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MSystems Apr 2024Secondary bacterial challenges during influenza virus infection "superinfection") cause excessive mortality and hospitalization. Here, we present a longitudinal study of...
UNLABELLED
Secondary bacterial challenges during influenza virus infection "superinfection") cause excessive mortality and hospitalization. Here, we present a longitudinal study of bulk gene expression changes in murine lungs during superinfection, with an initial influenza A virus infection and a subsequent infection. In addition to the well-characterized impairment of the host response, we identified superinfection-specific alterations in the global transcriptional program that are linked to the host's ability to resist the pathogens. Particularly, whereas superinfected mice manifested an excessive rapid induction of the resistance-to-infection program, there was a substantial tissue-level rewiring of this program: upon superinfection, interferon-regulated genes were switched from positive to negative correlations with the host's resistance state, whereas genes of fatty acid metabolism switched from negative to positive correlations with resistance states. Thus, the transcriptional resistance state in superinfection is reprogrammed toward repressed interferon signaling and induced fatty acid metabolism. Our findings suggest new insights into a tissue-level remodeling of the host defense upon superinfection, providing promising targets for future therapeutic interventions.
IMPORTANCE
Secondary bacterial infections are the most frequent complications during influenza A virus (IAV) pandemic outbreaks, contributing to excessive morbidity and mortality in the human population. Most IAV-related deaths are attributed to (SP) infections, which usually begin within the first week of IAV infection in the respiratory tracts. Here, we focused on longitudinal transcriptional responses during a superinfection model consisting of an SP infection that follows an initial IAV infection, comparing superinfection to an IAV-only infection, an SP-only infection, and control treatments. Our longitudinal data allowed a fine analysis of gene expression changes during superinfection. For instance, we found that superinfected mice exhibited rapid gene expression induction or reduction within the first 12 h after encountering the second pathogen. Cell proliferation and immune response activation processes were upregulated, while endothelial processes, vasculogenesis, and angiogenesis were downregulated, providing promising targets for future therapeutic interventions. We further analyzed the longitudinal transcriptional responses in the context of a previously defined spectrum of the host's resistance state, revealing superinfection-specific reprogramming of resistance states, such as reprogramming of fatty acid metabolism and interferon signaling. The reprogrammed functions are compelling new targets for switching the pathogenic superinfection state into a single-infection state.
Topics: Mice; Humans; Animals; Streptococcus pneumoniae; Influenza A virus; Superinfection; Longitudinal Studies; Influenza, Human; Pneumococcal Infections; Immunity, Innate; Interferons; Fatty Acids
PubMed: 38446104
DOI: 10.1128/msystems.01048-23 -
Malaria Journal Mar 2024Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programmes (NMCPs) assess parasite transmission....
BACKGROUND
Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programmes (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence.
METHODS
This study examined parasites from 3147 clinical infections sampled between the years 2012-2020 through passive case detection (PCD) across 16 clinic sites spread throughout Senegal. Samples were genotyped with a 24 single nucleotide polymorphism (SNP) molecular barcode that detects parasite strains, distinguishes polygenomic (multiple strain) from monogenomic (single strain) infections, and identifies clonal infections. To determine whether genetic signals can predict incidence, a series of Poisson generalized linear mixed-effects models were constructed to predict the incidence level at each clinical site from a set of genetic metrics designed to measure parasite clonality, superinfection, and co-transmission rates.
RESULTS
Model-predicted incidence was compared with the reported standard incidence data determined by the NMCP for each clinic and found that parasite genetic metrics generally correlated with reported incidence, with departures from expected values at very low annual incidence (< 10/1000/annual [‰]).
CONCLUSIONS
When transmission is greater than 10 cases per 1000 annual parasite incidence (annual incidence > 10‰), parasite genetics can be used to accurately infer incidence and is consistent with superinfection-based hypotheses of malaria transmission. When transmission was < 10‰, many of the correlations between parasite genetics and incidence were reversed, which may reflect the disproportionate impact of importation and focal transmission on parasite genetics when local transmission levels are low.
