Infectious Medicine最新文献

Background

People with cystic fibrosis (CF) may develop clinically significant chronic respiratory infections with Pseudomonas aeruginosa (PA) and non-tuberculous mycobacteria (NTM). Open water has been suggested to be an important source for continuous or intermittent exposure to these pathogens. To date, there has been a paucity of studies examining the relationship between chronic PA and NTM infection in CF patients and surfaces waters, including blue spaces. The aim of this study was therefore to examine the relationship between chronic pulmonary infection with PA and NTMs in children and adults with CF in European countries and area of surface waters, including blue spaces.

Methods

European CF registry data detailing incidence of chronic PA and NTM infection in adults and children with CF in Europe (n=41,486 in 24 European countries) was correlated with surface water area data from the same countries (approx. 678,278 km²) employing Spearman coefficients.

Results

Correlation of chronic PA infection in children and adults and surface water area were not significant (p=0.0680 and p=0.8448, respectively), as was NTM infection (p=0.7371 and p=0.0712, respectively).

Conclusions

Acquistion of PA and its avoidance in people with CF is a complicated dynamic, not solely driven by close association with surface water, but through the integration of several other factors, including mitigations by people with CF to avoid high risk scenarios with surface water. This study was unable to demonstrate a correlation between PA and NTM infection in people with cystic fibrosis and surface water area at a national level. CF patients should continue to be vigilant about potential infection risks posed by water and take evidence-based decisions regarding their behaviour around water to protect them for acquiring these organisms from these sources.

Health care-associated infections (HCAIs) pose a substantial threat to immunocompromised individuals and represent a frequent adverse event in health care delivery. The aim of this study was to evaluate the global research landscape of HCAIs among immunocompromised populations before and during the COVID-19 pandemic. A systematic search of articles published between 2013 and 2022 in the Web of Science Core Collection database was conducted, and content analytics and integrated science mapping were used for data analysis and interpretation. The review identified 1,473 articles. Only 633 articles authored by 4,151 individuals and published in 366 journals were included. The average citation rate was 14.27 per document, and research production grew annually by 9.07% peaking in 2021 during the COVID-19 pandemic but declining in 2022. The United States emerged as the most productive country, with 743 publication appearances and 2,485 citations. Keywords such as “epidemiology,” “infection,” “mortality,” and “risk factors” were frequently encountered in the analyzed literature. The main research themes, including “mortality,” “sepsis,” “immunosuppression,” “expression,” and “pneumonia,” underscored the focal points of importance within this domain. This study highlighted the growing interest regarding HCAIs in immunocompromised populations, especially during the COVID-19 pandemic. The study findings underscore the need to advance research efforts to understand different immunocompromised states, develop tailored infection prevention measures, and address health care disparities to mitigate the burden of HCAIs among immunocompromised individuals.

Background

The Alere PBP2a SA Culture Colony Test is an FDA-cleared in vitro immunochromatographic assay for rapid detection of penicillin-binding protein2a (PBP2a) in Staphylococcus aureus.

Methods

We investigated the performance of the PBP2a SA Culture Colony Test with 78 coagulase-negative Staphylococcus (CoNS) isolates from different body sites, with the Vitek 2 Antimicrobial Susceptibility Test (AST) as a reference standard.

Results

The CoNS species were 62 S. epidermidis; 6 S. lugdenensis; 3 S. hominis; 2 S. capitis; 2 S. haemolyticus; and 1 each of S. simulans, S. auricularis, and S. warneri. Of the 78 CoNS isolates, 68 showed concordance in the PBP2a IC assay and Vitek 2 AST. Discordance was seen for 10 S. epidermidis isolates, which showed negative in the PBP2a assay, despite oxacillin-resistance detection using the Vitek 2 AST (66.7% sensitivity and 100% specificity). All non-S. epidermidis CoNS were identified with 100% concordance using the PBP2a IC assay and Vitek 2 AST.

Conclusion

We demonstrated that, while the PBP2a IC assay has low sensitivity in determining the susceptibility of S. epidermidis to oxacillin, it highly accurately predicted the susceptibility of non-S. epidermidis CoNS to oxacillin. The diagnostic accuracy for non-S. epidermidis CoNS needs further assessment with more isolates to confirm our findings.

Background

Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis worldwide. JEV exhibits significant neuroinvasiveness and neurotoxicity, resulting in considerable damage to the nervous system. Japanese encephalitis is associated with high morbidity and mortality rate, seriously harming both human health and livestock production. The current lack of specific antiviral drugs means that the development of new therapeutic agents for JEV has become urgent.

