The lower Saint Lawrence River region of Quebec, a hot spot for sheepfold-associated Q fever in Canada: Review of 258 cases.

Background: The lower Saint Lawrence river region (LSLRR), in Quebec, has a 10-fold higher incidence of Q fever compared to the provincial rate. This study aimed to review clinical cases and the Q fever risk exposure in this region. Methods: Data were retrieved from microbiology laboratory, medical records from Rimouski Regional Hospital and Public Health reports between 1991 and 2018. They were analyzed with Epi Info 7.2.2.6. Patients with confirmed acute, probable acute, and chronic Q fever were classified using standard case definitions and mapped according to the postal code, to assess the correlation between cases and sheep distribution. Results: Out of 295 cases, 258 were included (241 confirmed acute, seven probable acute, 10 chronic). Median age was 49 years, 76% were male. For acute cases, the prominent symptoms were fever (99%), headache (83%), chills (80%), sweating (72%), myalgia (69%), and fatigue (67%). Clinical presentation was mostly febrile syndrome with mild hepatitis (84%). A seasonal peak was observed from May to July (56% of acute cases). Most cases (56%) occurred within the two counties where sheep production was highest. Exposure to sheep was prominent 93%, including 64% direct contact (15% shepherds, 49% sheepfold visitors), 14% indirect contact, and 15% sheepfold neighbors. Conclusions: To our knowledge, this is one of the largest retrospective studies of Q fever cases reported in Canada. Q fever in Quebec LSLRR is associated mainly with sheep exposure. Fever and hepatitis were the most common manifestations. Preventive measures should be considered in this region to protect sheepfold workers, visitors, and their neighbors.

Historique: La région du Bas-Saint-Laurent, au Québec, présente une incidence de fièvre Q dix fois plus élevée que le reste de la province. La présente étude visait à analyser les cas cliniques et l'exposition au risque de fièvre Q dans cette région. Méthodologie: Les chercheurs ont extrait les données du laboratoire de microbiologie, des dossiers médicaux de l'Hôpital régional de Rimouski et des rapports sanitaires émis entre 1991 et 2018 et les ont analysées à l'aide du logiciel Epi Info 7.2.2.6. Les patients atteints d'une fièvre Q aiguë confirmée, d'une fièvre Q aiguë probable, et d'une fièvre Q chronique ont été classés au moyen des définitions de cas standards et groupés par code postal afin d'évaluer la corrélation entre les cas et la répartition de moutons. Résultats: Des 295 cas, 258 ont été inclus (241 cas aigus confirmés, sept cas aigus probables, dix cas chroniques). Ils avaient un âge médian de 49 ans, et 76 % étaient de sexe masculin. Dans les cas aigus, la fièvre (99 %), les céphalées (83 %), les frissons (80 %), la sudation (72 %), les myalgies (69 %) et la fatigue (67 %) étaient les principaux symptômes. Le tableau clinique était surtout composé d'un syndrome fébrile accompagné d'une hépatite légère (84 %). Un pic saisonnier a été observé entre mai et juillet (56 % de cas aigus). La plupart des cas (56 %) se sont manifestés dans les deux comtés où la production de moutons était la plus élevée. L'exposition aux moutons atteignait une proportion importante de 93 %, y compris 64 % de contacts directs (15 % de bergers, 49 % de visiteurs des bergeries), 14 % de contacts indirects et 15 % de travailleurs en bergerie. Conclusions: À la connaissance des auteurs, il s'agit de l'une des plus vastes études rétrospectives des cas de fièvre Q signalés au Canada. Dans la région du Bas-Saint-Laurent, au Québec, la fièvre Q est surtout associée à l'exposition aux moutons. La fièvre et l'hépatite en sont les principales manifestations. Il faut envisager des mesures préventives dans cette région afin de protéger les travailleurs en bergerie et leurs voisins.

Gene activation precedes DNA demethylation in response to infection in human dendritic cells.

DNA methylation is considered to be a relatively stable epigenetic mark. However, a growing body of evidence indicates that DNA methylation levels can change rapidly; for example, in innate immune cells facing an infectious agent. Nevertheless, the causal relationship between changes in DNA methylation and gene expression during infection remains to be elucidated. Here, we generated time-course data on DNA methylation, gene expression, and chromatin accessibility patterns during infection of human dendritic cells with Mycobacterium tuberculosis We found that the immune response to infection is accompanied by active demethylation of thousands of CpG sites overlapping distal enhancer elements. However, virtually all changes in gene expression in response to infection occur before detectable changes in DNA methylation, indicating that the observed losses in methylation are a downstream consequence of transcriptional activation. Footprinting analysis revealed that immune-related transcription factors (TFs), such as NF-κB/Rel, are recruited to enhancer elements before the observed losses in methylation, suggesting that DNA demethylation is mediated by TF binding to cis-acting elements. Collectively, our results show that DNA demethylation plays a limited role to the establishment of the core regulatory program engaged upon infection.

BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis.

The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and location for generating such innate memory responses in vivo remain unknown. Here, we show that access of Bacillus Calmette-Guérin (BCG) to the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), leading to local cell expansion and enhanced myelopoiesis at the expense of lymphopoiesis. Importantly, BCG-educated HSCs generate epigenetically modified macrophages that provide significantly better protection against virulent M. tuberculosis infection than naïve macrophages. By using parabiotic and chimeric mice, as well as adoptive transfer approaches, we demonstrate that training of the monocyte/macrophage lineage via BCG-induced HSC reprogramming is sustainable in vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.