Control Infection
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mBio ◽  
2021 ◽  
David E. Place ◽  
Shelbi Christgen ◽  
Shraddha Tuladhar ◽  
Peter Vogel ◽  
R. K. Subbarao Malireddi ◽  

Burkholderia infections result in a high degree of mortality when left untreated; therefore, understanding the host immune response required to control infection is critical. In this study, we uncovered a hierarchical cell death program utilized by infected cells to disrupt the intracellular niche of Burkholderia thailandensis by limiting bacterial intercellular spread, host cell-cell fusion, and bacterial replication. In macrophages, combined loss of key PANoptosis components results in extensive B. thailandensis infection-induced cell-cell fusion, bacterial replication, and increased cell death at later stages of infection compared with both wild-type (WT) and pyroptosis-deficient cells.

2021 ◽  
pp. 00301-2021
June K. Marthin ◽  
Jane S. Lucas ◽  
Mieke Boon ◽  
Carmen Casaulta ◽  
Suzanne Crowley ◽  

IntroductionIn primary ciliary dyskinesia (PCD) impaired mucociliary clearance leads to recurrent airway infections and progressive lung destruction, and concern over chronic airway infection and patient-to-patient transmission is considerable. So far, there has been no defined consensus on how to control infection across centres caring for patients with PCD. Within the BEAT-PCD Network, COST Action and ERS CRC together with the ERN-Lung PCD core a first initiative was now taken towards creating such consensus statement.MethodsA multidisciplinary international PCD expert panel was set up to create a consensus statement for infection prevention and control (IP&C) for PCD, covering diagnostic microbiology, infection prevention for specific pathogens considered indicated for treatment, and segregation aspects. Using a modified Delphi process, consensus to a statement demanded at least 80% agreement within the PCD expert panel group. Patient organisation representatives were involved throughout the process.ResultsWe present a consensus statement on 20 IP&C statements for PCD including suggested actions for microbiological identification, indications for treatment of Pseudomonas aeruginosa, Burkholderia cepacia and nontuberculous mycobacteria and suggested segregation aspects aimed to minimise patient-to-patient transmission of infections whether in-hospital, in PCD clinics or wards, or out of hospital at meetings between people with PCD. The statement also includes segregation aspects adapted to the current COVID-19 pandemic.ConclusionThe first ever international consensus statement on IP&C intended specifically for PCD is presented and is targeted clinicians managing paediatric and adult patients with PCD, microbiologists, patient organisations and not least the patients and their families.

2021 ◽  
Vol 11 (1) ◽  
Laura Sibley ◽  
Andrew D. White ◽  
Karen E. Gooch ◽  
Lisa M. Stevens ◽  
Rachel Tanner ◽  

AbstractThis study describes the use of cynomolgus macaques of Chinese origin (CCM) to evaluate the efficacy and immunogenicity of the BCG vaccine against high dose aerosol Mycobacterium tuberculosis challenge. Progressive disease developed in three of the unvaccinated animals within 10 weeks of challenge, whereas all six vaccinated animals controlled disease for 26 weeks. Three unvaccinated animals limited disease progression, highlighting the intrinsic ability of this macaque species to control disease in comparison to macaques of other species and genotypes. Low levels of IFNγ were induced by BCG vaccination in CCM suggesting that IFNγ alone does not provide a sufficiently sensitive biomarker of vaccination in this model. An early response after challenge, together with the natural bias towards terminal effector memory T-cell populations and the contribution of monocytes appears to enhance the ability of CCM to naturally control infection. The high dose aerosol challenge model of CCM has value for examination of the host immune system to characterise control of infection which would influence future vaccine design. Although it may not be the preferred platform for the assessment of prophylactic vaccine candidates, the model could be well suited for testing post-exposure vaccination strategies and drug evaluation studies.

2021 ◽  
Vol 12 ◽  
Amber D. Jones ◽  
Svetlana Khakhina ◽  
Tara Jaison ◽  
Erin Santos ◽  
Stephen Smith ◽  

A unique population of HIV-1 infected individuals can control infection without antiretroviral therapy. These individuals fall into a myriad of categories based on the degree of control (low or undetectable viral load), the durability of control over time and the underlying mechanism (i.e., possession of protective HLA alleles or the absence of critical cell surface receptors). In this study, we examine a cohort of HIV-1 infected individuals with a documented history of sustained low viral loads in the absence of therapy. Through in vitro analyses of cells from these individuals, we have determined that infected individuals with naturally low viral loads are capable of controlling spreading infection in vitro in a CD8+ T-cell dependent manner. This control is lost when viral load is suppressed by antiretroviral therapy and correlates with a clinical CD4:CD8 ratio of <1. Our results support the conclusion that HIV-1 controllers with low, but detectable viral loads may be controlling the virus due to an effective CD8+ T-cell response. Understanding the mechanisms of control in these subjects may provide valuable understanding that could be applied to induce a functional cure in standard progressors.

