Journal of Microbiology Immunology and Infection最新文献

{"title":"Mitigating treatment failure of pulmonary pre-extensively drug-resistant tuberculosis: The role of new and repurposed drugs","authors":"","doi":"10.1016/j.jmii.2024.04.008","DOIUrl":"10.1016/j.jmii.2024.04.008","url":null,"abstract":"<div><h3>Background</h3><p>Pre-extensively drug-resistant tuberculosis (pre-XDR-TB), defined as multidrug-resistant TB (MDR-TB) with additional resistance to any fluoroquinolone (FQ) is difficult to treat. We assessed whether the use of new or repurposed drugs (bedaquiline, delamanid, linezolid, carbapenem, clofazimine, pretomanid) mitigated treatment failure of pre-XDR-TB.</p></div><div><h3>Methods</h3><p>MDR-TB patients managed in the Taiwan MDR-TB consortium between July 2009–December 2019 were eligible. Treatment outcomes at 30 months were assessed. Logistic regression models were constructed to investigate factors associated with treatment outcomes.</p></div><div><h3>Results</h3><p>109 patients with FQ-resistant MDR-TB and 218 patients with FQ-susceptible MDR-TB were included. 60 (55.1%) patients with FQ-resistant MDR-TB and 63 (28.9%) patients with FQ-susceptible MDR-TB have been treated with new or repurposed drugs (p &lt; 0.01). Of the 218 patients with FQ-susceptible MDR-TB, 187 (85.8%) had treatment success, 30 (13.8%) died, no treatment failure, and 1 (0.5%) was loss-to-follow-up; of the 109 patients with FQ-resistant MDR-TB, 78 (71.6%) had treatment success, 21 (19.3%) died, 9 (8.3%) had treatment failure, and 1 (0.9%) was loss-to-follow-up (p &lt; 0.01). The use of new or repurposed drugs was not associated with treatment outcomes among patients with FQ-susceptible MDR-TB. No patients with FQ-resistant MDR-TB treated with ≥2 new or repurposed drugs within 6 months of treatment initiation had treatment failure (p = 0.03). Patients with FQ-resistant MDR-TB treated with 1 new or repurposed drugs was more likely to have treatment failure as compared with patients not treated with new or repurposed drugs (adjOR 7.06, 95% CI 1.72–29.06).</p></div><div><h3>Conclusions</h3><p>Proper use of new or repurposed anti-TB drugs can mitigate treatment failure in FQ-resistant MDR-TB.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 4","pages":"Pages 617-628"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224000768/pdfft?md5=acafda013d3ca3c328b7bc6c8e30acd0&pid=1-s2.0-S1684118224000768-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140812158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Far-ultraviolet irradiation at 222 nm destroys and sterilizes the biofilms formed by periodontitis pathogens","authors":"","doi":"10.1016/j.jmii.2024.05.005","DOIUrl":"10.1016/j.jmii.2024.05.005","url":null,"abstract":"<div><h3>Background</h3><p>Periodontal disease is the leading cause of tooth loss, and an association between periodontal disease and non-oral systemic diseases has been shown. Formation of biofilm by periodontal pathogens such as <em>Fusobacterium nucleatum</em>, <em>Porphyromonas gingivalis, and Streptococcus mutans</em> and their resistance to antimicrobial agents are at the root of persistent and chronic bacterial infections.</p></div><div><h3>Methods</h3><p>The bactericidal effect of far-ultraviolet (F-UV) light irradiation at 222 nm on periodontal bacteria was assessed qualitatively and quantitatively. The effect of biofilm disruption by F-UV light on periodontal bacteria was examined by crystal violet staining, and the morphologic changes of the biofilm after F-UV irradiation were explored by confocal laser microscopy and scanning electron microscopy. We developed a thin fiber-type 222 nm F-UV irradiator and studied its safety and effect of reducing bacteria in rodent models.</p></div><div><h3>Results</h3><p>F-UV light at 222 nm had a bactericidal effect on <em>F. nucleatum</em>, <em>P. gingivalis</em>, and <em>S. mutans</em>. Irradiation with F-UV light reduced the biofilm formed by the bacteria and sterilized them from within. Confocal laser microscopy showed a clear reduction in biofilm thickness, and scanning electron microscopy confirmed disintegration of the biofilm architecture. F-UV irradiation was less damaging to DNA and less cytotoxic than deep-ultraviolet light, and it reduced bacterial counts on the tooth surface.