Operational models and criteria for incorporating microbial whole genome sequencing in hospital microbiology – A systematic literature review

BackgroundMicrobial whole genome sequencing (WGS) has many advantages over standard microbiological methods. However, it is not yet widely implemented in routine hospital diagnostics due to notable challenges.ObjectivesThe aim was to extract managerial, financial and clinical criteria supporting the decision to implement WGS in routine diagnostic microbiology, across different operational models of implementation in the hospital setting.MethodsThis was a systematic review of literature identified through PubMed and Web of Science. English literature studies discussing the applications of microbial WGS without limitation on publication date were eligible. A narrative approach for categorization and synthesis of the sources identified was adopted.ResultsA total of 98 sources were included. Four main alternative operational models for incorporating WGS in clinical microbiology laboratories were identified: full in-house sequencing and analysis, full outsourcing of sequencing and analysis and two hybrid models combining in-house/outsourcing of the sequencing and analysis components. Six main criteria (and multiple related sub-criteria) for WGS implementation emerged from our review and included cost (e.g. the availability of resources for capital and operational investment); manpower (e.g. the ability to provide training programmes or recruit trained personnel), laboratory infrastructure (e.g. the availability of supplies and consumables or sequencing platforms), bioinformatics requirements (e.g. the availability of valid analysis tools); computational infrastructure (e.g. the availability of storage space or data safety arrangements); and quality control (e.g. the existence of standardized procedures).ConclusionsThe decision to incorporate WGS in routine diagnostics involves multiple, sometimes competing, criteria and sub-criteria. Mapping these criteria systematically is an essential stage in developing policies for adoption of this technology, e.g. using a multicriteria decision tool. Future research that will prioritize criteria and sub-criteria that were identified in our review in the context of operational models will inform decision-making at clinical and managerial levels with respect to effective implementation of WGS for routine use. Beyond WGS, similar decision-making challenges are expected with respect to future integration of clinical metagenomics.     

Intestinal schistosomiasis: a very long-lived tropical parasite

We report a case of intestinal schistosomiasis in a patient who had not travelled outside Europe after migrating 20 years ago. Images of the Schistosoma mansoni eggs are shown that confirm the active nature of the infection.     

Copan WASPLab automation significantly reduces incubation times and allows earlier culture readings

ObjectiveThe aim was to evaluate whether laboratory automation (inoculation and automated incubation combined with timely defined high-resolution digital imaging) may help reduce the time required to obtain reliable culture analysis results.MethodsWe compared the results obtained by WASPLab automation against WASP-based automated inoculation coupled to conventional incubation and manual diagnostic on 1294 clinical samples (483 for the derivation set and 811 for the independent validation set) that included urine, genital tract and non-sterile site specimens, as well as ESwabs for screening of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus aureus (MSSA), extended-spectrum beta-lactamases (ESBLs) and carbapenemase-producing Enterobacteriaceae (CPE). We used sequential routine specimens referred to the bacteriology laboratory at Geneva University Hospitals between October 2018 and March 2019.ResultsThe detection sensitivity of MRSA and MSSA at 18 hr on WASPLab was 100% (95% confidence interval [CI], 94.48–100.00%). The detection sensitivity of ESBL and CPE at 16 hr on WASPLab was 100% (95% confidence interval [CI], 94.87% to 100.00%). For urine specimens, the similarity was 79% (295/375) between 18 hr and 24 hr of incubation on WASPLab. For genital tract and non-sterile site specimens, the similarity between 16 hr and 28 hr of incubation on WASPLab were 26% (72/281) and 77% (123/159) respectively. Thus, 28 hr was defined as the final incubation time on WASPLab for genital tract and non-sterile site specimens.ConclusionsThe results of this study show that WASPLab automation enables a reduction of the culture reading time for all specimens tested without affecting performances. Implementing the established and duly validated incubation times will allow appropriate laboratory workflows for improved efficiency to be built.     

Current Practice in Vitamin D Management in Allogeneic Hematopoietic Stem Cell Transplantation: A Survey by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation

Beyond its impact on bone health, numerous studies have investigated the immune-regulatory properties of vitamin D and shown how its deficiency can affect outcomes in allogeneic hematopoietic stem cell transplantation (HSCT), particularly in acute or chronic graft-versus-host disease. This survey, carried out by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation (EBMT), describes the current clinical practice discrepancies across the EBMT HSCT programs. We therefore recommend the development of evidence-based guidelines to standardize evaluation criteria and to harmonize the management of vitamin D deficiency in patients undergoing allogeneic HSCT.     

Effects of intermittent hypoxia training on leukocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and blood insulin level in prediabetes patients

Purpose

Intermittent hypoxia training/treatment (IHT) is an emerging therapeutic approach to alleviate chronic diseases, such as diabetes. The present study investigated the effects of IHT on blood leucocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and its relationship with the changes in blood insulin level.

Methods

Seven adult healthy volunteers and 11 prediabetic patients participated in this study. A 3-week course of IHT consisted of a 40-min session of 4 cycles of 5-min 12% O₂ and 5-min room air breathing per day, 3 sessions per week for 3 weeks (i.e., total 9 sessions of IHT). Plasma insulin levels and leukocyte PDK-1 mRNA expression were determined at various time points either under fasting condition or following oral glucose tolerance test (OGTT). Correlation between the IHT-induced changes in PDK-1 mRNA and insulin or glucose levels in the same serological samples was analyzed.

Results

At pre-IHT baseline, PDK-1 mRNA expression was two times higher in prediabetes than control subjects. IHT resulted in significant augmentation in PDK-1 mRNA expression (> twofold) in prediabetes at the end of 3-week IHT and remained elevated 1 month after IHT, which was correlated with a significantly reduced insulin release and lower blood glucose after glucose loading with OGTT.

Conclusion

IHT can trigger beneficial effects in normalizing blood insulin levels in prediabetic patients under oral glucose load, which were closely correlated with an enhanced mRNA expression of PDK-1 in leukocytes. Further clinical trials are warranted to validate the utility of IHT as a non-invasive complementary therapy against diabetes-associated pathologies.