Topics: Humans; Senegal; Incidence; Plasmodium falciparum; Superinfection; Malaria
PubMed: 38443939
DOI: 10.1186/s12936-024-04897-z -
Deutsches Arzteblatt International Apr 2024Postoperative surgical site infections (SSI) account for almost 25% of all nosocomial infections in Germany and are a source of increased morbidity and mortality. (Review)
Review
BACKGROUND
Postoperative surgical site infections (SSI) account for almost 25% of all nosocomial infections in Germany and are a source of increased morbidity and mortality.
METHODS
This review is based on pertinent publications retrieved by a selective search in PubMed and on national and international guidelines.
RESULTS
The individual risk factors for SSI must be assessed before any surgical procedure. A body-mass index above 30 kg/m2 is associated with an unadjusted risk ratio of 1.35 [1.28; 1.41] for SSI, which rises to 3.29 [2.99; 3.62] if the patient is also immunosuppressed. The risk of SSI is also significantly higher with certain types of procedure. Perioperative antibiotic prophylaxis (PAP) is clearly indicated for operations that carry a high risk of SSI (e.g., colorectal surgery) and for those that involve the implantation of alloplastic material (e.g., hip endoprostheses). PAP can usually be administered with basic antibiotics such as cefazoline. The basic principles of PAP are that it should be given by the anesthesia team in the interval from 60 minutes preoperatively up to shortly before the incision, and that its administration should only be for a short period of time, usually as a single shot. Continuing PAP onward into the postoperative period leads to increased toxicity, bacterial superinfections, and antibiotic resistance.
CONCLUSION
The evidence shows that perioperative antibiotic prophylaxis is a component of a bundle of measures that can help prevent SSI. Strict indications and adherence to the basic principles of PAP are essential for therapeutic success.
Topics: Humans; Surgical Wound Infection; Antibiotic Prophylaxis; Anti-Bacterial Agents; Perioperative Care; Treatment Outcome; Germany; Evidence-Based Medicine; Risk Factors
PubMed: 38440828
DOI: 10.3238/arztebl.m2024.0037 -
Cell Host & Microbe Mar 2024Several vaccines targeting bacterial pathogens show reduced efficacy upon concurrent viral infection, indicating that a new vaccinology approach is required. To identify...
Several vaccines targeting bacterial pathogens show reduced efficacy upon concurrent viral infection, indicating that a new vaccinology approach is required. To identify antigens for the human pathogen Streptococcus pneumoniae that are effective following influenza infection, we performed CRISPRi-seq in a murine model of superinfection and identified the conserved lafB gene as crucial for virulence. We show that LafB is a membrane-associated, intracellular protein that catalyzes the formation of galactosyl-glucosyl-diacylglycerol, a glycolipid important for cell wall homeostasis. Respiratory vaccination with recombinant LafB, in contrast to subcutaneous vaccination, was highly protective against S. pneumoniae serotypes 2, 15A, and 24F in a murine model. In contrast to standard capsule-based vaccines, protection did not require LafB-specific antibodies but was dependent on airway CD4 T helper 17 cells. Healthy human individuals can elicit LafB-specific immune responses, indicating LafB antigenicity in humans. Collectively, these findings present a universal pneumococcal vaccine antigen that remains effective following influenza infection.
Topics: Humans; Animals; Mice; Streptococcus pneumoniae; Pneumococcal Infections; Serogroup; Th17 Cells; Influenza, Human; Disease Models, Animal; Superinfection; Pneumococcal Vaccines; Antigens, Bacterial; Influenza Vaccines; Antibodies, Bacterial
PubMed: 38417443
DOI: 10.1016/j.chom.2024.02.002 -
Acta Dermato-venereologica Feb 2024In atopic dermatitis (AD), Staphylococcus aureus frequently colonizes lesions, leading to superinfections that can then lead to exacerbations. The presence of...
