Infectious Medicine最新文献

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.

Tuberculosis is a chronic infectious disease, caused by Mycobacterium tuberculosis, that seriously endangers human health. Skeletal tuberculosis is the most common type of extrapulmonary tuberculosis and tuberculous arthritis is the second most common type of skeletal tuberculosis. We report a case series of patients with tuberculous arthritis, two of whom had no joint disease in the past and presented as monoarthritis. The final patient had a history of rheumatoid arthritis, with polyarthritis that was aggravated during treatment with glucocorticoids and immunosuppressive drugs. This series of cases can contribute to early diagnosis and treatment with appropriate infection control measures.

Hand, foot, and mouth disease (HFMD) is one of the most common class C infectious diseases, posing a serious threat to public health worldwide. Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) have been regarded as the major pathogenic agents of HFMD; however, since an outbreak caused by coxsackievirus A6 (CV-A6) in France in 2008, CV-A6 has gradually become the predominant pathogen in many regions. CV-A6 infects not only children but also adults, and causes atypical clinical symptoms such as a more generalized rash, eczema herpeticum, high fever, and onychomadesis, which are different from the symptoms associated with EV-A71 and CV-A16. Importantly, the rate of genetic recombination of CV-A6 is high, which can lead to changes in virulence and the rapid evolution of other characteristics, thus posing a serious threat to public health. To date, no specific vaccines or therapeutics have been approved for CV-A6 prevention or treatment, hence it is essential to fully understand the relationship between recombination and evolution of this virus. Here, we systematically review the genetic recombination events of CV-A6 that have occurred worldwide and explore how these events have promoted virus evolution, thus providing important information regarding future HFMD surveillance and prevention.