2021 ◽  
Vol 19 (1) ◽  
Yongyong Wu ◽  
Zhongliang He ◽  
Weihua Xu ◽  
Guoxing Chen ◽  
Zhijun Liu ◽  

Abstract Background Bronchopleural fistula (BPF) refers to an abnormal channel between the pleural space and the bronchial tree. It is a potentially fatal postoperative complication after pulmonary resection and a complex challenge for thoracic surgeons because many patients with BPF ultimately develop refractory empyema, which is difficult to manage and has a major impact on quality of life and survival. Therefore, an operative intervention combined with conservative and endoscopic therapies may be required to control infection completely, to occlude BPF, and to obliterate the empyema cavity during treatment periods. Case presentation Two patients who suffered from BPF complicated with chronic empyema after lobectomy were treated in other hospitals for a long time and did not recover. In our department, we performed staged surgery and creatively combined an Amplatzer Septal Occluder (ASO) device (AGA Medical Corp, Golden Valley, MN, USA) with pedicled muscle flap transposition. First, open-window thoracostomy (OWT), or effective drainage, was performed according to the degree of contamination in the empyema cavity after the local infection was controlled. Second, Amplatzer device implantation and pedicled muscle flap transposition was performed at the same time, which achieved the purpose of obliterating the infection, closing the fistula, and tamponading the residual cavity. The patients recovered without complications and were discharged with short hospitalization stays. Conclusions We believe that the union of the Amplatzer device and pedicle muscle flap transposition seems to be a safe and effective treatment for BPF with chronic empyema and can shorten the length of the related hospital stay.

Enrico Maggi ◽  
Bruno Azzarone ◽  
Walter Canonica ◽  
Lorenzo Moretta

The coronavirus disease 2019 (COVID-19) pandemic started over one year ago and produced almost 3.5 million deaths worldwide. We have been recently overwhelmed by a wide literature on how the immune system recognizes Severe Acute Respiratory Syndrome Coronavirus 2 and contributes to COVID-19 pathogenesis. Although originally considered a respiratory viral disease, COVID-19 is recognized as a far more complex, multi-organ-, immuno-mediated-, and mostly heterogeneous disorder. Though efficient innate and adaptive immunity may control infection, when the patient fails to mount an adequate immune response, a high innate-induced inflammation can lead to different clinical outcomes through heterogeneous compensatory mechanisms. The variability of viral load and persistence, the genetic alterations of virus-driven receptors/signaling pathways and the plasticity of innate and adaptive responses may all account for the extreme heterogeneity of pathogenesis and clinical patterns. As recently done for some inflammatory disorders as asthma, rhinosinusitis with polyposis and atopic dermatitis, herein we suggest to define different endo-types and the related phenotypes along COVID-19. Patients should be stratified for evolving symptoms and tightly monitored for surrogate biomarkers of innate and adaptive immunity. This would allow to preventively identify each endo-type (and its related phenotype) and to treat patients precisely with agents targeting pathogenic mechanisms.

2021 ◽  
Vol 11 (1) ◽  
G. B. Almeida ◽  
T. N. Vilches ◽  
C. P. Ferreira ◽  
C. M. C. B. Fortaleza

AbstractIn 2020, the world experienced its very first pandemic of the globalized era. A novel coronavirus, SARS-CoV-2, is the causative agent of severe pneumonia and has rapidly spread through many nations, crashing health systems and leading a large number of people to death. In Brazil, the emergence of local epidemics in major metropolitan areas has always been a concern. In a vast and heterogeneous country, with regional disparities and climate diversity, several factors can modulate the dynamics of COVID-19. What should be the scenario for inner Brazil, and what can we do to control infection transmission in each of these locations? Here, a mathematical model is proposed to simulate disease transmission among individuals in several scenarios, differing by abiotic factors, social-economic factors, and effectiveness of mitigation strategies. The disease control relies on keeping all individuals’ social distancing and detecting, followed by isolating, infected ones. The model reinforces social distancing as the most efficient method to control disease transmission. Moreover, it also shows that improving the detection and isolation of infected individuals can loosen this mitigation strategy. Finally, the effectiveness of control may be different across the country, and understanding it can help set up public health strategies.

