The invasive pathogen Yersinia pestis disrupts host blood vasculature to spread and provoke hemorrhages.

Yersinia pestis is a powerful pathogen with a rare invasive capacity. After a flea bite, the plague bacillus can reach the bloodstream in a matter of days giving way to invade the whole organism reaching all organs and provoking disseminated hemorrhages. However, the mechanisms used by this bacterium to cross and disrupt the endothelial vascular barrier remain poorly understood. In this study, an innovative model of in vivo infection was used to focus on the interaction between Y. pestis and its host vascular system. In the draining lymph nodes and in secondary organs, bacteria provoked the porosity and disruption of blood vessels. An in vitro model of endothelial barrier showed a role in this phenotype for the pYV/pCD1 plasmid that carries a Type Three Secretion System. This work supports that the pYV/pCD1 plasmid is responsible for the powerful tissue invasiveness capacity of the plague bacillus and the hemorrhagic features of plague.

Type I IFN signaling limits hemorrhage-like disease after infection with Japanese encephalitis virus through modulating a prerequisite infection of CD11b+Ly-6C+ monocytes.

BACKGROUND: The crucial role of type I interferon (IFN-I, IFN-α/ß) is well known to control central nervous system (CNS) neuroinflammation caused by neurotrophic flaviviruses such as Japanese encephalitis virus (JEV) and West Nile virus. However, an in-depth analysis of IFN-I signal-dependent cellular factors that govern CNS-restricted tropism in JEV infection in vivo remains to be elucidated. METHODS: Viral dissemination, tissue tropism, and cytokine production were examined in IFN-I signal-competent and -incompetent mice after JEV inoculation in tissues distal from the CNS such as the footpad. Bone marrow (BM) chimeric models were used for defining hematopoietic and tissue-resident cells in viral dissemination and tissue tropism. RESULTS: The paradoxical and interesting finding was that IFN-I signaling was essentially required for CNS neuroinflammation following JEV inoculation in distal footpad tissue. IFN-I signal-competent mice died after a prolonged neurological illness, but IFN-I signal-incompetent mice all succumbed without neurological signs. Rather, IFN-I signal-incompetent mice developed hemorrhage-like disease as evidenced by thrombocytopenia, functional injury of the liver and kidney, increased vascular leakage, and excessive cytokine production. This hemorrhage-like disease was closely associated with quick viral dissemination and impaired IFN-I innate responses before invasion of JEV into the CNS. Using bone marrow (BM) chimeric models, we found that intrinsic IFN-I signaling in tissue-resident cells in peripheral organs played a major role in inducing the hemorrhage-like disease because IFN-I signal-incompetent recipients of BM cells from IFN-I signal-competent mice showed enhanced viral dissemination, uncontrolled cytokine production, and increased vascular leakage. IFN-I signal-deficient hepatocytes and enterocytes were permissive to JEV replication with impaired induction of antiviral IFN-stimulated genes, and neuron cells derived from both IFN-I signal-competent and -incompetent mice were vulnerable to JEV replication. Finally, circulating CD11b+Ly-6C+ monocytes infiltrated into the distal tissues inoculated by JEV participated in quick viral dissemination to peripheral organs of IFN-I signal-incompetent mice at an early stage. CONCLUSION: An IFN-I signal-dependent model is proposed to demonstrate how CD11b+Ly-6C+ monocytes are involved in restricting the tissue tropism of JEV to the CNS.

Spontaneous rupture of pyogenic liver abscess with subcapsular hemorrhage mimicking ruptured hepatocellular carcinoma: A case report.