In atopic dermatitis (AD), Staphylococcus aureus frequently colonizes lesions, leading to superinfections that can then lead to exacerbations. The presence of biofilm-producing isolates has been associated with worsening of the disease. Potassium permanganate is used as a topical treatment of infected eczema, blistering conditions, and wounds. Little is known of its effects against microbes in AD skin. The aim of this study was to explore antibacterial and antibiofilm properties of potassium permanganate against staphylococcal isolates derived from AD skin. Viable count and radial diffusion assays were used to investigate antibacterial effects of potassium permanganate against planktonic staphylococcal isolates. The antibiofilm effects were assessed using biofilm assays and scanning electron microscopy. The Staphylococcus aureus isolates were completely killed when exposed to 0.05% of potassium permanganate. In concentrations of 0.01%, potassium permanganate inhibited bacterial biofilm formation. Eradication of established staphylococcal biofilm was observed in concentrations of 1%. Electron microscopy revealed dense formations of coccoidal structures in growth control and looser formations of deformed bacteria when exposed to potassium permanganate. This suggests antibacterial and antibiofilm effects of potassium permanganate against staphylococcal isolates derived from AD skin, when tested in vitro, and a potential role in the treatment of superinfected AD skin.
Topics: Humans; Dermatitis, Atopic; Potassium Permanganate; Skin; Eczema; Staphylococcus aureus; Staphylococcal Infections; Anti-Bacterial Agents
PubMed: 38415865
DOI: 10.2340/actadv.v104.18642 -
EJVES Vascular Forum 2024Popliteal artery aneurysms (PAAs) pose some challenges in their surgical management and are often treated by exclusion and bypass procedures. However, post-operative...
INTRODUCTION
Popliteal artery aneurysms (PAAs) pose some challenges in their surgical management and are often treated by exclusion and bypass procedures. However, post-operative complications, such as endoleaks and sac growth, can occur, potentially leading to serious consequences. Endoleaks, characterised by persistent flow within the aneurysm sac after repair, can cause sac expansion, increasing the risk of adverse outcomes, including the formation of cutaneous fistulae, a rare but potentially severe complication.
REPORT
A 75 year old male with a history of previous bilateral PAA exclusion with a left femoropopliteal bypass using reversed great saphenous vein (GSV) graft in 2012 and a right femoropopliteal bypass using a PTFE prosthesis in 2017, both through medial approach, presented with pain and ulceration in the left popliteal region. Previous angiography had shown residual arterial flow through collateral vessels, requiring thrombin injection. Bilateral bypass thrombosis had also occurred after discontinuing anticoagulation. Computed tomography angiography confirmed a complicated excluded left popliteal aneurysm with superinfection. The patient underwent elective surgery, involving partial aneurysmectomy, endoaneurysmorrhaphy, and fistulectomy through a posterior approach. Post-operatively, the patient experienced resolution of symptoms and inflammatory signs.
DISCUSSION
The optimal approach for treating PAAs remains a subject of debate, with some experts advocating the posterior approach to prevent sac growth. However, others support the medial approach, reporting satisfactory results. In this case, the medial approach resulted in incomplete exclusion, leading to sac expansion and a cutaneous fistula. Timely re-intervention through the posterior approach successfully resolved the complication. This report highlights a rare but serious complication of incomplete PAA exclusion. Vigilant post-operative surveillance and intervention are crucial to manage such cases effectively. Further research is warranted to determine the optimal approach for PAA repair and prevent associated complications.
PubMed: 38414726
DOI: 10.1016/j.ejvsvf.2024.01.051 -
Cureus Jan 2024Coronavirus disease 2019 (COVID-19) is often linked to a broad range of opportunistic bacterial and fungal infections. The second wave of the COVID-19 pandemic has...
Coronavirus disease 2019 (COVID-19) is often linked to a broad range of opportunistic bacterial and fungal infections. The second wave of the COVID-19 pandemic has witnessed an unprecedented surge in mucormycosis cases, predominantly in India, while the disease remained relatively rare in Europe. The authors describe the case of a 62-year-old female patient admitted to the hospital for consolidation therapy with chemotherapy as a part of the treatment protocol for acute myeloid leukemia. During hospitalization, she was diagnosed with nosocomial COVID-19, which later progressed to respiratory deterioration. COVID-19 with bacterial superinfection was presumed, leading to the initiation of empirical antibiotic therapy. A bronchoscopy was performed several days later due to a lack of improvement, revealing an infection by the complex. Despite antifungal treatment, the patient experienced an unfavorable clinical course and ultimately died. Given the high index of suspicion required to diagnose pulmonary mucormycosis, which can lead to delays in appropriate treatment and increase the burden of disease, the authors are aiming to enhance its awareness.