Methods

Anti-JEV drugs were screened from 111 inhibitors of neurotransmitter receptor-related molecules by high content technology. The antiviral effects of clomipramine HCl were evaluated through plaque assay, real-time quantitative PCR, immunofluorescence assay and western blotting assay. Bioinformatic tools were utilized to cluster the altered signaling pathway members after clomipramine HCl treatment. Finally, the anti-JEV mechanism was deeply resolved in vivo via such molecular biology and virological detection techniques.

Results

In this study, we screened nine compounds with significant anti-JEV activity, of which clomipramine HCl demonstrated the most potent antiviral effect and exhibited dose-dependent activity. Mechanistically, clomipramine HCl may activate endoplasmic reticulum stress and modulate the unfolded protein response, thus inhibiting the assembly stage of JEV infection.

Conclusion

This study highlights the importance of clomipramine HCl as a promising approach for JEV infection protection, which may lead to new host-directed antiviral approaches to such mosquito-borne viruses.

Background

Objective

Methods

Results

Conclusion

Background

Scrub typhus, an acute febrile disease caused by Orientia tsutsugamushi, is transmitted to humans through infected chigger mites. We present a case of scrub typhus in a previously healthy man from Shandong Province diagnosed using next-generation sequencing (NGS) and PCR and review recent literature on NGS for scrub typhus diagnosis.

Methods

NGS was utilized for testing whole blood collected on admission. Confirmatory testing was done by detecting IgM and IgG antibodies to Orientia in acute and convalescent sera by ELISA. Orientia 47-kDa protein gene TaqMan and standard PCR of the 56-kDa protein gene and Sanger sequencing were performed on eschar scab DNA.

Results

The NGS diagnosis was confirmed by 47-kDa protein gene TaqMan and sequencing of a fragment of the O. tsutsugamushi 56-kDa protein gene from the eschar scab. Analysis of this sequence and the NGS data indicated O. tsutsugamushi strain Cheeloo2020 is a novel genotype. Mapping of the NGS data against the O. tsutsugamushi Gilliam strain genome sequence identified 304 reads with high similarity.

Conclusions

NGS is not only useful for multiplex diagnosis of scrub typhus, but also provides insight into the genetic diversity of O. tsutsugamushi. The common failure to submit sequences to databases makes it difficult to determine the minimal quantity and quality of NGS data being used for the positive identification of Orientia DNA in clinical specimens.

Background

Vibrio cholerae N-acetylglucosamine-binding protein (GbpA) is a four-domain, secretory colonization factor which is essential for chitin utilization in the environment, as well as in adherence to intestinal cells. GbpA is also involved in inducing intestinal inflammation by enhancing mucin and interleukin-8 secretion. The underlying cell signaling mechanism involved in the induction of the pro-inflammatory response and IL-8 secretion has yet to be deciphered in detail.

Methods

Herein, the process through which GbpA triggers the induction of IL-8 in intestinal cells was investigated by examining the role of GbpA in intestinal cell line HT 29.

Results

GbpA, specifically through the fourth domain, forms a binding connection with Toll-like receptor 2 (TLR2) and additionally, recruits TLR1 along with CD14 within a lipid raft micro-domain to initiate the signaling pathway. Notably, disruption of this micro-domain complex resulted in a reduction in IL-8 secretion. The lipid raft association served as the catalyst that invoked a downstream cellular inflammatory signaling pathway. This cascade involved the activation of various MAP kinases and NFκB and assembly of the AP-1 complex. This coordinated activation of signaling molecules eventually leads to enhanced IL-8 transcription via increased promoter activity. These findings suggested that GbpA is a crucial protein in V. cholerae, capable of inciting a pro-inflammatory response during infection by orchestrating the formation of the GbpA-TLR1/2-CD14 lipid raft complex. Activation of AP-1 and NFκB in the nucleus eventually enhanced IL-8 transcription through increased promoter activity.

Conclusion

Collectively, these findings indicated that GbpA plays a pivotal role within V. cholerae by triggering a pro-inflammatory response during infection. This response is instrumented by the formation of the GbpA-TLR1/2-CD14 lipid raft complex.

Background

Fujian Province has one of the highest reported incidences of hepatitis B virus infection in China. This study aimed to provide a theoretical framework for preventing and controlling hepatitis B in Fujian Province, and to assess the trends and the spatial-temporal distribution patterns of hepatitis B in this region.