RATIONALE: Spontaneous rupture of PLA (pyogenic liver abscess) is an extremely rare and life-threatening event. Ruptured PLA is very difficult to distinguish from malignant HCC (hepatocellular cancer) rupture or cholangiocarcinoma rupture on CT (computed tomography) scan. PATIENT CONCERNS: We describe the case of a 71-year-old man with fever, right upper abdominal pain, nausea with intermittent vomiting, and general fatigue. He had no medical or surgical history. DIAGNOSIS: CT scan showed a hypodense mass in right hepatic lobe and MRI (magnetic resonance imaging) revealed a heterogenous mass of ∼6 cm in segment VI of the liver and heterogenous fluid in the subcapsular region. We made a tentative diagnosis of HCC rupture with subcapsular hemorrhage based on these findings. INTERVENTION: After improving the patient's condition by administering empirical therapy consisting of intravenous antibiotics and fluids, we performed surgical exploration. Gross examination of the abdomen showed that almost the entire right hepatic lobe was hemorrhagic and affected by peritonitis. Therefore, we performed right hepatectomy. The intraoperative frozen biopsy revealed suspicious PLA with marked necrosis, neutrophil infiltration, and hemorrhagic rupture, although no malignant tissue or fungus was observed. The postoperative secondary pathology report confirmed the diagnosis of PLA with hemorrhagic rupture. OUTCOMES: The patient was discharged 13 days after the operation. Follow-up CT was performed 5 months after discharge and revealed no abnormal findings. LESSONS: A high index of suspicion is key to preventing misdiagnosis of ruptured PLA and improving prognosis. Furthermore, even if rupture of the PLA is initially localized, delayed peritonitis may occur during medical treatment. Therefore, vigilant monitoring is essential.

Pathogenesis of Pulmonary Hemorrhagic Syndrome in Human Leptospirosis.

Based on a previous study and by incorporating new knowledge, the goal of our study was to understand more fully the pathogenesis of hemorrhagic pneumonia of severe human leptospirosis, highlighting the onset of capillary lesions by Leptospira itself and/or its antigenic/toxic products acting on the endothelium and binding to cadherins. Both events lead to loss of endothelial integrity, alter permeability, cause rupture, and open intercellular junctions, contributing to the hemorrhagic phenomena associated with severe leptospirosis.

Mycoplasma pneumonia and atypical acute hemorrhagic edema of infancy.

Acute hemorrhagic edema of infancy is a benign rare presentation of leukocytoclastic vasculitis that affects children between 4 and 24 months of age. It usually involves the distal extremities, face, and ears. We report an atypical presentation of AHEI in a 1 year 5 months old boy starting initially over the trunk and back, then spreading to the face and extremities. Mycoplasma pneumonia IgM was found to be positive. The rash resolved spontaneously within two weeks. Herein we present a case of Mycoplasma induced AHEI with an atypical clinical presentation followed by a review of the literature.

The gut microbes, Enterococcus and Escherichia-Shigella, affect the responses of heart valve replacement patients to the anticoagulant warfarin.

Numerous algorithms based on patient genetic variants have been established with the aim of reducing the risk of GI bleeding and thromboembolism during warfarin administration. However, approximately 35 % of individual warfarin sensitivity still remains unexplained. Few of warfarin algorithms take into account gut microbiota profiles. The identification of certain microbiome will provide new targets and new strategies for reducing the risk of bleeding and thromboembolism during warfarin administration. In this study, we collected plasma and stool samples from 200 inpatients undergoing heart valve replacement (HVR), which were classified as low responder (LR), high responder (HR) and normal responder (NR). Significant differences were observed in the diversity and relative abundance of the gut microbiota among the three groups. The genus Escherichia-Shigella was enriched significantly in the LRs (P = 3.189e-11), while the genus Enterococcus was enriched significantly in the HRs (P = 1.249e-11). The amount of VK2 synthesized by gut microbiota in LR group was much higher than that in HR group (P = 0.005). Whole genome shotgun sequencing indicated that the relative abundance of enzymes and modules associated with VK biosynthesis was significantly higher in LRs than in HRs or NRs. The 12 microbial markers were identified through tenfold cross-validation with a random forest model. The results provided a new microbial diagnostic model that can be used to inform modulation of warfarin dosage on the basis of patient intestinal flora composition.

A salivary metabolite signature that reflects gingival host-microbe interactions: instability predicts gingivitis susceptibility.

