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Characterizing the Interaction Between Candida albicans and Two Enterobacter SpeciesCornett, Abigail 01 May 2022 (has links)
Candida albicans is the most common human fungal pathogen. The relationship between C. albicans and Enterobacter bacteria have yet to be explored. The hypothesis of this study is that C. albicans and both E. aerogenes and E. cloacae have a positive relationship and work together to infect the host. In this study, the physical cell-to-cell interaction, molecular components of said interaction, and the impact of the interaction on a live organism were explored. Results indicate that Enterobacter adheres to C. albicans and inhibits growth with unidentified secreted molecules. Als1p has potential involvement in the attachment of E. cloacae to C. albicans. Out of 480 E. cloacae mutants, 6 showed reductions in attachment to C. albicans. The presence of C. albicans in C. elegans may lead to less Enterobacter colonization. Future work involving this interaction should strive to identify the Enterobacter secreted molecules and genes necessary for their production.
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Comparison of Secondary Infections in patients with Corona Virus Disease (COVID-19) and Influenza : A retrospective cohort study in Stockholm SwedenOgunde, Lydia January 2021 (has links)
The aim of this study was to assess the prevalence and predictive factors of secondary infectionsin patients with coronavirus disease 2019 (COVID-19) and compare with influenza. A retrospective cohort study which included COVID-19 and influenza patients with samples processed at Karolinska University Hospital Laboratory between 1st March 2020 to 1st January2021 and 1st January 2015 to 1st January 2021 respectively. Blood, urine and respiratory culture results from 7 days before and 7 days after the primary diagnosis collected from laboratory information system. Chi-square and Mann-Whitney U test used for descriptive comparison. Predictive factors of secondary infections analyzed using logistic regression. Data includes 16,354 patients:7470 COVID-19 and 8884 influenza. Secondary infections were significantly fewer in COVID-19 patients (26.6%) compared to influenza patients (30%) p<0.01. Lower proportion of episodes with growth (EWG) in blood culture of COVID-19 patients (1.8%) compared to influenza (2.9%) p<0.001. Lower proportion of EWG in respiratory tract cultures of COVID-19 patients (11.1%) compared to influenza patients (24.5%) p<0.001. Higher proportionof EWG in urinary tract cultures of COVID-19 patients (24.5%) compared to influenza (20.1%)p<0.001. Staphylococcus aureus were common bacteria in blood and respiratory tract in both cohorts. Escherichia coli were the most common bacteria in urine in both cohorts. Fungi were least common with unspecified yeast being the most frequent. Likelihood of secondary infection lower in males compared to females AOR 0.70 (95%CI 0.66-0.76)), lower in other clinicalsettings AOR 0.65 (95%CI 0.56-0.76) and increased with age in both COVID-19 and influenza patients (AOR 1.03(95%CI 1.02-1.04)). Higher probability of secondary infections in young influenza patients compared to young COVID-19 patients. A lower prevalence of secondary infections in blood, respiratory tract cultures of COVID-19 patients compared to influenza. Olderage, female sex, intensive care were predictive factors for secondary infections. Findings important for planning of treatment protocols.
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Chlamydia Persistence - a Tool to Dissect Chlamydia-Host InteractionsSchoborg, R. V. 01 January 2011 (has links)
Under stress, chlamydiae can enter a non-infectious but viable state termed persistence. In the absence of a tractable genetic system, persistence induction provides an important experimental tool with which to study these fascinating organisms. This review will discuss examples of: i) persistence studies that have illuminated critical chlamydiae/host interactions; and ii) novel persistence models that will do so in the future.
