Does respiratory infection due to Chlamydia pneumoniae still exist?

Does respiratory infection due to Chlamydia pneumoniae still exist

Common skin infection due to Panton-Valentine leucocidin-producing Staphylococcus aureus strains in asylum seekers from Eritrea: a genome-based investigation of a suspected outbreak

Since late 2014, multiple cases of abscesses and boils due to methicillin-susceptible Staphylococcus aureus (MSSA) expressing the Panton-Valentine leucocidin (PVL) were observed in Eritrean asylum seekers in Lausanne, Switzerland. Strains isolated from infected Eritrean and non-Eritrean patients were compared by whole genome sequencing to determine whether these numerous cases result from an outbreak. The genome of S. aureus PVL-producing strains were sequenced and compared. Clinical and epidemiological characteristics of patients infected by PVL-producing strains were investigated. This work reports 15 cases of infections due to PVL-producing strains affecting mostly asylum seekers (n = 10), people working with refugees and/or exposed to Africans (n = 3). Most infections were due to closely related strains of CC152 (n = 8) and CC15 (n = 3), two distantly related (>34 000 core single nucleotide polymorphisms) clonal complexes. An epidemiological link between the 15 cases could be ruled out by whole genome sequencing (33 to 172 core single nucleotide polymorphisms between the different strains of a given complex). Altogether, these results reflect the probable high incidence of CC15 and CC152 PVL-producing strains in eastern Africa. Clinicians facing unusual skin infections in African refugees (or in any person returning from this region of high endemicity) should consider S. aureus PVL-producer before suspecting rare infections such as leishmaniasis or rickettsiosis. Clinicians should also remember that PVL are frequently expressed by MSSA in some regions of the world and that antibiotics that are efficient on toxin expression, such as clindamycin, represent the best therapeutic option

Chlamydia pneumoniae and Mycoplasma pneumoniae in children with cystic fibrosis: impact on bacterial respiratory microbiota diversity.

The contribution of intracellular and fastidious bacteria in Cystic fibrosis (CF) pulmonary exacerbations, and progressive lung function decline remains unknown. This project aimed to explore their impact on bacterial microbiota diversity over time in CF children. Sixty-one children enrolled in the MUCOVIB multicentre prospective cohort provided 746 samples, mostly nasopharyngeal swabs, throat swabs and sputa which were analysed using culture, specific real-time qPCRs and 16S rRNA amplicon metagenomics. Chlamydia pneumoniae (n = 3) and Mycoplasma pneumoniae (n = 1) were prospectively documented in 6.6% of CF children. Microbiota alpha-diversity in children with a documented C. pneumoniae was highly variable, similarly to children infected with Staphylococcus aureus or Pseudomonas aeruginosa. The transition from routine follow-up visits to pulmonary exacerbation (n = 17) yielded variable changes in diversity indexes with some extreme loss of diversity. The high rate of C. pneumoniae detection supports the need for regular screenings in CF patients. A minor impact of C. pneumoniae on the microbial community structure was documented. Although detected in a single patient, M. pneumoniae should also be considered as a possible aetiology of lung infection in CF subjects

Prevalence of <i>Anaplasma phagocytophilum</i> and <i>Coxiella burnetii</i> in <i>Ixodes ricinus</i> ticks in Switzerland: an underestimated epidemiologic risk.

Ticks are vectors of several microorganisms responsible for infectious diseases in human and animals, such as &lt;i&gt;Anaplasma phagocytophilum&lt;/i&gt; and &lt;i&gt;Coxiella burnetii.&lt;/i&gt; In this study, we investigated the prevalence of these two bacteria in 62 889 &lt;i&gt;Ixodes ricinus&lt;/i&gt; ticks in selected regions covering all Switzerland. A high prevalence of 11.9% of &lt;i&gt;A. phagocytophilum&lt;/i&gt; DNA was observed by real-time PCR on 8534 pools of ticks. This pool prevalence corresponds to an estimated prevalence of 1.71% in individual tick. A total of 144 of the 171 collection sites (84.2%) were positive for the presence of &lt;i&gt;A. phagocytophilum,&lt;/i&gt; and these sites were homogenously distributed throughout Switzerland. Such prevalence and geographical distribution underline the risk of human and animal exposure to &lt;i&gt;A. phagocytophilum&lt;/i&gt; and highlight the need to assess the epidemiology and clinical diagnosis of human and animal anaplasmosis in Switzerland. However, DNA of &lt;i&gt;C. burnetii&lt;/i&gt; was never found in any tick pool. This absence suggests a very low role of &lt;i&gt;I. ricinus&lt;/i&gt; ticks as vector and reservoir of &lt;i&gt;C. burnetii&lt;/i&gt; in Switzerland, and it supports previous reports demonstrating the role of sheep and goats in the epidemiology of Q fever. However, considering its pathogenic potential, it is necessary to keep monitoring for the possible reemergence of this bacterium in ticks in the future

Safety of human immunisation with a live-attenuated Mycobacterium tuberculosis vaccine: a randomised, double-blind, controlled phase I trial.