Several proteins and peptides in saliva were shown to stimulate gingival wound repair, but the role of salivary metabolites in this process remains unexplored. In vitro gingival re-epithelialization kinetics were determined using unstimulated saliva samples from healthy individuals collected during an experimental gingivitis study. Elastic net regression with stability selection identified a specific metabolite signature in a training dataset that was associated with the observed re-epithelialization kinetics and enabled its prediction for all saliva samples obtained in the clinical study. This signature encompassed ten metabolites, including plasmalogens, diacylglycerol and amino acid derivatives, which reflect enhanced host-microbe interactions. This association is in agreement with the positive correlation of the metabolite signature with the individual's gingival bleeding index. Remarkably, intra-individual signature-variation over time was associated with elevated risk for gingivitis development. Unravelling how these metabolites stimulate wound repair could provide novel avenues towards therapeutic approaches in patients with impaired wound healing capacity.

Feed-borne Bacillus cereus exacerbates respiratory distress in chickens infected with Chlamydia psittaci by inducing haemorrhagic pneumonia.

Chlamydia psittaci is an important zoonotic pathogen and its oral route of infection plays an important role in the transmission and persistence. Bacillus cereus (B. cereus) strain, a common contaminant of animal feed and feedstuffs, can cause severe diarrhoea and malnutrition in poultry. In our previous study, a B. cereus strain (Dawu C), isolated from the haemorrhagic lungs of infected chickens, was shown to harbour two virulence genes (hblC and cytk) and was able to induce haemorrhagic lesions in the lungs, as well as gizzard erosion and ulceration (GEU) syndrome in broilers. In the present study, we tested the hypothesis that B. cereus-induced GEU would aggravate C. psittaci infection. Our results showed that SPF chickens exposed to B. cereus developed a severe GEU syndrome. More interestingly, prior infection with B. cereus facilitated C. psittaci infection, and aggravated GEU and respiratory distress, which were accompanied by high chlamydial loads in the lungs and severe lesions in respiratory organs. Moreover, levels of local inflammatory cytokines were elevated and T cell responses were impaired in the infected birds. In conclusion, GEU caused by B. cereus may facilitate chlamydial transmission from the ventriculus to the lungs.RESEARCH HIGHLIGHTS Bacillus cereus contributes to the gizzard erosion and ulceration syndrome in chickens.Exposure to Bacillus cereus exacerbates pneumonia in birds following chlamydial infection.Bacillus cereus facilitates persistent chlamydial infection and exacerbates immune responses.

Clinical Characteristics of Rapidly Progressive Fatal Hemorrhagic Pneumonia Caused by Stenotrophomonas maltophilia.

Objective Hemorrhagic pneumonia due to Stenotrophomonas maltophilia (SM) in severely immunocompromised patients has a very poor prognosis. However, the risk factors for hemorrhagic pneumonia are not clear. Methods This study assessed the predictive factors of hemorrhagic pneumonia caused by SM. The medical records of patients admitted to Osaka City University Hospital with SM bacteremia between January 2008 and December 2017 were retrospectively reviewed. Patients All patients who had positive blood cultures for SM were included in this study. They were categorized into two groups: the SM bacteremia with hemorrhagic pneumonia group and the SM bacteremia without hemorrhagic pneumonia group. The clinical background characteristics and treatments were compared between these groups. Results The 35 patients with SM bacteremia included 4 with hemorrhagic pneumonia and 31 without hemorrhagic pneumonia. Hematologic malignancy (p=0.03) and thrombocytopenia (p=0.04) as well as the prior use of quinolone within 30 days (p=0.04) were more frequent in the SM bacteremia patients with hemorrhagic pneumonia than in those without hemorrhagic pneumonia. The mortality of the SM bacteremia patients with hemorrhagic pneumonia was higher than that of those without hemorrhagic pneumonia group (p=0.02). Conclusion Patients with SM bacteremia who have hematologic malignancy, thrombocytopenia, and a history of using quinolone within the past 30 days should be treated with deliberation.

Co-infection of H9N2 influenza virus and Pseudomonas aeruginosa contributes to the development of hemorrhagic pneumonia in mink.