2021 ◽  
Vol 24 (2) ◽  
pp. 151-153
Jennifer Bethell ◽  
Hannah M. O'Rourke ◽  
Heather Eagleson ◽  
Daniel Gaetano ◽  
Wayne Hykaway ◽  

COVID-19 has had a profound impact on long-term care (LTC) homes in Canada. But the measures put in place to control infection within LTC homes have also had devastating impacts on the health and well-being of residents through the effects on social connection. Here, we offer guiding principles to enable social connection and promote health and quality of life for LTC residents during COVID-19 and beyond. These principles were generated by a working group of the CO­VID-19 and Dementia Task Force, convened by the Alzheimer Society of Canada to identify the urgent and emerging issues raised by COVID-19 for Canadians with dementia.

Dr. Baneswar Kapasi ◽  
Dr. Mahesh Kumar Kurmi

COVID -19 has wedged all the major economies across the globe significantly. The World Health Organisation (WHO) first declared COVID-19 as a world health emergency in January 2020. The virus originated in Wuhan, China, but has been detected in over 200 countries. Amid the Coronavirus Pandemic, several countries worldwide resorted to lockdown to control infection. Due to lockdown, the production and distribution chains have been disrupted across the lands. All the segments of the economy have been impacted in different magnitude, and this has a direct impact on GDP, unemployment ratio, and tax collection. Goods and Services Tax (GST) is a harmonized tax of different indirect taxes in India. The GST collection reflects the volume of economic activities in India. Thus, in this paper, an attempt has been made to assess the impact of Covid-19 on the Indian economy concerning the quantum of Goods and Service collection in Indian during the lockdown period. For this study, secondary data relating to GST collection have been pooled from the official websites of the GST Council of India for the last three years, i.e., 2018 to 2020, and pair t-test have been run for testing statistical significance of the impact of COVID-19 on the quantum of the collection of Goods and Service Tax in India before and after lockdown announcement after adjusting the inflation factor. The results indicate no significant difference in the quantum of Goods and Services Tax Collection in India before and after the lockdown announcement due to the COVID-19 outbreak but a loss of Rs. 1,41,837 crore owing to the low collection of GST from March 2020 to August 2020 gives us a clear message that we should undoubtedly rethink the plans in more structural and more viable ways to reach a position to absorb any kinds of uncertain threats from the external environment. KEYWORDS: Covid-19, GST, Indian Economy, Pandemic, Lockdown

2021 ◽  
Vol 17 (5) ◽  
pp. 932-941
Gengqi Wang ◽  
Wenqiang Xu ◽  
Junjie Zhang ◽  
Tian Tang ◽  
Jing Chen ◽  

Repairing fractures in the presence of infection is a major challenge that is currently declining using nanotechnology. By producing iron oxide nanoparticles (NPs) containing hydroxyapatite and Raloxifene (R-IONPs-HA), this study tries to target drug delivery, control infection and promotion of the cells proliferation/differentiation to repair damaged tissue. After the production of R-IONPs-HA through co-precipitation, the physicochemical features of the NPs were considered by SEM, TEM, DLS and XRD methods, and the possibility of drug release. The effect of R-IONPs-HA on MC3T3-E1 cell proliferation/differentiation was determined by CCK-assay and microscopic observations. Also, Gram-negative and -positive bacteria were applied to evaluate the antibacterial activity. Finally, cell differentiation biomarkers like an ALP, OCN, and RUNX-2 genes were examined by real time (RT)-PCR. The results showed that R-IONPs-HA was spherical with dimensions of 98.1 ± 1.17 nm. In addition, the results of Zeta and XRD confirmed the loading HA and R on IONPs. Also, the release rate of R and HA in 64 h with pH 6 reached 61.4 and 30.4%, respectively. The anti-bacterial activity of R-IONPs-HA on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa bacteria showed a significant reduction in infection. Also, MC3T3-E1 cells showed greater proliferation and differentiation by R-IONPs-HA compared to other groups. Increased expression of ossification genes such as OCN, and RUNX-2 confirmed this claim. Finally, R-IONPs-HA with good biocompatibility, antibacterial activity and ossification induction has great potential to repair bone fractures and prevent infection.

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