Accuracy of diagnostic assays for the detection of Clostridioides difficile: A systematic review and meta-analysis.

INTRODUCTION: Clostridioides difficile Infection (CDI) has been identified as one of the main causes of nosocomial infection all across the world. Rapid diagnosis of CDI is difficult and poses a significant challenge to physicians worldwide. We undertook a systematic review and meta-analysis to evaluate rapid tests' diagnostic accuracy against toxigenic culture as the reference standard for CDI. METHOD: We searched the PubMed/MEDLINE and EMBASE databases for the relevant records. The QUADAS-2 tool was used to assess the quality of the studies. Diagnostic accuracy measures [i.e., sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and the area under the curve (AUC)] were pooled with a random-effects model. All statistical analyses were performed with Meta-DiSc (Version 1.4, Cochrane Colloquium, Barcelona, Spain) and RevMan (version 5.3; The Nordic Cochrane Centre, the Cochrane Collaboration, Copenhagen, Denmark). RESULTS: We reviewed retrieved records and identified 63 studies that met the inclusion criteria. 26 were about enzyme immunoassay (EIA) (our main index test). The sensitivity of GDH and Tox A/B EIAs were 82% (95% CI: 79-84) and 75% (95% CI: 70-79), respectively. On the other hand, the specificity of GDH EIA was 91% (95% CI: 90-92) and the specificity of Tox A/B EIA was 95% (95% CI: 94-96). Among other index tests, BD Max with 92% has the most sensitivity and cell cytotoxicity neutralization assay (CCNA) has the most specificity (100%). CONCLUSION: This meta-analysis demonstrated that EIAs could be reliable methods for detecting CDI based on their sensitivity, specificity, time and cost-effectiveness, and simplicity in the procedure. Further work to improve rapid tests would benefit from improvements to the methodology.

Immunopotentiation of the engineered low-molecular-weight pilin targeting Pseudomonas aeruginosa: A combination of immunoinformatics investigation and active immunization.

Several vaccine candidates have been introduced for immunization against Pseudomonas aeruginosa strains. Despite extensive efforts in recent decades, there is no accurate immunogenic candidate against this pathogen in the market yet. Due to the rapid increase in several drug-resistant strains, P. aeruginosa has caused various health concerns worldwide. It encodes many specific virulence features, which can be used as an appropriate vaccine candidate. The primary stage of the pathogenesis of P. aeruginosa is the expression of many dynamic adhesive molecules, such as type IV pili (T4P), which acts as a principal colonization factor. It has been confirmed that three different subtypes of T4P, including type IVa (T4aP), type IVb (T4bP) and tight adherence (Tad) pili are expressed by P. aeruginosa. The IVa fimbriae type is almost the main cause of challenges to design an effective pili based-immunotherapy method. Nevertheless, in terms of heterogeneity, variability and hidden conserved binding site of T4aP, this attitude has been remained controversial and there is no permitted human study based on IVa pilin commercially. The engineered synthetic peptide-based vaccines are highly talented to mimic the target. In this research, for the first time, some dominant immunogenic features of the Flp protein, such as both B- and T-cell-associated epitopes, presence of IgE-associated epitopes, solvent-accessible surface area were evaluated by analytical immunoinformatics methods. In addition, we designed the engineered Flp pilin as an effective immunogenic substance against several clinically important P. aeruginosa strains. Moreover, by practical active immunization approaches, the humoral and cellular immune response against the extremely conserved region of the engineered synthetic Flp (EFlp) formulated in Montanide ISA 266 compared to the control group. The results of active immunization against EFlp significantly signified that EFlp-Montanide ISA 266 (EFLP-M) strongly could induce both humoral and cellular immune responses. We concluded that Flp pilin has therapeutic potential against numerous clinically significant P. aeruginosa strains and can be served as a novel immunogen for further investigations for development of effective immunotherapy methods against P. aeruginosa as a dexterous pathogen.