepancies between gene expression and protein release of cytokines to ISF. The majority of investigated cytokines were elevated in muscle ISF during endotoxemia, and an analysis of cytokine mRNA levels revealed consistency between gene expression and protein release. The elevated cytokine level in ISF, in addition to elevated gene expression in muscle, indicated a significant local production and release of several proinflammatory cytokines and chemokines within skeletal muscle tissue during endotoxemia. Immunohistochemistry revealed that myocytes constituted a significant source of IL-1beta and TNF-alpha production during endotoxemia, whereas the contribution from inflammatory cells i.e., leukocytes, was found to be less significant. Muscle cells apparently constitute an important source of several different cytokines during endotoxemia, governing the level in the muscle microenvironment, and are likely to contribute significantly to cytokine levels in plasma.
Subject(s)
Cytokines/metabolism , Endotoxemia/immunology , Extracellular Fluid/immunology , Muscle Fibers, Skeletal/immunology , Animals , Blood Pressure , Cytokines/genetics , Disease Models, Animal , Endotoxemia/chemically induced , Endotoxemia/physiopathology , Female , Interleukin-1beta/metabolism , Lipopolysaccharides , RNA, Messenger/metabolism , Rats , Rats, Wistar , Time Factors , Tumor Necrosis Factor-alpha/metabolism , Up-RegulationABSTRACT
The composition and characteristics of the bone marrow extracellular fluid supposedly modify the transport of cytokines, drugs, and other signaling molecules involved in the regulation of bone marrow function. Direct access to the bone marrow extracellular fluid surrounding hematopoietic cells is complicated by the virtually noncompliant surrounding bone tissue. We examined the applicability of a centrifugation method to obtain representative samples of bone marrow extracellular fluid from rats and humans. Perforated rat bones or human bone marrow biopsies were wrapped in nylon mesh baskets before being centrifuged at 180-239 g. In the rats, we found an only minor contribution of fluid from other sources than the bone marrow extracellular fluid as indicated by the average ratio of centrifugate-to-plasma activity of the extracellular tracer fluid 51Cr-labeled EDTA of 0.85. The colloid osmotic pressure in the centrifugate was consistently lower than that in the corresponding plasma in both species. In rats and humans, high-performance liquid chromatography showed a protein elution pattern from the bone marrow fluid similar to that of plasma, except for a peak eluting in the approximately 40-kDa molecular mass range. Western blotting of the cytokines erythropoietin and granulocyte colony-stimulating factor revealed generally higher amounts in the centrifugate than in the plasma. This difference was augmented during increased hematopoietic activity induced by inflammation or bleeding in rats. We conclude that the centrifugation method provides representative samples of bone marrow extracellular fluid and that extracellular signaling responses to altered hematopoiesis are more clearly reflected locally in the bone marrow interstitium than in plasma.