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Human Papilloma Virus and Chlamydia trachomatis: Casual Acquaintances or Partners in Crime?Slade, Jessica A., Schoborg, Robert V. 15 June 2019 (has links)
Purpose of Review: Interactions between microorganisms can alter subsequent disease outcomes. Human papilloma virus (HPV) and Chlamydia trachomatis (CT) establish human genital co-infections, and CT infection is a co-factor for HPV-induced cervical cancer. This review focuses upon (i) data indicating that clinically significant interactions occur and (ii) proposed mechanisms underlying these outcomes. Recent Findings: Epidemiological surveys indicate that (i) simultaneous HPV/CT genital co-infections are common; (ii) CT co-infection accelerates HPV-induced cytopathology; and (iii) HPV infection facilitates CT infection. Single-infection studies suggest specific molecular mechanisms by which co-infection alters clinical outcomes, including (i) HPV E6/E7 protein modification of host cell pathways enhances CT replication or immune evasion and (ii) CT-mediated host cell or neutrophil dysfunctions promote HPV-mediated neoplasia. Summary: There are multiple avenues for future dissection of HPV/CT interactions. Moreover, the known and potential health consequences of co-infection highlight the need for improving current HPV vaccines and developing an effective CT vaccine.
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Does the inclusion of the cost and burden of adverse drug reactions associated with drug-resistant TB treatment affect the incremental cost-effectiveness of new treatment regimens? A case study from the introduction of bedaquiline in South Africa National TB ProgrammeBistline, Kathryn Lou 16 August 2018 (has links)
South Africa has one of the world’s highest burdens of TB, HIV/TB co-infection, and drug-resistant TB. Second-line TB treatment is less effective, more expensive, and more toxic than treatment for drug-sensitive TB. Nearly 1 in every 5 persons who starts treatment for drug-resistant TB in South Africa will die; 1 in every 3 persons who survives treatments experiences permanent, profound hearing loss. For decades there was little progress in TB research, however, and so treatment with old regimens continued despite safety concerns. In 2012 the US and European regulatory authorities approved a new drug, bedaquiline, but only for treatment in cases with no other options. In 2015, the South African Medicines Control Council approved bedaquiline for drug-resistant TB, but only a limited number of doses were approved in the 2016/2017 annual budget and the focus, again, was only for the patients who had no other options. In order to inform policy makers in planning and budgeting for drug-resistant TB treatment, the aim of this thesis was to determine whether the simple calculation that bedaquiline was too expensive relative to standard regimens using kanamycin was too simple. Particularly, given the high burden of adverse drug reactions (ADR) associated with kanamycin, would the inclusion of the cost and burden of ADR affect the incremental cost effectiveness ratio of a new treatment regimen where bedaquiline replaces kanamycin? Analysis of the national drug-resistant TB case register showed that mortality during second-line treatment was early, primarily in the first 6 months of treatment, even when patients do not have extensive drug resistance. HIV-positive patients not on anti-retroviral therapy (ART) at initiation of drug-resistant TB treatment have the highest risk of mortality. The high early mortality is a real risk that clinicians have to balance when deciding to initiate ART and effective second-line TB treatment both as quickly as possible. Daily injections coupled with taking more than 10 pills each day are a heavy burden for patient compliance, but also pose concerns in terms of overlapping and compounding toxicities; this burden was confirmed through a meta-analysis of the pooled frequency of adverse events among cohorts with at least 25% of the patients HIV-positive. A competing risk analysis of a cohort of drug-resistant TB patients from Johannesburg – addressing the reality that patients may not have experienced an ADR because they died rather than because they were at lower risk – indicated that HIV-infected patients who are not yet stable on ART and second-line TB treatment are at the highest risk of ADR. A Markov model built and parameterized using the data from the South African national TB programme indicates that bedaquiline for all drug-resistant TB led to a small gain in effectiveness at a cost that was under the costs of the drug itself, due to savings from daily injection visits. While cost-effective, it was not clear that South African policy makers needed to move beyond the offer of bedaquiline for patients with extensive drug resistance. However, the calculation, and the decision point, were different once the costs and disability associated with ADRs was included in the analysis. Bedaquiline-based regimens offer a cost-saving and more effective alternative to an injection-based regimen for drug-resistant TB patients treated in the public sector in South Africa.