Methods

Data on hepatitis B cases were extracted from the National Notifiable Infectious Disease Surveillance System. Spatial autocorrelation analysis, trend surface analysis, and spatial-temporal scanning statistics were used to identify the spatial and aggregation patterns at the county level. The Joinpoint was used to assess the reported incidence trends.

Results

The average reported incidence of hepatitis B in Fujian from 2012 to 2021 was 14.46/10,000 population, with 583,262 notified cases. The age-adjusted reported incidence of hepatitis B decreased from 17.44/10,000 population in 2012 to 11.88/10,000 population in 2021, with an average reduction in the annual percentage change of 4.5%. There were obvious spatial-temporal aggregation characteristics in hepatitis B cases, and a high-incidence area was located in eastern Fujian. Spatio-temporal scanning statistics revealed four levels of aggregation of hepatitis B reporting rates. The first level of aggregation area included Minhou, Gulou, Jin'an, Taijiang, and nine other districts and counties.

Conclusion

The incidence of hepatitis B is declining in Fujian Province. Spatial clusters of hepatitis B cases in Fujian Province were identified, and high-risk areas in eastern Fujian still exist. Closely monitoring the general patterns in the occurrence of hepatitis B and implementing focused control and preventative strategies are important.

Background

Swift and accurate detection of Vibrio parahaemolyticus, which is a prominent causative pathogen associated with seafood contamination, is required to effectively combat foodborne disease and wound infections. The toxR gene is relatively conserved within V. parahaemolyticus and is primarily involved in the expression and regulation of virulence genes with a notable degree of specificity. The aim of this study was to develop a rapid, simple, and constant temperature detection method for V. parahaemolyticus in clinical and nonspecialized laboratory settings.

Methods

In this study, specific primers and CRISPR RNA were used to target the toxR gene to construct a reaction system that combines recombinase polymerase amplification (RPA) with CRISPR‒Cas13a. The whole-genome DNA of the sample was extracted by self-prepared sodium dodecyl sulphate (SDS) nucleic acid rapid extraction reagent, and visual interpretation of the detection results was performed by lateral flow dipsticks (LFDs).

Results

The specificity of the RPA-CRISPR/Cas13a-LFD method was validated using V. parahaemolyticus strain ATCC-17802 and six other non-parahaemolytic Vibrio species. The results demonstrated a specificity of 100%. Additionally, the genomic DNA of V. parahaemolyticus was serially diluted and analysed, with a minimum detectable limit of 1 copy/µL for this method, which was greater than that of the TaqMan-qPCR method (10² copies/µL). The established methods were successfully applied to detect wild-type V. parahaemolyticus, yielding results consistent with those of TaqMan-qPCR and MALDI-TOF MS mass spectrometry identification. Finally, the established RPA-CRISPR/Cas13a-LFD method was applied to whole blood specimens from mice infected with V. parahaemolyticus, and the detection rate of V. parahaemolyticus by this method was consistent with that of the conventional PCR method.

Conclusions

In this study, we describe an RPA-CRISPR/Cas13a detection method that specifically targets the toxR gene and offers advantages such as simplicity, rapidity, high specificity, and visual interpretation. This method serves as a valuable tool for the prompt detection of V. parahaemolyticus in nonspecialized laboratory settings.

In a retrospective view, this review examines the impact of mucormycosis on health workers and researchers during the COVID era. The diagnostic and treatment challenges arising from unestablished underlying pathology and limited case studies add strain to healthcare systems. Mucormycosis, caused by environmental molds, poses a significant threat to COVID-19 patients, particularly those with comorbidities and compromised immune systems. Due to a variety of infectious Mucorales causes and regionally related risk factors, the disease's incidence is rising globally. Data on mucormycosis remains scarce in many countries, highlighting the urgent need for more extensive research on its epidemiology and prevalence. This review explores the associations between COVID-19 disease and mucormycosis pathology, shedding light on potential future diagnostic techniques based on the fungal agent's biochemical components. Medications used in ICUs and for life support in ventilated patients have been reported, revealing the challenge of managing this dual onslaught. To develop more effective treatment strategies, it is crucial to identify novel pharmacological targets through “pragmatic” multicenter trials and registries. In the absence of positive mycology culture data, early clinical detection, prompt treatment, and tissue biopsy are essential to confirm the specific morphologic features of the fungal agent. This review delves into the history, pathogens, and pathogenesis of mucormycosis, its opportunistic nature in COVID or immunocompromised individuals, and the latest advancements in therapeutics. Additionally, it offers a forward-looking perspective on potential pharmacological targets for future drug development.