</p></div><div><h3>Conclusion</h3><p>F-UV irradiation has the potential to destroy biofilm and act as a bactericide against pathogenic bacteria in the biofilm.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 4","pages":"Pages 533-545"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224000823/pdfft?md5=bc262f58af6f2fc0d7ec4dd2ca322da9&pid=1-s2.0-S1684118224000823-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and evolution of anti-SARS-CoV-2 spike protein titers after three doses of COVID-19 vaccination in people with HIV","authors":"","doi":"10.1016/j.jmii.2024.02.004","DOIUrl":"10.1016/j.jmii.2024.02.004","url":null,"abstract":"<div><h3>Background</h3><p>Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH).</p></div><div><h3>Methods</h3><p>PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-μg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1–3 months.</p></div><div><h3>Results</h3><p>Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-μg mRNA-1273, 467 (32.8%) 50-μg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers &gt;1047 BAU/mL included CD4 count &lt;200 cells/mm³ (adjusted odds ratio [aOR], 0.11; 95% CI, 0.04–0.31), plasma HIV RNA &gt;200 copies/mL (aOR, 0.27; 95% CI, 0.09–0.80), having achieved anti-spike IgG &gt;141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68–5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10–0.41; reference, 100-μg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine).</p></div><div><h3>Conclusions</h3><p>PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-μg mRNA-1273 could generate a higher antibody response than with 50-μg mRNA-1273 and BNT162b2 vaccine.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 4","pages":"Pages 554-563"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224000410/pdfft?md5=31ef3fdd8cb6b549e02ae531635d946c&pid=1-s2.0-S1684118224000410-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139988321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial resistance profile in Salmonella enterica serovar Choleraesuis isolates from diseased pigs in Taiwan","authors":"","doi":"10.1016/j.jmii.2024.04.005","DOIUrl":"10.1016/j.jmii.2024.04.005","url":null,"abstract":"<div><p>This study investigated antimicrobial resistance in <em>Salmonella enterica</em> serovar Choleraesuis (<em>S.</em> Choleraesuis) isolates from diseased pigs in Taiwan (2015–2020). Among 272 isolates, florfenicol (96.7%), enrofloxacin (96.3%), doxycycline (91.2%), gentamicin (84.6%), and tiamulin (80.5%) exhibited high resistance. 99.3% of the isolates were resistant to at least one antibiotic, and 97.8% of the isolates were multidrug resistant. This study illustrated that <em>S.</em> Choleraesuis isolates exhibited high resistance to antimicrobials currently used in the Taiwanese swine industry.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 4","pages":"Pages 660-664"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224000732/pdfft?md5=ac7d2f9c3b9251aeaa3e3923051f16dd&pid=1-s2.0-S1684118224000732-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of trichomonads in patients with lung cancer and transcription analysis on the response of human pulmonary epithelial cells to Trichomonas tenax invasion","authors":"","doi":"10.1016/j.jmii.2024.05.001","DOIUrl":"10.1016/j.jmii.2024.05.001","url":null,"abstract":"<div><h3>Introduction</h3><p>Lung cancer is one of the most prevalent malignancies worldwide. Substantial research has illuminated the intricate interplay between microorganisms and human health, revealing their role in disease regulation. Trichomonads is a flagellated protozoan in the human cavity and have been previously identified as a pathogen associated with pneumonia, contributing to tissue chronic inflammation and carcinogenesis.</p></div><div><h3>Methods</h3><p>Nested polymerase chain reaction methods were employed to scrutinize the prevalence of trichomonads in the bronchovesicular fluid of patients diagnosed with lung cancer. Subsequently, the influence of <em>Trichomonas tenax</em> invasion on lung cancer cells was elucidated through proliferation assays, migration assays, and transcription analysis.