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Risk Factors for Tuberculosis and Multidrug-Resistant Tuberculosis Complications among Foreign-Born Persons in Houston, TexasIsaboke, James N. 01 January 2016 (has links)
Tuberculosis (TB) is a leading public health problem across the world. For various reasons, TB and multidrug-resistant tuberculosis (MDR-TB) have increased. Clarification on TB/HIV co-infection and homelessness as risk factors for TB and MDR-TB is required to inform policy interventions to reduce TB-related morbidity, mortality, and healthcare costs. In this quantitative study, data from the Houston Health Department (N = 341) were analyzed to explore the relationship between TB and MDR-TB outcomes and TB/HIV co-infection and type of housing/homelessness. Foreign-born persons are disproportionately affected in the United States. The socio-ecological model provided a theoretical framework for the investigation. Multiple and logistic regression analyses were conducted to investigate the relationships between variables, controlling for age and gender. Results indicate that HIV infected persons were more likely than non-infected persons to contract TB, and homeless persons were more likely than non-homeless persons to contract TB/MDR-TB, suggesting that high TB/HIV co-infection rates increase prevalence of TB and MDR-TB while improvements in housing reduce prevalence of TB and MDR-TB. However, no significant associations between variables were found. The odds ratio, Exp(B) = 0.000, p -?¥ 0.90, 95% Cl [0.000, with no upper bound values] was observed for both independent variables. Regular screening for TB/HIV co-infection among persons with high TB and MDR-TB risk profiles is recommended. Further investigation is required. Inclusion of more covariates could further elucidate more evidence of an association between variables. Study findings may support interventions to reduce TB-related morbidity, leading to positive social change.
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Characterization of co-infections and minor variants of BK polyomavirus in clinical sample by NGSKhatoon, Safia January 2020 (has links)
BK polyomavirus (BKV) is associated with urinary apparatus pathogenesis in kidney transplant recipient. Immune suppression triggers BKV reactivation that potentially causes polyomavirus associated nephropathy (PVAN), a major post-transplant problem causes graft rejection. Antiviral immunity plays the key role in limiting the viral replication but selection by the immune system or antivirals may cause the evolvement of escape variants with higher fitness. Mutation in VP1, the major capsid protein can allow BKV to escape neutralizing antibodies. In an attempt to detect co-infection and minor variants, BKV VP1 genomic region was amplified by PCR and analysed by deep sequencing from plasma samples of four kidney transplant recipients. BKV genotype I and IV was identified in patients and each patient was detected with one BKV genotype. Multiple point mutations and subsequent changes in amino acid were detected in majority, three out of four, of the patients.
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Induction of the <em>Chlamydia trachomatis</em> Persistent State by Herpes simplex Virus Type 2 Does Not Require Productive Viral Replication.Deka, Srilekha 17 December 2005 (has links) (PDF)
Clinical and epidemiological studies have shown that multiple infection with HSV-2 and Chlamydia trachomatis occurs in vivo. We hypothesize that (i) HSV-2 co-infection of C. trachomatis infected cervical epithelial cells induces chlamydial persistence; (ii) productive HSV-2 replication is required for induction of persistence in C. trachomatis; (iii) co-infection with C. trachomatis and HSV-2 alters accumulation of immuno-modulatory molecules in infected cells. To test these hypotheses, a cell culture model of co-infection was established in HeLa cells. Transmission electron microscopic (TEM) analyses demonstrated aberrant chlamydial morphology in co-infected cells, which was apparent by 10 hours and prominent by 20 hours post HSV-2 infection. Moreover, co-infection reduced infectivity of progeny chlamydiae. These observations indicate chlamydial persistence and are consistent with certain historical 'markers' of persistence previously described. Since chlamydial persistence was being established, we were interested in unraveling the mechanism of induction. To determine whether HSV-2 replication was necessary, cyclohexamide (Cx), a eukaryotic protein synthesis inhibitor, was used. Cx inhibits host cell and viral protein synthesis by >95% and productive viral replication by >90%. Development of chlamydial persistence was observed in the presence of Cx. To analyze whether events during attachment and entry are sufficient for induction of chlamydial persistence, UV-inactivated, replication incompetent HSV-2 (HSV-2uv) was used. HSV-2uv is capable of attachment and entry but incapable of productive replication. Chlamydial persistence also developed during co-infection with C. trachomatis and HSV-2uv. Both of these observations suggest that an early event/s in HSV-2 replication, most probably occurring during HSV-2 attachment and entry, is sufficient for induction of chalmydial persistence. These observations also suggest that productive viral replication is not required for the induction of chlamydial persistence. Accumulation of chlamydial major outer membrane (MOMP) was decreased whereas pro-inflammatory chlamydial heat shock protein 60 (cHSP60) was increased in co-infected cells compared to C. trachomatis singly-infected cells. Among the cytokines looked at, an elevation in the levels of IL-6 was observed in HSV-2 infected and co-infected samples. Release of chlamydial antigens during chlamydial persistence increases inflammation and disease severity in vivo. Therefore, co-infection might increase immunopathology compared to that observed in C. trachomatis singly-infected individuals.