Influenza A virus (IAV) and bacteria co-infection can influence the host clinical conditions. Both H9N2 IAV and Pseudomonas aeruginosa (P. aeruginosa) are potential pathogens of respiratory diseases in mink. In this study, to clarify the effects of H9N2 IAV and P. aeruginosa co-infections on hemorrhagic pneumonia in mink, we carried out to establish the mink models of the two-pathogen co-infections in different orders. Compared with the single infections with H9N2 IAV or P. aeruginosa, the mink co-infected with H9N2 IAV and P. aeruginosa showed severe respiratory diseases, and exacerbated histopathological lesions and more obvious apoptosis in the lung tissues. H9N2 IAV shedding and viral loads in the lungs of the mink co-infected with H9N2 IAV and P. aeruginosa were higher than those in the mink with single H9N2 IAV infection. Furthermore, the clearance of P. aeruginosa in the co-infected mink lungs was delayed. In addition, the anti-H9N2 antibody titers in mink with P. aeruginosa co-infection following H9N2 IAV infection were significantly higher than those of the other groups. This implied that H9N2 IAV and P. aeruginosa co-infection contributed to the development of hemorrhagic pneumonia in mink, and that P. aeruginosa should play a major role in the disease. The exact interaction mechanism among H9N2 IAV, P. aeruginosa and the host needs to be further investigated.

Leptospirosis manifested with severe pulmonary haemorrhagic syndrome successfully treated with venovenous extracorporeal membrane oxygenation.

Leptospirosis, one of the most important of neglected tropical diseases, is a common zoonosis in the tropics. Recent reports have demonstrated that pulmonary haemorrhage is one of the fatal complications of severe leptospirosis. In this report, we present a case of leptospirosis manifested with severe pulmonary haemorrhagic syndrome successfully treated with venovenous extracorporeal membrane oxygenation (VV-ECMO). A 39-year-old man who lives in Bangkok presented with fever, severe myalgia and haemoptysis. With rapid progression of acute respiratory failure in 6 hours, he was intubated and a litre of fresh blood was suctioned. Chest x-ray showed diffuse alveolar infiltrates compatible with ARDS, then mechanical ventilator with lung protective strategy was used. Diagnosis of leptospirosis with diffuse alveolar haemorrhage was made. Refractory hypoxaemia was not responsive to positive end-expiratory pressure (PEEP); thus, VV-ECMO was initiated on the first day. Other treatments included plasmapheresis, intravenous pulse methylprednisolone and intravenous antibiotics. The outcome of treatment was successful, and this patient was discharged to home on day 14 after admission.

Insertion sequences drive the emergence of a highly adapted human pathogen.

Pseudomonas aeruginosa is a highly adaptive opportunistic pathogen that can have serious health consequences in patients with lung disorders. Taxonomic outliers of P. aeruginosa of environmental origin have recently emerged as infectious for humans. Here, we present the first genome-wide analysis of an isolate that caused fatal haemorrhagic pneumonia. In two clones, CLJ1 and CLJ3, sequentially recovered from a patient with chronic pulmonary disease, insertion of a mobile genetic element into the P. aeruginosa chromosome affected major virulence-associated phenotypes and led to increased resistance to the antibiotics used to combat the infection. Comparative genome, proteome and transcriptome analyses revealed that this ISL3-family insertion sequence disrupted the genes for flagellar components, type IV pili, O-specific antigens, translesion polymerase and enzymes producing hydrogen cyanide. Seven-fold more insertions were detected in the later isolate, CLJ3, than in CLJ1, some of which modified strain susceptibility to antibiotics by disrupting the genes for the outer-membrane porin OprD and the regulator of ß-lactamase expression AmpD. In the Galleria mellonella larvae model, the two strains displayed different levels of virulence, with CLJ1 being highly pathogenic. This study revealed insertion sequences to be major players in enhancing the pathogenic potential of a P. aeruginosa taxonomic outlier by modulating both its virulence and its resistance to antimicrobials, and explains how this bacterium adapts from the environment to a human host.

Epidemiology and molecular characterization of the antimicrobial resistance of Pseudomonas aeruginosa in Chinese mink infected by hemorrhagic pneumonia.