</p></div><div><h3>Results</h3><p>Bronchoalveolar fluid samples from lung cancer patients yielded positive nested PCR results for eight out of twenty-seven samples. Seven of these samples were identified as <em>Trichomonas tenax</em>, while one was identified as <em>Tetratrichomonas</em> spp. Our findings revealed a significant upregulation of pathways associated with carcinogenesis, including cellular proliferation, migration, and drug resistance, in response to <em>T. tenax</em> invasion.</p></div><div><h3>Conclusions</h3><p>This study underscores the importance of recognizing the presence of trichomonads and the influence of <em>T. tenax</em> invasion on host responses to respiratory diseases. The identified pathways implicated in cancer development may pave the way for developing targeted treatment strategies for pulmonary diseases. These findings hold promise for informing and improving the precision of therapeutic interventions in the context of pulmonary ailments.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 4","pages":"Pages 638-646"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224000781/pdfft?md5=103d79c06f12a3707ee52285f1cb6c60&pid=1-s2.0-S1684118224000781-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic characterization of respiratory syncytial virus surface glycoproteins F and G in Taiwan, 2017–2021","authors":"","doi":"10.1016/j.jmii.2024.06.003","DOIUrl":"10.1016/j.jmii.2024.06.003","url":null,"abstract":"<div><h3>Background</h3><p>Respiratory syncytial virus (RSV) infection imposes substantial health burden and disproportionally affects young infants, elderly, and immunocompromised hosts. RSV harbors key surface glycoproteins F and G, both crucial for viral infection and evolution.</p></div><div><h3>Methods</h3><p>In this study, we examined the genetic characteaistics of 179 RSV isolates collected between 2017 and 2021 in Taiwan. G ectodomain and whole F gene were sequenced and aligned with available references from GenBank.</p></div><div><h3>Results</h3><p>RSV ON1 and BA9 were two predominant genotypes throughout the study period. Genetic variations of G protein accumulated over time. New ON1 strains containing E257K and K204R-V225A-T238I-Y280H in combination emerged in 2019 and contributed to a local endemic in 2020. RSV-B strain with A131T and T137I substitution in G protein emerged in 2018. On the other hand, F protein of both RSV genotypes was generally conserved but some feature changes should be noted: RSV-B in Taiwan harbored 100% of I206M and Q209R in site Ø, and L172Q and S173L in site V. These amino acid changes do not affect the susceptibility of Nirsevimab but imply no effectiveness of Suptavumab.</p></div><div><h3>Conclusion</h3><p>RSV continuously evolves in Taiwan and accumulated signature genetic changes over time. Vigilant RSV genomic surveillance is important to monitor the viral evolution in the upcoming future of new RSV vaccines and prophylaxis.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 4","pages":"Pages 564-572"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224001105/pdfft?md5=b4d7ee89c8004cfe49b25c9bc35a52cc&pid=1-s2.0-S1684118224001105-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The real-world impact of the BioFire FilmArray blood culture identification 2 panel on antimicrobial stewardship among patients with bloodstream infections in intensive care units with a high burden of drug-resistant pathogens","authors":"","doi":"10.1016/j.jmii.2024.06.004","DOIUrl":"10.1016/j.jmii.2024.06.004","url":null,"abstract":"<div><h3>Background</h3><p>The increasing prevalence of drug-resistant pathogens leads to delays in adequate antimicrobial treatment in intensive care units (ICU). The real-world influence of the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel on pathogen identification, diagnostic concordance with conventional culture methods, and antimicrobial stewardship in the ICU remains unexplored.</p></div><div><h3>Methods</h3><p>This retrospective observational study, conducted from July 2021 to August 2023, involved adult ICU patients with positive blood cultures who underwent BCID2 testing. The concordance between BCID2 and conventional culture results was examined, and its impact on antimicrobial stewardship was assessed through a comprehensive retrospective review of patient records by intensivists.