- Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Hospitalization for Community-Acquired Pneumonia in Older US Adults: A Test-Negative Design. [Journal Article]
- CIClin Infect Dis 2018 May 21
- CONCLUSIONS: Our study is the first to demonstrate real-world effectiveness of PCV13 against vaccine-type CAP in adults aged ≥65 years following introduction into a national immunization program.
- Biofilm Destruction on Endotracheal Tube-associated Pneumonia by photodynamic Inactivation. [Journal Article]
- IDInfect Disord Drug Targets 2018 May 22
- Hospital infections is a public health problem that can occur with the use of catheters and endotracheal tubes (ETT). Pathogenic microorganisms may adhere to surfaces of these materials forming biofi...
Hospital infections is a public health problem that can occur with the use of catheters and endotracheal tubes (ETT). Pathogenic microorganisms may adhere to surfaces of these materials forming biofilm. Microbial biofilms presents an extracellular polymer matrix that promotes resistance of microorganisms to factors such as pH, temperature and drugs. The ETT is used to assist a patient with compromised breathing function. ETT biofilm may cause ventilator-associated pneumonia. Pseudomonas aeruginosa and Staphylococcus aureus pneumonia is associated with a 21-fold increase in risk for mechanical ventilation. According to the World Health Organization 1.6 million people die every year from pulmonary infections. These human health problem have have high costs. The conventional treatment is be made by antibiotics, which has serious adverse effects in immunocompromised patients. Bronchoaspiration is the preventive treatment for these diseases in bedridden patients using ETT. Photodynamic therapy (PDT) is an alternative for microbial inactivation noninvasive without stimule of microbial resistance. PDT combines light and a photosensitive molecule for produce reactive oxygen species leading to bacterial death. The objective of this study was to determine the efficacy of a PDT protocol in bacterial inactivation of biofilm ETT. The photosensitizer (PS) used was curcumin and the light source LED at 450nm. Statistical experimental design was used for optimization of antimicrobial PDT. The highest microbial inactivation was found with 70% biofilm reduction in conditions 1 mg/mL curcumin, 2 h of PS incubation and 30 J/cm2.
- Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) Study of Respiratory Syncytial Virus-Associated Deaths in Pediatric Patients in Canada: 2003 to 2013. [Journal Article]
- CIClin Infect Dis 2018 May 16
- CONCLUSIONS: RSV-associated deaths were predominantly associated with chronic medical conditions and immunocompromised states among infants; however, 1 in 5 deaths occurred among patients with no known risk factors for severe RSV. Mortality associated with HAI accounted for over a third of cases. These findings highlight patient groups that should be targeted for RSV prevention strategies such as infection control practices, immunoprophylaxis, and future vaccination programs. The precise impact of these strategies on RSV mortality, however, requires further study.
- Diagnosis and Management of Pulmonary Infection due to Rhodococcus equi. [Review]
- CMClin Microbiol Infect 2018 May 16
- CONCLUSIONS: Ten to 14 days of treatment may be effective for pneumonia due to R. equi. Our review suggests that longer courses of therapy are needed for cavitary lesions and lung masses. However, recommendations for excessively prolonged treatment of all pulmonary infections arose during a time that many cases occurred in AIDS patients and before effective antiretroviral therapy was available. We suggest that the rationale for prolonged therapy with multiple antibiotics needs to be re-evaluated.
- Summary of NACI Statement: Interim Recommendations on the Use of Pneumococcal Vaccines in Immunocompetent Adults 65 Years of Age and Older. [Journal Article]
- CCCan Commun Dis Rep 2016 Dec 01; 42(12):260-262
- CONCLUSIONS: Based on reviewed evidence, NACI issued new recommendations for the use of pneumococcal vaccines in immunocompetent adults 65 years of age and older.
- A Multifaceted Approach to RSV Vaccination. [Journal Article]
- HVHum Vaccin Immunother 2018 May 17; :1-44
- Respiratory Syncytial Virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants, resulting in significant morbidity and mortality worldwide. In addition, RSV infections occur through...