Hemorrhagic pneumonia in mink is a fatal disease caused by Pseudomonas aeruginosa. Very little is known about P. aeruginosa in relation to genotype and the mechanisms underlying antimicrobial resistance in mink. A total of 110 P. aeruginosa samples were collected from mink from Chinese mink farms between 2007 and 2015. Samples underwent molecular genotyping using pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST), antimicrobial susceptibility and its mechanism were investigated at the molecular level. The PFGE identified 73 unique types and 15 clusters, while MLST identified 43 (7 new) sequence types (ST) and 12 sequence type clonal complexes (STCC). Sequence types and PFGE showed persistence of endemic clones in cities Wendeng (Shandong, China) and Dalian (Liaoning, China), even in different timelines. The MLST also revealed the gene correlation of the mink P. aeruginosa across different time and place. The ST1058 (n = 14), ST882 (n = 11), and ST2442 (n = 10) were the predominant types, among which ST1058 was the only one found both in Shandong province and Dalian (Liaoning, China). The MLST for P. aeruginosa infection in mink was highly associated with that in humans and other animals, implying possible transmission events. A small proportion of mink exhibited drug resistance to P. aeruginosa (9/69, 13%) with resistance predominantly to fluoroquinolone, aminoglycoside, and ß-lactamase. Eight strains had mutations in the quinolone-resistance determining regions (QRDR). High proportions (65%; 72/110) of the fosA gene and 2 types of glpt deletion for fosmycin were detected. Furthermore, in the whole genome sequence of one multidrug resistant strain, we identified 27 genes that conferred resistance to 14 types of drugs.

La pneumonie hémorragique du vison est une maladie fatale causée par Pseudomonas aeruginosa. Très peu de choses sont connues à propos de P. aeruginosa en lien avec le génotype et les mécanismes sous-jacents à la résistance antimicrobienne chez les visons. Un total de 110 échantillons de P. aeruginosa furent prélevés de visons provenant de fermes de vison chinoises entre 2007 et 2015. Les échantillons ont été soumis à du génotypage moléculaire par électrophorèse en champs pulsés (PFGE) et typage de séquence multi-locus (MLST), des tests de sensibilité aux antibiotiques et ses mécanismes furent étudiés au niveau moléculaire. L'analyse par PFGE a identifié 73 types uniques et 15 regroupements, alors que le MLST a identifié 43 (7 nouveaux) types de séquences (ST) et 12 complexes clonaux de types de séquences (STCC). L'analyse des ST et du PFGE a montré la persistance de clones endémiques dans les villes de Wendeng (Shandong, Chine) et Dalian (Liaoning, Chine), même lors de différentes chronologies. Le MLST a également révélé la corrélation génétique des isolats de P. aeruginosa de vison de différentes locations et de temps différents. Les types ST1058 (n = 14), ST882 (n = 11), et ST2442 (n = 10) étaient les types prédominants, parmi lesquels ST1058 était le seul retrouvé dans la province de Shandong et à Dalian (Liaoning, Chine). Le MLST des isolats de P. aeruginosa provenant d'infection chez les visons était hautement associé à celui chez les humains et d'autres animaux, suggérant de possibles évènements de transmission. Une petite portion des isolats de P. aeruginosa de vison (9/69, 13 %) démontrait de la résistance aux antibiotiques, principalement envers les fluoroquinolones, les aminoglycosides et les ß-lactamines. Huit souches avaient des mutations dans les régions déterminant la résistance aux quinolones. Des proportions élevées (65 %, 72/110) du gène fosA et deux types de délétion glpt pour la fosmycine furent détectées. De plus, dans la séquence entière du génome d'une des souches multirésistantes, nous avons identifié 27 gènes conférant de la résistance à 14 types de médicaments.(Traduit par Docteur Serge Messier).

[Isolated hemorrhagic pleurisy due to Panton-Valentine leukocidin-positive Staphylococcus aureus]. / Pleurésie hémorragique isolée à Staphylococcus aureus à leucocidine de Panton-Valentine.

Panton-Valentine leucocidin is a major virulence factor produced by some strains of Staphylococcus aureus (SA-PVL). The best-described invasive infection is a necrotizing haemorrhagic pneumonia. Pleural effusion is not uncommon but is always associated with a parenchymal lesion. Here, we report a case of haemorrhagic pleurisy attributable to isolated SA-PVL.