BACKGROUND: Tuberculosis remains one of the world's deadliest transmissible diseases despite widespread use of the BCG vaccine. MTBVAC is a new live tuberculosis vaccine based on genetically attenuated Mycobacterium tuberculosis that expresses most antigens present in human isolates of M tuberculosis. We aimed to compare the safety of MTBVAC with BCG in healthy adult volunteers. METHODS: We did this single-centre, randomised, double-blind, controlled phase 1 study at the Centre Hospitalier Universitaire Vaudois (CHUV; Lausanne, Switzerland). Volunteers were eligible for inclusion if they were aged 18-45 years, clinically healthy, HIV-negative and tuberculosis-negative, and had no history of active tuberculosis, chemoprophylaxis for tuberculosis, or BCG vaccination. Volunteers fulfilling the inclusion criteria were randomly assigned to three cohorts in a dose-escalation manner. Randomisation was done centrally by the CHUV Pharmacy and treatments were masked from the study team and volunteers. As participants were recruited within each cohort, they were randomly assigned 3:1 to receive MTBVAC or BCG. Of the participants allocated MTBVAC, those in the first cohort received 5 × 10(3) colony forming units (CFU) MTBVAC, those in the second cohort received 5 × 10(4) CFU MTBVAC, and those in the third cohort received 5 × 10(5) CFU MTBVAC. In all cohorts, participants assigned to receive BCG were given 5 × 10(5) CFU BCG. Each participant received a single intradermal injection of their assigned vaccine in 0·1 mL sterile water in their non-dominant arm. The primary outcome was safety in all vaccinated participants. Secondary outcomes included whole blood cell-mediated immune response to live MTBVAC and BCG, and interferon γ release assays (IGRA) of peripheral blood mononuclear cells. This trial is registered with ClinicalTrials.gov, number NCT02013245. FINDINGS: Between Jan 23, 2013, and Nov 6, 2013, we enrolled 36 volunteers into three cohorts, each of which consisted of nine participants who received MTBVAC and three who received BCG. 34 volunteers completed the trial. The safety of vaccination with MTBVAC at all doses was similar to that of BCG, and vaccination did not induce any serious adverse events. All individuals were IGRA negative at the end of follow-up (day 210). After whole blood stimulation with live MTBVAC or BCG, MTBVAC was at least as immunogenic as BCG. At the same dose as BCG (5×10(5) CFU), although no statistical significance could be achieved, there were more responders in the MTBVAC group than in the BCG group, with a greater frequency of polyfunctional CD4+ central memory T cells. INTERPRETATION: To our knowledge, MTBVAC is the first live-attenuated M tuberculosis vaccine to reach clinical assessment, showing similar safety to BCG. MTBVAC seemed to be at least as immunogenic as BCG, but the study was not powered to investigate this outcome. Further plans to use more immunogenicity endpoints in a larger number of volunteers (adults and adolescents) are underway, with the aim to thoroughly characterise and potentially distinguish immunogenicity between MTBVAC and BCG in tuberculosis-endemic countries. Combined with an excellent safety profile, these data support advanced clinical development in high-burden tuberculosis endemic countries. FUNDING: Biofabri and Bill &amp; Melinda Gates Foundation through the TuBerculosis Vaccine Initiative (TBVI)

Multicenter analysis of sputum microbiota in tuberculosis patients.

The impact of tuberculosis and of anti-tuberculosis therapy on composition and modification of human lung microbiota has been the object of several investigations. However, no clear outcome has been presented so far and the relationship between M. tuberculosis pulmonary infection and the resident lung microbiota remains vague. In this work we describe the results obtained from a multicenter study of the microbiota of sputum samples from patients with tuberculosis or unrelated lung diseases and healthy donors recruited in Switzerland, Italy and Bangladesh, with the ultimate goal of discovering a microbiota-based biomarker associated with tuberculosis. Bacterial 16S rDNA amplification, high-throughput sequencing and extensive bioinformatic analyses revealed patient-specific flora and high variability in taxon abundance. No common signature could be identified among the individuals enrolled except for minor differences which were not consistent among the different geographical settings. Moreover, anti-tuberculosis therapy did not cause any important variation in microbiota diversity, thus precluding its exploitation as a biomarker for the follow up of tuberculosis patients undergoing treatment

Encephalopathies Associated With Severe COVID-19 Present Neurovascular Unit Alterations Without Evidence for Strong Neuroinflammation.