</p></div><div><h3>Results</h3><p>A total of 129 blood specimens from 113 patients were analysed. Among these patients, a high proportion of drug-resistant strains were noted, including carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP) (57.1%), carbapenem-resistant <em>Acinetobacter calcoaceticus-baumannii</em> complex (100%), methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) (70%), and vancomycin-resistant <em>Enterococcus faecium</em> (VRE) (100%). The time from blood culture collection to obtaining BCID2 results was significantly shorter than conventional culture (46.2 h vs. 86.9 h, <em>p</em> &lt; 0.001). BCID2 demonstrated 100% concordance in genotype–phenotype correlation in antimicrobial resistance (AMR) for CRKP, carbapenem-resistant <em>Escherichia coli</em>, MRSA, and VRE. A total of 40.5% of patients received inadequate empirical antimicrobial treatment. The antimicrobial regimen was adjusted or confirmed in 55.4% of patients following the BCID2 results.</p></div><div><h3>Conclusions</h3><p>In the context of a high burden of drug-resistant pathogens, BCID2 demonstrated rapid pathogen and AMR detection, with a noticeable impact on antimicrobial stewardship in BSI in the ICU.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 4","pages":"Pages 580-593"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224001117/pdfft?md5=4a1cb1945aa6343b71c491449fca86de&pid=1-s2.0-S1684118224001117-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mycoplasma genitalium infection and resistance-associated mutations to macrolides and fluoroquinolones among high-risk patients in Taiwan","authors":"","doi":"10.1016/j.jmii.2024.05.004","DOIUrl":"10.1016/j.jmii.2024.05.004","url":null,"abstract":"<div><h3>Background</h3><p><em>Mycoplasma genitalium</em> is an emerging etiology of sexually transmitted infections (STIs) with increasing resistance to antimicrobials. Surveillance on the epidemiology of <em>M. genitalium</em> infection and antimicrobial resistance is warranted.</p></div><div><h3>Methods</h3><p>Between September 2021 and August 2023, people with HIV (PWH) and people without HIV (PWoH) at risk of STIs were screened for <em>M. genitalium</em> infection using a multiplex polymerase-chain-reaction assay of specimens collected from the rectum, urethra, oral cavity, and vagina. The prevalences of resistance-associated mutations (RAMs) of <em>M. genitalium</em> to fluoroquinolones, macrolides, and tetracycline were investigated.</p></div><div><h3>Results</h3><p>During the 2-year study period, 1021 participants were enrolled, including 531 PWH and 490 PWoH. Overall, 83 (8.1%) and 34 (7.6%) participants had <em>M. genitalium</em> infection at baseline and during follow-up, respectively, with the rectum being the most common site of detection (61.5%). With the first course of antimicrobial treatment, 27 of 63 (42.9%) participants with <em>M. genitalium</em> infection were cured during follow-up, including 24 of 58 (41.4%) who received doxycycline monotherapy. The prevalence of RAMs to macrolides, fluoroquinolones, and tetracyclines at baseline were 24.3%, 22.4%, and 7.9%, respectively. Though PWH had more <em>M. genitalium</em> infection (10.2% vs 5.9%, p = 0.01), a higher rate of RAMs to macrolides (41.0% vs 14.7%, p &lt; 0.01) was found in PWoH.</p></div><div><h3>Conclusions</h3><p>Among high-risk populations, the prevalence of <em>M. genitalium</em> infection was 8.1%. The overall genotypic resistance of <em>M. genitalium</em> to macrolides and fluoroquinolones was moderately high in Taiwan. Detection of <em>M. genitalium</em> infection and antimicrobial resistance is warranted to ensure resistance-guided antimicrobial treatments to be administered.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 4","pages":"Pages 629-637"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224000811/pdfft?md5=f0b90b76c9b54a45745079ef52ea6df1&pid=1-s2.0-S1684118224000811-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141057384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burden of respiratory syncytial virus in older adults in Taiwan: An expert perspective on knowledge gaps","authors":"","doi":"10.1016/j.jmii.2024.05.009","DOIUrl":"10.1016/j.jmii.2024.05.009","url":null,"abstract":"<div><p>The burden of respiratory syncytial virus (RSV) infection among older adults in Taiwan is not well understood due to a scarcity of published epidemiological data. Nonetheless, the