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Herpes Simplex Virus Glycoprotein D/Host Cell Surface Interaction Stimulates <em>Chlamydia trachomatis</em> Persistence via a Novel Pathway.Vanover, Jennifer 13 December 2008 (has links) (PDF)
When presented with certain unfavorable environmental conditions, C. trachomatis reticulate bodies (RBs) enter into a viable, yet noncultivable state called persistence. Two hallmarks of persistent chlamydiae are swollen, aberrantly shaped RBs, as viewed by transmission electron microscopy and a decrease in infectious progeny. Several models of chlamydial persistence have been described, including interferon-γ (IFN-γ), IFN-α, IFN-β, and tumor necrosis factor-α-exposure and nutrient deprivation. Previously, we established an in vitro co-infection model of two of the most common sexually transmitted pathogens in the United States, C. trachomatis and Herpes Simplex Virus-2 (HSV). Data from this tissue culture model indicate that: i) viral co-infection stimulates the formation of persistent chlamydiae and ii) productive HSV replication is not required for persistence induction. Further studies indicate that, co-infection-induced persistence is not mediated by: i) any known anti-chlamydial cytokine; ii) activation of inducible nitric oxide synthase or indoleamine 2, 3-dioxygenase; iii) inhibition of vesicular trafficking or sphingomyelin transport to the inclusion or; iv) amino acid, iron or glucose deprivation. These data demonstrate that co-infection-induced persistence is mediated by a previously undescribed, novel mechanism. During long-term co-infection with UV-inactivated HSV-2, chlamydiae recover following an initial suppression of chlamydial infectivity. These data indicate that HSV-induced persistence, like other persistence models, is reversible. Co-incubation of fixed, HSV-2-infected inducer cells with viable, C. trachomatis infected responder cells suppresses production of infectious chlamydial progeny and stimulates the formation of swollen, aberrantly shaped RBs. Antibody neutralization of HSV glycoprotein D (gD), which prevents viral attachment to one of four known HSV co-receptors on the host cell surface, also prevents co-infection-induced persistence, suggesting that HSV gD interaction with host cell surface receptors can provide the necessary stimulus to alter C. trachomatis development. Finally, exposure of C. trachomatis infected cells to soluble, recombinant HSV-2 gD:Fc fusion proteins decreases production of infectious EBs to a similar degree observed in co-infected cultures. Thus, we hypothesize that interaction of HSV gD with the host cell surface triggers a novel host anti-chlamydial pathway that restricts chlamydial development.
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Studies on common viral and bacterial pathogens of Bovine Respiratory Disease during in vitro co-infectionCowick, Caitlyn 30 April 2021 (has links) (PDF)
Bovine Respiratory Disease Complex is a multifactorial disease affecting cattle worldwide resulting in high mortality and morbidity rates in the cattle farming industry. This complex is caused by multiple viral and bacterial pathogens such as Bovine Herpesvirus-1, Bovine Respiratory Syncytial Virus, Mannheimia haemolytica, and Pasteurella multocida; two of the main contributors to the initiation of this disease are Bovine Herpesvirus-1 and the bacteria, Mannheimia haemolytica. Together, these microbes co-infect immunocompromised cattle during times of increased stress and induce a severe pneumonic response along with other health complications. Research has been primarily focused on these microorganisms individually or their effect on the host, however there is a need to study them together due to the increased mortality rate associated with co-infections. In this study, we used Bovine Herpesvirus-1, Mannheimia haemolytica, Pasteurella multocida, and Bovine Respiratory Syncytial Virus to co-infect bovine tissue cultures to determine how they affect each other.
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