Respiratory Syncytial Virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants, resulting in significant morbidity and mortality worldwide. In addition, RSV infections occur throughout different ages, thus, maintaining the virus in circulation, and increasing health risk to more susceptible populations such as infants, the elderly, and the immunocompromised. To date, there is no vaccine approved to prevent RSV infection or minimize symptoms of infection. Current clinical trials for vaccines against RSV are being carried out in four very different populations. There are vaccines that target two different pediatric populations, infants 2 to 6 month of age and seropositive children over 6 months of age, as well as women (non-pregnant or pregnant in their third trimester). There are vaccines that target adult and elderly populations. In this review, we will present and discuss RSV vaccine candidates currently in clinical trials. We will describe the preclinical studies instrumental for their advancement, with the goal of introducing new preclinical models that may more accurately predict the outcome of clinical vaccine studies.
- Cotton rat model for testing vaccines and antivirals against respiratory syncytial virus. [Journal Article]
- ACAntivir Chem Chemother 2018 Jan-Dec; 26:2040206618770518
- Respiratory syncytial virus is the leading cause of pneumonia and bronchiolitis in infants and is a serious health risk for elderly and immunocompromised individuals. No vaccine has yet been approved...
Respiratory syncytial virus is the leading cause of pneumonia and bronchiolitis in infants and is a serious health risk for elderly and immunocompromised individuals. No vaccine has yet been approved to prevent respiratory syncytial virus infection and the only available treatment is immunoprophylaxis of severe respiratory syncytial virus disease in high-risk infants with Palivizumab (Synagis®). The development of respiratory syncytial virus vaccine has been hampered by the phenomenon of enhanced respiratory syncytial virus disease observed during trials of a formalin-inactivated respiratory syncytial virus in 1960s. A search for effective respiratory syncytial virus therapeutics has been complicated by the fact that some of the most advanced respiratory syncytial virus antivirals, while highly effective in a prophylactic setting, had not demonstrated clinical efficacy when given after infection. A number of respiratory syncytial virus vaccines and antivirals are currently under development, including several vaccines proposed for maternal immunization. The cotton rat Sigmodon hispidus is an animal model of respiratory syncytial virus infection with demonstrated translational value. Special cohort scenarios, such as infection under conditions of immunosuppression and maternal immunization have been modeled in the cotton rat and are summarized here. In this review, we focus on the recent use of the cotton rat model for testing respiratory syncytial virus vaccine and therapeutic candidates in preclinical setting, including the use of special cohort models. An overview of published studies spanning the period of the last three years is provided. The emphasis, where possible, is made on candidates in the latest stages of preclinical development or currently in clinical trials.
- Travel-related health problems in the immunocompromised traveller: An exploratory study. [Journal Article]
- TMTravel Med Infect Dis 2018 May 12
- CONCLUSIONS: Our findings substantiate the recommendation of on demand antibiotics. However, ICTs did often not use on demand antibiotics correctly; they therefore need very careful instructions.
- Gut Microbiota Contributes to Resistance Against Pneumococcal Pneumonia in Immunodeficient Rag-/- Mice. [Journal Article]
- FCFront Cell Infect Microbiol 2018; 8:118
- Streptococcus pneumoniae causes infection-related mortality worldwide. Immunocompromised individuals, including young children, the elderly, and those with immunodeficiency, are especially vulnerable...