Severe pulmonary haemorrhage syndrome in leptospirosis in a returning traveller.

Clinical presentation of leptospirosis ranges from asymptomatic infection to fulminant, life-threatening disease. Pulmonary involvement in terms of severe pulmonary haemorrhage syndrome (SPHS) has recently become a more frequently reported facet of leptospirosis and correlates with high mortality rates. It has not yet been described in returning German travellers. We present a case of a healthy young man developing massive pulmonary haemorrhage and severe ARDS requiring mechanical ventilation and high-dose catecholamines after travelling to Indonesia. Leptospirosis was verified by blood PCR as well as serology and treated with high-dose, intravenous penicillin. Outcome was favourable, the patient recovered completely. Leptospirosis and SPHS should be taken into account as an emerging infectious disease in patients with fever and lung involvement.

Polytrauma independent of therapeutic intervention alters the gastrointestinal microbiome.

BACKGROUND: This study characterizes the gastrointestinal (GI) microbiome in a pre-clinical polytrauma hemorrhage model. METHODS: Rats (n = 6) were anesthetized, hemorrhaged 20% of their blood volume, and subjected to a femur fracture and crush injuries to the small intestine, liver, and limb skeletal muscle without resuscitation. Fecal samples were collected pre-injury and 2 h post-injury. Purified DNA from the samples underwent 16s rRNA sequencing for microbial quantification. Bacterial diversity analysis and taxonomic classification were performed. RESULTS: Following injury, the gut microbial composition was altered with a shift in beta diversity and significant differences in the relative abundance of taxa. The relative abundance of the families Lachnospiraceae and Mogibacteriaceae was increased at 2 h, while Barnesiellaceae and Bacteroidaceae were decreased. Alpha diversity was unchanged. CONCLUSIONS: The GI microbiome is altered in rats subjected to a polytrauma hemorrhage model at 2 h post-injury in the absence of antibiotics or therapeutic interventions.

Case Report: A Cluster of Three Leptospirosis Cases in a New York City Abattoir and an Unusual Complication in the Index Case.

We report the case of a 46-year-old male abattoir worker who developed myalgias, shortness of breath, and irritability 2 weeks after sustaining a laceration to the hand with a knife at work. During his hospital evaluation for septic shock he was noted to be febrile, hypotensive, profoundly jaundiced with aseptic meningitis, and renal failure, and was diagnosed with Leptospirosis interrogans infection confirmed by serum and urine polymerase chain reaction. After standard antibiotic therapy and recovery from severe clinical illness, he developed unilateral orchitis with pyuria secondary to leptospirosis, a well-established complication in the veterinary literature, but of which we offer the first report in humans in the English literature. The case presented was also the index case that uncovered a cluster outbreak of leptospirosis in New York City during the winter of 2016-2017, involving a total of three patients who lived or worked within a block of the abattoir. Two patients survived whereas the third died of pulmonary hemorrhage shortly after seeking medical care.

Male-specific pulmonary hemorrhage and cytokine gene expression in golden hamster in early-phase Leptospira interrogans serovar Hebdomadis infection.

Leptospirosis causes severe clinical signs more frequently in men than in women, but the mechanism underlying the gender differences in leptospirosis remains unclear. In this study, petechial hemorrhage was observed in male but not in female hamster lung tissues infected with Leptospira interrogans serovar Hebdomadis at 120 h pi, demonstrating that male hamsters were more susceptible to the development of a severe disease upon Leptospira infection. No leptospiral DNA was detected in the lung tissues at 120 h pi when pulmonary hemorrhage was observed, indicating that pulmonary hemorrhage is attributable to the immune reactions of the host rather than from the direct effect of leptospires. The upregulation of nitric oxide synthase genes in the hamsters without pulmonary hemorrhage, inos and enos in female hamsters at 96 h pi and enos in male animals without hemorrhage at 120 h pi, may suggest that nitric oxide has a suppressive effect on leptospirosis-associated pulmonary hemorrhage.