increasing proportion of older adults is anticipated to translate to increased burden of RSV infection, presenting a challenge to the healthcare system. Thus, an expert meeting was convened among a panel of infectious disease specialists from Taiwan to evaluate the existing local evidence and data gaps related to RSV infection in older adults (aged ≥50 years), and propose steps to generating evidence on disease burden among this population. Overall, there are few studies on the clinical and economic burden of RSV infection in Taiwan, and existing data are limited by small sample sizes and highly selected populations. Inconsistent RSV testing practices among older adults contribute to under-diagnosis and under-reporting, driven by limitations to reimbursement policies that discourage proactive RSV testing in older adults, and the lack of appropriate, targeted RSV treatment. Crucially, the paucity of epidemiological data may perpetuate a lack of awareness of RSV among clinicians and the public, hinder investments into RSV testing at a policymaker level, and thereby impede implementation of consistent diagnostic practices, precluding a deeper understanding of RSV. To overcome these challenges, it is imperative to prioritize generation of epidemiological data to establish the burden of RSV infection among older adults in Taiwan. Such data would also support a multi-stakeholder group in assessing the impact of future RSV-related interventions, such as educational initiatives and preventative strategies including vaccines.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 4","pages":"Pages 523-532"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224001014/pdfft?md5=5d2d4d471e7d39fff28fcd775dc38c22&pid=1-s2.0-S1684118224001014-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curative effects and mechanisms of AG1296 and LY294002 co-therapy in Angiostrongylus cantonensis-induced neurovascular unit dysfunction and eosinophilic meningoencephalitis","authors":"","doi":"10.1016/j.jmii.2024.05.012","DOIUrl":"10.1016/j.jmii.2024.05.012","url":null,"abstract":"<div><h3>Background</h3><p>Co-therapy with albendazole and steroid is commonly used in patients with eosinophilic meningoencephalitis caused by <em>Angiostrongylus cantonensis</em> infections. However, anthelminthics often worsen symptoms, possibly due to the inflammatory reaction to antigens released by dying worms. Therefore, the present study was to investigate the curative effects and probable mechanisms of the platelet-derived growth factor receptor-beta (PDGFR-β) inhibitor AG1296 (AG) and the phosphoinositide 3-kinase inhibitor (PI3K) LY294002 (LY) in <em>A</em>. <em>cantonensis</em>-induced neurovascular unit dysfunction and eosinophilic meningoencephalitis.</p></div><div><h3>Methods</h3><p>Western blots were used to detect matrix protein degradation and the expressions of PDGFR-β/PI3K signaling pathway. The co-localization of PDGFR-β and vascular smooth muscle cells (VSMCs), and metalloproteinase-9 (MMP-9) and VSMCs on the blood vessels were measured by confocal laser scanning immunofluorescence microscopy. Sandwich enzyme-linked immunosorbent assays were used to test S100B<strong>,</strong> interleukin (IL)-6, and transforming growth factor beta in the cerebrospinal fluid to determine their possible roles in mouse resistance to <em>A. cantonensis</em>.</p></div><div><h3>Results</h3><p>The results showed that AG and LY cotherapy decreased the MMP-9 activity and inflammatory reaction. Furthermore, S100B, IL-6 and eosinophil counts were reduced by inhibitor treatment. The localization of PDGFR-β and MMP-9 was observed in VSMCs. Furthermore, we showed that the degradation of the neurovascular matrix and blood-brain barrier permeability were reduced in the mouse brain.</p></div><div><h3>Conclusions</h3><p>These findings demonstrate the potential of PDGFR-β inhibitor AG and PI3K inhibitor LY co-therapy as anti-<em>A. cantonensis</em> drug candidates through improved neurovascular unit dysfunction and reduced inflammatory response.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 4","pages":"Pages 647-659"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S168411822400104X/pdfft?md5=deb29d8c308c35460601c473db7ee61e&pid=1-s2.0-S168411822400104X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}