Streptococcus pneumoniae causes infection-related mortality worldwide. Immunocompromised individuals, including young children, the elderly, and those with immunodeficiency, are especially vulnerable, yet little is known regarding S. pneumoniae-related pathogenesis and protection in immunocompromised hosts. Recently, strong interest has emerged in the gut microbiota's impact on lung diseases, or the "gut-lung axis." However, the mechanisms of gut microbiota protection against gut-distal lung diseases like pneumonia remain unclear. We investigated the role of the gut commensal, segmented filamentous bacteria (SFB), against pneumococcal pneumonia in immunocompetent and immunocompromised mouse models. For the latter, we chose the Rag-/- model, with adaptive immune deficiency. Immunocompetent adaptive protection against S. pneumoniae infection is based on antibodies against pneumococcal capsular polysaccharides, prototypical T cell independent-II (TI-II) antigens. Although SFB colonization enhanced TI-II antibodies in C57BL/6 mice, our data suggest that SFB did not further protect these immunocompetent animals. Indeed, basal B cell activity in hosts without SFB is sufficient for essential protection against S. pneumoniae. However, in immunocompromised Rag-/- mice, we demonstrate a gut-lung axis of communication, as SFB influenced lung protection by regulating innate immunity. Neutrophil resolution is crucial to recovery, since an unchecked neutrophil response causes severe tissue damage. We found no early neutrophil recruitment differences between hosts with or without SFB; however, we observed a significant drop in lung neutrophils in the resolution phase of S. pneumoniae infection, which corresponded with lower CD47 expression, a molecule that inhibits phagocytosis of apoptotic cells, in SFB-colonized Rag-/- mice. SFB promoted a shift in lung neutrophil phenotype from inflammatory neutrophils expressing high levels of CD18 and low levels of CD62L, to pro-resolution neutrophils with low CD18 and high CD62L. Blocking CD47 in SFB(-) mice increased pro-resolution neutrophils, suggesting CD47 down-regulation may be one neutrophil-modulating mechanism SFB utilizes. The SFB-induced lung neutrophil phenotype remained similar with heat-inactivated S. pneumoniae treatment, indicating these SFB-induced changes in neutrophil phenotype during the resolution phase are not simply secondary to better bacterial clearance in SFB(+) than SFB(-) mice. Together, these data demonstrate that the gut commensal SFB may provide much-needed protection in immunocompromised hosts in part by promoting neutrophil resolution post lung infection.
New Search Next
- The Hyr1 protein from the fungus Candida albicans is a cross kingdom immunotherapeutic target for Acinetobacter bacterial infection. [Journal Article]
- PPPLoS Pathog 2018; 14(5):e1007056
- Different pathogens share similar medical settings and rely on similar virulence strategies to cause infections. We have previously applied 3-D computational modeling and bioinformatics to discover n...
Different pathogens share similar medical settings and rely on similar virulence strategies to cause infections. We have previously applied 3-D computational modeling and bioinformatics to discover novel antigens that target more than one human pathogen. Active and passive immunization with the recombinant N-terminus of Candida albicans Hyr1 (rHyr1p-N) protect mice against lethal candidemia. Here we determine that Hyr1p shares homology with cell surface proteins of the multidrug resistant Gram negative bacterium, Acinetobacter baumannii including hemagglutinin (FhaB) and outer membrane protein A (OmpA). The A. baumannii OmpA binds to C. albicans Hyr1p, leading to a mixed species biofilm. Deletion of HYR1, or blocking of Hyr1p using polyclonal antibodies, significantly reduce A. baumannii binding to C. albicans hyphae. Furthermore, active vaccination with rHyr1p-N or passive immunization with polyclonal antibodies raised against specific peptide motifs of rHyr1p-N markedly improve survival of diabetic or neutropenic mice infected with A. baumannii bacteremia or pneumonia. Antibody raised against one particular peptide of the rHyr1p-N sequence (peptide 5) confers majority of the protection through blocking A. baumannii invasion of host cells and inducing death of the bacterium by a putative iron starvation mechanism. Anti-Hyr1 peptide 5 antibodies also mitigate A. baumannii /C. albicans mixed biofilm formation in vitro. Consistent with our bioinformatic analysis and structural modeling of Hyr1p, anti-Hyr1p peptide 5 antibodies bound to A. baumannii FhaB, OmpA, and an outer membrane siderophore binding protein. Our studies highlight the concept of cross-kingdom vaccine protection against high priority human pathogens such as A. baumannii and C. albicans that share similar ecological niches in immunocompromised patients.