Coronavirus disease (COVID-19) has been associated with a large variety of neurologic disorders. However, the mechanisms underlying these neurologic complications remain elusive. In this study, we aimed at determining whether neurologic symptoms were caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) direct infection or by either systemic or local proinflammatory mediators. In this cross-sectional study, we checked for SARS-CoV-2 RNA by quantitative reverse transcription PCR, SARS-CoV-2-specific antibodies, and 49 cytokines/chemokines/growth factors (by Luminex) in the CSF +/- sera of a cohort of 22 COVID-19 patients with neurologic presentation and 55 neurologic control patients (inflammatory neurologic disorder [IND], noninflammatory neurologic disorder, and MS). We detected anti-SARS-CoV-2 immunoglobulin G in patients with severe COVID-19 with signs of intrathecal synthesis for some of them. Of the 4 categories of tested patients, the CSF of IND exhibited the highest level of cytokines, chemokines, and growth factors. By contrast, patients with COVID-19 did not present overall upregulation of inflammatory mediators in the CSF. However, patients with severe COVID-19 (intensive care unit patients) exhibited higher concentrations of CCL2, CXCL8, and vascular endothelium growth factor A (VEGF-A) in the CSF than patients with a milder form of COVID-19. In addition, we could show that intrathecal CXCL8 synthesis was linked to an elevated albumin ratio and correlated with the increase of peripheral inflammation (serum hepatocyte growth factor [HGF] and CXCL10). Our results do not indicate active replication of SARS-CoV-2 in the CSF or signs of massive inflammation in the CSF compartment but highlight a specific impairment of the neurovascular unit linked to intrathecal production of CXCL8

Case Report: Stepwise Anti-Inflammatory and Anti-SARS-CoV-2 Effects Following Convalescent Plasma Therapy With Full Clinical Recovery.

In these times of COVID-19 pandemic, concern has been raised about the potential effects of SARS-CoV-2 infection on immunocompromised patients, particularly on those receiving B-cell depleting agents and having therefore a severely depressed humoral response. Convalescent plasma can be a therapeutic option for these patients. Understanding the underlying mechanisms of convalescent plasma is crucial to optimize such therapeutic approach. Here, we describe a COVID-19 patient who was deeply immunosuppressed following rituximab (anti-CD20 monoclonal antibody) and concomitant chemotherapy for chronic lymphoid leukemia. His long-term severe T and B cell lymphopenia allowed to evaluate the treatment effects of convalescent plasma. Therapeutic outcome was monitored at the clinical, biological and radiological level. Moreover, anti-SARS-CoV-2 antibody titers (IgM, IgG and IgA) and neutralizing activity were assessed over time before and after plasma transfusions, alongside to SARS-CoV-2 RNA quantification and virus isolation from the upper respiratory tract. Already after the first cycle of plasma transfusion, the patient experienced rapid improvement of pneumonia, inflammation and blood cell counts, which may be related to the immunomodulatory properties of plasma. Subsequently, the cumulative increase in anti-SARS-CoV-2 neutralizing antibodies due to the three additional plasma transfusions was associated with progressive and finally complete viral clearance, resulting in full clinical recovery. In this case-report, administration of convalescent plasma revealed a stepwise effect with an initial and rapid anti-inflammatory activity followed by the progressive SARS-CoV-2 clearance. These data have potential implications for a more extended use of convalescent plasma and future monoclonal antibodies in the treatment of immunosuppressed COVID-19 patients

SARS-CoV-2, un point dans la tourmente [SARS-CoV-2, a point in the storm]

Since its emergence in December 2019, scientific knowledge about the SARS-CoV-2 virus has evolved rapidly but, due to the complexity and novelty of this infection and its political and economic stakes, much remains to be clarified. Thousands of studies have already been published and scientific research is constantly evolving. In this multitude of information, we offer an update of the knowledge currently available. A limitation of the propagation, the understanding of the functioning of the virus and its clinical manifestations, the administration of specific treatments, rapid and reliable diagnostic tools are the basis of the fight against this germ, which is still little known today