PubMed: 38406002
DOI: 10.7759/cureus.52849 -
Journal of Microbiology, Immunology,... Jun 2024The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive...
BACKGROUND
The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive mechanical ventilation. Nevertheless, the optimal timing to start dexamethasone remains uncertain.
METHODS
We conducted a quasi-experimental study at National Taiwan University Hospital (Taipei, Taiwan) using propensity score matching to simulate a randomized controlled trial to receive or not to receive early dexamethasone (6 mg/day) during the first 7 days following the onset of symptoms. Treatment was standard protocol-based, except for the timing to start dexamethasone, which was left to physicians' decision. The primary outcome is 28-day mortality. Secondary outcomes include secondary infection within 60 days and fulfilling the criteria of de-isolation within 20 days.
RESULTS
A total of 377 patients with COVID-19 were enrolled. Early dexamethasone did not decrease 28-day mortality in all patients (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.97-1.10) or in patients who required O2 for severe/critical disease at admission (aOR, 1.05; 95%CI, 0.94-1.18); but is associated with a 24% increase in superinfection in all patients (aOR, 1.24; 95% CI, 1.12-1.37) and a 23% increase in superinfection in patients of O2 for several/critical disease at admission (aOR, 1.23; 95% CI, 1.02-1.47). Moreover, early dexamethasone is associated with a 42% increase in likelihood of delayed clearance of SARS-CoV-2 virus (adjusted hazard ratio, 1.42; 95% CI, 1.01-1.98).
CONCLUSION
An early start of dexamethasone (within 7 days after the onset of symptoms) could be harmful to hospitalized patients with COVID-19.
Topics: Humans; Dexamethasone; Male; Propensity Score; Female; COVID-19 Drug Treatment; COVID-19; Middle Aged; Taiwan; Aged; SARS-CoV-2; Treatment Outcome; Respiration, Artificial; Aged, 80 and over; Hospitalization; Adult
PubMed: 38402071
DOI: 10.1016/j.jmii.2024.02.002 -
Vaccines Feb 2024Vaccination against COVID-19 has been the main strategy used by most countries to limit the spread of the virus. However, vaccine uptake has been low in Africa, leading...
Vaccination against COVID-19 has been the main strategy used by most countries to limit the spread of the virus. However, vaccine uptake has been low in Africa, leading to the implementation of several interventions in order to improve vaccine coverage. This study was conducted due to the lack of information about COVID-19 vaccine coverage and the factors associated with vaccine hesitancy. This cross-sectional study was carried out in Kinshasa city using multi-stage random sampling. A total of 2160 households were included in this study. The data were analyzed using Stata 17 software. The means and standard deviations were computed for continuous data that followed a normal distribution, whereas proportions together with their 95% confidence intervals (CIs) were computed for categorical variables. The connections between dependent variables and each independent variable were tested using either Pearson's chi-square test or Fisher's exact test. The logistic regression method was employed to determine the factors that are linked to hesitation in obtaining the COVID-19 immunization. The majority of respondents were aged between 25 and 34 and 35 and 49 (28.9%). During this study, 15% (95% CI [13.25-17.9]) of respondents had received at least one dose of the COVID-19 vaccine. The prevalence of vaccine hesitancy was 67% (CI95%:64.9-69.1). Among the reasons given for refusing to be vaccinated, most respondents cited concerns about the vaccine being unsafe or causing adverse reactions (45%). Among the reasons given for accepting the vaccine, 26% thought that the vaccine prevented superinfection. The factors associated with hesitancy toward the COVID-19 vaccine were female gender, an age of less than 35 years, and living in non-slum households. Despite the interventions implemented across the country, the reluctance to be vaccinated remains a problem; this could lead to poor health outcomes, especially among the elderly and those with pre-existing conditions. It is important to step up awareness-raising campaigns in the community in order to increase the uptake of vaccination.
PubMed: 38400171
DOI: 10.3390/vaccines12020188